cyclic C12/14-Glucamide;cyclic N-methyl-N-dodecanoyl/tetradecanoyl-glucamine;anhydro-N-dodecanoyl/tetradecanoyl-N-methylglucamine;Amides, C12-C14, N-(1-deoxy-D-glucitol-1-yl)-N-methyl, dehydrated

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Effects on fertility

Description of key information

Main OECD 421 Study (rat)

NOAEL (reproduction): 300 mg/kg

NOAEL (systemic): 150 mg/kg

Dose range finding study for OECD 421:

NOAEL (reproduction): 500 mg/kg NOAEL (systemic): 250 mg/kg

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

experimental study

Remarks:

As per OECD Guideline No. 421, “Reproduction/Developmental Toxicity Sc reening Test”, adopted on 29 July 2016

Adequacy of study:

key study

Study period:

From : 19 March 2022 to 18 November 2022

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

OECD Guideline No. 421, “Reproduction/Developmental Toxicity Screening Te st”, adopted on 29 July 2016

Qualifier:

according to guideline

Guideline:

OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)

Version / remarks:

Adopted on 29 July 2016

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Justification for study design:

SPECIFICATION OF STUDY DESIGN FOR EXTENDED ONE-GENERATION REPRODUCTION TOXICITY STUDY WITH JUSTIFICATIONS [please address all points below]:

- Premating exposure duration for parental (P0) animals: 2 weeks

- Basis for dose level selection: The doses of 150, 300 and 600 mg/kg body weight were selected as low (G2), mid (G3) and high dose (G4) levels, respectively for the present “Reproduction/ Developmental Toxicity Screening Test by Oral Gavage in Sprague Dawley rats” in consultation with sponsor based on the below mentioned toxicity information of the test item Cyclic Glucamide C12-C14.

- A dose range finding study (Bioneeds Study No. BIO-CTX 279) was conducted initially with the dose levels of 120, 300 and 750 mg/kg body weight/day by Oral Gavage in Sprague Dawley rats. The results of this study reveals that, the test item was non-toxic up to the dose level of 300 mg/kg body weight/day when administered for a period of 14 consecutive days repeatedly. An increase in creatinine and decrease in absolute and relative kidney weight were noted in males at the dose level of 750 mg/kg body weight/day. Thickened mucosa with uneven surface was observed in non-glandular part of the stomach in both males and females at the dose level of 750 mg/kg body weight/day during gross pathological examinations.

- Based on the results obtained from the above dose range finding study, another dose range finding study in lines with OECD TG 421, “Reproduction/Developmental Toxicity Screening Test” with the doses of 100, 250 and 500 mg/kg body weight was conducted (Bioneeds Study No. BIO-DTX 051). The oral administration of test item did not produce any indication of systemic, reproduction and developmental toxicity in either sex of both adults and pups at the tested dose levels of 100 and 250 mg/kg body weight/day. At dose level 500 mg/kg body weight/day, the test item did not produce any indication of reproduction and developmental toxicity in either sex of both adults and pups. However, systemic toxicity effects such as, clinical signs (wetness around mouth immediately after administration in both the sexes), reduced body weight and percent change in body weight gain in males and gross pathological changes (red discoloration of gastric and intestinal contents in 3 out of 6 males, thickened mucosa with uneven surface in non-glandular part of the stomach in 2 out 6 females) were noted at this dose level (500 mg/kg body weight/day).


- Route of administration: oral (gavage) route
- on choice of species, strain: Rat is one of the standard laboratory rodent species used for toxicity
assessment and also recommended by various regulatory authorities.
- vehicle : distilled water was used for the preparation of test item formulations, and it is one of the commonly used vehicle for toxicity studies.
- number of animals: 96 (48 Males + 48 Females) as per guideline

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source : manufacturer or supplier
- batch number of test material: S148866
- Purity : 100%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Ambient (21 to 29°C)
- Stability and homogeneity of the test material in the vehicle/solvent under test conditions (e.g. in the exposure medium) and during storage: dose concentration was stable up to
48 hours at room temperature.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Final preparation of a solid : . Required quantity of test item was weighed into a clean glass beaker, approximately 80-90% of the vehicle was added to the beaker containing test item, mixed well with clean glass rod under sonication until the test item dissolves completely and then transferred to a measuring cylinder. Finally, the volume was adjusted to required mark in measuring cylinder with vehicle to get a desired concentration

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Rat is one of the standard laboratory rodent species used for toxicity assessment and also recommended by various regulatory authorities.

Details on species / strain selection:

Rat is one of the standard laboratory rodent species used for toxicity assessment and also
recommended by various regulatory authorities.

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hylasco Biotechnology India Pvt. Ltd,
Charles River Technology Licensee,
CPCSEA (Committee for the Purpose of Control and Supervision of Experiments on Animals)
Registration No.: 1808/PO/RcBt/S/15/CPCSEA

- Females(nulliparous and non-pregnan)t: yes
- Age at study initiation: 8 to 9 weeks
- Weight at study initiation: Males: 210.23 to 264.08 g Females: 200.03 to 232.26 g
- Housing: During acclimatization - two animals, Pre-mating - two animals, Mating - two animals, Postmating : Males were housed two, while females were housed individually
- Diet : Altromin maintenance diet for rats and mice (manufactured by Altromin Spezialfutter GmbH &
Co. KG) was provided ad libitum
- Water : Deep bore-well water passed through reverse osmosis unit and was provided ad libitum
- Acclimation period: seven days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.1 to 23.8
- Humidity (%): 42 to 65
- Air changes (per hr):12 to 15 air changes per hour
- Photoperiod (hrs dark / hrs light):12 hours fluorescent light and 12 hours dark cycle
IN-LIFE DATES: From: 20 April 2022 To: 24 June 2022

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: Required quantity of test item was weighed into a clean glass beaker, approximately 80-90% of the vehicle was added to the beaker containing test item, mixed well with clean glass rod under sonication until the test item dissolves completely and then transferred to a measuring cylinder. Finally, the volume was adjusted to required mark in measuring cylinder with vehicle to get a desired concentration

VEHICLE
- Concentration in vehicle:
- Amount of vehicle (if gavage): 10mL/Kg
- batch no. : M017, M0324

Details on mating procedure:

- M/F ratio per cage: 1:1
- Length of cohabitation: 19 days
- Proof of pregnancy: sperm in vaginal smear referred to as gestation day 0 of pregnancy
- After 14 days of unsuccessful pairing replacement of first male by another male with proven fertility. Yes
- After successful mating each pregnant female was caged (how): individually
- Any other deviations from standard protocol: no

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

dose formulation analysis for dose concentration verification was performed during week 1 and 5 of the treatment. The results of dose concentration verifications for the prepared test item formulations and the mean results of analysis were within the rang

Duration of treatment / exposure:

Males: The males were treated for two weeks pre-mating, during mating period and up to the day before sacrifice (total of 35 days of administration).
Females:
-The pregnant animals were treated for a two-week pre-mating period (14-days), during mating until confirmed as mated, pregnancy (gestation) and up to lactation day 13 (ranging from a total period of 49 to 65 days).
-The non-pregnant animals were treated during two-week pre-mating period, during mating until confirmed as mated and further 24 days from the day of confirmation of mating

Frequency of treatment:

Once daily

Dose / conc.:

600 mg/kg bw/day

Remarks:

high dose

Dose / conc.:

300 mg/kg bw/day

Remarks:

mid dose

Dose / conc.:

150 mg/kg bw/day

Remarks:

low dose

No. of animals per sex per dose:

12 animals per sex per dose

Control animals:

yes

Details on study design:

- Dose selection rationale:
The doses of 150, 300 and 600 mg/kg body weight were selected as low (G2), mid (G3) and high dose (G4) levels, respectively for the present “Reproduction/ Developmental Toxicity Screening Test by Oral Gavage in Sprague Dawley rats” in consultation with sponsor based on the below mentioned toxicity information of the test item Cyclic Glucamide C12-C14.
- A dose range finding study (Bioneeds Study No. BIO-CTX 279) was conducted initially with the dose levels of 120, 300 and 750 mg/kg body weight/day by Oral Gavage in Sprague Dawley rats. The results of this study reveals that, the test item was non-toxic up to the dose level of 300 mg/kg body weight/day when administered for a period of 14 consecutive days repeatedly. An increase in creatinine and decrease in absolute and relative kidney weight were noted in males at the dose level of 750 mg/kg body weight/day. Thickened mucosa with uneven surface was observed in non-glandular part of the stomach in both males and females at the dose level of 750 mg/kg body weight/day during gross pathological examinations.
- Based on the results obtained from the above dose range finding study, another dose range finding study in lines with OECD TG 421, “Reproduction/Developmental Toxicity Screening Test” with the doses of 100, 250 and 500 mg/kg body weight was conducted (Bioneeds Study No. BIO-DTX 051). The oral administration of test item did not produce any indication of systemic, reproduction and developmental toxicity in either sex of both adults and pups at the tested dose levels of 100 and 250 mg/kg body weight/day. At dose level 500 mg/kg body weight/day, the test item did not produce any indication of reproduction and developmental toxicity in either sex of both adults and pups. However, systemic toxicity effects such as, clinical signs (wetness around mouth immediately after administration in both the sexes), reduced body weight and percent change in body weight gain in males and gross pathological changes (red discoloration of gastric and intestinal contents in 3 out of 6 males, thickened mucosa with uneven surface in non-glandular part of the stomach in 2 out 6 females) were noted at this dose level (500 mg/kg body weight/day).

- Rationale for animal assignment:
The animals were weighed and arranged in ascending order of their body weights. These body weight stratified animals were distributed to all the groups using Microsoft Excel Spreadsheet, such that body weight variation of animals selected for the study does not exceed ±20% (Males: -17.20 to 8.28%; Females: -6.03 to 5.64%) of the mean body weight of each sex. The grouping was done one day prior to initiation of treatment.
- Fasting period before blood sampling: 14 or 16 hours
- Other:

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Once daily

CLINICAL OBSERVATIONS: Yes
- Time schedule: These observations were made approximately at the same time on each day after dose administration for first three days of treatment and observed during pre and post dose administration from day 4 until termination.

BODY WEIGHT: Yes
- Time schedule for examinations:
Males: The males were weighed
- at the receipt
- on the day of randomization and grouping
- on the first day of dosing, weekly thereafter
- and at termination.
Females:
- The females were weighed
- at receipt
- on the day of randomization and grouping
- on the first day of dosing, weekly thereafter during pre-mating and until confirmation of mating.
- All the pregnant animals were weighed on gestation day (GD) 0, 7, 14, and 20 and on lactation day
(LD) 1, 4, 7, 13 and 14 (fasting/terminal body weight).
- The non-pregnant animals were weighed weekly once until termination and the fasting/terminal body
weights were also recorded before scheduled sacrifice.


FOOD CONSUMPTION : Males: Cage wise feed consumption was measured for all males once in a week during pre-mating
period coinciding with body weight recording.
Females:
- Cage wise feed consumption was measured for all females once in a week during premating period
coinciding with body weight recording.
- Cage wise feed consumption was measured for all pregnant animals during GD 0 to 7, 7 to 14 and
14 to 20, during LD 1 to 4, 4 to 7 and 7 to 13.
- Cage wise feed consumption was measured for all non-pregnant animals once in a week coinciding
with body weight recording.

Oestrous cyclicity (parental animals):

Oestrus cyclicity was monitored during
- two weeks after five days of acclimatization to screen the females for regular oestrus cyclicity
- two week pre-mating treatment period
- during mating treatment period until confirmation of mating
- at termination

Sperm parameters (parental animals):

Parameters examined in adult male (parents)generations:testis weight, epididymis weight

Litter observations:

STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: no, however one/ two pups were eliminated if more than 10 pups/
litter for measurement of serum total T4 levels

PARAMETERS EXAMINED
The following parameters were examined in [F1] offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies,
weight gain, physical or behavioural abnormalities, anogenital distance (AGD), pup weight on the
day of AGD, presence of nipples/areolae in male pups, other. Particular attention paid to the exter
nal reproductive genitals which were examined for signs of altered development; gross evaluation of
external genitalia

GROSS EXAMINATION OF DEAD PUPS: yes, for external and internal abnormalities.

Postmortem examinations (parental animals):

SACRIFICE
- Male animals: : The males were sacrificed after completion of 35 days of treatment
- Maternal animals: All the littered females were sacrificed on lactation day 14.
- The non-pregnant females were sacrificed after 26 days from the last day of confirmation of mating.

GROSS NECROPSY
- Gross necropsy consisted of careful examination of the external surface of the body, all orifices, and the cranial, thoracic and abdominal cavities and their contents as well as organs and tissues of each animal with special emphasis on reproductive organs.

HISTOPATHOLOGY / ORGAN WEIGHTS
Epididymides, Kidney, Ovaries, Prostate , Seminal vesicles and coagulating glands, Testes, Uterus with cervix, Thyroid along with parathyroid##(post fixation) were weighed,
Histopathological examination was conducted on all the tissues collected from the vehicle control and high dose group animals (with special emphasis on stages of spermatogenesis in the male gonads and histopathology of interstitial testicular cell structure - stage aware histopathological evaluation)

Postmortem examinations (offspring):

SACRIFICE
- These animals were subjected to postmortem examinations (macroscopic and/or microscopic examination) as follows:

GROSS NECROPSY
Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and
abdominal viscera and with particular attention to the external reproductive genitals and the findings
were recorded.

Statistics:

Parametric - One-way ANOVA with Dunnett’s post test
• Body weight (weekly/gestation/lactation)
• Percent Change in body weight (weekly/gestation/lactation)
• Feed consumption (weekly/gestation/lactation)
• Copulatory interval
• Gestation length
• Absolute/relative organ weights
• Mean pup weight per litter
• Mean pup anogenital distance ratio per litter
• Serum T4 values (adults/pups)
Non-Parametric -Kruskal-Wallis
• Implantations/litter
• No. of pups/litter
• Sex ratio/litter
• Litter size
• No. of early resorptions/litter
• No. of late resorptions/litter
• Prenatal loss/litter
• Postnatal loss/litter
Cross Tabs - Chi-square test
• Reproductive performances (frequency occurrences)
- mated/non-mated
- fertile/infertile
- pregnant/non-pregnant
- with/without live pups
- with/without dead pups

Reproductive indices:

Male and Female reproductive indices

Male mating index (%) = No. of males with confirmed mating / Total no. of males cohabited X 100

Female mating index (%) = No. of sperm-positive females / Total no. of females cohabited X 100

Male fertility index (%) = No. of males impregnating a female / Total no. of males mated X 100

Female fertility index (%) = No. of pregnant females / No. of sperm-positive females X 100

Gestation index (%) = No. of females with live born / No. of females with evidence of pregnancy X 100

Parturition index (%) = No. of females littered / No. of females with evidence of pregnancy X 100

Pregnancy index (%) = No. of pregnant females / No. of females with confirmed mating X 100

Post-implantation loss (%) = No. of implantations - No. of viable pups / No. of implantations X 100

Total postnatal loss (%) = Total no. of pups dead/cannibalized during postnatal period / Total no. of live pups delivered X 100

Offspring viability indices:

Live birth index (%) per litter = No. of pups born alive / Total no. of pups born X 100
Pup survival index (%) on LD 4/7/13 = Total No. of live pups on (LD 4/7/13) / No. of pups born/4/7 X 100
Other indices
Anogenital distance (AGD) ratio = Anogenital distance (mm) / Cube root of PND 4 pup weight X 100

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

There were no clinical signs of toxicity noted in any of the animals of both sexes from the tested dose groups, G2 (150 mg/kg body weight/day), G3 (300 mg/kg body weight/day) and vehicle control group G1 (0 mg/kg body weight/day) throughout the experimental period.
In group G4 males, there were no adverse clinical signs of toxicity noted in any of the animals throughout the experimental period. However, 8 out of 12 animals (from treatment day 3), 3 out of 12 animals (from treatment day 4) and 1 out of 12 animals (from treatment day 5) were noted with wetness around mouth after dose administration and continued until termination. These noted observations can be due to surfactant nature of the test item which led to form foam or wetness near to route of administration (mouth).
In group G4 females, there were no adverse clinical signs of toxicity noted in any of the animals except wetness around mouth in 9 out of 12 treated animals (from treatment day 3), 2 out of 12 animals (from treatment day 4) and 1 out of 12 animals (from treatment day 6) after dose administration (post dose) and continued until termination. These noted observations can be due to surfactant nature of the test item which led to form foam or wetness near to route of administration (mouth). Among the other 2 out 12 treated animals, one was noted with lethargy, perinasal staining and rough hair coat along with the post-dose wetness around mouth from treatment day 39 and found dead on treatment day 41. The other female was noted with lethargy between treatment day 39 to 41, with lethargy along with perinasal staining from treatment day 42 to 47.
Later, the animal was recovered from perinasal staining and lethargy but noted with wetness around mouth until termination.

Dermal irritation (if dermal study):

not examined

Mortality:

mortality observed, treatment-related

Description (incidence):

There were no mortality/morbidity noted in any of the animals of both sexes from the dose groups G1, G2 and G3 throughout the experimental period.
In group G4 females, 1 out of 12 females was found dead after parturition (on treatment day 41).

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Weekly body weights:
In group G2, there were no adverse effects noted in mean body weight and percent change in body weight gain of both sexes when compared with vehicle control group. However, a minimal reduction in both mean body weight and percent change in body weight gain was noted in males throughout the experimental period when compared with vehicle control group. The noted reductions are statistically significant during day 1 to 14, 1 to 21, 1 to 28 and 1 to 35. These changes are considered as treatment related noted due to stress induced by the test item exposure.

In group G3, there were no adverse effects noted in mean body weight and percent change in body weight gain in females when compared with vehicle control group. However, a moderate reduction in both mean body weight and percent change in body weight gain was noted in males throughout the experimental period when compared with vehicle control group. The noted reductions are statistically significant on day
28 and 35 for mean body weight and during day 1 to 21, 1 to 28 and 1 to 35 for percent change in mean body weight gain. These changes are considered as treatment related noted due to stress induced by the test item exposure.

In group G4 males, test item related effects were noted in both mean body weight and percent change in body weight gain when compared with vehicle control group throughout the experimental period. The noted reductions are statistically significant on day 14, 21 28 and 35 for mean body weight and during entire experimental period (1 to 7, 1 to 14, 1 to 21, 1 to 28 and 1 to 35) for percent change in mean body weight gain. These changes are considered as treatment related due to stress induced by the test item exposure and due to noted clinical signs of toxicity.

In group G4 females, there were no test item related effects noted in both mean body weight and percent change in body weight gain when compared with vehicle control group throughout the experimental period.

Gestation body weights:
In groups G2 and G3, there were no changes noted in both mean gestational body weight and percent change in mean gestational body weight gain when compared with the vehicle control group throughout gestation period.

In group G4, a minimal reduction in mean gestational body weight was noted throughout the pregnancy. However, the percent change in mean gestational body weight gain was comparable with vehicle control group. These changes are considered as treatment related due to stress induced by the test item exposure and due to noted clinical signs of toxicity.

Lactation body weight:
In groups G2 and G3, there were no changes noted in both mean lactation body weight and percent change in mean lactation body weight gain when compared with the vehicle control group throughout lactation period.

In group G4, a minimal reduction in both mean lactation body weight and percent change in mean lactation body weight gain was noted throughout the lactation period. These noted reductions are statistically significant for mean body weight on lactation day 13 and during lactation day 1 to 4 for percent change in mean lactation body weight gain when compared with vehicle control group. These changes are considered as treatment related due to stress induced by the test item exposure and due to noted clinical signs of toxicity.

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

effects observed, treatment-related

Description (incidence and severity):

There were no changes noted in mean feed consumption in all the tested dose groups of both sexes when compared with the vehicle control group.
There were no changes noted in mean feed consumption during gestation period in the tested dose groups G2 and G3 when compared with the vehicle control group.
In group G4, a minimal reduction in mean gestational feed consumption was noted throughout the gestational period and the noted reductions are statistically significant during gestation day (GD) 7 to 14 and 14 to 20 when compared with vehicle control group. These changes are considered as treatment related due to stress induced by the test item exposure, due to minimal reduction noted in mean gestational body weight and due to noted clinical signs of toxicity.
There were no changes noted in mean lactation feed consumption in all the tested dose groups when compared with the vehicle control group.

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, non-treatment-related

Description (incidence and severity):

There were no test item-related changes noted in obtained mean haematological values in all the tested dose groups of both sexes when compared with the vehicle control group.
However, the following statistically significant differences in mean haematological values were noted in the dose groups when compared with vehicle control group:
- decrease in mean corpuscular hemoglobin in group G2 males.
- decrease in mean neutrophils (absolute and %) in groups G2 and G4 males.
- increase in mean percent lymphocytes in groups G2, G3 and G4 males.
- increase in mean prothrombin time in group G3 males.
These statistically significant changes are considered as incidental and un-related to treatment, as the obtained mean values are within in-house historical control range of same species and strain.

Clinical biochemistry findings:

not examined

Endocrine findings:

effects observed, non-treatment-related

Description (incidence and severity):

There were no test item-related changes in mean serum T4 levels in any of the tested dose group males when compared with the vehicle control group.
However, statistically significant decrease in mean serum T4 levels in group G4 males was noted when compared with vehicle control group. This noted change is considered as incidental and un-related to treatment as the obtained mean value is within in-house historical control range of same species and strain and also no changes noted in thyroid along with parathyroid during gross examinations at this dose level.

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Microscopically, test item-related changes were observed in non-glandular part of stomach:
- G3 males: 12 (out of 12) - Hyperplasia, squamous cell, non-glandular (mild); 2 (out of 12) - Hyperkeratosis, non-glandular (minimal) and 1 (out of 12) - cyst, squamous, non-glandular.
- G3 females: 11 (out of 12) - Hyperplasia, squamous cell, non-glandular (mild).
- G4 males: 2 (out of 12) - Hyperplasia, squamous cell, non-glandular (moderate); 10 (out of 12) - Hyperplasia, squamous cell, non-glandular (marked); 2 (out of 12) - Hyperkeratosis, non-glandular (minimal); 10 (out of 12) - Hyperkeratosis, non-glandular (mild).
- G4 females: 3 (out of 12) - Hyperplasia, squamous cell, non-glandular (mild); 7 (out of 12) - Hyperplasia, squamous cell, non-glandular (marked); 1 (out of 12) - Hyperkeratosis, non-glandular (minimal); 6 (out of 12) - Hyperkeratosis, non-glandular (mild).

Histopathological findings: neoplastic:

not examined

Other effects:

no effects observed

Reproductive function: oestrous cycle:

effects observed, non-treatment-related

Description (incidence and severity):

There were no test item-related irregularities observed in oestrus cyclicity of females from any of the tested dose groups during treatment period. However, one animal from group G3 and two animals from group G4 were noted with single irregular oestrus cycle during treatment period. These noted irregularities are considered as incidental and unrelated to treatment as the same females were noted with normal preceding and proceeding oestrus cycles and there were no effects noted in reproductive performance of these females.

Reproductive function: sperm measures:

not examined

Reproductive performance:

effects observed, treatment-related

Description (incidence and severity):

Male Mating Index:
A total of 12 (out of 12), 12 (out of 12), 11 (out of 12) and 10 (out of 12) males were confirmed with mating during cohabitation period with a mating index of 100.00% 100.00, 91.67% and 83.33% from groups G1, G2, G3 and G4, respectively.
There were no statistically significant differences noted for male mating index in any of the tested dose groups when compared with the vehicle control group.
Male Fertility Index:
A total of 12 (out of 12), 11 (out of 12), 10 (out of 11) and 10 (out of 10) mated males were confirmed as fertile by impregnating a female or siring a litter with a fertility index of 100.00%, 91.67%, 90.91% and 100.00% from the tested dose groups G1, G2, G3 and G4 respectively.
There were no statistically significant differences noted for male fertility index in any of the tested dose groups when compared with the vehicle control group.
Female Mating Index:
A total of 12 (out of 12) females were confirmed as sperm positive during vaginal smear examination with a mating index of 100.0% from all the tested dose groups and vehicle control group.

Female Fertility Index:
A total of 12 (out of 12), 11 (out of 12), 10 (out of 12) and 11 (out of 12) mated females were confirmed with presence of implantations / presence of live or dead pups / evidence of parturition with a fertility index of 100.00%, 91.67%, 83.33% and 91.67% from groups G1, G2, G3 and G4 respectively.
There were no statistically significant differences noted for female fertility index in any of the tested dose groups when compared with the vehicle control group.
Pre-coital Interval/Copulatory Interval/Mean time to Mating:
A total of 12 pairs were left for cohabitation from each group. The mean
pre-coital interval was 2.67, 3.08, 4.75 and 6.33 days for groups G1, G2, G3 and G4 respectively.
There were no statistically significant differences noted for mean
pre-coital interval in any of the tested dose groups when compared with the vehicle control group.
Gestation Length/Duration of Pregnancy:
The mean gestation length [day of confirmed as successfully mated to day of parturition] was 22.00, 22.27, 22.20 and 22.18 days for groups G1, G2, G3 and G4 respectively.
There were no statistically significant differences noted for mean gestation length in any of the tested dose groups when compared with the vehicle control group.
Fecundity or Pregnancy Index:
A total of 12 (out of 12), 11 (out of 12), 10 (out of 12) and 11 (out of 12), mated females were confirmed as pregnant / with evidence of implantation sites with a fecundity index of 100.00%, 91.67%, 83.33% and 91.67% from groups G1, G2, G3 and G4 respectively.
There were no statistically significant differences noted for fecundity index in any of the tested dose groups when compared with the vehicle control group.
Gestation Index:
A total of 12 (out of 12), 11 (out of 11), 9 (out of 10) and 10 (out of 11) pregnant females were confirmed with live born pups with a gestation index of 100.00%, 100.00%, 90.00% and 90.91% from groups G1, G2, G3 and G4 respectively.
There were no statistically significant differences noted for gestation index in any of the tested dose groups when compared with the vehicle control group.
Parturition Index:
A total of 12 (out of 12), 11 (out of 11), 10 (out of 10) and 11 (out of 11), pregnant females were confirmed with parturition with a parturition index of 100.0% for all the tested dose groups and vehicle control group.
Implantation sites and Viable pups:
A mean number of 11.50, 10.00, 10.30 and 11.55 implantation sites and mean number of 10.58, 9.55, 9.10 and 9.82 viable pups were noted from groups G1, G2, G3 and G4 respectively.
There were no statistically significant changes noted for both mean implantation sites and viable pups in any of the tested dose groups when compared with the vehicle control group.
Post-implantation loss:
A mean number of 0.92, 0.45, 1.20 and 1.73 post-implantation losses with a percentage of 9.46%, 6.15%, 18.15% and 22.48% were noted from groups G1, G2, G3 and G4 respectively.
In group G3, the increase in mean number of post-implantation losses and its percentage can be due to total implantation loss noted in 1 out of 10 littered dams. The mean number of post-implantation loss is 0.67 with a percentage of 9.06 after excluding the data of the dam with total implantation loss at this dose level which is comparable with vehicle control group. Hence, this noted increase can be considered as incidental.
The increase in post-implantations losses from groups G4 is considered as secondary test item related effects caused due to clinical signs of toxicity and stress induced by the test item exposure. However, there were no statistically significant changes noted as for mean number and percentage of occurred post-implantation losses in any of the tested dose groups when compared with the vehicle control group.
Postnatal Loss:
A mean number of 0.17, 0.00, 0.22 and 1.50 postnatal losses with a percentage of 2.08, 0.00, 1.54 and 22.22 were noted from groups G1, G2, G3 and G4 respectively.
The increase in postnatal loss in group G4 (no. and %) is due to treatment related effects noted in dams, such as clinical signs of toxicity and effects on body weight.
There were no statistically significant changes noted for mean number and percentage of occurred postnatal losses in any of the tested dose groups when compared with the vehicle control group.
In conclusion, there were no adverse effects noted on male and female reproductive performance/indices of adults from the tested dose groups G2 and G3 when compared with vehicle control group.
In group G4, treatment related effects noted on some of the male and female reproductive performance/indices which can be due to stress induce by the test item exposure.

At the dose level of 150 mg/kg body weight/day, the test item did not reveal any adverse systemic toxicity effects except, a minimal reduction in body weights in males. However, there was no indication of reproduction and developmental toxicity at this dose level under experimental conditions employed.

At the dose level of 300 mg/kg body weight/day, animals noted with some effects such as moderately reduced body weights in males, and histopathological findings such as hyperplasia, squamous cell, non-glandular and hyperkeratosis, non-glandular in stomach. There were no test item related effects noted in any of the reproductive and developmental end points at this dose level, except a minimal and not statistically significant increase in post-implantation loss.

At the dose level of 600 mg/kg body weight/day, animals noted with treatment related clinical signs of toxicity, reduced body weights and feed consumption, increased post-implantation loss, increase in postnatal loss and histopathological findings such as hyperplasia, squamous cell, non-glandular and hyperkeratosis, non-glandular in stomach.

In conclusion, there were no adverse effects noted on male and female reproductive performance/indices of adults from the tested dose groups G2 and G3 when compared with vehicle control group.
In group G4, treatment related effects noted on some of the male and female reproductive performance/indices which can be due to stress induce by the test item exposure.

Key result

Dose descriptor:

NOAEL

Effect level:

150 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

mortality

body weight and weight gain

food consumption and compound intake

haematology

organ weights and organ / body weight ratios

gross pathology

histopathology: non-neoplastic

Remarks on result:

other: NOAEL for systemic toxicity

Key result

Dose descriptor:

NOAEL

Effect level:

300 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

reproductive performance

Remarks on result:

other: The effects on reproduction at the dose level of 600 mg/kg body weight/day is considered to be a secondary non-specific consequence of the other toxic effects.

Clinical signs:

no effects observed

Description (incidence and severity):

There were no test item related external abnormalities or behavioural changes noted in any of the pups during daily observation from all the tested dose groups and vehicle control group during postnatal period. All the pups had normal behaviour during daily observations.

Dermal irritation (if dermal study):

not examined

Mortality / viability:

mortality observed, treatment-related

Description (incidence and severity):

A total of 2 out of 127 pups were dead/cannibalized from group G1; a total of 4 out of 91 pups were found dead during lactation day 1 to 4 in group G3; a total of 15 out of 108 pups were found dead during lactation day 1 to 4 in group G4. The noted mortalities in group G3 and G4 can be due to test item induced stress on dams and effects on systemic endpoints in group G4.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

There were no changes noted in mean pup [both male and female] weight per litter in all the tested dose groups when compared with the vehicle control group, recorded on postnatal day (PND) 1, 4, 7 and 13.

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Sexual maturation:

not examined

Anogenital distance (AGD):

effects observed, non-treatment-related

Description (incidence and severity):

There were no changes in mean pup [both male and female] anogenital distance measurement (mm) and its ratio per litter in all the tested dose groups when compared with the vehicle control group, recorded on postnatal day 4. However, statistically significant decrease in mean male pup Anogenital distance and mean Anogenital distance ratio in group G4 was noted when compared with vehicle control group. This noted change is considered as incidental and un-related to treatment as the obtained mean value is within in-house historical control range of same species and strain.

Nipple retention in male pups:

no effects observed

Description (incidence and severity):

There were no occurrences or evidence of retention of nipples in any of the male pups examined on the postnatal day 13 from all the tested dose groups and vehicle control group litters.

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

effects observed, non-treatment-related

Description (incidence and severity):

There were no gross pathological changes observed during conduct of necropsy in any of the F1 pups of both sexes from all tested dose groups, except a single and incidental finding from group G3, where the pup was found dead and noted with discoloration in head region.

Histopathological findings:

not examined

Other effects:

no effects observed

Description (incidence and severity):

There were no changes in mean serum T4 hormone levels of pups at postnatal day 13 in any of the tested dose group litters when compared with vehicle control group litters.

Behaviour (functional findings):

not examined

Developmental immunotoxicity:

not examined

Delivery and Litter observations
In group G2, there were no test item related changes observed in birth parameters such as, total litter size, number of live pups born, sex ratio (m/f) and live birth index when compared with the vehicle control group. The pup survival index per litter during lactation period was unaffected by the test item when compared with the vehicle control group.
In group G3, there were no adverse test item related changes observed in birth parameters such as, total litter size, number of live pups born, sex ratio (m/f) and live birth index when compared with the vehicle control group. However, a minimal reduction in live birth index was noted from this dose level. This reduction is due to noted total litter loss in 1 out of 10 littered females. This can be considered as incidental, and the attained mean live birth index is within the in-house historical control range (In-house historical control range: 80 to 100%). The pup survival index per litter during lactation period was unaffected by the test item when compared with the vehicle control group.
In group G4, there were no changes observed in total litter size and number of live pups born. The live birth index was reduced due to increase in number of dead pups at birth. However, the attained mean live birth index is within the in-house historical control range (In-house historical control range: 80 to 100%). The pup survival index per litter during lactation day 1 to 4 was also reduced at this dose level and this reduction was due to total postnatal loss noted in 2 out of 11 littered dams. These effects are considered as treatment related due to noted clinical signs of toxicity and also due to stress induced by test item exposure. The noted statistically significant decrease in sex ratio at birth in group G4 when compared with the vehicle control group is considered as incidental and un-related to treatment.

Pup observations during Postnatal Period
There were no test item related external abnormalities or behavioural changes noted in any of the pups during daily observation from all the tested dose groups and vehicle control group during postnatal period. All the pups had normal behaviour during daily observations.
A total of 2 out of 127 pups were dead/cannibalized from group G1; a total of 4 out of 91 pups were found dead during lactation day 1 to 4 in group G3; a total of 15 out of 108 pups were found dead during lactation day 1 to 4 in group G4. The noted mortalities in group G3 and G4 can be due to test item induced stress on dams and effects on systemic endpoints in group G4.

Mean Pup Weight per Litter during Postnatal Period
There were no changes noted in mean pup [both male and female] weight per litter in all the tested dose groups when compared with the vehicle control group, recorded on postnatal day (PND) 1, 4, 7 and 13.


Mean Pup Anogenital distance and Anogenital distance Ratio per Litter
There were no changes in mean pup [both male and female] anogenital distance measurement (mm) and its ratio per litter in all the tested dose groups when compared with the vehicle control group, recorded on postnatal day 4. However, statistically significant decrease in mean male pup Anogenital distance in group G4 was noted when compared with vehicle control group. This noted change is considered as incidental and un-related to treatment as the obtained mean value is within in-house historical control range of same species and strain.

Nipple Retention in Male Pups per Litter
There were no occurrences or evidence of retention of nipples in any of the male pups examined on the postnatal day 13 from all the tested dose groups and vehicle control group litters.

Serum Thyroid Hormone (T4) Levels - Postnatal Pups
There were no changes in mean serum T4 hormone levels of pups at postnatal day 13 in any of the tested dose group litters when compared with vehicle control group litters.
Refer: Table 22 (Summary Data) and Appendices 22 (Individual Data)

Key result

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

ca. 300 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other:

Remarks on result:

other: Postnatal loss due to secondary effects (stress induce by the test item exposure)

Key result

Critical effects observed:

no

Key result

Reproductive effects observed:

yes

Lowest effective dose / conc.:

600 mg/kg bw/day

Treatment related:

yes

Relation to other toxic effects:

reproductive effects as a secondary non-specific consequence of other toxic effects

Dose response relationship:

not specified

Relevant for humans:

no

SUMMARY OF THE STUDY

Parameters ↓		Group, Sex & Dose (mg/kg body weight/day)
		G1 & 0	G2 & 150	G3 & 300	G4 & 600
Reproductive Indices
No. of Pairs started		12	12	12	12
Reproductive Performance / Indices (males)
Total No. of males cohabited		12	12	12	12
No. of males with confirmed mating		12	12	11	10
No. of males impregnating/siring a female		12	11	10	10
Male Mating Index (%)		100.00	100.00	91.67	83.33
Male Fertility Index (%)		100.00	91.67	90.91	100.00
Reproductive Performance and Indices (females)
Mean Oestrus cycle length (days)	Mean	4.65	4.53	4.46	4.59
	±SD	0.30	0.17	0.25	0.19
No. of females with regular oestrus cycle		12	12	11	10
Total No. of females cohabited		12	12	12	12
No. of sperm-positive females		12	12	12	12
No. of females with evidence of pregnancy		12	11	10	11
No. of females with live born pups		12	11	9	10
No. of females with conceiving days 1 to 5		11	11	8	7
No. of females with conceiving days >5		1	1	4	5
Pre-coital Interval (Days)	Mean	2.67	3.08	4.75	6.33
	±SD	2.39	3.03	5.05	6.24
Female Mating Index (%)		100.00	100.00	100.00	100.00
Female Fertility Index (%)		100.00	91.67	83.33	91.67
No. of females with Pregnancy≤21 days		2	1	2	2
No. of females with Pregnancy = 22 days		8	6	4	5
No. of females with Pregnancy = 23 days		2	4	4	4
Gestation Length (Days)	Mean	22.00	22.27	22.20	22.18
	±SD	0.60	0.65	0.79	0.75
Female Fecundity or Pregnancy Index (%)		100.00	91.67	83.33	91.67
Gestation Index (%)		100.00	100.00	90.00	90.91
Parturition index (%)		100.00	100.00	100.00	100.00

±SD: Standard deviation; %: Percent; No.: Number; >: Greater than; ≤: less than or equal to; =: Equal to.

 

 

SUMMARY OF THE STUDY (Contd…).

Parameters ↓		Group, Sex & Dose (mg/kg body weight/day)
		G1 & 0	G2 & 150	G3 & 300	G4 & 600
Delivery and Litter Observations
No. of Dams with live young born		12	11	10	11
No. of Dams with live young at PND 4		12	11	9	8
No. of Dams with live young at PND 7		12	11	9	8
No. of Dams with live young at PND 13		12	11	9	8
No. of Implants/dam	Mean	11.50	10.00	10.30	11.55
	±SD	2.47	3.58	3.92	4.41
No. of Live pups/dam at birth	Mean	10.58	9.55	9.10	9.82
	±SD	3.23	3.88	5.20	5.44
No. of Live pups/dam at PND 4	Mean	10.42	9.55	8.90	8.45
	±SD	3.42	3.88	4.95	6.07
No. of Live pups/dam at PND 7	Mean	9.50	9.00	9.22	10.63
	±SD	2.61	3.13	3.42	2.39
No. of Live pups/dam at PND 13	Mean	9.50	9.00	9.22	10.63
	±SD	2.61	3.13	3.42	2.39
Live Birth Index/dam (%)	Mean	100.00	97.79	85.90	81.25
	±SD	0.00	5.00	31.94	33.73
Pup Survival Index/dam on PND 4 (%)	Mean	97.92	100.00	98.46	77.78
	±SD	7.22	0.00	3.14	41.33
Pup Survival Index/dam on PND 7 (%)	Mean	100.00	100.00	100.00	100.00
	±SD	0.00	0.00	0.00	0.00
Pup Survival Index/dam on PND 13 (%)	Mean	100.00	100.00	100.00	100.00
	±SD	0.00	0.00	0.00	0.00
Sex ratio (m/f)/dam At Birth	Mean	1.37	1.12	1.43	0.72
	±SD	1.03	0.48	0.78	0.28
Sex ratio (m/f)/dam at PND 4	Mean	1.37	1.12	1.41	0.74
	±SD	1.03	0.48	0.75	0.27
Sex ratio (m/f)/dam at PND 7	Mean	2.02	1.22	1.60	0.90
	±SD	2.28	0.47	0.76	0.48
Sex ratio (m/f)/dam at PND 13	Mean	2.02	1.22	1.60	0.90
	±SD	2.28	0.47	0.76	0.48

m/f: male/female; No.: Number; PND: Postnatal Day; ±SD: Standard deviation; %: Percent.

 

 

SUMMARY OF THE STUDY (Contd…).

Parameters ↓			Group, Sex & Dose (mg/kg body weight/day)
			G1 & 0	G2 & 150	G3 & 300	G4 & 600
Delivery and Litter Observations
Mean Male Pup weight (g)/dam	At birth	Mean	6.78	6.79	6.79	6.34
		±SD	0.25	0.15	0.30	0.96
	PND 4	Mean	11.43	11.25	11.35	11.07
		±SD	0.49	0.49	0.53	0.57
	PND 7	Mean	15.37	15.26	15.40	15.03
		±SD	0.53	0.59	0.59	0.52
	PND 13	Mean	28.70	28.71	28.74	28.38
		±SD	0.87	0.78	0.84	0.63
Mean Female Pup weight (g)/dam	At Birth	Mean	6.47	6.40	6.43	6.15
		±SD	0.32	0.28	0.28	0.82
	PND 4	Mean	10.68	10.58	10.54	10.62
		±SD	0.40	0.48	0.35	0.67
	PND 7	Mean	14.62	14.52	14.78	14.63
		±SD	0.47	0.73	0.59	0.55
	PND 13	Mean	27.66	27.80	27.89	27.43
		±SD	0.83	0.72	0.66	0.29
Mean Male Pup AGD Measurement/dam (mm) on PND 4		Mean	5.20	5.15	5.10	4.99
		±SD	0.20	0.15	0.21	0.10
Mean Male Pup AGD ratio/dam on PND 4		Mean	2.31	2.30	2.24	2.24
		±SD	0.06	0.04	0.15	0.05
Mean Female Pup AGD Measurement/dam (mm) on PND 4		Mean	2.68	2.68	2.63	2.55
		±SD	0.15	0.20	0.15	0.12
Mean Female Pup AGD ratio/dam on PND 4		Mean	1.22	1.22	1.20	1.16
		±SD	0.06	0.07	0.06	0.04
Male Pup Nipple Retention/dam on PND 13		Mean	0.00	0.00	0.00	0.00
		±SD	0.00	0.00	0.00	0.00

AGD: Anogenital distance; PND: Postnatal Day; ±SD: Standard deviation.

 

 

SUMMARY OF THE STUDY (Contd…).

Parameters ↓		Group, Sex & Dose (mg/kg body weight/day)
		G1 & 0	G2 & 150	G3 & 300	G4 & 600
ABNORMAL PUPS DURING AT BIRTH
No. of Dams with live young born at birth		12	11	9	10
No. of Dams with 0 abnormal live pups		11	11	8	10
No. of Dams with ≥1 abnormal live pup		1	0	1	1
LOSS OF OFFSPRING
Pre-natal or post-implantation loss (implantations minus live births)
No. of Females with 0 post-implantation loss		6	6	5	4
No. of Females with 1 post-implantation loss		2	5	2	3
No. of Females with 2 post-implantation losses		3	0	2	0
No. of Females with 3 post-implantation losses		1	0	0	2
No. of Females with 4 post-implantation losses		0	0	0	1
No. of Females with 6 post-implantation losses		0	0	1	1
Post-implantation Loss (No.)	Mean	0.92	0.45	1.20	1.73
	±SD	1.08	0.52	1.87	2.00
Post-implantation Loss (%)	Mean	9.46	6.15	18.15	22.48
	±SD	12.29	7.58	31.69	33.98
Postnatal loss (live births minus alive at PND 13)
No. of Females with 0 Post-natal Loss		11	11	7	6
No. of Females with 1 Post-natal Loss		0	0	2	2
No. of Females with 2 Post-natal Loss		1	0	0	1
No. of Females with 11 Post-natal Loss		0	0	0	1
Postnatal loss (No.)	Mean	0.17	0.00	0.22	1.50
	±SD	0.58	0.00	0.44	3.41
Postnatal Loss (%)	Mean	2.08	0.00	1.54	22.22
	±SD	7.22	0.00	3.14	41.33

PND: Postnatal Day; ±SD: Standard deviation; ≥: Greater than or equal to; No.: Number; %: Percentage.

 

 

 

 

• SUMMARY OF CLINICAL SIGNS OF TOXICITY AND MORTALITY RECORD

Refer Appendix 1

Group, Sex & Dose (mg/kg body weight/day)	Total No. of Animals	Clinical Signs of Toxicity^a: Observation (No. of Animals revealed)		Mortality^b: No. of Mortalities (Total No. of Animals)
		Pre-dose	Post-dose
G1, M & 0	12	N (12)	N (12)	0 (12)
G2, M & 150	12	N (12)	N (12)	0 (12)
G3, M & 300	12	N (12)	N (12)	0 (12)
G4, M & 600	12	N (12)	6+ (12)	0 (12)

M: Male; N: Normal.

a: observed once daily; b: observed twice daily.

6: Wetness around mouth; +: Slight.

 

 

 

 

TABLE 1 (Contd…). SUMMARY OF CLINICAL SIGNS OF TOXICITY, DETAILED CLINICAL EXAMINATION
AND MORTALITY RECORD

Refer Appendix 1

Group, Sex & Dose (mg/kg body weight/day)	Total No. of Animals	Clinical Signs of Toxicity^a: Observation (No. of Animals revealed)		Mortality^b: No. of Mortalities (Total No. of Animals)
		Pre-dose	Post-dose
G1, F & 0	12	N (12)	N (12)	0 (12)
G2, F & 150	12	N (12)	N (12)	0 (12)
G3, F & 300	12	N (12)	N (12)	0 (12)
G4, F & 600	12	N (10), 1 (2), 82 (2),  116 (1)	6+ (12), 1 (2), 82 (2), 116 (1)	1 (12)

F: Female; N: Normal; NAD: No Abnormality Detected.
a: observed once daily; b: observed twice daily.

6: Wetness around mouth; +: Slight; 1: Lethargy; 82: Peri nasal Staining; 116: Rough hair coat.

 

 

 

 

 

• SUMMARY OF BODY WEIGHT (g) RECORD

   Refer Appendix 2

Group, Sex & Dose (mg/kg body weight/day)		Body Weight (g) on Day
		1	7	14	21	28	35
G1, M & 0	Mean	366.74	386.26	406.21	418.26	430.83	439.80
	±SD	22.32	28.19	33.98	32.17	29.87	33.17
	n	12	12	12	12	12	12
G2, M & 150	Mean	365.58	379.08	383.38	390.28	401.38	413.65
	±SD	21.46	28.35	32.41	30.93	28.18	27.05
	n	12	12	12	12	12	12
G3, M & 300	Mean	367.94	382.03	393.34	395.63	399.89*	404.92*
	±SD	25.28	29.11	32.78	36.99	34.89	34.66
	n	12	12	12	12	12	12
G4, M & 600	Mean	366.63	369.69	372.83*	373.40*	378.10*	379.83*
	±SD	22.08	26.35	31.29	27.44	28.31	29.06
	n	12	12	12	12	12	12

M: Male; SD: Standard Deviation; n: Number of Animals.
* Statistically significant (P<0.05) change than the vehicle control group.

 

 

 

 

 

TABLE 2 (Contd…). SUMMARY OF BODY WEIGHT (g) RECORD

Refer Appendix 2

Group, Sex & Dose (mg/kg body weight/day)		Body Weight (g) on Day
		1	7	14	21^#	28^#
G1, F & 0	Mean	258.75	265.07	271.98	290.01	-
	±SD	9.72	12.05	12.24	-	-
	n	12	12	12	1	-
G2, F & 150	Mean	258.43	265.55	273.91	291.08	-
	±SD	10.91	12.20	13.03	-	-
	n	12	12	12	1	-
G3, F & 300	Mean	259.83	264.42	269.00	285.11	279.42
	±SD	10.65	14.32	14.66	3.70	-
	n	12	12	12	3	1
G4, F & 600	Mean	259.58	266.45	271.14	265.77	290.14
	±SD	11.57	15.72	18.19	23.88	5.47
	n	12	12	12	3	2

F: Female; SD: Standard Deviation; n: Number of Animals.

#: The data obtained from females in cohabitation only considered for mean calculations.

The data of day 21 & 28 body weight was not subjected to statistical analysis due to uneven number of variables.

 

 

 

 

 

• SUMMARY RECORD OF GESTATION BODY WEIGHT (g)

Refer Appendix 3

Group, Sex & Dose (mg/kg body weight/day)		Body Weight (g) on Gestation Day
		0	7	14	20
G1, F & 0	Mean	279.28	296.44	328.88	392.71
	±SD	14.73	16.02	19.45	33.70
	n	12	12	12	12
G2, F & 150	Mean	277.34	294.62	324.67	371.36
	±SD	12.93	12.84	17.97	29.95
	n	11	11	11	11
G3, F & 300	Mean	280.03	294.55	323.78	374.48
	±SD	15.03	17.80	20.86	40.80
	n	10	10	10	10
G4, F & 600	Mean	273.37	288.21	313.29	367.02
	±SD	17.77	17.60	24.95	48.24
	n	11	11	11	11

F: Female; SD: Standard Deviation; n: Number of Dams.

Note: Excluded the data of non-pregnant females for mean calculations and statistical analysis but presented in individual animal data.

 

 

 

• SUMMARY RECORD OF LACTATION BODY WEIGHT (g)

Refer Appendix 4

Group, Sex & Dose (mg/kg body weight/day)		Body Weight (g) on Lactation Day
		1	4	7	13
G1, F & 0	Mean	303.09	308.32	316.87	331.86
	±SD	13.23	13.43	13.25	11.98
	n	12	12	12	12
G2, F & 150	Mean	296.63	299.90	307.99	322.06
	±SD	16.55	18.85	18.76	20.51
	n	11	11	11	11
G3, F & 300	Mean	302.09	305.21	311.05	326.37
	±SD	19.30	16.80	14.89	10.85
	n	10	10	10	10
G4, F & 600	Mean	292.13	290.14	299.99	312.93*
	±SD	16.98	21.53	21.24	25.12
	n	11	11	10	10

F: Female; SD: Standard Deviation; n: Number of Dams.

