Registration Dossier
Registration Dossier
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EC number: 221-424-4 | CAS number: 3089-17-6
Endpoint summary
Administrative data
Description of key information
No adverse effects observed in a subacute combined oral and reproductive toxicity study in rats using a cloese analogue substance at doses including 1000 mg/kg bw.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- repeated dose toxicity: oral, other
- Remarks:
- Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test by Oral Gavage in Sprague Dawley Rats
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 15 June 2021 to 22 December 2021
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- See read across justification document in chapter 13
- Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Version / remarks:
- adopted on 29 July 2016
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- 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 (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: Males: 254.36 to 291.64 g; Females: 200.54 to 211.92 g
- Housing: Animals were housed in a standard polypropylene cage (size: L 430 x B 285 x H 150 mm) with stainless steel mesh top grill having facilities for holding pelleted food and drinking water in water bottle fitted with stainless steel sipper tube. Clean sterilized paddy husk was provided as bedding material.
During acclimatization, two animals of same sex were housed.
i. Main Group Animals:
- Pre mating: Per cage two animals of same sex and group were housed.
- Cohabitation Period (mating): Per cage two animals (one male and one female) of same group were housed.
- Post-mating: After confirmation on presence of sperm in the vaginal smear (Day 0 of pregnancy), the mated pairs were separated. Males were housed with their former cage mates while females were housed individually. Sterilized paper shreds were provided as a nesting material for main group females from gestation day 20 onwards.
ii. Recovery Group Animals:
- Maximum of two animals per cage per group of same sex were housed, tunnels were provided as enrichment for the animals which were housed individually.
- Diet: Altromin maintenance diet for rats and mice (manufactured by Altromin Spezialfutter GmbH & Co. KG) was provided ad libitum to the animals throughout the experimental period.
- Water: Water was provided ad libitum throughout the experimental period. Deep bore-well water passed through reverse osmosis unit was provided in plastic water bottles with stainless steel sipper tubes.
- Acclimation period: 5 days
DETAILS OF FOOD AND WATER QUALITY: Analysis of food and water qaulity included as annexures in the study report.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.9 to 22.9 Degree Centigrade
- Humidity (%): 48 to 63%,
- 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: 24 June 2021; To: 16 September 2021 - Route of administration:
- oral: gavage
- Details on route of administration:
- The test item or vehicle were administered to the animals through the oral (gavage) route once daily.
- Vehicle:
- CMC (carboxymethyl cellulose)
- Remarks:
- 0.5% w/v CMC (carboxymethyl cellulose)
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
VEHICLE
- Justification for use and choice of vehicle (if other than water): The test item was insoluble in distilled water and uniformly suspended in 0.5% w/v Carboxy Methyl Cellulose at the concentration of 100 mg/mL (the highest dose concentration selected for the study considering the dose volume of 10 mL/kg body weight) as per in-house solubility/suspendibility test results.
Hence, 0.5% w/v Carboxymethyl Cellulose was used as vehicle for test item formulations in consultation with sponsor.
0.5% w/v Carboxymethyl Cellulose is a routinely used and universally accepted vehicle of choice for the oral toxicity studies
- Concentration in vehicle: The concentrations of of 0, 111, 333 and 1000 mg/kg body weight/day were selected as control, low, mid and high dose groups respectively
- Amount of vehicle (if gavage): 10mL/Kg body weight
- Batch no.: SLCH1520, expiry date: September 2026; Make Sigma Aldrich
- Purity: Medium viscocity grade - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The Dose formulation samples of the test item were analyzed for homogeneity and dose concentration by UV-Vis Method and the results are found within the range of 85 to 115% of the nominal concentration and the %RSD is <15%
Homogeneity and dose formulation analysis for dose concentration verification was performed during week 1 and week 5 of the treatment. The samples were collected in duplicates (5 mL each) from top, middle and bottom layers from low, mid and high dose concentrations and in duplicates from single layer from vehicle control.
The prepared test item formulations were stirred using magnetic stirrer during sampling.
The mean obtained results were within the range of 85 to 115% of the nominal concentration and the relative standard deviation (% RSD) is less than 15%. - Duration of treatment / exposure:
- Males: 31 Days
Females: The females were treated for a two-week pre-mating period (14-days), during mating, pregnancy (gestation) and up to lactation day 13 (ranging from a total period of 50 to 62 days).
The females with positive mating signal, but no-evidence of pregnancy / littering were treated during two-week pre-mating period, during mating and further 24 days from the day of positive mating signal (group G1 - one female until experimental day 39; group G2 - one female until experimental day 52, one female until experimental day 46; G3 - two females until experimental day 49; group G4 - one female until experimental day 39).
Recovery group animals: 52 Days - Frequency of treatment:
- Once Daily
- Dose / conc.:
- 0 other: mg/kg body weight/day
- Remarks:
- Vehicle Control
- Dose / conc.:
- 111 other: mg/kg body weight/day
- Remarks:
- Low Dose
- Dose / conc.:
- 333 other: mg/kg body weight/day
- Remarks:
- Mid Dose
- Dose / conc.:
- 1 000 other: mg/kg body weight/day
- Remarks:
- High Dose
- No. of animals per sex per dose:
- Main Group: 24 (12 Males + 12 Females)
Recovery Group: 10 (5 Males + 5 Females) - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: There was no information or data available from repeated dose/reproduction toxicity and teratology studies for the test item.
The doses of 0, 111, 333 and 1000 mg/kg body weight/day were selected as control, low, mid and high dose groups for the dose range finding study (BIO-DTX 056) in consultation with the sponsor.
There were no test item-related related changes noted in any of the systemic, reproduction and developmental parameters up to the dose level of 1000 mg/kg body weight/day in the Dose Range Finding Study (BIO-DTX 056).
Hence, the same doses of 0, 111, 333 and 1000 mg/kg body weight/day were selected as control, low, mid and high dose groups respectively, for the present study in consultation with the sponsor.
- 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 main and recovery groups using Microsoft Excel Spreadsheet, such that body weight variation of animals selected for the study does not exceed ±20% (Males: -6.80 to 11.14%; Females: -12.58 to 8.29%) of the mean body weight of each sex. The grouping was done one day prior to initiation of treatment. Body weight of the animals were analyzed statistically for mean body weight to rule out statistical significant differences between groups within each sex. - Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: All the animals were observed once daily for general clinical signs of toxicity. These observations were made approximately at the same time on each day after dose administration. All the animals were observed twice daily for mortality and morbidity.
- Cage side observations checked in table [No.1] were included.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: All the animals were subjected to detailed clinical examinations on day 1 before treatment and weekly thereafter during treatment. These observations were made outside the home cage and approximately at the same time.
BODY WEIGHT: Yes
- Time schedule for examinations: The main group males were weighed at receipt, on the first day of dosing, weekly thereafter and at termination.
The main group females were weighed at receipt, on the first day of dosing, weekly thereafter during pre-mating and until confirmation of mating. All the pregnant animals were weighed on gestation days (GD) 0, 7, 14 and 20 and on lactation days (LD) 1, 4, 7, 13 and 14 (terminal body weight). The non-pregnant animals were weighed weekly once until termination and the terminal body weights were recorded before scheduled sacrifice.
The recovery group animals were weighed at receipt, on the first day of dosing, weekly thereafter and at termination.
FOOD EFFICIENCY:
- Cage wise feed consumption was measured for all main group males and females, once in a week during premating period coinciding with body weight recording.
Cage wise feed consumption was measured for all pregnant animals during gestation day (GD) 0 to 7, 7 to 14 and 14 to 20, during lactation day (LD) 1 to 4, 4 to 7 and
7 to 13 coinciding with body weight recording.
Cage wise feed consumption was measured for all recovery group animals once in a week throughout the experimental period coinciding with body weight recording.
Average feed intake per animal (g/animal/day) was calculated using the amount of feed offered and left over in each cage and the number of rats per cage.
Feed consumption was not measured during following occasions, but offered ad libitum of feed:
- cohabitation period for both sexes of main groups;
- after GD 20 and until parturition for pregnant females;
- from day 20 after confirmation of mating until termination for non-pregnant females.
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Ophthalmological examination was carried out for all animals before initiation of treatment i.e. after grouping and randomization (last day of acclimatization). Ophthalmological examination was also carried out at the end of dosing period for all males (shortly prior to scheduled sacrifice, i.e. day 30) and during lactation period for females (shortly prior to scheduled sacrifice, i.e. on lactation day 13) and during last week (i.e. day 65) for the recovery group animals.
- Dose groups that were examined: G1/G1R, G2, G3 and G4/G4R.
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Blood samples of both males and females were collected on the day of scheduled terminal sacrifice (for main group males after completion of 31 days of dose administration, for main group females on lactation day 14 and for recovery group animals on the day of scheduled sacrifice.
- Anaesthetic used for blood collection: Yes
- Animals fasted: Yes
- How many animals: 12 Males and 12 Femles from all the main groups; 5 Males and 5 Females from all the recovery groups.
- Parameters checked in table [No.16] were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Blood samples of both males and females were collected on the day of scheduled terminal sacrifice (for main group males after completion of 31 days of dose administration, for main group females on lactation day 14 and for recovery group animals on the day of scheduled sacrifice.
- Animals fasted: Yes
- How many animals: 12 Males and 12 Femles from all the main groups; 5 Males and 5 Females from all the recovery groups.
- Parameters checked in table [No.17] were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: Urine was collected from five randomly selected males of each main group and for all recovery animals at termination. The selected animals were placed in urine collection cages overnight and not given access to feed but water was provided ad libitum during their stay in the urine collection cages. The overnight urine volume (mL) collected from these animals were measured.
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- Parameters checked in table [No.18] were examined.
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: Neurological/Functional examination was performed for five males and five females, randomly selected from each group, towards the end of the dosing period for males (shortly prior to scheduled sacrifice, i.e. on day 30) and during the lactation period for females (shortly prior to scheduled sacrifice, i.e. on lactation day 13). Neurological/Functional examination was performed for all recovery group animals towards the end of the recovery period (shortly prior to scheduled sacrifice, i.e.
on day 65.
- Dose groups that were examined: G1/G1R, G2, G3 and G4/G4R.
- Battery of functions tested: sensory activity, grip strength, motor activity and Hindlimb Footsplay.
Thyroid Hormone Estimations: Blood collection for Thyroxine (T4) Level estimation: Blood samples were collected from all the main group animals for measurement of serum T4 levels on the following schedule:
- All dams at termination (lactation day 14).
- All adult males, at termination (after completion of 31 days of treatment).
The assessment of serum T4 levels was performed for adult males. Further assessment of T4 levels in serum samples from the dams was not assessed as there were no treatment-related effects observed in the T4 levels of adult males.
The collected blood samples were centrifuged at 5000 rpm for 10 minutes; the serum was separated and stored at freezing conditions (-80ºC ± 10ºC) till estimation.
The serum samples were estimated for thyroid hormonal levels (Thyroxine - T4) by the ELISA method using commercial assay kits. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Statistics:
- The statistical analysis tests followed for the interpretation of data are as mentioned below:
• Body weight (weekly/gestation/lactation)
• Percent Change in body weight (weekly/gestation/lactation)
• Feed consumption (weekly/gestation/lactation)
• Hematology
• Clinical chemistry
• Urinalysis
• Absolute/relative organ weights
• Functional Observation parameters
• Thyroid hormonal levels - Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no clinical signs of toxicity recorded in any of the animals of both sexes from all the tested dose groups throughout the experimental period. However, dark purple colored faeces were noted from day 2 observation throughout the experiment period till termination of treatment in group G3 & G4/G4R animals. This coloration was due to colored nature of the test item but not any adverse signs.
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food efficiency:
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Other effects:
- no effects observed
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- behaviour (functional findings)
- body weight and weight gain
- clinical biochemistry
- clinical signs
- food efficiency
- gross pathology
- haematology
- histopathology: non-neoplastic
- mortality
- ophthalmological examination
- organ weights and organ / body weight ratios
- urinalysis
- other: THyroid hormonal lelves
- Key result
- Critical effects observed:
- no
- Conclusions:
- In conclusion, the oral administration of test item over the time of the study, carried out according to the OECD guideline 422 (for main group males with a total of 31 days, for main group females ranging from 50 to 62 days and for recovery group animals with a total period of 52 days) did not produce any indication of systemic, reproduction and developmental toxicity at the dose levels of 111, 333 and 1000 mg/kg body weight/day under experimental conditions employed.
Therefore, the no-observed-adverse-effect-level (NOAEL) of test item is considered as 1000 mg/kg body weight for systemic, reproduction and developmental toxicity end points. - Executive summary:
The objective of this Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test of the test item 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 an estimate of the No Observed Adverse Effect Level (NOAEL).
A total of 116 (58 males + 58 females) Sprague Dawley rats were selected for the study and distributed to four main (G1, G2, G3 and G4) and two recovery groups (G1R and G4R). Each main group consisted of 12 males and 12 females and each recovery group consisted of 5 males and 5 females. The animals in group G1/G1R were administered with vehicle [0.5% w/v Carboxymethyl Cellulose], animals in groups G2, G3 and G4/G4R were administered with test item at the dose levels of 111, 333 and 1000 mg/kg body weight/day for low, mid and high/high dose recovery, 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.All the main group males were administered with test item during pre-mating (14-days), during mating and during post-mating period (total of 31 days). The pregnant females from main groups were administered with test item during pre-mating (14-days), during mating, pregnancy (gestation) and up to lactation day 13.The females with positive mating signal, but no-evidence of pregnancy / litteringwere administered with test itemduringpre-mating (14-days),during mating, and further 24 days from the day of positive mating signal. All the recovery group animals were administered with test item for 50 days followed by a 14-day observation period without treatment.
The test item formulations werestable for 6 hours and 48 hours at room temperature in 0.5% w/v Carboxymethyl Cellulose with the concentrations of 5 mg/mL and 100 mg/mL.The homogeneity and dose form concentration analysis for preparedtest item formulations during treatment periodwas performed during week 1 and 5 and the mean results were within the range of 85 to 115% of the nominal concentration and the relative standard deviation (% RSD) is less than 15%.
For systemic toxicity assessment, all the animals (main and recovery groups) 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 animals (main and recovery groups) 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 animals of both sexes were recorded once in a week during pre-mating for main groups and throughout the experimental period for recovery groups. 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.Ophthalmological examination was carried out once before treatment and at the end of the dosing period for all males and females (main and recovery groups). Neurological/functional observations were performed for five randomly selected males and females from each main group, for all animals from recovery groups towards end of the dosing period. The investigations of haematology and clinical chemistry for all animals (main and recovery groups), investigations of urinalysis for five randomly selected males from each main group and for all recovery groups animals was conducted at termination. Serum thyroxine hormone (T4) levels were estimated for all main group males by ELISA. The organs were collected and weighed on the day of termination for all animals (main and recovery groups) of both sexes and organ weight relative to terminal body weight was calculated. All the animals (main and recovery groups) of both sexes were observed for both external and internal gross pathological changes during conduct of necropsy. Histopathological examination was conducted on all 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.
For reproductive toxicity assessment, all the males (main groups) were evaluated for reproductive performances such as, mating and fertility indices. All the females (main groups) 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.
There were no clinical signs of toxicity and no mortality/morbidity noted in any of the animals from all the tested dose groups, howeverdark purple colored faeces were noted from day 2 observation throughout the experiment period till termination of treatment in group G3 & G4/G4Ranimals. This coloration is due to colored nature of the test item but not any adverse sign. Detailed clinical examination did not reveal any changes in any of the tested dose group animals. No changes noted in mean body weight, percent change in mean body weight gain and mean feed consumption in all the tested dose groups of both sexes. The ophthalmological examination and neurological/functional examinations did not reveal any test item-related changes in any of the animals from all the tested dose groups of both sexes. The obtained mean haematology, clinical chemistry and urinalysis values did not reveal any test item-related changes in all the tested dose groups. The estimated serum T4 levels did not reveal any changes. The absolute and relative organ weights of both sexes did not reveal any changes from all the tested dose groups.
No treatment related gross pathological changes were noted in any of the animals from all the tested dose groups during necropsy, however in test item administered animals of both sexes, the contents of gastrointestinal tract were found to be violet in color which was attributed to the color of the test item and was considered as non-adverse effect as the mucosa of gastrointestinal tract was found to be within normal limits.
No treatment related microscopic findings noted in any of the tissues/organs subjected for histopathological evaluation from both high dose group and vehicle control group animals of both sexes.
There were no effects noted on reproductive performance of both sexes in all the tested dose groups. No test item-related irregularities observed in oestrus cyclicity of the females from all the tested dose groups during treatment period. No changes were noted in ‘at birth’ (delivery) and or ‘litter observations’ in all the tested dose groups. No effects were noted for live birth index and pup survival index in all the tested dose groups. No test item-related post-implantation losses were noted in all the tested dose groups.
There were no developmental/external behavioural changes noted and no test item-related mortalities noted during postnatal period in any of pups from all the tested dose group litters. The mean pup weight, mean anogenital distance and its ratio in either sex of pups per litter were un-affected by the test item in all the tested dose groups. There were no incidences of retention of nipples in male pups examined on PND 13 from all the tested dose and control group litters. The estimated serum T4 levels of PND 13 (from all litters) pups did not reveal any changes in all the tested dose group litters. There were no gross pathological changes noted in any of the pups during scheduled sacrifice from all the tested dose and control group litters
- Endpoint:
- repeated dose toxicity: oral, other
- Remarks:
- Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test by Oral Gavage in Sprague Dawley Rats
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 15 June 2021 to 22 December 2021
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Version / remarks:
- adopted on 29 July 2016
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
- Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Ambient (21 to 29ºC)
- Solubility and stability of the test substance in the solvent/vehicle: The test item was insoluble in distilled water and uniformly suspended in 0.5% w/v Carboxy Methyl Cellulose at the concentration of 100 mg/mL (the highest dose concentration selected for the study considering the dose volume of 10 mL/kg body weight) as per in-house solubility/suspendibility test results.
Hence, 0.5% w/v Carboxymethyl Cellulose was used as vehicle for test item formulations in consultation with sponsor.
0.5% w/v Carboxymethyl Cellulose is a routinely used and universally accepted vehicle of choice for the oral toxicity studies.
The test item was stable for 6 hours and 48 hours at room temperature in 0.5% w/v Carboxymethyl cellulose with the concentrations of 5 mg/mL and 100 mg/mL.
FORM AS APPLIED IN THE TEST: The test item or vehicle were administered to the animals through the oral (gavage) route once daily - Species:
- rat
- Strain:
- Sprague-Dawley
- 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 (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: Males: 254.36 to 291.64 g; Females: 200.54 to 211.92 g
- Housing: Animals were housed in a standard polypropylene cage (size: L 430 x B 285 x H 150 mm) with stainless steel mesh top grill having facilities for holding pelleted food and drinking water in water bottle fitted with stainless steel sipper tube. Clean sterilized paddy husk was provided as bedding material.
During acclimatization, two animals of same sex were housed.
i. Main Group Animals:
- Pre mating: Per cage two animals of same sex and group were housed.
- Cohabitation Period (mating): Per cage two animals (one male and one female) of same group were housed.
- Post-mating: After confirmation on presence of sperm in the vaginal smear (Day 0 of pregnancy), the mated pairs were separated. Males were housed with their former cage mates while females were housed individually. Sterilized paper shreds were provided as a nesting material for main group females from gestation day 20 onwards.
ii. Recovery Group Animals:
- Maximum of two animals per cage per group of same sex were housed, tunnels were provided as enrichment for the animals which were housed individually.
- Diet: Altromin maintenance diet for rats and mice (manufactured by Altromin Spezialfutter GmbH & Co. KG) was provided ad libitum to the animals throughout the experimental period.
- Water: Water was provided ad libitum throughout the experimental period. Deep bore-well water passed through reverse osmosis unit was provided in plastic water bottles with stainless steel sipper tubes.
- Acclimation period: 5 days
DETAILS OF FOOD AND WATER QUALITY: Analysis of food and water qaulity included as annexures in the study report.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.9 to 22.9 Degree Centigrade
- Humidity (%): 48 to 63%,
- 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: 24 June 2021; To: 16 September 2021 - Route of administration:
- oral: gavage
- Details on route of administration:
- The test item or vehicle were administered to the animals through the oral (gavage) route once daily.
- Vehicle:
- CMC (carboxymethyl cellulose)
- Remarks:
- 0.5% w/v CMC (carboxymethyl cellulose)
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
VEHICLE
- Justification for use and choice of vehicle (if other than water): The test item was insoluble in distilled water and uniformly suspended in 0.5% w/v Carboxy Methyl Cellulose at the concentration of 100 mg/mL (the highest dose concentration selected for the study considering the dose volume of 10 mL/kg body weight) as per in-house solubility/suspendibility test results.
Hence, 0.5% w/v Carboxymethyl Cellulose was used as vehicle for test item formulations in consultation with sponsor.
0.5% w/v Carboxymethyl Cellulose is a routinely used and universally accepted vehicle of choice for the oral toxicity studies
- Concentration in vehicle: The concentrations of of 0, 111, 333 and 1000 mg/kg body weight/day were selected as control, low, mid and high dose groups respectively
- Amount of vehicle (if gavage): 10mL/Kg body weight
- Batch no.: SLCH1520, expiry date: September 2026; Make Sigma Aldrich
- Purity: Medium viscocity grade - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The Dose formulation samples of the test item were analyzed for homogeneity and dose concentration by UV-Vis Method and the results are found within the range of 85 to 115% of the nominal concentration and the %RSD is <15%
Homogeneity and dose formulation analysis for dose concentration verification was performed during week 1 and week 5 of the treatment. The samples were collected in duplicates (5 mL each) from top, middle and bottom layers from low, mid and high dose concentrations and in duplicates from single layer from vehicle control.
The prepared test item formulations were stirred using magnetic stirrer during sampling.
The mean obtained results were within the range of 85 to 115% of the nominal concentration and the relative standard deviation (% RSD) is less than 15%. - Duration of treatment / exposure:
- Males: 31 Days
Females: The females were treated for a two-week pre-mating period (14-days), during mating, pregnancy (gestation) and up to lactation day 13 (ranging from a total period of 50 to 62 days).
The females with positive mating signal, but no-evidence of pregnancy / littering were treated during two-week pre-mating period, during mating and further 24 days from the day of positive mating signal (group G1 - one female until experimental day 39; group G2 - one female until experimental day 52, one female until experimental day 46; G3 - two females until experimental day 49; group G4 - one female until experimental day 39).
Recovery group animals: 52 Days - Frequency of treatment:
- Once Daily
- Dose / conc.:
- 0 other: mg/kg body weight/day
- Remarks:
- Vehicle Control
- Dose / conc.:
- 111 other: mg/kg body weight/day
- Remarks:
- Low Dose
- Dose / conc.:
- 333 other: mg/kg body weight/day
- Remarks:
- Mid Dose
- Dose / conc.:
- 1 000 other: mg/kg body weight/day
- Remarks:
- High Dose
- No. of animals per sex per dose:
- Main Group: 24 (12 Males + 12 Females)
Recovery Group: 10 (5 Males + 5 Females) - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: There was no information or data available from repeated dose/reproduction toxicity and teratology studies for the test item.
The doses of 0, 111, 333 and 1000 mg/kg body weight/day were selected as control, low, mid and high dose groups for the dose range finding study (BIO-DTX 056) in consultation with the sponsor.
There were no test item-related related changes noted in any of the systemic, reproduction and developmental parameters up to the dose level of 1000 mg/kg body weight/day in the Dose Range Finding Study (BIO-DTX 056).
Hence, the same doses of 0, 111, 333 and 1000 mg/kg body weight/day were selected as control, low, mid and high dose groups respectively, for the present study in consultation with the sponsor.
- 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 main and recovery groups using Microsoft Excel Spreadsheet, such that body weight variation of animals selected for the study does not exceed ±20% (Males: -6.80 to 11.14%; Females: -12.58 to 8.29%) of the mean body weight of each sex. The grouping was done one day prior to initiation of treatment. Body weight of the animals were analyzed statistically for mean body weight to rule out statistical significant differences between groups within each sex. - Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: All the animals were observed once daily for general clinical signs of toxicity. These observations were made approximately at the same time on each day after dose administration. All the animals were observed twice daily for mortality and morbidity.
- Cage side observations checked in table [No.1] were included.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: All the animals were subjected to detailed clinical examinations on day 1 before treatment and weekly thereafter during treatment. These observations were made outside the home cage and approximately at the same time.
BODY WEIGHT: Yes
- Time schedule for examinations: The main group males were weighed at receipt, on the first day of dosing, weekly thereafter and at termination.
The main group females were weighed at receipt, on the first day of dosing, weekly thereafter during pre-mating and until confirmation of mating. All the pregnant animals were weighed on gestation days (GD) 0, 7, 14 and 20 and on lactation days (LD) 1, 4, 7, 13 and 14 (terminal body weight). The non-pregnant animals were weighed weekly once until termination and the terminal body weights were recorded before scheduled sacrifice.
The recovery group animals were weighed at receipt, on the first day of dosing, weekly thereafter and at termination.
FOOD EFFICIENCY:
- Cage wise feed consumption was measured for all main group males and females, once in a week during premating period coinciding with body weight recording.
Cage wise feed consumption was measured for all pregnant animals during gestation day (GD) 0 to 7, 7 to 14 and 14 to 20, during lactation day (LD) 1 to 4, 4 to 7 and
7 to 13 coinciding with body weight recording.
Cage wise feed consumption was measured for all recovery group animals once in a week throughout the experimental period coinciding with body weight recording.
Average feed intake per animal (g/animal/day) was calculated using the amount of feed offered and left over in each cage and the number of rats per cage.
Feed consumption was not measured during following occasions, but offered ad libitum of feed:
- cohabitation period for both sexes of main groups;
- after GD 20 and until parturition for pregnant females;
- from day 20 after confirmation of mating until termination for non-pregnant females.
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Ophthalmological examination was carried out for all animals before initiation of treatment i.e. after grouping and randomization (last day of acclimatization). Ophthalmological examination was also carried out at the end of dosing period for all males (shortly prior to scheduled sacrifice, i.e. day 30) and during lactation period for females (shortly prior to scheduled sacrifice, i.e. on lactation day 13) and during last week (i.e. day 65) for the recovery group animals.
- Dose groups that were examined: G1/G1R, G2, G3 and G4/G4R.
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Blood samples of both males and females were collected on the day of scheduled terminal sacrifice (for main group males after completion of 31 days of dose administration, for main group females on lactation day 14 and for recovery group animals on the day of scheduled sacrifice.
- Anaesthetic used for blood collection: Yes
- Animals fasted: Yes
- How many animals: 12 Males and 12 Femles from all the main groups; 5 Males and 5 Females from all the recovery groups.
- Parameters checked in table [No.16] were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Blood samples of both males and females were collected on the day of scheduled terminal sacrifice (for main group males after completion of 31 days of dose administration, for main group females on lactation day 14 and for recovery group animals on the day of scheduled sacrifice.
