Sodium iodide

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Reproductive Toxicity Study:

A study was conducted with rats to determine the effects of intake of the test chemical. A total of 27 animals were used in this study. Females were bred to normal males, wherein the test chemical was added to the diet during the latter portion of gestation and the females were permitted to litter normally. The effect of the treatment on gestation period, lactation and survival of the young was observed.It was observed that, gestation time for rats was not affected ; however, prolonged parturition was observed in rats. In fetal parameters, average mortality was slightly greater of young from those fed with the test chemical, while the weaning weight was significantly less than that of controls.In other experiment, the female rats were re-bred after removal of dietary intake of the test chemical. It was observed that the females gave birth and nursed litters normally. Thus, from all the oabove observations,LOAEL was found to be 150 mg/kg bw andit is likely to be regarded that there is no reproductive toxicity at concentrations lower than 150 mg/kg bwwhen administered orally.

Link to relevant study records

Reference

Endpoint:

fertility, other

Remarks:

based on test type (migrated information)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from a publication.

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD 414: Pre-Natal Developmental toxicity screening test.

Principles of method if other than guideline:

The above experiment was performed to assess and evaluate the effects of the test chemical on Long-Evans rats.

GLP compliance:

not specified

Limit test:

no

Justification for study design:

No Data Available

Specific details on test material used for the study:

- Molecular weight (if other than submission substance): 149.89427 g/mol
- Substance type: Inorganic
- Physical state: Solid
- Impurities (identity and concentrations): N/A

Species:

rat

Strain:

Long-Evans

Details on species / strain selection:

No Data Available

Sex:

female

Details on test animals or test system and environmental conditions:

Details on test animal
TEST ANIMALS
- Housing: Animals were housed individually in wire cages. Prior to littering, rats were transferred to 3 X 3 mesh wire cages.
- Diet (e.g. ad libitum): Purina Laboratory Chow were provided ad libitum
- Water (e.g. ad libitum): Tap water was supplied ad libitum

Route of administration:

oral: feed

Vehicle:

other: Diet as Purina Laboratory Chow

Details on exposure:

Details on exposure
PREPARATION OF DOSING SOLUTIONS: The test chemical was administered through diet.

DIET PREPARATION
- Rate of preparation of diet (frequency): Daily
- Mixing appropriate amounts with (Type of food): No Data Available
- Storage temperature of food: No Data Available

VEHICLE
- Justification for use and choice of vehicle (if other than water): The test chemical was best miscible in corn oil.
- Concentration in vehicle: 0, 2500 ppm (150 mg/kg bw)
- Amount of vehicle (if gavage): No Data Available
- Lot/batch no. (if required): No Data Available
- Purity: No Data Available

Details on mating procedure:

- The sexually mature females were bred to normal males of the breed or strain. Monogamous pairs of rats were mated. When breeding occurred, the time of first copulation was recorded and gestation subsequently calculated from this time to birth of the first young of the litter. Fourteen female rats which had been fed the test chemical and had produced but lost all young in one or more litters were subsequently re-bred after removal from dietary iodine.

- After successful mating each pregnant female was caged (how): Individually

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No Data Available

Duration of treatment / exposure:

12 days

Frequency of treatment:

Daily

Details on study schedule:

No Data Available

Remarks:

Doses / Concentrations:
0 and 150 mg/kg bw (2500 ppm)
Basis:
Nominal in diet

No. of animals per sex per dose:

27 female rats were used

Control animals:

yes, concurrent vehicle

Details on study design:

- F1 parental animals not mated until weeks after selected from the F1 litters: No Data Available
- Selection of parents from F1 generation when pups were [...] days of age: No Data Available
- Age at mating of the mated animals in the study: No Data Available

Positive control:

No Data Available

Parental animals: Observations and examinations:

Observations were made for length of parturition time and number of young born dead and those born live. Periodic observations were made through the lactation period for mothering instinct, evidence of lactation .

Oestrous cyclicity (parental animals):

No Data Available

Sperm parameters (parental animals):

No Data Available

Litter observations:

Survival of young animals was observed.

Postmortem examinations (parental animals):

No Data Available

Postmortem examinations (offspring):

No Data Available

Statistics:

The data was subjected to statistical analysis. The analytical methods included Analysis of Variance (ANOVA).

Reproductive indices:

No Data Available

Offspring viability indices:

Pups Viability Index.