* Statistically significant (P<0.05) change than the vehicle control group.

Note: One female from group G4 was found dead on lactation day (LD 5).

• SUMMARY OF PERCENT CHANGE IN BODY WEIGHT GAIN (%)
  WITH RESPECT TO DAY 1 RECORD

Refer Appendix 5

Group, Sex & Dose (mg/kg body weight/day)		Percent Change in Body Weight (%) during Day
		1 to 7	1 to 14	1 to 21	1 to 28	1 to 35
G1, M & 0	Mean	5.28	10.67	14.01	17.50	19.92
	±SD	2.72	4.29	4.20	4.51	5.00
	n	12	12	12	12	12
G2, M & 150	Mean	3.63	4.82*	6.72*	9.79*	13.20*
	±SD	3.13	5.40	5.08	4.31	5.05
	n	12	12	12	12	12
G3, M & 300	Mean	3.82	6.92	7.53*	8.75*	10.15*
	±SD	3.11	5.46	6.98	7.21	7.67
	n	12	12	12	12	12
G4, M & 600	Mean	0.80*	1.64*	1.87*	3.16*	3.65*
	±SD	2.95	5.16	5.03	5.58	6.14
	n	12	12	12	12	12

M: Male; SD: Standard Deviation; n: Number of Animals.

* Statistically significant (P<0.05) change than the vehicle control group.

 

 

TABLE 5 (Contd…). SUMMARY OF PERCENT CHANGE IN BODY WEIGHT GAIN (%) WITH RESPECT TO DAY 1 RECORD

Refer Appendix 5

Group, Sex & Dose (mg/kg body weight/day)		Percent Change in Body Weight (%) during Day
		1 to 7	1 to 14	1 to 21^#	1 to 28^#
G1, F & 0	Mean	2.42	5.10	9.52	-
	±SD	1.56	2.16	-	-
	n	12	12	1	-
G2, F & 150	Mean	2.75	5.99	7.12	-
	±SD	1.66	2.04	-	-
	n	12	12	1	-
G3, F & 300	Mean	1.73	3.49	7.94	10.01
	±SD	2.30	2.21	3.47	-
	n	12	12	3	1
G4, F & 600	Mean	2.60	4.38	1.82	7.89
	±SD	2.56	3.31	4.91	5.41
	n	12	12	3	2

F: Female; SD: Standard Deviation; n: Number of Animals.

#: The data obtained from females in cohabitation only considered for mean calculations. The data of day 1 to 21 body weight was not subjected to statistical analysis due to uneven number of variables.

 

 

 

 

 

• SUMMARY RECORD OF PERCENT CHANGE IN BODY WEIGHT GAIN (%) DURING GESTATION PERIOD

Refer Appendix 6

Group, Sex & Dose (mg/kg body weight/day)		Percent Change in Body Weight Gain (%) during Gestation Day
		0 to 7	7 to 14	14 to 20
G1, F & 0	Mean	6.16	10.94	19.32
	±SD	2.03	2.87	6.18
	n	12	12	12
G2, F & 150	Mean	6.25	10.17	14.31
	±SD	1.37	2.60	5.06
	n	11	11	11
G3, F & 300	Mean	5.16	9.92	15.46
	±SD	1.80	2.02	6.58
	n	10	10	10
G4, F & 600	Mean	5.48	8.62	16.83
	±SD	2.61	3.56	8.00
	n	11	11	11

F: Female; SD: Standard Deviation; n: Number of Dams.

Note: Excluded the data of non-pregnant females for mean calculations and statistical analysis but presented in individual animal data.

 

 

 

 

 

• SUMMARY RECORD OF PERCENT CHANGE IN BODY WEIGHT GAIN (%) DURING LACTATION PERIOD

Refer Appendix 7

Group, Sex & Dose (mg/kg body weight/day)		Percent Change in Body Weight Gain (%)  during Lactation Day
		1 to 4	4 to 7	7 to 13
G1, F & 0	Mean	1.74	2.78	4.76
	±SD	1.92	0.63	1.74
	n	12	12	12
G2, F & 150	Mean	1.08	2.71	4.56
	±SD	1.89	0.46	1.23
	n	11	11	11
G3, F & 300	Mean	1.09	1.96	5.01
	±SD	1.62	1.59	2.77
	n	10	10	10
G4, F & 600	Mean	-0.75*	1.94	4.26
	±SD	2.67	1.69	1.69
	n	11	10	10

F: Female; SD: Standard Deviation; n: Number of Dams.

Note: One female from group G4 was found dead on lactation day (LD 5).

* Statistically significant (P<0.05) change than the vehicle control group.

 

 

 

• SUMMARY OF FEED CONSUMPTION (g/animal/day) RECORD

  Refer Appendix 8

Group, Sex & Dose (mg/kg body weight/day)		Feed Consumption (g/animal/day) during Pre-mating Period
		Week 1	Week 2
G1, M & 0	Mean	21.40	24.60
	±SD	2.66	1.34
	n	12 (6)	12 (6)
G2, M & 150	Mean	21.93	24.50
	±SD	2.19	0.86
	n	12 (6)	12 (6)
G3, M & 300	Mean	22.68	23.37
	±SD	1.63	1.21
	n	12 (6)	12 (6)
G4, M & 600	Mean	21.13	23.28
	±SD	1.97	0.94
	n	12 (6)	12 (6)

M: Male; SD: Standard Deviation; n: Number of Animals (Number of Cages).

 

 

 

 

TABLE 8 (Contd…). SUMMARY OF FEED CONSUMPTION (g/animal/day) RECORD

  Refer Appendix 8

Group, Sex & Dose (mg/kg body weight/day)		Feed Consumption (g/animal/day)  during Pre-mating Period
		Week 1	Week 2
G1, F & 0	Mean	18.07	18.30
	±SD	0.96	1.11
	n	12 (6)	12 (6)
G2, F & 150	Mean	18.03	18.15
	±SD	1.24	1.56
	n	12 (6)	12 (6)
G3, F & 300	Mean	17.93	17.68
	±SD	1.30	1.53
	n	12 (6)	12 (6)
G4, F & 600	Mean	17.36	17.07
	±SD	1.19	1.37
	n	12 (6)	12 (6)

F: Female; SD: Standard Deviation; n: Number of Animals (Number of Cages).

 

 

 

• SUMMARY RECORD OF FEED CONSUMPTION (g/animal/day) DURING GESTATION PERIOD

Refer Appendix 9

Group, Sex & Dose (mg/kg body weight/day)		Feed Consumption (g/animal/day) during Gestation Day (GD)
		0 to 7	7 to 14	14 to 20
G1, F & 0	Mean	19.85	21.88	26.70
	±SD	1.31	1.29	1.84
	n	12	12	12
G2, F & 150	Mean	19.73	21.62	25.95
	±SD	0.97	1.41	1.47
	n	11	11	11
G3, F & 300	Mean	19.33	21.67	26.32
	±SD	1.35	1.70	2.08
	n	10	10	10
G4, F & 600	Mean	18.79	20.36*	24.48*
	±SD	1.51	1.38	2.18
	n	11	11	11

F: Female; SD: Standard Deviation; n: Number of Dams.

Note: Excluded the data of non-pregnant females for mean calculations and statistical analysis but presented in individual animal data.

* Statistically significant (P<0.05) change than the vehicle control group.

 

 

• SUMMARY RECORD OF FEED CONSUMTION (g/animal/day) DURING LACTATION PERIOD

Refer Appendix 10

Group, Sex & Dose (mg/kg body weight/day)		Feed Consumption (g/animal/day) during Lactation Day (LD)
		1 to 4	4 to 7	7 to 13
G1, F & 0	Mean	27.67	32.58	41.73
	±SD	1.82	2.16	1.86
	n	12	12	12
G2, F & 150	Mean	28.39	32.99	41.15
	±SD	2.20	1.83	1.27
	n	11	11	11
G3, F & 300	Mean	27.10	32.04	40.94
	±SD	2.54	2.57	2.18
	n	10	10	10
G4, F & 600	Mean	25.93	31.34	40.07
	±SD	3.83	3.77	3.26
	n	11	10	10

F: Female; SD: Standard Deviation; n: Number of Dams.

Note: One female from group G4 was found dead on lactation day (LD 5).

 

• SUMMARY OF HAEMATOLOGY RECORD

Refer Appendix 11

Group, Sex & Dose (mg/kg body weight/day)		Total Leucocyte Count	Total Erythrocyte Count	Hemoglobin	Haematocrit	Mean Corpuscular Volume	Mean Corpuscular Hemoglobin	Mean Corpuscular Hemoglobin Concentration	Platelet Count
		(WBC)	(RBC)	(HGB)	(HCT)	(MCV)	(MCH)	(MCHC)	(PLT)
		(10^3 cells/µL)	(10^6 cells/µL)	(g/dL)	(%)	(fL)	(pg)	(g/dL)	(10^3 cells/µL)
G1, M & 0	Mean	14.50	8.80	16.12	48.28	54.93	18.33	33.37	940.42
	±SD	6.85	0.64	1.23	3.55	3.27	1.01	0.59	274.26
	n	12	12	12	12	12	12	12	12
G2, M & 150	Mean	12.28	8.93	15.58	47.84	53.64	17.45*	32.51	1046.58
	±SD	5.82	0.71	1.42	3.52	1.60	0.63	0.87	175.26
	n	12	12	12	12	12	12	12	12
G3, M & 300	Mean	13.12	8.83	15.83	47.93	54.37	17.97	33.04	970.42
	±SD	3.17	0.49	0.68	1.65	2.20	0.85	1.20	272.35
	n	12	12	12	12	12	12	12	12
G4, M & 600	Mean	10.85	9.15	16.21	48.92	53.57	17.76	33.16	870.75
	±SD	2.38	0.52	0.67	2.78	2.60	0.89	1.13	303.05
	n	12	12	12	12	12	12	12	12

M: Male; SD: Standard Deviation; n: Number of Animals.

* Statistically significant (P<0.05) change than the vehicle control group.

 

 

TABLE 11 (Contd…). SUMMARY OF HAEMATOLOGY RECORD

Refer Appendix 11

Group, Sex & Dose (mg/kg body weight/day)		Mean Platelet Volume	Reticulocyte Count	Neutrophils	Lymphocytes	Monocytes	Eosinophils	Basophils	Absolute Reticulocyte Count
		(MPV)	(Retic)	(Neut)	(Lymph)	(Mono)	(Eos)	(Baso)	(Retic)
		(fL)	(%)	(%)	(%)	(%)	(%)	(%)	(10^9 cells/L)
G1, M & 0	Mean	7.20	3.04	34.35	59.75	3.02	1.20	0.41	259.38
	±SD	0.24	1.84	11.35	12.04	1.13	0.52	0.12	129.15
	n	12	12	12	12	12	12	12	12
G2, M & 150	Mean	7.08	3.36	23.53*	71.46*	2.13	1.46	0.38	298.34
	±SD	0.42	0.62	6.29	5.61	0.76	0.84	0.09	49.66
	n	12	12	12	12	12	12	12	12
G3, M & 300	Mean	7.27	3.01	26.54	68.38*	2.53	1.10	0.38	261.83
	±SD	0.51	1.27	8.16	7.65	0.99	0.59	0.11	89.76
	n	12	12	12	12	12	12	12	12
G4, M & 600	Mean	7.24	3.25	25.14*	69.44*	2.85	1.08	0.34	293.83
	±SD	0.53	1.61	6.23	5.41	1.22	0.42	0.12	139.07
	n	12	12	12	12	12	12	12	12

M: Male; SD: Standard Deviation; n: Number of Animals.

* Statistically significant (P<0.05) change than the vehicle control group.

 

 

TABLE 11 (Contd…). SUMMARY OF HAEMATOLOGY RECORD

Refer Appendix 11

Group, Sex & Dose (mg/kg body weight/day)		Absolute Neutrophils	Absolute Lymphocytes	Absolute Monocytes	Absolute Eosinophils	Absolute Basophils	Prothrombin Time	Activated Prothrombin Time
		(Neut)	(Lymph)	(Mono)	(Eos)	(Baso)	(PT)	(APTT)
		(10^3 cells/µL)	(10^3 cells/µL)	(10^3 cells/µL)	(10^3 cells/µL)	(10^3 cells/µL)	(Seconds)	(Seconds)
G1, M & 0	Mean	5.48	8.12	0.47	0.17	0.06	19.44	18.53
	±SD	4.77	2.48	0.40	0.08	0.03	2.55	5.29
	n	12	12	12	12	12	12	12
G2, M & 150	Mean	2.67*	8.93	0.28	0.22	0.05	20.21	20.21
	±SD	0.61	4.97	0.23	0.30	0.04	2.63	5.46
	n	12	12	12	12	12	12	12
G3, M & 300	Mean	3.42	9.02	0.34	0.14	0.05	22.94*	22.13
	±SD	1.08	2.65	0.17	0.06	0.03	2.71	4.63
	n	12	12	12	12	12	12	12
G4, M & 600	Mean	2.75*	7.52	0.30	0.12	0.04	21.88	20.26
	±SD	0.93	1.73	0.11	0.06	0.02	1.99	9.25
	n	12	12	12	12	12	12	12

M: Male; SD: Standard Deviation; n: Number of Animals.

* Statistically significant (P<0.05) change than the vehicle control group.

 

 

TABLE 11 (Contd…). SUMMARY OF HAEMATOLOGY RECORD

Refer Appendix 11

Group, Sex & Dose (mg/kg body weight/day)		Total Leucocyte Count	Total Erythrocyte Count	Hemoglobin	Haematocrit	Mean Corpuscular Volume	Mean Corpuscular Hemoglobin	Mean Corpuscular Hemoglobin Concentration	Platelet Count
		(WBC)	(RBC)	(HGB)	(HCT)	(MCV)	(MCH)	(MCHC)	(PLT)
		(10^3 cells/µL)	(10^6 cells/µL)	(g/dL)	(%)	(fL)	(pg)	(g/dL)	(10^3 cells/µL)
G1, F & 0	Mean	10.32	7.83	14.93	45.49	58.28	19.13	32.86	1105.50
	±SD	3.70	0.61	1.02	2.83	3.56	1.22	0.96	204.53
	n	12	12	12	12	12	12	12	12
G2, F & 150	Mean	9.66	7.70	14.88	45.42	59.35	19.43	32.76	907.83
	±SD	4.16	0.84	1.00	2.65	4.46	1.24	0.76	288.00
	n	12	12	12	12	12	12	12	12
G3, F & 300	Mean	11.81	7.22	14.15	43.81	61.29	19.73	32.28	1016.75
	±SD	4.20	0.96	1.26	2.57	6.24	1.60	1.21	197.49
	n	12	12	12	12	12	12	12	12
G4, F & 600	Mean	11.70	7.92	15.40	47.00	59.46	19.46	32.77	1118.18
	±SD	3.22	0.44	0.70	2.27	3.83	1.13	0.62	313.07
	n	11	11	11	11	11	11	11	11

F: Female; SD: Standard Deviation; n: Number of Animals.

Note: One female from group G4 was found dead on lactation day (LD 5).

 

 

TABLE 11 (Contd…). SUMMARY OF HAEMATOLOGY RECORD

Refer Appendix 11

Group, Sex & Dose  (mg/kg body weight/day)		Mean Platelet Volume	Reticulocyte Count	Neutrophils	Lymphocytes	Monocytes	Eosinophils	Basophils	Absolute Reticulocyte Count
		(MPV)	(Retic)	(Neut)	(Lymph)	(Mono)	(Eos)	(Baso)	(Retic)
		(fL)	(%)	(%)	(%)	(%)	(%)	(%)	(10^9 cells/L)
G1, F & 0	Mean	7.49	4.23	31.80	60.46	4.18	1.67	0.27	321.19
	±SD	0.35	2.52	7.38	8.94	2.41	1.21	0.08	169.30
	n	12	12	12	12	12	12	12	12
G2, F & 150	Mean	7.78	4.16	28.93	63.97	3.58	1.89	0.27	308.49
	±SD	0.55	2.84	7.38	8.01	1.50	1.33	0.05	179.86
	n	12	12	12	12	12	12	12	12
G3, F & 300	Mean	7.77	6.67	30.85	61.76	3.46	1.18	0.29	392.06
	±SD	0.64	3.81	9.66	10.47	1.63	0.58	0.08	188.05
	n	12	12	12	12	12	12	12	12
G4, F & 600	Mean	7.67	3.49	26.70	67.96	2.55	1.36	0.30	274.01
	±SD	0.36	1.28	9.29	10.15	1.15	1.03	0.09	98.28
	n	11	11	11	11	11	11	11	11

F: Female; SD: Standard Deviation; n: Number of Animals.

Note: One female from group G4 was found dead on lactation day (LD 5).

TABLE 11 (Contd…). SUMMARY OF HAEMATOLOGY RECORD

Refer Appendix 11

Group, Sex & Dose (mg/kg body weight/day)		Absolute Neutrophils	Absolute Lymphocytes	Absolute Monocytes	Absolute Eosinophils	Absolute Basophils	Prothrombin Time	Activated Prothrombin Time
		(Neut)	(Lymph)	(Mono)	(Eos)	(Baso)	(PT)	(APTT)
		(10^3 cells/µL)	(10^3 cells/µL)	(10^3 cells/µL)	(10^3 cells/µL)	(10^3 cells/µL)	(Seconds)	(Seconds)
G1, F & 0	Mean	3.23	6.39	0.36	0.17	0.03	22.38	22.36
	±SD	1.29	2.78	0.11	0.13	0.01	3.14	3.80
	n	12	12	12	12	12	12	12
G2, F & 150	Mean	2.96	6.08	0.32	0.16	0.03	21.63	20.81
	±SD	1.82	2.30	0.12	0.09	0.02	3.31	6.12
	n	12	12	12	12	12	12	12
G3, F & 300	Mean	3.66	7.29	0.42	0.13	0.04	19.93	23.01
	±SD	1.86	2.99	0.25	0.06	0.02	2.65	6.71
	n	12	12	12	12	12	12	12
G4, F & 600	Mean	3.17	7.89	0.32	0.15	0.03	20.48	20.75
	±SD	1.68	2.30	0.21	0.11	0.01	2.01	3.90
	n	11	11	11	11	11	11	11

F: Female; SD: Standard Deviation; n: Number of Animals.

Note: One female from group G4 was found dead on lactation day (LD 5).

 

 

 

• SUMMARY OF VAGINAL SMEAR EXAMINATION RECORD FOR DETERMINATION OF OESTRUS CYCLICITY

Refer Appendix 12

Group, Sex & Dose (mg/kg body weight/day)	Total No. of Females Evaluated	-	No. of Females with Complete Regular Cycles	No. of Females with atleast one Irregular Oestrus Cycle	-	Mean Oestrus Cycle Length (days)
G1, F & 0	12	n	12	-	Mean	4.65
		%	100.00	-	±SD	0.30
					n	12
G2, F & 150	12	n	12	-	Mean	4.53
		%	100.00	-	±SD	0.17
					n	12
G3, F & 300	12	n	11	1	Mean	4.46
		%	91.67	8.33	±SD	0.25
					n	12
G4, F & 600	12	n	10	2	Mean	4.59
		%	83.33	16.67	±SD	0.19
					n	12

F: Female; SD: Standard Deviation; n: Number of Animals; -: Not Applicable.

 

 

 

 

• SUMMARY OF DELIVERY AND LITTER OBSERVATIONS RECORD

Refer Appendix 13

Group & Dose (mg/kg body weight/day)		Delivery Record At birth
		Litter Size (No.)		Live Pups (No.)				Dead Pups (No.)				Cannibalized Pups (No.)					Sex Ratio (m/f) at Birth		Live Birth Index (%)
				Male	Female	Total		Male	Female	Total		Undetermined	Male	Female	Total
G1 & 0	Mean	10.58		5.83	4.75	10.58		0.00	0.00	0.00		0.00	0.00	0.00	0.00		1.37		100.00
	±SD	3.23		2.48	1.42	3.23		0.00	0.00	0.00		0.00	0.00	0.00	0.00		1.03		0.00
	n	12		12	12	12		12	12	12		12	12	12	12		12		12
G2 & 150	Mean	9.73		4.91	4.64	9.55		0.18	0.00	0.18		0.00	0.00	0.00	0.00		1.12		97.79
	±SD	3.80		1.64	2.84	3.88		0.40	0.00	0.40		0.00	0.00	0.00	0.00		0.48		5.00
	n	11		11	11	11		11	11	11		11	11	11	11		10		11
G3 & 300	Mean	10.00		5.00	4.10	9.10		0.60	0.30	0.90		0.00	0.00	0.00	0.00		1.43		85.90
	±SD	4.11		2.36	3.31	5.20		1.26	0.67	1.91		0.00	0.00	0.00	0.00		0.78		31.94
	n	10		10	10	10		10	10	10		10	10	10	10		8		10
G4 & 600	Mean	11.09		4.09	5.73	9.82		0.55	0.73	1.27		0.00	0.00	0.00	0.00		0.72*		81.25
	±SD	4.61		2.51	3.29	5.44		0.82	1.35	2.00		0.00	0.00	0.00	0.00		0.28		33.73
	n	11		11	11	11		11	11	11		11	11	11	11		9		11

SD: Standard Deviation; n: Number of Dams; m/f: Male/Female; %: Percentage.

* Statistically significant (P<0.05) change than the vehicle control group.

 

 

TABLE 13 (Contd…). SUMMARY RECORD OF DELIVERY AND LITTER OBSERVATIONS

Refer Appendix 13

Group & Dose (mg/kg body weight/day)		LD 1 to 4												Sex Ratio (m/f) on LD 4		Pup Survival Index (%) [LD 1 to 4]
		Live Pups (No.)				Dead Pups (No.)				Cannibalized Pups (No.)
		Male	Female	Total		Male	Female	Total		Male	Female	Total
G1 & 0	Mean	5.75	4.67	10.42		0.00	0.08	0.08		0.08	0.00	0.08		1.37		97.92
	±SD	2.56	1.50	3.42		0.00	0.29	0.29		0.29	0.00	0.29		1.03		7.22
	n	12	12	12		12	12	12		12	12	12		12		12
G2 & 150	Mean	4.91	4.64	9.55		0.00	0.00	0.00		0.00	0.00	0.00		1.12		100.00
	±SD	1.64	2.84	3.88		0.00	0.00	0.00		0.00	0.00	0.00		0.48		0.00
	n	11	11	11		11	11	11		11	11	11		10		11
G3 & 300	Mean	4.90	4.00	8.90		0.22	0.22	0.44		0.00	0.00	0.00		1.41		98.46
	±SD	2.23	3.09	4.95		0.44	0.44	0.73		0.00	0.00	0.00		0.75		3.14
	n	10	10	10		9	9	9		9	9	9		8		9
G4 & 600	Mean	3.55	4.91	8.45		0.60	0.90	1.50		0.00	0.00	0.00		0.74		77.78
	±SD	2.77	3.53	6.07		0.97	2.51	3.41		0.00	0.00	0.00		0.27		41.33
	n	11	11	11		10	10	10		10	10	10		8		10

SD: Standard Deviation; n: Number of Dams; LD: Lactation day m/f: Male/Female; %: Percentage.

 

 

 

TABLE 13 (Contd…). SUMMARY RECORD OF DELIVERY AND LITTER OBSERVATIONS

Refer Appendix 13

Group & Dose (mg/kg body weight/day)		Pups Sacrificed for Hormonal analysis (No.)				Live Pups (No.) on LD 4 after sacrifice for Hormonal analysis (No.)				LD 5 to 7												Sex Ratio (m/f) on LD 7		Pup Survival Index (%) [LD 5 to 7]
										Live Pups (No.)				Dead Pups (No.)				Cannibalized (No.)
		Male	Female	Total		Male	Female	Total		Male	Female	Total		Male	Female	Total		Male	Female	Total
G1 & 0	Mean	0.00	0.92	0.92		5.75	3.75	9.50		5.75	3.75	9.50		0.00	0.00	0.00		0.00	0.00	0.00		2.02		100.00
	±SD	0.00	1.00	1.00		2.56	1.14	2.61		2.56	1.14	2.61		0.00	0.00	0.00		0.00	0.00	0.00		2.28		0.00
	n	12	12	12		12	12	12		12	12	12		12	12	12		12	12	12		12		12
G2 & 150	Mean	0.00	0.55	0.55		4.91	4.09	9.00		4.91	4.09	9.00		0.00	0.00	0.00		0.00	0.00	0.00		1.22		100.00
	±SD	0.00	0.93	0.93		1.64	2.21	3.13		1.64	2.21	3.13		0.00	0.00	0.00		0.00	0.00	0.00		0.47		0.00
	n	11	11	11		11	11	11		11	11	11		11	11	11		11	11	11		10		11
G3 & 300	Mean	0.00	0.67	0.67		5.33	3.67	9.00		5.44	3.78	9.22		0.00	0.00	0.00		0.00	0.00	0.00		1.59		100.00
	±SD	0.00	0.87	0.87		1.73	2.50	3.84		1.51	2.33	3.42		0.00	0.00	0.00		0.00	0.00	0.00		0.76		0.00
	n	9	9	9		9	9	9		9	9	9		9	9	9		9	9	9		8		9
G4 & 600	Mean	0.00	1.00	1.00		4.88	5.75	10.63		4.88	5.75	10.63		0.00	0.00	0.00		0.00	0.00	0.00		0.90		100.00
	±SD	0.00	1.07	1.07		1.89	1.39	2.39		1.89	1.39	2.39		0.00	0.00	0.00		0.00	0.00	0.00		0.48		0.00
	n	8	8	8		8	8	8		8	8	8		8	8	8		8	8	8		8		8

SD: Standard Deviation; n: Number of Dams; LD: Lactation Day; m/f: Male/Female; %: Percentage.

 

 

TABLE 13 (Contd…). SUMMARY RECORD OF DELIVERY AND LITTER OBSERVATIONS

Refer Appendix 13

Group & Dose (mg/kg body weight/day)		LD 8 to 13												Sex Ratio (m/f) on LD 13		Pup Survival Index (%) [LD 8 to 13]
		Live Pups (No.)				Dead Pups (No.)				Cannibalized (No.)
		Male	Female	Total		Male	Female	Total		Male	Female	Total
G1 & 0	Mean	5.75	3.75	9.50		0.00	0.00	0.00		0.00	0.00	0.00		2.02		100.00
	±SD	2.56	1.14	2.61		0.00	0.00	0.00		0.00	0.00	0.00		2.28		0.00
	n	12	12	12		12	12	12		12	12	12		12		12
G2 & 150	Mean	4.91	4.09	9.00		0.00	0.00	0.00		0.00	0.00	0.00		1.22		100.00
	±SD	1.64	2.21	3.13		0.00	0.00	0.00		0.00	0.00	0.00		0.47		0.00
	n	11	11	11		12	12	12		12	12	12		10		11
G3 & 300	Mean	5.44	3.78	9.22		0.00	0.00	0.00		0.00	0.00	0.00		1.59		100.00
	±SD	1.51	2.33	3.42		0.00	0.00	0.00		0.00	0.00	0.00		0.76		0.00
	n	9	9	9		9	9	9		9	9	9		8		9
G4 & 600	Mean	4.88	5.75	10.63		0.00	0.00	0.00		0.00	0.00	0.00		0.90		100.00
	±SD	1.89	1.39	2.39		0.00	0.00	0.00		0.00	0.00	0.00		0.48		0.00
	n	8	8	8		8	8	8		8	8	8		8		8

SD: Standard Deviation; n: Number of Dams; LD: Lactation Day; m/f: Male/Female; %: Percentage.

 

 

 

• SUMMARY RECORD OF REPRODUCTIVE PERFORMANCE

Refer Appendix 14

Group, Sex & Dose (mg/kg body weight/day)	No. of Males with Evidence of Mating (No. of Males used for Mating)	Male Mating Index (%)		No. of Males Capable of Impregnating a Female (No. of males used for Mating)	Male Fertility Index (%)
G1, M & 0	12 (12)	100.00		12 (12)	100.00
G2, M & 150	12 (12)	100.00		11 (12)	91.67
G3, M & 300	11 (12)	91.67		10 (11)	90.91
G4, M & 600	10 (12)	83.33		10 (10)	100.00

M: Male.

 

 

TABLE 14 (Contd…). SUMMARY RECORD OF REPRODUCTIVE PERFORMANCE

Refer Appendix 14

Group, Sex & Dose (mg/kg body weight/day)		Cohabitation Record and Pre-coital Interval (Mean Time of Mating)					Gestational Length (duration of pregnancy)
		Pre-coital Interval (Days)		Conceiving Days (1 to 5)	Conceiving Days (More than 5 days)		Gestation Length (Days)
G1, F & 0	Mean	2.67	N	11	1		22.00
	±SD	2.39	%	91.67	8.33		0.60
	n	12					12
G2, F & 150	Mean	3.08	N	11	1		22.27
	±SD	3.03	%	91.67	8.33		0.65
	n	12					11
G3, F & 300	Mean	4.75	N	8	4		22.20
	±SD	5.05	%	66.67	33.33		0.79
	n	12					10
G4, F & 600	Mean	6.33	N	7	5		22.18
	±SD	6.24	%	58.33	41.67		0.75
	n	12					11

F: Female; SD: Standard Deviation.

N: Number of females evaluated for pre-coital interval; n: Number of females (for pre-coital interval); n: Number of pregnants (for gestation length).

 

 

 

TABLE 14 (Contd…). SUMMARY RECORD OF REPRODUCTIVE PERFORMANCE

Refer Appendix 14

Group, Sex & Dose (mg/kg body weight/day)	Female Mating Index (%)			Female Fertility Index (%)
	No. of Females with Evidence of Mating (No. of Females used for Mating)	Female Mating Index (%)		No. of Females Confirmed as Fertile (No. of Females used for Mating)	Female Fertility Index (%)
G1, F & 0	12 (12)	100.00		12 (12)	100.00
G2, F & 150	12 (12)	100.00		11 (12)	91.67
G3, F & 300	12 (12)	100.00		10 (12)	83.33
G4, F & 600	12 (12)	100.00		11 (12)	91.67

F: Female.

 

 

TABLE 14 (Contd…). SUMMARY RECORD OF REPRODUCTIVE PERFORMANCE

Refer Appendix 14

Group, Sex & Dose                                      (mg/kg body weight/day)	Female Fecundity or Pregnancy Index (%)		Gestation Index (%)		Parturition index (%)
	No. of Pregnant Females (No. of Females Confirmed with Mating)	Female Fecundity or Pregnancy Index (%)	Females with Live Born Pups at Parturition (No. of Females with Evidence of Pregnancy)	Gestation Index (%)	No. of Females Littered  (No. of Females with evidence of pregnancy)	Parturition index (%)
G1, F & 0	12 (12)	100.00	12 (12)	100.00	12 (12)	100.00
G2, F & 150	11 (12)	91.67	11 (11)	100.00	11 (11)	100.00
G3, F & 300	10 (12)	83.33	9 (10)	90.00	10 (10)	100.00
G4, F & 600	11 (12)	91.67	10 (11)	90.91	11 (11)	100.00

F: Female.

 

 

TABLE 14 (Contd…). SUMMARY RECORD OF REPRODUCTIVE PERFORMANCE

Refer Appendix 14

Group, Sex & Dose (mg/kg body weight/day)		Post-implantation Loss					Post-natal Loss
		No. of Implantations	No. of Viable (Live) Pups	Post-implantation Loss (No.)	Post-implantation Loss (%)		Total No. of Pups Found Dead/ Cannibalized during lactation period	Post-natal Loss (%)
G1, F & 0	Mean	11.50	10.58	0.92	9.46		0.17	2.08
	±SD	2.47	3.23	1.08	12.29		0.58	7.22
	n	12	12	12	12		12	12
G2, F & 150	Mean	10.00	9.55	0.45	6.15		0.00	0.00
	±SD	3.58	3.88	0.52	7.58		0.00	0.00
	n	11	11	11	11		11	11
G3, F & 300	Mean	10.30	9.10	1.20	18.15		0.22	1.54
	±SD	3.92	5.20	1.87	31.69		0.44	3.14
	n	10	10	10	10		9	9
G4, F & 600	Mean	11.55	9.82	1.73	22.48		1.50	22.22
	±SD	4.41	5.44	2.00	33.98		3.41	41.33
	n	11	11	11	11		10	10

F: Female; n: Number of Dams; SD: Standard deviation.

 

 

• SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD

Refer Appendix 15

Group, Sex & Dose (mg/kg body weight/day)		Testes	Epididymides	Kidneys	Prostate	Seminal vesicles with coagulating glands	Thyroid along with parathyroid^WP
G1, M & 0	Mean	3.5167	1.4480	2.7957	1.3934	1.5711	0.0278
	±SD	0.2711	0.1446	0.3097	0.3304	0.4393	0.0056
	n	12	12	12	12	12	12
G2, M & 150	Mean	3.2816	1.4650	2.5982	1.2479	1.5978	0.0270
	±SD	0.3615	0.1751	0.2982	0.3783	0.5457	0.0081
	n	12	12	12	12	12	12
G3, M & 300	Mean	3.4600	1.4427	2.6737	1.3600	1.2867	0.0278
	±SD	0.1846	0.1390	0.3206	0.3427	0.5705	0.0090
	n	12	12	12	12	12	12
G4, M & 600	Mean	3.3491	1.3851	2.4600*	1.1554	1.0562*	0.0276
	±SD	0.2924	0.1634	0.2912	0.4617	0.3505	0.0080
	n	12	12	12	12	12	12

M: Male; SD: Standard Deviation; n: Number of Animals; WP: Weighed post fixation.

* Statistically significant (P<0.05) change than the vehicle control group.

 

 

TABLE 15 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD

 Refer Appendix 15

Group, Sex & Dose  (mg/kg body weight/day)		Ovaries	Uterus with cervix	Kidneys	Thyroid along with parathyroid^WP
G1, F & 0	Mean	0.1376	0.5899	1.9210	0.0328
	±SD	0.0206	0.1406	0.2379	0.0050
	n	12	12	12	12
G2, F & 150	Mean	0.1408	0.5771	1.8349	0.0222*
	±SD	0.0185	0.1734	0.2129	0.0047
	n	12	12	12	12
G3, F & 300	Mean	0.1301	0.5680	1.8861	0.0231*
	±SD	0.0147	0.0962	0.1785	0.0047
	n	12	12	12	12
G4, F & 600	Mean	0.1407	0.5646	1.9393	0.0204*
	±SD	0.0227	0.1826	0.2642	0.0065
	n	11	11	11	11

F: Female; SD: Standard Deviation; n: Number of Animals; WP: Weighed post fixation.

Note: One female from group G4 was found dead on lactation day (LD 5).

* Statistically significant (P<0.05) change than the vehicle control group.

 

 

• SUMMARY OF TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
  TERMINAL BODY WEIGHT (%) RECORD

Refer Appendix 16

Group, Sex & Dose (mg/kg body weight/day)		Terminal Body Weight (g)	Testes	Epididymides	Kidneys	Prostate	Seminal vesicles with coagulating glands	Thyroid along with parathyroid
G1, M & 0	Mean	421.70	0.8392	0.3445	0.6623	0.3291	0.3736	0.0066
	±SD	32.95	0.0973	0.0360	0.0392	0.0684	0.1050	0.0014
	n	12	12	12	12	12	12	12
G2, M & 150	Mean	393.03	0.8346	0.3727	0.6612	0.3200	0.4043	0.0068
	±SD	24.85	0.0732	0.0368	0.0622	0.1015	0.1287	0.0019
	n	12	12	12	12	12	12	12
G3, M & 300	Mean	386.45*	0.9022	0.3751	0.6916	0.3516	0.3378	0.0072
	±SD	34.48	0.0969	0.0422	0.0485	0.0782	0.1585	0.0024
	n	12	12	12	12	12	12	12
G4, M & 600	Mean	359.44*	0.9341*	0.3868*	0.6837	0.3219	0.2958	0.0077
	±SD	27.77	0.0794	0.0486	0.0511	0.1318	0.1006	0.0021
	n	12	12	12	12	12	12	12

M: Male; SD: Standard Deviation; n: Number of Animals.

* Statistically significant (P<0.05) change than the vehicle control group.

 

 

TABLE 16 (Contd…). SUMMARY OF TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD

Refer Appendix 16

Group, Sex & Dose (mg/kg body weight/day)		Terminal Body Weight (g)	Ovaries	Uterus with cervix	Kidneys	Thyroid along with parathyroid
G1, F & 0	Mean	315.07	0.0437	0.1874	0.6094	0.0104
	±SD	11.11	0.0064	0.0457	0.0687	0.0016
	n	12	12	12	12	12
G2, F & 150	Mean	305.52	0.0461	0.1875	0.6011	0.0073*
	±SD	18.23	0.0056	0.0495	0.0654	0.0014
	n	12	12	12	12	12
G3, F & 300	Mean	304.61	0.0428	0.1882	0.6236	0.0076*
	±SD	21.37	0.0051	0.0401	0.0923	0.0018
	n	12	12	12	12	12
G4, F & 600	Mean	299.44	0.0473	0.1932	0.6476	0.0068*
	±SD	25.80	0.0087	0.0769	0.0657	0.0021
	n	11	11	11	11	11

F: Female; SD: Standard Deviation; n: Number of Animals.

Note: One female from group G4 was found dead on lactation day (LD 5).

* Statistically significant (P<0.05) change than the vehicle control group.

 

• SUMMARY OF SERUM T4 HORMONE LEVELS (ng/mL) RECORD - ADULTS

Refer Appendix 17

Group, Sex & Dose (mg/kg body weight/day)		Serum T4 Levels (ng/mL)
G1, M & 0	Mean	75.850
	±SD	6.853
	n	12
G2, M & 150	Mean	78.693
	±SD	8.670
	n	12
G3, M & 300	Mean	72.972
	±SD	4.821
	n	12
G4, M & 600	Mean	68.263*
	±SD	5.591
	n	12

M: Male; SD: Standard Deviation; n: Number of Animals; ng/mL: Nanogram per milliliter.

* Statistically significant (P<0.05) change than the vehicle control group.

 

 

 

 

 

• SUMMARY RECORD OF PUP OBSERVATIONS DURING POSTNATAL PERIOD

Refer Appendix 18

Group & Dose (mg/kg body weight/day)		At Birth (PND 1)	PND 1 to 4	Pups Sacrificed for Blood Collection on PND 4 (No.) *	PND 5 to 7^$	PND 8 to 13^$
G1 & 0	No. of Dams^#	12	12	6	12	12
	No. of Live Pups	127	125	11	114	114
	Pup Observation/ No. of Pups observed	N/126, P/1	N/125, D/1, C/1, P/1	-	N/114	N/114
G2 & 150	No. of Dams^#	11	11	3	11	11
	No. of Live Pups	105	105	6	99	99
	Pup Observation/ No. of Pups observed	N/105	N/105	-	N/99	N/99
G3 & 300	No. of Dams^#	10	10	4	10	10
	No. of Live Pups	91	87	6	81	81
	Pup Observation/ No. of Pups observed	N/91	N/87, D/4	-	N/81	N/81
G4 & 600	No. of Dams^#	11	8	4	8	8
	No. of Live Pups	108	93	8	85	85
	Pup Observation/ No. of Pups observed	N/108	N/93, D/15	-	N/85	N/85

N: Normal; PND: Postnatal Day; #: Dams confirmed with littering.

*: Pups selected for blood collection from dams with litter size of more than 10; $: Pups sacrificed on PND 4 were excluded.

D: Dead; C: Cannibalized; P: Pale coloured.

• SUMMARY RECORD OF MEAN PUP WEIGHT (g) PER LITTER

Refer Appendix 19

Group & Dose (mg/kg body weight/day)		PND 1			PND 4			PND 7			PND 13
		Mean Male Pup Weight (g)	Mean Female Pup Weight (g)		Mean Male Pup Weight (g)	Mean Female Pup Weight (g)		Mean Male Pup Weight (g)	Mean Female Pup Weight (g)		Mean Male Pup Weight (g)	Mean Female Pup Weight (g)
G1 & 0	Mean	6.78	6.47		11.43	10.68		15.37	14.62		28.70	27.66
	±SD	0.25	0.32		0.49	0.40		0.53	0.47		0.87	0.83
	n	12	12		12	12		12	12		12	12
G2 & 150	Mean	6.79	6.40		11.25	10.58		15.26	14.52		28.71	27.80
	±SD	0.15	0.28		0.49	0.48		0.59	0.73		0.78	0.72
	n	11	10		11	10		11	10		11	10
G3 & 300	Mean	6.79	6.43		11.35	10.54		15.40	14.78		28.74	27.89
	±SD	0.30	0.28		0.53	0.35		0.59	0.59		0.84	0.66
	n	9	8		9	8		9	8		9	8
G4 & 600	Mean	6.34	6.15		11.07	10.62		15.03	14.63		28.38	27.43
	±SD	0.96	0.82		0.57	0.67		0.52	0.55		0.63	0.29
	n	10	9		8	8		8	8		8	8

SD: Standard Deviation; n: Number of Litters; PND: Postnatal Day.

 

• SUMMARY RECORD OF MEAN PUP ANOGENITAL DISTANCE (AGD) MEASUREMENT (mm) AND ANOGENITAL DISTANCE (AGD) RATIO PER LITTER ON POSTNATAL DAY 4

Refer Appendix 20

Group & Dose (mg/kg body weight/day)		AGD Measurement (mm)			AGD Ratio
		Male	Female		Male	Female
G1 & 0	Mean	5.20	2.68		2.31	1.22
	±SD	0.20	0.15		0.06	0.06
	n	12	12		12	12
G2 & 150	Mean	5.15	2.68		2.30	1.22
	±SD	0.15	0.20		0.04	0.07
	n	11	10		11	10
G3 & 300	Mean	5.10	2.63		2.24	1.20
	±SD	0.21	0.15		0.15	0.06
	n	9	8		9	8
G4 & 600	Mean	4.99*	2.55		2.24	1.16
	±SD	0.10	0.12		0.05	0.04
	n	8	8		8	8

SD: Standard Deviation; n: Number of Litters; AGD: Anogenital Distance; mm: Millimetre.

* Statistically significant (P<0.05) change than the vehicle control group.

 

 

• SUMMARY RECORD OF OBSERVATION OF MALE PUPS FOR RETENTION OF NIPPLE/AREOLAE (No.) RECORD

Refer Appendix 21

Group & Dose (mg/kg body weight/day)		Mean No. of Pups with Retention of Nipples/ Areolae on Postnatal Day 13
G1 & 0	Mean	0.00
	±SD	0.00
	n	12 (69)
G2 & 150	Mean	0.00
	±SD	0.00
	n	11 (54)
G3 & 300	Mean	0.00
	±SD	0.00
	n	9 (48)
G4 & 600	Mean	0.00
	±SD	0.00
	n	8 (39)

SD: Standard Deviation; n: Number of Litters (number of male pups).

 

 

 

 

• SUMMARY OF SERUM T4 HORMONE LEVELS (ng/mL) RECORD - POSTNATAL DAY (PND) 13 PUPS

Refer Appendix 22

Group & Dose (mg/kg body weight/day)		Serum T4 Levels (ng/mL)
G1 & 0	Mean	70.116
	±SD	6.744
	n	12
G2 & 150	Mean	70.333
	±SD	5.589
	n	11
G3 & 300	Mean	68.587
	±SD	4.778
	n	9
G4 & 600	Mean	67.837
	±SD	9.360
	n	8

SD: Standard Deviation; n: Number of Litters; PND: Postnatal Day; ng/mL: Nanogram per milliliter

• INDIVIDUAL ANIMAL CLINICAL SIGNS OF TOXICITY AND MORTALITY RECORD

Group, Sex & Dose (mg/kg body weight/day)

Animal No.

Clinical Signs of Toxicity and Mortality Record on Day

1

2

3

4^Pr

4^Po

5^Pr

5^Po

6^Pr

6^Po

7^Pr

7^Po

8^Pr

8^Po

9^Pr

9^Po

10^Pr

10^Po

G1, M & 0

Rg7881

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7882

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7883

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7884

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7885

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7886

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7887

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7888

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7889

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7890

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7891

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7892

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

G2, M & 150

Rg7893

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7894

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7895

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7896

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7897

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7898

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7899

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7900

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7901

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7902

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7903

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7904

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

M: Male; N: Normal; Pr: Pre-dose; Po: Post-dose.

 

 

APPENDIX 1 (Contd…). INDIVIDUAL ANIMAL CLINICAL SIGNS OF TOXICITY AND MORTALITY RECORD

Group, Sex & Dose (mg/kg body weight/day)

Animal No.

Clinical Signs of Toxicity and Mortality Record on Day

11^Pr

11^Po

12^Pr

12^Po

13^Pr

13^Po

14^Pr

14^Po

15^Pr

15^Po

16^Pr

16^Po

17^Pr

17^Po

18^Pr

18^Po

19^Pr

19^Po

20^Pr

20^Po

G1, M & 0

Rg7881

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7882

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7883

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7884

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7885

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7886

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7887

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7888

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7889

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7890

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7891

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7892

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

G2, M & 150

Rg7893

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7894

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7895

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7896

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7897

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7898

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7899

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7900

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7901

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7902

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7903

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7904

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

M: Male; N: Normal; Pr: Pre-dose; Po: Post-dose.

 

APPENDIX 1 (Contd…). INDIVIDUAL ANIMAL CLINICAL SIGNS OF TOXICITY AND MORTALITY RECORD

Group, Sex & Dose (mg/kg body weight/day)

Animal No.

Clinical Signs of Toxicity and Mortality Record on Day

21^Pr

21^Po

22^Pr

22^Po

23^Pr

23^Po

24^Pr

24^Po

25^Pr

25^Po

26^Pr

26^Po

27^Pr

27^Po

28^Pr

28^Po

G1, M & 0

Rg7881

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7882

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7883

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7884

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7885

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7886

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7887

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7888

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7889

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7890

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7891

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7892

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

G2, M & 150

Rg7893

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7894

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7895

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7896

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7897

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7898

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7899

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7900

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7901

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7902

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7903

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7904

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

M: Male; N: Normal; Pr: Pre-dose; Po: Post-dose.

 

APPENDIX 1 (Contd…). INDIVIDUAL ANIMAL CLINICAL SIGNS OF TOXICITY AND MORTALITY RECORD

Group, Sex & Dose (mg/kg body weight/day)

Animal No.

Clinical Signs of Toxicity and Mortality Record on Day

29^Pr

29^Po

30^Pr

30^Po

31^Pr

31^Po

32^Pr

32^Po

33^Pr

33^Po

34^Pr

34^Po

35^Pr

35^Po

36^T

G1, M & 0

Rg7881

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7882

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7883

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7884

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7885

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7886

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7887

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7888

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7889

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7890

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7891

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7892

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

G2, M & 150

Rg7893

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7894

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7895

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7896

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7897

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7898

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7899

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7900

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7901

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7902

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7903

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7904

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

M: Male; N: Normal; Pr: Pre-dose; Po: Post-dose: T: Day of termination.

 

 

APPENDIX 1 (Contd…). INDIVIDUAL ANIMAL CLINICAL SIGNS OF TOXICITY AND MORTALITY RECORD

Group, Sex & Dose (mg/kg body weight/day)

Animal No.

Clinical Signs of Toxicity and Mortality Record on Day

1

2

3

4^Pr

4^Po

5^Pr

5^Po

6^Pr

6^Po

7^Pr

7^Po

8^Pr

8^Po

9^Pr

9^Po

10^Pr

10^Po

G3, M & 300

Rg7905

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7906

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7907

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7908

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7909

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7910

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7911

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7912

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7913

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7914

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7915

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7916

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

G4, M & 600

Rg7917

N

N

N

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7918

N

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7919

N

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7920

N

N

N

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7921

N

N

N

N

N

N

N

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7922

N

N

N

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7923

N

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7924

N

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7925

N

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7926

N

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7927

N

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7928

N

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

M: Male; N: Normal; Pr: Pre-dose; Po: Post-dose.

6: Wetness around mouth; +: Slight.

 

APPENDIX 1 (Contd…). INDIVIDUAL ANIMAL CLINICAL SIGNS OF TOXICITY AND MORTALITY RECORD

Group, Sex & Dose (mg/kg body weight/day)

Animal No.

Clinical Signs of Toxicity and Mortality Record on Day

11^Pr

11^Po

12^Pr

12^Po

13^Pr

13^Po

14^Pr

14^Po

15^Pr

15^Po

16^Pr

16^Po

17^Pr

17^Po

18^Pr

18^Po

19^Pr

19^Po

20^Pr

20^Po

G3, M & 300

Rg7905

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7906

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7907

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7908

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7909

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7910

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7911

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7912

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7913

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7914

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7915

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7916

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

G4, M & 600

Rg7917

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7918

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7919

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7920

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7921

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7922

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7923

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7924

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7925

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7926

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7927

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7928

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

M: Male; N: Normal; Pr: Pre-dose; Po: Post-dose.

6: Wetness around mouth; +: Slight.

 

APPENDIX 1 (Contd…). INDIVIDUAL ANIMAL CLINICAL SIGNS OF TOXICITY AND MORTALITY RECORD

Group, Sex & Dose (mg/kg body weight/day)

Animal No.