- Animals fasted: Yes
- How many animals: 12 Males and 12 Femles from all the main groups; 5 Males and 5 Females from all the recovery groups.
- Parameters checked in table [No.17] were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: Urine was collected from five randomly selected males of each main group and for all recovery animals at termination. The selected animals were placed in urine collection cages overnight and not given access to feed but water was provided ad libitum during their stay in the urine collection cages. The overnight urine volume (mL) collected from these animals were measured.
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- Parameters checked in table [No.18] were examined.
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: Neurological/Functional examination was performed for five males and five females, randomly selected from each group, towards the end of the dosing period for males (shortly prior to scheduled sacrifice, i.e. on day 30) and during the lactation period for females (shortly prior to scheduled sacrifice, i.e. on lactation day 13). Neurological/Functional examination was performed for all recovery group animals towards the end of the recovery period (shortly prior to scheduled sacrifice, i.e.
on day 65.
- Dose groups that were examined: G1/G1R, G2, G3 and G4/G4R.
- Battery of functions tested: sensory activity, grip strength, motor activity and Hindlimb Footsplay.
Thyroid Hormone Estimations: Blood collection for Thyroxine (T4) Level estimation: Blood samples were collected from all the main group animals for measurement of serum T4 levels on the following schedule:
- All dams at termination (lactation day 14).
- All adult males, at termination (after completion of 31 days of treatment).
The assessment of serum T4 levels was performed for adult males. Further assessment of T4 levels in serum samples from the dams was not assessed as there were no treatment-related effects observed in the T4 levels of adult males.
The collected blood samples were centrifuged at 5000 rpm for 10 minutes; the serum was separated and stored at freezing conditions (-80ºC ± 10ºC) till estimation.
The serum samples were estimated for thyroid hormonal levels (Thyroxine - T4) by the ELISA method using commercial assay kits. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Statistics:
- The statistical analysis tests followed for the interpretation of data are as mentioned below:
• Body weight (weekly/gestation/lactation)
• Percent Change in body weight (weekly/gestation/lactation)
• Feed consumption (weekly/gestation/lactation)
• Hematology
• Clinical chemistry
• Urinalysis
• Absolute/relative organ weights
• Functional Observation parameters
• Thyroid hormonal levels - Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no clinical signs of toxicity recorded in any of the animals of both sexes from all the tested dose groups throughout the experimental period. However, dark purple colored faeces were noted from day 2 observation throughout the experiment period till termination of treatment in group G3 & G4/G4R animals. This coloration was due to colored nature of the test item but not any adverse signs.
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food efficiency:
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Other effects:
- no effects observed
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- behaviour (functional findings)
- body weight and weight gain
- clinical biochemistry
- clinical signs
- food efficiency
- gross pathology
- haematology
- histopathology: non-neoplastic
- mortality
- ophthalmological examination
- organ weights and organ / body weight ratios
- urinalysis
- other: THyroid hormonal lelves
- Key result
- Critical effects observed:
- no
- Conclusions:
- In conclusion, the oral administration of test item over the time of the study, carried out according to the OECD guideline 422 (for main group males with a total of 31 days, for main group females ranging from 50 to 62 days and for recovery group animals with a total period of 52 days) did not produce any indication of systemic, reproduction and developmental toxicity at the dose levels of 111, 333 and 1000 mg/kg body weight/day under experimental conditions employed.
Therefore, the no-observed-adverse-effect-level (NOAEL) of test item is considered as 1000 mg/kg body weight for systemic, reproduction and developmental toxicity end points. - Executive summary:
The objective of this Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test of the test item 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 an estimate of the No Observed Adverse Effect Level (NOAEL).
A total of 116 (58 males + 58 females) Sprague Dawley rats were selected for the study and distributed to four main (G1, G2, G3 and G4) and two recovery groups (G1R and G4R). Each main group consisted of 12 males and 12 females and each recovery group consisted of 5 males and 5 females. The animals in group G1/G1R were administered with vehicle [0.5% w/v Carboxymethyl Cellulose], animals in groups G2, G3 and G4/G4R were administered with test item at the dose levels of 111, 333 and 1000 mg/kg body weight/day for low, mid and high/high dose recovery, 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.All the main group males were administered with test item during pre-mating (14-days), during mating and during post-mating period (total of 31 days). The pregnant females from main groups were administered with test item during pre-mating (14-days), during mating, pregnancy (gestation) and up to lactation day 13.The females with positive mating signal, but no-evidence of pregnancy / litteringwere administered with test itemduringpre-mating (14-days),during mating, and further 24 days from the day of positive mating signal. All the recovery group animals were administered with test item for 50 days followed by a 14-day observation period without treatment.
The test item formulations werestable for 6 hours and 48 hours at room temperature in 0.5% w/v Carboxymethyl Cellulose with the concentrations of 5 mg/mL and 100 mg/mL.The homogeneity and dose form concentration analysis for preparedtest item formulations during treatment periodwas performed during week 1 and 5 and the mean results were within the range of 85 to 115% of the nominal concentration and the relative standard deviation (% RSD) is less than 15%.
For systemic toxicity assessment, all the animals (main and recovery groups) 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 animals (main and recovery groups) 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 animals of both sexes were recorded once in a week during pre-mating for main groups and throughout the experimental period for recovery groups. 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.Ophthalmological examination was carried out once before treatment and at the end of the dosing period for all males and females (main and recovery groups). Neurological/functional observations were performed for five randomly selected males and females from each main group, for all animals from recovery groups towards end of the dosing period. The investigations of haematology and clinical chemistry for all animals (main and recovery groups), investigations of urinalysis for five randomly selected males from each main group and for all recovery groups animals was conducted at termination. Serum thyroxine hormone (T4) levels were estimated for all main group males by ELISA. The organs were collected and weighed on the day of termination for all animals (main and recovery groups) of both sexes and organ weight relative to terminal body weight was calculated. All the animals (main and recovery groups) of both sexes were observed for both external and internal gross pathological changes during conduct of necropsy. Histopathological examination was conducted on all 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.
For reproductive toxicity assessment, all the males (main groups) were evaluated for reproductive performances such as, mating and fertility indices. All the females (main groups) 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.
There were no clinical signs of toxicity and no mortality/morbidity noted in any of the animals from all the tested dose groups, howeverdark purple colored faeces were noted from day 2 observation throughout the experiment period till termination of treatment in group G3 & G4/G4Ranimals. This coloration is due to colored nature of the test item but not any adverse sign. Detailed clinical examination did not reveal any changes in any of the tested dose group animals. No changes noted in mean body weight, percent change in mean body weight gain and mean feed consumption in all the tested dose groups of both sexes. The ophthalmological examination and neurological/functional examinations did not reveal any test item-related changes in any of the animals from all the tested dose groups of both sexes. The obtained mean haematology, clinical chemistry and urinalysis values did not reveal any test item-related changes in all the tested dose groups. The estimated serum T4 levels did not reveal any changes. The absolute and relative organ weights of both sexes did not reveal any changes from all the tested dose groups.
No treatment related gross pathological changes were noted in any of the animals from all the tested dose groups during necropsy, however in test item administered animals of both sexes, the contents of gastrointestinal tract were found to be violet in color which was attributed to the color of the test item and was considered as non-adverse effect as the mucosa of gastrointestinal tract was found to be within normal limits.
No treatment related microscopic findings noted in any of the tissues/organs subjected for histopathological evaluation from both high dose group and vehicle control group animals of both sexes.
There were no effects noted on reproductive performance of both sexes in all the tested dose groups. No test item-related irregularities observed in oestrus cyclicity of the females from all the tested dose groups during treatment period. No changes were noted in ‘at birth’ (delivery) and or ‘litter observations’ in all the tested dose groups. No effects were noted for live birth index and pup survival index in all the tested dose groups. No test item-related post-implantation losses were noted in all the tested dose groups.
There were no developmental/external behavioural changes noted and no test item-related mortalities noted during postnatal period in any of pups from all the tested dose group litters. The mean pup weight, mean anogenital distance and its ratio in either sex of pups per litter were un-affected by the test item in all the tested dose groups. There were no incidences of retention of nipples in male pups examined on PND 13 from all the tested dose and control group litters. The estimated serum T4 levels of PND 13 (from all litters) pups did not reveal any changes in all the tested dose group litters. There were no gross pathological changes noted in any of the pups during scheduled sacrifice from all the tested dose and control group litters
Referenceopen allclose all
TABLE 1. SUMMARY
OF CLINICAL SIGNS OF TOXICITY, DETAILED CLINICAL EXAMINATION AND
MORTALITY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total No. of Animals |
Clinical Signs of Toxicitya: Observation |
Detailed Clinical Examinationb: Observation |
Mortalityc: No. of Mortalities |
G1, M & 0 |
12 |
N (12) |
NAD (12) |
0 (12) |
G2, M & 111 |
12 |
N (12) |
NAD (12) |
0 (12) |
G3, M & 333 |
12 |
N (12) |
NAD (12) |
0 (12) |
G4, M & 1000 |
12 |
N (12) |
NAD (12) |
0 (12) |
M:
Male; N: Normal; NAD: No Abnormality Detected.
a: observed once daily; b: observed once weekly; c: observed twice daily.
Note:Dark purple colored faeces were noted from day 2 observation throughout the experiment period till termination in group G3 & G4 animals.
TABLE 1 (Contd…). SUMMARY
OF CLINICAL SIGNS OF TOXICITY, DETAILED CLINICAL EXAMINATION
AND MORTALITY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total No. of Animals |
Clinical Signs of Toxicitya: Observation |
Detailed Clinical Examinationb: Observation |
Mortalityc: No. of Mortalities |
G1, F & 0 |
12 |
N (12) |
NAD (12) |
0 (12) |
G2, F & 111 |
12 |
N (12) |
NAD (12) |
0 (12) |
G3, F & 333 |
12 |
N (12) |
NAD (12) |
0 (12) |
G4, F & 1000 |
12 |
N (12) |
NAD (12) |
0 (12) |
F:
Female; N: Normal; NAD: No Abnormality Detected.
a: observed once daily; b: observed once weekly; c: observed twice daily.
Note:Dark purple colored faeces were noted from day 2 observation throughout the experiment period till termination in group G3 & G4 animals.
TABLE 1 (Contd…). SUMMARY
OF CLINICAL SIGNS OF TOXICITY, DETAILED CLINICAL EXAMINATION
AND MORTALITY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total No. of Animals |
Clinical Signs of Toxicitya: Observation |
Detailed Clinical Examinationb: Observation |
Mortalityc: No. of Mortalities |
G1R, M & 0 |
5 |
N (5) |
NAD (5) |
0 (5) |
G4R, M & 1000 |
5 |
N (5) |
NAD (5) |
0 (5) |
G1R, F & 0 |
5 |
N (5) |
NAD (5) |
0 (5) |
G4R, F & 1000 |
5 |
N (5) |
NAD (5) |
0 (5) |
M:
Male; F: Female; R: Recovery; N: Normal; NAD: No abnormality detected.
a: observed once daily; b: observed once weekly; c: observed twice daily.
Note:Dark purple colored faeces were noted from day 2 throughout the experiment period till termination in group G4R animals.
TABLE 2. SUMMARY OF BODY WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Body Weight (g) on Day |
|||||
1 |
7 |
14 |
21 |
28 |
|||
G1, M & 0 |
Mean |
400.75 |
421.20 |
438.19 |
446.01 |
458.77 |
|
±SD |
22.07 |
32.34 |
36.49 |
37.08 |
38.53 |
||
n |
12 |
12 |
12 |
12 |
12 |
||
G2, M & 111 |
Mean |
401.74 |
417.26 |
433.41 |
442.75 |
452.56 |
|
±SD |
20.39 |
24.35 |
30.70 |
31.29 |
30.16 |
||
n |
12 |
12 |
12 |
12 |
12 |
||
G3, M & 333 |
Mean |
402.72 |
419.51 |
438.54 |
444.84 |
456.36 |
|
±SD |
19.35 |
23.54 |
30.11 |
27.23 |
24.95 |
||
n |
12 |
12 |
12 |
12 |
12 |
||
G4, M & 1000 |
Mean |
401.99 |
422.76 |
443.74 |
453.94 |
463.38 |
|
±SD |
21.50 |
27.21 |
34.32 |
36.83 |
39.17 |
||
n |
12 |
12 |
12 |
12 |
12 |
||
M: Male; SD: Standard Deviation; n: Number of Animals.
TABLE 2 (Contd…). SUMMARY OF BODY WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Body Weight (g) on Day |
||||
1 |
7 |
14 |
21# |
|||
G1, F & 0 |
Mean |
250.88 |
257.35 |
267.91 |
280.34 |
|
±SD |
14.86 |
17.17 |
18.25 |
26.26 |
||
n |
12 |
12 |
12 |
3 |
||
G2, F & 111 |
Mean |
251.05 |
256.43 |
266.53 |
272.56 |
|
±SD |
12.78 |
15.62 |
15.30 |
25.98 |
||
n |
12 |
12 |
12 |
3 |
||
G3, F & 333 |
Mean |
251.13 |
256.32 |
261.08 |
260.46 |
|
±SD |
13.59 |
14.00 |
15.94 |
17.45 |
||
n |
12 |
12 |
12 |
4 |
||
G4, F & 1000 |
Mean |
251.24 |
261.46 |
265.51 |
269.05 |
|
±SD |
15.56 |
18.91 |
20.71 |
24.37 |
||
n |
12 |
12 |
12 |
4 |
||
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 body weight was not subjected to statistical analysis due to uneven number of variables.
TABLE 2 (Contd…). SUMMARY OF BODY WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Body Weight (g) on Day |
||||||||||
1 |
7 |
14 |
21 |
28 |
35 |
42 |
49 |
56 |
63 |
|||
G1R, M & 0 |
Mean |
395.45 |
407.17 |
422.63 |
436.11 |
448.75 |
458.35 |
473.23 |
489.33 |
502.87 |
514.37 |
|
±SD |
21.72 |
21.10 |
31.29 |
32.45 |
32.78 |
34.62 |
33.67 |
33.58 |
34.92 |
37.99 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, M & 1000 |
Mean |
396.36 |
412.35 |
430.15 |
444.31 |
454.98 |
464.82 |
475.04 |
493.68 |
508.20 |
519.69 |
|
±SD |
20.86 |
20.17 |
12.53 |
16.96 |
17.27 |
14.72 |
15.50 |
9.28 |
11.65 |
11.69 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G1R, F & 0 |
Mean |
245.24 |
250.97 |
262.44 |
268.72 |
277.56 |
284.92 |
295.96 |
306.72 |
315.86 |
324.75 |
|
±SD |
10.97 |
10.11 |
13.68 |
15.80 |
15.60 |
15.72 |
19.40 |
19.59 |
17.41 |
15.21 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, F & 1000 |
Mean |
245.66 |
248.99 |
264.41 |
270.43 |
278.43 |
286.33 |
298.35 |
308.32 |
318.51 |
327.87 |
|
±SD |
12.82 |
12.43 |
13.84 |
12.16 |
11.19 |
12.10 |
12.79 |
13.72 |
10.97 |
12.44 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals.
TABLE 3. SUMMARY RECORD OF GESTATION BODY WEIGHT (g)
Group, Sex & Dose (mg/kg body weight/day) |
Body Weight (g) on Gestation Day (GD) |
||||
0 |
7 |
14 |
20 |
||
G1, F & 0 |
Mean |
272.42 |
287.38 |
319.92 |
375.62 |
±SD |
18.33 |
21.41 |
28.89 |
35.87 |
|
n |
11 |
11 |
11 |
11 |
|
G2, F & 111 |
Mean |
269.81 |
286.87 |
328.45 |
391.71 |
±SD |
11.98 |
12.37 |
15.11 |
22.46 |
|
n |
10 |
10 |
10 |
10 |
|
G3, F & 333 |
Mean |
264.91 |
282.42 |
317.51 |
369.85 |
±SD |
15.69 |
14.58 |
20.68 |
32.90 |
|
n |
10 |
10 |
10 |
10 |
|
G4, F & 1000 |
Mean |
273.49 |
291.35 |
327.07 |
382.89 |
±SD |
17.37 |
17.37 |
23.26 |
39.30 |
|
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.
TABLE 4. SUMMARY RECORD OF LACTATION BODY WEIGHT (g)
Group, Sex & Dose (mg/kg body weight/day) |
Body Weight (g) on Lactation Day (LD) |
||||
1 |
4 |
7 |
13 |
||
G1, F & 0 |
Mean |
294.60 |
300.48 |
308.18 |
323.25 |
±SD |
22.07 |
22.28 |
22.06 |
20.39 |
|
n |
11 |
11 |
11 |
11 |
|
G2, F & 111 |
Mean |
306.24 |
309.48 |
314.78 |
330.57 |
±SD |
22.46 |
21.39 |
20.72 |
19.26 |
|
n |
10 |
10 |
10 |
10 |
|
G3, F & 333 |
Mean |
293.35 |
297.31 |
304.48 |
319.65 |
±SD |
19.47 |
20.23 |
20.46 |
22.22 |
|
n |
10 |
10 |
10 |
10 |
|
G4, F & 1000 |
Mean |
303.31 |
306.82 |
313.01 |
325.64 |
±SD |
22.77 |
24.10 |
23.73 |
23.27 |
|
n |
11 |
11 |
11 |
11 |
|
F: Female; SD: Standard Deviation; n: Number of Dams.
TABLE 5. SUMMARY
OF PERCENT CHANGE IN BODY WEIGHT GAIN (%)
WITH RESPECT TO DAY 1 RECORD
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, M & 0 |
Mean |
5.01 |
9.25 |
11.19 |
14.36 |
|
±SD |
3.10 |
4.96 |
4.86 |
4.98 |
||
n |
12 |
12 |
12 |
12 |
||
G2, M & 111 |
Mean |
3.84 |
7.80 |
10.13 |
12.59 |
|
±SD |
2.04 |
3.09 |
3.48 |
3.20 |
||
n |
12 |
12 |
12 |
12 |
||
G3, M & 333 |
Mean |
4.15 |
8.89 |
10.50 |
13.42 |
|
±SD |
2.15 |
5.14 |
5.14 |
5.61 |
||
n |
12 |
12 |
12 |
12 |
||
G4, M & 1000 |
Mean |
5.12 |
10.29 |
12.82 |
15.16 |
|
±SD |
1.91 |
3.83 |
4.55 |
5.27 |
||
n |
12 |
12 |
12 |
12 |
||
M: Male; SD: Standard Deviation; n: Number of Animals.
TABLE 5 (Contd…). SUMMARY OF PERCENTCHANGE IN BODY WEIGHT GAIN (%) WITH RESPECT TO DAY 1 RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Percent Change in Body Weight (%) during Day |
|||
1 to 7 |
1 to 14 |
1 to 21# |
|||
G1, F & 0 |
Mean |
2.56 |
6.78 |
10.07 |
|
±SD |
2.21 |
3.23 |
3.01 |
||
n |
12 |
12 |
3 |
||
G2, F & 111 |
Mean |
2.12 |
6.21 |
9.94 |
|
±SD |
2.46 |
4.16 |
1.49 |
||
n |
12 |
12 |
3 |
||
G3, F & 333 |
Mean |
2.08 |
3.94 |
5.98 |
|
±SD |
1.81 |
2.08 |
1.64 |
||
n |
12 |
12 |
4 |
||
G4, F & 1000 |
Mean |
4.05 |
5.61 |
9.37 |
|
±SD |
3.24 |
3.20 |
3.75 |
||
n |
12 |
12 |
4 |
||
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.
TABLE 5 (Contd…). SUMMARY OF PERCENT CHANGE IN BODY WEIGHT GAIN (%) WITH RESPECT TO DAY1 RECORD
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 |
1 to 42 |
1 to 49 |
1 to 56 |
1 to 63 |
|||
G1R, M & 0 |
Mean |
2.98 |
6.83 |
10.25 |
13.47 |
15.92 |
19.69 |
23.73 |
27.13 |
30.00 |
|
±SD |
0.92 |
4.09 |
4.67 |
5.29 |
6.27 |
5.81 |
4.88 |
4.25 |
4.30 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, M & 1000 |
Mean |
4.06 |
8.66 |
12.20 |
14.91 |
17.44 |
20.09 |
24.77 |
28.45 |
31.32 |
|
±SD |
1.73 |
3.60 |
3.33 |
3.84 |
4.90 |
6.78 |
5.51 |
6.10 |
5.14 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G1R, F & 0 |
Mean |
2.35 |
7.00 |
9.55 |
13.20 |
16.19 |
20.62 |
25.02 |
28.77 |
32.44 |
|
±SD |
0.72 |
2.36 |
3.15 |
4.61 |
4.45 |
4.14 |
4.54 |
3.55 |
3.44 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, F & 1000 |
Mean |
1.37 |
7.66 |
10.20 |
13.45 |
16.65 |
21.52 |
25.60 |
29.78 |
33.57 |
|
±SD |
1.07 |
2.71 |
4.80 |
4.07 |
3.73 |
3.02 |
4.10 |
3.75 |
3.31 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals.
TABLE 6. SUMMARY RECORD OF PERCENT CHANGE IN BODY WEIGHT GAIN (%) DURING GESTATION PERIOD
Group, Sex & Dose (mg/kg body weight/day) |
Percent Change in Body Weight Gain (%) during Gestation Day (GD) |
|||
0 to 7 |
7 to 14 |
14 to 20 |
||
G1, F & 0 |
Mean |
5.46 |
11.22 |
17.44 |
±SD |
1.77 |
2.82 |
4.18 |
|
n |
11 |
11 |
11 |
|
G2, F & 111 |
Mean |
6.35 |
14.52 |
19.23 |
±SD |
2.12 |
3.20 |
3.16 |
|
n |
10 |
10 |
10 |
|
G3, F & 333 |
Mean |
6.67 |
12.40 |
16.35 |
±SD |
1.92 |
3.55 |
3.43 |
|
n |
10 |
10 |
10 |
|
G4, F & 1000 |
Mean |
6.56 |
12.23 |
16.88 |
±SD |
1.60 |
3.35 |
4.81 |
|
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.
TABLE 7. SUMMARY RECORD OF PERCENT CHANGE IN BODY WEIGHT GAIN (%) DURING LACTATION PERIOD
Group, Sex & Dose (mg/kg body weight/day) |
Percent Change in Body Weight Gain (%) during Lactation Day (LD) |
|||
1 to 4 |
4 to 7 |
7 to 13 |
||
G1, F & 0 |
Mean |
2.01 |
2.58 |
4.96 |
±SD |
0.96 |
0.73 |
1.51 |
|
n |
11 |
11 |
11 |
|
G2, F & 111 |
Mean |
1.08 |
1.74 |
5.07 |
±SD |
0.86 |
0.95 |
1.60 |
|
n |
10 |
10 |
10 |
|
G3, F & 333 |
Mean |
1.35 |
2.42 |
4.98 |
±SD |
0.95 |
1.29 |
1.32 |
|
n |
10 |
10 |
10 |
|
G4, F & 1000 |
Mean |
1.14 |
2.04 |
4.06 |
±SD |
1.00 |
0.93 |
0.83 |
|
n |
11 |
11 |
11 |
|
F: Female; SD: Standard Deviation; n: Number of Dams.
TABLE 8. SUMMARY OF FEED CONSUMPTION (g/animal/day) RECORD
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 |
21.31 |
24.01 |
±SD |
2.38 |
1.81 |
|
n |
12 (6) |
12 (6) |
|
G2, M & 111 |
Mean |
21.39 |
23.12 |
±SD |
1.76 |
0.75 |
|
n |
12 (6) |
12 (6) |
|
G3, M & 333 |
Mean |
22.25 |
23.93 |
±SD |
2.39 |
1.85 |
|
n |
12 (6) |
12 (6) |
|
G4, M & 1000 |
Mean |
22.28 |
24.17 |
±SD |
1.23 |
0.67 |
|
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
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 |
18.14 |
19.17 |
±SD |
1.56 |
1.22 |
|
n |
12 (6) |
12 (6) |
|
G2, F & 111 |
Mean |
17.79 |
20.11 |
±SD |
1.85 |
1.70 |
|
n |
12 (6) |
12 (6) |
|
G3, F & 333 |
Mean |
18.26 |
19.22 |
±SD |
1.99 |
1.31 |
|
n |
12 (6) |
12 (6) |
|
G4, F & 1000 |
Mean |
18.43 |
20.07 |
±SD |
2.28 |
1.22 |
|
n |
12 (6) |
12 (6) |
|
F: Female; SD: Standard Deviation; n: Number of Animals (Number of cages).
TABLE 8 (Contd…). SUMMARY OF FEED CONSUMPTION (g/animal/day) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Feed Consumption (g/animal/day) |
||||||||
Week 1 |
Week 2 |
Week 3 |
Week 4 |
Week 5 |
Week 6 |
Week 7 |
Week 8 |
Week 9 |
||
G1R, M & 0 |
Mean |
23.52 |
24.34 |
25.11 |
26.35 |
27.86 |
29.05 |
30.75 |
31.83 |
32.47 |
±SD |
3.71 |
1.67 |
1.55 |
1.27 |
0.97 |
1.11 |
0.47 |
3.66 |
3.01 |
|
n |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
|
G4R, M & 1000 |
Mean |
22.84 |
23.75 |
24.26 |
27.17 |
28.86 |
30.05 |
31.07 |
32.19 |
33.03 |
±SD |
0.77 |
1.04 |
1.34 |
2.09 |
2.61 |
2.18 |
2.12 |
1.59 |
1.67 |
|
n |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
|
G1R, F & 0 |
Mean |
17.44 |
18.36 |
19.45 |
10.21 |
23.17 |
24.20 |
25.35 |
26.19 |
27.04 |
±SD |
1.79 |
0.40 |
0.40 |
9.72 |
0.99 |
0.82 |
0.62 |
0.41 |
0.99 |
|
n |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
|
G4R, F & 1000 |
Mean |
17.21 |
19.05 |
20.42 |
11.29 |
24.18 |
25.37 |
26.19 |
27.14 |
27.89 |
±SD |
0.69 |
1.77 |
0.91 |
10.38 |
0.03 |
0.80 |
0.84 |
0.69 |
0.68 |
|
n |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
|
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals(Number of cages).
TABLE 9. SUMMARY RECORD OF FEED CONSUMPTION (g/animal/day) DURING GESTATION PERIOD
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 |
19.02 |
21.07 |
25.81 |
SD |
0.70 |
1.95 |
1.63 |
|
n |
11 |
11 |
11 |
|
G2, F & 111 |
Mean |
19.23 |
22.20 |
26.84 |
SD |
0.88 |
1.81 |
1.78 |
|
n |
10 |
10 |
10 |
|
G3, F & 333 |
Mean |
19.00 |
21.49 |
26.11 |
SD |
0.74 |
1.39 |
1.26 |
|
n |
10 |
10 |
10 |
|
G4, F & 1000 |
Mean |
19.43 |
22.01 |
26.67 |
SD |
0.58 |
1.70 |
1.97 |
|
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.