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality:

not specified

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

Voluntary feed intake of rats fed with the test chemical was about 6 to 7% less than that of control rats and this reduced feed intake

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

effects observed, treatment-related

Description (incidence and severity):

REPRODUCTIVE PERFORMANCE: Gestation time for rats was not affected by the test chemical; however, prolonged parturition was observed in rats.No signs of the beginning of lactation were observed.

Dose descriptor:

LOAEL

Effect level:

150 other: mg/kg bw

Based on:

test mat.

Sex:

female

Basis for effect level:

other: Effects observed on the following parameters : Gestation time, Parturition and No signs of the beginning of lactation were observed.

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality / viability:

mortality observed, treatment-related

Description (incidence and severity):

Average mortality was slightly greater of young from those fed with the test chemical.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Weaning weight was significantly less than that of controls.

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings:

not specified

Other effects:

not specified

Behaviour (functional findings):

not specified

Dose descriptor:

LOAEL

Generation:

F1

Effect level:

150 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

viability

mortality

body weight and weight gain

Remarks on result:

other: Not Specified

Critical effects observed:

not specified

System:

other: Not Specified

Reproductive effects observed:

not specified

Treatment related:

not specified

Conclusions:

The LOAEL value of orally administered test chemical in Long-Evans rats was determined to be 150mg/kg bw.

Executive summary:

A study was conducted with rats to determine the effects of intake of the test chemical. A total of 27 animals were used in this study. Females were bred to normal males, wherein the test chemical was added to the diet during the latter portion of gestation and the females were permitted to litter normally. The effect of the treatment on gestation period, lactation and survival of the young was observed. It was observed that, gestation time for rats was not affected ; however, prolonged parturition was observed in rats. In fetal parameters, average mortality was slightly greater of young from those fed with the test chemical, while the weaning weight was significantly less than that of controls. In other experiment, the female rats were re-bred after removal of dietary intake of the test chemical. It was observed that the females gave birth and nursed litters normally. Thus, from all the oabove observations, LOAEL was found to be 150 mg/kg bw and it is likely to be regarded that there is no reproductive toxicity at concentrations lower than 150 mg/kg bw when administered orally.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LOAEL

150 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The data is from a Klimisch 2 database.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Reproductive toxicity study:

Data available from different studies were reviewed to determine the reproductive toxicity of testchemical.The studies are as mentioned below:

Reproductive Toxicity Study 1:

A study was conducted with rats to determine the effects of intake of the test chemical. A total of 27 animals were used in this study. Females were bred to normal males, wherein the test chemical was added to the diet during the latter portion of gestation and the females were permitted to litter normally. The effect of the treatment on gestation period, lactation and survival of the young was observed.It was observed that, gestation time for rats was not affected ; however, prolonged parturition was observed in rats. In fetal parameters, average mortality was slightly greater of young from those fed with the test chemical, while the weaning weight was

significantly less than that of controls.In other experiment, the female rats were re-bred after removal of dietary intake of the test chemical. It was observed that the females gave birth and nursed litters normally. Thus, from all the oabove observations,LOAEL was found to be150 mg/kg bw andit is likely to be regarded that there is no reproductive toxicity at concentrations lower than150 mg/kg bw when administered orally.

Reproductive Toxicity Study 2:

The effect of the test chemical on the reproductive performance of female minks was investigated.Female minks were administered with 0, 10, 100, or 1000 ppm of the test chemical, in diet for 18 days, from breeding through lactation. A total of 60 animals were used in the study. The animals were grouped in to 4 test groups 10 animals per group. The test animals were observed for , In litter observations, the kits were counted, weighed and sexed. From all the observations, it was found that, the gestation periods of the test chemical-treated mink were shorter than the controls. Kit birth weights were not significantly different from the controls. The average number of kits whelped per female mated in the control group was 5.0. Only 2.1 kits per female mated were whelped by the mink fed 100 ppm supplemental test chemical and none of the females that received the 1000 ppm supplemental test chemical diet whelped. Body weights of kits whelped and nursed by the females that received the 100 ppm supplemental test chemical diet were significantly lighter at 4 weeks of age.No detrimental effects were observed on litter size or kit survival in the group fed 10 ppm supplemental test chemical, and hence the NOAEL for reproductive toxicity in female minks is determined to be 10 ppm of the test chemical in the diet.