Clinical Signs of Toxicity and Mortality Record on Day

21^Pr

21^Po

22^Pr

22^Po

23^Pr

23^Po

24^Pr

24^Po

25^Pr

25^Po

26^Pr

26^Po

27^Pr

27^Po

28^Pr

28^Po

G3, M & 300

Rg7905

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7906

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7907

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7908

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7909

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7910

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7911

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7912

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7913

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7914

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7915

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7916

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

G4, M & 600

Rg7917

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7918

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7919

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7920

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7921

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7922

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7923

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7924

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7925

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7926

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7927

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7928

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

M: Male; N: Normal; Pr: Pre-dose; Po: Post-dose.

6: Wetness around mouth; +: Slight.

 

APPENDIX 1 (Contd…). INDIVIDUAL ANIMAL CLINICAL SIGNS OF TOXICITY AND MORTALITY RECORD

Group, Sex & Dose (mg/kg body weight/day)

Animal No.

Clinical Signs of Toxicity and Mortality Record on Day

29^Pr

29^Po

30^Pr

30^Po

31^Pr

31^Po

32^Pr

32^Po

33^Pr

33^Po

34^Pr

34^Po

35^Pr

35^Po

36^T

G3, M & 300

Rg7905

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7906

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7907

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7908

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7909

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7910

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7911

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7912

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7913

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7914

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7915

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7916

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

G4, M & 600

Rg7917

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

Rg7918

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

Rg7919

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

Rg7920

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

Rg7921

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

Rg7922

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

Rg7923

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

Rg7924

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

Rg7925

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

Rg7926

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

Rg7927

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

Rg7928

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

M: Male; N: Normal; Pr: Pre-dose; Po: Post-dose; T: Day of termination.

6: Wetness around mouth; +: Slight.

 

APPENDIX 1 (Contd…). INDIVIDUAL ANIMAL CLINICAL SIGNS OF TOXICITY AND MORTALITY RECORD

Group, Sex & Dose (mg/kg body weight/day)

Animal No.

Clinical Signs of Toxicity and Mortality Record on Day

1

2

3

4^Pr

4^Po

5^Pr

5^Po

6^Pr

6^Po

7^Pr

7^Po

8^Pr

8^Po

9^Pr

9^Po

10^Pr

10^Po

G1, F & 0

Rg7929

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7930

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7931

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7932

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7933

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7934

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7935

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7936

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7937

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7938

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7939

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7940

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

G2, F & 150

Rg7941

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7942

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7943

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7944

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7945

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7946

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7947

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7948

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7949^NP

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7950

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7951

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7952

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

F: Female; N: Normal; Pr: Pre-dose; Po: Post-dose; NP: Non-pregnant.

 

 

APPENDIX 1 (Contd…). INDIVIDUAL ANIMAL CLINICAL SIGNS OF TOXICITY AND MORTALITY RECORD

Group, Sex & Dose (mg/kg body weight/day)

Animal No.

Clinical Signs of Toxicity and Mortality Record on Day

11^Pr

11^Po

12^Pr

12^Po

13^Pr

13^Po

14^Pr

14^Po

15^Pr

15^Po

16^Pr

16^Po

17^Pr

17^Po

18^Pr

18^Po

19^Pr

19^Po

20^Pr

20^Po

G1, F & 0

Rg7929

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7930

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7931

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7932

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7933

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7934

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7935

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7936

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7937

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7938

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7939

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7940

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

G2, F & 150

Rg7941

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7942

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7943

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7944

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7945

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7946

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7947

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7948

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7949^NP

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7950

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7951

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7952

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

F: Female; N: Normal; Pr: Pre-dose; Po: Post-dose; NP: Non-pregnant.

 

APPENDIX 1 (Contd…). INDIVIDUAL ANIMAL CLINICAL SIGNS OF TOXICITY AND MORTALITY RECORD

Group, Sex & Dose (mg/kg body weight/day)

Animal No.

Clinical Signs of Toxicity and Mortality Record on Day

21^Pr

21^Po

22^Pr

22^Po

23^Pr

23^Po

24^Pr

24^Po

25^Pr

25^Po

26^Pr

26^Po

27^Pr

27^Po

28^Pr

28^Po

29^Pr

29^Po

30^Pr

30^Po

G1, F & 0

Rg7929

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7930

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7931

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7932

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7933

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7934

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7935

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7936

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7937

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7938

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7939

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7940

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

G2, F & 150

Rg7941

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7942

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7943

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7944

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7945

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7946

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7947

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7948

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7949^NP

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7950

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7951

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7952

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

F: Female; N: Normal; Pr: Pre-dose; Po: Post-dose; NP: Non-pregnant.

 

APPENDIX 1 (Contd…). INDIVIDUAL ANIMAL CLINICAL SIGNS OF TOXICITY AND MORTALITY RECORD

Group, Sex & Dose (mg/kg body weight/day)

Animal No.

Clinical Signs of Toxicity and Mortality Record on Day

31^Pr

31^Po

32^Pr

32^Po

33^Pr

33^Po

34^Pr

34^Po

35^Pr

35^Po

36^Pr

36^Po

37^Pr

37^Po

38^Pr

38^Po

39^Pr

39^Po

40^Pr

40^Po

G1, F & 0

Rg7929

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7930

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7931

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7932

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7933

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7934

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7935

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7936

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7937

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7938

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7939

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7940

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

G2, F & 150

Rg7941

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7942

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7943

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7944

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7945

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7946

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7947

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7948

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7949^NP

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7950

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7951

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7952

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

F: Female; N: Normal; Pr: Pre-dose; Po: Post-dose; NP: Non-pregnant.

 

 

APPENDIX 1 (Contd…). INDIVIDUAL ANIMAL CLINICAL SIGNS OF TOXICITY AND MORTALITY RECORD

Group, Sex & Dose (mg/kg body weight/day)

Animal No.

Clinical Signs of Toxicity and Mortality Record on Day

41^Pr

41^Po

42^Pr

42^Po

43^Pr

43^Po

44^Pr

44^Po

45^Pr

45^Po

46^Pr

46^Po

47^Pr

47^Po

48^Pr

48^Po

49^Pr

49^Po

50^Pr

50^Po

G1, F & 0

Rg7929

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

-

Rg7930

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7931

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7932

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

-

Rg7933

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7934

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7935

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7936

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7937

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7938

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7939

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

-

Rg7940

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

G2, F & 150

Rg7941

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

-

Rg7942

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7943

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7944

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7945

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7946

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7947

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7948

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

-

Rg7949^NP

N

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Rg7950

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7951

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7952

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

F: Female; N: Normal; Pr: Pre-dose; Po: Post-dose; -: Not applicable.

NP: Non-pregnant (sacrificed after 24 days from the day of confirmation of mating and found as non-pregnant).

Note: All the littered females were observed until termination i.e., up to lactation day 14.

APPENDIX 1 (Contd…). INDIVIDUAL ANIMAL CLINICAL SIGNS OF TOXICITY AND MORTALITY RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Clinical Signs of Toxicity and Mortality Record on Day
		51^Pr	51^Po	52^Pr	52^Po	53^Pr	53^Po	54^Pr	54^Po	55^Pr	55^Po	56^Pr	56^Po	57^Pr	57^Po	58^Pr	58^Po	59^Pr	59^Po	60^Pr	60^Po	61
G1, F & 0	Rg7929	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7930	N	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7931	N	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7932	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7933	N	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7934	N	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7935	N	N	N	N	N	N	N	N	N	N	N	N	N	N	N	-	-	-	-	-	-
	Rg7936	N	N	N	N	N	N	N	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7937	N	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7938	N	N	N	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7939	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7940	N	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
G2, F & 150	Rg7941	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7942	N	N	N	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7943	N	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7944	N	N	N	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7945	N	N	N	N	N	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7946	N	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7947	N	N	N	N	N	N	N	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7948	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7949^NP	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7950	N	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7951	N	N	N	N	N	N	N	N	N	N	N	N	N	N	N	N	N	N	N	N	N
	Rg7952	N	N	N	N	N	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-

F: Female; N: Normal; Pr: Pre-dose; Po: Post-dose; -: Not applicable.

NP: Non-pregnant (sacrificed after 24 days from the day of confirmation of mating and found as non-pregnant).

Note: All the littered females were observed until termination i.e., up to lactation day 14.

APPENDIX 1 (Contd…). INDIVIDUAL ANIMAL CLINICAL SIGNS OF TOXICITY AND MORTALITY RECORD

Group, Sex & Dose (mg/kg body weight/day)

Animal No.

Clinical Signs of Toxicity and Mortality Record on Day

1

2

3

4^Pr

4^Po

5^Pr

5^Po

6^Pr

6^Po

7^Pr

7^Po

8^Pr

8^Po

9^Pr

9^Po

10^Pr

10^Po

G3, F & 300

Rg7953^NP

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7954

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7955

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7956

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7957^NP

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7958

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7959

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7960

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7961

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7962

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7963^TL

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7964

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

G4, F & 600

Rg7965^TL

N

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7966

N

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7967^TL

N

N

N

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7968

N

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7969

N

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7970

N

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7971

N

N

N

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7972^TL

N

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7973^NP

N

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7974

N

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7975

N

N

N

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7976

N

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

F: Female; N: Normal; Pr: Pre-dose; Po: Post-dose; NP: Non-pregnant; TL: Total litter loss.

6: Wetness around mouth; +: Slight.

 

APPENDIX 1 (Contd…). INDIVIDUAL ANIMAL CLINICAL SIGNS OF TOXICITY AND MORTALITY RECORD

Group, Sex & Dose (mg/kg body weight/day)

Animal No.

Clinical Signs of Toxicity and Mortality Record on Day

11^Pr

11^Po

12^Pr

12^Po

13^Pr

13^Po

14^Pr

14^Po

15^Pr

15^Po

16^Pr

16^Po

17^Pr

17^Po

18^Pr

18^Po

19^Pr

19^Po

20^Pr

20^Po

G3, F & 300

Rg7953^NP

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7954

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7955

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7956

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7957^NP

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7958

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7959

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7960

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7961

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7962

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7963^TL

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7964

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

G4, F & 600

Rg7965^TL

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7966

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7967^TL

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7968

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7969

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7970

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7971

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7972^TL

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7973^NP

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7974

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7975

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7976

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

F: Female; N: Normal; Pr: Pre-dose; Po: Post-dose; NP: Non-pregnant; TL: Total litter loss.

6: Wetness around mouth; +: Slight.

APPENDIX 1 (Contd…). INDIVIDUAL ANIMAL CLINICAL SIGNS OF TOXICITY AND MORTALITY RECORD

Group, Sex & Dose (mg/kg body weight/day)

Animal No.

Clinical Signs of Toxicity and Mortality Record on Day

21^Pr

21^Po

22^Pr

22^Po

23^Pr

23^Po

24^Pr

24^Po

25^Pr

25^Po

26^Pr

26^Po

27^Pr

27^Po

28^Pr

28^Po

29^Pr

29^Po

30^Pr

30^Po

G3, F & 300

Rg7953^NP

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7954

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7955

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7956

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7957^NP

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7958

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7959

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7960

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7961

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7962

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7963^TL

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7964

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

G4, F & 600

Rg7965^TL

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7966

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7967^TL

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7968

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7969

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7970

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7971

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7972^TL

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7973^NP

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7974

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7975

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7976

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

F: Female; N: Normal; Pr: Pre-dose; Po: Post-dose; NP: Non-pregnant; TL: Total litter loss.

6: Wetness around mouth; +: Slight.

 

APPENDIX 1 (Contd…). INDIVIDUAL ANIMAL CLINICAL SIGNS OF TOXICITY AND MORTALITY RECORD

Group, Sex & Dose (mg/kg body weight/day)

Animal No.

Clinical Signs of Toxicity and Mortality Record on Day

31^Pr

31^Po

32^Pr

32^Po

33^Pr

33^Po

34^Pr

34^Po

35^Pr

35^Po

36^Pr

36^Po

37^Pr

37^Po

38^Pr

38^Po

39^Pr

39^Po

40^Pr

40^Po

G3, F & 300

Rg7953^NP

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7954

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7955

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7956

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7957^NP

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7958

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7959

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7960

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7961

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7962

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7963^TL

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7964

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

G4, F & 600

Rg7965^TL

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7966

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7967^TL

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

1

6+

1

6+

Rg7968

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7969

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7970

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7971

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7972^TL

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

1, 82, 116

6+, 1, 82,116

1, 82, 116

6+, 1, 82, 116

Rg7973^NP

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7974

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7975

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7976

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

F: Female; N: Normal; Pr: Pre-dose; Po: Post-dose; NP: Non-pregnant; TL: Total litter loss.

6: Wetness around mouth; +: Slight; 1: Lethargy; 82: Perinasal Staining; 116: Rough hair coat.   

APPENDIX 1 (Contd…). INDIVIDUAL ANIMAL CLINICAL SIGNS OF TOXICITY AND MORTALITY RECORD

Group, Sex & Dose (mg/kg body weight/day)

Animal No.

Clinical Signs of Toxicity and Mortality Record on Day

41^Pr

41^Po

42^Pr

42^Po

43^Pr

43^Po

44^Pr

44^Po

45^Pr

45^Po

46^Pr

46^Po

47^Pr

47^Po

48^Pr

48^Po

49^Pr

49^Po

50^Pr

50^Po

G3, F & 300

Rg7953^NP

N

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Rg7954

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7955

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

-

Rg7956

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7957^NP

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

-

-

-

-

-

Rg7958

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7959

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7960

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

-

Rg7961

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7962

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7963^TL

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg7964

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

G4, F & 600

Rg7965^TL

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7966

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7967^TL

1

6+

1, 82

6+, 1, 82

1, 82

6+, 1, 82

1, 82

6+, 1, 82

1, 82

6+, 1, 82

1, 82

6+, 1, 82

1, 82

6+, 1, 82

1

6+

1

6+

1

6+

Rg7968

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7969

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7970

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7971

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

-

Rg7972^TL

D

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Rg7973^NP

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7974

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7975

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

Rg7976

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

N

6+

F: Female; N: Normal; Pr: Pre-dose; Po: Post-dose; -: Not applicable; TL: Total litter loss.

NP: Non-pregnant (sacrificed after 24 days from the day of confirmation of mating and found as non-pregnant).

6: Wetness around mouth; +: Slight; D: Dead; 1: Lethargy; 82: Perinasal Staining.          

Note: All the littered females were observed until termination i.e., up to lactation day 14.

APPENDIX 1 (Contd…). INDIVIDUAL ANIMAL CLINICAL SIGNS OF TOXICITY AND MORTALITY RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Clinical Signs of Toxicity and Mortality Record on Day
		51^Pr	51^Po	52^Pr	52^Po	53^Pr	53^Po	54^Pr	54^Po	55^Pr	55^Po	56^Pr	56^Po	57^Pr	57^Po	58^Pr	58^Po
G3, F & 300	Rg7953^NP	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7954	N	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7955	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7956	N	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7957^NP	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7958	N	N	N	N	N	N	N	N	N	N	N	N	N	N	N	N
	Rg7959	N	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7960	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7961	N	N	N	N	N	-	-	-	-	-	-	-	-	-	-	-
	Rg7962	N	N	N	N	N	N	N	N	N	N	N	N	N	N	N	N
	Rg7963^TL	N	N	N	N	N	N	N	N	N	N	N	N	N	N	N	-
	Rg7964	N	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
G4, F & 600	Rg7965^TL	N	6+	N	6+	N	6+	N	6+	N	6+	N	6+	N	6+	N	-
	Rg7966	N	6+	N	6+	N	6+	N	6+	N	6+	N	6+	N	-	-	-
	Rg7967^TL	1	6+	N	6+	N	-	-	-	-	-	-	-	-	-	-	-
	Rg7968	N	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7969	N	6+	N	6+	N	6+	N	6+	N	6+	N	6+	N	-	-	-
	Rg7970	N	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7971	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7972^TL	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7973^NP	N	6+	N	6+	N	6+	N	6+	N	6+	N	6+	N	6+	N	6+
	Rg7974	N	6+	N	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7975	N	6+	N	6+	N	-	-	-	-	-	-	-	-	-	-	-
	Rg7976	N	6+	N	6+	N	6+	N	6+	N	6+	N	6+	N	6+	N	6+

F: Female; N: Normal; Pr: Pre-dose; Po: Post-dose; -: Not applicable; TL: Total litter loss; 6: Wetness around mouth; +: Slight.

NP: Non-pregnant (sacrificed after 24 to 26 days from the day of confirmation of mating and found as non-pregnant).

Note: All the littered females were observed until termination i.e., up to lactation day 14.

APPENDIX 1 (Contd…). INDIVIDUAL ANIMAL CLINICAL SIGNS OF TOXICITY AND MORTALITY RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Clinical Signs of Toxicity and Mortality Record on Day
		59^Pr	59^Po	60^Pr	60^Po	61^Pr	61^Po	62^Pr	62^Po	63^Pr	63^Po	64^Pr	64^Po	65^Pr	65^Po	66
G3, F & 300	Rg7953^NP	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7954	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7955	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7956	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7957^NP	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7958	N	N	N	N	N	N	N	N	N	N	N	N	N	N	N
	Rg7959	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7960	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7961	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7962	N	N	N	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7963^TL	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7964	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
G4, F & 600	Rg7965^TL	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7966	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7967^TL	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7968	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7969	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7970	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7971	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7972^TL	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7973^NP	N	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7974	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7975	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7976	N	6+	N	6+	N	6+	N	6+	N	6+	N	6+	N	6+	N

F: Female; N: Normal; Pr: Pre-dose; Po: Post-dose; -: Not applicable; TL: Total litter loss; 6: Wetness around mouth; +: Slight.

NP: Non-pregnant (sacrificed after 24 to 26 days from the day of confirmation of mating and found as non-pregnant).

Note: All the littered females were observed until termination i.e., up to lactation day 14.

 

• INDIVIDUAL ANIMAL BODY WEIGHT (g) RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Body Weight (g) on Day
		1	7	14	21	28	35
G1, M & 0	Rg7881	332.74	360.61	374.71	394.34	411.20	417.89
	Rg7882	338.31	353.49	370.33	386.90	394.76	394.99
	Rg7883	341.49	337.74	348.61	381.74	405.68	413.90
	Rg7884	351.67	373.17	398.01	396.08	417.34	428.37
	Rg7885	362.41	375.02	392.01	402.12	424.88	434.89
	Rg7886	373.01	383.21	385.16	387.15	404.90	434.47
	Rg7887	367.53	384.66	405.29	409.93	406.26	404.10
	Rg7888	379.05	401.87	429.20	444.84	444.78	447.81
	Rg7889	377.28	400.47	426.65	442.14	460.30	467.89
	Rg7890	382.92	415.44	440.19	449.31	465.98	482.48
	Rg7891	387.16	418.15	446.64	445.19	443.52	441.68
	Rg7892	407.36	431.33	457.76	479.38	490.36	509.12
G2, M & 150	Rg7893	334.94	341.34	346.12	347.10	361.14	374.85
	Rg7894	343.96	338.16	349.26	346.80	354.24	365.11
	Rg7895	343.44	367.83	377.74	390.11	388.63	404.21
	Rg7896	354.64	376.29	384.74	394.74	414.86	427.80
	Rg7897	356.25	370.55	379.69	382.24	389.28	412.62
	Rg7898	360.13	358.24	355.42	369.05	386.08	403.15
	Rg7899	366.10	367.04	347.77	355.54	384.16	404.93
	Rg7900	371.54	380.88	366.71	400.94	433.94	452.17
	Rg7901	375.24	400.06	413.40	416.72	412.71	410.76
	Rg7902	377.55	405.36	424.70	426.02	423.28	418.10
	Rg7903	395.81	411.50	419.55	416.15	428.79	455.63
	Rg7904	407.36	431.73	435.46	437.90	439.46	434.48
G3, M & 300	Rg7905	337.81	335.86	356.03	351.69	358.27	353.18
	Rg7906	337.28	349.30	354.28	350.09	345.15	349.33
	Rg7907	339.90	360.12	382.79	386.02	401.92	405.25
	Rg7908	355.30	376.11	403.88	416.62	420.32	422.40
	Rg7909	358.48	372.71	367.49	370.07	386.44	402.95
	Rg7910	363.65	355.55	348.53	339.99	348.27	363.01
	Rg7911	374.06	392.11	411.60	431.29	434.58	454.33
	Rg7912	369.93	390.89	414.64	413.36	422.97	436.47
	Rg7913	384.94	415.47	435.10	441.25	436.32	428.59
	Rg7914	385.76	413.73	399.64	397.54	401.76	396.80
	Rg7915	383.28	391.30	394.16	398.46	394.88	405.56
	Rg7916	424.91	431.26	451.92	451.18	447.84	441.19
G4, M & 600	Rg7917	340.98	334.17	329.74	338.70	358.51	362.21
	Rg7918	338.31	337.67	331.32	325.25	320.55	330.75
	Rg7919	342.73	335.77	327.79	340.03	348.72	340.38
	Rg7920	351.10	361.03	376.12	385.68	379.66	372.53
	Rg7921	358.81	365.05	368.05	361.59	356.56	358.90
	Rg7922	362.18	350.19	348.13	364.44	383.60	413.88
	Rg7923	365.00	380.56	400.21	400.33	416.14	417.46
	Rg7924	373.30	374.73	385.91	379.26	372.38	368.37
	Rg7925	382.72	396.05	408.64	401.16	414.48	396.89
	Rg7926	384.83	400.08	410.02	404.38	400.24	391.18
	Rg7927	390.68	406.11	398.22	400.92	396.04	415.90
	Rg7928	408.96	394.86	389.79	379.02	390.26	389.55

M: Male.

APPENDIX 2 (Contd…). INDIVIDUAL ANIMAL BODY WEIGHT (g) RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Body Weight (g) on Day
		1	7	14	21^#	28^#
G1, F & 0	Rg7929	248.22	247.36	255.45	-	-
	Rg7930	245.21	253.07	258.31	-	-
	Rg7931	251.50	256.72	267.01	-	-
	Rg7932	251.34	258.40	265.08	-	-
	Rg7933	247.85	252.31	264.51	-	-
	Rg7934	258.86	260.39	261.94	-	-
	Rg7935	264.81	268.64	272.44	290.01	-
	Rg7936	259.29	270.29	276.21	-	-
	Rg7937	268.76	282.75	292.75	-	-
	Rg7938	267.33	274.71	276.39	-	-
	Rg7939	268.45	272.71	281.79	-	-
	Rg7940	273.34	283.43	291.83	-	-
G2, F & 150	Rg7941	241.75	248.06	262.99	-	-
	Rg7942	244.27	251.76	260.26	-	-
	Rg7943	250.97	253.76	259.10	-	-
	Rg7944	254.05	255.56	259.01	-	-
	Rg7945	254.64	263.39	269.91	-	-
	Rg7946	250.58	259.98	264.49	-	-
	Rg7947	259.73	268.97	280.24	-	-
	Rg7948	263.06	265.08	283.42	-	-
	Rg7949^NP	266.79	283.19	281.36	-	-
	Rg7950	266.57	277.18	278.08	-	-
	Rg7951	271.74	280.32	293.06	291.08	-
	Rg7952	276.95	279.34	295.04	-	-
G3, F & 300	Rg7953^NP	246.88	249.47	244.84	-	-
	Rg7954	251.20	252.10	260.73	-	-
	Rg7955	253.76	249.27	258.72	-	-
	Rg7956	247.18	248.59	256.94	-	-
	Rg7957^NP	249.95	258.93	255.16	-	-
	Rg7958	253.99	260.56	267.65	284.26	279.42
	Rg7959	261.36	264.71	273.72	-	-
	Rg7960	270.69	283.88	291.31	-	-
	Rg7961	267.74	265.25	274.29	-	-
	Rg7962	265.18	272.73	269.49	281.90	-
	Rg7963^TL	273.85	274.96	283.88	289.16	-
	Rg7964	276.21	292.60	291.28	-	-
G4, F & 600	Rg7965^TL	244.15	240.44	238.71	238.37	-
	Rg7966	248.71	247.53	253.78	-	-
	Rg7967^TL	246.74	259.19	259.71	-	-
	Rg7968	246.12	251.16	251.64	-	-
	Rg7969	255.79	260.19	267.66	-	-
	Rg7970	255.48	265.50	275.49	-	-
	Rg7971	268.69	285.59	283.83	-	-
	Rg7972^TL	265.86	262.66	272.48	-	-
	Rg7973^NP	263.17	276.31	275.58	282.17	294.00
	Rg7974	276.12	287.03	305.52	-	-
	Rg7975	269.01	276.36	287.27	-	-
	Rg7976	275.10	285.39	282.06	276.77	286.27

F: Female; NP: Non-pregnant; TL: total litter loss; -: Not applicable (recorded under gestation body weight).

^#: The presented values represent data obtained from females under cohabitation only.

Note 1: The data of females confirmed with mating is excluded under this Appendix and presented as gestation body weight record under Appendix 3.

Note 2: The day 21 & 28 body weight data was not subjected to statistical analysis due to uneven number of variables.

• INDIVIDUAL ANIMAL GESTATION BODY WEIGHT (g) RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Body Weight (g) on Gestation Day
		0	7	14	20
G1, F & 0	Rg7929	259.62	280.33	315.14	386.74
	Rg7930	257.43	275.28	300.55	337.92
	Rg7931	275.73	296.72	324.16	389.04
	Rg7932	269.67	277.10	299.18	325.14
	Rg7933	275.51	288.54	331.45	411.46
	Rg7934	269.35	292.38	331.75	389.30
	Rg7935	306.88	328.31	362.28	409.24
	Rg7936	279.07	301.67	337.38	425.18
	Rg7937	293.10	310.60	330.12	379.23
	Rg7938	284.75	301.24	348.97	441.16
	Rg7939	283.55	289.90	315.05	401.13
	Rg7940	296.73	315.24	350.52	416.92
G2, F & 150	Rg7941	262.49	283.63	317.75	389.38
	Rg7942	258.05	276.85	295.36	331.79
	Rg7943	265.60	287.41	323.33	359.76
	Rg7944	270.09	285.37	303.19	335.18
	Rg7945	281.16	292.63	321.75	357.36
	Rg7946	267.03	279.89	304.08	341.56
	Rg7947	287.16	302.43	337.50	368.22
	Rg7948	289.56	307.18	342.92	429.48
	Rg7949^NP	282.73	289.26	308.91	314.63
	Rg7950	285.08	306.22	345.49	394.33
	Rg7951	289.52	304.57	343.54	391.76
	Rg7952	295.04	314.68	336.45	386.12
G3, F & 300	Rg7953^NP	250.63	258.10	269.81	270.34
	Rg7954	268.18	277.81	308.73	358.53
	Rg7955	264.02	281.16	319.97	372.12
	Rg7956	256.17	268.14	293.99	331.82
	Rg7957^NP	259.31	269.73	274.80	281.62
	Rg7958	276.73	283.87	306.97	347.26
	Rg7959	274.25	283.25	301.36	334.01
	Rg7960	296.35	317.35	348.86	391.22
	Rg7961	280.81	303.10	331.23	372.88
	Rg7962	292.20	304.36	331.11	370.25
	Rg7963^TL	288.45	307.52	340.38	392.75
	Rg7964	303.17	318.98	355.23	473.94
G4, F & 600	Rg7965^TL	242.22	257.29	281.46	320.96
	Rg7966	255.36	278.45	304.55	343.22
	Rg7967^TL	262.43	267.64	271.55	292.30
	Rg7968	259.20	280.76	316.27	405.46
	Rg7969	271.59	280.06	301.39	365.37
	Rg7970	278.06	299.85	315.42	344.16
	Rg7971	284.92	299.72	326.87	396.61
	Rg7972^TL	275.92	283.45	299.26	328.05
	Rg7973^NP	291.39	306.17	318.46	315.18
	Rg7974	306.21	313.09	343.71	436.77
	Rg7975	286.50	308.76	352.41	442.61
	Rg7976	284.70	301.27	333.27	361.72

F: Female; TL: Total litter loss; NP: Non-pregnant (data excluded for mean calculations and statistical analysis).

 

• INDIVIDUAL ANIMAL LACTATION BODY WEIGHT (g) RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Body Weight (g) on Lactation Day
		1	4	7	13
G1, F & 0	Rg7929	299.65	310.76	319.02	323.56
	Rg7930	281.79	290.05	301.13	317.77
	Rg7931	298.10	294.94	302.10	321.33
	Rg7932	293.35	302.99	311.48	327.26
	Rg7933	297.10	305.65	313.01	324.72
	Rg7934	289.43	300.24	310.03	333.92
	Rg7935	319.62	317.39	323.17	337.36
	Rg7936	301.68	306.38	317.28	331.41
	Rg7937	326.68	337.94	345.12	352.56
	Rg7938	305.56	302.76	309.25	327.63
	Rg7939	304.25	303.68	312.63	327.83
	Rg7940	319.81	327.00	338.24	356.97
G2, F & 150	Rg7941	271.19	267.87	276.39	285.16
	Rg7942	277.56	285.63	296.63	311.38
	Rg7943	290.82	289.79	297.62	310.49
	Rg7944	281.37	279.46	285.91	299.86
	Rg7945	297.58	308.52	316.27	332.71
	Rg7946	284.65	286.32	293.61	308.11
	Rg7947	306.18	314.81	322.51	331.26
	Rg7948	312.02	309.11	317.64	331.37
	Rg7949^NP	-	-	-	-
	Rg7950	305.96	314.26	323.16	347.18
	Rg7951	319.46	328.37	336.16	351.28
	Rg7952	316.11	314.81	321.96	333.90
G3, F & 300	Rg7953^NP	-	-	-	-
	Rg7954	284.46	291.68	300.11	326.17
	Rg7955	306.72	316.30	315.03	328.10
	Rg7956	269.36	273.11	281.16	303.09
	Rg7957^NP	-	-	-	-
	Rg7958	288.19	295.36	300.13	321.48
	Rg7959	293.51	298.16	308.15	322.37
	Rg7960	308.16	306.63	315.18	334.90
	Rg7961	301.79	303.29	310.53	327.98
	Rg7962	311.16	318.21	330.74	346.11
	Rg7963^TL	337.13	332.54	330.18	328.91
	Rg7964	320.37	316.79	319.30	324.54
G4, F & 600	Rg7965^TL	273.45	270.68	267.44	274.45
	Rg7966	293.57	298.46	305.90	321.42
	Rg7967^TL	271.78	267.16	264.81	277.18
	Rg7968	283.58	289.53	300.26	309.18
	Rg7969	286.52	284.13	292.81	302.41
	Rg7970	291.82	288.64	295.37	298.82
	Rg7971	317.61	320.20	330.19	347.83
	Rg7972^TL	271.79	250.11	D	D
	Rg7973^NP	-	-	-	-
	Rg7974	314.79	316.41	320.92	337.12
	Rg7975	311.76	309.79	316.48	337.71
	Rg7976	297.31	296.38	305.71	323.18

F: Female; TL: Total litter loss; NP: Non-pregnant; -: Not applicable.

D: Found dead on Lactation day 5.

• INDIVIDUAL ANIMAL PERCENT CHANGE IN BODY WEIGHT GAIN (%) WITH RESPECT TO DAY 1 RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Percent Change in Body Weight (%) during Day
		1 to 7	1 to 14	1 to 21	1 to 28	1 to 35
G1, M & 0	Rg7881	8.38	12.61	18.51	23.58	25.59
	Rg7882	4.49	9.46	14.36	16.69	16.75
	Rg7883	-1.10	2.08	11.79	18.80	21.20
	Rg7884	6.11	13.18	12.63	18.67	21.81
	Rg7885	3.48	8.17	10.96	17.24	20.00
	Rg7886	2.73	3.26	3.79	8.55	16.48
	Rg7887	4.66	10.27	11.54	10.54	9.95
	Rg7888	6.02	13.23	17.36	17.34	18.14
	Rg7889	6.15	13.09	17.19	22.00	24.02
	Rg7890	8.49	14.96	17.34	21.69	26.00
	Rg7891	8.00	15.36	14.99	14.56	14.08
	Rg7892	5.88	12.37	17.68	20.38	24.98
G2, M & 150	Rg7893	1.91	3.34	3.63	7.82	11.92
	Rg7894	-1.69	1.54	0.83	2.99	6.15
	Rg7895	7.10	9.99	13.59	13.16	17.69
	Rg7896	6.10	8.49	11.31	16.98	20.63
	Rg7897	4.01	6.58	7.30	9.27	15.82
	Rg7898	-0.52	-1.31	2.48	7.21	11.95
	Rg7899	0.26	-5.01	-2.88	4.93	10.61
	Rg7900	2.51	-1.30	7.91	16.79	21.70
	Rg7901	6.61	10.17	11.05	9.99	9.47
	Rg7902	7.37	12.49	12.84	12.11	10.74
	Rg7903	3.96	6.00	5.14	8.33	15.11
	Rg7904	5.98	6.90	7.50	7.88	6.66
G3, M & 300	Rg7905	-0.58	5.39	4.11	6.06	4.55
	Rg7906	3.56	5.04	3.80	2.33	3.57
	Rg7907	5.95	12.62	13.57	18.25	19.23
	Rg7908	5.86	13.67	17.26	18.30	18.89
	Rg7909	3.97	2.51	3.23	7.80	12.41
	Rg7910	-2.23	-4.16	-6.51	-4.23	-0.18
	Rg7911	4.83	10.04	15.30	16.18	21.46
	Rg7912	5.67	12.09	11.74	14.34	17.99
	Rg7913	7.93	13.03	14.63	13.35	11.34
	Rg7914	7.25	3.60	3.05	4.15	2.86
	Rg7915	2.09	2.84	3.96	3.03	5.81
	Rg7916	1.49	6.36	6.18	5.40	3.83
G4, M & 600	Rg7917	-2.00	-3.30	-0.67	5.14	6.23
	Rg7918	-0.19	-2.07	-3.86	-5.25	-2.23
	Rg7919	-2.03	-4.36	-0.79	1.75	-0.69
	Rg7920	2.83	7.13	9.85	8.13	6.10
	Rg7921	1.74	2.58	0.77	-0.63	0.03
	Rg7922	-3.31	-3.88	0.62	5.91	14.27
	Rg7923	4.26	9.65	9.68	14.01	14.37
	Rg7924	0.38	3.38	1.60	-0.25	-1.32
	Rg7925	3.48	6.77	4.82	8.30	3.70
	Rg7926	3.96	6.55	5.08	4.00	1.65
	Rg7927	3.95	1.93	2.62	1.37	6.46
	Rg7928	-3.45	-4.69	-7.32	-4.57	-4.75

M: Male.

APPENDIX 5 (Contd…). INDIVIDUAL ANIMAL PERCENT CHANGE IN

BODY WEIGHT GAIN (%) WITH RESPECT TO DAY 1 RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Percent Change in Body Weight (%) during Day
		1 to 7	1 to 14	1 to 21^#	1 to 28^#
G1, F & 0	Rg7929	-0.35	2.91	-	-
	Rg7930	3.21	5.34	-	-
	Rg7931	2.08	6.17	-	-
	Rg7932	2.81	5.47	-	-
	Rg7933	1.80	6.72	-	-
	Rg7934	0.59	1.19	-	-
	Rg7935	1.45	2.88	9.52	-
	Rg7936	4.24	6.53	-	-
	Rg7937	5.21	8.93	-	-
	Rg7938	2.76	3.39	-	-
	Rg7939	1.59	4.97	-	-
	Rg7940	3.69	6.76	-	-
G2, F & 150	Rg7941	2.61	8.79	-	-
	Rg7942	3.07	6.55	-	-
	Rg7943	1.11	3.24	-	-
	Rg7944	0.59	1.95	-	-
	Rg7945	3.44	6.00	-	-
	Rg7946	3.75	5.55	-	-
	Rg7947	3.56	7.90	-	-
	Rg7948	0.77	7.74	-	-
	Rg7949^NP	6.15	5.46	-	-
	Rg7950	3.98	4.32	-	-
	Rg7951	3.16	7.85	7.12	-
	Rg7952	0.86	6.53	-	-
G3, F & 300	Rg7953^NP	1.05	-0.83	-	-
	Rg7954	0.36	3.79	-	-
	Rg7955	-1.77	1.95	-	-
	Rg7956	0.57	3.95	-	-
	Rg7957^NP	3.59	2.08	-	-
	Rg7958	2.59	5.38	11.92	10.01
	Rg7959	1.28	4.73	-	-
	Rg7960	4.87	7.62	-	-
	Rg7961	-0.93	2.45	-	-
	Rg7962	2.85	1.63	6.31	-
	Rg7963^TL	0.41	3.66	5.59	-
	Rg7964	5.93	5.46	-	-
G4, F & 600	Rg7965^TL	-1.52	-2.23	-2.37	-
	Rg7966	-0.47	2.04	-	-
	Rg7967^TL	5.05	5.26	-	-
	Rg7968	2.05	2.24	-	-
	Rg7969	1.72	4.64	-	-
	Rg7970	3.92	7.83	-	-
	Rg7971	6.29	5.63	-	-
	Rg7972^TL	-1.20	2.49	-	-
	Rg7973^NP	4.99	4.72	7.22	11.71
	Rg7974	3.95	10.65	-	-
	Rg7975	2.73	6.79	-	-
	Rg7976	3.74	2.53	0.61	4.06

F: Female; NP: Non-pregnant; TL: total litter loss; -: Not applicable (recorded under gestation body weight).

^#: The presented values represent data obtained from females under cohabitation. The data of females confirmed with mating was excluded under this appendix and presented under gestation body weight gain record (Appendix 6).

Note: The day 1 to 21 & 1 to 28 body weight gain data was not subjected to statistical analysis due to uneven number of variables.

 

• INDIVIDUAL ANIMAL PERCENT CHANGE IN GESTATION BODY WEIGHT GAIN (%) RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Percent Change in Body Weight Gain (%) during Gestation Day
		0 to 7	7 to 14	14 to 20
G1, F & 0	Rg7929	7.98	12.42	22.72
	Rg7930	6.93	9.18	12.43
	Rg7931	7.61	9.25	20.01
	Rg7932	2.76	7.97	8.68
	Rg7933	4.73	14.87	24.14
	Rg7934	8.55	13.47	17.35
	Rg7935	6.98	10.35	12.96
	Rg7936	8.10	11.84	26.02
	Rg7937	5.97	6.28	14.88
	Rg7938	5.79	15.84	26.42
	Rg7939	2.24	8.68	27.32
	Rg7940	6.24	11.19	18.94
G2, F & 150	Rg7941	8.05	12.03	22.54
	Rg7942	7.29	6.69	12.33
	Rg7943	8.21	12.50	11.27
	Rg7944	5.66	6.24	10.55
	Rg7945	4.08	9.95	11.07
	Rg7946	4.82	8.64	12.33
	Rg7947	5.32	11.60	9.10
	Rg7948	6.09	11.63	25.24
	Rg7949^NP	2.31	6.79	1.85
	Rg7950	7.42	12.82	14.14
	Rg7951	5.20	12.80	14.04
	Rg7952	6.66	6.92	14.76
G3, F & 300	Rg7953^NP	2.98	4.54	0.20
	Rg7954	3.59	11.13	16.13
	Rg7955	6.49	13.80	16.30
	Rg7956	4.67	9.64	12.87
	Rg7957^NP	4.02	1.88	2.48
	Rg7958	2.58	8.14	13.13
	Rg7959	3.28	6.39	10.83
	Rg7960	7.09	9.93	12.14
	Rg7961	7.94	9.28	12.57
	Rg7962	4.16	8.79	11.82
	Rg7963^TL	6.61	10.69	15.39
	Rg7964	5.21	11.36	33.42
G4, F & 600	Rg7965^TL	6.22	9.39	14.03
	Rg7966	9.04	9.37	12.70
	Rg7967^TL	1.99	1.46	7.64
	Rg7968	8.32	12.65	28.20
	Rg7969	3.12	7.62	21.23
	Rg7970	7.84	5.19	9.11
	Rg7971	5.19	9.06	21.34
	Rg7972^TL	2.73	5.58	9.62
	Rg7973^NP	5.07	4.01	-1.03
	Rg7974	2.25	9.78	27.08
	Rg7975	7.77	14.14	25.60
	Rg7976	5.82	10.62	8.54

F: Female; TL: Total litter loss; NP: Non-pregnant (data excluded for mean calculations and statistical analysis).

 

• INDIVIDUAL ANIMAL PERCENT CHANGE IN LACTATION BODY WEIGHT GAIN (%) RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Percent Change in Body Weight Gain (%) during Lactation Day
		1 to 4	4 to 7	7 to 13
G1, F & 0	Rg7929	3.71	2.66	1.42
	Rg7930	2.93	3.82	5.53
	Rg7931	-1.06	2.43	6.37
	Rg7932	3.29	2.80	5.07
	Rg7933	2.88	2.41	3.74
	Rg7934	3.73	3.26	7.71
	Rg7935	-0.70	1.82	4.39
	Rg7936	1.56	3.56	4.45
	Rg7937	3.45	2.12	2.16
	Rg7938	-0.92	2.14	5.94
	Rg7939	-0.19	2.95	4.86
	Rg7940	2.25	3.44	5.54
G2, F & 150	Rg7941	-1.22	3.18	3.17
	Rg7942	2.91	3.85	4.97
	Rg7943	-0.35	2.70	4.32
	Rg7944	-0.68	2.31	4.88
	Rg7945	3.68	2.51	5.20
	Rg7946	0.59	2.55	4.94
	Rg7947	2.82	2.45	2.71
	Rg7948	-0.93	2.76	4.32
	Rg7949^NP	-	-	-
	Rg7950	2.71	2.83	7.43
	Rg7951	2.79	2.37	4.50
	Rg7952	-0.41	2.27	3.71
G3, F & 300	Rg7953^NP	-	-	-
	Rg7954	2.54	2.89	8.68
	Rg7955	3.12	-0.40	4.15
	Rg7956	1.39	2.95	7.80
	Rg7957^NP	-	-	-
	Rg7958	2.49	1.61	7.11
	Rg7959	1.58	3.35	4.61
	Rg7960	-0.50	2.79	6.26
	Rg7961	0.50	2.39	5.62
	Rg7962	2.27	3.94	4.65
	Rg7963^TL	-1.36	-0.71	-0.38
	Rg7964	-1.12	0.79	1.64
G4, F & 600	Rg7965^TL	-1.01	-1.20	2.62
	Rg7966	1.67	2.49	5.07
	Rg7967^TL	-1.48	-0.88	4.67
	Rg7968	2.10	3.71	2.97
	Rg7969	-0.83	3.05	3.28
	Rg7970	-1.09	2.33	1.17
	Rg7971	0.82	3.12	5.34
	Rg7972^TL	-7.98	D	D
	Rg7973^NP	-	-	-
	Rg7974	0.51	1.43	5.05
	Rg7975	-0.63	2.16	6.71
	Rg7976	-0.31	3.15	5.71

F: Female; TL: Total litter loss; NP: Non-pregnant; -: Not applicable.

D: Found dead on Lactation day 5.

• INDIVIDUAL ANIMAL FEED CONSUMPTION (g/animal/day) RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Feed Consumption (g/animal/day) during Pre-mating period
		Week 1	Week 2
G1, M & 0	Rg7881 & Rg7882	23.0	26.5
	Rg7883 & Rg7884	17.5	25.2
	Rg7885 & Rg7886	19.0	22.9
	Rg7887 & Rg7888	21.4	23.7
	Rg7889 & Rg7890	23.2	23.8
	Rg7891 & Rg7892	24.3	25.5
G2, M & 150	Rg7893 & Rg7894	19.7	24.6
	Rg7895 & Rg7896	24.5	25.4
	Rg7897 & Rg7898	21.8	23.4
	Rg7899 & Rg7900	19.0	25.4
	Rg7901 & Rg7902	23.7	24.6
	Rg7903 & Rg7904	23.0	23.5
G3, M & 300	Rg7905 & Rg7906	21.2	23.6
	Rg7907 & Rg7908	24.2	22.6
	Rg7909 & Rg7910	21.9	21.6
	Rg7911 & Rg7912	23.5	24.8
	Rg7913 & Rg7914	24.6	23.1
	Rg7915 & Rg7916	20.7	24.5
G4, M & 600	Rg7917 & Rg7918	18.9	23.5
	Rg7919 & Rg7920	19.4	22.8
	Rg7921 & Rg7922	20.0	23.5
	Rg7923 & Rg7924	22.3	22.7
	Rg7925 & Rg7926	23.8	24.9
	Rg7927 & Rg7928	22.5	22.2

M: Male.

 

 

 

APPENDIX 8 (Cond…). INDIVIDUAL ANIMAL FEED CONSUMPTION (g/animal/day) RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Feed Consumption (g/animal/day) during Pre-mating period
		Week 1	Week 2
G1, F & 0	Rg7929 & Rg7930	16.8	17.8
	Rg7931 & Rg7932	18.5	19.6
	Rg7933 & Rg7934	17.4	17.8
	Rg7935 & Rg7936	17.6	17.4
	Rg7937 & Rg7938	18.9	19.8
	Rg7939 & Rg7940	19.2	17.3
G2, F & 150	Rg7941 & Rg7942	17.7	18.9
	Rg7943 & Rg7944	16.1	15.6
	Rg7945 & Rg7946	17.6	16.9
	Rg7947 & Rg7948	18.8	19.4
	Rg7949 & Rg7950	19.7	19.5
	Rg7951 & Rg7952	18.5	18.7
G3, F & 300	Rg7953 & Rg7954	17.0	15.7
	Rg7955 & Rg7956	16.7	17.1
	Rg7957 & Rg7958	18.2	18.1
	Rg7959 & Rg7960	18.4	19.8
	Rg7961 & Rg7962	17.1	16.4
	Rg7963 & Rg7964	20.2	18.9
G4, F & 600	Rg7965 & Rg7966	17.2	15.1
	Rg7967 & Rg7968	16.0	16.6
	Rg7969 & Rg7970	16.7	16.9
	Rg7971 & Rg7972	16.7	17.9
	Rg7973 & Rg7974	19.0	19.2
	Rg7974 & Rg7976	18.6	16.9

F: Female.

 

 

 

 

• INDIVIDUAL ANIMAL FEED CONSUMPTION RECORD (g/animal/day) DURING GESTATION PERIOD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Feed Consumption (g/animal/day) during Gestation Day (GD)
		0 to 7	7 to 14	14 to 20
G1, F & 0	Rg7929	20.4	23.1	27.5
	Rg7930	19.7	21.2	25.3
	Rg7931	21.3	23.6	28.0
	Rg7932	17.9	19.8	22.9
	Rg7933	18.7	21.7	28.2
	Rg7934	21.7	23.2	28.0
	Rg7935	21.2	22.5	28.0
	Rg7936	19.6	21.0	26.2
	Rg7937	19.5	21.0	25.6
	Rg7938	19.5	22.5	28.7
	Rg7939	17.7	20.0	24.2
	Rg7940	21.0	22.9	27.9
G2, F & 150	Rg7941	20.7	23.3	26.4
	Rg7942	19.2	20.2	24.0
	Rg7943	20.3	22.7	27.2
	Rg7944	19.6	19.8	24.0
	Rg7945	18.0	19.9	24.3
	Rg7946	19.1	20.2	24.6
	Rg7947	19.6	21.7	26.5
	Rg7948	20.3	22.4	26.5
	Rg7949^NP	17.4	19.6	21.8
	Rg7950	21.7	23.8	28.4
	Rg7951	19.1	22.0	27.2
	Rg7952	19.6	21.6	26.3
G3, F & 300	Rg7953^NP	17.6	18.9	21.0
	Rg7954	17.4	20.1	24.9
	Rg7955	19.6	23.3	28.0
	Rg7956	19.1	21.7	26.1
	Rg7957^NP	18.4	16.8	18.8
	Rg7958	17.7	19.5	23.2
	Rg7959	18.1	19.6	23.8
	Rg7960	21.0	23.2	28.0
	Rg7961	20.0	22.8	27.2
	Rg7962	19.1	20.4	24.7
	Rg7963^TL	21.5	24.3	28.9
	Rg7964	19.9	21.8	28.6
G4, F & 600	Rg7965^TL	18.8	20.9	22.9
	Rg7966	19.0	20.9	25.1
	Rg7967^TL	16.9	17.5	19.5
	Rg7968	19.2	20.7	25.6
	Rg7969	17.7	19.3	23.5
	Rg7970	20.6	21.9	25.3
	Rg7971	19.0	20.3	24.2
	Rg7972^TL	17.3	19.6	23.9
	Rg7973^NP	18.7	17.5	19.3
	Rg7974	17.4	19.8	25.3
	Rg7975	22.0	22.8	28.1
	Rg7976	18.8	20.4	26.1

F: Female; TL: Total litter loss; NP: Non-pregnant (data excluded for mean calculations and statistical analysis).