TABLE 10. SUMMARY RECORD OF FEED CONSUMTION (g/animal/day) DURING LACTATION PERIOD
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 |
25.21 |
35.80 |
40.88 |
SD |
1.20 |
7.26 |
1.43 |
|
n |
11 |
11 |
11 |
|
G2, F & 111 |
Mean |
24.58 |
32.72 |
41.09 |
SD |
1.34 |
0.99 |
0.98 |
|
n |
10 |
10 |
10 |
|
G3, F & 333 |
Mean |
25.11 |
32.75 |
40.54 |
SD |
1.42 |
1.16 |
0.94 |
|
n |
10 |
10 |
10 |
|
G4, F & 1000 |
Mean |
23.94 |
33.14 |
39.84 |
SD |
5.99 |
1.28 |
1.03 |
|
n |
11 |
11 |
11 |
|
F: Female; SD: Standard Deviation; n: Number of Dams.
TABLE 11. SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day -1 (Grouping and randomization) |
||||||||
Group, Sex & Dose weight/day) → |
G1, M & 0 |
G2, M & 111 |
G3, M & 333 |
G4, M & 1000 |
||||
Number of Animals→ |
12 |
12 |
12 |
12 |
||||
Observations↓ |
||||||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
N |
N |
N |
N |
M: Male; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day -1 (Grouping and randomization) |
||||||||
Group, Sex & Dose weight/day) → |
G1, F & 0 |
G2, F & 111 |
G3, F & 333 |
G4, F & 1000 |
||||
Number of Animals→ |
12 |
12 |
12 |
12 |
||||
Observations↓ |
||||||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
N |
N |
N |
N |
F: Female; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day -1 (Grouping and randomization) |
||||
Group, Sex & Dose weight/day) → |
G1R, M & 0 |
G4R, M & 1000 |
||
Number of Animals→ |
5 |
5 |
||
Observations↓ |
||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
M: Male; R: Recovery; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day -1 (Grouping and randomization) |
||||
Group, Sex & Dose weight/day) → |
G1R, F & 0 |
G4R, F & 1000 |
||
Number of Animals→ |
5 |
5 |
||
Observations↓ |
||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
F: Female; R: Recovery; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day 30 |
||||||||
Group, Sex & Dose weight/day) → |
G1, M & 0 |
G2, M & 111 |
G3, M & 333 |
G4, M & 1000 |
||||
Number of Animals→ |
12 |
12 |
12 |
12 |
||||
Observations↓ |
||||||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
N |
N |
N |
N |
Other findings: |
N |
N |
N |
N |
N |
N |
N |
N |
M: Male; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Pregnant/Littered females: Lactation day 13; Non-pregnant females: (Experimental day 39 to 52) |
||||||||
Group, Sex & Dose weight/day) → |
G1, F & 0 |
G2, F & 111 |
G3, F & 333 |
G4, F & 1000 |
||||
Number of Animals→ |
12 |
12 |
12 |
12 |
||||
Observations↓ |
||||||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
N |
N |
N |
N |
Other findings: |
N |
N |
N |
N |
N |
N |
N |
N |
F: Female; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day 65 |
||||
Group, Sex & Dose weight/day) → |
G1R, M & 0 |
G4R, M & 1000 |
||
Number of Animals→ |
5 |
5 |
||
Observations↓ |
||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
Other findings: |
N |
N |
N |
N |
M: Male; R: Recovery; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day 65 |
||||
Group, Sex & Dose weight/day) → |
G1R, F & 0 |
G4R, F & 1000 |
||
Number of Animals→ |
5 |
5 |
||
Observations↓ |
||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
Other findings: |
N |
N |
N |
N |
F: Female; R: Recovery; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 12. SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD
Day 30 |
||||||
Parameters↓ |
Group & Sex |
G1 & M |
G2 & M |
G3 & M |
G4 & M |
|
Dose (mg/kg body weight/day) |
0 |
111 |
333 |
1000 |
||
Number of Animals (randomly selected) |
5 |
5 |
5 |
5 |
||
Home Cage Observations |
||||||
Home cage posture |
1 |
1 |
1 |
1 |
||
Respiratory pattern |
1 |
1 |
1 |
1 |
||
Clonic involuntary movements |
1 |
1 |
1 |
1 |
||
Tonic involuntary movements |
1 |
1 |
1 |
1 |
||
Vocalization |
1 |
1 |
1 |
1 |
||
Palpebral closure |
1 |
1 |
1 |
1 |
||
Handling Observations |
||||||
Ease of removal from the cage |
2 |
2 |
2 |
2 |
||
Ease of handling animal in hand |
2 |
2 |
2 |
2 |
||
Red or crusty deposits |
Eyes |
1 |
1 |
1 |
1 |
|
Nose |
1 |
1 |
1 |
1 |
||
Mouth |
1 |
1 |
1 |
1 |
||
Lacrimation |
1 |
1 |
1 |
1 |
||
Salivation |
1 |
1 |
1 |
1 |
||
Fur appearance |
1 |
1 |
1 |
1 |
||
Piloerection |
1 |
1 |
1 |
1 |
||
Eye prominence |
1 |
1 |
1 |
1 |
||
Muscle tone |
1 |
1 |
1 |
1 |
||
Home Cage Observations:Home cage posture - 1=Normal; Respiratory pattern - 1=Normal; Clonic involuntary movements - 1=None; Tonic involuntary movements - 1=None; Vocalization - 1=None; Palpebral closure - 1=Normal;Handling Observations:Ease of removal from the cage - 2=Normal; Ease of handling animal in hand - 2=Normal; Red or crusty deposits - 1=Absent; Lacrimation - 1=None; Salivation- 1=None; Fur appearance - 1=Normal; Piloerection - 1=None; Eye Prominence - 1=Normal; Muscle tone - 1=Normal |
||||||
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD
Day 30 |
||||||
Parameters↓ |
Group & Sex |
G1 & M |
G2 & M |
G3 & M |
G4 & M |
|
Dose (mg/kg body weight/day) |
0 |
111 |
333 |
1000 |
||
Number of Animals (randomly selected) |
5 |
5 |
5 |
5 |
||
Open Field Observations |
||||||
Mobility |
1 |
1 |
1 |
1 |
||
Gait |
1 |
1 |
1 |
1 |
||
Arousal |
3 |
3 |
3 |
3 |
||
Number of rearing |
Mean |
4.4 |
4.8 |
4.8 |
4.8 |
|
±SD |
1.1 |
0.8 |
0.8 |
0.8 |
||
Number of urine pools |
Mean |
3.4 |
3.8 |
3.8 |
3.8 |
|
±SD |
0.5 |
0.8 |
0.8 |
0.8 |
||
Number of defecations |
Mean |
3.4 |
3.2 |
3.4 |
3.2 |
|
±SD |
0.5 |
0.8 |
0.5 |
0.4 |
||
Clonic involuntary movement |
1 |
1 |
1 |
1 |
||
Tonic involuntary movement |
1 |
1 |
1 |
1 |
||
Stereotype behaviour |
1 |
1 |
1 |
1 |
||
Number of grooming |
Mean |
3.4 |
3.2 |
3.4 |
3.2 |
|
±SD |
0.5 |
0.8 |
0.5 |
0.8 |
||
Sensory Observations |
||||||
Approach response |
2 |
2 |
2 |
2 |
||
Auditory response |
2 |
2 |
2 |
2 |
||
Touch response |
2 |
2 |
2 |
2 |
||
Pupil reflex |
2 |
2 |
2 |
2 |
||
Tail pinch response |
2 |
2 |
2 |
2 |
||
Righting reflex |
1 |
1 |
1 |
1 |
||
Physiological Observation |
||||||
Body temperature (°F) |
Mean |
98.4 |
98.4 |
98.1 |
98.4 |
|
±SD |
0.5 |
0.4 |
0.3 |
0.5 |
||
Open Field Observations: Mobility- 1=Normal;Gait- 1=Normal;Arousal- 3=Normal;Clonic involuntary movement- 1=None;Tonic involuntary movement -1=None;Stereotype behaviour -1=Absent;Sensory Observations:Approach response- 2=Normal;Auditory response- 2=Normal;Touch response -2=Normal;Pupil reflex- 2=Normal;Tail pinch response- 2=Normal;Righting reflex- 1=Present |
||||||
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)
Lactation Day 13 |
||||||
Parameters↓ |
Group & Sex |
G1 & F |
G2 & F |
G3 & F |
G4 & F |
|
Dose (mg/kg body weight/day) |
0 |
111 |
333 |
1000 |
||
Number of Animals (randomly selected) |
5 |
5 |
5 |
5 |
||
Home Cage Observations |
||||||
Home cage posture |
1 |
1 |
1 |
1 |
||
Respiratory pattern |
1 |
1 |
1 |
1 |
||
Clonic involuntary movements |
1 |
1 |
1 |
1 |
||
Tonic involuntary movements |
1 |
1 |
1 |
1 |
||
Vocalization |
1 |
1 |
1 |
1 |
||
Palpebral closure |
1 |
1 |
1 |
1 |
||
Handling Observations |
||||||
Ease of removal from the cage |
2 |
2 |
2 |
2 |
||
Ease of handling animal in hand |
2 |
2 |
2 |
2 |
||
Red or crusty deposits |
Eyes |
1 |
1 |
1 |
1 |
|
Nose |
1 |
1 |
1 |
1 |
||
Mouth |
1 |
1 |
1 |
1 |
||
Lacrimation |
1 |
1 |
1 |
1 |
||
Salivation |
1 |
1 |
1 |
1 |
||
Fur appearance |
1 |
1 |
1 |
1 |
||
Piloerection |
1 |
1 |
1 |
1 |
||
Eye prominence |
1 |
1 |
1 |
1 |
||
Muscle tone |
1 |
1 |
1 |
1 |
||
Home Cage Observations:Home cage posture - 1=Normal; Respiratory pattern - 1=Normal; Clonic involuntary movements - 1=None; Tonic involuntary movements - 1=None; Vocalization - 1=None; Palpebral closure - 1=Normal;Handling Observations:Ease of removal from the cage - 2=Normal; Ease of handling animal in hand - 2=Normal; Red or crusty deposits - 1=Absent; Lacrimation - 1=None; Salivation- 1=None; Fur appearance - 1=Normal; Piloerection - 1=None; Eye Prominence - 1=Normal; Muscle tone - 1=Normal |
||||||
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)
Lactation Day 13 |
||||||
Parameters↓ |
Group & Sex |
G1 & F |
G2 & F |
G3 & F |
G4 & F |
|
Dose (mg/kg body weight/day) |
0 |
111 |
333 |
1000 |
||
Number of Animals (randomly selected) |
5 |
5 |
5 |
5 |
||
Open Field Observations |
||||||
Mobility |
1 |
1 |
1 |
1 |
||
Gait |
1 |
1 |
1 |
1 |
||
Arousal |
3 |
3 |
3 |
3 |
||
Number of rearing |
Mean |
4.8 |
4.8 |
4.8 |
4.8 |
|
±SD |
0.8 |
0.8 |
0.8 |
0.8 |
||
Numbers of urine pools |
Mean |
3.6 |
3.8 |
3.6 |
3.8 |
|
±SD |
0.5 |
0.8 |
0.5 |
0.8 |
||
Number of defecations |
Mean |
3.4 |
3.0 |
2.8 |
3.2 |
|
±SD |
0.9 |
0.7 |
0.8 |
0.4 |
||
Clonic involuntary movement |
1 |
1 |
1 |
1 |
||
Tonic involuntary movement |
1 |
1 |
1 |
1 |
||
Stereotype behaviour |
1 |
1 |
1 |
1 |
||
Number of grooming |
Mean |
3.2 |
3.2 |
2.6 |
3.0 |
|
±SD |
0.4 |
0.8 |
0.5 |
0.7 |
||
Sensory Observations |
||||||
Approach response |
2 |
2 |
2 |
2 |
||
Auditory response |
2 |
2 |
2 |
2 |
||
Touch response |
2 |
2 |
2 |
2 |
||
Pupil reflex |
2 |
2 |
2 |
2 |
||
Tail pinch response |
2 |
2 |
2 |
2 |
||
Righting reflex |
1 |
1 |
1 |
1 |
||
Physiological Observation |
||||||
Body temperature (°F) |
Mean |
98.4 |
98.4 |
98.8 |
98.7 |
|
±SD |
0.6 |
0.5 |
0.5 |
0.8 |
||
Open Field Observations: Mobility- 1=Normal;Gait- 1=Normal;Arousal- 3=Normal;Clonic involuntary movement- 1=None;Tonic involuntary movement -1=None;Stereotype behaviour -1=Absent;Sensory Observations:Approach response- 2=Normal;Auditory response- 2=Normal;Touch response -2=Normal;Pupil reflex- 2=Normal;Tail pinch response- 2=Normal;Righting reflex- 1=Present |
||||||
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)
Day 65 |
||||
Parameters↓ |
Group & Sex |
G1R & M |
G4R & M |
|
Dose (mg/kg body weight/day) |
0 |
1000 |
||
Number of Animals |
5 |
5 |
||
Home Cage Observations |
||||
Home cage posture |
1 |
1 |
||
Respiratory pattern |
1 |
1 |
||
Clonic involuntary movements |
1 |
1 |
||
Tonic involuntary movements |
1 |
1 |
||
Vocalization |
1 |
1 |
||
Palpebral closure |
1 |
1 |
||
Handling Observations |
||||
Ease of removal from the cage |
2 |
2 |
||
Ease of handling animal in hand |
2 |
2 |
||
Red or crusty deposits |
Eyes |
1 |
1 |
|
Nose |
1 |
1 |
||
Mouth |
1 |
1 |
||
Lacrimation |
1 |
1 |
||
Salivation |
1 |
1 |
||
Fur appearance |
1 |
1 |
||
Piloerection |
1 |
1 |
||
Eye prominence |
1 |
1 |
||
Muscle tone |
1 |
1 |
||
Home Cage Observations:Home cage posture - 1=Normal; Respiratory pattern - 1=Normal; Clonic involuntary movements - 1=None; Tonic involuntary movements - 1=None; Vocalization - 1=None; Palpebral closure - 1=Normal;Handling Observations:Ease of removal from the cage - 2=Normal; Ease of handling animal in hand - 2=Normal; Red or crusty deposits - 1=Absent; Lacrimation - 1=None; Salivation- 1=None; Fur appearance - 1=Normal; Piloerection - 1=None; Eye Prominence - 1=Normal; Muscle tone - 1=Normal |
||||
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)
Day 65 |
||||
Parameters↓ |
Group & Sex |
G1R & M |
G4R & M |
|
Dose (mg/kg body weight/day) |
0 |
1000 |
||
Number of Animals |
5 |
5 |
||
Open Field Observations |
||||
Mobility |
1 |
1 |
||
Gait |
1 |
1 |
||
Arousal |
3 |
3 |
||
Number of rearing |
Mean |
5.0 |
4.4 |
|
±SD |
1.0 |
1.1 |
||
Numbers of urine pools |
Mean |
3.6 |
3.4 |
|
±SD |
0.5 |
0.5 |
||
Number of defecations |
Mean |
3.6 |
3.4 |
|
±SD |
0.5 |
0.5 |
||
Clonic involuntary movement |
1 |
1 |
||
Tonic involuntary movement |
1 |
1 |
||
Stereotype behaviour |
1 |
1 |
||
Number of grooming |
Mean |
3.6 |
3.2 |
|
±SD |
0.5 |
0.4 |
||
Sensory Observations |
||||
Approach response |
2 |
2 |
||
Auditory response |
2 |
2 |
||
Touch response |
2 |
2 |
||
Pupil reflex |
2 |
2 |
||
Tail pinch response |
2 |
2 |
||
Righting reflex |
1 |
1 |
||
Physiological Observation |
||||
Body temperature (°F) |
Mean |
98.5 |
98.6 |
|
±SD |
0.5 |
0.5 |
||
Open Field Observations: Mobility- 1=Normal;Gait- 1=Normal;Arousal- 3=Normal;Clonic involuntary movement- 1=None;Tonic involuntary movement -1=None;Stereotype behaviour -1=Absent;Sensory Observations:Approach response- 2=Normal;Auditory response- 2=Normal;Touch response -2=Normal;Pupil reflex- 2=Normal;Tail pinch response- 2=Normal;Righting reflex- 1=Present |
||||
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)
Day 65 |
||||
Parameters↓ |
Group & Sex |
G1R & F |
G4R & F |
|
Dose (mg/kg body weight/day) |
0 |
1000 |
||
Number of Animals |
5 |
5 |
||
Home Cage Observations |
||||
Home cage posture |
1 |
1 |
||
Respiratory pattern |
1 |
1 |
||
Clonic involuntary movements |
1 |
1 |
||
Tonic involuntary movements |
1 |
1 |
||
Vocalization |
1 |
1 |
||
Palpebral closure |
1 |
1 |
||
Handling Observations |
||||
Ease of removal from the cage |
2 |
2 |
||
Ease of handling animal in hand |
2 |
2 |
||
Red or crusty deposits |
Eyes |
1 |
1 |
|
Nose |
1 |
1 |
||
Mouth |
1 |
1 |
||
Lacrimation |
1 |
1 |
||
Salivation |
1 |
1 |
||
Fur appearance |
1 |
1 |
||
Piloerection |
1 |
1 |
||
Eye prominence |
1 |
1 |
||
Muscle tone |
1 |
1 |
||
Home Cage Observations:Home cage posture - 1=Normal; Respiratory pattern - 1=Normal; Clonic involuntary movements - 1=None; Tonic involuntary movements - 1=None; Vocalization - 1=None; Palpebral closure - 1=Normal;Handling Observations:Ease of removal from the cage - 2=Normal; Ease of handling animal in hand - 2=Normal; Red or crusty deposits - 1=Absent; Lacrimation - 1=None; Salivation- 1=None; Fur appearance - 1=Normal; Piloerection - 1=None; Eye Prominence - 1=Normal; Muscle tone - 1=Normal |
||||
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)
Day 65 |
||||
Parameters↓ |
Group & Sex |
G1R & F |
G4R & F |
|
Dose (mg/kg body weight/day) |
0 |
1000 |
||
Number of Animals |
5 |
5 |
||
Open Field Observations |
||||
Mobility |
1 |
1 |
||
Gait |
1 |
1 |
||
Arousal |
3 |
3 |
||
Number of rearing |
Mean |
5.0 |
4.8 |
|
±SD |
1.0 |
0.8 |
||
Numbers of urine pools |
Mean |
3.6 |
3.8 |
|
±SD |
0.5 |
0.8 |
||
Number of defecations |
Mean |
3.4 |
3.0 |
|
±SD |
0.9 |
0.7 |
||
Clonic involuntary movement |
1 |
1 |
||
Tonic involuntary movement |
1 |
1 |
||
Stereotype behaviour |
1 |
1 |
||
Number of grooming |
Mean |
3.2 |
3.2 |
|
±SD |
0.4 |
0.8 |
||
Sensory Observations |
||||
Approach response |
2 |
2 |
||
Auditory response |
2 |
2 |
||
Touch response |
2 |
2 |
||
Pupil reflex |
2 |
2 |
||
Tail pinch response |
2 |
2 |
||
Righting reflex |
1 |
1 |
||
Physiological Observation |
||||
Body temperature (°F) |
Mean |
98.4 |
98.3 |
|
±SD |
0.5 |
0.7 |
||
Open Field Observations: Mobility- 1=Normal;Gait- 1=Normal;Arousal- 3=Normal;Clonic involuntary movement- 1=None;Tonic involuntary movement -1=None;Stereotype behaviour -1=Absent;Sensory Observations:Approach response- 2=Normal;Auditory response- 2=Normal;Touch response -2=Normal;Pupil reflex- 2=Normal;Tail pinch response- 2=Normal;Righting reflex- 1=Present |
||||
TABLE 13. SUMMARY OF LOCOMOTOR ACTIVITY / MOVEMENT COUNTS RECORD
Day 30 |
||
Group, Sex & Dose (mg/kg body weight/day) |
Movement Counts (no.) |
|
G1, M & 0 |
Mean |
1911.4 |
±SD |
108.9 |
|
n |
5 |
|
G2, M & 111 |
Mean |
1961.8 |
±SD |
138.9 |
|
n |
5 |
|
G3, M & 333 |
Mean |
1954.2 |
±SD |
126.1 |
|
n |
5 |
|
G4, M & 1000 |
Mean |
1931.4 |
±SD |
104.0 |
|
n |
5 |
|
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 13 (Contd…). SUMMARY OF LOCOMOTOR ACTIVITY / MOVEMENT COUNTS RECORD
Lactation Day 13 |
||
Group, Sex & Dose (mg/kg body weight/day) |
Movement Counts (no.) |
|
G1, F & 0 |
Mean |
1923.4 |
±SD |
102.7 |
|
n |
5 |
|
G2, F & 111 |
Mean |
1941.4 |
±SD |
125.1 |
|
n |
5 |
|
G3, F & 333 |
Mean |
1989.0 |
±SD |
103.1 |
|
n |
5 |
|
G4, F & 1000 |
Mean |
1973.2 |
±SD |
84.7 |
|
n |
5 |
|
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 13 (Contd…). SUMMARY OF LOCOMOTOR ACTIVITY / MOVEMENT COUNTS RECORD
Day 65 |
||
Group, Sex & Dose (mg/kg body weight/day) |
Movement Counts (no.) |
|
G1R, M & 0 |
Mean |
2014.2 |
±SD |
210.7 |
|
n |
5 |
|
G4R, M & 1000 |
Mean |
1980.6 |
±SD |
197.8 |
|
n |
5 |
|
G1R, F & 0 |
Mean |
1943.4 |
±SD |
87.8 |
|
n |
5 |
|
G4R, F & 1000 |
Mean |
1956.2 |
±SD |
91.6 |
|
n |
5 |
|
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals.
TABLE 14. SUMMARY OF AVERAGE GRIP STRENGTH (kgf) MEASUREMENT RECORD
Day 30 |
|||
Group, Sex & Dose (mg/kg body weight/day) |
Grip Strength (kgf) |
||
Forelimb |
Hindlimb |
||
G1, M & 0 |
Mean |
1.529 |
0.510 |
±SD |
0.023 |
0.025 |
|
n |
5 |
5 |
|
G2, M & 111 |
Mean |
1.501 |
0.539 |
±SD |
0.020 |
0.021 |
|
n |
5 |
5 |
|
G3, M & 333 |
Mean |
1.521 |
0.552* |
±SD |
0.048 |
0.008 |
|
n |
5 |
5 |
|
G4, M & 1000 |
Mean |
1.539 |
0.544* |
±SD |
0.040 |
0.015 |
|
n |
5 |
5 |
|
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected); *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 14 (Contd…). SUMMARY OF AVERAGE GRIP STRENGTH (kgf) MEASUREMENT RECORD
Lactation Day 13 |
|||
Group, Sex & Dose (mg/kg body weight/day) |
Grip Strength (kgf) |
||
Forelimb |
Hindlimb |
||
G1, F & 0 |
Mean |
1.496 |
0.508 |
±SD |
0.009 |
0.008 |
|
n |
5 |
5 |
|
G2, F & 111 |
Mean |
1.493 |
0.488 |
±SD |
0.010 |
0.015 |
|
n |
5 |
5 |
|
G3, F & 333 |
Mean |
1.496 |
0.493 |
±SD |
0.009 |
0.021 |
|
n |
5 |
5 |
|
G4, F & 1000 |
Mean |
1.498 |
0.499 |
±SD |
0.011 |
0.020 |
|
n |
5 |
5 |
|
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 14 (Contd…). SUMMARY OF AVERAGE GRIP STRENGTH (kgf) MEASUREMENT RECORD
Day 65 |
|||
Group, Sex & Dose (mg/kg body weight/day) |
Grip Strength (kgf) |
||
Forelimb |
Hindlimb |
||
G1R, M & 0 |
Mean |
1.515 |
0.534 |
±SD |
0.020 |
0.035 |
|
n |
5 |
5 |
|
G4R, M & 1000 |
Mean |
1.528 |
0.533 |
±SD |
0.029 |
0.009 |
|
n |
5 |
5 |
|
G1R, F & 0 |
Mean |
1.516 |
0.499 |
±SD |
0.031 |
0.021 |
|
n |
5 |
5 |
|
G4R, F & 1000 |
Mean |
1.503 |
0.481 |
±SD |
0.012 |
0.012 |
|
n |
5 |
5 |
|
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals.