• INDIVIDUAL ANIMAL FEED CONSUMPTION (g/animal/day) RECORD DURING LACTATION PERIOD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Feed Consumption (g/animal/day) during Lactation Day (LD)
		1 to 4	4 to 7	7 to 13
G1, F & 0	Rg7929	28.0	33.0	39.5
	Rg7930	24.3	27.3	37.9
	Rg7931	29.7	33.7	43.0
	Rg7932	25.4	31.0	41.2
	Rg7933	28.0	33.2	40.4
	Rg7934	29.3	34.5	42.7
	Rg7935	27.3	34.2	40.2
	Rg7936	25.2	30.4	42.5
	Rg7937	27.7	32.9	43.0
	Rg7938	28.7	31.7	44.0
	Rg7939	29.9	34.4	42.9
	Rg7940	28.7	34.7	43.6
G2, F & 150	Rg7941	32.9	35.8	43.8
	Rg7942	26.5	30.9	41.5
	Rg7943	25.8	31.0	41.3
	Rg7944	27.5	31.8	42.2
	Rg7945	28.0	34.2	41.0
	Rg7946	27.7	32.7	40.2
	Rg7947	27.0	31.7	40.5
	Rg7948	32.1	35.4	42.1
	Rg7949^NP	-	-	-
	Rg7950	28.3	31.9	41.1
	Rg7951	27.6	32.3	39.0
	Rg7952	29.0	35.3	40.2
G3, F & 300	Rg7953^NP	-	-	-
	Rg7954	27.2	33.1	39.3
	Rg7955	29.7	33.8	41.5
	Rg7956	27.6	32.6	43.7
	Rg7957^NP	-	-	-
	Rg7958	28.2	33.5	40.4
	Rg7959	26.6	32.4	40.3
	Rg7960	28.5	32.7	43.7
	Rg7961	26.5	30.7	38.9
	Rg7962	25.1	30.4	39.9
	Rg7963^TL	21.3	26.0	37.9
	Rg7964	30.3	35.4	44.0
G4, F & 600	Rg7965^TL	16.9	22.4	33.8
	Rg7966	25.5	31.4	37.0
	Rg7967^TL	24.3	27.2	38.5
	Rg7968	29.5	33.6	42.9
	Rg7969	27.1	34.0	42.7
	Rg7970	26.9	32.0	37.7
	Rg7971	27.9	31.6	42.3
	Rg7972^TL	21.3	-	-
	Rg7973^NP	-	-	-
	Rg7974	29.2	34.0	43.6
	Rg7975	28.9	34.1	42.3
	Rg7976	27.7	33.0	40.0

F: Female; NP: Non-pregnant; TL: Total litter loss; -: Not applicable.

 

• INDIVIDUAL ANIMAL HAEMATOLOGY RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Total Leucocyte Count	Total Erythrocyte Count	Hemoglobin	Haematocrit	Mean Corpuscular Volume	Mean Corpuscular Hemoglobin	Mean Corpuscular Hemoglobin Concentration	Platelet Count
		(WBC)	(RBC)	(HGB)	(HCT)	(MCV)	(MCH)	(MCHC)	(PLT)
		(10^3 cells/µL)	(10^6 cells/µL)	(g/dL)	(%)	(fL)	(pg)	(g/dL)	(10^3 cells/µL)
G1, M & 0	Rg7881	9.39	7.73	15.8	48.6	62.9	20.4	32.4	952
	Rg7882	29.13	7.46	12.6	38.0	50.9	16.8	33.0	1011
	Rg7883	15.96	8.94	17.1	51.5	57.7	19.1	33.2	990
	Rg7884	11.57	9.00	16.5	48.6	54.0	18.4	34.0	1218
	Rg7885	9.28	9.13	17.0	51.5	56.4	18.7	33.1	957
	Rg7886	14.21	8.57	16.7	48.7	56.8	19.5	34.3	1051
	Rg7887	27.64	9.02	16.7	50.2	55.7	18.5	33.2	1303
	Rg7888	11.82	8.80	15.6	47.1	53.5	17.7	33.1	748
	Rg7889	11.01	9.07	16.4	48.1	53.0	18.1	34.1	369
	Rg7890	11.85	9.18	16.0	48.9	53.2	17.4	32.7	992
	Rg7891	8.24	9.86	17.2	50.7	51.4	17.4	33.9	519
	Rg7892	13.88	8.84	15.8	47.4	53.6	17.9	33.4	1175
G2, M & 150	Rg7893	10.71	8.90	15.2	46.2	51.9	17.1	32.9	1159
	Rg7894	14.14	8.43	14.8	45.7	54.2	17.6	32.5	1068
	Rg7895	8.25	9.73	17.2	52.0	53.4	17.6	33.0	879
	Rg7896	12.03	9.22	16.2	49.8	54.0	17.5	32.4	1244
	Rg7897	8.52	8.51	15.1	45.1	53.0	17.7	33.4	809
	Rg7898	29.97	7.14	11.6	38.8	54.4	16.3	29.9	864
	Rg7899	9.31	9.20	16.5	50.5	54.9	18.0	32.7	1048
	Rg7900	12.22	9.57	16.0	49.4	51.6	16.8	32.5	943
	Rg7901	11.20	9.30	16.3	50.0	53.8	17.5	32.5	1009
	Rg7902	11.40	9.62	16.2	49.5	51.5	16.8	32.6	1438
	Rg7903	10.24	8.57	16.0	49.1	57.3	18.7	32.6	1013
	Rg7904	9.37	8.93	15.9	48.0	53.7	17.8	33.1	1085

 M: Male.

 

 

APPENDIX 11 (Contd…). INDIVIDUAL ANIMAL HAEMATOLOGY RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Mean Platelet Volume	Reticulocyte Count	Neutrophils	Lymphocytes	Monocytes	Eosinophils	Basophils	Absolute Reticulocyte Count
		(MPV)	(Retic)	(Neut)	(Lymph)	(Mono)	(Eos)	(Baso)	(Retic)
		(fL)	(%)	(%)	(%)	(%)	(%)	(%)	(10^9 cells/L)
G1, M & 0	Rg7881	6.9	2.94	30.8	62.5	3.5	1.9	0.3	227.5
	Rg7882	7.5	8.46	60.9	29.9	5.6	1.0	0.3	631.4
	Rg7883	6.9	1.86	25.8	67.5	3.1	0.7	0.6	166.7
	Rg7884	7.1	3.04	18.8	75.5	2.6	1.0	0.4	273.8
	Rg7885	7.3	2.73	29.5	65.0	3.1	0.6	0.5	249.3
	Rg7886	7.1	3.82	25.7	68.7	2.6	1.3	0.3	327.7
	Rg7887	7.3	1.85	46.5	48.7	2.8	0.9	0.4	166.9
	Rg7888	7.2	3.18	33.4	60.8	3.0	1.3	0.5	279.6
	Rg7889	7.7	2.44	44.2	50.5	1.7	2.4	0.6	221.2
	Rg7890	6.9	2.11	35.2	58.0	4.4	0.8	0.3	194.0
	Rg7891	7.3	1.37	33.2	62.3	2.4	1.0	0.3	135.3
	Rg7892	7.2	2.70	28.2	67.6	1.4	1.5	0.4	239.2
G2, M & 150	Rg7893	6.7	3.19	20.6	75.5	1.5	1.0	0.4	284.1
	Rg7894	6.8	3.53	18.2	77.3	2.0	1.0	0.3	298.0
	Rg7895	7.2	2.56	28.0	67.5	1.8	1.6	0.5	248.9
	Rg7896	7.1	2.85	26.1	68.3	2.6	1.5	0.3	262.4
	Rg7897	7.0	3.98	18.3	77.5	1.6	1.2	0.4	338.2
	Rg7898	8.0	4.28	10.2	80.4	3.2	3.8	0.6	305.6
	Rg7899	6.9	3.63	29.9	65.1	2.2	1.2	0.4	334.3
	Rg7900	7.3	3.22	26.8	67.4	2.7	2.2	0.3	308.1
	Rg7901	6.9	2.95	33.7	62.8	1.5	0.9	0.4	274.8
	Rg7902	6.9	4.29	26.2	69.5	2.4	1.0	0.3	412.5
	Rg7903	7.7	3.45	21.5	75.6	0.7	0.7	0.3	295.9
	Rg7904	6.5	2.43	22.9	70.6	3.3	1.4	0.4	217.3

 M: Male.

 

 

APPENDIX 11 (Contd…). INDIVIDUAL ANIMAL HAEMATOLOGY RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Absolute Neutrophils	Absolute Lymphocytes	Absolute Monocytes	Absolute Eosinophils	Absolute Basophils	Prothrombin Time	Activated Prothrombin Time
		(Neut)	(Lymph)	(Mono)	(Eos)	(Baso)	(PT)	(APTT)
		(10^3 cells/µL)	(10^3 cells/µL)	(10^3 cells/µL)	(10^3 cells/µL)	(10^3 cells/µL)	(Seconds)	(Seconds)
G1, M & 0	Rg7881	2.89	5.87	0.33	0.18	0.02	20.1	20.5
	Rg7882	17.75	8.72	1.64	0.29	0.08	24.7	16.4
	Rg7883	4.11	10.77	0.50	0.12	0.09	20.2	22.9
	Rg7884	2.17	8.73	0.30	0.12	0.04	20.5	29.5
	Rg7885	2.74	6.03	0.29	0.06	0.05	14.1	21.5
	Rg7886	3.66	9.76	0.37	0.19	0.05	20.0	13.9
	Rg7887	12.86	13.45	0.77	0.24	0.10	20.2	22.1
	Rg7888	3.95	7.18	0.35	0.15	0.06	18.9	12.4
	Rg7889	4.86	5.56	0.18	0.27	0.06	19.2	19.0
	Rg7890	4.17	6.88	0.53	0.09	0.04	20.9	13.4
	Rg7891	2.73	5.13	0.20	0.08	0.02	17.3	11.3
	Rg7892	3.91	9.38	0.20	0.21	0.06	17.2	19.5
G2, M & 150	Rg7893	2.20	8.09	0.16	0.11	0.04	17.5	18.2
	Rg7894	2.57	10.92	0.29	0.14	0.05	20.3	12.7
	Rg7895	2.31	5.57	0.15	0.13	0.04	21.3	18.4
	Rg7896	3.14	8.22	0.31	0.18	0.04	24.2	27.0
	Rg7897	1.56	6.60	0.14	0.10	0.03	20.3	21.2
	Rg7898	3.06	24.09	0.95	1.15	0.17	24.8	30.2
	Rg7899	2.78	6.06	0.20	0.11	0.04	17.6	13.5
	Rg7900	3.27	8.24	0.33	0.27	0.04	17.8	25.8
	Rg7901	3.77	7.03	0.17	0.10	0.04	21.3	17.4
	Rg7902	2.98	7.93	0.27	0.11	0.04	17.0	14.8
	Rg7903	2.21	7.74	0.08	0.07	0.04	18.4	21.6
	Rg7904	2.14	6.62	0.31	0.14	0.04	22.0	21.7

 M: Male.

 

 

APPENDIX 11 (Contd…). INDIVIDUAL ANIMAL HAEMATOLOGY RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Total Leucocyte Count	Total Erythrocyte Count	Hemoglobin	Haematocrit	Mean Corpuscular Volume	Mean Corpuscular Hemoglobin	Mean Corpuscular Hemoglobin Concentration	Platelet Count
		(WBC)	(RBC)	(HGB)	(HCT)	(MCV)	(MCH)	(MCHC)	(PLT)
		(10^3 cells/µL)	(10^6 cells/µL)	(g/dL)	(%)	(fL)	(pg)	(g/dL)	(10^3 cells/µL)
G3, M & 300	Rg7905	11.12	8.82	15.7	48.4	54.9	17.9	32.5	1265
	Rg7906	13.66	9.14	17.5	50.5	55.3	19.2	34.7	364
	Rg7907	11.87	8.33	14.7	46.5	55.9	17.7	31.7	1024
	Rg7908	11.01	9.08	15.5	48.7	53.7	17.1	31.8	1359
	Rg7909	10.55	8.44	15.3	47.2	55.9	18.2	32.5	1048
	Rg7910	11.16	7.71	15.2	46.0	59.6	19.7	33.1	1228
	Rg7911	9.20	9.09	16.0	49.1	54.0	17.6	32.6	932
	Rg7912	13.04	9.52	16.0	49.0	51.5	16.8	32.6	1099
	Rg7913	17.95	8.84	16.2	47.1	53.3	18.3	34.3	875
	Rg7914	12.22	9.13	15.9	47.8	52.4	17.4	33.2	893
	Rg7915	19.62	9.24	16.0	49.9	54.0	17.3	32.0	899
	Rg7916	16.00	8.65	15.9	44.9	51.9	18.4	35.5	659
G4, M & 600	Rg7917	10.38	8.40	16.6	50.7	60.4	19.8	32.7	1018
	Rg7918	6.75	8.40	15.5	44.7	53.2	18.4	34.6	971
	Rg7919	9.99	9.56	16.7	51.2	53.6	17.4	32.5	1185
	Rg7920	8.65	8.88	15.1	45.8	51.5	17.0	32.9	1156
	Rg7921	12.29	9.72	16.8	52.1	53.6	17.3	32.3	711
	Rg7922	10.58	8.82	15.7	49.4	56.1	17.8	31.8	824
	Rg7923	12.51	9.43	17.2	51.7	54.8	18.3	33.3	694
	Rg7924	10.64	8.91	15.3	45.9	51.6	17.2	33.3	1436
	Rg7925	10.59	8.76	16.4	45.5	52.0	18.7	36.0	309
	Rg7926	16.68	9.21	16.0	48.0	52.2	17.4	33.3	852
	Rg7927	11.02	9.79	16.8	51.7	52.8	17.1	32.5	605
	Rg7928	10.12	9.87	16.4	50.3	51.0	16.7	32.7	688

M: Male.

 

APPENDIX 11 (Contd…). INDIVIDUAL ANIMAL HAEMATOLOGY RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Mean Platelet Volume	Reticulocyte Count	Neutrophils	Lymphocytes	Monocytes	Eosinophils	Basophils	Absolute Reticulocyte Count
		(MPV)	(Retic)	(Neut)	(Lymph)	(Mono)	(Eos)	(Baso)	(Retic)
		(fL)	(%)	(%)	(%)	(%)	(%)	(%)	(10^9 cells/L)
G3, M & 300	Rg7905	6.9	2.58	35.5	59.5	2.6	0.8	0.5	227.5
	Rg7906	8.6	2.00	34.3	60.7	2.5	1.3	0.4	182.6
	Rg7907	7.8	2.98	25.0	69.4	3.5	0.8	0.3	248.2
	Rg7908	6.9	2.93	17.0	76.8	3.8	0.7	0.3	265.6
	Rg7909	7.3	3.56	38.8	55.9	1.7	2.6	0.3	300.7
	Rg7910	7.0	6.77	37.5	59.5	1.2	0.5	0.2	522.2
	Rg7911	7.3	2.18	23.4	72.2	1.3	1.8	0.3	198.6
	Rg7912	6.8	2.43	17.7	77.3	2.7	0.9	0.4	231.6
	Rg7913	6.9	2.65	29.3	67.2	1.5	0.8	0.4	234.6
	Rg7914	7.1	2.27	19.4	75.5	2.3	1.3	0.3	207.1
	Rg7915	7.1	3.25	18.9	75.0	3.1	0.9	0.6	300.5
	Rg7916	7.5	2.57	21.7	71.5	4.2	0.8	0.5	222.8
G4, M & 600	Rg7917	7.8	2.63	25.1	69.2	3.3	1.2	0.3	220.4
	Rg7918	7.1	4.17	19.7	73.8	3.5	1.4	0.2	350.1
	Rg7919	7.3	1.22	20.7	73.0	4.2	1.0	0.3	116.7
	Rg7920	7.2	2.96	20.6	72.9	4.7	0.6	0.3	262.8
	Rg7921	7.0	4.09	20.1	74.7	2.1	1.6	0.3	397.5
	Rg7922	7.0	4.24	30.5	64.9	2.9	0.5	0.2	373.5
	Rg7923	6.9	1.75	28.2	67.1	2.2	0.8	0.3	165.3
	Rg7924	6.8	2.94	15.8	77.9	4.4	0.6	0.4	262.0
	Rg7925	8.6	7.40	34.6	61.1	1.1	1.7	0.5	648.7
	Rg7926	6.6	2.26	25.7	70.0	1.6	1.6	0.4	207.7
	Rg7927	7.2	2.96	24.8	68.3	2.9	0.9	0.6	289.4
	Rg7928	7.4	2.35	35.9	60.4	1.3	1.1	0.3	231.9

M: Male.

 

APPENDIX 11 (Contd…). INDIVIDUAL ANIMAL HAEMATOLOGY RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Absolute Neutrophils	Absolute Lymphocytes	Absolute Monocytes	Absolute Eosinophils	Absolute Basophils	Prothrombin Time	Activated Prothrombin Time
		(Neut)	(Lymph)	(Mono)	(Eos)	(Baso)	(PT)	(APTT)
		(10^3 cells/µL)	(10^3 cells/µL)	(10^3 cells/µL)	(10^3 cells/µL)	(10^3 cells/µL)	(Seconds)	(Seconds)
G3, M & 300	Rg7905	3.95	6.62	0.29	0.09	0.05	29.0	25.6
	Rg7906	4.69	8.29	0.34	0.18	0.06	23.9	26.7
	Rg7907	2.97	8.23	0.41	0.09	0.03	22.9	26.8
	Rg7908	1.87	8.45	0.41	0.08	0.04	21.4	15.2
	Rg7909	4.10	5.90	0.18	0.27	0.03	20.0	20.4
	Rg7910	4.18	6.64	0.14	0.06	0.02	20.0	19.5
	Rg7911	2.15	6.64	0.12	0.17	0.02	22.4	23.0
	Rg7912	2.31	10.08	0.35	0.12	0.06	22.0	28.2
	Rg7913	5.26	12.06	0.27	0.14	0.07	24.2	21.0
	Rg7914	2.38	9.22	0.28	0.16	0.03	26.2	13.1
	Rg7915	3.71	14.71	0.60	0.18	0.11	19.8	22.4
	Rg7916	3.47	11.45	0.67	0.14	0.09	23.5	23.7
G4, M & 600	Rg7917	2.61	7.19	0.35	0.13	0.03	18.0	18.3
	Rg7918	1.33	4.98	0.24	0.10	0.01	22.9	14.4
	Rg7919	2.06	7.29	0.42	0.10	0.03	19.3	15.2
	Rg7920	1.78	6.30	0.41	0.05	0.03	21.3	16.0
	Rg7921	2.47	9.18	0.25	0.20	0.03	22.3	16.9
	Rg7922	3.23	6.87	0.31	0.06	0.02	24.7	17.8
	Rg7923	3.53	8.40	0.27	0.10	0.04	23.6	17.8
	Rg7924	1.68	8.28	0.47	0.06	0.04	22.8	21.7
	Rg7925	3.66	6.47	0.12	0.18	0.05	23.1	46.1
	Rg7926	4.28	11.68	0.26	0.26	0.06	20.6	11.5
	Rg7927	2.74	7.52	0.32	0.10	0.07	20.3	29.4
	Rg7928	3.63	6.12	0.13	0.12	0.03	23.6	18.0

M: Male.

 

 

APPENDIX 11 (Contd…). INDIVIDUAL ANIMAL HAEMATOLOGY RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Total Leucocyte Count	Total Erythrocyte Count	Hemoglobin	Haematocrit	Mean Corpuscular Volume	Mean Corpuscular Hemoglobin	Mean Corpuscular Hemoglobin Concentration	Platelet Count
		(WBC)	(RBC)	(HGB)	(HCT)	(MCV)	(MCH)	(MCHC)	(PLT)
		(10^3 cells/µL)	(10^6 cells/µL)	(g/dL)	(%)	(fL)	(pg)	(g/dL)	(10^3 cells/µL)
G1, F & 0	Rg7929	10.60	8.19	15.7	47.5	58.0	19.2	33.2	1443
	Rg7930	10.65	7.59	14.7	43.2	56.9	19.3	34.0	1233
	Rg7931	11.90	8.00	14.8	46.6	58.2	18.5	31.8	962
	Rg7932	9.57	7.51	15.3	46.6	62.1	20.4	32.9	897
	Rg7933	11.79	8.20	14.3	44.5	54.2	17.5	32.3	1134
	Rg7934	18.27	8.12	14.4	43.9	54.0	17.8	32.9	1130
	Rg7935	12.12	6.27	13.6	42.1	67.2	21.7	32.3	1478
	Rg7936	5.12	8.19	16.2	48.4	59.0	19.8	33.6	816
	Rg7937	12.05	7.88	15.7	44.8	56.9	19.9	35.0	913
	Rg7938	4.28	8.72	16.8	51.8	59.4	19.3	32.4	1053
	Rg7939	6.84	7.88	14.2	44.4	56.4	18.0	31.9	1136
	Rg7940	10.70	7.38	13.5	42.1	57.1	18.2	32.0	1071
G2, F & 150	Rg7941	3.86	7.55	15.7	47.2	62.6	20.8	33.2	764
	Rg7942	7.43	7.92	15.1	44.4	56.1	19.0	34.0	975
	Rg7943	15.17	9.05	16.5	50.8	56.1	18.2	32.4	314
	Rg7944	5.17	7.21	14.1	44.6	61.8	19.5	31.5	1062
	Rg7945	7.93	8.49	15.6	46.3	54.5	18.4	33.7	1198
	Rg7946	9.57	7.51	14.5	45.4	60.5	19.3	31.9	573
	Rg7947	9.91	6.74	14.0	43.0	63.8	20.8	32.6	1277
	Rg7948	6.38	8.40	16.0	48.2	57.3	19.1	33.3	1041
	Rg7949	6.80	8.37	14.9	45.2	54.0	17.9	33.1	999
	Rg7950	13.60	8.20	15.1	45.5	55.5	18.4	33.1	1158
	Rg7951	13.47	6.53	12.9	40.2	61.5	19.8	32.1	924
	Rg7952	16.68	6.46	14.2	44.2	68.5	22.0	32.2	609

F: Female.

 

 

APPENDIX 11 (Contd…). INDIVIDUAL ANIMAL HAEMATOLOGY RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Mean Platelet Volume	Reticulocyte Count	Neutrophils	Lymphocytes	Monocytes	Eosinophils	Basophils	Absolute Reticulocyte Count
		(MPV)	(Retic)	(Neut)	(Lymph)	(Mono)	(Eos)	(Baso)	(Retic)
		(fL)	(%)	(%)	(%)	(%)	(%)	(%)	(10^9 cells/L)
G1, F & 0	Rg7929	7.2	2.90	33.2	54.6	4.9	5.3	0.3	237.7
	Rg7930	7.5	9.91	27.3	67.8	1.3	2.2	0.3	752.5
	Rg7931	7.4	2.74	43.1	52.5	1.9	1.1	0.2	218.9
	Rg7932	7.8	3.76	36.4	55.3	5.1	1.1	0.2	282.1
	Rg7933	7.5	2.14	39.3	54.6	3.3	1.8	0.2	175.6
	Rg7934	8.1	2.17	28.2	67.6	1.7	0.8	0.2	176.1
	Rg7935	8.0	8.88	18.0	77.4	2.6	0.8	0.4	556.4
	Rg7936	7.2	4.42	37.9	48.6	8.8	1.5	0.4	362.1
	Rg7937	7.1	3.87	31.1	63.2	3.4	1.2	0.3	305.1
	Rg7938	7.7	2.82	36.8	50.5	8.2	1.6	0.2	245.6
	Rg7939	7.4	3.52	22.4	67.9	5.3	1.4	0.3	277.3
	Rg7940	7.0	3.59	27.7	65.5	3.7	1.2	0.2	264.9
G2, F & 150	Rg7941	8.6	2.37	33.7	51.1	7.3	4.9	0.2	178.9
	Rg7942	7.5	2.60	22.8	71.1	3.3	1.8	0.2	206.1
	Rg7943	7.6	4.73	34.6	59.6	2.1	1.9	0.3	427.9
	Rg7944	7.7	0.00	21.6	71.3	4.3	0.9	0.2	0.0
	Rg7945	8.7	2.81	15.3	78.7	2.3	2.4	0.3	238.7
	Rg7946	7.9	4.52	28.6	63.7	5.2	1.3	0.3	339.4
	Rg7947	7.5	7.42	37.3	57.8	3.1	0.5	0.3	500.5
	Rg7948	7.2	3.12	29.7	63.6	3.8	1.3	0.2	262.3
	Rg7949	7.3	2.02	20.5	71.8	2.1	4.0	0.3	169.2
	Rg7950	7.4	3.30	34.2	59.0	3.8	1.2	0.3	270.7
	Rg7951	7.3	6.52	30.2	64.6	3.1	0.6	0.3	426.0
	Rg7952	8.6	10.56	38.7	55.3	2.5	1.9	0.3	682.2

F: Female.

 

 

APPENDIX 11 (Contd…). INDIVIDUAL ANIMAL HAEMATOLOGY RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Absolute Neutrophils	Absolute Lymphocytes	Absolute Monocytes	Absolute Eosinophils	Absolute Basophils	Prothrombin Time	Activated Prothrombin Time
		(Neut)	(Lymph)	(Mono)	(Eos)	(Baso)	(PT)	(APTT)
		(10^3 cells/µL)	(10^3 cells/µL)	(10^3 cells/µL)	(10^3 cells/µL)	(10^3 cells/µL)	(Seconds)	(Seconds)
G1, F & 0	Rg7929	3.52	5.79	0.52	0.56	0.04	19.9	20.2
	Rg7930	2.90	7.21	0.14	0.23	0.03	21.3	27.5
	Rg7931	5.13	6.25	0.23	0.13	0.02	22.0	20.4
	Rg7932	3.49	5.29	0.49	0.11	0.02	18.5	24.9
	Rg7933	4.63	6.43	0.39	0.21	0.02	23.6	20.3
	Rg7934	5.15	12.35	0.31	0.14	0.04	22.5	17.6
	Rg7935	2.18	9.39	0.32	0.09	0.04	22.0	29.3
	Rg7936	1.94	2.49	0.45	0.08	0.02	21.4	22.3
	Rg7937	3.74	7.61	0.41	0.15	0.03	23.9	26.4
	Rg7938	1.57	2.16	0.35	0.07	0.01	21.1	17.9
	Rg7939	1.53	4.65	0.36	0.10	0.02	21.2	20.0
	Rg7940	2.97	7.01	0.40	0.13	0.02	31.2	21.5
G2, F & 150	Rg7941	1.30	1.97	0.28	0.19	0.01	22.4	26.4
	Rg7942	1.70	5.29	0.24	0.14	0.01	19.7	16.7
	Rg7943	5.25	9.05	0.33	0.28	0.04	26.5	20.0
	Rg7944	1.12	3.68	0.22	0.05	0.01	20.1	25.3
	Rg7945	1.21	6.25	0.18	0.19	0.03	18.4	15.1
	Rg7946	2.74	6.10	0.49	0.12	0.03	21.7	29.5
	Rg7947	3.69	5.72	0.30	0.05	0.03	21.6	31.6
	Rg7948	1.89	4.06	0.24	0.09	0.01	21.0	17.2
	Rg7949	1.39	4.88	0.14	0.27	0.02	17.6	11.9
	Rg7950	4.65	8.03	0.52	0.17	0.04	23.9	18.7
	Rg7951	4.07	8.71	0.42	0.08	0.05	28.4	21.1
	Rg7952	6.45	9.23	0.42	0.31	0.06	18.2	16.2

F: Female.

 

 

APPENDIX 11 (Contd…). INDIVIDUAL ANIMAL HAEMATOLOGY RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Total Leucocyte Count	Total Erythrocyte Count	Hemoglobin	Haematocrit	Mean Corpuscular Volume	Mean Corpuscular Hemoglobin	Mean Corpuscular Hemoglobin Concentration	Platelet Count
		(WBC)	(RBC)	(HGB)	(HCT)	(MCV)	(MCH)	(MCHC)	(PLT)
		(10^3 cells/µL)	(10^6 cells/µL)	(g/dL)	(%)	(fL)	(pg)	(g/dL)	(10^3 cells/µL)
G3, F & 300	Rg7953	11.24	8.08	13.8	42.3	52.3	17.1	32.6	1324
	Rg7954	11.74	8.14	15.6	46.2	56.8	19.1	33.7	1021
	Rg7955	9.91	8.34	16.1	48.2	57.8	19.3	33.4	1057
	Rg7956	16.54	5.95	12.3	41.3	69.4	20.7	29.8	899
	Rg7957	9.20	6.50	14.2	43.0	66.2	21.8	33.0	1147
	Rg7958	13.57	7.52	14.4	45.8	59.3	18.7	31.5	911
	Rg7959	8.79	5.64	12.2	39.6	70.1	21.6	30.8	607
	Rg7960	5.58	7.40	15.1	45.7	61.8	20.4	33.0	985
	Rg7961	19.84	6.02	12.9	41.6	69.2	21.5	31.1	891
	Rg7962	7.68	8.28	14.7	44.7	53.9	17.8	33.0	1239
	Rg7963	10.61	7.41	13.4	41.7	56.3	18.1	32.2	1223
	Rg7964	17.00	7.30	15.1	45.6	62.4	20.7	33.2	897
G4, F & 600	Rg7965	13.42	7.85	16.7	50.4	64.2	21.3	33.2	794
	Rg7966	10.04	8.58	16.3	50.7	59.1	19.0	32.2	1040
	Rg7967	7.05	7.99	15.1	45.0	56.2	18.9	33.5	1438
	Rg7968	17.02	8.11	15.4	46.5	57.3	18.9	33.1	1059
	Rg7969	14.81	7.92	15.8	49.5	62.5	19.9	31.9	1248
	Rg7970	7.46	7.37	14.8	46.4	63.0	20.1	31.9	1737
	Rg7971	12.64	7.56	15.2	46.0	60.9	20.1	33.0	1037
	Rg7972	-	-	-	-	-	-	-	-
	Rg7973	8.66	8.33	15.8	46.7	56.1	18.9	33.7	1043
	Rg7974	13.31	8.51	14.7	45.2	53.1	17.3	32.6	1400
	Rg7975	14.06	7.66	14.4	43.7	57.0	18.8	33.0	710
	Rg7976	10.21	7.26	15.2	46.9	64.7	20.9	32.4	794

F: Female.

Note: Animal number Rg7972 from group G4 was found dead on lactation day (LD) 5.

APPENDIX 11 (Contd…). INDIVIDUAL ANIMAL HAEMATOLOGY RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Mean Platelet Volume	Reticulocyte Count	Neutrophils	Lymphocytes	Monocytes	Eosinophils	Basophils	Absolute Reticulocyte Count
		(MPV)	(Retic)	(Neut)	(Lymph)	(Mono)	(Eos)	(Baso)	(Retic)
		(fL)	(%)	(%)	(%)	(%)	(%)	(%)	(10^9 cells/L)
G3, F & 300	Rg7953	7.9	4.03	26.4	69.1	2.0	1.5	0.3	325.9
	Rg7954	7.1	3.74	31.3	63.3	3.1	1.1	0.3	304.6
	Rg7955	8.3	3.82	41.8	53.1	2.4	1.4	0.2	318.3
	Rg7956	7.6	11.09	29.0	65.0	3.6	0.6	0.2	659.5
	Rg7957	7.1	5.34	28.5	65.5	2.3	1.6	0.3	346.9
	Rg7958	8.6	2.71	41.9	42.8	4.4	0.2	0.4	209.0
	Rg7959	8.6	9.70	21.1	64.7	7.6	0.7	0.3	547.5
	Rg7960	7.9	4.49	39.5	53.6	1.8	1.2	0.2	332.2
	Rg7961	8.5	12.76	19.6	73.1	4.5	1.3	0.4	767.9
	Rg7962	6.8	12.49	24.2	68.4	3.8	2.5	0.2	170.4
	Rg7963	7.2	6.89	19.3	76.1	2.0	1.2	0.4	510.3
	Rg7964	7.6	2.91	47.6	46.4	4.0	0.9	0.3	212.2
G4, F & 600	Rg7965	7.6	4.77	21.3	71.2	3.4	3.0	0.3	374.8
	Rg7966	7.6	4.19	27.6	67.9	2.2	0.6	0.3	359.2
	Rg7967	7.7	4.65	27.3	68.1	1.2	2.2	0.3	371.6
	Rg7968	6.9	2.05	39.2	54.0	4.6	0.2	0.3	166.3
	Rg7969	7.6	3.62	17.8	77.9	2.1	0.5	0.4	286.4
	Rg7970	7.5	3.11	23.8	71.4	1.8	1.4	0.4	229.3
	Rg7971	7.6	5.03	37.3	55.5	4.5	1.2	0.2	380.1
	Rg7972	-	-	-	-	-	-	-	-
	Rg7973	8.4	2.85	32.3	60.6	2.4	3.3	0.4	237.7
	Rg7974	7.9	1.06	13.1	82.7	1.9	1.1	0.3	89.9
	Rg7975	7.7	2.51	38.4	57.2	2.5	0.9	0.1	192.3
	Rg7976	7.9	4.50	15.6	81.1	1.4	0.6	0.3	326.5

F: Female.

Note: Animal number Rg7972 from group G4 was found dead on lactation day (LD) 5.

 

 

APPENDIX 11 (Contd…). INDIVIDUAL ANIMAL HAEMATOLOGY RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Absolute Neutrophils	Absolute Lymphocytes	Absolute Monocytes	Absolute Eosinophils	Absolute Basophils	Prothrombin Time	Activated Prothrombin Time
		(Neut)	(Lymph)	(Mono)	(Eos)	(Baso)	(PT)	(APTT)
		(10^3 cells/µL)	(10^3 cells/µL)	(10^3 cells/µL)	(10^3 cells/µL)	(10^3 cells/µL)	(Seconds)	(Seconds)
G3, F & 300	Rg7953	2.97	7.77	0.23	0.17	0.04	21.4	33.9
	Rg7954	3.68	7.44	0.36	0.13	0.03	21.0	18.4
	Rg7955	4.15	5.27	0.24	0.14	0.02	23.0	15.1
	Rg7956	4.80	10.75	0.60	0.09	0.04	18.7	30.1
	Rg7957	2.62	6.03	0.21	0.15	0.03	20.7	21.5
	Rg7958	5.69	5.81	0.60	0.03	0.05	17.2	19.5
	Rg7959	1.86	5.69	0.67	0.06	0.03	22.4	30.2
	Rg7960	2.20	2.99	0.10	0.07	0.01	17.4	15.5
	Rg7961	3.90	14.50	0.89	0.26	0.09	17.9	21.9
	Rg7962	1.86	5.25	0.29	0.19	0.02	15.1	19.4
	Rg7963	2.04	8.07	0.21	0.13	0.04	23.7	32.2
	Rg7964	8.09	7.88	0.68	0.15	0.04	20.7	18.4
G4, F & 600	Rg7965	2.86	9.56	0.46	0.40	0.04	22.5	16.8
	Rg7966	2.77	6.82	0.22	0.07	0.03	21.4	19.2
	Rg7967	1.92	4.80	0.09	0.16	0.02	18.1	26.6
	Rg7968	6.68	9.19	0.78	0.04	0.05	20.8	21.1
	Rg7969	2.63	11.53	0.31	0.07	0.06	16.6	19.4
	Rg7970	1.78	5.33	0.13	0.11	0.03	21.4	19.6
	Rg7971	4.71	7.01	0.57	0.15	0.02	20.5	16.1
	Rg7972	-	-	-	-	-	-	-
	Rg7973	2.80	5.24	0.21	0.28	0.04	23.2	19.7
	Rg7974	1.74	11.01	0.26	0.14	0.03	22.3	20.1
	Rg7975	5.40	8.05	0.35	0.13	0.02	19.4	20.4
	Rg7976	1.59	8.28	0.14	0.06	0.03	19.1	29.3

F: Female.

Note: Animal number Rg7972 from group G4 was found dead on lactation day (LD) 5.

 

 

 

• INDIVIDUAL ANIMAL VAGINAL SMEAR EXAMINATION RECORD FOR DETERMINATION OF
  OESTRUS CYCLICITY

Group, Sex & Dose (mg/kg body weight/day)

Animal No.

Stages of the Oestrus Cyclicity on Experimental Day

Pre-mating period

Mating period

At termination

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

G1 & 0

Rg7929

M

D

D

P

E

M

D

P

E

M

D

D

P

E

E+

-

-

-

-

-

-

-

-

-

-

-

D

Rg7930

M

D

P

E

M

D

D

P

E

M

D

D

P

E

E+

-

-

-

-

-

-

-

-

-

-

-

P

Rg7931

P

E

M

D

D

P

E

M

D

D

P

E

M

D

P

E+

-

-

-

-

-

-

-

-

-

-

D

Rg7932

E

M

D

D

P

E

M

D

P

E

M

D

P

E

E+

-

-

-

-

-

-

-

-

-

-

-

D

Rg7933

D

P

E

M

D

D

P

E

M

D

D

P

E

M

D

D

E+

-

-

-

-

-

-

-

-

-

D

Rg7934

D

P

E

M

D

P

E

M

D

D

P

E

M

D

P

E+

-

-

-

-

-

-

-

-

-

-

D

Rg7935

D

P

E

M

D

D

P

E

M

D

D

P

E

M

D

D

P

E

M

D

D

P

E+

-

-

-

D

Rg7936

D

P

E

M

D

D

P

E

M

D

D

P

E

M

D

D

P

E

E+

-

-

-

-

-

-

-

D

Rg7937

M

D

P

E

M

D

D

P

E

M

D

D

P

E

E+

-

-

-

-

-

-

-

-

-

-

-

D

Rg7938

E

M

D

D

P

E

M

D

P

E

M

D

P

E

D

D

P

E+

-

-

-

-

-

-

-

-

D

Rg7939

E

M

D

D

P

E

M

D

D

P

E

M

D

D

E+

-

-

-

-

-

-

-

-

-

-

-

D

Rg7940

D

P

E

M

D

D

P

E

M

D

P

E

M

D

D

E+

-

-

-

-

-

-

-

-

-

-

D

G2 & 150

Rg7941

E

M

D

D

P

E

M

D

P

E

M

D

P

E

E+

-

-

-

-

-

-

-

-

-

-

-

M

Rg7942

D

P

E

M

D

D

P

E

M

D

P

E

M

D

D

E+

-

-

-

-

-

-

-

-

-

-

P

Rg7943

D

P

E

M

D

D

P

E

M

D

D

P

E

M

D

D

E+

-

-

-

-

-

-

-

-

-

D

Rg7944

D

P

E

M

D

D

P

E

M

D

D

P

E

M

D

D

E+

-

-

-

-

-

-

-

-

-

E

Rg7945

M

D

D

P

E

M

D

P

E

M

D

D

P

E

M

D

P

E+

-

-

-

-

-

-

-

-

P

Rg7946

M

D

D

P

E

M

D

P

E

M

D

D

P

E

E+

-

-

-

-

-

-

-

-

-

-

-

D

Rg7947

D

P

E

M

D

D

P

E

M

D

P

E

M

D

D

P

E

E+

-

-

-

-

-

-

-

-

D

Rg7948

M

D

D

P

E

M

D

P

E

M

D

D

P

E

E+

-

-

-

-

-

-

-

-

-

-

-

D

Rg7949^NP

M

D

D

P

E

M

D

P

E

M

D

D

P

E

E+

-

-

-

-

-

-

-

-

-

-

-

P

Rg7950

D

P

E

M

D

D

P

E

M

D

P

E

M

D

D

E+

-

-

-

-

-

-

-

-

-

-

D

Rg7951

E

M

D

D

P

E

M

D

D

P

E

M

D

D

P

E

M

D

D

P

E

M

D

P

E

E+

D

Rg7952

D

P

E

M

D

P

E

M

D

D

P

E

M

D

D

P

E+

-

-

-

-

-

-

-

-

-

D

F: Female; P: Proestrus: E: Oestrus: M: Metestrus: D: Diestrus; -: Not applicable; NP: Non-pregnant.

APPENDIX 12 (Contd…). INDIVIDUAL ANIMAL VAGINAL SMEAR EXAMINATION RECORD FOR DETERMINATION OF
OESTRUS CYCLICITY

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Stages of the Oestrus Cyclicity on Experimental Day
		Pre-mating period															Mating period																				At termination
		1	2	3	4	5	6	7	8	9	10	11	12	13	14		15	16	17	18	19	20	21	22	23	24	25	26	27	28	29	30	31	32	33
G3 & 300	Rg7953^NP	M	D	D	P	E	M	D	P	E	M	D	D	P	E		E+	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-		E
	Rg7954	D	P	E	M	D	D	P	E	M	D	D	P	E	M		D	D	E+	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-		D
	Rg7955	D	P	E	M	D	D	P	E	M	D	P	E	M	D		E+	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-		D
	Rg7956	E	M	D	D	P	E	M	D	D	P	E	M	D	D		E+	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-		D
	Rg7957^NP	D	P	E	M	D	D	P	E	M	D	D	P	E	M		D	P	E	M	D	P	E+	-	-	-	-	-	-	-	-	-	-	-	-		P
	Rg7958	D	P	E	M	D	D	P	E	M	D	D	P	E	M		D	D	P	E	M	D	D	P	E	D	D	P	E	M	D	P	E+	-	-		M
	Rg7959	D	P	E	D	D	P	E	M	D	P	E	M	D	D		E+	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-		D
	Rg7960	E	M	D	D	P	E	M	D	P	E	M	D	P	E		E+	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-		M
	Rg7961	P	E	D	D	P	E	M	D	D	P	E	M	D	D		P	E	E+	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-		D
	Rg7962	M	D	D	P	E	M	D	P	E	M	D	D	P	E		D	D	P	E	M	D	D	P	E	E+	-	-	-	-	-	-	-	-	-		M
	Rg7963^TL	E	M	D	P	E	M	D	D	P	E	M	D	P	E		M	D	D	P	E	M	D	P	E+	-	-	-	-	-	-	-	-	-	-		E
	Rg7964	D	P	E	M	D	D	P	E	M	D	D	P	E	M		D	D	E+	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-		D
G4 & 600	Rg7965^TL	M	D	D	P	E	M	D	P	E	M	D	D	P	E		D	D	D	P	E	M	D	D	E+	-	-	-	-	-	-	-	-	-	-		P
	Rg7966	P	E	M	D	D	P	E	M	D	P	E	M	D	P		E	M	D	D	P	E	E+	-	-	-	-	-	-	-	-	-	-	-	-		D
	Rg7967^TL	D	P	E	M	D	D	P	E	M	D	D	P	E	M		D	D	E+	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-		P
	Rg7968	D	P	E	M	D	D	P	E	M	D	D	P	E	M		D	P	E+	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-		D
	Rg7969	D	P	E	M	D	D	P	E	M	D	P	E	M	D		D	P	E	M	D	D	E+	-	-	-	-	-	-	-	-	-	-	-	-		M
	Rg7970	E	M	D	D	P	E	M	D	P	E	M	D	P	E		E+	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-		M
	Rg7971	E	M	D	D	P	E	M	D	D	P	E	M	D	D		E+	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-		D
	Rg7972^TL	E	M	D	D	P	E	M	D	D	P	E	M	D	D		E+	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-		-
	Rg7973^NP	D	P	E	M	D	D	P	E	M	D	D	P	E	M		D	D	P	E	M	D	D	P	E	D	D	P	E	M	D	D	D	P	E+		E
	Rg7974	D	P	E	M	D	D	P	E	M	D	D	P	E	M		D	D	E+	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-		D
	Rg7975	E	M	D	D	P	E	M	D	P	E	M	D	P	E		M	D	P	E+	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-		D
	Rg7976	D	P	E	M	D	D	P	E	M	D	D	P	E	M		D	D	P	E	M	D	D	P	E	M	D	D	P	E	D	D	E	E+	-		D

F: Female; P: Proestrus: E: Oestrus: M: Metestrus: D: Diestrus; -: Not applicable; NP: Non-pregnant; TL: Total litter loss.

APPENDIX 12 (Contd…). INDIVIDUAL ANIMAL VAGINAL SMEAR EXAMINATION RECORD FOR DETERMINATION OF
OESTRUS CYCLICITY

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	No. of Oestrus Cycles				Length of Oestrus Cycle (Days)					Mean Oestrus Cycle Length (Days)
		Total	Regular	Irregular		Cycle 1	Cycle 2	Cycle 3	Cycle 4	Cycle 5
G1 & 0	Rg7929	2	2	0		4	5	-	-	-	4.5
	Rg7930	2	2	0		5	5	-	-	-	5.0
	Rg7931	3	3	0		5	5	4	-	-	4.7
	Rg7932	3	3	0		5	4	4	-	-	4.3
	Rg7933	3	3	0		5	5	4	-	-	4.7
	Rg7934	3	3	0		4	5	4	-	-	4.3
	Rg7935	4	4	0		5	5	5	5	-	5.0
	Rg7936	3	3	0		5	5	5	-	-	5.0
	Rg7937	2	2	0		5	5	-	-	-	5.0
	Rg7938	4	4	0		5	4	4	4	-	4.3
	Rg7939	3	3	0		5	5	4	-	-	4.7
	Rg7940	3	3	0		5	4	4	-	-	4.3
G2 & 150	Rg7941	3	3	0		5	4	4	-	-	4.3
	Rg7942	3	3	0		5	4	4	-	-	4.3
	Rg7943	3	3	0		5	5	4	-	-	4.7
	Rg7944	3	3	0		5	5	4	-	-	4.7
	Rg7945	3	3	0		4	5	4	-	-	4.3
	Rg7946	2	2	0		4	5	-	-	-	4.5
	Rg7947	3	3	0		5	4	5	-	-	4.7
	Rg7948	2	2	0		4	5	-	-	-	4.5
	Rg7949^NP	2	2	0		4	5	-	-	-	4.5
	Rg7950	3	3	0		5	4	4	-	-	4.3
	Rg7951	5	5	0		5	5	5	5	4	4.8
	Rg7952	3	3	0		4	5	5	-	-	4.7

F: Female; -: Not applicable; NP: Non-pregnant.

 

APPENDIX 12 (Contd…). INDIVIDUAL ANIMAL VAGINAL SMEAR EXAMINATION RECORD FOR DETERMINATION OF
OESTRUS CYCLICITY

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	No. of Oestrus Cycles				Length of Oestrus Cycle (Days)						Mean Oestrus Cycle Length (Days)
		Total	Regular	Irregular		Cycle 1	Cycle 2	Cycle 3	Cycle 4	Cycle 5	Cycle 6
G3 & 300	Rg7953^NP	2	2	0		4	5	-	-	-	-	4.5
	Rg7954	3	3	0		5	5	4	-	-	-	4.7
	Rg7955	3	2	1		5	4	3	-	-	-	4.0
	Rg7956	3	3	0		5	5	4	-	-	-	4.7
	Rg7957^NP	4	4	0		5	5	4	4	-	-	4.5
	Rg7958	6	6	0		5	5	5	5	4	4	4.7
	Rg7959	3	3	0		4	4	4	-	-	-	4.0
	Rg7960	3	3	0		5	4	4	-	-	-	4.3
	Rg7961	3	3	0		4	5	5	-	-	-	4.7
	Rg7962	4	4	0		4	5	4	5	-	-	4.5
	Rg7963^TL	5	5	0		4	5	4	5	4	-	4.4
	Rg7964	3	3	0		5	5	4	-	-	-	4.7
G4 & 600	Rg7965^TL	4	4	0		4	5	5	4	-	-	4.5
	Rg7966	4	4	0		5	4	4	5	-	-	4.5
	Rg7967^TL	3	3	0		5	5	4	-	-	-	4.7
	Rg7968	3	3	0		5	5	4	-	-	-	4.7
	Rg7969	4	4	0		5	4	5	4	-	-	4.5
	Rg7970	3	3	0		5	4	4	-	-	-	4.3
	Rg7971	3	3	0		5	5	4	-	-	-	4.7
	Rg7972^TL	3	3	0		5	5	4	-	-	-	4.7
	Rg7973^NP	6	5	1		5	5	5	5	4	6	5.0
	Rg7974	3	3	0		5	5	4	-	-	-	4.7
	Rg7975	4	4	0		5	4	4	4	-	-	4.3
	Rg7976	6	5	1		5	5	5	5	5	3	4.7

F: Female; -: Not applicable; NP: Non-pregnant; TL: Total litter loss.

• INDIVIDUAL DAM/LITTER DELIVERY AND LITTER OBSERVATIONS RECORD

Group & Dose (mg/kg body weight/day)	Dam No.	Delivery Record At birth															Sex Ratio (m/f) at Birth		Live Birth Index (%)
		Litter Size (No.)		Live Pups (No.)				Dead Pups (No.)				Cannibalized Pups (No.)
				Male	Female	Total		Male	Female	Total		Undetermined	Male	Female	Total
G1 & 0	Rg7929	10		6	4	10		0	0	0		0	0	0	0		1.5		100.00
	Rg7930	8		3	5	8		0	0	0		0	0	0	0		0.6		100.00
	Rg7931	13		7	6	13		0	0	0		0	0	0	0		1.2		100.00
	Rg7932	8		4	4	8		0	0	0		0	0	0	0		1.0		100.00
	Rg7933	11		9	2	11		0	0	0		0	0	0	0		4.5		100.00
	Rg7934	9		4	5	9		0	0	0		0	0	0	0		0.8		100.00
	Rg7935	13		7	6	13		0	0	0		0	0	0	0		1.2		100.00
	Rg7936	12		6	6	12		0	0	0		0	0	0	0		1.0		100.00
	Rg7937	5		2	3	5		0	0	0		0	0	0	0		0.7		100.00
	Rg7938	17		10	7	17		0	0	0		0	0	0	0		1.4		100.00
	Rg7939	13		8	5	13		0	0	0		0	0	0	0		1.6		100.00
	Rg7940	8		4	4	8		0	0	0		0	0	0	0		1.0		100.00
G2 & 150	Rg7941	16		6	10	16		0	0	0		0	0	0	0		0.6		100.00
	Rg7942	8		4	4	8		0	0	0		0	0	0	0		1.0		100.00
	Rg7943	10		6	3	9		1	0	1		0	0	0	0		2.0		90.00
	Rg7944	10		3	7	10		0	0	0		0	0	0	0		0.4		100.00
	Rg7945	8		5	3	8		0	0	0		0	0	0	0		1.7		100.00
	Rg7946	7		3	3	6		1	0	1		0	0	0	0		1.0		85.71
	Rg7947	10		6	4	10		0	0	0		0	0	0	0		1.5		100.00
	Rg7948	16		8	8	16		0	0	0		0	0	0	0		1.0		100.00
	Rg7949^NP	-		-	-	-		-	-	-		-	-	-	-		-		-
	Rg7950	4		4	0	4		0	0	0		0	0	0	0		-		100.00
	Rg7951	6		3	3	6		0	0	0		0	0	0	0		1.0		100.00
	Rg7952	12		6	6	12		0	0	0		0	0	0	0		1.0		100.00

m/f: Male/Female; NP: Non-pregnant; -: Not applicable; %: Percentage

 

APPENDIX 13 (Contd…). INDIVIDUAL DAM/LITTER DELIVERY AND LITTER OBSERVATIONS RECORD

Group & Dose (mg/kg body weight/day)	Dam No.	Delivery Record At birth															Sex Ratio (m/f) at Birth		Live Birth Index (%)
		Litter Size (No.)		Live Pups (No.)				Dead Pups (No.)				Cannibalized Pups (No.)
				Male	Female	Total		Male	Female	Total		Undetermined	Male	Female	Total
G3 & 300	Rg7953^NP	-		-	-	-		-	-	-		-	-	-	-		-		-
	Rg7954	4		4	0	4		0	0	0		0	0	0	0		-		100.00
	Rg7955	10		6	4	10		0	0	0		0	0	0	0		1.5		100.00
	Rg7956	13		7	6	13		0	0	0		0	0	0	0		1.2		100.00
	Rg7957^NP	-		-	-	-		-	-	-		-	-	-	-		-		-
	Rg7958	6		3	1	4		1	1	2		0	0	0	0		3.0		66.67
	Rg7959	9		4	5	9		0	0	0		0	0	0	0		0.8		100.00
	Rg7960	13		8	4	12		1	0	1		0	0	0	0		2.0		92.31
	Rg7961	11		5	6	11		0	0	0		0	0	0	0		0.8		100.00
	Rg7962	10		6	4	10		0	0	0		0	0	0	0		1.5		100.00
	Rg7963^TL	6		0	0	0		4	2	6		0	0	0	0		-		0.00
	Rg7964	18		7	11	18		0	0	0		0	0	0	0		0.6		100.00
G4 & 600	Rg7965^TL	3		1	0	1		0	2	2		0	0	0	0		-		33.33
	Rg7966	7		3	4	7		0	0	0		0	0	0	0		0.8		100.00
	Rg7967^TL	6		0	0	0		2	4	6		0	0	0	0		-		0.00
	Rg7968	14		8	6	14		0	0	0		0	0	0	0		1.3		100.00
	Rg7969	13		4	8	12		1	0	1		0	0	0	0		0.5		92.31
	Rg7970	10		4	6	10		0	0	0		0	0	0	0		0.7		100.00
	Rg7971	12		4	8	12		0	0	0		0	0	0	0		0.5		100.00
	Rg7972^TL	15		3	8	11		2	2	4		0	0	0	0		0.4		73.33
	Rg7973^NP	-		-	-	-		-	-	-		-	-	-	-		-		-
	Rg7974	19		8	10	18		1	0	1		0	0	0	0		0.8		94.74
	Rg7975	14		6	8	14		0	0	0		0	0	0	0		0.8		100.00
	Rg7976	9		4	5	9		0	0	0		0	0	0	0		0.8		100.00

m/f: Male/Female; NP: Non-pregnant; TL: Total litter loss; -: Not applicable; %: Percentage.

 

APPENDIX 13 (Contd…). INDIVIDUAL DAM/LITTER DELIVERY AND LITTER OBSERVATIONS RECORD

Group & Dose (mg/kg body weight/day)	Dam No.	LD 1 to 4												Sex Ratio (m/f) on LD 4		Pup Survival Index (%) [LD 1 to 4]
		Live Pups (No.)				Dead Pups (No.)				Cannibalized Pups (No.)
		Male	Female	Total		Male	Female	Total		Male	Female	Total
G1 & 0	Rg7929	6	4	10		0	0	0		0	0	0		1.5		100.00
	Rg7930	3	5	8		0	0	0		0	0	0		0.6		100.00
	Rg7931	7	6	13		0	0	0		0	0	0		1.2		100.00
	Rg7932	3	3	6		0	1	1		1	0	1		1.0		75.00
	Rg7933	9	2	11		0	0	0		0	0	0		4.5		100.00
	Rg7934	4	5	9		0	0	0		0	0	0		0.8		100.00
	Rg7935	7	6	13		0	0	0		0	0	0		1.2		100.00
	Rg7936	6	6	12		0	0	0		0	0	0		1.0		100.00
	Rg7937	2	3	5		0	0	0		0	0	0		0.7		100.00
	Rg7938	10	7	17		0	0	0		0	0	0		1.4		100.00
	Rg7939	8	5	13		0	0	0		0	0	0		1.6		100.00
	Rg7940	4	4	8		0	0	0		0	0	0		1.0		100.00
G2 & 150	Rg7941	6	10	16		0	0	0		0	0	0		0.6		100.00
	Rg7942	4	4	8		0	0	0		0	0	0		1.0		100.00
	Rg7943	6	3	9		0	0	0		0	0	0		2.0		100.00
	Rg7944	3	7	10		0	0	0		0	0	0		0.4		100.00
	Rg7945	5	3	8		0	0	0		0	0	0		1.7		100.00
	Rg7946	3	3	6		0	0	0		0	0	0		1.0		100.00
	Rg7947	6	4	10		0	0	0		0	0	0		1.5		100.00
	Rg7948	8	8	16		0	0	0		0	0	0		1.0		100.00
	Rg7949^NP	-	-	-		-	-	-		-	-	-		-		-
	Rg7950	4	0	4		0	0	0		0	0	0		-		100.00
	Rg7951	3	3	6		0	0	0		0	0	0		1.0		100.00
	Rg7952	6	6	12		0	0	0		0	0	0		1.0		100.00

m/f: Male/Female; LD: Lactation Day; NP: Non-pregnant; -: Not applicable; %: Percentage.

 

 

APPENDIX 13 (Contd…). INDIVIDUAL DAM/LITTER DELIVERY AND LITTER OBSERVATIONS RECORD

Group & Dose (mg/kg body weight/day)	Dam No.	LD 1 to 4												Sex Ratio (m/f) on LD 4		Pup Survival Index (%) [LD 1 to 4]
		Live Pups (No.)				Dead Pups (No.)				Cannibalized Pups (No.)
		Male	Female	Total		Male	Female	Total		Male	Female	Total
G3 & 300	Rg7953^NP	-	-	-		-	-	-		-	-	-		-		-
	Rg7954	4	0	4		0	0	0		0	0	0		-		100.00
	Rg7955	6	4	10		0	0	0		0	0	0		1.5		100.00
	Rg7956	7	6	13		0	0	0		0	0	0		1.2		100.00
	Rg7957^NP	-	-	-		-	-	-		-	-	-		-		-
	Rg7958	3	1	4		1	1	2		0	0	0		3.0		50.00
	Rg7959	4	5	9		0	0	0		0	0	0		0.8		100.00
	Rg7960	7	4	11		1	0	1		0	0	0		1.8		91.67
	Rg7961	5	6	11		0	0	0		0	0	0		0.8		100.00
	Rg7962	6	4	10		0	0	0		0	0	0		1.5		100.00
	Rg7963^TL	-	-	-		-	-	-		-	-	-		-		-
	Rg7964	7	10	17		0	1	1		0	0	0		0.7		94.44
G4 & 600	Rg7965^TL	0	0	0		1	0	1		0	0	0		-		0.00
	Rg7966	3	4	7		0	0	0		0	0	0		0.8		100.00
	Rg7967^TL	-	-	-		-	-	-		-	-	-		-		-
	Rg7968	8	6	14		0	0	0		0	0	0		1.3		100.00
	Rg7969	3	7	10		1	1	2		0	0	0		0.4		83.33
	Rg7970	4	6	10		0	0	0		0	0	0		0.7		100.00
	Rg7971	4	8	12		0	0	0		0	0	0		0.5		100.00
	Rg7972^TL	0	0	0		3	8	11		0	0	0		-		0.00
	Rg7973^NP	-	-	-		-	-	-		-	-	-		-		-
	Rg7974	7	10	17		1	0	1		0	0	0		0.7		94.44
	Rg7975	6	8	14		0	0	0		0	0	0		0.8		100.00
	Rg7976	4	5	9		0	0	0		0	0	0		0.8		100.00

m/f: Male/Female; LD: Lactation Day; NP: Non-pregnant; TL: Total litter loss; -: Not applicable; %: Percentage.

 

APPENDIX 13 (Contd…). INDIVIDUAL DAM/LITTER DELIVERY AND LITTER OBSERVATIONS RECORD

Group & Dose (mg/kg body weight/day)	Dam No.	Pups Sacrificed for Litter Standardization / Hormonal analysis (No.)				Live Pups (No.) on LD 4 after Litter Standardization / Hormonal analysis (No.)				LD 5 to 7												Sex Ratio (m/f) on LD 7		Pup Survival Index (%) [LD 5 to 7]
										Live Pups (No.)				Dead Pups (No.)				Cannibalized (No.)
		Male	Female	Total		Male	Female	Total		Male	Female	Total		Male	Female	Total		Male	Female	Total
G1 & 0	Rg7929	0	0	0		6	4	10		6	4	10		0	0	0		0	0	0		1.5		100.00
	Rg7930	0	0	0		3	5	8		3	5	8		0	0	0		0	0	0		0.6		100.00
	Rg7931	0	2	2		7	4	11		7	4	11		0	0	0		0	0	0		1.8		100.00
	Rg7932	0	0	0		3	3	6		3	3	6		0	0	0		0	0	0		1.0		100.00
	Rg7933	0	1	1		9	1	10		9	1	10		0	0	0		0	0	0		9.0		100.00
	Rg7934	0	0	0		4	5	9		4	5	9		0	0	0		0	0	0		0.8		100.00
	Rg7935	0	2	2		7	4	11		7	4	11		0	0	0		0	0	0		1.8		100.00
	Rg7936	0	2	2		6	4	10		6	4	10		0	0	0		0	0	0		1.5		100.00
	Rg7937	0	0	0		2	3	5		2	3	5		0	0	0		0	0	0		0.7		100.00
	Rg7938	0	2	2		10	5	15		10	5	15		0	0	0		0	0	0		2.0		100.00
	Rg7939	0	2	2		8	3	11		8	3	11		0	0	0		0	0	0		2.7		100.00
	Rg7940	0	0	0		4	4	8		4	4	8		0	0	0		0	0	0		1.0		100.00
G2 & 150	Rg7941	0	2	2		6	8	14		6	8	14		0	0	0		0	0	0		0.8		100.00
	Rg7942	0	0	0		4	4	8		4	4	8		0	0	0		0	0	0		1.0		100.00
	Rg7943	0	0	0		6	3	9		6	3	9		0	0	0		0	0	0		2.0		100.00
	Rg7944	0	0	0		3	7	10		3	7	10		0	0	0		0	0	0		0.4		100.00
	Rg7945	0	0	0		5	3	8		5	3	8		0	0	0		0	0	0		1.7		100.00
	Rg7946	0	0	0		3	3	6		3	3	6		0	0	0		0	0	0		1.0		100.00
	Rg7947	0	0	0		6	4	10		6	4	10		0	0	0		0	0	0		1.5		100.00
	Rg7948	0	2	2		8	6	14		8	6	14		0	0	0		0	0	0		1.3		100.00
	Rg7949^NP	-	-	-		-	-	-		-	-	-		-	-	-		-	-	-		-		-
	Rg7950	0	0	0		4	0	4		4	0	4		0	0	0		0	0	0		-		100.00
	Rg7951	0	0	0		3	3	6		3	3	6		0	0	0		0	0	0		1.0		100.00
	Rg7952	0	2	2		6	4	10		6	4	10		0	0	0		0	0	0		1.5		100.00

m/f: Male/Female; LD: Lactation Day; NP: Non-pregnant; -: Not applicable; %: Percentage.

 

APPENDIX 13 (Contd…). INDIVIDUAL DAM/LITTER DELIVERY AND LITTER OBSERVATIONS RECORD

Group & Dose (mg/kg body weight/day)	Dam No..	Pups Sacrificed for Litter Standardization / Hormonal analysis (No.)				Live Pups (No.) on LD 4 after Litter Standardization / Hormonal analysis (No.)				LD 5 to 7												Sex Ratio (m/f) on LD 7		Pup Survival Index (%) [LD 5 to 7]
										Live Pups (No.)				Dead Pups (No.)				Cannibalized (No.)
		Male	Female	Total		Male	Female	Total		Male	Female	Total		Male	Female	Total		Male	Female	Total
G3 & 300	Rg7953^NP	-	-	-		-	-	-		-	-	-		-	-	-		-	-	-		-		-
	Rg7954	0	0	0		4	0	4		4	0	4		0	0	0		0	0	0		-		100.00
	Rg7955	0	0	0		6	4	10		6	4	10		0	0	0		0	0	0		1.5		100.00
	Rg7956	0	2	2		7	4	11		7	4	11		0	0	0		0	0	0		1.8		100.00
	Rg7957^NP	-	-	-		-	-	-		-	-	-		-	-	-		-	-	-		-		-
	Rg7958	0	0	0		3	1	4		3	1	4		0	0	0		0	0	0		3.0		100.00
	Rg7959	0	0	0		4	5	9		4	5	9		0	0	0		0	0	0		0.8		100.00
	Rg7960	0	1	1		7	3	10		7	3	10		0	0	0		0	0	0		2.3		100.00
	Rg7961	0	1	1		5	5	10		5	5	10		0	0	0		0	0	0		1.0		100.00
	Rg7962	0	0	0		6	4	10		6	4	10		0	0	0		0	0	0		1.5		100.00
	Rg7963^TL	-	-	-		-	-	-		-	-	-		-	-	-		-	-	-		-		-
	Rg7964	0	2	2		7	8	15		7	8	15		0	0	0		0	0	0		0.9		100.00
G4 & 600	Rg7965^TL	-	-	-		-	-	-		-	-	-		-	-	-		-	-	-		-		-
	Rg7966	0	0	0		3	4	7		3	4	7		0	0	0		0	0	0		0.8		100.00
	Rg7967^TL	-	-	-		-	-	-		-	-	-		-	-	-		-	-	-		-		-
	Rg7968	0	2	2		8	4	12		8	4	12		0	0	0		0	0	0		2.0		100.00
	Rg7969	0	0	0		3	7	10		3	7	10		0	0	0		0	0	0		0.4		100.00
	Rg7970	0	0	0		4	6	10		4	6	10		0	0	0		0	0	0		0.7		100.00
	Rg7971	0	2	2		4	6	10		4	6	10		0	0	0		0	0	0		0.7		100.00
	Rg7972^TL	-	-	-		-	-	-		-	-	-		-	-	-		-	-	-		-		-
	Rg7973^NP	-	-	-		-	-	-		-	-	-		-	-	-		-	-	-		-		-
	Rg7974	0	2	2		7	8	15		7	8	15		0	0	0		0	0	0		0.9		100.00
	Rg7975	0	2	2		6	6	12		6	6	12		0	0	0		0	0	0		1.0		100.00
	Rg7976	0	0	0		4	5	9		4	5	9		0	0	0		0	0	0		0.8		100.00

m/f: Male/Female; LD: Lactation Day; NP: Non-pregnant; TL: Total litter loss; -: Not applicable; %: Percentage.

 

 

APPENDIX 13 (Contd…). INDIVIDUAL DAM/LITTER DELIVERY AND LITTER OBSERVATIONS RECORD

Group & Dose (mg/kg body weight/day)	Dam No.	LD 8 to 13												Sex Ratio (m/f) on LD 13		Pup Survival Index (%) [LD 8 to 13]
		Live Pups (No.)				Dead Pups (No.)				Cannibalized (No.)
		Male	Female	Total		Male	Female	Total		Male	Female	Total
G1 & 0	Rg7929	6	4	10		0	0	0		0	0	0		1.5		100.00
	Rg7930	3	5	8		0	0	0		0	0	0		0.6		100.00
	Rg7931	7	4	11		0	0	0		0	0	0		1.8		100.00
	Rg7932	3	3	6		0	0	0		0	0	0		1.0		100.00
	Rg7933	9	1	10		0	0	0		0	0	0		9.0		100.00
	Rg7934	4	5	9		0	0	0		0	0	0		0.8		100.00
	Rg7935	7	4	11		0	0	0		0	0	0		1.8		100.00
	Rg7936	6	4	10		0	0	0		0	0	0		1.5		100.00
	Rg7937	2	3	5		0	0	0		0	0	0		0.7		100.00
	Rg7938	10	5	15		0	0	0		0	0	0		2.0		100.00
	Rg7939	8	3	11		0	0	0		0	0	0		2.7		100.00
	Rg7940	4	4	8		0	0	0		0	0	0		1.0		100.00
G2 & 150	Rg7941	6	8	14		0	0	0		0	0	0		0.8		100.00
	Rg7942	4	4	8		0	0	0		0	0	0		1.0		100.00
	Rg7943	6	3	9		0	0	0		0	0	0		2.0		100.00
	Rg7944	3	7	10		0	0	0		0	0	0		0.4		100.00
	Rg7945	5	3	8		0	0	0		0	0	0		1.7		100.00
	Rg7946	3	3	6		0	0	0		0	0	0		1.0		100.00
	Rg7947	6	4	10		0	0	0		0	0	0		1.5		100.00
	Rg7948	8	6	14		0	0	0		0	0	0		1.3		100.00
	Rg7949^NP	-	-	-		-	-	-		-	-	-		-		-
	Rg7950	4	0	4		0	0	0		0	0	0		-		100.00
	Rg7951	3	3	6		0	0	0		0	0	0		1.0		100.00
	Rg7952	6	4	10		0	0	0		0	0	0		1.5		100.00

m/f: Male/Female; LD: Lactation Day; NP: Non-pregnant; -: Not applicable; %: Percentage.

 

 

APPENDIX 13 (Contd…). INDIVIDUAL DAM/LITTER DELIVERY AND LITTER OBSERVATIONS RECORD

Group & Dose (mg/kg body weight/day)	Dam No.	LD 8 to 13												Sex Ratio (m/f) on LD 13		Pup Survival Index (%) [LD 8 to 13]
		Live Pups (No.)				Dead Pups (No.)				Cannibalized (No.)
		Male	Female	Total		Male	Female	Total		Male	Female	Total
G3 & 300	Rg7953^NP	-	-	-		-	-	-		-	-	-		-		-
	Rg7954	4	0	4		0	0	0		0	0	0		-		100.00
	Rg7955	6	4	10		0	0	0		0	0	0		1.5		100.00
	Rg7956	7	4	11		0	0	0		0	0	0		1.8		100.00
	Rg7957^NP	-	-	-		-	-	-		-	-	-		-		-
	Rg7958	3	1	4		0	0	0		0	0	0		3.0		100.00
	Rg7959	4	5	9		0	0	0		0	0	0		0.8		100.00
	Rg7960	7	3	10		0	0	0		0	0	0		2.3		100.00
	Rg7961	5	5	10		0	0	0		0	0	0		1.0		100.00
	Rg7962	6	4	10		0	0	0		0	0	0		1.5		100.00
	Rg7963^TL	-	-	-		-	-	-		-	-	-		-		-
	Rg7964	7	8	15		0	0	0		0	0	0		0.9		100.00
G4 & 600	Rg7965^TL	-	-	-		-	-	-		-	-	-		-		-
	Rg7966	3	4	7		0	0	0		0	0	0		0.8		100.00
	Rg7967^TL	-	-	-		-	-	-		-	-	-		-		-
	Rg7968	8	4	12		0	0	0		0	0	0		2.0		100.00
	Rg7969	3	7	10		0	0	0		0	0	0		0.4		100.00
	Rg7970	4	6	10		0	0	0		0	0	0		0.7		100.00
	Rg7971	4	6	10		0	0	0		0	0	0		0.7		100.00
	Rg7972^TL	-	-	-		-	-	-		-	-	-		-		-
	Rg7973^NP	-	-	-		-	-	-		-	-	-		-		-
	Rg7974	7	8	15		0	0	0		0	0	0		0.9		100.00
	Rg7975	6	6	12		0	0	0		0	0	0		1.0		100.00
	Rg7976	4	5	9		0	0	0		0	0	0		0.8		100.00

m/f: Male/Female; LD: Lactation Day; NP: Non-pregnant; TL: Total litter loss; -: Not applicable; %: Percentage.

 

 

• INDIVIDUAL ANIMAL REPRODUCTIVE PERFORMANCE RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Initiation of Cohabitation  (Date)	Confirmation of Mating  (Date)	Status of Mating (Evident of mating or not-mated)	Capability of Impregnating a Female (Capable/In-capable)
G1, M & 0	Rg7881	3-May-2022	4-May-2022	Evident of mating	Capable
	Rg7882	3-May-2022	4-May-2022	Evident of mating	Capable
	Rg7883	3-May-2022	5-May-2022	Evident of mating	Capable
	Rg7884	3-May-2022	4-May-2022	Evident of mating	Capable
	Rg7885	3-May-2022	6-May-2022	Evident of mating	Capable
	Rg7886	3-May-2022	5-May-2022	Evident of mating	Capable
	Rg7887	3-May-2022	12-May-2022	Evident of mating	Capable
	Rg7888	3-May-2022	8-May-2022	Evident of mating	Capable
	Rg7889	3-May-2022	4-May-2022	Evident of mating	Capable
	Rg7890	3-May-2022	7-May-2022	Evident of mating	Capable
	Rg7891	3-May-2022	4-May-2022	Evident of mating	Capable
	Rg7892	3-May-2022	5-May-2022	Evident of mating	Capable
G2, M & 150	Rg7893	3-May-2022	4-May-2022	Evident of mating	Capable
	Rg7894	3-May-2022	5-May-2022	Evident of mating	Capable
	Rg7895	3-May-2022	6-May-2022	Evident of mating	Capable
	Rg7896	3-May-2022	6-May-2022	Evident of mating	Capable
	Rg7897	3-May-2022	7-May-2022	Evident of mating	Capable
	Rg7898	3-May-2022	4-May-2022	Evident of mating	Capable
	Rg7899	3-May-2022	7-May-2022	Evident of mating	Capable
	Rg7900	3-May-2022	4-May-2022	Evident of mating	Capable
	Rg7901	3-May-2022	4-May-2022	Evident of mating	In-capable
	Rg7902	3-May-2022	5-May-2022	Evident of mating	Capable
	Rg7903	3-May-2022	15-May-2022	Evident of mating	Capable
	Rg7904	3-May-2022	6-May-2022	Evident of mating	Capable

M: Male.

 

 

APPENDIX 14 (Contd…). INDIVIDUAL ANIMAL REPRODUCTIVE PERFORMANCE RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Initiation of Cohabitation (Date)	Confirmation of Mating (Date)	Status of Mating (Evident of mating or not-mated)	Capability of Impregnating a Female (Capable/In-capable)
G3, M & 300	Rg7905	3-May-2022	4-May-2022	Evident of mating	Capable
	Rg7906	3-May-2022	6-May-2022	Evident of mating	Capable
	Rg7907	3-May-2022	4-May-2022	Evident of mating	Capable
	Rg7908	3-May-2022	4-May-2022	Evident of mating	Capable
	Rg7909	3-May-2022	10-May-2022	Evident of mating	In-capable
	Rg7910	3-May-2022	-	-	In-capable
	Rg7911	3-May-2022	4-May-2022	Evident of mating	Capable
	Rg7912	3-May-2022	4-May-2022	Evident of mating	Capable
	Rg7913	3-May-2022	6-May-2022	Evident of mating	Capable
	Rg7914	3-May-2022	13-May-2022	Evident of mating	Capable
	Rg7915	3-May-2022	12-May-2022	Evident of mating	Capable
	Rg7916	3-May-2022	6-May-2022	Evident of mating	Capable
G4, M & 600	Rg7917	3-May-2022	12-May-2022	Evident of mating	Capable
	Rg7918	3-May-2022	10-May-2022	Evident of mating	Capable
	Rg7919	3-May-2022	6-May-2022	Evident of mating	Capable
	Rg7920	3-May-2022	6-May-2022	Evident of mating	Capable
	Rg7921	3-May-2022	10-May-2022	Evident of mating	Capable
	Rg7922	3-May-2022	4-May-2022	Evident of mating	Capable
	Rg7923	3-May-2022	4-May-2022	Evident of mating	Capable
	Rg7924	3-May-2022	4-May-2022	Evident of mating	Capable
	Rg7925	3-May-2022	-	-	In-capable
	Rg7926	3-May-2022	6-May-2022	Evident of mating	Capable
	Rg7927	3-May-2022	7-May-2022	Evident of mating	Capable
	Rg7928	3-May-2022	-	-	In-capable

M: Male; -: Not applicable.

APPENDIX 14 (Contd…). INDIVIDUAL ANIMAL REPRODUCTIVE PERFORMANCE RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Initiation of Cohabitation (Date)	Confirmation of Mating (Date)	Pre-Coital Interval / Copulatory Interval		Parturition (Date)	Gestation Length (Days)
G1, F & 0	Rg7929	3-May-2022	4-May-2022	1		26-May-22	22
	Rg7930	3-May-2022	4-May-2022	1		27-May-22	23
	Rg7931	3-May-2022	5-May-2022	2		27-May-22	22
	Rg7932	3-May-2022	4-May-2022	1		26-May-22	22
	Rg7933	3-May-2022	6-May-2022	3		27-May-22	21
	Rg7934	3-May-2022	5-May-2022	2		27-May-22	22
	Rg7935	3-May-2022	12-May-2022	9		03-Jun-22	22
	Rg7936	3-May-2022	8-May-2022	5		30-May-22	22
	Rg7937	3-May-2022	4-May-2022	1		27-May-22	23
	Rg7938	3-May-2022	7-May-2022	4		28-May-22	21
	Rg7939	3-May-2022	4-May-2022	1		26-May-22	22
	Rg7940	3-May-2022	5-May-2022	2		27-May-22	22
G2, F & 150	Rg7941	3-May-2022	4-May-2022	1		26-May-22	22
	Rg7942	3-May-2022	5-May-2022	2		28-May-22	23
	Rg7943	3-May-2022	6-May-2022	3		27-May-22	21
	Rg7944	3-May-2022	6-May-2022	3		28-May-22	22
	Rg7945	3-May-2022	7-May-2022	4		29-May-22	22
	Rg7946	3-May-2022	4-May-2022	1		27-May-22	23
	Rg7947	3-May-2022	7-May-2022	4		30-May-22	23
	Rg7948	3-May-2022	4-May-2022	1		26-May-22	22
	Rg7949^NP	3-May-2022	4-May-2022	1		-	-
	Rg7950	3-May-2022	5-May-2022	2		27-May-22	22
	Rg7951	3-May-2022	15-May-2022	12		06-Jun-22	22
	Rg7952	3-May-2022	6-May-2022	3		29-May-22	23

F: Female; NP: Non-pregnant; -: Not applicable.

 

 

APPENDIX 14 (Contd…). INDIVIDUAL ANIMAL REPRODUCTIVE PERFORMANCE RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Initiation of Cohabitation (Date)	Cohabitation with Proven Male (Date)	Proven Male No.	Confirmation of Mating (Date)	Pre-Coital Interval / Copulatory Interval		Parturition (Date)	Gestation Length (Days)
G3, F & 300	Rg7953^NP	3-May-2022	-	-	4-May-2022	1		-	-
	Rg7954	3-May-2022	-	-	6-May-2022	3		27-May-22	21
	Rg7955	3-May-2022	-	-	4-May-2022	1		26-May-22	22
	Rg7956	3-May-2022	-	-	4-May-2022	1		27-May-22	23
	Rg7957^NP	3-May-2022	-	-	10-May-2022	7		-	-
	Rg7958	3-May-2022	17-May-2022	Rg7905	20-May-2022	17		11-Jun-22	22
	Rg7959	3-May-2022	-	-	4-May-2022	1		27-May-22	23
	Rg7960	3-May-2022	-	-	4-May-2022	1		26-May-22	22
	Rg7961	3-May-2022	-	-	6-May-2022	3		29-May-22	23
	Rg7962	3-May-2022	-	-	13-May-2022	10		05-Jun-22	23
	Rg7963^TL	3-May-2022	-	-	12-May-2022	9		03-Jun-22	22
	Rg7964	3-May-2022	-	-	6-May-2022	3		27-May-22	21
G4, F & 600	Rg7965^TL	3-May-2022	-	-	12-May-2022	9		03-Jun-22	22
	Rg7966	3-May-2022	-	-	10-May-2022	7		02-Jun-22	23
	Rg7967^TL	3-May-2022	-	-	6-May-2022	3		29-May-22	23
	Rg7968	3-May-2022	-	-	6-May-2022	3		27-May-22	21
	Rg7969	3-May-2022	-	-	10-May-2022	7		02-Jun-22	23
	Rg7970	3-May-2022	-	-	4-May-2022	1		27-May-22	23
	Rg7971	3-May-2022	-	-	4-May-2022	1		26-May-22	22
	Rg7972^TL	3-May-2022	-	-	4-May-2022	1		26-May-22	22
	Rg7973^NP	3-May-2022	17-May-2022	Rg7922	22-May-2022	19		-	-
	Rg7974	3-May-2022	-	-	6-May-2022	3		28-May-22	22
	Rg7975	3-May-2022	-	-	7-May-2022	4		29-May-22	22
	Rg7976	3-May-2022	17-May-2022	Rg7923	21-May-2022	18		11-Jun-22	21

F: Female; NP: Non-pregnant; TL: Total litter loss; -: Not applicable.

 

 

APPENDIX 14 (Contd…). INDIVIDUAL ANIMAL REPRODUCTIVE PERFORMANCE RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Status of Mating (Evident of mating or not-mated)	Status of Fertility (Fertile or In-Fertile) - with evidence of implantations	Status of Pregnancy (Pregnant/Non-pregnant/ Dam with total implantation loss)	Gestation Status (with live born pups/without live born pups/non-pregnant)	Status of Parturition (Littered/ Not Littered/ Non-pregnant)
G1, F & 0	Rg7929	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7930	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7931	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7932	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7933	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7934	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7935	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7936	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7937	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7938	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7939	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7940	Evident of mating	Fertile	Pregnant	with live born pups	Littered
G2, F & 150	Rg7941	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7942	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7943	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7944	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7945	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7946	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7947	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7948	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7949	Evident of mating	In-Fertile	Non-pregnant	Non-pregnant	Non-pregnant
	Rg7950	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7951	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7952	Evident of mating	Fertile	Pregnant	with live born pups	Littered

F: Female.

 

 

APPENDIX 14 (Contd…). INDIVIDUAL ANIMAL REPRODUCTIVE PERFORMANCE RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Status of Mating (Evident of mating or not-mated)	Status of Fertility (Fertile or In-Fertile) - with evidence of implantations	Status of Pregnancy (Pregnant/Non-pregnant/ Dam with total implantation loss)	Gestation Status (with live born pups/without live born pups/non-pregnant)	Status of Parturition (Littered/ Not Littered/ Non-pregnant)
G3, F & 300	Rg7953	Evident of mating	In-Fertile	Non-pregnant	Non-pregnant	Non-pregnant
	Rg7954	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7955	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7956	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7957	Evident of mating	In-Fertile	Non-pregnant	Non-pregnant	Non-pregnant
	Rg7958	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7959	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7960	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7961	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7962	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7963	Evident of mating	Fertile	Pregnant	without live born pups	Littered
	Rg7964	Evident of mating	Fertile	Pregnant	with live born pups	Littered
G4, F & 600	Rg7965	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7966	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7967	Evident of mating	Fertile	Pregnant	without live born pups	Littered
	Rg7968	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7969	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7970	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7971	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7972	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7973	Evident of mating	In-Fertile	Non-pregnant	Non-pregnant	Non-pregnant
	Rg7974	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7975	Evident of mating	Fertile	Pregnant	with live born pups	Littered
	Rg7976	Evident of mating	Fertile	Pregnant	with live born pups	Littered

F: Female.

 

 

APPENDIX 14 (Contd…). INDIVIDUAL ANIMAL REPRODUCTIVE PERFORMANCE RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Post-implantation Loss					Post-natal Loss (%
		No. of Implantations	No. of Viable (Live) Pups	Post-implantation Loss (No.)	Post-implantation Loss (%)		Total No. of Pups Found Dead/ Cannibalized during lactation period	Post-natal Loss (%)
G1, F & 0	Rg7929	10	10	0	0.00		0	0.00
	Rg7930	10	8	2	20.00		0	0.00
	Rg7931	13	13	0	0.00		0	0.00
	Rg7932	10	8	2	20.00		2	25.00
	Rg7933	12	11	1	8.33		0	0.00
	Rg7934	9	9	0	0.00		0	0.00
	Rg7935	13	13	0	0.00		0	0.00
	Rg7936	13	12	1	7.69		0	0.00
	Rg7937	8	5	3	37.50		0	0.00
	Rg7938	17	17	0	0.00		0	0.00
	Rg7939	13	13	0	0.00		0	0.00
	Rg7940	10	8	2	20.00		0	0.00
G2, F & 150	Rg7941	16	16	0	0.00		0	0.00
	Rg7942	8	8	0	0.00		0	0.00
	Rg7943	10	9	1	10.00		0	0.00
	Rg7944	10	10	0	0.00		0	0.00
	Rg7945	8	8	0	0.00		0	0.00
	Rg7946	7	6	1	14.29		0	0.00
	Rg7947	11	10	1	9.09		0	0.00
	Rg7948	16	16	0	0.00		0	0.00
	Rg7949^NP	-	-	-	-		-	-
	Rg7950	5	4	1	20.00		0	0.00
	Rg7951	7	6	1	14.29		0	0.00
	Rg7952	12	12	0	0.00		0	0.00

F: Female; NP: Non-pregnant; -: Not applicable. The uterus of each dam was observed for implantation sites and recorded the count for comparison of number of implantation sites with the number of pups born for each litter to calculate the post-implantation loss. The uterus of females with no visible implantation sites (non-pregnants) was immersed in 10% v/v Ammonium Sulphide staining solution under fume hood to visualize the implantation sites that might have undergone very early resorptions, there were no such incidences noted.

APPENDIX 14 (Contd…). INDIVIDUAL ANIMAL REPRODUCTIVE PERFORMANCE RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Post-implantation Loss					Post-natal Loss
		No. of Implantations	No. of Viable (Live) Pups	Post-implantation Loss (No.)	Post-implantation Loss (%)		Total No. of Pups Found Dead/ Cannibalized during lactation period	Post-natal Loss (%)
G3, F & 300	Rg7953^NP	-	-	-	-		-	-
	Rg7954	6	4	2	33.33		0	0.00
	Rg7955	10	10	0	0.00		0	0.00
	Rg7956	14	13	1	7.14		0	0.00
	Rg7957^NP	-	-	-	-		-	-
	Rg7958	6	4	2	33.33		0	0.00
	Rg7959	9	9	0	0.00		0	0.00
	Rg7960	13	12	1	7.69		1	8.33
	Rg7961	11	11	0	0.00		0	0.00
	Rg7962	10	10	0	0.00		0	0.00
	Rg7963^TL	6	0	6	100.00		-	-
	Rg7964	18	18	0	0.00		1	5.56
G4, F & 600	Rg7965^TL	4	1	3	75.00		1	100.00
	Rg7966	7	7	0	0.00		0	0.00
	Rg7967^TL	6	0	6	100.00		-	-
	Rg7968	14	14	0	0.00		0	0.00
	Rg7969	13	12	1	7.69		2	16.67
	Rg7970	10	10	0	0.00		0	0.00
	Rg7971	13	12	1	7.69		0	0.00
	Rg7972^TL	15	11	4	26.67		11	100.00
	Rg7973^NP	-	-	-	-		-	-
	Rg7974	19	18	1	5.26		1	5.56
	Rg7975	14	14	0	0.00		0	0.00
	Rg7976	12	9	3	25.00		0	0.00

F: Female; NP: Non-pregnant; -: Not applicable. The uterus of each dam was observed for implantation sites and recorded the count for comparison of number of implantation sites with the number of pups born for each litter to calculate the post-implantation loss. The uterus of females with no visible implantation sites (non-pregnants) was immersed in 10% v/v Ammonium Sulphide staining solution under fume hood to visualize the implantation sites that might have undergone very early resorptions, there were no such incidences noted; TL: Total litter loss.

• INDIVIDUAL ANIMAL ABSOLUTE ORGAN WEIGHT (g) RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Testes	Epididymides	Kidneys	Prostate	Seminal vesicles with coagulating glands	Thyroid along with parathyroid^WP
G1, M & 0	Rg7881	3.8807	1.4964	2.5304	1.1093	1.4062	0.0340
	Rg7882	3.4921	1.3721	2.5656	1.2260	2.2563	0.0302
	Rg7883	3.8659	1.3228	2.6587	0.8776	1.2015	0.0212
	Rg7884	3.4098	1.5214	2.4207	1.1282	1.6421	0.0316
	Rg7885	3.4133	1.3702	2.6790	1.7690	0.9984	0.0265
	Rg7886	3.5072	1.5137	2.5259	1.5692	1.9274	0.0247
	Rg7887	3.4715	1.3974	2.7676	1.1128	1.6104	0.0242
	Rg7888	3.0776	1.1773	2.7656	1.1395	1.3014	0.0197
	Rg7889	3.0928	1.3721	3.2424	1.5711	1.6984	0.0213
	Rg7890	3.9113	1.7116	3.1429	1.8321	1.3481	0.0351
	Rg7891	3.5321	1.6449	2.8530	1.8289	1.0841	0.0352
	Rg7892	3.5457	1.4755	3.3962	1.5568	2.3786	0.0302
G2, M & 150	Rg7893	2.4986	1.2463	2.4540	1.6181	0.9306	0.0161
	Rg7894	3.1687	1.3139	2.4160	1.4580	0.9316	0.0180
	Rg7895	2.8852	1.3895	2.4815	1.2402	2.0428	0.0164
	Rg7896	3.1300	1.6499	2.7928	2.1846	0.7481	0.0229
	Rg7897	3.1559	1.4758	2.7684	1.3075	1.3608	0.0232
	Rg7898	3.3664	1.6931	2.1196	0.9316	1.5001	0.0364
	Rg7899	3.3915	1.4012	2.7685	1.2040	1.9423	0.0360
	Rg7900	3.8532	1.6340	3.2447	0.9630	2.4361	0.0355
	Rg7901	3.6580	1.4233	2.3119	0.8082	2.2596	0.0242
	Rg7902	3.6148	1.2703	2.5002	1.2016	1.7682	0.0374
	Rg7903	3.2487	1.3287	2.4755	1.1664	1.3909	0.0320
	Rg7904	3.4087	1.7544	2.8452	0.8920	1.8619	0.0263

M: Male; WP: Weighed post-fixation.

 

 

 

APPENDIX 15 (Contd…). INDIVIDUAL ANIMAL ABSOLUTE ORGAN WEIGHT (g) RECORD

Group, Sex  & Dose (mg/kg body weight/day)	Animal No.	Testes	Epididymides	Kidneys	Prostate	Seminal vesicles with coagulating glands	Thyroid along with parathyroid^WP
G3, M & 300	Rg7905	3.6763	1.6759	2.3142	1.1524	1.9635	0.0118
	Rg7906	3.4168	1.1793	2.3490	1.1240	1.3095	0.0242
	Rg7907	3.2109	1.5249	2.6119	1.1680	2.5289	0.0182
	Rg7908	3.7364	1.4106	2.5556	1.6398	1.3295	0.0361
	Rg7909	3.3085	1.3697	2.6053	1.9112	0.6056	0.0423
	Rg7910	3.3714	1.4084	2.4193	1.2204	1.0983	0.0357
	Rg7911	3.5574	1.6958	2.8582	1.8926	0.9801	0.0285
	Rg7912	3.1496	1.4567	3.0852	1.6232	1.3842	0.0246
	Rg7913	3.4221	1.4231	2.7552	1.2292	0.6750	0.0187
	Rg7914	3.4968	1.3689	2.3712	1.4957	0.6719	0.0362
	Rg7915	3.6762	1.4170	2.7818	0.9372	1.7386	0.0317
	Rg7916	3.4978	1.3815	3.3779	0.9268	1.1547	0.0261
G4, M & 600	Rg7917	3.4384	1.6469	2.7352	1.7403	0.9210	0.0416
	Rg7918	3.0408	1.2076	2.0371	0.5184	1.3941	0.0197
	Rg7919	3.4915	1.2366	2.1886	1.0257	1.0894	0.0282
	Rg7920	3.3301	1.4170	2.1523	2.1602	0.8860	0.0288
	Rg7921	3.0049	1.4437	2.3150	1.0912	0.8026	0.0219
	Rg7922	3.5876	1.3914	3.0741	1.1245	1.1757	0.0331
	Rg7923	3.6243	1.2751	2.6246	1.1896	1.2759	0.0201
	Rg7924	2.9285	1.2562	2.3008	1.0067	1.0249	0.0212
	Rg7925	3.7875	1.3375	2.4083	1.0365	1.2819	0.0337
	Rg7926	3.0179	1.2915	2.6101	1.0935	0.4108	0.0157
	Rg7927	3.2982	1.3757	2.6425	1.4034	0.6823	0.0379
	Rg7928	3.6400	1.7420	2.4308	0.4752	1.7295	0.0287

M: Male; WP: Weighed post-fixation.

 

 

APPENDIX 15 (Contd…). INDIVIDUAL ANIMAL ABSOLUTE ORGAN WEIGHT (g) RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Ovaries	Uterus with cervix	Kidneys	Thyroid along with parathyroid^WP
G1, F & 0	Rg7929	0.1181	0.5310	1.7077	0.02864
	Rg7930	0.1328	0.8546	1.6728	0.03684
	Rg7931	0.1223	0.4808	1.6902	0.02470
	Rg7932	0.1070	0.7679	2.1539	0.03747
	Rg7933	0.1406	0.4739	1.8975	0.03321
	Rg7934	0.1414	0.4182	2.0847	0.02780
	Rg7935	0.1562	0.6886	2.4033	0.03828
	Rg7936	0.1361	0.4991	1.6651	0.03298
	Rg7937	0.1602	0.6584	2.0873	0.03185
	Rg7938	0.1789	0.6217	1.9246	0.02671
	Rg7939	0.1422	0.4219	2.0432	0.03960
	Rg7940	0.1156	0.6629	1.7216	0.03583
G2, F & 150	Rg7941	0.1268	0.3975	1.6917	0.01541
	Rg7942	0.1179	0.5863	1.8526	0.02073
	Rg7943	0.1350	0.4152	1.7113	0.02153
	Rg7944	0.1433	0.6231	1.5743	0.02570
	Rg7945	0.1750	0.8359	2.0521	0.02124
	Rg7946	0.1369	0.3726	1.7433	0.02393
	Rg7947	0.1291	0.6467	1.6569	0.01932
	Rg7948	0.1368	0.5693	2.0950	0.02191
	Rg7949^NP	0.1519	0.4048	2.2494	0.02786
	Rg7950	0.1768	0.8803	1.8787	0.01944
	Rg7951	0.1337	0.7270	1.9202	0.03247
	Rg7952	0.1263	0.4659	1.5930	0.01747

F: Female; NP: Non-pregnant; WP: Weighed post-fixation.

 

APPENDIX 15 (Contd…). INDIVIDUAL ANIMAL ABSOLUTE ORGAN WEIGHT (g) RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Ovaries	Uterus with cervix	Kidneys	Thyroid along with parathyroid^WP
G3, F & 300	Rg7953^NP	0.1232	0.6151	2.2932	0.02201
	Rg7954	0.1501	0.4777	1.6953	0.01979
	Rg7955	0.1611	0.5942	1.9249	0.02605
	Rg7956	0.1197	0.5203	1.7678	0.02112
	Rg7957^NP	0.1203	0.7372	1.7257	0.03071
	Rg7958	0.1458	0.6352	1.9085	0.02138
	Rg7959	0.1234	0.6019	1.9338	0.02453
	Rg7960	0.1254	0.4293	2.1321	0.03188
	Rg7961	0.1339	0.5447	1.6980	0.02225
	Rg7962	0.1121	0.6214	1.8164	0.01622
	Rg7963^TL	0.1206	0.6354	1.8296	0.01791
	Rg7964	0.1253	0.4037	1.9074	0.02302
G4, F & 600	Rg7965^TL	0.1629	0.8380	1.8342	0.01252
	Rg7966	0.1508	0.3943	1.9646	0.01632
	Rg7967^TL	0.1312	0.7546	1.6219	0.02677
	Rg7968	0.0963	0.3517	1.7453	0.01378
	Rg7969	0.1219	0.4040	1.5696	0.02414
	Rg7970	0.1570	0.7175	1.8822	0.01929
	Rg7971	0.1267	0.4595	1.9943	0.02474
	Rg7972^TL	-	-	-	-
	Rg7973^NP	0.1287	0.8198	2.0372	0.02226
	Rg7974	0.1763	0.5460	1.9225	0.03069
	Rg7975	0.1384	0.4911	2.4342	0.02382
	Rg7976	0.1573	0.4341	2.3267	0.01030

F: Female; NP: Non-pregnant; TL: Total litter loss; WP: Weighed post-fixation; -: Not applicable.

Note: Animal number Rg7972 from group G4 was found dead on lactation day (LD) 5.

 

 

 

• INDIVIDUAL ANIMAL TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
  TERMINAL BODY WEIGHT (%) RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Terminal Body Weight (g)	Testes	Epididymides	Kidneys	Prostate	Seminal vesicles with coagulating glands	Thyroid along with parathyroid
G1, M & 0	Rg7881	400.74	0.9684	0.3734	0.6314	0.2768	0.3509	0.0085
	Rg7882	377.23	0.9257	0.3637	0.6801	0.3250	0.5981	0.0080
	Rg7883	391.41	0.9877	0.3380	0.6793	0.2242	0.3070	0.0054
	Rg7884	413.61	0.8244	0.3678	0.5853	0.2728	0.3970	0.0076
	Rg7885	413.37	0.8257	0.3315	0.6481	0.4279	0.2415	0.0064
	Rg7886	411.07	0.8532	0.3682	0.6145	0.3817	0.4689	0.0060
	Rg7887	391.54	0.8866	0.3569	0.7068	0.2842	0.4113	0.0062
	Rg7888	432.57	0.7115	0.2722	0.6393	0.2634	0.3009	0.0046
	Rg7889	451.83	0.6845	0.3037	0.7176	0.3477	0.3759	0.0047
	Rg7890	457.36	0.8552	0.3742	0.6872	0.4006	0.2948	0.0077
	Rg7891	426.27	0.8286	0.3859	0.6693	0.4290	0.2543	0.0083
	Rg7892	493.34	0.7187	0.2991	0.6884	0.3156	0.4821	0.0061
G2, M & 150	Rg7893	354.36	0.7051	0.3517	0.6925	0.4566	0.2626	0.0045
	Rg7894	350.63	0.9037	0.3747	0.6890	0.4158	0.2657	0.0051
	Rg7895	382.88	0.7536	0.3629	0.6481	0.3239	0.5335	0.0043
	Rg7896	413.40	0.7571	0.3991	0.6756	0.5284	0.1810	0.0055
	Rg7897	387.44	0.8146	0.3809	0.7145	0.3375	0.3512	0.0060
	Rg7898	391.43	0.8600	0.4325	0.5415	0.2380	0.3832	0.0093
	Rg7899	385.14	0.8806	0.3638	0.7188	0.3126	0.5043	0.0093
	Rg7900	437.49	0.8808	0.3735	0.7417	0.2201	0.5568	0.0081
	Rg7901	392.72	0.9315	0.3624	0.5887	0.2058	0.5754	0.0062
	Rg7902	396.26	0.9122	0.3206	0.6309	0.3032	0.4462	0.0094
	Rg7903	421.09	0.7715	0.3155	0.5879	0.2770	0.3303	0.0076
	Rg7904	403.50	0.8448	0.4348	0.7051	0.2211	0.4614	0.0065

M: Male.