TABLE 15. SUMMARY OF AVERAGE HINDLIMB FOOT SPLAY (cm) RECORD
Day 30 |
||
Group, Sex & Dose (mg/kg body weight/day) |
Hindlimb Foot Splay (cm) |
|
G1, M & 0 |
Mean |
9.0 |
±SD |
1.0 |
|
n |
5 |
|
G2, M & 111 |
Mean |
8.8 |
±SD |
1.3 |
|
n |
5 |
|
G3, M & 333 |
Mean |
9.3 |
±SD |
0.6 |
|
n |
5 |
|
G4, M & 1000 |
Mean |
8.6 |
±SD |
0.6 |
|
n |
5 |
|
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 15 (Contd…). SUMMARY OF AVERAGE HINDLIMB FOOT SPLAY (cm) RECORD
Lactation Day 13 |
||
Group, Sex & Dose (mg/kg body weight/day) |
Hindlimb Foot Splay (cm) |
|
G1, F & 0 |
Mean |
8.0 |
±SD |
0.5 |
|
n |
5 |
|
G2, F & 111 |
Mean |
7.9 |
±SD |
0.5 |
|
n |
5 |
|
G3, F & 333 |
Mean |
8.1 |
±SD |
1.0 |
|
n |
5 |
|
G4, F & 1000 |
Mean |
8.5 |
±SD |
0.9 |
|
n |
5 |
|
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 15 (Contd…). SUMMARY OF AVERAGE HINDLIMB FOOT SPLAY (cm) RECORD
Day 65 |
||
Group, Sex & Dose (mg/kg body weight/day) |
Hindlimb Foot Splay (cm) |
|
G1R, M & 0 |
Mean |
8.6 |
±SD |
0.3 |
|
n |
5 |
|
G4R, M & 1000 |
Mean |
9.0 |
±SD |
0.4 |
|
n |
5 |
|
G1R, F & 0 |
Mean |
8.4 |
±SD |
0.4 |
|
n |
5 |
|
G4R, F & 1000 |
Mean |
7.6* |
±SD |
0.2 |
|
n |
5 |
|
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 16. SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total Leucocyte Count |
Total Erythrocyte Count |
Haemoglobin |
Haematocrit |
Mean Corpuscular Volume |
Mean Corpuscular Haemoglobin |
Mean Corpuscular Haemoglobin Concentration |
Platelet Count |
Mean Platelet Volume |
|
(WBC) |
(RBC) |
(HGB) |
(HCT) |
(MCV) |
(MCH) |
(MCHC) |
(PLT) |
(MPV) |
||
(103cells/µL) |
(106cells/µL) |
(g/dL) |
(%) |
(fL) |
(pg) |
(g/dL) |
(103cells/µL) |
(fL) |
||
G1, M & 0 |
Mean |
8.26 |
9.64 |
17.56 |
52.80 |
55.00 |
18.30 |
33.26 |
776.40 |
7.72 |
±SD |
1.95 |
1.09 |
1.34 |
4.49 |
3.09 |
1.14 |
0.53 |
330.86 |
0.52 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
9.68 |
9.37 |
16.82 |
51.32 |
54.72 |
17.94 |
32.80 |
1135.20 |
7.46 |
±SD |
2.59 |
0.15 |
0.33 |
0.89 |
1.12 |
0.29 |
0.58 |
184.30 |
0.19 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
8.67 |
9.40 |
16.58 |
50.78 |
54.12 |
17.64 |
32.62 |
962.60 |
7.72 |
±SD |
3.67 |
0.62 |
0.87 |
1.91 |
1.72 |
0.59 |
0.70 |
256.00 |
0.52 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
8.14 |
9.35 |
16.88 |
52.02 |
55.74 |
18.06 |
32.46 |
1017.60 |
7.50 |
±SD |
2.42 |
0.54 |
0.55 |
1.58 |
2.71 |
0.74 |
0.53 |
93.02 |
0.38 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Reticulocyte Count |
Neutrophils |
Lymphocytes |
Monocytes |
Eosinophils |
Basophils |
|
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
||
(%) |
(%) |
(%) |
(%) |
(%) |
(%) |
||
G1, M & 0 |
Mean |
2.25 |
23.48 |
72.02 |
2.38 |
0.44 |
0.80 |
±SD |
1.24 |
9.09 |
9.80 |
1.15 |
0.17 |
0.49 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
1.87 |
19.66 |
75.74 |
2.28 |
1.04 |
0.54 |
±SD |
0.64 |
3.44 |
3.55 |
0.74 |
0.59 |
0.23 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
1.87 |
21.98 |
70.58 |
2.40 |
1.04 |
0.62 |
±SD |
0.60 |
5.35 |
7.57 |
2.37 |
0.34 |
0.61 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
2.01 |
20.86 |
75.78 |
1.42 |
0.72 |
0.54 |
±SD |
0.79 |
3.34 |
2.92 |
0.23 |
0.25 |
0.15 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Absolute Reticulocyte Count |
Absolute Neutrophils |
Absolute Lymphocytes |
Absolute Monocytes |
Absolute Eosinophils |
Absolute Basophils |
Prothrombin Time |
Activated Prothrombin Time |
|
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
(PT) |
(APTT) |
||
(109cells/L) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(Seconds) |
(Seconds) |
||
G1, M & 0 |
Mean |
212.96 |
1.83 |
6.07 |
0.19 |
0.04 |
0.07 |
15.54 |
22.26 |
±SD |
101.87 |
0.42 |
2.01 |
0.08 |
0.02 |
0.06 |
0.78 |
6.12 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
174.50 |
1.91 |
7.33 |
0.23 |
0.10* |
0.05 |
15.72 |
25.28 |
±SD |
56.93 |
0.64 |
1.96 |
0.10 |
0.04 |
0.02 |
1.03 |
1.56 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
175.20 |
1.80 |
5.98 |
0.27 |
0.09* |
0.07 |
16.72 |
24.30 |
±SD |
59.25 |
0.52 |
1.97 |
0.39 |
0.03 |
0.11 |
1.49 |
1.59 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
184.78 |
1.70 |
6.17 |
0.11 |
0.06 |
0.04 |
15.98 |
26.78 |
±SD |
67.09 |
0.55 |
1.89 |
0.04 |
0.02 |
0.02 |
0.89 |
1.29 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected); *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total Leucocyte Count |
Total Erythrocyte Count |
Haemoglobin |
Haematocrit |
Mean Corpuscular Volume |
Mean Corpuscular Haemoglobin |
Mean Corpuscular Haemoglobin Concentration |
Platelet Count |
Mean Platelet Volume |
|
(WBC) |
(RBC) |
(HGB) |
(HCT) |
(MCV) |
(MCH) |
(MCHC) |
(PLT) |
(MPV) |
||
(103cells/µL) |
(106cells/µL) |
(g/dL) |
(%) |
(fL) |
(pg) |
(g/dL) |
(103cells/µL) |
(fL) |
||
G1, F & 0 |
Mean |
10.56 |
7.85 |
15.74 |
46.26 |
59.02 |
20.04 |
34.04 |
752.60 |
6.02 |
±SD |
3.78 |
0.45 |
0.65 |
3.16 |
4.16 |
1.08 |
0.91 |
361.58 |
0.64 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 111 |
Mean |
11.38 |
7.41 |
14.66 |
44.60 |
60.26 |
19.74 |
32.82 |
1130.00 |
6.72 |
±SD |
3.45 |
0.68 |
1.58 |
3.35 |
1.37 |
0.42 |
1.34 |
672.21 |
0.54 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 333 |
Mean |
9.62 |
7.95 |
15.56 |
46.34 |
58.34 |
19.60 |
33.60 |
1030.20 |
6.42 |
±SD |
3.95 |
0.28 |
0.72 |
2.05 |
3.12 |
0.81 |
1.07 |
104.22 |
0.57 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
12.38 |
7.39 |
14.68 |
43.46 |
59.06 |
19.98 |
33.80 |
1003.00 |
6.92 |
±SD |
3.58 |
0.76 |
0.89 |
2.75 |
3.76 |
1.58 |
0.63 |
227.17 |
0.68 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Reticulocyte Count |
Neutrophils |
Lymphocytes |
Monocytes |
Eosinophils |
Basophils |
|
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
||
(%) |
(%) |
(%) |
(%) |
(%) |
(%) |
||
G1, F & 0 |
Mean |
2.28 |
32.72 |
60.66 |
3.68 |
1.46 |
0.60 |
±SD |
0.87 |
15.77 |
16.88 |
1.06 |
0.98 |
0.23 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 111 |
Mean |
4.52 |
30.00 |
62.56 |
4.60 |
1.18 |
0.42 |
±SD |
4.56 |
11.00 |
11.24 |
1.35 |
0.63 |
0.19 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 333 |
Mean |
1.49 |
25.26 |
66.92 |
4.46 |
1.22 |
0.80 |
±SD |
0.67 |
9.73 |
12.89 |
4.23 |
0.33 |
1.12 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
4.16 |
37.00 |
57.76 |
3.10 |
0.88 |
0.28 |
±SD |
2.72 |
20.56 |
20.80 |
0.97 |
0.47 |
0.11 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Absolute Reticulocyte Count |
Absolute Neutrophils |
Absolute Lymphocytes |
Absolute Monocytes |
Absolute Eosinophils |
Absolute Basophils |
Prothrombin Time |
Activated Prothrombin Time |
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
(PT) |
(APTT) |
||
(109cells/L) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(Seconds) |
(Seconds) |
||
G1, F & 0 |
Mean |
177.36 |
3.64 |
6.21 |
0.40 |
0.15 |
0.06 |
17.60 |
23.34 |
±SD |
60.94 |
2.11 |
2.30 |
0.19 |
0.09 |
0.03 |
1.02 |
2.05 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 111 |
Mean |
313.86 |
3.59 |
6.91 |
0.56 |
0.12 |
0.05 |
22.06 |
27.48 |
±SD |
276.22 |
2.17 |
1.72 |
0.29 |
0.04 |
0.02 |
8.41 |
10.47 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 333 |
Mean |
117.60 |
2.64 |
6.29 |
0.39 |
0.12 |
0.06 |
16.88 |
22.08 |
±SD |
50.69 |
2.06 |
2.26 |
0.31 |
0.07 |
0.08 |
3.84 |
7.81 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
291.70 |
4.81 |
6.94 |
0.38 |
0.10 |
0.04 |
15.66 |
19.92 |
±SD |
145.98 |
3.66 |
3.06 |
0.17 |
0.03 |
0.02 |
3.85 |
5.41 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total Leucocyte Count |
Total Erythrocyte Count |
Haemoglobin |
Haematocrit |
Mean Corpuscular Volume |
Mean Corpuscular Haemoglobin |
Mean Corpuscular Haemoglobin Concentration |
Platelet Count |
Mean Platelet Volume |
|
(WBC) |
(RBC) |
(HGB) |
(HCT) |
(MCV) |
(MCH) |
(MCHC) |
(PLT) |
(MPV) |
||
(103cells/µL) |
(106cells/µL) |
(g/dL) |
(%) |
(fL) |
(pg) |
(g/dL) |
(103cells/µL) |
(fL) |
||
G1R, M & 0 |
Mean |
9.13 |
9.21 |
16.04 |
48.76 |
52.94 |
17.42 |
32.92 |
894.80 |
6.50 |
±SD |
0.78 |
0.14 |
0.43 |
1.79 |
1.78 |
0.39 |
0.42 |
134.10 |
0.31 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
9.55 |
9.14 |
15.80 |
48.54 |
53.08 |
17.30 |
32.62 |
1071.80 |
6.42 |
±SD |
1.05 |
0.32 |
0.65 |
2.25 |
0.91 |
0.30 |
0.57 |
268.87 |
0.37 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
6.97 |
7.65 |
14.26 |
42.16 |
55.20 |
18.64 |
33.78 |
873.60 |
6.32 |
±SD |
2.14 |
0.43 |
0.65 |
2.05 |
1.99 |
0.70 |
0.29 |
80.79 |
0.19 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
7.59 |
7.73 |
14.32 |
42.78 |
55.34 |
18.48 |
33.46 |
739.60 |
6.52 |
±SD |
3.51 |
0.22 |
0.57 |
1.63 |
2.15 |
0.70 |
0.25 |
253.21 |
0.13 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals.
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Reticulocyte Count |
Neutrophils |
Lymphocytes |
Monocytes |
Eosinophils |
Basophils |
|
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
||
(%) |
(%) |
(%) |
(%) |
(%) |
(%) |
||
G1R, M & 0 |
Mean |
1.63 |
25.28 |
69.00 |
1.76 |
2.30 |
0.88 |
±SD |
0.26 |
6.62 |
7.82 |
0.49 |
0.89 |
0.26 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
2.03 |
21.70 |
73.32 |
1.48 |
2.02 |
0.60 |
±SD |
0.50 |
5.52 |
5.80 |
0.37 |
0.36 |
0.29 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
1.84 |
26.12 |
68.68 |
2.30 |
1.34 |
0.68 |
±SD |
0.36 |
9.06 |
8.57 |
1.19 |
0.45 |
0.15 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
2.48* |
29.02 |
64.16 |
2.40 |
2.86* |
0.64 |
±SD |
0.39 |
7.89 |
6.96 |
0.87 |
1.30 |
0.13 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Absolute Reticulocyte Count |
Absolute Neutrophils |
Absolute Lymphocytes |
Absolute Monocytes |
Absolute Eosinophils |
Absolute Basophils |
Prothrombin Time |
Activated Prothrombin Time |
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
(PT) |
(APTT) |
||
(109cells/L) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(Seconds) |
(Seconds) |
||
G1R, M & 0 |
Mean |
150.40 |
2.27 |
6.35 |
0.16 |
0.21 |
0.08 |
16.00 |
21.56 |
±SD |
23.36 |
0.40 |
1.23 |
0.04 |
0.07 |
0.02 |
2.04 |
2.05 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
186.92 |
2.06 |
7.02 |
0.14 |
0.19 |
0.05 |
15.50 |
22.48 |
±SD |
52.68 |
0.53 |
1.09 |
0.04 |
0.04 |
0.03 |
1.17 |
3.12 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
140.08 |
1.78 |
4.83 |
0.15 |
0.09 |
0.05 |
14.98 |
24.56 |
±SD |
23.05 |
0.73 |
1.73 |
0.05 |
0.02 |
0.01 |
0.53 |
1.98 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
192.10* |
2.06 |
4.98 |
0.17 |
0.25 |
0.05 |
15.92 |
19.34* |
±SD |
30.17 |
0.60 |
2.77 |
0.07 |
0.24 |
0.02 |
1.17 |
2.34 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 17. SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Glucose |
Urea |
Creatinine |
Total Cholesterol |
Triglycerides |
Total Protein |
Albumin |
|
(GLU) |
- |
(CRE) |
(CHO) |
(TRI) |
(TPR) |
(ALB) |
||
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(g/dL) |
||
G1, M & 0 |
Mean |
126.60 |
30.52 |
0.58 |
51.60 |
25.60 |
7.74 |
3.47 |
±SD |
15.47 |
2.56 |
0.03 |
3.36 |
2.30 |
0.26 |
0.19 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
123.60 |
33.30 |
0.57 |
60.60 |
30.40 |
7.24* |
3.55 |
±SD |
5.55 |
3.91 |
0.04 |
4.83 |
6.07 |
0.33 |
0.15 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
122.60 |
33.78 |
0.60 |
58.00 |
29.40 |
7.44 |
3.65 |
±SD |
12.92 |
2.83 |
0.03 |
6.71 |
7.73 |
0.22 |
0.29 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
131.00 |
36.04 |
0.59 |
56.00 |
27.00 |
7.58 |
3.68 |
±SD |
19.79 |
4.26 |
0.02 |
9.57 |
6.16 |
0.29 |
0.24 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected); *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Alanine |
Aspartate |
Alkaline |
Total Bilirubin |
Calcium |
Phosphorous |
|
(ALT) |
(AST) |
(ALP) |
(BIT) |
(CAL) |
(PHO) |
||
(U/L) |
(U/L) |
(U/L) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
||
G1, M & 0 |
Mean |
61.20 |
111.20 |
125.80 |
0.05 |
9.36 |
6.48 |
±SD |
16.93 |
12.34 |
21.11 |
0.01 |
0.11 |
0.58 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
47.40 |
93.20 |
120.00 |
0.06 |
9.64 |
6.54 |
±SD |
8.96 |
13.46 |
31.92 |
0.03 |
0.47 |
0.62 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
40.00 |
81.60* |
127.20 |
0.06 |
10.40* |
6.82 |
±SD |
5.96 |
12.30 |
38.01 |
0.03 |
1.05 |
0.62 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
52.20 |
91.80 |
114.80 |
0.06 |
9.94 |
6.62 |
±SD |
24.52 |
18.69 |
28.70 |
0.02 |
0.30 |
0.49 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected) ; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Globulin |
Albumin/ Globulin ratio |
Blood Urea Nitrogen |
Sodium |
Potassium |
Chloride |
|
(GLO) |
(A/G Ratio) |
(BUN) |
(Na) |
(K) |
(CLO) |
||
(g/dL) |
- |
(mg/dL) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
||
G1, M & 0 |
Mean |
4.27 |
0.82 |
14.24 |
141.64 |
3.96 |
104.10 |
±SD |
0.30 |
0.09 |
1.19 |
0.94 |
0.25 |
2.51 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
3.69* |
0.97 |
15.54 |
142.16 |
3.71 |
105.38 |
±SD |
0.38 |
0.12 |
1.83 |
0.53 |
0.15 |
1.40 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
3.79* |
0.97 |
15.77 |
142.44 |
3.86 |
105.78 |
±SD |
0.12 |
0.10 |
1.32 |
0.93 |
0.36 |
1.73 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
3.90 |
0.95 |
16.82 |
142.76 |
3.85 |
106.40 |
±SD |
0.29 |
0.11 |
1.99 |
0.66 |
0.09 |
0.86 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected); *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Glucose |
Urea |
Creatinine |
Total Cholesterol |
Triglycerides |
Total Protein |
Albumin |
|
(GLU) |
- |
(CRE) |
(CHO) |
(TRI) |
(TPR) |
(ALB) |
||
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(g/dL) |
||
G1, F & 0 |
Mean |
102.20 |
48.68 |
0.54 |
76.60 |
78.60 |
7.32 |
3.63 |
±SD |
26.22 |
8.11 |
0.05 |
22.67 |
26.83 |
1.08 |
0.67 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 111 |
Mean |
121.20 |
51.14 |
0.52 |
67.80 |
59.40 |
7.34 |
3.41 |
±SD |
29.64 |
13.28 |
0.03 |
17.67 |
23.65 |
0.75 |
0.30 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 333 |
Mean |
103.80 |
44.78 |
0.57 |
75.60 |
43.20 |
7.56 |
3.58 |
±SD |
13.81 |
19.81 |
0.04 |
14.91 |
21.48 |
0.29 |
0.32 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
114.60 |
51.66 |
0.57 |
75.80 |
105.20 |
7.76 |
3.70 |
±SD |
16.44 |
16.16 |
0.07 |
20.44 |
68.28 |
0.58 |
0.11 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Alanine |
Aspartate |
Alkaline |
Total Bilirubin |
Calcium |
Phosphorous |
|
(ALT) |
(AST) |
(ALP) |
(BIT) |
(CAL) |
(PHO) |
||
(U/L) |
(U/L) |
(U/L) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
||
G1, F & 0 |
Mean |
84.60 |
119.40 |
164.40 |
0.03 |
10.06 |
5.92 |
±SD |
14.43 |
14.31 |
75.62 |
0.04 |
1.06 |
0.95 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 111 |
Mean |
113.80 |
143.80 |
420.00 |
0.02 |
9.42 |
5.50 |
±SD |
66.08 |
71.78 |
367.29 |
0.02 |
0.64 |
1.64 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 333 |
Mean |
96.20 |
99.40 |
305.80 |
0.06 |
10.04 |
6.06 |
±SD |
82.35 |
16.01 |
412.83 |
0.02 |
0.85 |
1.93 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
88.60 |
101.80 |
212.40 |
0.03 |
10.38 |
6.38 |
±SD |
46.69 |
22.65 |
81.17 |
0.04 |
0.91 |
3.11 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Globulin |
Albumin/Globulin ratio |
Blood Urea Nitrogen |
Sodium |
Potassium |
Chloride |
|
(GLO) |
(A/G Ratio) |
(BUN) |
(Na) |
(K) |
(CLO) |
||
(g/dL) |
- |
(mg/dL) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
||
G1, F & 0 |
Mean |
3.69 |
0.98 |
22.72 |
143.04 |
4.02 |
106.18 |
±SD |
0.50 |
0.11 |
3.79 |
1.34 |
0.81 |
2.96 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 111 |
Mean |
3.93 |
0.88 |
23.87 |
142.18 |
3.57 |
107.22 |
±SD |
0.66 |
0.14 |
6.20 |
1.47 |
0.28 |
3.01 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 333 |
Mean |
3.98 |
0.91 |
20.90 |
142.36 |
3.60 |
107.94 |
±SD |
0.40 |
0.16 |
9.25 |
1.61 |
0.33 |
2.63 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
4.06 |
0.92 |
24.11 |
142.62 |
3.86 |
107.06 |
±SD |
0.50 |
0.09 |
7.55 |
1.62 |
0.40 |
3.20 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Glucose |
Urea |
Creatinine |
Total Cholesterol |
Triglycerides |
Total Protein |
Albumin |
|
(GLU) |
- |
(CRE) |
(CHO) |
(TRI) |
(TPR) |
(ALB) |
||
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(g/dL) |
||
G1R, M & 0 |
Mean |
99.80 |
27.36 |
0.55 |
59.60 |
23.00 |
6.98 |
3.10 |
±SD |
6.53 |
3.92 |
0.02 |
16.21 |
5.52 |
0.26 |
0.07 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
99.40 |
25.74 |
0.56 |
68.80 |
31.60 |
7.12 |
3.05 |
±SD |
10.53 |
1.19 |
0.03 |
8.76 |
10.78 |
0.11 |
0.04 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
120.40 |
35.68 |
0.61 |
106.40 |
49.60 |
8.44 |
4.10 |
±SD |
7.16 |
7.57 |
0.02 |
17.07 |
34.09 |
0.56 |
0.18 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
104.00* |
31.42 |
0.59 |
89.20 |
41.60 |
8.04 |
3.70 |
±SD |
13.49 |
2.25 |
0.01 |
16.98 |
11.87 |
0.42 |
0.44 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Alanine aminotransferase |
Aspartate aminotransferase |
Alkaline phosphatase |
Total Bilirubin |
Calcium |
Phosphorous |
|
(ALT) |
(AST) |
(ALP) |
(BIT) |
(CAL) |
(PHO) |
||
(U/L) |
(U/L) |
(U/L) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
||
G1R, M & 0 |
Mean |
52.00 |
101.80 |
99.00 |
0.02 |
10.42 |
5.72 |
±SD |
40.34 |
53.17 |
23.40 |
0.02 |
0.37 |
0.34 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
42.60 |
98.40 |
105.20 |
0.02 |
10.02 |
5.26 |
±SD |
9.86 |
18.49 |
29.84 |
0.01 |
0.15 |
0.50 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
54.00 |
94.00 |
70.80 |
0.02 |
11.20 |
4.20 |
±SD |
28.82 |
36.89 |
40.92 |
0.02 |
0.45 |
0.38 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
53.80 |
103.20 |
69.00 |
0.04 |
10.90 |
4.42 |
±SD |
21.53 |
39.30 |
60.10 |
0.02 |
0.37 |
0.18 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals.
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Globulin |
Albumin/ Globulin ratio |
Blood Urea Nitrogen |
Sodium |
Potassium |
Chloride |
|
(GLO) |
(A/G Ratio) |
(BUN) |
(Na) |
(K) |
(CLO) |
||
(g/dL) |
- |
(mg/dL) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
||
G1R, M & 0 |
Mean |
3.88 |
0.80 |
12.77 |
142.82 |
3.56 |
105.48 |
±SD |
0.27 |
0.06 |
1.83 |
0.36 |
0.41 |
0.92 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
4.07 |
0.75 |
12.01 |
143.16 |
3.59 |
108.06* |
±SD |
0.15 |
0.04 |
0.56 |
0.68 |
0.41 |
1.65 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
4.34 |
0.95 |
16.65 |
142.62 |
3.45 |
105.76 |
±SD |
0.42 |
0.08 |
3.53 |
0.94 |
0.17 |
1.52 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
4.34 |
0.85 |
14.66 |
142.26 |
3.62 |
106.40 |
±SD |
0.21 |
0.12 |
1.05 |
1.41 |
0.48 |
2.88 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 18. SUMMARY OF URINALYSIS RECORD
Examination |
Group, Sex & Dose (mg/kg body weight/day) |
G1, M & 0 |
G2, M & 111 |
G3, M & 333 |
G4, M & 1000 |
|
Number of Animals (randomly selected) |
5 |
5 |
5 |
5 |
||
Physical Examination |
Color |
Pale Yellow |
5 |
5 |
5 |
5 |
Appearance |
Clear |
5 |
5 |
5 |
5 |
|
Volume (mL) |
Mean |
10.6 |
10.2 |
11.0 |
11.4 |
|
±SD |
0.7 |
1.4 |
0.8 |
0.4 |
||
Chemical Examination |
pH |
Mean |
7.5 |
7.4 |
7.4 |
7.5 |
±SD |
0.0 |
0.4 |
0.5 |
0.0 |
||
Specific Gravity |
Mean |
1.008 |
1.011 |
1.009 |
1.009 |
|
±SD |
0.003 |
0.002 |
0.002 |
0.002 |
||
Urobilinogen (mg/dL) |
Mean |
0.2 |
0.2 |
0.2 |
0.2 |
|
±SD |
0.0 |
0.0 |
0.0 |
0.0 |
||
Bilirubin (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
|
Ketones (mg/dL) |
Neg |
2 |
- |
2 |
1 |
|
5 |
3 |
5 |
3 |
4 |
||
Blood (Ery/µL) |
Neg |
5 |
4 |
5 |
5 |
|
Ca80 |
- |
1 |
- |
- |
||
Protein (mg/dL) |
Neg |
3 |
- |
3 |
1 |
|
Trace |
2 |
4 |
1 |
4 |
||
30 |
- |
1 |
1 |
- |
||
Nitrite |
Neg |
4 |
4 |
5 |
1 |
|
Pos |
1 |
1 |
- |
4 |
||
Leucocytes |
Neg |
3 |
- |
3 |
1 |
|
Ca15 |
1 |
1 |
1 |
2 |
||
Ca70 |
1 |
3 |
1 |
2 |
||
Ca125 |
- |
1 |
- |
- |
||
Glucose (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
|
Microalbumin (mg/dL) |
Neg |
- |
- |
2 |
1 |
|
>15 |
2 |
5 |
2 |
4 |
||
15 |
3 |
- |
1 |
- |
||
Microscopic Examination |
Epi Cells |
0 |
3 |
4 |
2 |
4 |
0-1 |
1 |
1 |
2 |
1 |
||
1-2 |
1 |
- |
1 |
- |
||
Casts |
Absent |
4 |
4 |
4 |
5 |
|
Present |
1 |
1 |
1 |
- |
||
Crystals |
Present |
5 |
5 |
5 |
5 |
|
M:
Male; SD: Standard Deviation; Pos: Positive; Neg: Negative; Ca:
Calculated.
>=:
Greater than or equal to; >: Greater than.
TABLE 18 (Contd…). SUMMARY OF URINALYSIS RECORD
Examination |
Group, Sex & Dose (mg/kg body weight/day) |
G1R, M & 0 |
G4R, M &1000 |
G1R, F & 0 |
G4R, F & 1000 |
|
Number of Animals (randomly selected) |
5 |
5 |
5 |
5 |
||
Physical Examination |
Color |
Pale Yellow |
2 |
5 |
3 |
3 |
Yellow |
3 |
- |
2 |
2 |
||
Appearance |
Clear |
3 |
2 |
4 |
4 |
|
Turbid |
2 |
3 |
1 |
1 |
||
Volume (mL) |
Mean |
6.4 |
8.6 |
7.9 |
7.8 |
|
±SD |
1.7 |
3.1 |
2.2 |
0.8 |
||
Chemical Examination |
pH |
Mean |
6.7 |
7.3 |
6.8 |
7.6 |
±SD |
0.9 |
0.4 |
1.0 |
1.0 |
||
Specific Gravity |
Mean |
1.020 |
1.014 |
1.014 |
1.012 |
|
±SD |
0.007 |
0.002 |
0.007 |
0.008 |
||
Urobilinogen (mg/dL) |
Mean |
0.2 |
0.2 |
0.2 |
0.6 |
|
±SD |
0.0 |
0.0 |
0.0 |
0.8 |
||
Bilirubin (mg/dL) |
Neg |
2 |
5 |
5 |
2 |
|
1 |
3 |
- |
- |
3 |
||
Ketones (mg/dL) |
Neg |
1 |
2 |
5 |
5 |
|
5 |
4 |
3 |
- |
- |
||
Blood (Ery/µL) |
Neg |
5 |
5 |
5 |
4 |
|
Ca10 |
- |
- |
- |
1 |
||
Protein (mg/dL) |
Neg |
2 |
5 |
4 |
2 |
|
Trace |
2 |
- |
1 |
- |
||
30 |
1 |
- |
- |
- |
||
100 |
- |
- |
- |
1 |
||
>=300 |
- |
- |
- |
2 |
||
Nitrite |
Neg |
3 |
5 |
5 |
5 |
|
Pos |
2 |
- |
- |
- |
||
Leucocytes |
Neg |
- |
1 |
3 |
2 |
|
Ca15 |
1 |
4 |
2 |
- |
||
Ca70 |
4 |
- |
- |
3 |
||
Glucose (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
|
Microalbumin (mg/dL) |
Neg |
- |
1 |
3 |
1 |
|
>15 |
3 |
- |
1 |
3 |
||
15 |
2 |
4 |
1 |
1 |
||
Microscopic Examination\ |
Epi Cells |
0 |
3 |
3 |
2 |
2 |
0-1 |
1 |
2 |
2 |
1 |
||
1-2 |
1 |
- |
1 |
- |
||
2-3 |
- |
- |
- |
2 |
||
Casts |
Absent |
5 |
2 |
5 |
4 |
|
Present |
- |
3 |
- |
1 |
||
Crystals |
Absent |
- |
2 |
1 |
2 |
|
Present |
5 |
3 |
4 |
3 |
||
M:
Male; F: Female; R: Recovery; SD: Standard Deviation; Pos: Positive;
Neg: Negative.