APPENDIX 16 (Contd…). INDIVIDUAL ANIMAL TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO TERMINAL BODY WEIGHT (%) RECORD

Group, Sex & Dose  (mg/kg body weight/day)	Animal No.	Terminal Body Weight (g)	Testes	Epididymides	Kidneys	Prostate	Seminal vesicles with coagulating glands	Thyroid along with parathyroid
G3, M & 300	Rg7905	343.35	1.0707	0.4881	0.6740	0.3356	0.5719	0.0034
	Rg7906	327.46	1.0434	0.3601	0.7173	0.3432	0.3999	0.0074
	Rg7907	384.58	0.8349	0.3965	0.6792	0.3037	0.6576	0.0047
	Rg7908	406.90	0.9183	0.3467	0.6281	0.4030	0.3267	0.0089
	Rg7909	386.59	0.8558	0.3543	0.6739	0.4944	0.1567	0.0109
	Rg7910	343.56	0.9813	0.4099	0.7042	0.3552	0.3197	0.0104
	Rg7911	439.84	0.8088	0.3855	0.6498	0.4303	0.2228	0.0065
	Rg7912	419.47	0.7509	0.3473	0.7355	0.3870	0.3300	0.0059
	Rg7913	402.79	0.8496	0.3533	0.6840	0.3052	0.1676	0.0046
	Rg7914	372.72	0.9382	0.3673	0.6362	0.4013	0.1803	0.0097
	Rg7915	391.09	0.9400	0.3623	0.7113	0.2396	0.4446	0.0081
	Rg7916	419.06	0.8347	0.3297	0.8061	0.2212	0.2755	0.0062
G4, M & 600	Rg7917	348.19	0.9875	0.4730	0.7855	0.4998	0.2645	0.0119
	Rg7918	313.48	0.9700	0.3852	0.6498	0.1654	0.4447	0.0063
	Rg7919	322.85	1.0815	0.3830	0.6779	0.3177	0.3374	0.0087
	Rg7920	346.65	0.9607	0.4088	0.6209	0.6232	0.2556	0.0083
	Rg7921	339.92	0.8840	0.4247	0.6810	0.3210	0.2361	0.0064
	Rg7922	393.75	0.9111	0.3534	0.7807	0.2856	0.2986	0.0084
	Rg7923	399.47	0.9073	0.3192	0.6570	0.2978	0.3194	0.0050
	Rg7924	346.13	0.8461	0.3629	0.6647	0.2908	0.2961	0.0061
	Rg7925	372.23	1.0175	0.3593	0.6470	0.2785	0.3444	0.0091
	Rg7926	368.77	0.8184	0.3502	0.7078	0.2965	0.1114	0.0043
	Rg7927	391.73	0.8420	0.3512	0.6746	0.3583	0.1742	0.0097
	Rg7928	370.06	0.9836	0.4707	0.6569	0.1284	0.4674	0.0078

M: Male.

APPENDIX 16 (Contd…). INDIVIDUAL ANIMAL TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO TERMINAL BODY WEIGHT (%) RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Terminal Body Weight (g)	Ovaries	Uterus with cervix	Kidneys	Thyroid along with parathyroid
G1, F & 0	Rg7929	304.16	0.0388	0.1746	0.5614	0.00942
	Rg7930	299.84	0.0443	0.2850	0.5579	0.01229
	Rg7931	306.57	0.0399	0.1568	0.5513	0.00806
	Rg7932	313.64	0.0341	0.2448	0.6867	0.01195
	Rg7933	308.76	0.0455	0.1535	0.6146	0.01076
	Rg7934	324.76	0.0435	0.1288	0.6419	0.00856
	Rg7935	321.88	0.0485	0.2139	0.7466	0.01189
	Rg7936	315.28	0.0432	0.1583	0.5281	0.01046
	Rg7937	335.78	0.0477	0.1961	0.6216	0.00949
	Rg7938	310.83	0.0576	0.2000	0.6192	0.00859
	Rg7939	308.19	0.0461	0.1369	0.6630	0.01285
	Rg7940	331.14	0.0349	0.2002	0.5199	0.01082
G2, F & 150	Rg7941	273.38	0.0464	0.1454	0.6188	0.00564
	Rg7942	296.71	0.0397	0.1976	0.6244	0.00699
	Rg7943	293.81	0.0459	0.1413	0.5825	0.00733
	Rg7944	282.18	0.0508	0.2208	0.5579	0.00911
	Rg7945	315.96	0.0554	0.2646	0.6495	0.00672
	Rg7946	294.75	0.0464	0.1264	0.5915	0.00812
	Rg7947	319.18	0.0404	0.2026	0.5191	0.00605
	Rg7948	314.44	0.0435	0.1811	0.6663	0.00696
	Rg7949^NP	301.78	0.0503	0.1341	0.7454	0.00921
	Rg7950	326.83	0.0541	0.2693	0.5748	0.00595
	Rg7951	334.76	0.0399	0.2172	0.5736	0.00968
	Rg7952	312.51	0.0404	0.1491	0.5097	0.00560

F: Female; NP: Non-pregnant.

APPENDIX 16 (Contd…). INDIVIDUAL ANIMAL TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO TERMINAL BODY WEIGHT (%) RECORD

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Terminal Body Weight (g)	Ovaries	Uterus with cervix	Kidneys	Thyroid along with parathyroid
G3, F & 300	Rg7953^NP	258.11	0.0477	0.2383	0.8885	0.00852
	Rg7954	311.78	0.0481	0.1532	0.5437	0.00635
	Rg7955	312.06	0.0516	0.1904	0.6168	0.00835
	Rg7956	289.18	0.0414	0.1799	0.6113	0.00730
	Rg7957^NP	271.07	0.0444	0.2720	0.6366	0.01133
	Rg7958	311.54	0.0468	0.2039	0.6126	0.00686
	Rg7959	309.11	0.0399	0.1947	0.6256	0.00794
	Rg7960	320.99	0.0391	0.1337	0.6642	0.00993
	Rg7961	313.83	0.0427	0.1736	0.5411	0.00709
	Rg7962	333.01	0.0337	0.1866	0.5454	0.00487
	Rg7963^TL	317.14	0.0380	0.2004	0.5769	0.00565
	Rg7964	307.46	0.0408	0.1313	0.6204	0.00749
G4, F & 600	Rg7965^TL	256.98	0.0634	0.3261	0.7138	0.00487
	Rg7966	313.88	0.0480	0.1256	0.6259	0.00520
	Rg7967^TL	266.11	0.0493	0.2836	0.6095	0.01006
	Rg7968	294.08	0.0327	0.1196	0.5935	0.00469
	Rg7969	288.79	0.0422	0.1399	0.5435	0.00836
	Rg7970	276.25	0.0568	0.2597	0.6813	0.00698
	Rg7971	330.30	0.0384	0.1391	0.6038	0.00749
	Rg7972^TL	-	-	-	-	-
	Rg7973^NP	294.59	0.0437	0.2783	0.6915	0.00756
	Rg7974	324.31	0.0544	0.1684	0.5928	0.00946
	Rg7975	328.14	0.0422	0.1497	0.7418	0.00726
	Rg7976	320.36	0.0491	0.1355	0.7263	0.00322

F: Female; NP: Non-pregnant; TL: Total litter loss; -: Not applicable.

Note: Animal number Rg7972 from group G4 was found dead on lactation day (LD) 5.

 

• INDIVIDUAL ANIMAL SERUM T4 LEVELS (ng/mL) RECORD - ADULTS

Group, Sex & Dose (mg/kg body weight/day)	Animal No.	Serum T4 Levels Adj. Result (ng/mL)
G1, M & 0	Rg7881	79.075
	Rg7882	66.183
	Rg7883	71.065
	Rg7884	78.519
	Rg7885	87.218
	Rg7886	75.502
	Rg7887	75.771
	Rg7888	88.909
	Rg7889	75.524
	Rg7890	72.562
	Rg7891	70.901
	Rg7892	68.967
G2, M & 150	Rg7893	96.343
	Rg7894	83.789
	Rg7895	82.394
	Rg7896	67.584
	Rg7897	71.482
	Rg7898	69.949
	Rg7899	83.568
	Rg7900	88.183
	Rg7901	79.215
	Rg7902	71.961
	Rg7903	79.171
	Rg7904	70.679
G3, M & 300	Rg7905	70.061
	Rg7906	79.718
	Rg7907	66.205
	Rg7908	77.560
	Rg7909	71.735
	Rg7910	68.674
	Rg7911	72.812
	Rg7912	76.587
	Rg7913	78.949
	Rg7914	71.682
	Rg7915	65.586
	Rg7916	76.096
G4, M & 600	Rg7917	67.635
	Rg7918	65.066
	Rg7919	65.783
	Rg7920	62.272
	Rg7921	60.302
	Rg7922	79.287
	Rg7923	67.910
	Rg7924	72.162
	Rg7925	73.517
	Rg7926	71.682
	Rg7927	71.632
	Rg7928	61.909

M: Male; ng/mL: nanogram per mL.

 

 

 

• INDIVIDUAL PUP OBSERVATION PER LITTER RECORD DURING POSTNATAL PERIOD

Group & Dose (mg/kg body weight/day)

Dam No.

Pup No. →

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

G1 & 0

Rg7929

Sex →

M

M

M

M

M

M

F

F

F

F

-

-

-

-

-

-

-

PND 1 to 13

N

N

N

N

N

N

N

N

N

N

-

-

-

-

-

-

-

Rg7930

Sex →

M

M

M

F

F

F

F

F

-

-

-

-

-

-

-

-

-

PND 1 to 13

N

N

N

N

N

N

N

N

-

-

-

-

-

-

-

-

-

Rg7931

Sex →

M

M

M

M

M

M

M

F

F

F

F

F

F

-

-

-

-

PND 1 to 13

N

N

N

N

N

N

N

N

N

N

N

N^TS

N^TS

-

-

-

-

Rg7932

Sex →

M

M

M

M

F

F

F

F

-

-

-

-

-

-

-

-

-

PND 1 to 13

N

N

N

$

N

N

N

@

-

-

-

-

-

-

-

-

-

Rg7933

Sex →

M

M

M

M

M

M

M

M

M

F

F

-

-

-

-

-

-

PND 1 to 13

N

N

N

N

N

N

N

N

N

N

N^TS

-

-

-

-

-

-

Rg7934

Sex →

M

M

M

M

F

F

F

F

F

-

-

-

-

-

-

-

-

PND 1 to 13

N

N

N

N

N

N

N

N

N

-

-

-

-

-

-

-

-

Rg7935

Sex →

M

M

M

M

M

M

M

F

F

F

F

F

F

-

-

-

-

PND 1 to 13

N

N

N

N

N

N

N

N

N

N

N

N^TS

N^TS

-

-

-

-

Rg7936

Sex →

M

M

M

M

M

M

F

F

F

F

F

F

-

-

-

-

-

PND 1 to 13

N

N

N

N

N

N

N

N

N

N

N^TS

N^TS

-

-

-

-

-

Rg7937

Sex →

M

M

F

F

F

-

-

-

-

-

-

-

-

-

-

-

-

PND 1 to 13

N

N

N

N

N

-

-

-

-

-

-

-

-

-

-

-

-

Rg7938

Sex →

M

M

M

M

M

M

M

M

M

M

F

F

F

F

F

F

F

PND 1 to 13

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N^TS

N^TS

Rg7939

Sex →

M

M

M

M

M

M

M

M

F

F

F

F

F

-

-

-

-

PND 1 to 13

N

N

N

N

N

N

N

N

N

N

N

N^TS

N^TS

-

-

-

-

Rg7940

Sex →

M

M

M

M

F

F

F

F

-

-

-

-

-

-

-

-

-

PND 1 to 13

N

N

N

N

N

N

N

N

-

-

-

-

-

-

-

-

-

N: Normal; PND: Postnatal day; M: Male; F: Female; -: Not applicable.
TS: Observed until PND 4 and terminally sacrificed for blood collection.

@: Pale coloured PND 1 to 3, Dead on PND 4; $: Normal PND 1 and Cannibalized on PND 2.

 

 

APPENDIX 18 (Contd…). INDIVIDUAL PUP OBSERVATION PER LITTER RECORD DURING POSTNATAL PERIOD

Group & Dose (mg/kg body weight/day)

Dam No.

Pup No. →

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

G2 & 150

Rg7941

Sex →

M

M

M

M

M

M

F

F

F

F

F

F

F

F

F

F

PND 1 to 13

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N^TS

N^TS

Rg7942

Sex →

M

M

M

M

F

F

F

F

-

-

-

-

-

-

-

-

PND 1 to 13

N

N

N

N

N

N

N

N

-

-

-

-

-

-

-

-

Rg7943

Sex →

M

M

M

M

M

M

F

F

F

-

-

-

-

-

-

-

PND 1 to 13

N

N

N

N

N

N

N

N

N

-

-

-

-

-

-

-

Rg7944

Sex →

M

M

M

F

F

F

F

F

F

F

-

-

-

-

-

-

PND 1 to 13

N

N

N

N

N

N

N

N

N

N

-

-

-

-

-

-

Rg7945

Sex →

M

M

M

M

M

F

F

F

-

-

-

-

-

-

-

-

PND 1 to 13

N

N

N

N

N

N

N

N

-

-

-

-

-

-

-

-

Rg7946

Sex →

M

M

M

F

F

F

-

-

-

-

-

-

-

-

-

-

PND 1 to 13

N

N

N

N

N

N

-

-

-

-

-

-

-

-

-

-

Rg7947

Sex →

M

M

M

M

M

M

F

F

F

F

-

-

-

-

-

-

PND 1 to 13

N

N

N

N

N

N

N

N

N

N

-

-

-

-

-

-

Rg7948

Sex →

M

M

M

M

M

M

M

M

F

F

F

F

F

F

F

F

PND 1 to 13

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N^TS

N^TS

Rg7949

Non-pregnant

Rg7950

Sex →

M

M

M

M

-

-

-

-

-

-

-

-

-

-

-

-

PND 1 to 13

N

N

N

N

-

-

-

-

-

-

-

-

-

-

-

-

Rg7951

Sex →

M

M

M

F

F

F

-

-

-

-

-

-

-

-

-

-

PND 1 to 13

N

N

N

N

N

N

-

-

-

-

-

-

-

-

-

-

Rg7952

Sex →

M

M

M

M

M

M

F

F

F

F

F

F

-

-

-

-

PND 1 to 13

N

N

N

N

N

N

N

N

N

N

N^TS

N^TS

-

-

-

-

N: Normal; PND: Postnatal day; M: Male; F: Female; -: Not applicable.
TS: Observed until PND 4 and terminally sacrificed for blood collection.

 

APPENDIX 18 (Contd…). INDIVIDUAL PUP OBSERVATION PER LITTER RECORD DURING POSTNATAL PERIOD

Group & Dose (mg/kg body weight/day)	Dam No.	Pup No. →	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18
G3 & 300	Rg7953		Non-pregnant
	Rg7954	Sex →	M	M	M	M	-	-	-	-	-	-	-	-	-	-	-	-	-	-
		PND 1 to 13	N	N	N	N	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7955	Sex →	M	M	M	M	M	M	F	F	F	F	-	-	-	-	-	-	-	-
		PND 1 to 13	N	N	N	N	N	N	N	N	N	N	-	-	-	-	-	-	-	-
	Rg7956	Sex →	M	M	M	M	M	M	M	F	F	F	F	F	F	-	-	-	-	-
		PND 1 to 13	N	N	N	N	N	N	N	N	N	N	N	N^TS	N^TS	-	-	-	-	-
	Rg7957		Non-pregnant
	Rg7958	Sex →	M	M	M	F	-	-	-	-	-	-	-	-	-	-	-	-	-	-
		PND 1 to 13	N	N	N	N	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Rg7959	Sex →	M	M	M	M	F	F	F	F	F	-	-	-	-	-	-	-	-	-
		PND 1 to 13	N	N	N	N	N	N	N	N	N	-	-	-	-	-	-	-	-	-
	Rg7960	Sex →	M	M	M	M	M	M	M	M	F	F	F	F	-	-	-	-	-	-
		PND 1 to 13	N	N	N	N	N	N	HS	N	N	N	N	N^TS	-	-	-	-	-	-
	Rg7961	Sex →	M	M	M	M	M	F	F	F	F	F	F	-	-	-	-	-	-	-
		PND 1 to 13	N	N	N	N	N	N	N	N	N	N	N^TS	-	-	-	-	-	-	-
	Rg7962	Sex →	M	M	M	M	M	M	F	F	F	F	-	-	-	-	-	-	-	-
		PND 1 to 13	N	N	N	N	N	N	N	N	N	N	-	-	-	-	-	-	-	-
	Rg7963		Total litter loss
	Rg7964	Sex →	M	M	M	M	M	M	M	F	F	F	F	F	F	F	F	F	F	F
		PND 1 to 13	N	N	N	N	N	N	N	N	N	N	N	N	N	N (PND1) D (PND2)	N	N	N^TS	N^TS

N: Normal; PND: Postnatal day; M: Male; F: Female; -: Not applicable; D: Dead.
TS: Observed until PND 4 and terminally sacrificed for blood collection.

HS: Haemorrhagic Spot on nose and head region on PND 1 and Dead on PND 2.

 

 

APPENDIX 18 (Contd…). INDIVIDUAL PUP OBSERVATION PER LITTER RECORD DURING POSTNATAL PERIOD

Group & Dose (mg/kg body weight/day)

Dam No.

Pup No. →

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

G4 & 600

Rg7965

Sex →

M

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

PND 1 to 4

N (PND 1 to 3) D (PND 4)

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Rg7966

Sex →

M

M

M

F

F

F

F

-

-

-

-

-

-

-

-

-

-

-

PND 1 to 13

N

N

N

N

N

N

N

-

-

-

-

-

-

-

-

-

-

-

Rg7967

Total litter loss

Rg7968

Sex →

M

M

M

M

M

M

M

M

F

F

F

F

F

F

-

-

-

-

PND 1 to 13

N

N

N

N

N

N

N

N

N

N

N

N

N^TS

N^TS

-

-

-

-

Rg7969

Sex →

M

M

M

M

F

F

F

F

F

F

F

F

-

-

-

-

-

-

PND 1 to 13

N

N

N (PND1) D (PND2)

N

N

N

N

N

N

N

N (PND1) D (PND2)

N

-

-

-

-

-

-

Rg7970

Sex →

M

M

M

M

F

F

F

F

F

F

-

-

-

-

-

-

-

-

PND 1 to 13

N

N

N

N

N

N

N

N

N

N

-

-

-

-

-

-

-

-

Rg7971

Sex →

M

M

M

M

F

F

F

F

F

F

F

F

-

-

-

-

-

-

PND 1 to 13

N

N

N

N

N

N

N

N

N

N

N^TS

N^TS

-

-

-

-

-

-

Rg7972

Sex →

M

M

M

F

F

F

F

F

F

F

F

-

-

-

-

-

-

-

PND 1 to 2

@

@

@

@

@

@

@

@

@

@

@

-

-

-

-

-

-

-

Rg7973

Non-pregnant

Rg7974

Sex →

M

M

M

M

M

M

M

M

F

F

F

F

F

F

F

F

F

F

PND 1 to 13

N (PND1) D (PND2)

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N^TS

N^TS

Rg7975

Sex →

M

M

M

M

M

M

F

F

F

F

F

F

F

F

-

-

-

-

PND 1 to 13

N

N

N

N

N

N

N

N

N

N

N

N

N^TS

N^TS

-

-

-

-

Rg7976

Sex →

M

M

M

M

F

F

F

F

F

-

-

-

-

-

-

-

-

-

PND 1 to 13

N

N

N

N

N

N

N

N

N

-

-

-

-

-

-

-

-

-

N: Normal; PND: Postnatal day; M: Male; F: Female; -: Not applicable; D: Dead.
TS: Observed until PND 4 and terminally sacrificed for blood collection.

@: Noted with hypothermia on PND 1 and found dead on PND 2.

 

• INDIVIDUAL PUP WEIGHT (g) AND MEAN PUP WEIGHT (g) PER LITTER RECORD

Group & Dose (mg/kg body weight/day)	Dam No.	Post-natal Day ↓	Pup No. →                  Sex↓	1	2	3	4	5	6	7	8	9	10	11	12	13		Mean
																		Male	Female
G1 & 0	Rg7929	PND 1	M	7.19	6.94	7.23	6.87	6.81	6.79	-	-	-	-	-	-	-		6.97	6.79
			F	-	-	-	-	-	-	6.66	6.92	6.81	6.77	-	-	-
		PND 4	M	12.04	11.79	12.14	11.26	11.57	11.41	-	-	-	-	-	-	-		11.70	11.04
			F	-	-	-	-	-	-	11.08	11.21	10.98	10.87	-	-	-
		PND 7	M	16.74	15.27	16.01	15.54	15.72	15.16	-	-	-	-	-	-	-		15.74	15.02
			F	-	-	-	-	-	-	15.01	14.98	14.96	15.13	-	-	-
		PND 13	M	29.81	28.46	30.03	27.47	27.36	26.67	-	-	-	-	-	-	-		28.30	26.82
			F	-	-	-	-	-	-	24.78	27.81	27.22	27.48	-	-	-
	Rg7930	PND 1	M	7.07	6.96	6.91	-	-	-	-	-	-	-	-	-	-		6.98	6.80
			F	-	-	-	6.79	6.83	6.92	6.77	6.68	-	-	-	-	-
		PND 4	M	12.47	12.04	11.85	-	-	-	-	-	-	-	-	-	-		12.12	11.55
			F	-	-	-	11.43	11.62	11.71	11.53	11.48	-	-	-	-	-
		PND 7	M	16.08	15.90	15.63	-	-	-	-	-	-	-	-	-	-		15.87	15.33
			F	-	-	-	15.21	15.46	15.51	15.08	15.38	-	-	-	-	-
		PND 13	M	30.81	29.47	29.83	-	-	-	-	-	-	-	-	-	-		30.04	28.80
			F	-	-	-	28.79	29.86	28.27	28.75	28.34	-	-	-	-	-
	Rg7931	PND 1	M	7.20	6.89	6.40	6.58	6.73	6.81	6.95	-	-	-	-	-	-		6.79	6.60
			F	-	-	-	-	-	-	-	6.98	6.80	6.56	6.44	6.48	6.36
		PND 4	M	12.01	11.41	10.72	10.61	10.81	10.94	11.27	-	-	-	-	-	-		11.11	10.64
			F	-	-	-	-	-	-	-	11.49	10.67	10.48	10.51	10.37	10.31
		PND 7	M	16.32	15.58	15.39	14.78	14.94	15.12	15.36	-	-	-	-	-	-		15.36	14.51
			F	-	-	-	-	-	-	-	14.93	14.34	14.31	14.47	-	-
		PND 13	M	29.73	28.16	27.49	28.03	28.56	29.01	28.16	-	-	-	-	-	-		28.45	27.09
			F	-	-	-	-	-	-	-	26.42	27.03	26.88	28.03	-	-

M: Male; F: Female; PND: Postnatal Day; -: Not applicable.

 

 

 

 

APPENDIX 19 (Contd…). INDIVIDUAL PUP WEIGHT (g) AND MEAN PUP WEIGHT (g) PER LITTER RECORD

Group & Dose (mg/kg body weight/day)	Dam No.	Post-natal Day ↓	Pup No. →                  Sex↓	1	2	3	4	5	6	7	8	9	10	11		Mean
																Male	Female
G1 & 0	Rg7932	PND 1	M	6.89	7.35	7.08	3.66	-	-	-	-	-	-	-		6.25	5.81
			F	-	-	-	-	6.72	6.29	6.96	3.25	-	-	-
		PND 4	M	11.91	12.41	12.01	-	-	-	-	-	-	-	-		12.11	10.87
			F	-	-	-	-	10.94	10.57	11.11	-	-	-	-
		PND 7	M	16.01	16.54	15.78	-	-	-	-	-	-	-	-		16.11	14.99
			F	-	-	-	-	14.92	14.66	15.38	-	-	-	-
		PND 13	M	29.54	30.21	28.91	-	-	-	-	-	-	-	-		29.55	28.10
			F	-	-	-	-	28.26	27.74	28.31	-	-	-	-
	Rg7933	PND 1	M	6.83	7.16	6.94	6.68	7.03	6.71	6.89	6.77	6.96	-	-		6.89	6.47
			F	-	-	-	-	-	-	-	-	-	6.55	6.39
		PND 4	M	11.42	12.16	11.39	10.47	12.08	10.84	10.77	10.61	11.47	-	-		11.25	10.57
			F	-	-	-	-	-	-	-	-	-	10.72	10.41
		PND 7	M	15.38	16.01	15.61	14.86	15.78	14.67	15.03	14.76	15.11	-	-		15.25	14.51
			F	-	-	-	-	-	-	-	-	-	14.51	-
		PND 13	M	28.48	30.01	29.16	28.33	29.04	27.66	28.09	27.76	28.24	-	-		28.53	27.56
			F	-	-	-	-	-	-	-	-	-	27.56	-
	Rg7934	PND 1	M	6.69	6.94	6.73	7.06	-	-	-	-	-	-	-		6.86	6.49
			F	-	-	-	-	6.47	6.41	6.66	6.39	6.54	-	-
		PND 4	M	10.72	11.41	10.91	12.16	-	-	-	-	-	-	-		11.30	10.50
			F	-	-	-	-	10.61	10.54	10.49	10.41	10.44	-	-
		PND 7	M	14.67	15.49	15.13	16.27	-	-	-	-	-	-	-		15.39	14.51
			F	-	-	-	-	14.66	14.41	14.64	14.31	14.51	-	-
		PND 13	M	28.06	28.46	28.73	30.14	-	-	-	-	-	-	-		28.85	27.84
			F	-	-	-	-	28.36	27.38	28.14	27.06	28.27	-	-

M: Male; F: Female; PND: Postnatal Day; -: Not applicable.

 

 

 

 

 

APPENDIX 19 (Contd…). INDIVIDUAL PUP WEIGHT (g) AND MEAN PUP WEIGHT (g) PER LITTER RECORD

Group & Dose (mg/kg body weight/day)	Dam No.	Post-natal Day ↓	Pup No. →                  Sex↓	1	2	3	4	5	6	7	8	9	10	11	12	13		Mean
																		Male	Female
G1 & 0	Rg7935	PND 1	M	6.48	6.30	6.17	7.22	6.91	6.76	6.26	-	-	-	-	-	-		6.59	6.48
			F	-	-	-	-	-	-	-	6.45	6.69	6.53	6.17	6.08	6.94
		PND 4	M	10.23	10.47	10.36	12.03	11.98	10.67	10.41	-	-	-	-	-	-		10.88	10.41
			F	-	-	-	-	-	-	-	10.33	10.51	10.63	10.08	10.11	10.79
		PND 7	M	14.24	14.57	14.72	15.97	15.88	14.72	14.46	-	-	-	-	-	-		14.94	14.30
			F	-	-	-	-	-	-	-	14.31	14.27	14.58	14.03	-	-
		PND 13	M	27.68	28.01	27.98	29.14	28.86	27.66	27.24	-	-	-	-	-	-		28.08	27.57
			F	-	-	-	-	-	-	-	27.43	28.03	26.98	27.84	-	-
	Rg7936	PND 1	M	6.89	7.21	7.01	6.95	6.81	6.61	-	-	-	-	-	-	-		6.91	6.37
			F	-	-	-	-	-	-	6.43	6.37	6.31	6.54	6.18	6.41	-
		PND 4	M	11.11	12.06	11.47	10.72	10.94	10.58	-	-	-	-	-	-	-		11.15	10.36
			F	-	-	-	-	-	-	10.31	10.33	10.45	10.62	10.27	10.19	-
		PND 7	M	15.35	15.20	14.91	14.97	15.05	15.33	-	-	-	-	-	-	-		15.14	14.82
			F	-	-	-	-	-	-	14.90	14.84	15.01	14.52	-	-	-
		PND 13	M	28.14	28.06	27.79	28.25	28.14	28.65	-	-	-	-	-	-	-		28.17	27.92
			F	-	-	-	-	-	-	27.63	28.03	28.34	27.66	-	-	-
	Rg7937	PND 1	M	6.83	7.16	-	-	-	-	-	-	-	-	-	-	-		7.00	6.82
			F	-	-	6.79	6.92	6.74	-	-	-	-	-	-	-	-
		PND 4	M	11.27	12.21	-	-	-	-	-	-	-	-	-	-	-		11.74	10.94
			F	-	-	10.94	11.01	10.87	-	-	-	-	-	-	-	-
		PND 7	M	15.87	14.98	-	-	-	-	-	-	-	-	-	-	-		15.43	14.81
			F	-	-	14.72	15.04	14.68	-	-	-	-	-	-	-	-
		PND 13	M	29.47	30.08	-	-	-	-	-	-	-	-	-	-	-		29.78	28.50
			F	-	-	27.96	28.49	29.06	-	-	-	-	-	-	-	-

M: Male; F: Female; PND: Postnatal Day; -: Not applicable.

 

 

APPENDIX 19 (Contd…). INDIVIDUAL PUP WEIGHT (g) AND MEAN PUP WEIGHT (g) PER LITTER RECORD

Group & Dose (mg/kg body weight/day)	Dam No.	Post-natal Day ↓	Pup No. →                  Sex↓	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17		Mean
																						Male	Female
G1 & 0	Rg7938	PND 1	M	6.27	6.44	5.93	6.31	6.25	6.19	6.78	6.47	6.58	6.41	-	-	-	-	-	-	-		6.36	5.92
			F	-	-	-	-	-	-	-	-	-	-	5.88	6.14	6.01	6.00	5.69	5.93	5.76
		PND 4	M	10.14	10.53	10.02	10.29	10.37	10.41	10.89	10.63	10.44	10.93	-	-	-	-	-	-	-		10.47	9.97
			F	-	-	-	-	-	-	-	-	-	-	9.91	10.17	10.03	9.97	9.86	10.03	9.84
		PND 7	M	14.60	14.36	14.18	14.26	14.51	14.12	13.98	13.62	14.22	13.59	-	-	-	-	-	-	-		14.14	13.70
			F	-	-	-	-	-	-	-	-	-	-	13.96	14.01	13.19	13.37	13.99	-	-
		PND 13	M	27.59	27.14	27.36	27.01	28.11	27.19	26.76	26.88	27.43	26.19	-	-	-	-	-	-	-		27.17	26.16
			F	-	-	-	-	-	-	-	-	-	-	25.98	26.27	26.11	25.43	27.03	-	-
	Rg7939	PND 1	M	6.79	7.12	6.88	6.73	6.99	7.08	7.01	6.63	-	-	-	-	-	-	-	-	-		6.90	6.39
			F	-	-	-	-	-	-	-	-	6.41	6.39	6.58	6.27	6.31	-	-	-	-
		PND 4	M	10.91	12.16	11.41	11.09	12.01	12.11	12.07	11.26	-	-	-	-	-	-	-	-	-		11.63	10.54
			F	-	-	-	-	-	-	-	-	10.72	10.51	10.79	10.38	10.29	-	-	-	-
		PND 7	M	15.14	15.57	14.96	15.01	15.69	15.23	14.78	14.69	-	-	-	-	-	-	-	-	-		15.13	13.93
			F	-	-	-	-	-	-	-	-	14.16	13.97	13.67	-	-	-	-	-	-
		PND 13	M	27.91	28.32	27.81	29.03	28.44	27.61	26.94	27.03	-	-	-	-	-	-	-	-	-		27.89	26.81
			F	-	-	-	-	-	-	-	-	28.11	26.34	25.99	-	-	-	-	-	-
	Rg7940	PND 1	M	7.11	6.87	6.91	6.81	-	-	-	-	-	-	-	-	-	-	-	-	-		6.93	6.65
			F	-	-	-	-	6.66	6.75	6.49	6.71	-	-	-	-	-	-	-	-	-
		PND 4	M	12.31	11.41	11.72	11.27	-	-	-	-	-	-	-	-	-	-	-	-	-		11.68	10.81
			F	-	-	-	-	10.94	10.81	10.66	10.84	-	-	-	-	-	-	-	-	-
		PND 7	M	16.27	15.86	15.71	15.76	-	-	-	-	-	-	-	-	-	-	-	-	-		15.90	14.95
			F	-	-	-	-	14.96	15.03	14.89	14.93	-	-	-	-	-	-	-	-	-
		PND 13	M	30.41	29.71	28.97	29.12	-	-	-	-	-	-	-	-	-	-	-	-	-		29.55	28.75
			F	-	-	-	-	28.69	28.95	28.66	28.71	-	-	-	-	-	-	-	-	-

M: Male; F: Female; PND: Postnatal Day; -: Not applicable.

 

 

 

 

APPENDIX 19 (Contd…). INDIVIDUAL PUP WEIGHT (g) AND MEAN PUP WEIGHT (g) PER LITTER RECORD

Group & Dose (mg/kg body weight/day)	Dam No.	Post-natal Day ↓	Pup No. →                  Sex↓	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16		Mean
																					Male	Female
G2 & 150	Rg7941	PND 1	M	6.45	6.71	6.29	6.83	6.66	6.59	-	-	-	-	-	-	-	-	-	-		6.59	6.02
			F	-	-	-	-	-	-	6.11	6.38	6.01	5.93	5.49	6.21	6.17	6.03	5.86	5.97
		PND 4	M	10.27	10.58	10.11	10.94	10.87	10.41	-	-	-	-	-	-	-	-	-	-		10.53	10.02
			F	-	-	-	-	-	-	10.01	10.21	9.97	9.86	9.72	10.11	10.31	10.00	9.94	10.04
		PND 7	M	14.16	14.47	13.98	15.03	14.79	14.26	-	-	-	-	-	-	-	-	-	-		14.45	13.41
			F	-	-	-	-	-	-	13.83	13.49	12.86	13.10	12.94	13.37	13.54	14.15	-	-
		PND 13	M	28.11	27.91	26.98	28.23	28.46	27.81	-	-	-	-	-	-	-	-	-	-		27.92	26.81
			F	-	-	-	-	-	-	26.54	27.23	26.71	25.83	27.26	26.49	26.41	28.00	-	-
	Rg7942	PND 1	M	6.79	7.06	6.81	6.75	-	-	-	-	-	-	-	-	-	-	-	-		6.85	6.59
			F	-	-	-	-	6.61	6.59	6.73	6.41	-	-	-	-	-	-	-	-
		PND 4	M	11.14	12.26	11.07	11.44	-	-	-	-	-	-	-	-	-	-	-	-		11.48	10.77
			F	-	-	-	-	10.91	10.97	10.46	10.73	-	-	-	-	-	-	-	-
		PND 7	M	15.49	15.33	16.13	15.67	-	-	-	-	-	-	-	-	-	-	-	-		15.66	14.84
			F	-	-	-	-	14.90	14.75	15.06	14.65	-	-	-	-	-	-	-	-
		PND 13	M	28.59	28.16	29.38	28.41	-	-	-	-	-	-	-	-	-	-	-	-		28.64	28.10
			F	-	-	-	-	27.96	28.14	28.33	27.98	-	-	-	-	-	-	-	-
	Rg7943	PND 1	M	6.70	6.53	6.19	6.87	6.63	6.76	-	-	-	-	-	-	-	-	-	-		6.61	6.43
			F	-	-	-	-	-	-	6.32	6.25	6.71	-	-	-	-	-	-	-
		PND 4	M	10.94	10.72	10.49	11.01	10.83	10.69	-	-	-	-	-	-	-	-	-	-		10.78	10.44
			F	-	-	-	-	-	-	10.41	10.29	10.63	-	-	-	-	-	-	-
		PND 7	M	15.76	15.11	14.38	15.24	14.79	14.77	-	-	-	-	-	-	-	-	-	-		15.01	14.32
			F	-	-	-	-	-	-	14.34	14.26	14.36	-	-	-	-	-	-	-
		PND 13	M	29.79	28.56	27.94	28.48	27.66	28.12	-	-	-	-	-	-	-	-	-	-		28.43	27.99
			F	-	-	-	-	-	-	27.34	27.62	29.01	-	-	-	-	-	-	-

M: Male; F: Female; PND: Postnatal Day; -: Not applicable.

 

 

 

APPENDIX 19 (Contd…). INDIVIDUAL PUP WEIGHT (g) AND MEAN PUP WEIGHT (g) PER LITTER RECORD

Group & Dose (mg/kg body weight/day)	Dam No.	Post-natal Day ↓	Pup No. →                  Sex↓	1	2	3	4	5	6	7	8	9	10		Mean
															Male	Female
G2 & 150	Rg7944	PND 1	M	6.61	6.74	6.58	-	-	-	-	-	-	-		6.64	6.25
			F	-	-	-	6.91	6.01	6.32	6.14	6.11	6.07	6.21
		PND 4	M	11.20	10.89	11.04	-	-	-	-	-	-	-		11.04	10.54
			F	-	-	-	10.14	10.57	10.26	10.93	10.49	10.72	10.66
		PND 7	M	15.41	15.17	14.96	-	-	-	-	-	-	-		15.18	14.70
			F	-	-	-	15.01	14.73	14.58	14.46	14.82	14.93	14.36
		PND 13	M	28.79	28.46	27.85	-	-	-	-	-	-	-		28.37	27.58
			F	-	-	-	27.96	27.67	27.32	27.43	27.41	28.02	27.26
	Rg7945	PND 1	M	6.92	7.11	6.87	6.97	6.68	-	-	-	-	-		6.91	6.57
			F	-	-	-	-	-	6.57	6.72	6.41	-	-
		PND 4	M	11.16	12.11	10.99	11.16	10.84	-	-	-	-	-		11.25	10.54
			F	-	-	-	-	-	10.47	10.76	10.38	-	-
		PND 7	M	15.56	15.21	15.38	14.87	14.76	-	-	-	-	-		15.16	14.95
			F	-	-	-	-	-	15.05	14.98	14.83	-	-
		PND 13	M	29.16	28.72	29.14	28.96	27.16	-	-	-	-	-		28.63	27.94
			F	-	-	-	-	-	28.14	28.01	27.68	-	-
	Rg7946	PND 1	M	7.03	6.95	6.56	-	-	-	-	-	-	-		6.85	6.51
			F	-	-	-	6.83	6.42	6.29	-	-	-	-
		PND 4	M	12.19	11.87	10.94	-	-	-	-	-	-	-		11.67	10.92
			F	-	-	-	10.99	11.01	10.76	-	-	-	-
		PND 7	M	16.01	15.59	15.14	-	-	-	-	-	-	-		15.58	15.09
			F	-	-	-	15.03	15.27	14.96	-	-	-	-
		PND 13	M	30.26	29.18	29.04	-	-	-	-	-	-	-		29.49	28.49
			F	-	-	-	28.89	28.47	28.12	-	-	-	-

M: Male; F: Female; PND: Postnatal Day; -: Not applicable.

 

 

 

APPENDIX 19 (Contd…). INDIVIDUAL PUP WEIGHT (g) AND MEAN PUP WEIGHT (g) PER LITTER RECORD

Group & Dose (mg/kg body weight/day)	Dam No.	Post-natal Day ↓	Pup No. →                  Sex↓	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16		Mean
																					Male	Female
G2 & 150	Rg7947	PND 1	M	6.71	6.59	7.14	7.02	6.84	6.92	-	-	-	-	-	-	-	-	-	-		6.87	6.39
			F	-	-	-	-	-	-	6.41	6.49	6.34	6.33	-	-	-	-	-	-
		PND 4	M	10.57	10.63	12.27	11.88	10.91	10.83	-	-	-	-	-	-	-	-	-	-		11.18	10.38
			F	-	-	-	-	-	-	10.34	10.61	10.14	10.43	-	-	-	-	-	-
		PND 7	M	15.45	15.91	15.87	14.99	16.02	15.33	-	-	-	-	-	-	-	-	-	-		15.60	14.79
			F	-	-	-	-	-	-	14.90	14.75	14.84	14.66	-	-	-	-	-	-
		PND 13	M	28.76	28.69	29.12	28.03	29.84	27.96	-	-	-	-	-	-	-	-	-	-		28.73	28.01
			F	-	-	-	-	-	-	28.34	28.66	27.39	27.64	-	-	-	-	-	-
	Rg7948	PND 1	M	6.39	6.61	6.48	6.57	6.94	6.77	6.63	6.42	-	-	-	-	-	-	-	-		6.60	6.04
			F	-	-	-	-	-	-	-	-	6.10	6.05	6.25	5.91	6.17	6.02	5.83	6.00
		PND 4	M	10.51	10.79	10.41	10.38	11.01	10.86	10.58	10.39	-	-	-	-	-	-	-	-		10.62	10.06
			F	-	-	-	-	-	-	-	-	10.08	9.97	10.19	9.88	10.29	10.00	9.97	10.06
		PND 7	M	13.93	14.16	14.44	13.73	15.41	14.87	14.35	13.23	-	-	-	-	-	-	-	-		14.27	13.29
			F	-	-	-	-	-	-	-	-	13.61	12.94	13.29	13.18	13.62	13.08	-	-
		PND 13	M	26.83	27.54	27.91	26.88	28.14	27.39	27.76	27.18	-	-	-	-	-	-	-	-		27.45	26.70
			F	-	-	-	-	-	-	-	-	27.03	26.14	26.44	27.01	26.84	26.72	-	-
	Rg7949	Non-pregnant
	Rg7950	PND 1	M	6.57	6.88	6.99	7.18	-	-	-	-	-	-	-	-	-	-	-	-		6.91	-
		PND 4	M	11.27	11.72	12.11	12.34	-	-	-	-	-	-	-	-	-	-	-	-		11.86	-
		PND 7	M	16.14	15.85	15.97	15.78	-	-	-	-	-	-	-	-	-	-	-	-		15.94	-
		PND 13	M	30.76	29.78	30.04	28.99	-	-	-	-	-	-	-	-	-	-	-	-		29.89	-

M: Male; F: Female; PND: Postnatal Day; -: Not applicable.

 

 

 

APPENDIX 19 (Contd…). INDIVIDUAL PUP WEIGHT (g) AND MEAN PUP WEIGHT (g) PER LITTER RECORD

Group & Dose (mg/kg body weight/day)	Dam No.	Post-natal Day ↓	Pup No. →                  Sex↓	1	2	3	4	5	6	7	8	9	10	11	12		Mean
																	Male	Female
G2 & 150	Rg7951	PND 1	M	7.16	6.98	6.95	-	-	-	-	-	-	-	-	-		7.03	6.96
			F	-	-	-	7.10	6.90	6.87	-	-	-	-	-	-
		PND 4	M	12.23	12.01	11.83	-	-	-	-	-	-	-	-	-		12.02	11.69
			F	-	-	-	11.79	11.58	11.69	-	-	-	-	-	-
		PND 7	M	16.13	16.27	15.98	-	-	-	-	-	-	-	-	-		16.13	15.63
			F	-	-	-	15.47	15.63	15.79	-	-	-	-	-	-
		PND 13	M	30.03	29.97	29.78	-	-	-	-	-	-	-	-	-		29.93	29.02
			F	-	-	-	29.06	28.86	29.13	-	-	-	-	-	-
	Rg7952	PND 1	M	6.69	6.74	7.07	6.59	6.88	7.03	-	-	-	-	-	-		6.83	6.29
			F	-	-	-	-	-	-	6.43	6.27	6.09	6.51	6.34	6.11
		PND 4	M	11.33	11.14	12.08	10.84	10.75	11.96	-	-	-	-	-	-		11.35	10.45
			F	-	-	-	-	-	-	10.67	10.53	10.32	10.76	10.15	10.28
		PND 7	M	15.11	14.83	14.92	14.37	14.90	15.06	-	-	-	-	-	-		14.87	14.23
			F	-	-	-	-	-	-	14.54	14.25	14.18	13.94	-	-
		PND 13	M	28.64	28.14	27.77	28.16	28.11	29.08	-	-	-	-	-	-		28.32	27.33
			F	-	-	-	-	-	-	27.46	27.53	27.36	26.98	-	-

M: Male; F: Female; PND: Postnatal Day; -: Not applicable.

 

 

APPENDIX 19 (Contd…). INDIVIDUAL PUP WEIGHT (g) AND MEAN PUP WEIGHT (g) PER LITTER RECORD

Group & Dose (mg/kg body weight/day)	Dam No.	Post-natal Day ↓	Pup No. →                  Sex↓	1	2	3	4	5	6	7	8	9	10	11	12	13		Mean
																		Male	Female
G3 & 300	Rg7953	Non-pregnant
	Rg7954	PND 1	M	6.69	6.83	7.18	6.54	-	-	-	-	-	-	-	-	-		6.81	-
		PND 4	M	11.21	11.76	12.31	10.97	-	-	-	-	-	-	-	-	-		11.56	-
		PND 7	M	15.91	15.98	16.13	15.75	-	-	-	-	-	-	-	-	-		15.94	-
		PND 13	M	30.26	30.17	30.28	30.11	-	-	-	-	-	-	-	-	-		30.21	-
	Rg7955	PND 1	M	6.97	7.03	6.86	6.81	6.79	7.08	-	-	-	-	-	-	-		6.92	6.53
			F	-	-	-	-	-	-	6.44	6.59	6.48	6.61	-	-	-
		PND 4	M	11.49	12.17	11.58	11.56	10.94	12.01	-	-	-	-	-	-	-		11.63	10.70
			F	-	-	-	-	-	-	10.59	10.43	10.66	11.13	-	-	-
		PND 7	M	15.75	16.41	16.14	15.93	15.27	16.13	-	-	-	-	-	-	-		15.94	15.14
			F	-	-	-	-	-	-	15.08	14.93	14.98	15.56	-	-	-
		PND 13	M	28.44	29.91	30.06	29.41	28.47	29.76	-	-	-	-	-	-	-		29.34	28.47
			F	-	-	-	-	-	-	28.51	28.23	28.47	28.66	-	-	-
	Rg7956	PND 1	M	6.95	6.72	6.88	6.91	6.60	6.77	7.16	-	-	-	-	-	-		6.86	6.53
			F	-	-	-	-	-	-	-	6.40	6.48	6.36	6.66	6.75	6.52
		PND 4	M	11.41	10.93	11.16	12.01	10.44	10.68	11.94	-	-	-	-	-	-		11.22	10.49
			F	-	-	-	-	-	-	-	10.51	10.29	10.31	10.56	10.79	10.48
		PND 7	M	15.90	15.82	14.98	14.86	15.48	15.33	15.72	-	-	-	-	-	-		15.44	15.11
			F	-	-	-	-	-	-	-	14.93	15.16	15.25	15.10	-	-
		PND 13	M	28.19	28.27	28.16	27.91	28.46	28.67	28.97	-	-	-	-	-	-		28.38	27.72
			F	-	-	-	-	-	-	-	27.45	28.12	27.63	27.66	-	-
	Rg7957	Non-pregnant

M: Male; F: Female; PND: Postnatal Day; -: Not applicable.

 

 

APPENDIX 19 (Contd…). INDIVIDUAL PUP WEIGHT (g) AND MEAN PUP WEIGHT (g) PER LITTER RECORD

Group & Dose (mg/kg body weight/day)	Dam No.	Post-natal Day ↓	Pup No. →                  Sex↓	1	2	3	4	5	6	7	8	9	10	11	12		Mean
																	Male	Female
G3 & 300	Rg7958	PND 1	M	7.11	6.98	7.02	-	-	-	-	-	-	-	-	-		7.04	6.87
			F	-	-	-	6.87	-	-	-	-	-	-	-	-
		PND 4	M	12.34	11.53	12.42	-	-	-	-	-	-	-	-	-		12.10	11.18
			F	-	-	-	11.18	-	-	-	-	-	-	-	-
		PND 7	M	16.31	15.94	16.27	-	-	-	-	-	-	-	-	-		16.17	15.66
			F	-	-	-	15.66	-	-	-	-	-	-	-	-
		PND 13	M	29.69	29.52	28.97	-	-	-	-	-	-	-	-	-		29.39	28.90
			F	-	-	-	28.90	-	-	-	-	-	-	-	-
	Rg7959	PND 1	M	6.93	6.85	7.10	6.96	-	-	-	-	-	-	-	-		6.96	6.55
			F	-	-	-	-	6.49	6.77	6.50	6.61	6.38	-	-	-
		PND 4	M	11.72	11.21	12.16	11.81	-	-	-	-	-	-	-	-		11.73	10.66
			F	-	-	-	-	10.72	10.58	10.72	10.81	10.47	-	-	-
		PND 7	M	15.70	15.25	15.38	14.67	-	-	-	-	-	-	-	-		15.25	14.98
			F	-	-	-	-	14.53	15.16	15.25	15.06	14.92	-	-	-
		PND 13	M	28.97	29.05	28.71	28.69	-	-	-	-	-	-	-	-		28.86	28.04
			F	-	-	-	-	27.49	28.17	28.56	27.93	28.04	-	-	-
	Rg7960	PND 1	M	6.73	6.49	7.07	6.88	6.71	6.64	6.41	6.79	-	-	-	-		6.72	6.37
			F	-	-	-	-	-	-	-	-	6.29	6.48	6.37	6.35
		PND 4	M	10.88	10.57	12.14	11.71	11.08	10.72	-	11.01	-	-	-	-		11.16	10.45
			F	-	-	-	-	-	-	-	-	10.49	10.61	10.41	10.29
		PND 7	M	14.69	14.47	16.17	15.87	15.61	14.76	-	15.01	-	-	-	-		15.23	14.17
			F	-	-	-	-	-	-	-	-	13.92	14.46	14.13	-
		PND 13	M	27.53	27.85	29.91	28.78	29.03	27.47	-	28.11	-	-	-	-		28.38	27.61
			F	-	-	-	-	-	-	-	-	27.43	27.31	28.08	-

M: Male; F: Female; PND: Postnatal Day; -: Not applicable.

 

 

 

APPENDIX 19 (Contd…). INDIVIDUAL PUP WEIGHT (g) AND MEAN PUP WEIGHT (g) PER LITTER RECORD

Group & Dose (mg/kg body weight/ day)	Dam No.	Post-natal Day ↓	Pup No. →                  Sex↓	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18		Mean
																							Male	Female
G3 & 300	Rg7961	PND 1	M	6.77	6.95	7.01	7.21	6.83	-	-	-	-	-	-	-	-	-	-	-	-	-		6.95	6.34
			F	-	-	-	-	-	6.47	6.41	6.37	6.54	6.19	6.07	-	-	-	-	-	-	-
		PND 4	M	10.91	11.16	12.05	12.10	10.88	-	-	-	-	-	-	-	-	-	-	-	-	-		11.42	10.35
			F	-	-	-	-	-	10.22	10.37	10.42	10.19	10.50	10.40	-	-	-	-	-	-	-
		PND 7	M	14.63	14.98	14.44	14.85	15.02	-	-	-	-	-	-	-	-	-	-	-	-	-		14.78	14.17
			F	-	-	-	-	-	14.26	14.19	13.94	13.99	14.47	-	-	-	-	-	-	-	-
		PND 13	M	28.17	28.61	27.75	28.03	28.68	-	-	-	-	-	-	-	-	-	-	-	-	-		28.25	27.50
			F	-	-	-	-	-	27.67	27.46	26.98	27.43	27.95	-	-	-	-	-	-	-	-
	Rg7962	PND 1	M	6.93	6.49	6.85	6.99	7.06	6.40	-	-	-	-	-	-	-	-	-	-	-	-		6.79	6.40
			F	-	-	-	-	-	-	6.53	6.16	6.70	6.21	-	-	-	-	-	-	-	-
		PND 4	M	11.29	10.47	10.93	11.47	12.11	10.58	-	-	-	-	-	-	-	-	-	-	-	-		11.14	10.56
			F	-	-	-	-	-	-	10.72	10.39	10.67	10.44	-	-	-	-	-	-	-	-
		PND 7	M	15.87	15.03	15.41	15.36	16.41	14.98	-	-	-	-	-	-	-	-	-	-	-	-		15.51	14.97
			F	-	-	-	-	-	-	15.03	14.76	14.93	15.14	-	-	-	-	-	-	-	-
		PND 13	M	28.73	28.14	28.36	28.47	30.03	28.11	-	-	-	-	-	-	-	-	-	-	-	-		28.64	28.15
			F	-	-	-	-	-	-	28.26	27.99	27.78	28.58	-	-	-	-	-	-	-	-
	Rg7963	Total litter loss
	Rg7964	PND 1	M	6.23	5.94	6.01	6.41	6.26	5.88	6.07	-	-	-	-	-	-	-	-	-	-	-		6.11	5.84
			F	-	-	-	-	-	-	-	5.51	5.83	6.00	5.81	5.92	6.04	5.47	5.76	5.94	5.91	6.04
		PND 4	M	10.47	10.03	10.14	10.63	10.38	10.01	10.16	-	-	-	-	-	-	-	-	-	-	-		10.26	9.94
			F	-	-	-	-	-	-	-	9.84	10.01	10.07	9.98	10.04	10.10	-	9.47	10.00	9.89	10.01
		PND 7	M	14.78	14.11	14.36	14.51	14.03	13.98	15.16	-	-	-	-	-	-	-	-	-	-	-		14.42	13.98
			F	-	-	-	-	-	-	-	13.73	13.91	14.02	14.26	13.93	14.41	-	13.72	13.89	-	-
		PND 13	M	26.97	27.03	27.41	27.66	27.38	26.89	28.14	-	-	-	-	-	-	-	-	-	-	-		27.35	26.73
			F	-	-	-	-	-	-	-	26.58	26.81	27.00	27.18	25.94	27.48	-	26.74	26.08	-	-

M: Male; F: Female; PND: Postnatal Day; -: Not applicable.

 

APPENDIX 19 (Contd…). INDIVIDUAL PUP WEIGHT (g) AND MEAN PUP WEIGHT (g) PER LITTER RECORD

Group & Dose (mg/kg body weight/day)	Dam No.	Post-natal Day ↓	Pup No. →                  Sex↓	1	2	3	4	5	6	7	8	9	10	11	12	13	14		Mean
																			Male	Female
G4 & 600	Rg7965	PND 1	M	5.01	-	-	-	-	-	-	-	-	-	-	-	-	-		5.01	-
	Rg7966	PND 1	M	6.97	7.22	7.12	-	-	-	-	-	-	-	-	-	-	-		7.10	6.92
			F	-	-	-	6.80	6.92	6.86	7.09	-	-	-	-	-	-	-
		PND 4	M	12.34	12.28	12.30	-	-	-	-	-	-	-	-	-	-	-		12.31	12.07
			F	-	-	-	12.18	11.96	12.05	12.09	-	-	-	-	-	-	-
		PND 7	M	15.94	16.08	16.11	-	-	-	-	-	-	-	-	-	-	-		16.04	15.84
			F	-	-	-	15.73	15.66	16.03	15.94	-	-	-	-	-	-	-
		PND 13	M	28.46	29.31	29.73	-	-	-	-	-	-	-	-	-	-	-		29.17	27.86
			F	-	-	-	28.53	27.49	28.46	26.94	-	-	-	-	-	-	-
	Rg7967	Total litter loss
	Rg7968	PND 1	M	6.88	6.50	6.73	6.95	7.10	6.47	6.80	6.64	-	-	-	-	-	-		6.76	6.40
			F	-	-	-	-	-	-	-	-	6.43	6.54	6.35	6.70	6.25	6.12
		PND 4	M	11.27	10.46	10.69	11.41	12.03	10.51	10.72	10.46	-	-	-	-	-	-		10.94	10.38
			F	-	-	-	-	-	-	-	-	10.29	10.71	10.38	10.64	10.09	10.17
		PND 7	M	14.86	15.20	14.42	14.68	14.74	15.15	14.27	14.90	-	-	-	-	-	-		14.78	14.34
			F	-	-	-	-	-	-	-	-	13.96	14.55	14.69	14.16	-	-
		PND 13	M	28.18	29.14	27.76	27.94	27.73	28.41	27.28	28.03	-	-	-	-	-	-		28.06	27.21
			F	-	-	-	-	-	-	-	-	26.44	27.67	27.33	27.40	-	-
	Rg7969	PND 1	M	6.55	6.93	6.86	6.99	-	-	-	-	-	-	-	-	-	-		6.83	6.47
			F	-	-	-	-	6.18	6.35	6.50	6.72	6.38	6.41	6.61	6.64	-	-
		PND 4	M	11.26	11.13	-	10.96	-	-	-	-	-	-	-	-	-	-		11.12	11.03
			F	-	-	-	-	11.39	11.03	10.90	11.17	10.87	10.56	-	11.31	-	-
		PND 7	M	15.56	15.79	-	14.98	-	-	-	-	-	-	-	-	-	-		15.44	14.90
			F	-	-	-	-	15.31	15.05	14.59	15.21	14.39	14.27	-	15.46	-	-
		PND 13	M	29.24	28.17	-	27.36	-	-	-	-	-	-	-	-	-	-		28.26	27.58
			F	-	-	-	-	28.42	27.61	27.42	28.41	27.36	26.59	-	27.27	-	-

M: Male; F: Female; PND: Postnatal Day; -: Not applicable.

 

 

APPENDIX 19 (Contd…). INDIVIDUAL PUP WEIGHT (g) AND MEAN PUP WEIGHT (g) PER LITTER RECORD

Group & Dose (mg/kg body weight /day)	Dam No.	Post-natal Day ↓	Pup No. →                  Sex↓	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18		Mean
																							Male	Female
G4 & 600	Rg7970	PND 1	M	6.73	6.96	6.60	7.01	-	-	-	-	-	-	-	-	-	-	-	-	-	-		6.83	6.52
			F	-	-	-	-	6.72	6.42	6.50	6.38	6.42	6.68	-	-	-	-	-	-	-	-
		PND 4	M	10.87	11.41	10.78	12.21	-	-	-	-	-	-	-	-	-	-	-	-	-	-		11.32	10.56
			F	-	-	-	-	10.81	10.57	10.36	10.27	10.58	10.77	-	-	-	-	-	-	-	-
		PND 7	M	14.31	14.96	14.40	14.17	-	-	-	-	-	-	-	-	-	-	-	-	-	-		14.46	14.48
			F	-	-	-	-	14.85	13.99	14.16	14.58	14.60	14.70	-	-	-	-	-	-	-	-
		PND 13	M	27.78	28.94	27.66	28.11	-	-	-	-	-	-	-	-	-	-	-	-	-	-		28.12	27.41
			F	-	-	-	-	27.86	26.45	27.31	27.63	27.42	27.77	-	-	-	-	-	-	-	-
	Rg7971	PND 1	M	6.72	6.91	6.58	6.71	-	-	-	-	-	-	-	-	-	-	-	-	-	-		6.73	6.32
			F	-	-	-	-	6.28	6.21	6.37	6.54	6.41	6.35	6.26	6.14	-	-	-	-	-	-
		PND 4	M	10.69	11.09	10.76	10.51	-	-	-	-	-	-	-	-	-	-	-	-	-	-		10.76	10.28
			F	-	-	-	-	10.37	10.48	10.21	10.56	10.60	10.10	10.19	9.74	-	-	-	-	-	-
		PND 7	M	14.97	15.61	14.86	14.79	-	-	-	-	-	-	-	-	-	-	-	-	-	-		15.06	14.60
			F	-	-	-	-	14.78	15.01	14.32	14.54	14.46	14.51	-	-	-	-	-	-	-	-
		PND 13	M	28.01	28.61	28.43	27.94	-	-	-	-	-	-	-	-	-	-	-	-	-	-		28.25	27.50
			F	-	-	-	-	27.27	28.24	26.98	27.23	27.54	27.73	-	-	-	-	-	-	-	-
	Rg7972	PND 1	M	4.79	3.86	3.83	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-		4.16	4.10
			F	-	-	-	4.11	4.35	4.21	3.28	3.96	4.49	4.28	4.12	-	-	-	-	-	-	-
	Rg7973	Non-pregnant
	Rg7974	PND 1	M	6.01	6.09	6.27	6.33	6.17	5.94	6.87	6.73	-	-	-	-	-	-	-	-	-	-		6.30	5.92
			F	-	-	-	-	-	-	-	-	5.47	6.21	6.07	5.88	5.91	5.66	6.04	6.11	6.01	5.86
		PND 4	M	-	10.23	10.46	10.19	10.08	10.00	11.14	10.86	-	-	-	-	-	-	-	-	-	-		10.42	9.99
			F	-	-	-	-	-	-	-	-	9.91	10.10	10.02	9.76	10.03	9.74	10.14	10.21	10.06	9.92
		PND 7	M	-	14.51	14.67	14.91	14.38	14.05	15.23	13.92	-	-	-	-	-	-	-	-	-	-		14.52	13.97
			F	-	-	-	-	-	-	-	-	14.35	13.87	14.06	13.98	13.77	14.13	13.66	13.95	-	-
		PND 13	M	-	27.23	28.01	27.96	27.78	27.49	28.17	26.38	-	-	-	-	-	-	-	-	-	-		27.57	26.87
			F	-	-	-	-	-	-	-	-	27.41	26.21	26.97	26.87	26.91	27.04	26.44	27.11	-	-

M: Male; F: Female; PND: Postnatal Day; -: Not applicable.

APPENDIX 19 (Contd…). INDIVIDUAL PUP WEIGHT (g) AND MEAN PUP WEIGHT (g) PER LITTER RECORD

Group & Dose (mg/kg body weight/day)	Dam No.	Post-natal Day ↓	Pup No. →                  Sex↓	1	2	3	4	5	6	7	8	9	10	11	12	13	14		Mean
																			Male	Female
G4 & 600	Rg7975	PND 1	M	6.81	6.09	6.93	7.11	6.97	6.68	-	-	-	-	-	-	-	-		6.77	6.19
			F	-	-	-	-	-	-	6.07	5.98	6.21	6.37	6.18	6.47	6.06	6.21
		PND 4	M	10.63	10.27	11.11	12.03	10.87	10.76	-	-	-	-	-	-	-	-		10.95	10.12
			F	-	-	-	-	-	-	9.98	10.01	10.07	10.26	10.19	10.52	9.81	10.14
		PND 7	M	14.40	14.63	14.95	14.72	15.01	14.95	-	-	-	-	-	-	-	-		14.78	14.38
			F	-	-	-	-	-	-	13.84	14.16	14.24	14.60	14.87	14.59	-	-
		PND 13	M	28.11	27.92	28.69	27.17	28.79	28.03	-	-	-	-	-	-	-	-		28.12	27.40
			F	-	-	-	-	-	-	26.98	26.94	27.27	27.63	28.10	27.46	-	-
	Rg7976	PND 1	M	6.67	6.83	6.89	7.11	-	-	-	-	-	-	-	-	-	-		6.88	6.52
			F	-	-	-	-	6.57	6.49	6.81	6.43	6.32	-	-	-	-	-
		PND 4	M	10.35	10.42	10.81	11.33	-	-	-	-	-	-	-	-	-	-		10.73	10.49
			F	-	-	-	-	10.73	10.68	10.45	9.79	10.82	-	-	-	-	-
		PND 7	M	14.79	15.01	15.28	15.46	-	-	-	-	-	-	-	-	-	-		15.14	14.56
			F	-	-	-	-	14.83	14.61	14.37	14.08	14.91	-	-	-	-	-
		PND 13	M	29.77	30.11	29.48	28.63	-	-	-	-	-	-	-	-	-	-		29.50	27.61
			F	-	-	-	-	27.94	27.41	27.28	28.06	27.38	-	-	-	-	-

M: Male; F: Female; PND: Postnatal Day; -: Not applicable.

 

 

 

 

• INDIVIDUAL PUP ANOGENITAL DISTANCE (mm) AND MEAN ANOGENITAL DISTANCE (AGD) RATIO
  PER LITTER ON POSTNATAL DAY 4 RECORD

Group & Dose (mg/kg body weight/day)	Dam No.		Pup No.→   Sex↓	1	2	3	4	5	6	7	8	9	10	11	12	13		Mean
																		Male	Female
G1 & 0	Rg7929	P.Wt. (g)	M	12.04	11.79	12.14	11.26	11.57	11.41	-	-	-	-	-	-	-		11.70	11.04
			F	-	-	-	-	-	-	11.08	11.21	10.98	10.87	-	-	-
		AGD Measurement (mm)	M	5.61	5.29	5.58	5.08	5.31	5.14	-	-	-	-	-	-	-		5.34	2.73
			F	-	-	-	-	-	-	2.79	2.63	2.81	2.67	-	-	-
		Cube Root of P.Wt.	M	2.29	2.28	2.30	2.24	2.26	2.25	-	-	-	-	-	-	-		2.27	2.23
			F	-	-	-	-	-	-	2.23	2.24	2.22	2.22	-	-	-
		AGD Ratio	M	2.45	2.32	2.43	2.27	2.35	2.28	-	-	-	-	-	-	-		2.35	1.22
			F	-	-	-	-	-	-	1.25	1.18	1.26	1.21	-	-	-
	Rg7930	P.Wt. (g)	M	12.47	12.04	11.85	-	-	-	-	-	-	-	-	-	-		12.12	11.55
			F	-	-	-	11.43	11.62	11.71	11.53	11.48	-	-	-	-	-
		AGD Measurement (mm)	M	5.49	5.26	5.41	-	-	-	-	-	-	-	-	-	-		5.39	2.86
			F	-	-	-	2.79	2.92	2.93	2.88	2.77	-	-	-	-	-
		Cube Root of P.Wt.	M	2.32	2.29	2.28	-	-	-	-	-	-	-	-	-	-		2.30	2.26
			F	-	-	-	2.25	2.27	2.27	2.26	2.26	-	-	-	-	-
		AGD Ratio	M	2.37	2.29	2.37	-	-	-	-	-	-	-	-	-	-		2.35	1.26
			F	-	-	-	1.24	1.29	1.29	1.27	1.23	-	-	-	-	-
	Rg7931	P.Wt. (g)	M	12.01	11.41	10.72	10.61	10.81	10.94	11.27	-	-	-	-	-	-		11.11	10.64
			F	-	-	-	-	-	-	-	11.49	10.67	10.48	10.51	10.37	10.31
		AGD Measurement (mm)	M	5.33	5.17	4.96	4.83	5.07	5.11	5.42	-	-	-	-	-	-		5.13	2.59
			F	-	-	-	-	-	-	-	2.86	2.69	2.48	2.71	2.42	2.38
		Cube Root of P.Wt.	M	2.29	2.25	2.20	2.20	2.21	2.22	2.24	-	-	-	-	-	-		2.23	2.20
			F	-	-	-	-	-	-	-	2.26	2.20	2.19	2.19	2.18	2.18
		AGD Ratio	M	2.33	2.30	2.25	2.20	2.29	2.30	2.42	-	-	-	-	-	-		2.30	1.18
			F	-	-	-	-	-	-	-	1.27	1.22	1.13	1.24	1.11	1.09

M: Male; F: Female; mm: Millimetre; P.Wt.: Pup weight; -: Not applicable.

 

 

 

 

APPENDIX 20 (Contd…). INDIVIDUAL PUP ANOGENITAL DISTANCE (mm) AND MEAN ANOGENITAL DISTANCE (AGD) RATIO PER LITTER ON POSTNATAL DAY 4 RECORD

Group & Dose (mg/kg body weight/day)	Dam No.		Pup No.→   Sex↓	1	2	3	4	5	6	7	8	9	10	11		Mean
																Male	Female
G1 & 0	Rg7932	P.Wt. (g)	M	11.91	12.41	12.01	-	-	-	-	-	-	-	-		12.11	10.87
			F	-	-	-	-	10.94	10.57	11.11	-	-	-	-
		AGD Measurement (mm)	M	5.46	5.67	5.31	-	-	-	-	-	-	-	-		5.48	2.78
			F	-	-	-	-	2.86	2.58	2.91	-	-	-	-
		Cube Root of P.Wt.	M	2.28	2.32	2.29	-	-	-	-	-	-	-	-		2.30	2.22
			F	-	-	-	-	2.22	2.19	2.23	-	-	-	-
		AGD Ratio	M	2.39	2.45	2.32	-	-	-	-	-	-	-	-		2.39	1.26
			F	-	-	-	-	1.29	1.18	1.30	-	-	-	-
	Rg7933	P.Wt. (g)	M	11.42	12.16	11.39	10.47	12.08	10.84	10.77	10.61	11.47	-	-		11.25	10.57
			F	-	-	-	-	-	-	-	-	-	10.72	10.41
		AGD Measurement (mm)	M	5.24	5.61	5.39	4.74	5.48	5.03	4.87	4.72	5.27	-	-		5.15	2.67
			F	-	-	-	-	-	-	-	-	-	2.82	2.51
		Cube Root of P.Wt.	M	2.25	2.30	2.25	2.19	2.29	2.21	2.21	2.20	2.26	-	-		2.24	2.19
			F	-	-	-	-	-	-	-	-	-	2.20	2.18
		AGD Ratio	M	2.33	2.44	2.40	2.17	2.39	2.27	2.21	2.15	2.34	-	-		2.30	1.21
			F	-	-	-	-	-	-	-	-	-	1.28	1.15
	Rg7934	P.Wt. (g)	M	10.72	11.41	10.91	12.16	-	-	-	-	-	-	-		11.30	10.50
			F	-	-	-	-	10.61	10.54	10.49	10.41	10.44	-	-
		AGD Measurement (mm)	M	4.84	5.14	5.01	5.47	-	-	-	-	-	-	-		5.12	2.62
			F	-	-	-	-	2.61	2.53	2.72	2.66	2.57	-	-
		Cube Root of P.Wt.	M	2.20	2.25	2.22	2.30	-	-	-	-	-	-	-		2.24	2.19
			F	-	-	-	-	2.20	2.19	2.19	2.18	2.19	-	-
		AGD Ratio	M	2.20	2.28	2.26	2.38	-	-	-	-	-	-	-		2.28	1.20
			F	-	-	-	-	1.19	1.15	1.24	1.22	1.18	-	-

M: Male; F: Female; mm: Millimetre; P.Wt.: Pup weight; -: Not applicable.

 

 

 

 

APPENDIX 20 (Contd…). INDIVIDUAL PUP ANOGENITAL DISTANCE (mm) AND MEAN ANOGENITAL DISTANCE (AGD) RATIO PER LITTER ON POSTNATAL DAY 4 RECORD

Group & Dose (mg/kg body weight/day)	Dam No.		Pup No.→   Sex↓	1	2	3	4	5	6	7	8	9	10	11	12	13		Mean
																		Male	Female
G1 & 0	Rg7935	P.Wt. (g)	M	10.23	10.47	10.36	12.03	11.98	10.67	10.41	-	-	-	-	-	-		10.88	10.41
			F	-	-	-	-	-	-	-	10.33	10.51	10.63	10.08	10.11	10.79
		AGD Measurement (mm)	M	4.86	5.21	5.11	4.93	4.77	4.88	4.92	-	-	-	-	-	-		4.95	2.61
			F	-	-	-	-	-	-	-	2.90	2.49	2.66	2.87	2.33	2.42
		Cube Root of P.Wt.	M	2.17	2.19	2.18	2.29	2.29	2.20	2.18	-	-	-	-	-	-		2.21	2.18
			F	-	-	-	-	-	-	-	2.18	2.19	2.20	2.16	2.16	2.21
		AGD Ratio	M	2.24	2.38	2.34	2.15	2.08	2.22	2.25	-	-	-	-	-	-		2.24	1.20
			F	-	-	-	-	-	-	-	1.33	1.14	1.21	1.33	1.08	1.10
	Rg7936	P.Wt. (g)	M	11.11	12.06	11.47	10.72	10.94	10.58	-	-	-	-	-	-	-		11.15	10.36
			F	-	-	-	-	-	-	10.31	10.33	10.45	10.62	10.27	10.19	-
		AGD Measurement (mm)	M	5.08	5.37	5.14	4.96	4.99	5.01	-	-	-	-	-	-	-		5.09	2.50
			F	-	-	-	-	-	-	2.41	2.38	2.66	2.72	2.47	2.34	-
		Cube Root of P.Wt.	M	2.23	2.29	2.26	2.20	2.22	2.20	-	-	-	-	-	-	-		2.23	2.18
			F	-	-	-	-	-	-	2.18	2.18	2.19	2.20	2.17	2.17	-
		AGD Ratio	M	2.28	2.34	2.28	2.25	2.25	2.28	-	-	-	-	-	-	-		2.28	1.14
			F	-	-	-	-	-	-	1.11	1.09	1.22	1.24	1.14	1.08	-
	Rg7937	P.Wt. (g)	M	11.27	12.21	-	-	-	-	-	-	-	-	-	-	-		11.74	10.94
			F	-	-	10.94	11.01	10.87	-	-	-	-	-	-	-	-
		AGD Measurement (mm)	M	5.27	5.66	-	-	-	-	-	-	-	-	-	-	-		5.47	2.91
			F	-	-	2.91	2.97	2.86	-	-	-	-	-	-	-	-
		Cube Root of P.Wt.	M	2.24	2.30	-	-	-	-	-	-	-	-	-	-	-		2.27	2.22
			F	-	-	2.22	2.22	2.22	-	-	-	-	-	-	-	-
		AGD Ratio	M	2.35	2.46	-	-	-	-	-	-	-	-	-	-	-		2.40	1.31
			F	-	-	1.31	1.34	1.29	-	-	-	-	-	-	-	-

M: Male; F: Female; mm: Millimetre; P.Wt.: Pup weight; -: Not applicable.

 

 

 

 

APPENDIX 20 (Contd…). INDIVIDUAL PUP ANOGENITAL DISTANCE (mm) AND MEAN ANOGENITAL DISTANCE (AGD) RATIO PER LITTER ON POSTNATAL DAY 4 RECORD

Group & Dose (mg/kg body weight/ day)	Dam No.		Pup No.→   Sex↓	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17		Mean
																						Male	Female
G1 & 0	Rg7938	P.Wt. (g)	M	10.14	10.53	10.02	10.29	10.37	10.41	10.89	10.63	10.44	10.93	-	-	-	-	-	-	-		10.47	9.97
			F	-	-	-	-	-	-	-	-	-	-	9.91	10.17	10.03	9.97	9.86	10.03	9.84
		AGD Measurement (mm)	M	4.69	4.83	4.61	4.72	4.73	4.92	5.01	4.78	4.66	5.11	-	-	-	-	-	-	-		4.81	2.42
			F	-	-	-	-	-	-	-	-	-	-	2.37	2.43	2.31	2.52	2.47	2.38	2.43
		Cube Root of P.Wt.	M	2.16	2.19	2.16	2.18	2.18	2.18	2.22	2.20	2.19	2.22	-	-	-	-	-	-	-		2.19	2.15
			F	-	-	-	-	-	-	-	-	-	-	2.15	2.17	2.16	2.15	2.14	2.16	2.14
		AGD Ratio	M	2.17	2.20	2.14	2.17	2.17	2.25	2.26	2.17	2.13	2.30	-	-	-	-	-	-	-		2.20	1.12
			F	-	-	-	-	-	-	-	-	-	-	1.10	1.12	1.07	1.17	1.15	1.10	1.13
	Rg7939	P.Wt. (g)	M	10.91	12.16	11.41	11.09	12.01	12.11	12.07	11.26	-	-	-	-	-	-	-	-	-		11.63	10.54
			F	-	-	-	-	-	-	-	-	10.72	10.51	10.79	10.38	10.29	-	-	-	-
		AGD Measurement (mm)	M	5.01	5.53	5.21	5.19	5.46	5.63	5.28	5.14	-	-	-	-	-	-	-	-	-		5.31	2.63
			F	-	-	-	-	-	-	-	-	2.79	2.61	2.84	2.48	2.41	-	-	-	-
		Cube Root of P.Wt.	M	2.22	2.30	2.25	2.23	2.29	2.30	2.29	2.24	-	-	-	-	-	-	-	-	-		2.27	2.19
			F	-	-	-	-	-	-	-	-	2.20	2.19	2.21	2.18	2.18	-	-	-	-
		AGD Ratio	M	2.26	2.40	2.31	2.33	2.38	2.45	2.30	2.29	-	-	-	-	-	-	-	-	-		2.34	1.20
			F	-	-	-	-	-	-	-	-	1.27	1.19	1.29	1.14	1.11	-	-	-	-
	Rg7940	P.Wt. (g)	M	12.31	11.41	11.72	11.27	-	-	-	-	-	-	-	-	-	-	-	-	-		11.68	10.81
			F	-	-	-	-	10.94	10.81	10.66	10.84	-	-	-	-	-	-	-	-	-
		AGD Measurement (mm)	M	5.41	5.07	5.26	5.18	-	-	-	-	-	-	-	-	-	-	-	-	-		5.23	2.88
			F	-	-	-	-	2.94	2.88	2.73	2.96	-	-	-	-	-	-	-	-	-
		Cube Root of P.Wt.	M	2.31	2.25	2.27	2.24	-	-	-	-	-	-	-	-	-	-	-	-	-		2.27	2.21
			F	-	-	-	-	2.22	2.21	2.20	2.21	-	-	-	-	-	-	-	-	-
		AGD Ratio	M	2.34	2.25	2.32	2.31	-	-	-	-	-	-	-	-	-	-	-	-	-		2.31	1.30
			F	-	-	-	-	1.32	1.30	1.24	1.34	-	-	-	-	-	-	-	-	-

M: Male; F: Female; mm: Millimetre; P.Wt.: Pup weight; -: Not applicable.

 

 

APPENDIX 20 (Contd…). INDIVIDUAL PUP ANOGENITAL DISTANCE (mm) AND MEAN ANOGENITAL DISTANCE (AGD) RATIO PER LITTER ON POSTNATAL DAY 4 RECORD

Group & Dose (mg/kg body weight/day)	Dam No.		Pup No.→   Sex↓	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16		Mean
																					Male	Female
G2 & 150	Rg7941	P.Wt. (g)	M	10.27	10.58	10.11	10.94	10.87	10.41	-	-	-	-	-	-	-	-	-	-		10.53	10.02
			F	-	-	-	-	-	-	10.01	10.21	9.97	9.86	9.72	10.11	10.31	10.00	9.94	10.04
		AGD Measurement (mm)	M	4.98	4.87	4.81	5.14	5.01	4.93	-	-	-	-	-	-	-	-	-	-		4.96	2.44
			F	-	-	-	-	-	-	2.39	2.61	2.33	2.37	2.48	2.51	2.46	2.36	2.40	2.44
		Cube Root of P.Wt.	M	2.17	2.20	2.16	2.22	2.22	2.18	-	-	-	-	-	-	-	-	-	-		2.19	2.16
			F	-	-	-	-	-	-	2.16	2.17	2.15	2.14	2.13	2.16	2.18	2.15	2.15	2.16
		AGD Ratio	M	2.29	2.22	2.22	2.32	2.26	2.26	-	-	-	-	-	-	-	-	-	-		2.26	1.13
			F	-	-	-	-	-	-	1.11	1.20	1.08	1.11	1.16	1.16	1.13	1.10	1.12	1.13
	Rg7942	P.Wt. (g)	M	11.14	12.26	11.07	11.44	-	-	-	-	-	-	-	-	-	-	-	-		11.48	10.77
			F	-	-	-	-	10.91	10.97	10.46	10.73	-	-	-	-	-	-	-	-
		AGD Measurement (mm)	M	5.27	5.56	5.19	5.21	-	-	-	-	-	-	-	-	-	-	-	-		5.31	2.90
			F	-	-	-	-	2.91	3.02	2.86	2.81	-	-	-	-	-	-	-	-
		Cube Root of P.Wt.	M	2.23	2.31	2.23	2.25	-	-	-	-	-	-	-	-	-	-	-	-		2.26	2.21
			F	-	-	-	-	2.22	2.22	2.19	2.21	-	-	-	-	-	-	-	-
		AGD Ratio	M	2.36	2.41	2.33	2.31	-	-	-	-	-	-	-	-	-	-	-	-		2.35	1.31
			F	-	-	-	-	1.31	1.36	1.31	1.27	-	-	-	-	-	-	-	-
	Rg7943	P.Wt. (g)	M	10.94	10.72	10.49	11.01	10.83	10.69	-	-	-	-	-	-	-	-	-	-		10.78	10.44
			F	-	-	-	-	-	-	10.41	10.29	10.63	-	-	-	-	-	-	-
		AGD Measurement (mm)	M	5.11	4.96	4.81	5.27	5.03	4.86	-	-	-	-	-	-	-	-	-	-		5.01	2.64
			F	-	-	-	-	-	-	2.72	2.36	2.83	-	-	-	-	-	-	-
		Cube Root of P.Wt.	M	2.22	2.20	2.19	2.22	2.21	2.20	-	-	-	-	-	-	-	-	-	-		2.21	2.19
			F	-	-	-	-	-	-	2.18	2.18	2.20	-	-	-	-	-	-	-
		AGD Ratio	M	2.30	2.25	2.20	2.37	2.27	2.21	-	-	-	-	-	-	-	-	-	-		2.27	1.21
			F	-	-	-	-	-	-	1.25	1.09	1.29	-	-	-	-	-	-	-

M: Male; F: Female; mm: Millimetre; P.Wt.: Pup weight; -: Not applicable.

 

 

APPENDIX 20 (Contd…). INDIVIDUAL PUP ANOGENITAL DISTANCE (mm) AND MEAN ANOGENITAL DISTANCE (AGD) RATIO PER LITTER ON POSTNATAL DAY 4 RECORD

Group & Dose (mg/kg body weight/day)	Dam No.		Pup No.→   Sex↓	1	2	3	4	5	6	7	8	9	10		Mean
															Male	Female
G2 & 150	Rg7944	P.Wt. (g)	M	11.20	10.89	11.04	-	-	-	-	-	-	-		11.04	10.54
			F	-	-	-	10.14	10.57	10.26	10.93	10.49	10.72	10.66
		AGD Measurement (mm)	M	5.13	4.96	5.08	-	-	-	-	-	-	-		5.06	2.73
			F	-	-	-	2.64	2.75	2.62	2.96	2.59	2.82	2.76
		Cube Root of P.Wt.	M	2.24	2.22	2.23	-	-	-	-	-	-	-		2.23	2.19
			F	-	-	-	2.16	2.19	2.17	2.22	2.19	2.20	2.20
		AGD Ratio	M	2.29	2.24	2.28	-	-	-	-	-	-	-		2.27	1.25
			F	-	-	-	1.22	1.25	1.21	1.33	1.18	1.28	1.25
	Rg7945	P.Wt. (g)	M	11.16	12.11	10.99	11.16	10.84	-	-	-	-	-		11.25	10.54
			F	-	-	-	-	-	10.47	10.76	10.38	-	-
		AGD Measurement (mm)	M	5.21	5.48	5.03	5.16	5.04	-	-	-	-	-		5.18	2.70
			F	-	-	-	-	-	2.74	2.86	2.49	-	-
		Cube Root of P.Wt.	M	2.23	2.30	2.22	2.23	2.21	-	-	-	-	-		2.24	2.19
			F	-	-	-	-	-	2.19	2.21	2.18	-	-
		AGD Ratio	M	2.33	2.39	2.26	2.31	2.28	-	-	-	-	-		2.31	1.23
			F	-	-	-	-	-	1.25	1.30	1.14	-	-
	Rg7946	P.Wt. (g)	M	12.19	11.87	10.94	-	-	-	-	-	-	-		11.67	10.92
			F	-	-	-	10.99	11.01	10.76	-	-	-	-
		AGD Measurement (mm)	M	5.57	5.31	5.08	-	-	-	-	-	-	-		5.32	2.95
			F	-	-	-	2.93	3.06	2.87	-	-	-	-
		Cube Root of P.Wt.	M	2.30	2.28	2.22	-	-	-	-	-	-	-		2.27	2.22
			F	-	-	-	2.22	2.22	2.21	-	-	-	-
		AGD Ratio	M	2.42	2.33	2.29	-	-	-	-	-	-	-		2.35	1.33
			F	-	-	-	1.32	1.38	1.30	-	-	-	-

M: Male; F: Female; mm: Millimetre; P.Wt.: Pup weight; -: Not applicable.

 

 

APPENDIX 20 (Contd…). INDIVIDUAL PUP ANOGENITAL DISTANCE (mm) AND MEAN ANOGENITAL DISTANCE (AGD) RATIO PER LITTER ON POSTNATAL DAY 4 RECORD

Group & Dose (mg/kg body weight/day)	Dam No.		Pup No.→   Sex↓	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16		Mean
																					Male	Female
G2 & 150	Rg7947	P.Wt. (g)	M	10.57	10.63	12.27	11.88	10.91	10.83	-	-	-	-	-	-	-	-	-	-		11.18	10.38
			F	-	-	-	-	-	-	10.34	10.61	10.14	10.43	-	-	-	-	-	-
		AGD Measurement (mm)	M	4.75	4.92	5.58	5.28	5.11	4.96	-	-	-	-	-	-	-	-	-	-		5.10	2.51
			F	-	-	-	-	-	-	2.43	2.71	2.38	2.53	-	-	-	-	-	-
		Cube Root of P.Wt.	M	2.19	2.20	2.31	2.28	2.22	2.21	-	-	-	-	-	-	-	-	-	-		2.24	2.18
			F	-	-	-	-	-	-	2.18	2.20	2.16	2.18	-	-	-	-	-	-
		AGD Ratio	M	2.16	2.24	2.42	2.31	2.30	2.24	-	-	-	-	-	-	-	-	-	-		2.28	1.15
			F	-	-	-	-	-	-	1.12	1.23	1.10	1.16	-	-	-	-	-	-
	Rg7948	P.Wt. (g)	M	10.51	10.79	10.41	10.38	11.01	10.86	10.58	10.39	-	-	-	-	-	-	-	-		10.62	10.06
			F	-	-	-	-	-	-	-	-	10.08	9.97	10.19	9.88	10.29	10.00	9.97	10.06
		AGD Measurement (mm)	M	4.79	4.93	4.68	4.72	5.33	5.26	4.97	4.79	-	-	-	-	-	-	-	-		4.93	2.43
			F	-	-	-	-	-	-	-	-	2.38	2.41	2.34	2.66	2.47	2.31	2.44	2.41
		Cube Root of P.Wt.	M	2.19	2.21	2.18	2.18	2.22	2.21	2.20	2.18	-	-	-	-	-	-	-	-		2.20	2.16
			F	-	-	-	-	-	-	-	-	2.16	2.15	2.17	2.15	2.18	2.15	2.15	2.16
		AGD Ratio	M	2.19	2.23	2.14	2.16	2.40	2.38	2.26	2.20	-	-	-	-	-	-	-	-		2.24	1.12
			F	-	-	-	-	-	-	-	-	1.10	1.12	1.08	1.24	1.14	1.07	1.13	1.12
	Rg7949	Non-pregnant
	Rg7950	P.Wt. (g)	M	11.27	11.72	12.11	12.34	-	-	-	-	-	-	-	-	-	-	-	-		11.86
		AGD Measurement (mm)	M	5.21	5.11	5.43	5.57	-	-	-	-	-	-	-	-	-	-	-	-		5.33
		Cube Root of P.Wt.	M	2.24	2.27	2.30	2.31	-	-	-	-	-	-	-	-	-	-	-	-		2.28
		AGD Ratio	M	2.32	2.25	2.36	2.41	-	-	-	-	-	-	-	-	-	-	-	-		2.34

M: Male; F: Female; mm: Millimetre; P.Wt.: Pup weight; -: Not applicable.

 

 

 

APPENDIX 20 (Contd…). INDIVIDUAL PUP ANOGENITAL DISTANCE (mm) AND MEAN ANOGENITAL DISTANCE (AGD) RATIO PER LITTER ON POSTNATAL DAY 4 RECORD

Group & Dose (mg/kg body weight/day)	Dam No.		Pup No.→   Sex↓	1	2	3	4	5	6	7	8	9	10	11	12		Mean
																	Male	Female
G2 & 150	Rg7951	P.Wt. (g)	M	12.23	12.01	11.83	-	-	-	-	-	-	-	-	-		12.02	11.69
			F	-	-	-	11.79	11.58	11.69	-	-	-	-	-	-
		AGD Measurement (mm)	M	5.47	5.33	5.18	-	-	-	-	-	-	-	-	-		5.33	2.90
			F	-	-	-	2.93	2.87	2.91	-	-	-	-	-	-
		Cube Root of P.Wt.	M	2.30	2.29	2.28	-	-	-	-	-	-	-	-	-		2.29	2.27
			F	-	-	-	2.28	2.26	2.27	-	-	-	-	-	-
		AGD Ratio	M	2.37	2.33	2.27	-	-	-	-	-	-	-	-	-		2.32	1.28
			F	-	-	-	1.29	1.27	1.28	-	-	-	-	-	-
	Rg7952	P.Wt. (g)	M	11.33	11.14	12.08	10.84	10.75	11.96	-	-	-	-	-	-		11.35	10.45
			F	-	-	-	-	-	-	10.67	10.53	10.32	10.76	10.15	10.28
		AGD Measurement (mm)	M	4.98	5.06	5.49	4.93	4.88	5.26	-	-	-	-	-	-		5.10	2.57
			F	-	-	-	-	-	-	2.69	2.63	2.42	2.81	2.38	2.47
		Cube Root of P.Wt.	M	2.25	2.23	2.29	2.21	2.21	2.29	-	-	-	-	-	-		2.25	2.19
			F	-	-	-	-	-	-	2.20	2.19	2.18	2.21	2.17	2.17
		AGD Ratio	M	2.22	2.27	2.39	2.23	2.21	2.30	-	-	-	-	-	-		2.27	1.17
			F	-	-	-	-	-	-	1.22	1.20	1.11	1.27	1.10	1.14

M: Male; F: Female; mm: Millimetre; P.Wt.: Pup weight; -: Not applicable.

 

 

 

 

APPENDIX 20 (Contd…). INDIVIDUAL PUP ANOGENITAL DISTANCE (mm) AND MEAN ANOGENITAL DISTANCE (AGD) RATIO PER LITTER ON POSTNATAL DAY 4 RECORD

Group & Dose (mg/kg body weight/day)	Dam No.		Pup No.→   Sex↓	1	2	3	4	5	6	7	8	9	10	11	12	13		Mean
																		Male	Female
G3 & 300	Rg7953	Non-pregnant
	Rg7954	P.Wt. (g)	M	11.21	11.76	12.31	10.97	-	-	-	-	-	-	-	-	-		11.56	-
		AGD Measurement (mm)	M	5.01	5.36	5.47	4.99	-	-	-	-	-	-	-	-	-		5.21	-
		Cube Root of P.Wt.	M	2.24	2.27	2.31	2.22	-	-	-	-	-	-	-	-	-		2.26	-
		AGD Ratio	M	2.24	2.36	2.37	2.25	-	-	-	-	-	-	-	-	-		2.30	-
	Rg7955	P.Wt. (g)	M	11.49	12.17	11.58	11.56	10.94	12.01	-	-	-	-	-	-	-		11.63	10.70
			F	-	-	-	-	-	-	10.59	10.43	10.66	11.13	-	-	-
		AGD Measurement (mm)	M	5.24	5.66	5.37	5.49	5.18	5.53	-	-	-	-	-	-	-		5.41	2.83
			F	-	-	-	-	-	-	2.86	2.69	2.81	2.97	-	-	-
		Cube Root of P.Wt.	M	2.26	2.30	2.26	2.26	2.22	2.29	-	-	-	-	-	-	-		2.27	2.20
			F	-	-	-	-	-	-	2.20	2.18	2.20	2.23	-	-	-
		AGD Ratio	M	2.32	2.46	2.37	2.43	2.33	2.41	-	-	-	-	-	-	-		2.39	1.29
			F	-	-	-	-	-	-	1.30	1.23	1.28	1.33	-	-	-
	Rg7956	P.Wt. (g)	M	11.41	10.93	11.16	12.01	10.44	10.68	11.94	-	-	-	-	-	-		11.22	10.49
			F	-	-	-	-	-	-	-	10.51	10.29	10.31	10.56	10.79	10.48
		AGD Measurement (mm)	M	5.14	4.98	5.26	5.51	4.76	4.83	5.11	-	-	-	-	-	-		5.08	2.58
			F	-	-	-	-	-	-	-	2.51	2.36	2.47	2.68	2.81	2.63
		Cube Root of P.Wt.	M	2.25	2.22	2.23	2.29	2.19	2.20	2.29	-	-	-	-	-	-		2.24	2.19
			F	-	-	-	-	-	-	-	2.19	2.18	2.18	2.19	2.21	2.19
		AGD Ratio	M	2.28	2.24	2.35	2.41	2.18	2.19	2.24	-	-	-	-	-	-		2.27	1.18
			F	-	-	-	-	-	-	-	1.15	1.09	1.13	1.22	1.27	1.20
	Rg7957	Non-pregnant

M: Male; F: Female; mm: Millimetre; P.Wt.: Pup weight; -: Not applicable.

 

 

APPENDIX 20 (Contd…). INDIVIDUAL PUP ANOGENITAL DISTANCE (mm) AND MEAN ANOGENITAL DISTANCE (AGD) RATIO PER LITTER ON POSTNATAL DAY 4 RECORD

Group & Dose (mg/kg body weight/day)	Dam No.		Pup No.→   Sex↓	1	2	3	4	5	6	7	8	9	10	11	12		Mean
																	Male	Female
G3 & 300	Rg7958	P.Wt. (g)	M	12.34	11.53	12.42	-	-	-	-	-	-	-	-	-		12.10	11.18
			F	-	-	-	11.18	-	-	-	-	-	-	-	-
		AGD Measurement (mm)	M	4.82	5.03	4.65	-	-	-	-	-	-	-	-	-		4.83	2.79
			F	-	-	-	2.79	-	-	-	-	-	-	-	-
		Cube Root of P.Wt.	M	2.31	2.26	2.32	-	-	-	-	-	-	-	-	-		2.30	2.24
			F	-	-	-	2.24	-	-	-	-	-	-	-	-
		AGD Ratio	M	2.09	2.23	2.01	-	-	-	-	-	-	-	-	-		2.11	1.25
			F	-	-	-	1.25	-	-	-	-	-	-	-	-
	Rg7959	P.Wt. (g)	M	11.72	11.21	12.16	11.81	-	-	-	-	-	-	-	-		11.73	10.66
			F	-	-	-	-	10.72	10.58	10.72	10.81	10.47	-	-	-
		AGD Measurement (mm)	M	5.15	5.01	5.48	5.21	-	-	-	-	-	-	-	-		5.21	2.73
			F	-	-	-	-	2.72	2.68	2.79	2.94	2.54	-	-	-
		Cube Root of P.Wt.	M	2.27	2.24	2.30	2.28	-	-	-	-	-	-	-	-		2.27	2.20
			F	-	-	-	-	2.20	2.20	2.20	2.21	2.19	-	-	-
		AGD Ratio	M	2.27	2.24	2.38	2.29	-	-	-	-	-	-	-	-		2.29	1.24
			F	-	-	-	-	1.23	1.22	1.27	1.33	1.16	-	-	-
	Rg7960	P.Wt. (g)	M	10.88	10.57	12.14	11.71	11.08	10.72	-	11.01	-	-	-	-		11.16	10.45
			F	-	-	-	-	-	-	-	-	10.49	10.61	10.41	10.29
		AGD Measurement (mm)	M	5.09	4.96	5.62	5.37	5.01	4.88	-	5.08	-	-	-	-		5.14	2.57
			F	-	-	-	-	-	-	-	-	2.59	2.71	2.52	2.46
		Cube Root of P.Wt.	M	2.22	2.19	2.30	2.27	2.23	2.20	-	2.22	-	-	-	-		2.23	2.19
			F	-	-	-	-	-	-	-	-	2.19	2.20	2.18	2.18
		AGD Ratio	M	2.30	2.26	2.45	2.36	2.25	2.21	-	2.28	-	-	-	-		2.30	1.18
			F	-	-	-	-	-	-	-	-	1.18	1.23	1.15	1.13

M: Male; F: Female; mm: Millimetre; P.Wt.: Pup weight; -: Not applicable.

 

 

 

APPENDIX 20 (Contd…). INDIVIDUAL PUP ANOGENITAL DISTANCE (mm) AND MEAN ANOGENITAL DISTANCE (AGD) RATIO PER LITTER ON POSTNATAL DAY 4 RECORD

Group & Dose (mg/kg body weight/ day)	Dam No.		Pup No.→   Sex↓	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18		Mean
																							Male	Female
G3 & 300	Rg7961	P.Wt. (g)	M	10.91	11.16	12.05	12.10	10.88	-	-	-	-	-	-	-	-	-	-	-	-	-		11.42	10.35
			F	-	-	-	-	-	10.22	10.37	10.42	10.19	10.50	10.40	-	-	-	-	-	-	-
		AGD Measurement (mm)	M	5.03	5.16	5.53	5.47	4.96	-	-	-	-	-	-	-	-	-	-	-	-	-		5.23	2.48
			F	-	-	-	-	-	2.48	2.41	2.56	2.36	2.61	2.44	-	-	-	-	-	-	-
		Cube Root of P.Wt.	M	2.22	2.23	2.29	2.30	2.22	-	-	-	-	-	-	-	-	-	-	-	-	-		2.25	2.18
			F	-	-	-	-	-	2.17	2.18	2.18	2.17	2.19	2.18	-	-	-	-	-	-	-
		AGD Ratio	M	2.27	2.31	2.41	2.38	2.24	-	-	-	-	-	-	-	-	-	-	-	-	-		2.32	1.14
			F	-	-	-	-	-	1.14	1.11	1.17	1.09	1.19	1.12	-	-	-	-	-	-	-
	Rg7962	P.Wt. (g)	M	11.29	10.47	10.93	11.47	12.11	10.58	-	-	-	-	-	-	-	-	-	-	-	-		11.14	10.56
			F	-	-	-	-	-	-	10.72	10.39	10.67	10.44	-	-	-	-	-	-	-	-
		AGD Measurement (mm)	M	5.21	4.77	5.01	5.31	5.46	4.63	-	-	-	-	-	-	-	-	-	-	-	-		5.07	2.63
			F	-	-	-	-	-	-	2.72	2.41	2.83	2.54	-	-	-	-	-	-	-	-
		Cube Root of P.Wt.	M	2.24	2.19	2.22	2.26	2.30	2.20	-	-	-	-	-	-	-	-	-	-	-	-		2.23	2.19
			F	-	-	-	-	-	-	2.20	2.18	2.20	2.19	-	-	-	-	-	-	-	-
		AGD Ratio	M	2.32	2.18	2.26	2.35	2.38	2.11	-	-	-	-	-	-	-	-	-	-	-	-		2.27	1.20
			F	-	-	-	-	-	-	1.23	1.10	1.29	1.16	-	-	-	-	-	-	-	-
	Rg7963	Total litter loss
	Rg7964	P.Wt. (g)	M	10.47	10.03	10.14	10.63	10.38	10.01	10.16	-	-	-	-	-	-	-	-	-	-	-		10.26	9.94
			F	-	-	-	-	-	-	-	9.84	10.01	10.07	9.98	10.04	10.10	-	9.47	10.00	9.89	10.01
		AGD Measurement (mm)	M	4.58	4.71	4.66	4.92	4.61	4.68	4.79	-	-	-	-	-	-	-	-	-	-	-		4.71	2.42
			F	-	-	-	-	-	-	-	2.31	2.37	2.41	2.36	2.51	2.44	-	2.38	2.49	2.41	2.48
		Cube Root of P.Wt.	M	2.19	2.16	2.16	2.20	2.18	2.16	2.17	-	-	-	-	-	-	-	-	-	-	-		2.17	2.15
			F	-	-	-	-	-	-	-	2.14	2.16	2.16	2.15	2.16	2.16	-	2.12	2.15	2.15	2.16
		AGD Ratio	M	2.09	2.18	2.15	2.24	2.11	2.17	2.21	-	-	-	-	-	-	-	-	-	-	-		2.17	1.12
			F	-	-	-	-	-	-	-	1.08	1.10	1.12	1.10	1.16	1.13	-	1.12	1.16	1.12	1.15

M: Male; F: Female; mm: Millimetre; P.Wt.: Pup weight; -: Not applicable.