Ca: Calculated; >=: Greater than
or equal to; >: Greater than.
TABLE 19. SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Adrenals |
Thymus |
Spleen |
Testes |
Epididymides |
Heart |
Kidneys |
Brain |
|
G1, M & 0 |
Mean |
0.0667 |
0.2891 |
0.7915 |
3.3315 |
1.4198 |
1.3943 |
2.9537 |
2.1193 |
±SD |
0.0045 |
0.0466 |
0.2701 |
0.3035 |
0.1420 |
0.2048 |
0.2510 |
0.0321 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
0.0719 |
0.3589 |
0.8023 |
3.4284 |
1.4112 |
1.5033 |
2.8196 |
2.1336 |
±SD |
0.0094 |
0.0292 |
0.0928 |
0.1782 |
0.1365 |
0.1061 |
0.1723 |
0.0957 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
0.0709 |
0.4450* |
0.8041 |
3.3728 |
1.4195 |
1.4754 |
2.8317 |
2.1467 |
±SD |
0.0060 |
0.0665 |
0.1455 |
0.2771 |
0.1776 |
0.1560 |
0.1507 |
0.0446 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
0.0716 |
0.4129* |
0.8155 |
3.3454 |
1.5221 |
1.5218 |
3.0082 |
2.2033 |
±SD |
0.0115 |
0.1013 |
0.1404 |
0.2101 |
0.1812 |
0.3979 |
0.7565 |
0.1355 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 19 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Liver |
Prostate |
Seminal vesicles with coagulating glands |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
G1, M & 0 |
Mean |
10.0491 |
1.1499 |
1.6300 |
1.9467 |
0.0208 |
0.0296 |
±SD |
1.6192 |
0.1975 |
0.4468 |
0.1258 |
0.0014 |
0.0017 |
|
n |
5 |
12 |
12 |
5 |
5 |
12 |
|
G2, M & 111 |
Mean |
10.3930 |
1.1988 |
1.6027 |
2.0659 |
0.0197 |
0.0290 |
±SD |
0.4389 |
0.2552 |
0.3454 |
0.1175 |
0.0013 |
0.0020 |
|
n |
5 |
12 |
12 |
5 |
5 |
12 |
|
G3, M & 333 |
Mean |
10.6576 |
1.3430 |
1.7846 |
2.0478 |
0.0203 |
0.0301 |
±SD |
0.7376 |
0.3501 |
0.3700 |
0.1024 |
0.0009 |
0.0013 |
|
n |
5 |
12 |
12 |
5 |
5 |
12 |
|
G4, M & 1000 |
Mean |
10.8065 |
1.2209 |
1.9124 |
2.0837 |
0.0205 |
0.0305 |
±SD |
2.8155 |
0.3931 |
0.5906 |
0.1492 |
0.0015 |
0.0023 |
|
n |
5 |
12 |
12 |
5 |
5 |
12 |
M: Male; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation.
TABLE 19 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Adrenals |
Thymus |
Spleen |
Ovaries |
Uterus with Cervix |
Heart |
|
G1, F & 0 |
Mean |
0.0741 |
0.2781 |
0.7048 |
0.1738 |
0.5901 |
1.1848 |
±SD |
0.0083 |
0.0317 |
0.0646 |
0.0299 |
0.1167 |
0.1262 |
|
n |
5 |
5 |
5 |
12 |
11@ |
5 |
|
G2, F & 111 |
Mean |
0.0884 |
0.2632 |
0.7503 |
0.1432* |
0.5097 |
1.1940 |
±SD |
0.0110 |
0.0345 |
0.1289 |
0.0332 |
0.1138 |
0.0729 |
|
n |
5 |
5 |
5 |
12 |
11@ |
5 |
|
G3, F & 333 |
Mean |
0.0728 |
0.2267* |
0.6584 |
0.1291* |
0.5413 |
1.2001 |
±SD |
0.0094 |
0.0282 |
0.1051 |
0.0193 |
0.0886 |
0.0513 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
|
G4, F & 1000 |
Mean |
0.0775 |
0.2179* |
0.6109 |
0.1466* |
0.5283 |
1.3318 |
±SD |
0.0093 |
0.0063 |
0.0413 |
0.0190 |
0.1008 |
0.3482 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
@: One animal data from group G1 and G2 is excluded for mean calculations as the weight varies from normal uterus due to presence of dead foetus during necropsy, but the data is presented in individual animal data. (Appendix 22).
TABLE 19 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Kidneys |
Brain |
Liver |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
|
G1, F & 0 |
Mean |
2.2668 |
2.0179 |
11.5641 |
1.2626 |
0.0179 |
0.0266 |
±SD |
0.1164 |
0.0746 |
0.5339 |
0.1185 |
0.0011 |
0.0015 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
|
G2, F & 111 |
Mean |
2.0463* |
2.0056 |
12.5985 |
1.5260 |
0.0183 |
0.0272 |
±SD |
0.1081 |
0.1131 |
2.0359 |
0.2954 |
0.0014 |
0.0015 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
|
G3, F & 333 |
Mean |
2.0269* |
1.9917 |
10.1148 |
1.3551 |
0.0176 |
0.0265 |
±SD |
0.0937 |
0.0552 |
1.8164 |
0.1082 |
0.0008 |
0.0015 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
|
G4, F & 1000 |
Mean |
1.9230* |
2.0216 |
10.2708 |
1.3780 |
0.0180 |
0.0275 |
±SD |
0.0912 |
0.0446 |
1.3180 |
0.1188 |
0.0010 |
0.0014 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
F: Female; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 19 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Adrenals |
Thymus |
Spleen |
Testes |
Epididymides |
Heart |
Kidneys |
Brain |
|
G1R, M & 0 |
Mean |
0.0671 |
0.2367 |
0.8804 |
3.3055 |
1.6954 |
1.6355 |
2.2619 |
2.0448 |
±SD |
0.0080 |
0.0348 |
0.0907 |
0.1930 |
0.0763 |
0.1477 |
0.3680 |
0.1172 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
0.0638 |
0.2709 |
0.7442* |
3.4656 |
1.6882 |
1.6050 |
2.3506 |
2.0483 |
±SD |
0.0051 |
0.0738 |
0.0528 |
0.1133 |
0.0690 |
0.3581 |
0.3464 |
0.1621 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 19 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Liver |
Prostate |
Seminal vesicles with coagulating glands |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
|
G1R, M & 0 |
Mean |
12.6730 |
1.3824 |
1.8300 |
2.0437 |
0.0207 |
0.0299 |
±SD |
1.2027 |
0.2475 |
0.4858 |
0.5420 |
0.0009 |
0.0015 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
12.5717 |
1.6038 |
1.8342 |
1.9398 |
0.0210 |
0.0306 |
±SD |
1.2099 |
0.1130 |
0.4887 |
0.0584 |
0.0011 |
0.0008 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation.
TABLE 19 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Adrenals |
Thymus |
Spleen |
Ovaries |
Uterus with Cervix |
Heart |
G1R, F & 0 |
Mean |
0.0706 |
0.2511 |
0.6464 |
0.1265 |
0.6499 |
1.0512 |
±SD |
0.0064 |
0.0443 |
0.0886 |
0.0164 |
0.0920 |
0.0882 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
0.0702 |
0.2467 |
0.6261 |
0.1543* |
0.6334 |
1.0135 |
±SD |
0.0121 |
0.0337 |
0.1113 |
0.0105 |
0.0853 |
0.0746 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 19 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Kidneys |
Brain |
Liver |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
|
G1R, F & 0 |
Mean |
1.9138 |
2.0075 |
9.6308 |
1.8480 |
0.0185 |
0.0278 |
±SD |
0.0978 |
0.0986 |
0.9760 |
0.0946 |
0.0009 |
0.0014 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
1.8218 |
1.9767 |
8.6614 |
2.0609 |
0.0193 |
0.0271 |
±SD |
0.1551 |
0.0844 |
1.7719 |
0.4014 |
0.0014 |
0.0006 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation.
TABLE 20. SUMMARY
OF TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Terminal Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Testes |
Epididymides |
Heart |
|
G1, M & 0 |
Mean |
440.14 |
0.0150 |
0.0648 |
0.1748 |
0.7637 |
0.3257 |
0.3099 |
±SD |
38.09 |
0.0018 |
0.0115 |
0.0484 |
0.1095 |
0.0493 |
0.0251 |
|
n |
12 |
5 |
5 |
5 |
12 |
12 |
5 |
|
G2, M & 111 |
Mean |
433.53 |
0.0162 |
0.0812 |
0.1809 |
0.7928 |
0.3262 |
0.3390 |
±SD |
29.89 |
0.0021 |
0.0090 |
0.0188 |
0.0447 |
0.0319 |
0.0185 |
|
n |
12 |
5 |
5 |
5 |
12 |
12 |
5 |
|
G3, M & 333 |
Mean |
437.73 |
0.0159 |
0.0995* |
0.1797 |
0.7734 |
0.3250 |
0.3314 |
±SD |
26.65 |
0.0016 |
0.0135 |
0.0302 |
0.0792 |
0.0413 |
0.0427 |
|
n |
12 |
5 |
5 |
5 |
12 |
12 |
5 |
|
G4, M & 1000 |
Mean |
443.94 |
0.0156 |
0.0891* |
0.1779 |
0.7570 |
0.3432 |
0.3304 |
±SD |
38.78 |
0.0013 |
0.0124 |
0.0187 |
0.0592 |
0.0298 |
0.0626 |
|
n |
12 |
5 |
5 |
5 |
12 |
12 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals.
TABLE 20 (Contd…).
SUMMARY OF TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Kidneys |
Brain |
Liver |
Prostate |
Seminal vesicles with coagulating glands |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
|
G1, M & 0 |
Mean |
0.6591 |
0.4745 |
2.2336 |
0.2614 |
0.3768 |
0.4360 |
0.0047 |
0.0067 |
±SD |
0.0371 |
0.0334 |
0.2239 |
0.0389 |
0.1233 |
0.0428 |
0.0003 |
0.0004 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
12 |
|
G2, M & 111 |
Mean |
0.6380 |
0.4818 |
2.3449 |
0.2758 |
0.3681 |
0.4668 |
0.0044 |
0.0067 |
±SD |
0.0606 |
0.0272 |
0.0585 |
0.0505 |
0.0681 |
0.0350 |
0.0003 |
0.0006 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
12 |
|
G3, M & 333 |
Mean |
0.6350 |
0.4812 |
2.3924 |
0.3052 |
0.4081 |
0.4594 |
0.0046 |
0.0069 |
±SD |
0.0467 |
0.0237 |
0.2415 |
0.0710 |
0.0824 |
0.0376 |
0.0001 |
0.0004 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
12 |
|
G4, M & 1000 |
Mean |
0.6545 |
0.4865 |
2.3426 |
0.2767 |
0.4271 |
0.4575 |
0.0045 |
0.0069 |
±SD |
0.1286 |
0.0618 |
0.4199 |
0.0940 |
0.1161 |
0.0285 |
0.0002 |
0.0004 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
12 |
M: Male; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation.
TABLE 20 (Contd…).
SUMMARY OF TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Terminal Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Ovaries |
Uterus with Cervix |
Heart |
|
G1, F & 0 |
Mean |
305.54 |
0.0242 |
0.0912 |
0.2307 |
0.0571 |
0.1938 |
0.3872 |
±SD |
21.99 |
0.0035 |
0.0163 |
0.0360 |
0.0100 |
0.0422 |
0.0618 |
|
n |
12 |
5 |
5 |
5 |
12 |
11@ |
5 |
|
G2, F & 111 |
Mean |
314.85 |
0.0286 |
0.0853 |
0.2428 |
0.0458* |
0.1635 |
0.3854 |
±SD |
19.21 |
0.0044 |
0.0142 |
0.0457 |
0.0115 |
0.0448 |
0.0220 |
|
n |
12 |
5 |
5 |
5 |
12 |
11@ |
5 |
|
G3, F & 333 |
Mean |
302.78 |
0.0236 |
0.0730 |
0.2142 |
0.0431* |
0.1801 |
0.3879 |
±SD |
22.49 |
0.0038 |
0.0045 |
0.0429 |
0.0092 |
0.0352 |
0.0151 |
|
n |
12 |
5 |
5 |
5 |
12 |
12 |
5 |
|
G4, F & 1000 |
Mean |
306.64 |
0.0245 |
0.0690* |
0.1938 |
0.0483 |
0.1749 |
0.4241 |
±SD |
25.44 |
0.0033 |
0.0062 |
0.0238 |
0.0080 |
0.0430 |
0.1222 |
|
n |
12 |
5 |
5 |
5 |
12 |
12 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals.
@: One animal data from group G1 and G2 is excluded for mean calculations as the weight varies from normal uterus due to presence of dead foetus during necropsy, but the data is presented in individual animal data. (Appendix 23).
TABLE 20 (Contd…). SUMMARY OF TERMINAL BODY WEIGHT (g) AND
ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Kidneys |
Brain |
Liver |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
|
G1, F & 0 |
Mean |
0.7409 |
0.6583 |
3.7703 |
0.4138 |
0.0058 |
0.0087 |
±SD |
0.0909 |
0.0663 |
0.3600 |
0.0696 |
0.0003 |
0.0005 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
|
G2, F & 111 |
Mean |
0.6618 |
0.6488 |
4.0668 |
0.4903 |
0.0059 |
0.0087 |
±SD |
0.0563 |
0.0584 |
0.6665 |
0.0770 |
0.0002 |
0.0009 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
|
G3, F & 333 |
Mean |
0.6560 |
0.6443 |
3.2646 |
0.4388 |
0.0057 |
0.0088 |
±SD |
0.0476 |
0.0330 |
0.5652 |
0.0452 |
0.0002 |
0.0007 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
|
G4, F & 1000 |
Mean |
0.6097* |
0.6402 |
3.2355 |
0.4353 |
0.0057 |
0.0090 |
±SD |
0.0642 |
0.0516 |
0.3329 |
0.0373 |
0.0008 |
0.0007 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
F: Female; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 20 (Contd…). SUMMARY OF TERMINAL BODY WEIGHT (g) AND
ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Terminal Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Testes |
Epididymides |
Heart |
|
G1R, M & 0 |
Mean |
496.58 |
0.0136 |
0.0476 |
0.1785 |
0.6684 |
0.3430 |
0.3320 |
±SD |
40.88 |
0.0022 |
0.0051 |
0.0257 |
0.0554 |
0.0286 |
0.0478 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
502.58 |
0.0127 |
0.0538 |
0.1482* |
0.6902 |
0.3358 |
0.3184 |
±SD |
12.09 |
0.0010 |
0.0137 |
0.0126 |
0.0356 |
0.0088 |
0.0643 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 20 (Contd…).
SUMMARY OF TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Kidneys |
Brain |
Liver |
Prostate |
Seminal vesicles with coagulating glands |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
|
G1R, M & 0 |
Mean |
0.4554 |
0.4147 |
2.5665 |
0.2783 |
0.3746 |
0.4088 |
0.0042 |
0.0060 |
±SD |
0.0586 |
0.0488 |
0.3239 |
0.0415 |
0.1185 |
0.0840 |
0.0002 |
0.0003 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
0.4682 |
0.4080 |
2.4984 |
0.3193 |
0.3643 |
0.3862 |
0.0042 |
0.0061 |
±SD |
0.0730 |
0.0361 |
0.1858 |
0.0248 |
0.0941 |
0.0153 |
0.0002 |
0.0003 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation.
TABLE 20 (Contd…).
SUMMARY OF TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Terminal Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Ovaries |
Uterus with Cervix |
Heart |
G1R, F & 0 |
Mean |
308.17 |
0.0229 |
0.0822 |
0.2106 |
0.0410 |
0.2112 |
0.3432 |
±SD |
16.88 |
0.0016 |
0.0185 |
0.0336 |
0.0043 |
0.0292 |
0.0498 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
311.82 |
0.0225 |
0.0791 |
0.2015 |
0.0495* |
0.2026 |
0.3256 |
±SD |
12.71 |
0.0037 |
0.0102 |
0.0405 |
0.0029 |
0.0205 |
0.0293 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 1. SUMMARY
OF CLINICAL SIGNS OF TOXICITY, DETAILED CLINICAL EXAMINATION AND
MORTALITY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total No. of Animals |
Clinical Signs of Toxicitya: Observation |
Detailed Clinical Examinationb: Observation |
Mortalityc: No. of Mortalities |
G1, M & 0 |
12 |
N (12) |
NAD (12) |
0 (12) |
G2, M & 111 |
12 |
N (12) |
NAD (12) |
0 (12) |
G3, M & 333 |
12 |
N (12) |
NAD (12) |
0 (12) |
G4, M & 1000 |
12 |
N (12) |
NAD (12) |
0 (12) |
M:
Male; N: Normal; NAD: No Abnormality Detected.
a: observed once daily; b: observed once weekly; c: observed twice daily.
Note:Dark purple colored faeces were noted from day 2 observation throughout the experiment period till termination in group G3 & G4 animals.
TABLE 1 (Contd…). SUMMARY
OF CLINICAL SIGNS OF TOXICITY, DETAILED CLINICAL EXAMINATION
AND MORTALITY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total No. of Animals |
Clinical Signs of Toxicitya: Observation |
Detailed Clinical Examinationb: Observation |
Mortalityc: No. of Mortalities |
G1, F & 0 |
12 |
N (12) |
NAD (12) |
0 (12) |
G2, F & 111 |
12 |
N (12) |
NAD (12) |
0 (12) |
G3, F & 333 |
12 |
N (12) |
NAD (12) |
0 (12) |
G4, F & 1000 |
12 |
N (12) |
NAD (12) |
0 (12) |
F:
Female; N: Normal; NAD: No Abnormality Detected.
a: observed once daily; b: observed once weekly; c: observed twice daily.
Note:Dark purple colored faeces were noted from day 2 observation throughout the experiment period till termination in group G3 & G4 animals.
TABLE 1 (Contd…). SUMMARY
OF CLINICAL SIGNS OF TOXICITY, DETAILED CLINICAL EXAMINATION
AND MORTALITY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total No. of Animals |
Clinical Signs of Toxicitya: Observation |
Detailed Clinical Examinationb: Observation |
Mortalityc: No. of Mortalities |
G1R, M & 0 |
5 |
N (5) |
NAD (5) |
0 (5) |
G4R, M & 1000 |
5 |
N (5) |
NAD (5) |
0 (5) |
G1R, F & 0 |
5 |
N (5) |
NAD (5) |
0 (5) |
G4R, F & 1000 |
5 |
N (5) |
NAD (5) |
0 (5) |
M:
Male; F: Female; R: Recovery; N: Normal; NAD: No abnormality detected.
a: observed once daily; b: observed once weekly; c: observed twice daily.
Note:Dark purple colored faeces were noted from day 2 throughout the experiment period till termination in group G4R animals.
TABLE 2. SUMMARY OF BODY WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Body Weight (g) on Day |
|||||
1 |
7 |
14 |
21 |
28 |
|||
G1, M & 0 |
Mean |
400.75 |
421.20 |
438.19 |
446.01 |
458.77 |
|
±SD |
22.07 |
32.34 |
36.49 |
37.08 |
38.53 |
||
n |
12 |
12 |
12 |
12 |
12 |
||
G2, M & 111 |
Mean |
401.74 |
417.26 |
433.41 |
442.75 |
452.56 |
|
±SD |
20.39 |
24.35 |
30.70 |
31.29 |
30.16 |
||
n |
12 |
12 |
12 |
12 |
12 |
||
G3, M & 333 |
Mean |
402.72 |
419.51 |
438.54 |
444.84 |
456.36 |
|
±SD |
19.35 |
23.54 |
30.11 |
27.23 |
24.95 |
||
n |
12 |
12 |
12 |
12 |
12 |
||
G4, M & 1000 |
Mean |
401.99 |
422.76 |
443.74 |
453.94 |
463.38 |
|
±SD |
21.50 |
27.21 |
34.32 |
36.83 |
39.17 |
||
n |
12 |
12 |
12 |
12 |
12 |
||
M: Male; SD: Standard Deviation; n: Number of Animals.
TABLE 2 (Contd…). SUMMARY OF BODY WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Body Weight (g) on Day |
||||
1 |
7 |
14 |
21# |
|||
G1, F & 0 |
Mean |
250.88 |
257.35 |
267.91 |
280.34 |
|
±SD |
14.86 |
17.17 |
18.25 |
26.26 |
||
n |
12 |
12 |
12 |
3 |
||
G2, F & 111 |
Mean |
251.05 |
256.43 |
266.53 |
272.56 |
|
±SD |
12.78 |
15.62 |
15.30 |
25.98 |
||
n |
12 |
12 |
12 |
3 |
||
G3, F & 333 |
Mean |
251.13 |
256.32 |
261.08 |
260.46 |
|
±SD |
13.59 |
14.00 |
15.94 |
17.45 |
||
n |
12 |
12 |
12 |
4 |
||
G4, F & 1000 |
Mean |
251.24 |
261.46 |
265.51 |
269.05 |
|
±SD |
15.56 |
18.91 |
20.71 |
24.37 |
||
n |
12 |
12 |
12 |
4 |
||
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 body weight was not subjected to statistical analysis due to uneven number of variables.
TABLE 2 (Contd…). SUMMARY OF BODY WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Body Weight (g) on Day |
||||||||||
1 |
7 |
14 |
21 |
28 |
35 |
42 |
49 |
56 |
63 |
|||
G1R, M & 0 |
Mean |
395.45 |
407.17 |
422.63 |
436.11 |
448.75 |
458.35 |
473.23 |
489.33 |
502.87 |
514.37 |
|
±SD |
21.72 |
21.10 |
31.29 |
32.45 |
32.78 |
34.62 |
33.67 |
33.58 |
34.92 |
37.99 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, M & 1000 |
Mean |
396.36 |
412.35 |
430.15 |
444.31 |
454.98 |
464.82 |
475.04 |
493.68 |
508.20 |
519.69 |
|
±SD |
20.86 |
20.17 |
12.53 |
16.96 |
17.27 |
14.72 |
15.50 |
9.28 |
11.65 |
11.69 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G1R, F & 0 |
Mean |
245.24 |
250.97 |
262.44 |
268.72 |
277.56 |
284.92 |
295.96 |
306.72 |
315.86 |
324.75 |
|
±SD |
10.97 |
10.11 |
13.68 |
15.80 |
15.60 |
15.72 |
19.40 |
19.59 |
17.41 |
15.21 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, F & 1000 |
Mean |
245.66 |
248.99 |
264.41 |
270.43 |
278.43 |
286.33 |
298.35 |
308.32 |
318.51 |
327.87 |
|
±SD |
12.82 |
12.43 |
13.84 |
12.16 |
11.19 |
12.10 |
12.79 |
13.72 |
10.97 |
12.44 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals.
TABLE 3. SUMMARY RECORD OF GESTATION BODY WEIGHT (g)
Group, Sex & Dose (mg/kg body weight/day) |
Body Weight (g) on Gestation Day (GD) |
||||
0 |
7 |
14 |
20 |
||
G1, F & 0 |
Mean |
272.42 |
287.38 |
319.92 |
375.62 |
±SD |
18.33 |
21.41 |
28.89 |
35.87 |
|
n |
11 |
11 |
11 |
11 |
|
G2, F & 111 |
Mean |
269.81 |
286.87 |
328.45 |
391.71 |
±SD |
11.98 |
12.37 |
15.11 |
22.46 |
|
n |
10 |
10 |
10 |
10 |
|
G3, F & 333 |
Mean |
264.91 |
282.42 |
317.51 |
369.85 |
±SD |
15.69 |
14.58 |
20.68 |
32.90 |
|
n |
10 |
10 |
10 |
10 |
|
G4, F & 1000 |
Mean |
273.49 |
291.35 |
327.07 |
382.89 |
±SD |
17.37 |
17.37 |
23.26 |
39.30 |
|
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.
TABLE 4. SUMMARY RECORD OF LACTATION BODY WEIGHT (g)
Group, Sex & Dose (mg/kg body weight/day) |
Body Weight (g) on Lactation Day (LD) |
||||
1 |
4 |
7 |
13 |
||
G1, F & 0 |
Mean |
294.60 |
300.48 |
308.18 |
323.25 |
±SD |
22.07 |
22.28 |
22.06 |
20.39 |
|
n |
11 |
11 |
11 |
11 |
|
G2, F & 111 |
Mean |
306.24 |
309.48 |
314.78 |
330.57 |
±SD |
22.46 |
21.39 |
20.72 |
19.26 |
|
n |
10 |
10 |
10 |
10 |
|
G3, F & 333 |
Mean |
293.35 |
297.31 |
304.48 |
319.65 |
±SD |
19.47 |
20.23 |
20.46 |
22.22 |
|
n |
10 |
10 |
10 |
10 |
|
G4, F & 1000 |
Mean |
303.31 |
306.82 |
313.01 |
325.64 |
±SD |
22.77 |
24.10 |
23.73 |
23.27 |
|
n |
11 |
11 |
11 |
11 |
|
F: Female; SD: Standard Deviation; n: Number of Dams.
TABLE 5. SUMMARY
OF PERCENT CHANGE IN BODY WEIGHT GAIN (%)
WITH RESPECT TO DAY 1 RECORD
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, M & 0 |
Mean |
5.01 |
9.25 |
11.19 |
14.36 |
|
±SD |
3.10 |
4.96 |
4.86 |
4.98 |
||
n |
12 |
12 |
12 |
12 |
||
G2, M & 111 |
Mean |
3.84 |
7.80 |
10.13 |
12.59 |
|
±SD |
2.04 |
3.09 |
3.48 |
3.20 |
||
n |
12 |
12 |
12 |
12 |
||
G3, M & 333 |
Mean |
4.15 |
8.89 |
10.50 |
13.42 |
|
±SD |
2.15 |
5.14 |
5.14 |
5.61 |
||
n |
12 |
12 |
12 |
12 |
||
G4, M & 1000 |
Mean |
5.12 |
10.29 |
12.82 |
15.16 |
|
±SD |
1.91 |
3.83 |
4.55 |
5.27 |
||
n |
12 |
12 |
12 |
12 |
||
M: Male; SD: Standard Deviation; n: Number of Animals.
TABLE 5 (Contd…). SUMMARY OF PERCENTCHANGE IN BODY WEIGHT GAIN (%) WITH RESPECT TO DAY 1 RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Percent Change in Body Weight (%) during Day |
|||
1 to 7 |
1 to 14 |
1 to 21# |
|||
G1, F & 0 |
Mean |
2.56 |
6.78 |
10.07 |
|
±SD |
2.21 |
3.23 |
3.01 |
||
n |
12 |
12 |
3 |
||
G2, F & 111 |
Mean |
2.12 |
6.21 |
9.94 |
|
±SD |
2.46 |
4.16 |
1.49 |
||
n |
12 |
12 |
3 |
||
G3, F & 333 |
Mean |
2.08 |
3.94 |
5.98 |
|
±SD |
1.81 |
2.08 |
1.64 |
||
n |
12 |
12 |
4 |
||
G4, F & 1000 |
Mean |
4.05 |
5.61 |
9.37 |
|
±SD |
3.24 |
3.20 |
3.75 |
||
n |
12 |
12 |
4 |
||
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.
TABLE 5 (Contd…). SUMMARY OF PERCENT CHANGE IN BODY WEIGHT GAIN (%) WITH RESPECT TO DAY1 RECORD
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 |
1 to 42 |
1 to 49 |
1 to 56 |
1 to 63 |
|||
G1R, M & 0 |
Mean |
2.98 |
6.83 |
10.25 |
13.47 |
15.92 |
19.69 |
23.73 |
27.13 |
30.00 |
|
±SD |
0.92 |
4.09 |
4.67 |
5.29 |
6.27 |
5.81 |
4.88 |
4.25 |
4.30 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, M & 1000 |
Mean |
4.06 |
8.66 |
12.20 |
14.91 |
17.44 |
20.09 |
24.77 |
28.45 |
31.32 |
|
±SD |
1.73 |
3.60 |
3.33 |
3.84 |
4.90 |
6.78 |
5.51 |
6.10 |
5.14 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G1R, F & 0 |
Mean |
2.35 |
7.00 |
9.55 |
13.20 |
16.19 |
20.62 |
25.02 |
28.77 |
32.44 |
|
±SD |
0.72 |
2.36 |
3.15 |
4.61 |
4.45 |
4.14 |
4.54 |
3.55 |
3.44 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, F & 1000 |
Mean |
1.37 |
7.66 |
10.20 |
13.45 |
16.65 |
21.52 |
25.60 |
29.78 |
33.57 |
|
±SD |
1.07 |
2.71 |
4.80 |
4.07 |
3.73 |
3.02 |
4.10 |
3.75 |
3.31 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals.
TABLE 6. SUMMARY RECORD OF PERCENT CHANGE IN BODY WEIGHT GAIN (%) DURING GESTATION PERIOD
Group, Sex & Dose (mg/kg body weight/day) |
Percent Change in Body Weight Gain (%) during Gestation Day (GD) |
|||
0 to 7 |
7 to 14 |
14 to 20 |
||
G1, F & 0 |
Mean |
5.46 |
11.22 |
17.44 |
±SD |
1.77 |
2.82 |
4.18 |
|
n |
11 |
11 |
11 |
|
G2, F & 111 |
Mean |
6.35 |
14.52 |
19.23 |
±SD |
2.12 |
3.20 |
3.16 |
|
n |
10 |
10 |
10 |
|
G3, F & 333 |
Mean |
6.67 |
12.40 |
16.35 |
±SD |
1.92 |
3.55 |
3.43 |
|
n |
10 |
10 |
10 |
|
G4, F & 1000 |
Mean |
6.56 |
12.23 |
16.88 |
±SD |
1.60 |
3.35 |
4.81 |
|
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.
TABLE 7. SUMMARY RECORD OF PERCENT CHANGE IN BODY WEIGHT GAIN (%) DURING LACTATION PERIOD
Group, Sex & Dose (mg/kg body weight/day) |
Percent Change in Body Weight Gain (%) during Lactation Day (LD) |
|||
1 to 4 |
4 to 7 |
7 to 13 |
||
G1, F & 0 |
Mean |
2.01 |
2.58 |
4.96 |
±SD |
0.96 |
0.73 |
1.51 |
|
n |
11 |
11 |
11 |
|
G2, F & 111 |
Mean |
1.08 |
1.74 |
5.07 |
±SD |
0.86 |
0.95 |
1.60 |
|
n |
10 |
10 |
10 |
|
G3, F & 333 |
Mean |
1.35 |
2.42 |
4.98 |
±SD |
0.95 |
1.29 |
1.32 |
|
n |
10 |
10 |
10 |
|
G4, F & 1000 |
Mean |
1.14 |
2.04 |
4.06 |
±SD |
1.00 |
0.93 |
0.83 |
|
n |
11 |
11 |
11 |
|
F: Female; SD: Standard Deviation; n: Number of Dams.
TABLE 8. SUMMARY OF FEED CONSUMPTION (g/animal/day) RECORD
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 |
21.31 |
24.01 |
±SD |
2.38 |
1.81 |
|
n |
12 (6) |
12 (6) |
|
G2, M & 111 |
Mean |
21.39 |
23.12 |
±SD |
1.76 |
0.75 |
|
n |
12 (6) |
12 (6) |
|
G3, M & 333 |
Mean |
22.25 |
23.93 |
±SD |
2.39 |
1.85 |
|
n |
12 (6) |
12 (6) |
|
G4, M & 1000 |
Mean |
22.28 |
24.17 |
±SD |
1.23 |
0.67 |
|
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
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 |
18.14 |
19.17 |
±SD |
1.56 |
1.22 |
|
n |
12 (6) |
12 (6) |
|
G2, F & 111 |
Mean |
17.79 |
20.11 |
±SD |
1.85 |
1.70 |
|
n |
12 (6) |
12 (6) |
|
G3, F & 333 |
Mean |
18.26 |
19.22 |
±SD |
1.99 |
1.31 |
|
n |
12 (6) |
12 (6) |
|
G4, F & 1000 |
Mean |
18.43 |
20.07 |
±SD |
2.28 |
1.22 |
|
n |
12 (6) |
12 (6) |
|
F: Female; SD: Standard Deviation; n: Number of Animals (Number of cages).
TABLE 8 (Contd…). SUMMARY OF FEED CONSUMPTION (g/animal/day) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Feed Consumption (g/animal/day) |
||||||||
Week 1 |
Week 2 |
Week 3 |
Week 4 |
Week 5 |
Week 6 |
Week 7 |
Week 8 |
Week 9 |
||
G1R, M & 0 |
Mean |
23.52 |
24.34 |
25.11 |
26.35 |
27.86 |
29.05 |
30.75 |
31.83 |
32.47 |
±SD |
3.71 |
1.67 |
1.55 |
1.27 |
0.97 |
1.11 |
0.47 |
3.66 |
3.01 |
|
n |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
|
G4R, M & 1000 |
Mean |
22.84 |
23.75 |
24.26 |
27.17 |
28.86 |
30.05 |
31.07 |
32.19 |
33.03 |
±SD |
0.77 |
1.04 |
1.34 |
2.09 |
2.61 |
2.18 |
2.12 |
1.59 |
1.67 |
|
n |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
|
G1R, F & 0 |
Mean |
17.44 |
18.36 |
19.45 |
10.21 |
23.17 |
24.20 |
25.35 |
26.19 |
27.04 |
±SD |
1.79 |
0.40 |
0.40 |
9.72 |
0.99 |
0.82 |
0.62 |
0.41 |
0.99 |
|
n |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
|
G4R, F & 1000 |
Mean |
17.21 |
19.05 |
20.42 |
11.29 |
24.18 |
25.37 |
26.19 |
27.14 |
27.89 |
±SD |
0.69 |
1.77 |
0.91 |
10.38 |
0.03 |
0.80 |
0.84 |
0.69 |
0.68 |
|
n |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
|
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals(Number of cages).
TABLE 9. SUMMARY RECORD OF FEED CONSUMPTION (g/animal/day) DURING GESTATION PERIOD
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 |
19.02 |
21.07 |
25.81 |
SD |
0.70 |
1.95 |
1.63 |
|
n |
11 |
11 |
11 |
|
G2, F & 111 |
Mean |
19.23 |
22.20 |
26.84 |
SD |
0.88 |
1.81 |
1.78 |
|
n |
10 |
10 |
10 |
|
G3, F & 333 |
Mean |
19.00 |
21.49 |
26.11 |
SD |
0.74 |
1.39 |
1.26 |
|
n |
10 |
10 |
10 |
|
G4, F & 1000 |
Mean |
19.43 |
22.01 |
26.67 |
SD |
0.58 |
1.70 |
1.97 |
|
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.
TABLE 10. SUMMARY RECORD OF FEED CONSUMTION (g/animal/day) DURING LACTATION PERIOD
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 |
25.21 |
35.80 |
40.88 |
SD |
1.20 |
7.26 |
1.43 |
|
n |
11 |
11 |
11 |
|
G2, F & 111 |
Mean |
24.58 |
32.72 |
41.09 |
SD |
1.34 |
0.99 |
0.98 |
|
n |
10 |
10 |
10 |
|
G3, F & 333 |
Mean |
25.11 |
32.75 |
40.54 |
SD |
1.42 |
1.16 |
0.94 |
|
n |
10 |
10 |
10 |
|
G4, F & 1000 |
Mean |
23.94 |
33.14 |
39.84 |
SD |
5.99 |
1.28 |
1.03 |
|
n |
11 |
11 |
11 |
|
F: Female; SD: Standard Deviation; n: Number of Dams.
TABLE 11. SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day -1 (Grouping and randomization) |
||||||||
Group, Sex & Dose weight/day) → |
G1, M & 0 |
G2, M & 111 |
G3, M & 333 |
G4, M & 1000 |
||||
Number of Animals→ |
12 |
12 |
12 |
12 |
||||
Observations↓ |
||||||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
N |
N |
N |
N |
M: Male; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day -1 (Grouping and randomization) |
||||||||
Group, Sex & Dose weight/day) → |
G1, F & 0 |
G2, F & 111 |
G3, F & 333 |
G4, F & 1000 |
||||
Number of Animals→ |
12 |
12 |
12 |
12 |
||||
Observations↓ |
||||||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
N |
N |
N |
N |
F: Female; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day -1 (Grouping and randomization) |
||||
Group, Sex & Dose weight/day) → |
G1R, M & 0 |
G4R, M & 1000 |
||
Number of Animals→ |
5 |
5 |
||
Observations↓ |
||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
M: Male; R: Recovery; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day -1 (Grouping and randomization) |
||||
Group, Sex & Dose weight/day) → |
G1R, F & 0 |
G4R, F & 1000 |
||
Number of Animals→ |
5 |
5 |
||
Observations↓ |
||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
F: Female; R: Recovery; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day 30 |
||||||||
Group, Sex & Dose weight/day) → |
G1, M & 0 |
G2, M & 111 |
G3, M & 333 |
G4, M & 1000 |
||||
Number of Animals→ |
12 |
12 |
12 |
12 |
||||
Observations↓ |
||||||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
N |
N |
N |
N |
Other findings: |
N |
N |
N |
N |
N |
N |
N |
N |
M: Male; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Pregnant/Littered females: Lactation day 13; Non-pregnant females: (Experimental day 39 to 52) |
||||||||
Group, Sex & Dose weight/day) → |
G1, F & 0 |
G2, F & 111 |
G3, F & 333 |
G4, F & 1000 |
||||
Number of Animals→ |
12 |
12 |
12 |
12 |
||||
Observations↓ |
||||||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
N |
N |
N |
N |
Other findings: |
N |
N |
N |
N |
N |
N |
N |
N |
F: Female; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day 65 |
||||
Group, Sex & Dose weight/day) → |
G1R, M & 0 |
G4R, M & 1000 |
||
Number of Animals→ |
5 |
5 |
||
Observations↓ |
||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
Other findings: |
N |
N |
N |
N |
M: Male; R: Recovery; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day 65 |
||||
Group, Sex & Dose weight/day) → |
G1R, F & 0 |
G4R, F & 1000 |
||
Number of Animals→ |
5 |
5 |
||
Observations↓ |
||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
Other findings: |
N |
N |
N |
N |
F: Female; R: Recovery; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 12. SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD
Day 30 |
||||||
Parameters↓ |
Group & Sex |
G1 & M |
G2 & M |
G3 & M |
G4 & M |
|
Dose (mg/kg body weight/day) |
0 |
111 |
333 |
1000 |
||
Number of Animals (randomly selected) |
5 |
5 |
5 |
5 |
||
Home Cage Observations |
||||||
Home cage posture |
1 |
1 |
1 |
1 |
||
Respiratory pattern |
1 |
1 |
1 |
1 |
||
Clonic involuntary movements |
1 |
1 |
1 |
1 |
||
Tonic involuntary movements |
1 |
1 |
1 |
1 |
||
Vocalization |
1 |
1 |
1 |
1 |
||
Palpebral closure |
1 |
1 |
1 |
1 |
||
Handling Observations |
||||||
Ease of removal from the cage |
2 |
2 |
2 |
2 |
||
Ease of handling animal in hand |
2 |
2 |
2 |
2 |
||
Red or crusty deposits |
Eyes |
1 |
1 |
1 |
1 |
|
Nose |
1 |
1 |
1 |
1 |
||
Mouth |
1 |
1 |
1 |
1 |
||
Lacrimation |
1 |
1 |
1 |
1 |
||
Salivation |
1 |
1 |
1 |
1 |
||
Fur appearance |
1 |
1 |
1 |
1 |
||
Piloerection |
1 |
1 |
1 |
1 |
||
Eye prominence |
1 |
1 |
1 |
1 |
||
Muscle tone |
1 |
1 |
1 |
1 |
||
Home Cage Observations:Home cage posture - 1=Normal; Respiratory pattern - 1=Normal; Clonic involuntary movements - 1=None; Tonic involuntary movements - 1=None; Vocalization - 1=None; Palpebral closure - 1=Normal;Handling Observations:Ease of removal from the cage - 2=Normal; Ease of handling animal in hand - 2=Normal; Red or crusty deposits - 1=Absent; Lacrimation - 1=None; Salivation- 1=None; Fur appearance - 1=Normal; Piloerection - 1=None; Eye Prominence - 1=Normal; Muscle tone - 1=Normal |
||||||
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD
Day 30 |
||||||
Parameters↓ |
Group & Sex |
G1 & M |
G2 & M |
G3 & M |
G4 & M |
|
Dose (mg/kg body weight/day) |
0 |
111 |
333 |
1000 |
||
Number of Animals (randomly selected) |
5 |
5 |
5 |
5 |
||
Open Field Observations |
||||||
Mobility |
1 |
1 |
1 |
1 |
||
Gait |
1 |
1 |
1 |
1 |
||
Arousal |
3 |
3 |
3 |
3 |
||
Number of rearing |
Mean |
4.4 |
4.8 |
4.8 |
4.8 |
|
±SD |
1.1 |
0.8 |
0.8 |
0.8 |
||
Number of urine pools |
Mean |
3.4 |
3.8 |
3.8 |
3.8 |
|
±SD |
0.5 |
0.8 |
0.8 |
0.8 |
||
Number of defecations |
Mean |
3.4 |
3.2 |
3.4 |
3.2 |
|
±SD |
0.5 |
0.8 |
0.5 |
0.4 |
||
Clonic involuntary movement |
1 |
1 |
1 |
1 |
||
Tonic involuntary movement |
1 |
1 |
1 |
1 |
||
Stereotype behaviour |
1 |
1 |
1 |
1 |
||
Number of grooming |
Mean |
3.4 |
3.2 |
3.4 |
3.2 |
|
±SD |
0.5 |
0.8 |
0.5 |
0.8 |
||
Sensory Observations |
||||||
Approach response |
2 |
2 |
2 |
2 |
||
Auditory response |
2 |
2 |
2 |
2 |
||
Touch response |
2 |
2 |
2 |
2 |
||
Pupil reflex |
2 |
2 |
2 |
2 |
||
Tail pinch response |
2 |
2 |
2 |
2 |
||
Righting reflex |
1 |
1 |
1 |
1 |
||
Physiological Observation |
||||||
Body temperature (°F) |
Mean |
98.4 |
98.4 |
98.1 |
98.4 |
|
±SD |
0.5 |
0.4 |
0.3 |
0.5 |
||
Open Field Observations: Mobility- 1=Normal;Gait- 1=Normal;Arousal- 3=Normal;Clonic involuntary movement- 1=None;Tonic involuntary movement -1=None;Stereotype behaviour -1=Absent;Sensory Observations:Approach response- 2=Normal;Auditory response- 2=Normal;Touch response -2=Normal;Pupil reflex- 2=Normal;Tail pinch response- 2=Normal;Righting reflex- 1=Present |
||||||
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)
Lactation Day 13 |
||||||
Parameters↓ |
Group & Sex |
G1 & F |
G2 & F |
G3 & F |
G4 & F |
|
Dose (mg/kg body weight/day) |
0 |
111 |
333 |
1000 |
||
Number of Animals (randomly selected) |
5 |
5 |
5 |
5 |
||
Home Cage Observations |
||||||
Home cage posture |
1 |
1 |
1 |
1 |
||
Respiratory pattern |
1 |
1 |
1 |
1 |
||
Clonic involuntary movements |
1 |
1 |
1 |
1 |
||
Tonic involuntary movements |
1 |
1 |
1 |
1 |
||
Vocalization |
1 |
1 |
1 |
1 |
||
Palpebral closure |
1 |
1 |
1 |
1 |
||
Handling Observations |
||||||
Ease of removal from the cage |
2 |
2 |
2 |
2 |
||
Ease of handling animal in hand |
2 |
2 |
2 |
2 |
||
Red or crusty deposits |
Eyes |
1 |
1 |
1 |
1 |
|
Nose |
1 |
1 |
1 |
1 |
||
Mouth |
1 |
1 |
1 |
1 |
||
Lacrimation |
1 |
1 |
1 |
1 |
||
Salivation |
1 |
1 |
1 |
1 |
||
Fur appearance |
1 |
1 |
1 |
1 |
||
Piloerection |
1 |
1 |
1 |
1 |
||
Eye prominence |
1 |
1 |
1 |
1 |
||
Muscle tone |
1 |
1 |
1 |
1 |
||
Home Cage Observations:Home cage posture - 1=Normal; Respiratory pattern - 1=Normal; Clonic involuntary movements - 1=None; Tonic involuntary movements - 1=None; Vocalization - 1=None; Palpebral closure - 1=Normal;Handling Observations:Ease of removal from the cage - 2=Normal; Ease of handling animal in hand - 2=Normal; Red or crusty deposits - 1=Absent; Lacrimation - 1=None; Salivation- 1=None; Fur appearance - 1=Normal; Piloerection - 1=None; Eye Prominence - 1=Normal; Muscle tone - 1=Normal |
||||||
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)
Lactation Day 13 |
||||||
Parameters↓ |
Group & Sex |
G1 & F |
G2 & F |
G3 & F |
G4 & F |
|
Dose (mg/kg body weight/day) |
0 |
111 |
333 |
1000 |
||
Number of Animals (randomly selected) |
5 |
5 |
5 |
5 |
||
Open Field Observations |
||||||
Mobility |
1 |
1 |
1 |
1 |
||
Gait |
1 |
1 |
1 |
1 |
||
Arousal |
3 |
3 |
3 |
3 |
||
Number of rearing |
Mean |
4.8 |
4.8 |
4.8 |
4.8 |
|
±SD |
0.8 |
0.8 |
0.8 |
0.8 |
||
Numbers of urine pools |
Mean |
3.6 |
3.8 |
3.6 |
3.8 |
|
±SD |
0.5 |
0.8 |
0.5 |
0.8 |
||
Number of defecations |
Mean |
3.4 |
3.0 |
2.8 |
3.2 |
|
±SD |
0.9 |
0.7 |
0.8 |
0.4 |
||
Clonic involuntary movement |
1 |
1 |
1 |
1 |
||
Tonic involuntary movement |
1 |
1 |
1 |
1 |
||
Stereotype behaviour |
1 |
1 |
1 |
1 |
||
Number of grooming |
Mean |
3.2 |
3.2 |
2.6 |
3.0 |
|
±SD |
0.4 |
0.8 |
0.5 |
0.7 |
||
Sensory Observations |
||||||
Approach response |
2 |
2 |
2 |
2 |
||
Auditory response |
2 |
2 |
2 |
2 |
||
Touch response |
2 |
2 |
2 |
2 |
||
Pupil reflex |
2 |
2 |
2 |
2 |
||
Tail pinch response |
2 |
2 |
2 |
2 |
||
Righting reflex |
1 |
1 |
1 |
1 |
||
Physiological Observation |
||||||
Body temperature (°F) |
Mean |
98.4 |
98.4 |
98.8 |
98.7 |
|
±SD |
0.6 |
0.5 |
0.5 |
0.8 |
||
Open Field Observations: Mobility- 1=Normal;Gait- 1=Normal;Arousal- 3=Normal;Clonic involuntary movement- 1=None;Tonic involuntary movement -1=None;Stereotype behaviour -1=Absent;Sensory Observations:Approach response- 2=Normal;Auditory response- 2=Normal;Touch response -2=Normal;Pupil reflex- 2=Normal;Tail pinch response- 2=Normal;Righting reflex- 1=Present |
||||||
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)
Day 65 |
||||
Parameters↓ |
Group & Sex |
G1R & M |
G4R & M |
|
Dose (mg/kg body weight/day) |
0 |
1000 |
||
Number of Animals |
5 |
5 |
||
Home Cage Observations |
||||
Home cage posture |
1 |
1 |
||
Respiratory pattern |
1 |
1 |
||
Clonic involuntary movements |
1 |
1 |
||
Tonic involuntary movements |
1 |
1 |
||
Vocalization |
1 |
1 |
||
Palpebral closure |
1 |
1 |
||
Handling Observations |
||||
Ease of removal from the cage |
2 |
2 |
||
Ease of handling animal in hand |
2 |
2 |
||
Red or crusty deposits |
Eyes |
1 |
1 |
|
Nose |
1 |
1 |
||
Mouth |
1 |
1 |
||
Lacrimation |
1 |
1 |
||
Salivation |
1 |
1 |
||
Fur appearance |
1 |
1 |
||
Piloerection |
1 |
1 |
||
Eye prominence |
1 |
1 |
||
Muscle tone |
1 |
1 |
||
Home Cage Observations:Home cage posture - 1=Normal; Respiratory pattern - 1=Normal; Clonic involuntary movements - 1=None; Tonic involuntary movements - 1=None; Vocalization - 1=None; Palpebral closure - 1=Normal;Handling Observations:Ease of removal from the cage - 2=Normal; Ease of handling animal in hand - 2=Normal; Red or crusty deposits - 1=Absent; Lacrimation - 1=None; Salivation- 1=None; Fur appearance - 1=Normal; Piloerection - 1=None; Eye Prominence - 1=Normal; Muscle tone - 1=Normal |
||||
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)
Day 65 |
||||
Parameters↓ |
Group & Sex |
G1R & M |
G4R & M |
|
Dose (mg/kg body weight/day) |
0 |
1000 |
||
Number of Animals |
5 |
5 |
||
Open Field Observations |
||||
Mobility |
1 |
1 |
||
Gait |
1 |
1 |
||
Arousal |
3 |
3 |
||
Number of rearing |
Mean |
5.0 |
4.4 |
|
±SD |
1.0 |
1.1 |
||
Numbers of urine pools |
Mean |
3.6 |
3.4 |
|
±SD |
0.5 |
0.5 |
||
Number of defecations |
Mean |
3.6 |
3.4 |
|
±SD |
0.5 |
0.5 |
||
Clonic involuntary movement |
1 |
1 |
||
Tonic involuntary movement |
1 |
1 |
||
Stereotype behaviour |
1 |
1 |
||
Number of grooming |
Mean |
3.6 |
3.2 |
|
±SD |
0.5 |
0.4 |
||
Sensory Observations |
||||
Approach response |
2 |
2 |
||
Auditory response |
2 |
2 |
||
Touch response |
2 |
2 |
||
Pupil reflex |
2 |
2 |
||
Tail pinch response |
2 |
2 |
||
Righting reflex |
1 |
1 |
||
Physiological Observation |
||||
Body temperature (°F) |
Mean |
98.5 |
98.6 |
|
±SD |
0.5 |
0.5 |
||
Open Field Observations: Mobility- 1=Normal;Gait- 1=Normal;Arousal- 3=Normal;Clonic involuntary movement- 1=None;Tonic involuntary movement -1=None;Stereotype behaviour -1=Absent;Sensory Observations:Approach response- 2=Normal;Auditory response- 2=Normal;Touch response -2=Normal;Pupil reflex- 2=Normal;Tail pinch response- 2=Normal;Righting reflex- 1=Present |
||||
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)
Day 65 |
||||
Parameters↓ |
Group & Sex |
G1R & F |
G4R & F |
|
Dose (mg/kg body weight/day) |
0 |
1000 |
||
Number of Animals |
5 |
5 |
||
Home Cage Observations |
||||
Home cage posture |
1 |
1 |
||
Respiratory pattern |
1 |
1 |
||
Clonic involuntary movements |
1 |
1 |
||
Tonic involuntary movements |
1 |
1 |
||
Vocalization |
1 |
1 |
||
Palpebral closure |
1 |
1 |
||
Handling Observations |
||||
Ease of removal from the cage |
2 |
2 |
||
Ease of handling animal in hand |
2 |
2 |
||
Red or crusty deposits |
Eyes |
1 |
1 |
|
Nose |
1 |
1 |
||
Mouth |
1 |
1 |
||
Lacrimation |
1 |
1 |
||
Salivation |
1 |
1 |
||
Fur appearance |
1 |
1 |
||
Piloerection |
1 |
1 |
||
Eye prominence |
1 |
1 |
||
Muscle tone |
1 |
1 |
||
Home Cage Observations:Home cage posture - 1=Normal; Respiratory pattern - 1=Normal; Clonic involuntary movements - 1=None; Tonic involuntary movements - 1=None; Vocalization - 1=None; Palpebral closure - 1=Normal;Handling Observations:Ease of removal from the cage - 2=Normal; Ease of handling animal in hand - 2=Normal; Red or crusty deposits - 1=Absent; Lacrimation - 1=None; Salivation- 1=None; Fur appearance - 1=Normal; Piloerection - 1=None; Eye Prominence - 1=Normal; Muscle tone - 1=Normal |
||||
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)
Day 65 |
||||
Parameters↓ |
Group & Sex |
G1R & F |
G4R & F |
|
Dose (mg/kg body weight/day) |
0 |
1000 |
||
Number of Animals |
5 |
5 |
||
Open Field Observations |
||||
Mobility |
1 |
1 |
||
Gait |
1 |
1 |
||
Arousal |
3 |
3 |
||
Number of rearing |
Mean |
5.0 |
4.8 |
|
±SD |
1.0 |
0.8 |
||
Numbers of urine pools |
Mean |
3.6 |
3.8 |
|
±SD |
0.5 |
0.8 |
||
Number of defecations |
Mean |
3.4 |
3.0 |
|
±SD |
0.9 |
0.7 |
||
Clonic involuntary movement |
1 |
1 |
||
Tonic involuntary movement |
1 |
1 |
||
Stereotype behaviour |
1 |
1 |
||
Number of grooming |
Mean |
3.2 |
3.2 |
|
±SD |
0.4 |
0.8 |
||
Sensory Observations |
||||
Approach response |
2 |
2 |
||
Auditory response |
2 |
2 |
||
Touch response |
2 |
2 |
||
Pupil reflex |
2 |
2 |
||
Tail pinch response |
2 |
2 |
||
Righting reflex |
1 |
1 |
||
Physiological Observation |
||||
Body temperature (°F) |
Mean |
98.4 |
98.3 |
|
±SD |
0.5 |
0.7 |
||
Open Field Observations: Mobility- 1=Normal;Gait- 1=Normal;Arousal- 3=Normal;Clonic involuntary movement- 1=None;Tonic involuntary movement -1=None;Stereotype behaviour -1=Absent;Sensory Observations:Approach response- 2=Normal;Auditory response- 2=Normal;Touch response -2=Normal;Pupil reflex- 2=Normal;Tail pinch response- 2=Normal;Righting reflex- 1=Present |
||||
TABLE 13. SUMMARY OF LOCOMOTOR ACTIVITY / MOVEMENT COUNTS RECORD
Day 30 |
||
Group, Sex & Dose (mg/kg body weight/day) |
Movement Counts (no.) |
|
G1, M & 0 |
Mean |
1911.4 |
±SD |
108.9 |
|
n |
5 |
|
G2, M & 111 |
Mean |
1961.8 |
±SD |
138.9 |
|
n |
5 |
|
G3, M & 333 |
Mean |
1954.2 |
±SD |
126.1 |
|
n |
5 |
|
G4, M & 1000 |
Mean |
1931.4 |
±SD |
104.0 |
|
n |
5 |
|
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 13 (Contd…). SUMMARY OF LOCOMOTOR ACTIVITY / MOVEMENT COUNTS RECORD
Lactation Day 13 |
||
Group, Sex & Dose (mg/kg body weight/day) |
Movement Counts (no.) |
|
G1, F & 0 |
Mean |
1923.4 |
±SD |
102.7 |
|
n |
5 |
|
G2, F & 111 |
Mean |
1941.4 |
±SD |
125.1 |
|
n |
5 |
|
G3, F & 333 |
Mean |
1989.0 |
±SD |
103.1 |
|
n |
5 |
|
G4, F & 1000 |
Mean |
1973.2 |
±SD |
84.7 |
|
n |
5 |
|
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 13 (Contd…). SUMMARY OF LOCOMOTOR ACTIVITY / MOVEMENT COUNTS RECORD
Day 65 |
||
Group, Sex & Dose (mg/kg body weight/day) |
Movement Counts (no.) |
|
G1R, M & 0 |
Mean |
2014.2 |
±SD |
210.7 |
|
n |
5 |
|
G4R, M & 1000 |
Mean |
1980.6 |
±SD |
197.8 |
|
n |
5 |
|
G1R, F & 0 |
Mean |
1943.4 |
±SD |
87.8 |
|
n |
5 |
|
G4R, F & 1000 |
Mean |
1956.2 |
±SD |
91.6 |
|
n |
5 |
|
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals.