 

APPENDIX 20 (Contd…). INDIVIDUAL PUP ANOGENITAL DISTANCE (mm) AND MEAN ANOGENITAL DISTANCE (AGD) RATIO PER LITTER ON POSTNATAL DAY 4 RECORD

Group & Dose (mg/kg body weight/day)	Dam No.		Pup No.→   Sex↓	1	2	3	4	5	6	7	8	9	10	11	12	13	14		Mean
																			Male	Female
G4 & 600	Rg7965	Total litter loss
	Rg7966	P.Wt. (g)	M	12.34	12.28	12.30	-	-	-	-	-	-	-	-	-	-	-		12.31	12.07
			F	-	-	-	12.18	11.96	12.05	12.09	-	-	-	-	-	-	-
		AGD Measurement (mm)	M	4.94	4.80	5.11	-	-	-	-	-	-	-	-	-	-	-		4.95	2.69
			F	-	-	-	2.45	2.73	2.91	2.66	-	-	-	-	-	-	-
		Cube Root of P.Wt.	M	2.31	2.31	2.31	-	-	-	-	-	-	-	-	-	-	-		2.31	2.29
			F	-	-	-	2.30	2.29	2.29	2.30	-	-	-	-	-	-	-
		AGD Ratio	M	2.14	2.08	2.21	-	-	-	-	-	-	-	-	-	-	-		2.14	1.17
			F	-	-	-	1.06	1.19	1.27	1.16	-	-	-	-	-	-	-
	Rg7967	Total litter loss
	Rg7968	P.Wt. (g)	M	11.27	10.46	10.69	11.41	12.03	10.51	10.72	10.46	-	-	-	-	-	-		10.94	10.38
			F	-	-	-	-	-	-	-	-	10.29	10.71	10.38	10.64	10.09	10.17
		AGD Measurement (mm)	M	5.27	4.69	4.83	5.14	5.30	4.71	4.92	4.64	-	-	-	-	-	-		4.94	2.56
			F	-	-	-	-	-	-	-	-	2.39	2.76	2.48	2.74	2.34	2.65
		Cube Root of P.Wt.	M	2.24	2.19	2.20	2.25	2.29	2.19	2.20	2.19	-	-	-	-	-	-		2.22	2.18
			F	-	-	-	-	-	-	-	-	2.18	2.20	2.18	2.20	2.16	2.17
		AGD Ratio	M	2.35	2.14	2.19	2.28	2.31	2.15	2.23	2.12	-	-	-	-	-	-		2.22	1.17
			F	-	-	-	-	-	-	-	-	1.10	1.25	1.14	1.25	1.08	1.22
	Rg7969	P.Wt. (g)	M	11.26	11.13	-	10.96	-	-	-	-	-	-	-	-	-	-		11.12	11.03
			F	-	-	-	-	11.39	11.03	10.90	11.17	10.87	10.56	-	11.31	-	-
		AGD Measurement (mm)	M	5.18	4.96	-	5.08	-	-	-	-	-	-	-	-	-	-		5.07	2.72
			F	-	-	-	-	2.60	2.79	2.93	2.62	2.76	2.81	-	2.54	-	-
		Cube Root of P.Wt.	M	2.24	2.23	-	2.22	-	-	-	-	-	-	-	-	-	-		2.23	2.23
			F	-	-	-	-	2.25	2.23	2.22	2.24	2.22	2.19	-	2.24	-	-
		AGD Ratio	M	2.31	2.22	-	2.29	-	-	-	-	-	-	-	-	-	-		2.27	1.22
			F	-	-	-	-	1.16	1.25	1.32	1.17	1.25	1.28	-	1.13	-	-

M: Male; F: Female; mm: Millimetre; P.Wt.: Pup weight; -: Not applicable.

 

APPENDIX 20 (Contd…). INDIVIDUAL PUP ANOGENITAL DISTANCE (mm) AND MEAN ANOGENITAL DISTANCE (AGD) RATIO PER LITTER ON POSTNATAL DAY 4 RECORD

Group & Dose (mg/kg body weight/ day)	Dam No.		Pup No.→   Sex↓	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18		Mean
																							Male	Female
G4 & 600	Rg7970	P.Wt. (g)	M	10.87	11.41	10.78	12.21	-	-	-	-	-	-	-	-	-	-	-	-	-	-		11.32	10.56
			F	-	-	-	-	10.81	10.57	10.36	10.27	10.58	10.77	-	-	-	-	-	-	-	-
		AGD Measurement (mm)	M	4.97	5.34	4.87	5.58	-	-	-	-	-	-	-	-	-	-	-	-	-	-		5.19	2.66
			F	-	-	-	-	2.81	2.59	2.63	2.38	2.62	2.91	-	-	-	-	-	-	-	-
		Cube Root of P.Wt.	M	2.22	2.25	2.21	2.30	-	-	-	-	-	-	-	-	-	-	-	-	-	-		2.24	2.19
			F	-	-	-	-	2.21	2.19	2.18	2.17	2.20	2.21	-	-	-	-	-	-	-	-
		AGD Ratio	M	2.24	2.37	2.20	2.42	-	-	-	-	-	-	-	-	-	-	-	-	-	-		2.31	1.21
			F	-	-	-	-	1.27	1.18	1.21	1.09	1.19	1.32	-	-	-	-	-	-	-	-
	Rg7971	P.Wt. (g)	M	10.69	11.09	10.76	10.51	-	-	-	-	-	-	-	-	-	-	-	-	-	-		10.76	10.28
			F	-	-	-	-	10.37	10.48	10.21	10.56	10.60	10.10	10.19	9.74	-	-	-	-	-	-
		AGD Measurement (mm)	M	4.88	5.11	5.01	4.91	-	-	-	-	-	-	-	-	-	-	-	-	-	-		4.98	2.48
			F	-	-	-	-	2.48	2.52	2.66	2.69	2.41	2.39	2.34	2.31	-	-	-	-	-	-
		Cube Root of P.Wt.	M	2.20	2.23	2.21	2.19	-	-	-	-	-	-	-	-	-	-	-	-	-	-		2.21	2.17
			F	-	-	-	-	2.18	2.19	2.17	2.19	2.20	2.16	2.17	2.14	-	-	-	-	-	-
		AGD Ratio	M	2.22	2.29	2.27	2.24	-	-	-	-	-	-	-	-	-	-	-	-	-	-		2.25	1.14
			F	-	-	-	-	1.14	1.15	1.23	1.23	1.10	1.11	1.08	1.08	-	-	-	-	-	-
	Rg7972	Total litter loss
	Rg7973	Non-pregnant
	Rg7974	P.Wt. (g)	M	-	10.23	10.46	10.19	10.08	10.00	11.14	10.86	-	-	-	-	-	-	-	-	-	-		10.42	9.99
			F	-	-	-	-	-	-	-	-	9.91	10.10	10.02	9.76	10.03	9.74	10.14	10.21	10.06	9.92
		AGD Measurement (mm)	M	-	4.68	4.90	4.63	4.71	4.77	5.16	5.03	-	-	-	-	-	-	-	-	-	-		4.84	2.44
			F	-	-	-	-	-	-	-	-	2.36	2.46	2.51	2.33	2.29	2.45	2.66	2.47	2.53	2.36
		Cube Root of P.Wt.	M	-	2.17	2.19	2.17	2.16	2.15	2.23	2.21	-	-	-	-	-	-	-	-	-	-		2.18	2.15
			F	-	-	-	-	-	-	-	-	2.15	2.16	2.16	2.14	2.16	2.14	2.16	2.17	2.16	2.15
		AGD Ratio	M	-	2.16	2.24	2.14	2.18	2.21	2.31	2.27	-	-	-	-	-	-	-	-	-	-		2.22	1.13
			F	-	-	-	-	-	-	-	-	1.10	1.14	1.16	1.09	1.06	1.15	1.23	1.14	1.17	1.10

M: Male; F: Female; mm: Millimetre; P.Wt.: Pup weight; -: Not applicable.

APPENDIX 20 (Contd…). INDIVIDUAL PUP ANOGENITAL DISTANCE (mm) AND MEAN ANOGENITAL DISTANCE (AGD) RATIO PER LITTER ON POSTNATAL DAY 4 RECORD

Group & Dose (mg/kg body weight/day)	Dam No.		Pup No.→   Sex↓	1	2	3	4	5	6	7	8	9	10	11	12	13	14		Mean
																			Male	Female
G4 & 600	Rg7975	P.Wt. (g)	M	10.63	10.27	11.11	12.03	10.87	10.76	-	-	-	-	-	-	-	-		10.95	10.12
			F	-	-	-	-	-	-	9.98	10.01	10.07	10.26	10.19	10.52	9.81	10.14
		AGD Measurement (mm)	M	4.78	4.63	5.11	5.43	5.01	4.96	-	-	-	-	-	-	-	-		4.99	2.46
			F	-	-	-	-	-	-	2.33	2.38	2.52	2.47	2.64	2.41	2.53	2.41
		Cube Root of P.Wt.	M	2.20	2.17	2.23	2.29	2.22	2.21	-	-	-	-	-	-	-	-		2.22	2.16
			F	-	-	-	-	-	-	2.15	2.16	2.16	2.17	2.17	2.19	2.14	2.16
		AGD Ratio	M	2.17	2.13	2.29	2.37	2.26	2.25	-	-	-	-	-	-	-	-		2.25	1.14
			F	-	-	-	-	-	-	1.08	1.10	1.17	1.14	1.22	1.10	1.18	1.11
	Rg7976	P.Wt. (g)	M	10.35	10.42	10.81	11.33	-	-	-	-	-	-	-	-	-	-		10.73	10.49
			F	-	-	-	-	10.73	10.68	10.45	9.79	10.82	-	-	-	-	-
		AGD Measurement (mm)	M	5.05	4.73	4.89	5.10	-	-	-	-	-	-	-	-	-	-		4.94	2.42
			F	-	-	-	-	2.42	2.38	2.51	2.35	2.46	-	-	-	-	-
		Cube Root of P.Wt.	M	2.18	2.18	2.21	2.25	-	-	-	-	-	-	-	-	-	-		2.21	2.19
			F	-	-	-	-	2.21	2.20	2.19	2.14	2.21	-	-	-	-	-
		AGD Ratio	M	2.32	2.17	2.21	2.27	-	-	-	-	-	-	-	-	-	-		2.24	1.11
			F	-	-	-	-	1.10	1.08	1.15	1.10	1.11	-	-	-	-	-

M: Male; F: Female; mm: Millimetre; P.Wt.: Pup weight; -: Not applicable.

 

 

 

 

• OBSERVATION RECORD OF INDIVIDUAL MALE PUP/S FOR RETENTION OF NIPPLE/AREOLAE (No.) PER LITTER ON
  POSTNATAL DAY 13

Group & Dose (mg/kg body weight/day)	Dam No.	No. of male pups observed for retention of nipple	No. of male pups observed with retention of nipple
G1 & 0	Rg7929	6	0
	Rg7930	3	0
	Rg7931	7	0
	Rg7932	3	0
	Rg7933	9	0
	Rg7934	4	0
	Rg7935	7	0
	Rg7936	6	0
	Rg7937	2	0
	Rg7938	10	0
	Rg7939	7	0
	Rg7940	4	0
G2 & 150	Rg7941	6	0
	Rg7942	4	0
	Rg7943	6	0
	Rg7944	3	0
	Rg7945	5	0
	Rg7946	3	0
	Rg7947	6	0
	Rg7948	8	0
	Rg7949	Non-pregnant
	Rg7950	4	0
	Rg7951	3	0
	Rg7952	6	0
G3 & 300	Rg7953	Non-pregnant
	Rg7954	4	0
	Rg7955	6	0
	Rg7956	7	0
	Rg7957	Non-pregnant
	Rg7958	3	0
	Rg7959	4	0
	Rg7960	7	0
	Rg7961	5	0
	Rg7962	6	0
	Rg7963	Total litter loss
	Rg7964	7	0
G4 & 600	Rg7965	Total litter loss
	Rg7966	3	0
	Rg7967	Total litter loss
	Rg7968	8	0
	Rg7969	3	0
	Rg7970	4	0
	Rg7971	4	0
	Rg7972	Total litter loss
	Rg7973	Non-pregnant
	Rg7974	7	0
	Rg7975	6	0
	Rg7976	4	0

PND: Postnatal day.

 

 

• INDIVIDUAL PUP SERUM T4 LEVELS (ng/mL) RECORD - POSTNATAL DAY (PND) 13 PUPS

Group & Dose (mg/kg body weight/day)	PND 13 Pups of Dam No.	Serum T4 Levels (ng/mL)
G1 & 0	Rg7929	72.036
	Rg7930	73.297
	Rg7931	76.932
	Rg7932	67.019
	Rg7933	68.273
	Rg7934	78.125
	Rg7935	56.910
	Rg7936	61.920
	Rg7937	74.127
	Rg7938	78.793
	Rg7939	64.721
	Rg7940	69.237
G2 & 150	Rg7941	71.908
	Rg7942	70.305
	Rg7943	73.968
	Rg7944	69.914
	Rg7945	68.930
	Rg7946	63.802
	Rg7947	65.542
	Rg7948	74.004
	Rg7949	Non-pregnant
	Rg7950	69.219
	Rg7951	83.023
	Rg7952	63.045
G3 & 300	Rg7953	Non-pregnant
	Rg7954	69.133
	Rg7955	72.622
	Rg7956	76.274
	Rg7957	Non-pregnant
	Rg7958	73.188
	Rg7959	68.655
	Rg7960	65.898
	Rg7961	62.987
	Rg7962	66.473
	Rg7963	Total litter loss
	Rg7964	62.050
G4 & 600	Rg7965	Total litter loss
	Rg7966	83.026
	Rg7967	Total litter loss
	Rg7968	78.716
	Rg7969	59.340
	Rg7970	63.219
	Rg7971	64.132
	Rg7972	Total litter loss
	Rg7973	Non-pregnant
	Rg7974	65.965
	Rg7975	56.200
	Rg7976	72.101

ng/mL: nano gram per mL.

 

Pathology report

TABLE 1.            SUMMARY OF GROSS PATHOLOGY FINDINGS

Reference Appendices 1 and 2

Sex	Male				Female
Route of administration	Oral Gavage
Treatment	Vehicle Control	Low dose	Mid dose	High dose	Vehicle Control	Low dose	Mid dose	High dose
Group	G1	G2	G3	G4	G1	G2	G3	G4
Dose (mg/kg body weight/day)	0	150	300	600	0	150	300	600
Number of animals	12	12	12	12	12	12	12	12
No. of dead rats during treatment	-	-	-	-	-	-	-	1
No. of moribund sacrificed rats	-	-	-	-	-	-	-	-
No. of terminally sacrificed rats	12	12	12	12	12	12	12	11
No of rats showing gross pathology	-	-	-	12	-	-	-	8
Stomach (non-glandular)- Thickened, mucosa	-	-	-	12	-	-	-	7
Uterus-implantation, present	-	-	-	-	-	-	-	1
Autolyzed	-	-	-	-	-	-	-	1

G: Group; -: Not applicable.

 

 

 

 

TABLE 2.            SUMMARY OF GROSS PATHOLOGY FINDINGS RECORD OF PUPS

Reference Appendices3, 4 and 5

Group		G1		G2		G3		G4
Dose (mg/kg body weight/day)		0		150		300		600
Sex		Male	Female	Male	Female	Male	Female	Male	Female
No. of Dead Pups at Birth		-	-	2	-	6	3	6	8
External Gross Pathology Findings	NAD	-	-	2	-	6	3	6	8
Internal Gross Pathology Findings	NAD	-	-	2	-	6	3	6	8
No. of cannabalised pups on PND 2		1	-	-	-	-	-	-	-
External Gross Pathology Findings	Preclude evaluation	1	-	-	-	-	-	-	-
Internal Gross Pathology Findings	Not applicable	1	-	-	-	-	-	-	-
No. of dead pups on PND 2		-	-	-	-	1	-	-	-
External Gross Pathology Findings	Skin -forehead discoloration, red	-	-	-	-	1	-	-	-
	NAD	-	-	-	-	-	-	5	9
Internal Gross Pathology Findings	NAD	-	-	-	-	1	-	5	9
No. of dead pups on PND 3		-	-	-	-	-	1	-	-
External Gross Pathology Findings	NAD	-	-	-	-	-	1	-	-
Internal Gross Pathology Findings	NAD	-	-	-	-	-	1	-	-
No. of dead pups on PND 4		-	1	-	-	-	-	1	-
External Gross Pathology Findings	NAD	-	-	-	-	-	-	-	-
Internal Gross Pathology Findings	NAD	-	-	-	-	-	-	-	-
No. of pups sacrificed on PND 4		-	11	-	6	-	6	-	8
External Gross Pathology Findings	NAD	-	11	-	6	-	6	-	8
Internal Gross Pathology Findings	NAD	-	11	-	6	-	6	-	8
No. of pups sacrificed on lactation PND 13		69	45	54	45	49	34	39	46
External Gross Pathology Findings	NAD	69	45	54	45	49	34	39	46
Internal Gross Pathology Findings	NAD	69	45	54	45	49	34	39	46

NAD: No Abnormality Detected; PND: Post-natal Day; -: Not Applicable.

 

TABLE 3.            SUMMARY OF HISTOPATHOLOGY FINDINGS

Reference Appendices 6 and 7

Route of administration		Oral Gavage
Sex		Male		Female
Vehicle /Test item		Vehicle Control	High dose	Vehicle Control	High dose
Dose (mg/kg body weight/day)		0	600	0	600
Group		G1	G4	G1	G4
Number of Animals		12	12	12	12
Epididymides	Number examined	12	12	X	X
	Within normal limits	12	12	X	X
Testes	Number examined	12	12	X	X
	Within normal limits	12	12	X	X
Stomach	Number examined	12	12	12	12
	Within normal limits	12	-	12	1
Autolysis precluded evaluation		-	-	-	1
Hyperplasia, squamous cell, non-glandular	Mild	-	-	-	3
	Moderate	-	2	-	-
	Marked	-	10	-	7
Hyperkeratosis, non-glandular	Minimal	-	2	-	1
	Mild	-	10	-	6
Ovaries	Number examined	X	X	12	12
	Within normal limits	X	X	12	11
	Partially autolyzed	X	X	X	1
Vagina	Number examined	X	X	12	12
	Within normal limits	X	X	12	12
Stages of estrus cycle	Proestrus	X	X	7	3
	Estrus	X	X	-	1
	Metestrus	X	X	1	-
	Diestrus	X	X	4	8

X: Not applicable; -:

 

 

 

 

TABLE 4.            SUMMARY OF HISTOPATHOLOGY FINDINGS OF TARGET ORGAN

Reference Appendices 8 and 9

Route of administration		Oral Gavage
Vehicle /Test item		Low dose		Mid dose
Dose (mg/kg body weight/day)		150		300
Group		G2		G3
Sex		Male	Female	Male	Female
Number of Animals		12	12	12	12
Stomach	Number examined	12	12	12	12
	Within normal limits	12	12	-	1
Hyperplasia, squamous cell, non-glandular	Mild	-	-	12	11
Hyperkeratosis, non-glandular	Minimal	-	-	2	-
Cyst, squamous, non-glandular	Present	-	-	1	-

-: Not applicable.

 

 

APPENDIX 1.        INDIVIDUAL ANIMAL GROSS PATHOLOGY FINDINGS OF MALES

Group & Dose (mg/kg body weight/day)	Animal No.	Type of Sacrifice	Gross Pathology Observations
			External	Internal
G1 & 0	Rg7881	TS	NAD	NAD
	Rg7882	TS	NAD	NAD
	Rg7883	TS	NAD	NAD
	Rg7884	TS	NAD	NAD
	Rg7885	TS	NAD	NAD
	Rg7886	TS	NAD	NAD
	Rg7887	TS	NAD	NAD
	Rg7888	TS	NAD	NAD
	Rg7889	TS	NAD	NAD
	Rg7890	TS	NAD	NAD
	Rg7891	TS	NAD	NAD
	Rg7892	TS	NAD	NAD
G2 & 150	Rg7893	TS	NAD	NAD
	Rg7894	TS	NAD	NAD
	Rg7895	TS	NAD	NAD
	Rg7896	TS	NAD	NAD
	Rg7897	TS	NAD	NAD
	Rg7898	TS	NAD	NAD
	Rg7899	TS	NAD	NAD
	Rg7900	TS	NAD	NAD
	Rg7901	TS	NAD	NAD
	Rg7902	TS	NAD	NAD
	Rg7903	TS	NAD	NAD
	Rg7904	TS	NAD	NAD

TS: Terminal Sacrifice; NAD: No Abnormality Detected.

 

 

 

APPENDIX 1 (Contd..,) INDIVIDUAL ANIMAL GROSS PATHOLOGY FINDINGS OF MALES

Group & Dose (mg/kg body weight/day)	Animal No.	Type of Sacrifice	Gross Pathology Observations
			External	Internal
G3 & 300	Rg7905	TS	NAD	NAD
	Rg7906	TS	NAD	NAD
	Rg7907	TS	NAD	NAD
	Rg7908	TS	NAD	NAD
	Rg7909	TS	NAD	NAD
	Rg7910	TS	NAD	NAD
	Rg7911	TS	NAD	NAD
	Rg7912	TS	NAD	NAD
	Rg7913	TS	NAD	NAD
	Rg7914	TS	NAD	NAD
	Rg7915	TS	NAD	NAD
	Rg7916	TS	NAD	NAD
G4 & 600	Rg7917	TS	NAD	Stomach (non-glandular)- Thickened, mucosa
	Rg7918	TS	NAD	Stomach (non-glandular)- Thickened, mucosa
	Rg7919	TS	NAD	Stomach (non-glandular)- Thickened, mucosa
	Rg7920	TS	NAD	Stomach (non-glandular)- Thickened, mucosa
	Rg7921	TS	NAD	Stomach (non-glandular)- Thickened, mucosa
	Rg7922	TS	NAD	Stomach (non-glandular)- Thickened, mucosa
	Rg7923	TS	NAD	Stomach (non-glandular)- Thickened, mucosa
	Rg7924	TS	NAD	Stomach (non-glandular)- Thickened, mucosa
	Rg7925	TS	NAD	Stomach (non-glandular)- Thickened, mucosa
	Rg7926	TS	NAD	Stomach (non-glandular)- Thickened, mucosa
	Rg7927	TS	NAD	Stomach (non-glandular)- Thickened, mucosa
	Rg7928	TS	NAD	Stomach (non-glandular)- Thickened, mucosa

TS: Terminal Sacrifice; NAD: No Abnormality Detected.

 

APPENDIX 2.        INDIVIDUAL ANIMAL GROSS PATHOLOGY FINDINGS OF FEMALES

Group & Dose (mg/kg body weight/day)	Animal No.	Type of Sacrifice	Gross Pathology Observations
			External	Internal
G1 & 0	Rg7929	TS	NAD	NAD
	Rg7930	TS	NAD	NAD
	Rg7931	TS	NAD	NAD
	Rg7932	TS	NAD	NAD
	Rg7933	TS	NAD	NAD
	Rg7934	TS	NAD	NAD
	Rg7935	TS	NAD	NAD
	Rg7936	TS	NAD	NAD
	Rg7937	TS	NAD	NAD
	Rg7938	TS	NAD	NAD
	Rg7939	TS	NAD	NAD
	Rg7940	TS	NAD	NAD
G2 & 150	Rg7941	TS	NAD	NAD
	Rg7942	TS	NAD	NAD
	Rg7943	TS	NAD	NAD
	Rg7944	TS	NAD	NAD
	Rg7945	TS	NAD	NAD
	Rg7946	TS	NAD	NAD
	Rg7947	TS	NAD	NAD
	Rg7948	TS	NAD	NAD
	Rg7949	TS	NAD	NAD
	Rg7950	TS	NAD	NAD
	Rg7951	TS	NAD	NAD
	Rg7952	TS	NAD	NAD

TS: Terminal Sacrifice; NAD: No Abnormality Detected.

 

 

 

APPENDIX 2 (Contd…) INDIVIDUAL ANIMAL GROSS PATHOLOGY FINDINGS OF FEMALES

Group & Dose (mg/kg body weight/day)	Animal No.	Type of Sacrifice	Gross Pathology Observations
			External	Internal
G3 & 300	Rg7953	TS	NAD	NAD
	Rg7954	TS	NAD	NAD
	Rg7955	TS	NAD	NAD
	Rg7956	TS	NAD	NAD
	Rg7957	TS	NAD	NAD
	Rg7958	TS	NAD	NAD
	Rg7959	TS	NAD	NAD
	Rg7960	TS	NAD	NAD
	Rg7961	TS	NAD	NAD
	Rg7962	TS	NAD	NAD
	Rg7963	TS	NAD	NAD
	Rg7964	TS	NAD	NAD
G4 & 600	Rg7965	TS	NAD	Stomach (non-glandular)- Thickened, mucosa
	Rg7966	TS	NAD	Stomach (non-glandular)- Thickened, mucosa
	Rg7967	TS	NAD	NAD
	Rg7968	TS	NAD	Stomach (non-glandular)- Thickened, mucosa
	Rg7969	TS	NAD	Stomach (non-glandular)- Thickened, mucosa
	Rg7970	TS	NAD	NAD
	Rg7971	TS	NAD	NAD
	Rg7972	D	NAD	Autolyzed ^#Uterus-implantation, present
	Rg7973	TS	NAD	Stomach (non-glandular)- Thickened, mucosa
	Rg7974	TS	NAD	Stomach (non-glandular)- Thickened, mucosa
	Rg7975	TS	NAD	NAD
	Rg7976	TS	NAD	Stomach (non-glandular)- Thickened, mucosa

TS: Terminal Sacrifice; D: Dead; NAD: No Abnormality Detected; # Normal observation and not a pathological change.

 

 

APPENDIX 3.        INDIVIDUAL GROSS PATHOLOGY FINDINGS RECORD OF DEAD PUPS

Group & Dose (mg/kg body weight/day)	Dam No.	Type of Sacrifice	On PND	No. of Pups Dead		Pup No.		Gross Pathological Observations
				M	F	M	F	External	Internal
G1 & 0	Rg7932	C	2	-	-	4	-	Cannibalized preclude examination	NA
G2 & 150	Rg7943	D	1	1	-	-	-	NAD	NAD
	Rg7946	D	1	1	-	-	-	NAD	NAD
G3 & 300	Rg7958	D	1	1	1	-	-	NAD	NAD
	Rg7960	D	1	1	-	-	-	NAD	NAD
		D	2	-	-	7	-	Skin- Forehead, discoloration, red	NAD
	Rg7963	D	1	4	2	-	-	NAD	NAD
	Rg7964	D	3	-	-	-	14	NAD	NAD
G4 & 600	Rg7965	D	1	-	2	-	-	NAD	NAD
		D	4	-	-	1	-	NAD	NAD
	Rg7967	D	1	2	4	-	-	NAD	NAD
	Rg7969	D	2	-	-	2	11	NAD	NAD
	Rg7972	D	1	2	2	-	-	NAD	NAD
		D	2	-	-	1 to 3	4 to 11	NAD	NAD
	Rg7974	D	1	-	-	-	-	NAD	NAD
		D	2	-	-	1	-	NAD	NAD

M: Male; F: Female; D: Dead; C: Cannabalised; NAD: No Abnormality Detected; PND: Post-Natal Day;

-: Not Applicable.

 

 

 

 

 

 

 

 

 

 

APPENDIX 4.        INDIVIDUAL GROSS PATHOLOGY FINDINGS RECORD OF PUPS – PND 4

Group & Dose      (mg/kg body weight/day)	Animal No.	Type of Sacrifice (on PND 4)	Pup No.	Gross Pathological Observations
			F	External	Internal
G1 & 0	Rg7939	TS	12 & 13	NAD	NAD
	Rg7931	TS	12 & 13	NAD	NAD
	Rg7933	TS	11	NAD	NAD
	Rg7938	TS	16 & 17	NAD	NAD
	Rg7936	TS	11 & 12	NAD	NAD
	Rg7935	TS	12 & 13	NAD	NAD
G2 & 150	Rg7941	TS	15 & 16	NAD	NAD
	Rg7948	TS	15 & 16	NAD	NAD
	Rg7952	TS	11 & 12	NAD	NAD
G3 & 300	Rg7960	TS	12	NAD	NAD
	Rg7956	TS	12 & 13	NAD	NAD
	Rg7964	TS	17 & 18	NAD	NAD
	Rg7961	TS	11	NAD	NAD
G4 & 600	Rg7971	TS	11 & 12	NAD	NAD
	Rg7968	TS	13 & 14	NAD	NAD
	Rg7974	TS	17 & 18	NAD	NAD
	Rg7975	TS	13 & 14	NAD	NAD

TS: Terminal sacrifice; M: Male; F: Female; NAD: No Abnormality Detected; PND: Post-Natal Day.

 

 

APPENDIX 5.        INDIVIDUAL GROSS PATHOLOGY FINDINGS RECORD OF PUPS – PND 13

Group & Dose (mg/kg body weight/day)	Animal No.	Type of Sacrifice (on PND 13)	Pup No.		Gross Pathological Observations
			M	F	External	Internal
G1 & 0	Rg7929	TS	1 & 6	7 to 10	NAD	NAD
	Rg7930	TS	1 to 3	4 to 8	NAD	NAD
	Rg7931	TS	1 to 7	8 to 11	NAD	NAD
	Rg7932	TS	1 to 3	5 to 7	NAD	NAD
	Rg7933	TS	1 to 9	10	NAD	NAD
	Rg7934	TS	1 to 4	5 to 9	NAD	NAD
	Rg7935	TS	1 to 7	8 to 11	NAD	NAD
	Rg7936	TS	1 to 6	7 to 10	NAD	NAD
	Rg7937	TS	1 & 2	3 to 5	NAD	NAD
	Rg7938	TS	1 to 10	11 to 15	NAD	NAD
	Rg7939	TS	1 to 8	9 to 11	NAD	NAD
	Rg7940	TS	1 to 4	5 to 8	NAD	NAD
G2 & 150	Rg7941	TS	1 to 6	7 to 14	NAD	NAD
	Rg7942	TS	1 to 4	5 to 8	NAD	NAD
	Rg7943	TS	1 to 6	7 to 9	NAD	NAD
	Rg7944	TS	1 to 3	4 to 10	NAD	NAD
	Rg7945	TS	1 to 5	6 to 8	NAD	NAD
	Rg7946	TS	1 to 3	4 to 6	NAD	NAD
	Rg7947	TS	1 to 6	7 to 10	NAD	NAD
	Rg7948	TS	1 to 8	9 to 14	NAD	NAD
	Rg7950	TS	1 to 4	-	NAD	NAD
	Rg7951	TS	1 to 3	4 to 6	NAD	NAD
	Rg7952	TS	1 to 6	7 to 10	NAD	NAD

TS: Terminal sacrifice; M: Male; F: Female; NAD: No Abnormality Detected; PND: Post-Natal Day.

 

APPENDIX 5 (Contd..,) INDIVIDUAL GROSS PATHOLOGY FINDINGS RECORD OF PUPS – PND 13

Group & Dose (mg/kg body weight/day)	Animal No.	Type of Sacrifice (on PND 13)	Pup No.		Gross Pathological Observations
			M	F	External	Internal
G3 & 300	Rg7954	TS	1 to 4	-	NAD	NAD
	Rg7955	TS	1 to 6	7 to 10	NAD	NAD
	Rg7956	TS	1 to 7	8 to 11	NAD	NAD
	Rg7958	TS	1 to 3	4	NAD	NAD
	Rg7959	TS	1 to 4	5 to 9	NAD	NAD
	Rg7960	TS	1 to 6 & 8	9 to 11	NAD	NAD
	Rg7961	TS	1 to 5	6 to 10	NAD	NAD
	Rg7962	TS	1 to 6	7 to 10	NAD	NAD
	Rg7964	TS	1 to 7	8 to 13 15 & 16	NAD	NAD
G4 & 600	Rg7966	TS	1 to 3	4 to 7	NAD	NAD
	Rg7968	TS	1 to 8	9 to 12	NAD	NAD
	Rg7969	TS	1, 2 & 4	5 to 10 & 12	NAD	NAD
	Rg7970	TS	1 to 4	5 to 10	NAD	NAD
	Rg7971	TS	1 to 4	5 to 10	NAD	NAD
	Rg7974	TS	2 to 8	9 to 16	NAD	NAD
	Rg7975	TS	1 to 6	7 to 12	NAD	NAD
	Rg7976	TS	1 to 4	5 to 9	NAD	NAD

TS: Terminal sacrifice; M: Male; F: Female; NAD: No Abnormality Detected; PND: Post-Natal Day.

 

 

APPENDIX 6.        INDIVIDUAL ANIMAL HISTOPATHOLOGY FINDINGS OF MALES

Group Details

G1, Vehicle Control

Dose (mg/kg body weight/day)

0

Animal Numbers

Rg7881

Rg7882

Rg7883

Rg7884

Rg7885

Rg7886

Rg7887

Rg7888

Rg7889

Rg7890

Rg7891

Rg7892

ORGANS / LESIONS

Epididymides

N

N

N

N

N

N

N

N

N

N

N

N

Testes

N

N

N

N

N

N

N

N

N

N

N

N

Stomach

N

N

N

N

N

N

N

N

N

N

N

N

 

 

 

 

Group Details

G4, High Dose

Dose (mg/kg body weight/day)

600

Animal Numbers

Rg7917

Rg7918

Rg7919

Rg7920

Rg7921

Rg7922

Rg7923

Rg7924

Rg7925

Rg7926

Rg7927

Rg7928

ORGANS / LESIONS

Epididymides

N

N

N

N

N

N

N

N

N

N

N

N

Testes

N

N

N

N

N

N

N

N

N

N

N

N

Stomach

N

N

N

N

N

N

N

N

N

N

N

N

Hyperplasia, squamous cell, non-glandular

d-3

d-3

d-4

d-4

d-4

d-4

d-4

d-4

d-4

d-4

d-4

d-4

Hyperkeratosis, non-glandular

d-2

d-1

d-2

d-1

d-2

d-2

d-2

d-2

d-2

d-2

d-2

d-2

1: Minimal; 2: Mild; 3: Moderate; 4: Marked; d: Diffuse; N: Normal or within normal histological limits unless specified        

 

 

 

APPENDIX 7.        INDIVIDUAL ANIMAL HISTOPATHOLOGY FINDINGS OF FEMALES

Group Details

G1, Vehicle Control

Dose (mg/kg body weight/day)

0

Animal Numbers

Rg7929

Rg7930

Rg7931

Rg7932

Rg7933

Rg7934

Rg7935

Rg7936

Rg7937

Rg7938

Rg7939

Rg7940

ORGANS / LESIONS

Ovaries

N

N

N

N

N

N

N

N

N

N

N

N

Stomach

N

N

N

N

N

N

N

N

N

N

N

N

Vagina

N

N

N

N

N

N

N

N

N

N

N

N

Stages of estrus cycle

D

P

P

P

D

D

P

M

P

P

D

P

 

 

Group Details

G4, High dose

Dose (mg/kg body weight/day)

600

Animal Numbers

Rg7965

Rg7966

Rg7967

Rg7968

Rg7969

Rg7970

Rg7971

Rg7972

Rg7973

Rg7974

Rg7975

Rg7976

ORGANS / LESIONS

Ovaries

N

N

N

N

N

N

N

PA

N

N

N

N

Stomach

N

N

N

N

N

N

N

A

N

N

N

N

Hyperplasia, squamous cell, non-glandular

d-4

d-4

d-2

d-4

d-4

d-2

-

-

d-4

d-4

d-2

d-4

Hyperkeratosis, non-glandular

d-1

d-2

-

d-2

d-2

-

-

-

d-2

d-2

-

d-2

Vagina

N

N

N

N

N

N

N

N

N

N

N

N

Stages of estrus cycle

D

D

P

P

D

D

D

E

D

P

D

D

1: Minimal; 2: Mild; 3: Moderate; 4: Marked; d: Diffuse; N: Normal or within normal histological limits unless specified; A: Autolysis precluded evaluation; PA: Partially autolysed; P: Proestrus; E: Estrus; M: Metestrus; D: Diestrus; -: No incidence

 

 

APPENDIX 8.        INDIVIDUAL ANIMAL HISTOPATHOLOGY FINDINGS OF MALES (TARGET ORGAN)

Group Details

G2, Low dose

Dose (mg/kg body weight/day)

150

Animal Numbers

Rg7893

Rg7894

Rg7895

Rg7896

Rg7897

Rg7898

Rg7899

Rg7900

Rg7901

Rg7902

Rg7903

Rg7904

ORGANS / LESIONS

Stomach

N

N

N

N

N

N

N

N

N

N

N

N

 

 

 

Group Details

G3, Mid dose

Dose (mg/kg body weight/day)

300

Animal Numbers

Rg7905

Rg7906

Rg7907

Rg7908

Rg7909

Rg7910

Rg7911

Rg7912

Rg7913

Rg7914

Rg7915

Rg7916

ORGANS / LESIONS

Stomach

Hyperplasia, squamous cell, non-glandular

d-2

d-2

d-2

d-2

d-2

d-2

d-2

d-2

d-2

d-2

d-2

d-2

Hyperkeratosis, non-glandular

d-1

-

-

-

-

-

d-1

-

-

-

-

-

Cyst, squamous, non-glandular

-

-

-

-

-

-

P

-

-

-

-

-

1: Minimal; 2: Mild; d: Diffuse; N: Normal or within normal histological limits unless specified; P: Lesion present but not graded; -: No incidence

 

 

 

 

APPENDIX 9.        INDIVIDUAL ANIMAL HISTOPATHOLOGY FINDINGS OF FEMALES (TARGET ORGAN)

Group Details

G2, Low dose

Dose (mg/kg body weight/day)

150

Animal Numbers

Rg7941

Rg7942

Rg7943

Rg7944

Rg7945

Rg7946

Rg7947

Rg7948

Rg7949

Rg7950

Rg7951

Rg7952

ORGANS / LESIONS

Stomach

N

N

N

N

N

N

N

N

N

N

N

N

 

Group Details

G3, Mid dose

Dose (mg/kg body weight/day)

300

Animal Numbers

Rg7953

Rg7954

Rg7955

Rg7956

Rg7957

Rg7958

Rg7959

Rg7960

Rg7961

Rg7962

Rg7963

Rg7964

ORGANS / LESIONS

Stomach

N

N

N

N

N

N

N

N

N

N

N

N

Hyperplasia, squamous cell, non-glandular

d-2

d-2

d-2

d-2

d-2

-

d-2

d-2

d-2

d-2

d-2

d-2

2: Mild; d: Diffuse; N: Normal or within normal histological limits unless specified; -: No incidence

 

 

APPENDIX 10.    INDIVIDUAL ANIMAL HISTOPATHOLOGY FINDINGS OF GROSS LESION

Group Details	G3, Mid dose
Dose (mg/kg body weight/day)	300
Dam Number/ Pup Number/ Sex	Rg7960/ 7/ Male
ORGANS / LESIONS
Skin	N
Haemorrhage	2
Infiltrate, mononuclear cell	mf-2

                             2: Mild; mf: Multifocal; N: Normal or within normal histological limits unless specified

 

Conclusions:

Conclusion:

In conclusion, the oral administration of test item Cyclic Glucamide C12-C14 over the time of the study, carried out according to the OECD guideline 421 (for males with a total of 35 days and for females ranging from 50 to 65 days) with the dose levels of 150, 300 and 600 mg/kg body weight/day noted with below mentioned results.

At the dose level of 150 mg/kg body weight/day, the test item did not reveal any adverse systemic toxicity effects except, a minimal reduction in body weights in males. However, there was no indication of reproduction and developmental toxicity at this dose level under experimental conditions employed.

At the dose level of 300 mg/kg body weight/day, animals noted with some of the systemic toxicity effects such as reduced body weights in males, minimal increase in post-implantation loss, and histopathological findings such as hyperplasia, squamous cell, non-glandular and hyperkeratosis, non-glandular in stomach. No adverse test item related changes were observed in birth parameters. There were no test item related effects noted in any of the reproductive and developmental end points at this dose level, except a minimal and not statistically significant increase in post-implantation loss.

It was concluded that there were no adverse effects noted on male and female reproductive performance/indices of adult animals from the tested dose groups
G2 (150 mg/kg body weight/day) and G3 (300 mg/kg body weight/day) when compared with vehicle control group.

At the dose level of 600 mg/kg body weight/day, animals noted with treatment related clinical signs of toxicity, reduced body weights and feed consumption, increased post-implantation loss, increase in postnatal loss and histopathological findings such as hyperplasia, squamous cell, non-glandular and hyperkeratosis, non-glandular in stomach.

Executive summary:

The objective of this Reproduction/ Developmental Toxicity Screening Test of Cyclic Glucamide C12-C14 by Oral Gavage in Sprague Dawley rats was to determine the possible health hazards likely to arise from repeated exposure to the test item over a relatively limited period of time. This study was also conducted to provide initial information on possible effects on male and female reproductive performance such as gonadal function, mating behavior, conception, development of the conceptus and parturition and to estimate the No Observed Effect Level (NOEL).

A total of 96 (48 males + 48 females) Sprague Dawley rats were selected for the study and distributed to four groups (G1, G2, G3 and G4). Each group consisted of 12 males and 12 females. The animals in group G1 were administered with vehicle [distilled water], animals in groups G2, G3 and G4 were administered with test item at the dose levels of 150, 300 and 600 mg/kg body weight/day for low, mid and high dose levels, respectively. Vehicle and test item formulations were administered orally by gavage with the dose volume of 10 mL/kg body weight/day once daily at similar times on each day for 7 days a week.

The males from all groups were administered with test item during pre-mating
(14-days), during mating and during post-mating period (total of 35 days). The pregnant females from all groups were administered with test item during pre-mating (14-days), during mating, pregnancy (gestation) and up to lactation day 13, ranging from 49 to 65 days. The non-pregnant females were administered with test item during pre-mating (14-days), during mating until confirmed as mated and further 25 to 26 days from the day of confirmation of mating, ranging from 40 to 58 days.

The test item formulations were stable up to 48 hours at room temperature in distilled water with the concentrations of 15 mg/mL and 60 mg/mL. The dose concentration analysis for prepared test item formulations during treatment period was performed during week 1 and 4. The obtained mean results were within the range of 90 to 110% of nominal concentration and the relative standard deviation (% RSD) was less than 10%.

For systemic toxicity assessment, all the survived animals of both sexes were observed once daily for clinical signs, twice daily for mortality and morbidity and once in a week for detailed clinical examination. Body weight of all the survived animals of both sexes were recorded once in a week until termination. Further, the body weight of all pregnant females was recorded on gestation day (GD) 0, 7, 14 and 20 during pregnancy and on lactation day (LD) 1, 4, 7, 13 and 14 during lactation. Body weight of all non-pregnant females was recorded once in a week until termination. Feed consumption for all the survived animals of both sexes were recorded once in a week during pre-mating. Further, feed consumption of all pregnant females was recorded during GD 0 to 7, 7 to 14 and 14 to 20 and during LD 1 to 4, 4 to 7 and 7 to 13. The investigations of haematology for all males and survived females from all groups was conducted at termination. Serum thyroxine hormone (T4) levels were estimated for all group males by ELISA method. The organs were collected and weighed on the day of termination for all males and survived females and organ weight relative to terminal body weight was calculated. All the animals of both sexes were observed for both external and internal gross pathological changes during conduct of necropsy. Histopathological examination was conducted on the tissues collected from the groups G1 and G4 animals with special emphasis on stages of spermatogenesis in the male gonads and histopathology of interstitial testicular cell structure, stomach (both sexes). Histopathological examination was extended to lower dose groups G2 and G3 due to noted microscopic changes in non-glandular part of stomach.

For reproductive toxicity assessment, all the males were evaluated for reproductive performances such as, mating and fertility indices. All the females were evaluated for reproductive performances such as, mating, fertility, gestation and parturition indices. The females were also evaluated for pre-coital interval and gestation length. All females were evaluated for oestrus cyclicity during pre-mating period and the vaginal smear examination was continued until evidence of mating. At birth (delivery) parameters such as, number of live/dead pups born, litter size, sex ratio (m/f) and live birth index per litter were observed / calculated. The litter observations during lactation period such as, number of survived or dead pups, sex ratio (m/f) and pup survival index per litter were observed / calculated. The total number of implantation sites was recorded for each litter during necropsy and the post-implantation and postnatal losses per litter was calculated.

For developmental toxicity assessment, all survived pups from each litter were observed once daily for external behavioural changes and twice daily for mortality until termination [postnatal day (PND) 13]. All pups from each litter were weighed individually on PND 1, 4, 7 and 13 and measured for anogenital distance on PND 4. All male pups were observed for retention of nipples on PND 13. All the pups were subjected for both external and internal gross pathological changes during conduct of necropsy. The collected serum from PND 13 pups was subjected to estimation of thyroxine hormone (T4) levels using ELISA method.

In group G2, there were no clinical signs of toxicity and no mortality/morbidity noted in any of the animals of both sexes. A minimal reduction in mean body weight and percent change in mean body weight gain was noted in males. There were no changes noted in mean feed consumption during all phases of the treatment period. The investigations of haematology and serum thyroxine hormone (T4) levels did not affect by the test item exposure. The absolute and relative organ weights did not reveal any changes in both sexes. The gross pathological examinations did not reveal any changes in both sexes. The histopathological examination of stomach did not reveal any changes in both sexes. There were no test item related effects noted in any of the reproductive and developmental end points at this dose level.

In group G3, there were no clinical signs of toxicity and no mortality/morbidity noted in any of the animals of both sexes. A minimal to moderate reduction in mean body weight and percent change in mean body weight gain was noted in males. No changes were noted in mean feed consumption during all phases of the treatment period. The investigations of haematology and serum thyroxine hormone (T4) levels did not affect by the test item exposure. The absolute and relative organ weights did not reveal any changes in both sexes. The gross pathological examinations did not reveal any changes in both sexes. The histopathological examination of stomach noted with hyperplasia, cyst, squamous cell, non-glandular and hyperkeratosis, non-glandular in stomach. There were no test item related effects noted in any of the reproductive and developmental end points at this dose level, except a minimal and not statistically significant increase in post-implantation loss.

In group G4, all the animals of both sexes were noted with wetness around mouth after dose administration and continued until termination. These noted observations can be due to surfactant nature of the test item which led to form foam or wetness near to route of administration (mouth). However, 1 out 12 treated females, noted with lethargy, perinasal staining and rough hair coat along with the post-dose wetness around mouth from treatment day 39 and found dead on treatment day 41. A reduction in mean body weight, percent change in mean body weight gain and feed consumption was noted. The investigations of haematology and serum thyroxine hormone (T4) levels did not affect by the test item exposure. The absolute and relative organ weights did not reveal any changes in both sexes. Majority of the animals noted with treatment related thickened mucosa of non-glandular part of stomach during conduct of necropsy. The histopathological examination of stomach noted with hyperplasia, squamous cell, non-glandular and hyperkeratosis, non-glandular in stomach. There were no test item related effects noted in any of the reproductive and developmental end points at this dose level, except an increase in post-implantation loss. There were no adverse test item related effects noted on reproductive and developmental end points at this dose level. However, treatment related increase in post-implantation loss and postnatal loss was noted at this dose level.

 

Effect on fertility: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

300 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

In a OECD Guideline No. 421, “Reproduction/Developmental Toxicity Screening Test”, it was concluded that there were no adverse effects noted on male and female reproductive performance/indices of adult animals from the tested dose groups G2 (150 mg/kg body weight/day) and G3 (300 mg/kg body weight/day) when compared with vehicle control group. The minimal effects at the dose level of 600 mg/kg body weight/day, eon reproduction is considered to be a secondary non-specific consequence of the other toxic effects.

Justification for classification or non-classification

In a OECD Guideline No. 421, “Reproduction/Developmental Toxicity Screening Test”, it was concluded that there were no adverse effects noted on male and female reproductive performance/indices of adult animals from the tested dose groups G2 (150 mg/kg body weight/day) and G3 (300 mg/kg body weight/day) when compared with vehicle control group. The minimal effects at the dose level of 600 mg/kg body weight/day, on reproduction is considered to be a secondary non-specific consequence of the other toxic effects. Based hereupon classification and labelling of the registered substance concerning reproductive toxicity is not warranted.