TABLE 14. SUMMARY OF AVERAGE GRIP STRENGTH (kgf) MEASUREMENT RECORD
Day 30 |
|||
Group, Sex & Dose (mg/kg body weight/day) |
Grip Strength (kgf) |
||
Forelimb |
Hindlimb |
||
G1, M & 0 |
Mean |
1.529 |
0.510 |
±SD |
0.023 |
0.025 |
|
n |
5 |
5 |
|
G2, M & 111 |
Mean |
1.501 |
0.539 |
±SD |
0.020 |
0.021 |
|
n |
5 |
5 |
|
G3, M & 333 |
Mean |
1.521 |
0.552* |
±SD |
0.048 |
0.008 |
|
n |
5 |
5 |
|
G4, M & 1000 |
Mean |
1.539 |
0.544* |
±SD |
0.040 |
0.015 |
|
n |
5 |
5 |
|
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected); *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 14 (Contd…). SUMMARY OF AVERAGE GRIP STRENGTH (kgf) MEASUREMENT RECORD
Lactation Day 13 |
|||
Group, Sex & Dose (mg/kg body weight/day) |
Grip Strength (kgf) |
||
Forelimb |
Hindlimb |
||
G1, F & 0 |
Mean |
1.496 |
0.508 |
±SD |
0.009 |
0.008 |
|
n |
5 |
5 |
|
G2, F & 111 |
Mean |
1.493 |
0.488 |
±SD |
0.010 |
0.015 |
|
n |
5 |
5 |
|
G3, F & 333 |
Mean |
1.496 |
0.493 |
±SD |
0.009 |
0.021 |
|
n |
5 |
5 |
|
G4, F & 1000 |
Mean |
1.498 |
0.499 |
±SD |
0.011 |
0.020 |
|
n |
5 |
5 |
|
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 14 (Contd…). SUMMARY OF AVERAGE GRIP STRENGTH (kgf) MEASUREMENT RECORD
Day 65 |
|||
Group, Sex & Dose (mg/kg body weight/day) |
Grip Strength (kgf) |
||
Forelimb |
Hindlimb |
||
G1R, M & 0 |
Mean |
1.515 |
0.534 |
±SD |
0.020 |
0.035 |
|
n |
5 |
5 |
|
G4R, M & 1000 |
Mean |
1.528 |
0.533 |
±SD |
0.029 |
0.009 |
|
n |
5 |
5 |
|
G1R, F & 0 |
Mean |
1.516 |
0.499 |
±SD |
0.031 |
0.021 |
|
n |
5 |
5 |
|
G4R, F & 1000 |
Mean |
1.503 |
0.481 |
±SD |
0.012 |
0.012 |
|
n |
5 |
5 |
|
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals.
TABLE 15. SUMMARY OF AVERAGE HINDLIMB FOOT SPLAY (cm) RECORD
Day 30 |
||
Group, Sex & Dose (mg/kg body weight/day) |
Hindlimb Foot Splay (cm) |
|
G1, M & 0 |
Mean |
9.0 |
±SD |
1.0 |
|
n |
5 |
|
G2, M & 111 |
Mean |
8.8 |
±SD |
1.3 |
|
n |
5 |
|
G3, M & 333 |
Mean |
9.3 |
±SD |
0.6 |
|
n |
5 |
|
G4, M & 1000 |
Mean |
8.6 |
±SD |
0.6 |
|
n |
5 |
|
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 15 (Contd…). SUMMARY OF AVERAGE HINDLIMB FOOT SPLAY (cm) RECORD
Lactation Day 13 |
||
Group, Sex & Dose (mg/kg body weight/day) |
Hindlimb Foot Splay (cm) |
|
G1, F & 0 |
Mean |
8.0 |
±SD |
0.5 |
|
n |
5 |
|
G2, F & 111 |
Mean |
7.9 |
±SD |
0.5 |
|
n |
5 |
|
G3, F & 333 |
Mean |
8.1 |
±SD |
1.0 |
|
n |
5 |
|
G4, F & 1000 |
Mean |
8.5 |
±SD |
0.9 |
|
n |
5 |
|
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 15 (Contd…). SUMMARY OF AVERAGE HINDLIMB FOOT SPLAY (cm) RECORD
Day 65 |
||
Group, Sex & Dose (mg/kg body weight/day) |
Hindlimb Foot Splay (cm) |
|
G1R, M & 0 |
Mean |
8.6 |
±SD |
0.3 |
|
n |
5 |
|
G4R, M & 1000 |
Mean |
9.0 |
±SD |
0.4 |
|
n |
5 |
|
G1R, F & 0 |
Mean |
8.4 |
±SD |
0.4 |
|
n |
5 |
|
G4R, F & 1000 |
Mean |
7.6* |
±SD |
0.2 |
|
n |
5 |
|
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 16. SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total Leucocyte Count |
Total Erythrocyte Count |
Haemoglobin |
Haematocrit |
Mean Corpuscular Volume |
Mean Corpuscular Haemoglobin |
Mean Corpuscular Haemoglobin Concentration |
Platelet Count |
Mean Platelet Volume |
|
(WBC) |
(RBC) |
(HGB) |
(HCT) |
(MCV) |
(MCH) |
(MCHC) |
(PLT) |
(MPV) |
||
(103cells/µL) |
(106cells/µL) |
(g/dL) |
(%) |
(fL) |
(pg) |
(g/dL) |
(103cells/µL) |
(fL) |
||
G1, M & 0 |
Mean |
8.26 |
9.64 |
17.56 |
52.80 |
55.00 |
18.30 |
33.26 |
776.40 |
7.72 |
±SD |
1.95 |
1.09 |
1.34 |
4.49 |
3.09 |
1.14 |
0.53 |
330.86 |
0.52 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
9.68 |
9.37 |
16.82 |
51.32 |
54.72 |
17.94 |
32.80 |
1135.20 |
7.46 |
±SD |
2.59 |
0.15 |
0.33 |
0.89 |
1.12 |
0.29 |
0.58 |
184.30 |
0.19 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
8.67 |
9.40 |
16.58 |
50.78 |
54.12 |
17.64 |
32.62 |
962.60 |
7.72 |
±SD |
3.67 |
0.62 |
0.87 |
1.91 |
1.72 |
0.59 |
0.70 |
256.00 |
0.52 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
8.14 |
9.35 |
16.88 |
52.02 |
55.74 |
18.06 |
32.46 |
1017.60 |
7.50 |
±SD |
2.42 |
0.54 |
0.55 |
1.58 |
2.71 |
0.74 |
0.53 |
93.02 |
0.38 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Reticulocyte Count |
Neutrophils |
Lymphocytes |
Monocytes |
Eosinophils |
Basophils |
|
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
||
(%) |
(%) |
(%) |
(%) |
(%) |
(%) |
||
G1, M & 0 |
Mean |
2.25 |
23.48 |
72.02 |
2.38 |
0.44 |
0.80 |
±SD |
1.24 |
9.09 |
9.80 |
1.15 |
0.17 |
0.49 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
1.87 |
19.66 |
75.74 |
2.28 |
1.04 |
0.54 |
±SD |
0.64 |
3.44 |
3.55 |
0.74 |
0.59 |
0.23 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
1.87 |
21.98 |
70.58 |
2.40 |
1.04 |
0.62 |
±SD |
0.60 |
5.35 |
7.57 |
2.37 |
0.34 |
0.61 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
2.01 |
20.86 |
75.78 |
1.42 |
0.72 |
0.54 |
±SD |
0.79 |
3.34 |
2.92 |
0.23 |
0.25 |
0.15 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Absolute Reticulocyte Count |
Absolute Neutrophils |
Absolute Lymphocytes |
Absolute Monocytes |
Absolute Eosinophils |
Absolute Basophils |
Prothrombin Time |
Activated Prothrombin Time |
|
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
(PT) |
(APTT) |
||
(109cells/L) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(Seconds) |
(Seconds) |
||
G1, M & 0 |
Mean |
212.96 |
1.83 |
6.07 |
0.19 |
0.04 |
0.07 |
15.54 |
22.26 |
±SD |
101.87 |
0.42 |
2.01 |
0.08 |
0.02 |
0.06 |
0.78 |
6.12 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
174.50 |
1.91 |
7.33 |
0.23 |
0.10* |
0.05 |
15.72 |
25.28 |
±SD |
56.93 |
0.64 |
1.96 |
0.10 |
0.04 |
0.02 |
1.03 |
1.56 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
175.20 |
1.80 |
5.98 |
0.27 |
0.09* |
0.07 |
16.72 |
24.30 |
±SD |
59.25 |
0.52 |
1.97 |
0.39 |
0.03 |
0.11 |
1.49 |
1.59 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
184.78 |
1.70 |
6.17 |
0.11 |
0.06 |
0.04 |
15.98 |
26.78 |
±SD |
67.09 |
0.55 |
1.89 |
0.04 |
0.02 |
0.02 |
0.89 |
1.29 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected); *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total Leucocyte Count |
Total Erythrocyte Count |
Haemoglobin |
Haematocrit |
Mean Corpuscular Volume |
Mean Corpuscular Haemoglobin |
Mean Corpuscular Haemoglobin Concentration |
Platelet Count |
Mean Platelet Volume |
|
(WBC) |
(RBC) |
(HGB) |
(HCT) |
(MCV) |
(MCH) |
(MCHC) |
(PLT) |
(MPV) |
||
(103cells/µL) |
(106cells/µL) |
(g/dL) |
(%) |
(fL) |
(pg) |
(g/dL) |
(103cells/µL) |
(fL) |
||
G1, F & 0 |
Mean |
10.56 |
7.85 |
15.74 |
46.26 |
59.02 |
20.04 |
34.04 |
752.60 |
6.02 |
±SD |
3.78 |
0.45 |
0.65 |
3.16 |
4.16 |
1.08 |
0.91 |
361.58 |
0.64 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 111 |
Mean |
11.38 |
7.41 |
14.66 |
44.60 |
60.26 |
19.74 |
32.82 |
1130.00 |
6.72 |
±SD |
3.45 |
0.68 |
1.58 |
3.35 |
1.37 |
0.42 |
1.34 |
672.21 |
0.54 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 333 |
Mean |
9.62 |
7.95 |
15.56 |
46.34 |
58.34 |
19.60 |
33.60 |
1030.20 |
6.42 |
±SD |
3.95 |
0.28 |
0.72 |
2.05 |
3.12 |
0.81 |
1.07 |
104.22 |
0.57 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
12.38 |
7.39 |
14.68 |
43.46 |
59.06 |
19.98 |
33.80 |
1003.00 |
6.92 |
±SD |
3.58 |
0.76 |
0.89 |
2.75 |
3.76 |
1.58 |
0.63 |
227.17 |
0.68 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Reticulocyte Count |
Neutrophils |
Lymphocytes |
Monocytes |
Eosinophils |
Basophils |
|
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
||
(%) |
(%) |
(%) |
(%) |
(%) |
(%) |
||
G1, F & 0 |
Mean |
2.28 |
32.72 |
60.66 |
3.68 |
1.46 |
0.60 |
±SD |
0.87 |
15.77 |
16.88 |
1.06 |
0.98 |
0.23 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 111 |
Mean |
4.52 |
30.00 |
62.56 |
4.60 |
1.18 |
0.42 |
±SD |
4.56 |
11.00 |
11.24 |
1.35 |
0.63 |
0.19 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 333 |
Mean |
1.49 |
25.26 |
66.92 |
4.46 |
1.22 |
0.80 |
±SD |
0.67 |
9.73 |
12.89 |
4.23 |
0.33 |
1.12 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
4.16 |
37.00 |
57.76 |
3.10 |
0.88 |
0.28 |
±SD |
2.72 |
20.56 |
20.80 |
0.97 |
0.47 |
0.11 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Absolute Reticulocyte Count |
Absolute Neutrophils |
Absolute Lymphocytes |
Absolute Monocytes |
Absolute Eosinophils |
Absolute Basophils |
Prothrombin Time |
Activated Prothrombin Time |
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
(PT) |
(APTT) |
||
(109cells/L) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(Seconds) |
(Seconds) |
||
G1, F & 0 |
Mean |
177.36 |
3.64 |
6.21 |
0.40 |
0.15 |
0.06 |
17.60 |
23.34 |
±SD |
60.94 |
2.11 |
2.30 |
0.19 |
0.09 |
0.03 |
1.02 |
2.05 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 111 |
Mean |
313.86 |
3.59 |
6.91 |
0.56 |
0.12 |
0.05 |
22.06 |
27.48 |
±SD |
276.22 |
2.17 |
1.72 |
0.29 |
0.04 |
0.02 |
8.41 |
10.47 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 333 |
Mean |
117.60 |
2.64 |
6.29 |
0.39 |
0.12 |
0.06 |
16.88 |
22.08 |
±SD |
50.69 |
2.06 |
2.26 |
0.31 |
0.07 |
0.08 |
3.84 |
7.81 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
291.70 |
4.81 |
6.94 |
0.38 |
0.10 |
0.04 |
15.66 |
19.92 |
±SD |
145.98 |
3.66 |
3.06 |
0.17 |
0.03 |
0.02 |
3.85 |
5.41 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total Leucocyte Count |
Total Erythrocyte Count |
Haemoglobin |
Haematocrit |
Mean Corpuscular Volume |
Mean Corpuscular Haemoglobin |
Mean Corpuscular Haemoglobin Concentration |
Platelet Count |
Mean Platelet Volume |
|
(WBC) |
(RBC) |
(HGB) |
(HCT) |
(MCV) |
(MCH) |
(MCHC) |
(PLT) |
(MPV) |
||
(103cells/µL) |
(106cells/µL) |
(g/dL) |
(%) |
(fL) |
(pg) |
(g/dL) |
(103cells/µL) |
(fL) |
||
G1R, M & 0 |
Mean |
9.13 |
9.21 |
16.04 |
48.76 |
52.94 |
17.42 |
32.92 |
894.80 |
6.50 |
±SD |
0.78 |
0.14 |
0.43 |
1.79 |
1.78 |
0.39 |
0.42 |
134.10 |
0.31 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
9.55 |
9.14 |
15.80 |
48.54 |
53.08 |
17.30 |
32.62 |
1071.80 |
6.42 |
±SD |
1.05 |
0.32 |
0.65 |
2.25 |
0.91 |
0.30 |
0.57 |
268.87 |
0.37 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
6.97 |
7.65 |
14.26 |
42.16 |
55.20 |
18.64 |
33.78 |
873.60 |
6.32 |
±SD |
2.14 |
0.43 |
0.65 |
2.05 |
1.99 |
0.70 |
0.29 |
80.79 |
0.19 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
7.59 |
7.73 |
14.32 |
42.78 |
55.34 |
18.48 |
33.46 |
739.60 |
6.52 |
±SD |
3.51 |
0.22 |
0.57 |
1.63 |
2.15 |
0.70 |
0.25 |
253.21 |
0.13 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals.
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Reticulocyte Count |
Neutrophils |
Lymphocytes |
Monocytes |
Eosinophils |
Basophils |
|
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
||
(%) |
(%) |
(%) |
(%) |
(%) |
(%) |
||
G1R, M & 0 |
Mean |
1.63 |
25.28 |
69.00 |
1.76 |
2.30 |
0.88 |
±SD |
0.26 |
6.62 |
7.82 |
0.49 |
0.89 |
0.26 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
2.03 |
21.70 |
73.32 |
1.48 |
2.02 |
0.60 |
±SD |
0.50 |
5.52 |
5.80 |
0.37 |
0.36 |
0.29 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
1.84 |
26.12 |
68.68 |
2.30 |
1.34 |
0.68 |
±SD |
0.36 |
9.06 |
8.57 |
1.19 |
0.45 |
0.15 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
2.48* |
29.02 |
64.16 |
2.40 |
2.86* |
0.64 |
±SD |
0.39 |
7.89 |
6.96 |
0.87 |
1.30 |
0.13 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Absolute Reticulocyte Count |
Absolute Neutrophils |
Absolute Lymphocytes |
Absolute Monocytes |
Absolute Eosinophils |
Absolute Basophils |
Prothrombin Time |
Activated Prothrombin Time |
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
(PT) |
(APTT) |
||
(109cells/L) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(Seconds) |
(Seconds) |
||
G1R, M & 0 |
Mean |
150.40 |
2.27 |
6.35 |
0.16 |
0.21 |
0.08 |
16.00 |
21.56 |
±SD |
23.36 |
0.40 |
1.23 |
0.04 |
0.07 |
0.02 |
2.04 |
2.05 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
186.92 |
2.06 |
7.02 |
0.14 |
0.19 |
0.05 |
15.50 |
22.48 |
±SD |
52.68 |
0.53 |
1.09 |
0.04 |
0.04 |
0.03 |
1.17 |
3.12 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
140.08 |
1.78 |
4.83 |
0.15 |
0.09 |
0.05 |
14.98 |
24.56 |
±SD |
23.05 |
0.73 |
1.73 |
0.05 |
0.02 |
0.01 |
0.53 |
1.98 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
192.10* |
2.06 |
4.98 |
0.17 |
0.25 |
0.05 |
15.92 |
19.34* |
±SD |
30.17 |
0.60 |
2.77 |
0.07 |
0.24 |
0.02 |
1.17 |
2.34 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 17. SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Glucose |
Urea |
Creatinine |
Total Cholesterol |
Triglycerides |
Total Protein |
Albumin |
|
(GLU) |
- |
(CRE) |
(CHO) |
(TRI) |
(TPR) |
(ALB) |
||
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(g/dL) |
||
G1, M & 0 |
Mean |
126.60 |
30.52 |
0.58 |
51.60 |
25.60 |
7.74 |
3.47 |
±SD |
15.47 |
2.56 |
0.03 |
3.36 |
2.30 |
0.26 |
0.19 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
123.60 |
33.30 |
0.57 |
60.60 |
30.40 |
7.24* |
3.55 |
±SD |
5.55 |
3.91 |
0.04 |
4.83 |
6.07 |
0.33 |
0.15 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
122.60 |
33.78 |
0.60 |
58.00 |
29.40 |
7.44 |
3.65 |
±SD |
12.92 |
2.83 |
0.03 |
6.71 |
7.73 |
0.22 |
0.29 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
131.00 |
36.04 |
0.59 |
56.00 |
27.00 |
7.58 |
3.68 |
±SD |
19.79 |
4.26 |
0.02 |
9.57 |
6.16 |
0.29 |
0.24 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected); *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Alanine |
Aspartate |
Alkaline |
Total Bilirubin |
Calcium |
Phosphorous |
|
(ALT) |
(AST) |
(ALP) |
(BIT) |
(CAL) |
(PHO) |
||
(U/L) |
(U/L) |
(U/L) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
||
G1, M & 0 |
Mean |
61.20 |
111.20 |
125.80 |
0.05 |
9.36 |
6.48 |
±SD |
16.93 |
12.34 |
21.11 |
0.01 |
0.11 |
0.58 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
47.40 |
93.20 |
120.00 |
0.06 |
9.64 |
6.54 |
±SD |
8.96 |
13.46 |
31.92 |
0.03 |
0.47 |
0.62 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
40.00 |
81.60* |
127.20 |
0.06 |
10.40* |
6.82 |
±SD |
5.96 |
12.30 |
38.01 |
0.03 |
1.05 |
0.62 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
52.20 |
91.80 |
114.80 |
0.06 |
9.94 |
6.62 |
±SD |
24.52 |
18.69 |
28.70 |
0.02 |
0.30 |
0.49 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected) ; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Globulin |
Albumin/ Globulin ratio |
Blood Urea Nitrogen |
Sodium |
Potassium |
Chloride |
|
(GLO) |
(A/G Ratio) |
(BUN) |
(Na) |
(K) |
(CLO) |
||
(g/dL) |
- |
(mg/dL) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
||
G1, M & 0 |
Mean |
4.27 |
0.82 |
14.24 |
141.64 |
3.96 |
104.10 |
±SD |
0.30 |
0.09 |
1.19 |
0.94 |
0.25 |
2.51 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
3.69* |
0.97 |
15.54 |
142.16 |
3.71 |
105.38 |
±SD |
0.38 |
0.12 |
1.83 |
0.53 |
0.15 |
1.40 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
3.79* |
0.97 |
15.77 |
142.44 |
3.86 |
105.78 |
±SD |
0.12 |
0.10 |
1.32 |
0.93 |
0.36 |
1.73 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
3.90 |
0.95 |
16.82 |
142.76 |
3.85 |
106.40 |
±SD |
0.29 |
0.11 |
1.99 |
0.66 |
0.09 |
0.86 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected); *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Glucose |
Urea |
Creatinine |
Total Cholesterol |
Triglycerides |
Total Protein |
Albumin |
|
(GLU) |
- |
(CRE) |
(CHO) |
(TRI) |
(TPR) |
(ALB) |
||
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(g/dL) |
||
G1, F & 0 |
Mean |
102.20 |
48.68 |
0.54 |
76.60 |
78.60 |
7.32 |
3.63 |
±SD |
26.22 |
8.11 |
0.05 |
22.67 |
26.83 |
1.08 |
0.67 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 111 |
Mean |
121.20 |
51.14 |
0.52 |
67.80 |
59.40 |
7.34 |
3.41 |
±SD |
29.64 |
13.28 |
0.03 |
17.67 |
23.65 |
0.75 |
0.30 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 333 |
Mean |
103.80 |
44.78 |
0.57 |
75.60 |
43.20 |
7.56 |
3.58 |
±SD |
13.81 |
19.81 |
0.04 |
14.91 |
21.48 |
0.29 |
0.32 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
114.60 |
51.66 |
0.57 |
75.80 |
105.20 |
7.76 |
3.70 |
±SD |
16.44 |
16.16 |
0.07 |
20.44 |
68.28 |
0.58 |
0.11 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Alanine |
Aspartate |
Alkaline |
Total Bilirubin |
Calcium |
Phosphorous |
|
(ALT) |
(AST) |
(ALP) |
(BIT) |
(CAL) |
(PHO) |
||
(U/L) |
(U/L) |
(U/L) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
||
G1, F & 0 |
Mean |
84.60 |
119.40 |
164.40 |
0.03 |
10.06 |
5.92 |
±SD |
14.43 |
14.31 |
75.62 |
0.04 |
1.06 |
0.95 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 111 |
Mean |
113.80 |
143.80 |
420.00 |
0.02 |
9.42 |
5.50 |
±SD |
66.08 |
71.78 |
367.29 |
0.02 |
0.64 |
1.64 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 333 |
Mean |
96.20 |
99.40 |
305.80 |
0.06 |
10.04 |
6.06 |
±SD |
82.35 |
16.01 |
412.83 |
0.02 |
0.85 |
1.93 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
88.60 |
101.80 |
212.40 |
0.03 |
10.38 |
6.38 |
±SD |
46.69 |
22.65 |
81.17 |
0.04 |
0.91 |
3.11 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Globulin |
Albumin/Globulin ratio |
Blood Urea Nitrogen |
Sodium |
Potassium |
Chloride |
|
(GLO) |
(A/G Ratio) |
(BUN) |
(Na) |
(K) |
(CLO) |
||
(g/dL) |
- |
(mg/dL) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
||
G1, F & 0 |
Mean |
3.69 |
0.98 |
22.72 |
143.04 |
4.02 |
106.18 |
±SD |
0.50 |
0.11 |
3.79 |
1.34 |
0.81 |
2.96 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 111 |
Mean |
3.93 |
0.88 |
23.87 |
142.18 |
3.57 |
107.22 |
±SD |
0.66 |
0.14 |
6.20 |
1.47 |
0.28 |
3.01 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 333 |
Mean |
3.98 |
0.91 |
20.90 |
142.36 |
3.60 |
107.94 |
±SD |
0.40 |
0.16 |
9.25 |
1.61 |
0.33 |
2.63 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
4.06 |
0.92 |
24.11 |
142.62 |
3.86 |
107.06 |
±SD |
0.50 |
0.09 |
7.55 |
1.62 |
0.40 |
3.20 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Glucose |
Urea |
Creatinine |
Total Cholesterol |
Triglycerides |
Total Protein |
Albumin |
|
(GLU) |
- |
(CRE) |
(CHO) |
(TRI) |
(TPR) |
(ALB) |
||
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(g/dL) |
||
G1R, M & 0 |
Mean |
99.80 |
27.36 |
0.55 |
59.60 |
23.00 |
6.98 |
3.10 |
±SD |
6.53 |
3.92 |
0.02 |
16.21 |
5.52 |
0.26 |
0.07 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
99.40 |
25.74 |
0.56 |
68.80 |
31.60 |
7.12 |
3.05 |
±SD |
10.53 |
1.19 |
0.03 |
8.76 |
10.78 |
0.11 |
0.04 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
120.40 |
35.68 |
0.61 |
106.40 |
49.60 |
8.44 |
4.10 |
±SD |
7.16 |
7.57 |
0.02 |
17.07 |
34.09 |
0.56 |
0.18 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
104.00* |
31.42 |
0.59 |
89.20 |
41.60 |
8.04 |
3.70 |
±SD |
13.49 |
2.25 |
0.01 |
16.98 |
11.87 |
0.42 |
0.44 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Alanine aminotransferase |
Aspartate aminotransferase |
Alkaline phosphatase |
Total Bilirubin |
Calcium |
Phosphorous |
|
(ALT) |
(AST) |
(ALP) |
(BIT) |
(CAL) |
(PHO) |
||
(U/L) |
(U/L) |
(U/L) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
||
G1R, M & 0 |
Mean |
52.00 |
101.80 |
99.00 |
0.02 |
10.42 |
5.72 |
±SD |
40.34 |
53.17 |
23.40 |
0.02 |
0.37 |
0.34 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
42.60 |
98.40 |
105.20 |
0.02 |
10.02 |
5.26 |
±SD |
9.86 |
18.49 |
29.84 |
0.01 |
0.15 |
0.50 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
54.00 |
94.00 |
70.80 |
0.02 |
11.20 |
4.20 |
±SD |
28.82 |
36.89 |
40.92 |
0.02 |
0.45 |
0.38 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
53.80 |
103.20 |
69.00 |
0.04 |
10.90 |
4.42 |
±SD |
21.53 |
39.30 |
60.10 |
0.02 |
0.37 |
0.18 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals.
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Globulin |
Albumin/ Globulin ratio |
Blood Urea Nitrogen |
Sodium |
Potassium |
Chloride |
|
(GLO) |
(A/G Ratio) |
(BUN) |
(Na) |
(K) |
(CLO) |
||
(g/dL) |
- |
(mg/dL) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
||
G1R, M & 0 |
Mean |
3.88 |
0.80 |
12.77 |
142.82 |
3.56 |
105.48 |
±SD |
0.27 |
0.06 |
1.83 |
0.36 |
0.41 |
0.92 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
4.07 |
0.75 |
12.01 |
143.16 |
3.59 |
108.06* |
±SD |
0.15 |
0.04 |
0.56 |
0.68 |
0.41 |
1.65 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
4.34 |
0.95 |
16.65 |
142.62 |
3.45 |
105.76 |
±SD |
0.42 |
0.08 |
3.53 |
0.94 |
0.17 |
1.52 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
4.34 |
0.85 |
14.66 |
142.26 |
3.62 |
106.40 |
±SD |
0.21 |
0.12 |
1.05 |
1.41 |
0.48 |
2.88 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 18. SUMMARY OF URINALYSIS RECORD
Examination |
Group, Sex & Dose (mg/kg body weight/day) |
G1, M & 0 |
G2, M & 111 |
G3, M & 333 |
G4, M & 1000 |
|
Number of Animals (randomly selected) |
5 |
5 |
5 |
5 |
||
Physical Examination |
Color |
Pale Yellow |
5 |
5 |
5 |
5 |
Appearance |
Clear |
5 |
5 |
5 |
5 |
|
Volume (mL) |
Mean |
10.6 |
10.2 |
11.0 |
11.4 |
|
±SD |
0.7 |
1.4 |
0.8 |
0.4 |
||
Chemical Examination |
pH |
Mean |
7.5 |
7.4 |
7.4 |
7.5 |
±SD |
0.0 |
0.4 |
0.5 |
0.0 |
||
Specific Gravity |
Mean |
1.008 |
1.011 |
1.009 |
1.009 |
|
±SD |
0.003 |
0.002 |
0.002 |
0.002 |
||
Urobilinogen (mg/dL) |
Mean |
0.2 |
0.2 |
0.2 |
0.2 |
|
±SD |
0.0 |
0.0 |
0.0 |
0.0 |
||
Bilirubin (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
|
Ketones (mg/dL) |
Neg |
2 |
- |
2 |
1 |
|
5 |
3 |
5 |
3 |
4 |
||
Blood (Ery/µL) |
Neg |
5 |
4 |
5 |
5 |
|
Ca80 |
- |
1 |
- |
- |
||
Protein (mg/dL) |
Neg |
3 |
- |
3 |
1 |
|
Trace |
2 |
4 |
1 |
4 |
||
30 |
- |
1 |
1 |
- |
||
Nitrite |
Neg |
4 |
4 |
5 |
1 |
|
Pos |
1 |
1 |
- |
4 |
||
Leucocytes |
Neg |
3 |
- |
3 |
1 |
|
Ca15 |
1 |
1 |
1 |
2 |
||
Ca70 |
1 |
3 |
1 |
2 |
||
Ca125 |
- |
1 |
- |
- |
||
Glucose (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
|
Microalbumin (mg/dL) |
Neg |
- |
- |
2 |
1 |
|
>15 |
2 |
5 |
2 |
4 |
||
15 |
3 |
- |
1 |
- |
||
Microscopic Examination |
Epi Cells |
0 |
3 |
4 |
2 |
4 |
0-1 |
1 |
1 |
2 |
1 |
||
1-2 |
1 |
- |
1 |
- |
||
Casts |
Absent |
4 |
4 |
4 |
5 |
|
Present |
1 |
1 |
1 |
- |
||
Crystals |
Present |
5 |
5 |
5 |
5 |
|
M:
Male; SD: Standard Deviation; Pos: Positive; Neg: Negative; Ca:
Calculated.
>=:
Greater than or equal to; >: Greater than.
TABLE 18 (Contd…). SUMMARY OF URINALYSIS RECORD
Examination |
Group, Sex & Dose (mg/kg body weight/day) |
G1R, M & 0 |
G4R, M &1000 |
G1R, F & 0 |
G4R, F & 1000 |
|
Number of Animals (randomly selected) |
5 |
5 |
5 |
5 |
||
Physical Examination |
Color |
Pale Yellow |
2 |
5 |
3 |
3 |
Yellow |
3 |
- |
2 |
2 |
||
Appearance |
Clear |
3 |
2 |
4 |
4 |
|
Turbid |
2 |
3 |
1 |
1 |
||
Volume (mL) |
Mean |
6.4 |
8.6 |
7.9 |
7.8 |
|
±SD |
1.7 |
3.1 |
2.2 |
0.8 |
||
Chemical Examination |
pH |
Mean |
6.7 |
7.3 |
6.8 |
7.6 |
±SD |
0.9 |
0.4 |
1.0 |
1.0 |
||
Specific Gravity |
Mean |
1.020 |
1.014 |
1.014 |
1.012 |
|
±SD |
0.007 |
0.002 |
0.007 |
0.008 |
||
Urobilinogen (mg/dL) |
Mean |
0.2 |
0.2 |
0.2 |
0.6 |
|
±SD |
0.0 |
0.0 |
0.0 |
0.8 |
||
Bilirubin (mg/dL) |
Neg |
2 |
5 |
5 |
2 |
|
1 |
3 |
- |
- |
3 |
||
Ketones (mg/dL) |
Neg |
1 |
2 |
5 |
5 |
|
5 |
4 |
3 |
- |
- |
||
Blood (Ery/µL) |
Neg |
5 |
5 |
5 |
4 |
|
Ca10 |
- |
- |
- |
1 |
||
Protein (mg/dL) |
Neg |
2 |
5 |
4 |
2 |
|
Trace |
2 |
- |
1 |
- |
||
30 |
1 |
- |
- |
- |
||
100 |
- |
- |
- |
1 |
||
>=300 |
- |
- |
- |
2 |
||
Nitrite |
Neg |
3 |
5 |
5 |
5 |
|
Pos |
2 |
- |
- |
- |
||
Leucocytes |
Neg |
- |
1 |
3 |
2 |
|
Ca15 |
1 |
4 |
2 |
- |
||
Ca70 |
4 |
- |
- |
3 |
||
Glucose (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
|
Microalbumin (mg/dL) |
Neg |
- |
1 |
3 |
1 |
|
>15 |
3 |
- |
1 |
3 |
||
15 |
2 |
4 |
1 |
1 |
||
Microscopic Examination\ |
Epi Cells |
0 |
3 |
3 |
2 |
2 |
0-1 |
1 |
2 |
2 |
1 |
||
1-2 |
1 |
- |
1 |
- |
||
2-3 |
- |
- |
- |
2 |
||
Casts |
Absent |
5 |
2 |
5 |
4 |
|
Present |
- |
3 |
- |
1 |
||
Crystals |
Absent |
- |
2 |
1 |
2 |
|
Present |
5 |
3 |
4 |
3 |
||
M:
Male; F: Female; R: Recovery; SD: Standard Deviation; Pos: Positive;
Neg: Negative.
Ca: Calculated; >=: Greater than
or equal to; >: Greater than.
TABLE 19. SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Adrenals |
Thymus |
Spleen |
Testes |
Epididymides |
Heart |
Kidneys |
Brain |
|
G1, M & 0 |
Mean |
0.0667 |
0.2891 |
0.7915 |
3.3315 |
1.4198 |
1.3943 |
2.9537 |
2.1193 |
±SD |
0.0045 |
0.0466 |
0.2701 |
0.3035 |
0.1420 |
0.2048 |
0.2510 |
0.0321 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
0.0719 |
0.3589 |
0.8023 |
3.4284 |
1.4112 |
1.5033 |
2.8196 |
2.1336 |
±SD |
0.0094 |
0.0292 |
0.0928 |
0.1782 |
0.1365 |
0.1061 |
0.1723 |
0.0957 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
0.0709 |
0.4450* |
0.8041 |
3.3728 |
1.4195 |
1.4754 |
2.8317 |
2.1467 |
±SD |
0.0060 |
0.0665 |
0.1455 |
0.2771 |
0.1776 |
0.1560 |
0.1507 |
0.0446 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
0.0716 |
0.4129* |
0.8155 |
3.3454 |
1.5221 |
1.5218 |
3.0082 |
2.2033 |
±SD |
0.0115 |
0.1013 |
0.1404 |
0.2101 |
0.1812 |
0.3979 |
0.7565 |
0.1355 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 19 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Liver |
Prostate |
Seminal vesicles with coagulating glands |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
G1, M & 0 |
Mean |
10.0491 |
1.1499 |
1.6300 |
1.9467 |
0.0208 |
0.0296 |
±SD |
1.6192 |
0.1975 |
0.4468 |
0.1258 |
0.0014 |
0.0017 |
|
n |
5 |
12 |
12 |
5 |
5 |
12 |
|
G2, M & 111 |
Mean |
10.3930 |
1.1988 |
1.6027 |
2.0659 |
0.0197 |
0.0290 |
±SD |
0.4389 |
0.2552 |
0.3454 |
0.1175 |
0.0013 |
0.0020 |
|
n |
5 |
12 |
12 |
5 |
5 |
12 |
|
G3, M & 333 |
Mean |
10.6576 |
1.3430 |
1.7846 |
2.0478 |
0.0203 |
0.0301 |
±SD |
0.7376 |
0.3501 |
0.3700 |
0.1024 |
0.0009 |
0.0013 |
|
n |
5 |
12 |
12 |
5 |
5 |
12 |
|
G4, M & 1000 |
Mean |
10.8065 |
1.2209 |
1.9124 |
2.0837 |
0.0205 |
0.0305 |
±SD |
2.8155 |
0.3931 |
0.5906 |
0.1492 |
0.0015 |
0.0023 |
|
n |
5 |
12 |
12 |
5 |
5 |
12 |
M: Male; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation.
TABLE 19 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Adrenals |
Thymus |
Spleen |
Ovaries |
Uterus with Cervix |
Heart |
|
G1, F & 0 |
Mean |
0.0741 |
0.2781 |
0.7048 |
0.1738 |
0.5901 |
1.1848 |
±SD |
0.0083 |
0.0317 |
0.0646 |
0.0299 |
0.1167 |
0.1262 |
|
n |
5 |
5 |
5 |
12 |
11@ |
5 |
|
G2, F & 111 |
Mean |
0.0884 |
0.2632 |
0.7503 |
0.1432* |
0.5097 |
1.1940 |
±SD |
0.0110 |
0.0345 |
0.1289 |
0.0332 |
0.1138 |
0.0729 |
|
n |
5 |
5 |
5 |
12 |
11@ |
5 |
|
G3, F & 333 |
Mean |
0.0728 |
0.2267* |
0.6584 |
0.1291* |
0.5413 |
1.2001 |
±SD |
0.0094 |
0.0282 |
0.1051 |
0.0193 |
0.0886 |
0.0513 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
|
G4, F & 1000 |
Mean |
0.0775 |
0.2179* |
0.6109 |
0.1466* |
0.5283 |
1.3318 |
±SD |
0.0093 |
0.0063 |
0.0413 |
0.0190 |
0.1008 |
0.3482 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
@: One animal data from group G1 and G2 is excluded for mean calculations as the weight varies from normal uterus due to presence of dead foetus during necropsy, but the data is presented in individual animal data. (Appendix 22).
TABLE 19 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Kidneys |
Brain |
Liver |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
|
G1, F & 0 |
Mean |
2.2668 |
2.0179 |
11.5641 |
1.2626 |
0.0179 |
0.0266 |
±SD |
0.1164 |
0.0746 |
0.5339 |
0.1185 |
0.0011 |
0.0015 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
|
G2, F & 111 |
Mean |
2.0463* |
2.0056 |
12.5985 |
1.5260 |
0.0183 |
0.0272 |
±SD |
0.1081 |
0.1131 |
2.0359 |
0.2954 |
0.0014 |
0.0015 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
|
G3, F & 333 |
Mean |
2.0269* |
1.9917 |
10.1148 |
1.3551 |
0.0176 |
0.0265 |
±SD |
0.0937 |
0.0552 |
1.8164 |
0.1082 |
0.0008 |
0.0015 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
|
G4, F & 1000 |
Mean |
1.9230* |
2.0216 |
10.2708 |
1.3780 |
0.0180 |
0.0275 |
±SD |
0.0912 |
0.0446 |
1.3180 |
0.1188 |
0.0010 |
0.0014 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
F: Female; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 19 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Adrenals |
Thymus |
Spleen |
Testes |
Epididymides |
Heart |
Kidneys |
Brain |
|
G1R, M & 0 |
Mean |
0.0671 |
0.2367 |
0.8804 |
3.3055 |
1.6954 |
1.6355 |
2.2619 |
2.0448 |
±SD |
0.0080 |
0.0348 |
0.0907 |
0.1930 |
0.0763 |
0.1477 |
0.3680 |
0.1172 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
0.0638 |
0.2709 |
0.7442* |
3.4656 |
1.6882 |
1.6050 |
2.3506 |
2.0483 |
±SD |
0.0051 |
0.0738 |
0.0528 |
0.1133 |
0.0690 |
0.3581 |
0.3464 |
0.1621 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 19 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Liver |
Prostate |
Seminal vesicles with coagulating glands |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
|
G1R, M & 0 |
Mean |
12.6730 |
1.3824 |
1.8300 |
2.0437 |
0.0207 |
0.0299 |
±SD |
1.2027 |
0.2475 |
0.4858 |
0.5420 |
0.0009 |
0.0015 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
12.5717 |
1.6038 |
1.8342 |
1.9398 |
0.0210 |
0.0306 |
±SD |
1.2099 |
0.1130 |
0.4887 |
0.0584 |
0.0011 |
0.0008 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation.
TABLE 19 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Adrenals |
Thymus |
Spleen |
Ovaries |
Uterus with Cervix |
Heart |
G1R, F & 0 |
Mean |
0.0706 |
0.2511 |
0.6464 |
0.1265 |
0.6499 |
1.0512 |
±SD |
0.0064 |
0.0443 |
0.0886 |
0.0164 |
0.0920 |
0.0882 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
0.0702 |
0.2467 |
0.6261 |
0.1543* |
0.6334 |
1.0135 |
±SD |
0.0121 |
0.0337 |
0.1113 |
0.0105 |
0.0853 |
0.0746 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 19 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Kidneys |
Brain |
Liver |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
|
G1R, F & 0 |
Mean |
1.9138 |
2.0075 |
9.6308 |
1.8480 |
0.0185 |
0.0278 |
±SD |
0.0978 |
0.0986 |
0.9760 |
0.0946 |
0.0009 |
0.0014 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
1.8218 |
1.9767 |
8.6614 |
2.0609 |
0.0193 |
0.0271 |
±SD |
0.1551 |
0.0844 |
1.7719 |
0.4014 |
0.0014 |
0.0006 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation.
TABLE 20. SUMMARY
OF TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Terminal Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Testes |
Epididymides |
Heart |
|
G1, M & 0 |
Mean |
440.14 |
0.0150 |
0.0648 |
0.1748 |
0.7637 |
0.3257 |
0.3099 |
±SD |
38.09 |
0.0018 |
0.0115 |
0.0484 |
0.1095 |
0.0493 |
0.0251 |
|
n |
12 |
5 |
5 |
5 |
12 |
12 |
5 |
|
G2, M & 111 |
Mean |
433.53 |
0.0162 |
0.0812 |
0.1809 |
0.7928 |
0.3262 |
0.3390 |
±SD |
29.89 |
0.0021 |
0.0090 |
0.0188 |
0.0447 |
0.0319 |
0.0185 |
|
n |
12 |
5 |
5 |
5 |
12 |
12 |
5 |
|
G3, M & 333 |
Mean |
437.73 |
0.0159 |
0.0995* |
0.1797 |
0.7734 |
0.3250 |
0.3314 |
±SD |
26.65 |
0.0016 |
0.0135 |
0.0302 |
0.0792 |
0.0413 |
0.0427 |
|
n |
12 |
5 |
5 |
5 |
12 |
12 |
5 |
|
G4, M & 1000 |
Mean |
443.94 |
0.0156 |
0.0891* |
0.1779 |
0.7570 |
0.3432 |
0.3304 |
±SD |
38.78 |
0.0013 |
0.0124 |
0.0187 |
0.0592 |
0.0298 |
0.0626 |
|
n |
12 |
5 |
5 |
5 |
12 |
12 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals.
TABLE 20 (Contd…).
SUMMARY OF TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Kidneys |
Brain |
Liver |
Prostate |
Seminal vesicles with coagulating glands |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
|
G1, M & 0 |
Mean |
0.6591 |
0.4745 |
2.2336 |
0.2614 |
0.3768 |
0.4360 |
0.0047 |
0.0067 |
±SD |
0.0371 |
0.0334 |
0.2239 |
0.0389 |
0.1233 |
0.0428 |
0.0003 |
0.0004 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
12 |
|
G2, M & 111 |
Mean |
0.6380 |
0.4818 |
2.3449 |
0.2758 |
0.3681 |
0.4668 |
0.0044 |
0.0067 |
±SD |
0.0606 |
0.0272 |
0.0585 |
0.0505 |
0.0681 |
0.0350 |
0.0003 |
0.0006 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
12 |
|
G3, M & 333 |
Mean |
0.6350 |
0.4812 |
2.3924 |
0.3052 |
0.4081 |
0.4594 |
0.0046 |
0.0069 |
±SD |
0.0467 |
0.0237 |
0.2415 |
0.0710 |
0.0824 |
0.0376 |
0.0001 |
0.0004 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
12 |
|
G4, M & 1000 |
Mean |
0.6545 |
0.4865 |
2.3426 |
0.2767 |
0.4271 |
0.4575 |
0.0045 |
0.0069 |
±SD |
0.1286 |
0.0618 |
0.4199 |
0.0940 |
0.1161 |
0.0285 |
0.0002 |
0.0004 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
12 |
M: Male; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation.
TABLE 20 (Contd…).
SUMMARY OF TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Terminal Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Ovaries |
Uterus with Cervix |
Heart |
|
G1, F & 0 |
Mean |
305.54 |
0.0242 |
0.0912 |
0.2307 |
0.0571 |
0.1938 |
0.3872 |
±SD |
21.99 |
0.0035 |
0.0163 |
0.0360 |
0.0100 |
0.0422 |
0.0618 |
|
n |
12 |
5 |
5 |
5 |
12 |
11@ |
5 |
|
G2, F & 111 |
Mean |
314.85 |
0.0286 |
0.0853 |
0.2428 |
0.0458* |
0.1635 |
0.3854 |
±SD |
19.21 |
0.0044 |
0.0142 |
0.0457 |
0.0115 |
0.0448 |
0.0220 |
|
n |
12 |
5 |
5 |
5 |
12 |
11@ |
5 |
|
G3, F & 333 |
Mean |
302.78 |
0.0236 |
0.0730 |
0.2142 |
0.0431* |
0.1801 |
0.3879 |
±SD |
22.49 |
0.0038 |
0.0045 |
0.0429 |
0.0092 |
0.0352 |
0.0151 |
|
n |
12 |
5 |
5 |
5 |
12 |
12 |
5 |
|
G4, F & 1000 |
Mean |
306.64 |
0.0245 |
0.0690* |
0.1938 |
0.0483 |
0.1749 |
0.4241 |
±SD |
25.44 |
0.0033 |
0.0062 |
0.0238 |
0.0080 |
0.0430 |
0.1222 |
|
n |
12 |
5 |
5 |
5 |
12 |
12 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals.
@: One animal data from group G1 and G2 is excluded for mean calculations as the weight varies from normal uterus due to presence of dead foetus during necropsy, but the data is presented in individual animal data. (Appendix 23).
TABLE 20 (Contd…). SUMMARY OF TERMINAL BODY WEIGHT (g) AND
ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Kidneys |
Brain |
Liver |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
|
G1, F & 0 |
Mean |
0.7409 |
0.6583 |
3.7703 |
0.4138 |
0.0058 |
0.0087 |
±SD |
0.0909 |
0.0663 |
0.3600 |
0.0696 |
0.0003 |
0.0005 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
|
G2, F & 111 |
Mean |
0.6618 |
0.6488 |
4.0668 |
0.4903 |
0.0059 |
0.0087 |
±SD |
0.0563 |
0.0584 |
0.6665 |
0.0770 |
0.0002 |
0.0009 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
|
G3, F & 333 |
Mean |
0.6560 |
0.6443 |
3.2646 |
0.4388 |
0.0057 |
0.0088 |
±SD |
0.0476 |
0.0330 |
0.5652 |
0.0452 |
0.0002 |
0.0007 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
|
G4, F & 1000 |
Mean |
0.6097* |
0.6402 |
3.2355 |
0.4353 |
0.0057 |
0.0090 |
±SD |
0.0642 |
0.0516 |
0.3329 |
0.0373 |
0.0008 |
0.0007 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
F: Female; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 20 (Contd…). SUMMARY OF TERMINAL BODY WEIGHT (g) AND
ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Terminal Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Testes |
Epididymides |
Heart |
|
G1R, M & 0 |
Mean |
496.58 |
0.0136 |
0.0476 |
0.1785 |
0.6684 |
0.3430 |
0.3320 |
±SD |
40.88 |
0.0022 |
0.0051 |
0.0257 |
0.0554 |
0.0286 |
0.0478 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
502.58 |
0.0127 |
0.0538 |
0.1482* |
0.6902 |
0.3358 |
0.3184 |
±SD |
12.09 |
0.0010 |
0.0137 |
0.0126 |
0.0356 |
0.0088 |
0.0643 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 20 (Contd…).
SUMMARY OF TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Kidneys |
Brain |
Liver |
Prostate |
Seminal vesicles with coagulating glands |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
|
G1R, M & 0 |
Mean |
0.4554 |
0.4147 |
2.5665 |
0.2783 |
0.3746 |
0.4088 |
0.0042 |
0.0060 |
±SD |
0.0586 |
0.0488 |
0.3239 |
0.0415 |
0.1185 |
0.0840 |
0.0002 |
0.0003 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
0.4682 |
0.4080 |
2.4984 |
0.3193 |
0.3643 |
0.3862 |
0.0042 |
0.0061 |
±SD |
0.0730 |
0.0361 |
0.1858 |
0.0248 |
0.0941 |
0.0153 |
0.0002 |
0.0003 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation.
TABLE 20 (Contd…).
SUMMARY OF TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Terminal Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Ovaries |
Uterus with Cervix |
Heart |
G1R, F & 0 |
Mean |
308.17 |
0.0229 |
0.0822 |
0.2106 |
0.0410 |
0.2112 |
0.3432 |
±SD |
16.88 |
0.0016 |
0.0185 |
0.0336 |
0.0043 |
0.0292 |
0.0498 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
311.82 |
0.0225 |
0.0791 |
0.2015 |
0.0495* |
0.2026 |
0.3256 |
±SD |
12.71 |
0.0037 |
0.0102 |
0.0405 |
0.0029 |
0.0205 |
0.0293 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subchronic
- Experimental exposure time per week (hours/week):
- 168
- Species:
- rat
- Quality of whole database:
- reliable
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Justification for classification or non-classification
No classification
The NOAEL found in an oral subchronic study was 1000 mg/kg bw.
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