Reproductive Toxicity Study 3:

The above experiment was performed to study the effect of ingestion of the test chemical by parental examinations on the behavioural competence of developing animals is studied.The test chemicalwas administered in diet to male and female Sprague-Dawley rats before and during breeding, to females only during gestation and lactation, at levels of 0, about 23,45 and 90 mg/kg bw [0, 0.025, 0.05 or 0.1% (w/w)]. Dams in a positive control group were given 4 mg/kg ip of the anti-mitotic/cytotoxic drug 5-azacytidine on day 17 of gestation.The LOAEL value for the test chemical in rats is found to be about 90 mg/kg/day (0.1%). At this dose level, the test chemical did not produce any significant reduction in parental body weight or food consumption, though it significantly reduced litter size and increased offspring mortality.The LOAEL value for the test chemical is found to be about 45 mg/kg/day (0.05%) for the F1 generation based on the effect of decreased pre-weaning body weights in the offspring, delay in auditory startle and delayed olfactory orientation from the home-cage scent.Overall, the data in this experiment support the view that the test chemical at doses of up to 0.1% in the diet of growing rats produces evidence of developmental toxicity.

Reproductive Toxicity Study 4:

In a one-generation (experiment I) and fertility (experiment II) reproductive study, pregnant female Wistar rats were given fluid orally on a regular basis at dose levels of 0.1% (w/v) or 1% (w/v) of the test chemical.Treatment with 1% (w/v) solution led to reduced body weight and fluid intake, their adrenal glands were enlarged and the level of implementation was prevented. No change in food or fluid intake was seen for rats treated with 0.1% (w/v) solution. In addition, the 0.1% (w/v) of the test chemical solution-treated rats showed a high rate of implantation.Since 0.1% (w/v) of the test chemical is regarded as a high value intake and it is concluded that the test chemical has no effect on reproductive toxicity when orally administered. Neither has it provided any further information about the possible functional significance of the test chemical endometrial concentration in female rats during early pregnancy.

Effects on developmental toxicity

Description of key information

Developmental toxicity study:

A study was conducted with rats to determine the effects of intake of the test chemical. A total of 27 animals were used in this study. Females were bred to normal males, wherein the test chemical was added to the diet during the latter portion of gestation and the females were permitted to litter normally. The effect of the treatment on gestation period, lactation and survival of the young was observed.It was observed that, gestation time for rats was not affected ; however, prolonged parturition was observed in rats. In fetal parameters, average mortality was slightly greater of young from those fed with the test chemical, while the weaning weight was significantly less than that of controls.In other experiment, the female rats were re-bred after removal of dietary intake of the test chemical. It was observed that the females gave birth and nursed litters normally. Thus, from all the oabove observations, LOAEL was found to be150 mg/kg bw and it is likely to be regarded that there is no reproductive and developmental toxicity at concentrations lower than150 mg/kg bwwhen administered orally.

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from a publication.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Principles of method if other than guideline:

The above experiment was conducted to evaluate and assess the effects of the test chemical on the developmental parameters of the Long-Evans Rats.

GLP compliance:

not specified

Specific details on test material used for the study:

- Molecular weight (if other than submission substance):149.89427
- Substance type:Inorganic
- Physical state:Solid

Species:

rat

Strain:

Long-Evans

Details on test animals or test system and environmental conditions:

Details on test animal
TEST ANIMALS
- Housing:Animals were housed individually in wire cages. Prior to littering, rats were transferred to 3 X 3 mesh wire cages.
- Diet (e.g. ad libitum):Purina Laboratory Chow were provided ad libitum
- Water (e.g. ad libitum):Tap water was supplied ad libitum

Route of administration:

oral: feed

Vehicle:

other: Diet as Purina Laboratory Chow

Details on exposure:

No Data Available

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No Data Available

Details on mating procedure:

- The sexually mature females were bred to normal males of the breed or strain.

- Monogamous pairs of rats were mated. When breeding occurred, the time of first copulation was recorded and gestation subsequently calculated from this time to birth of the first young of the litter. Fourteen female rats which had been fed with the test chemical and had produced but lost all young in one or more litters were subsequently re-bred after removal of the test chemical

- After successful mating each pregnant female was caged (how): Individually

Duration of treatment / exposure:

12 days

Frequency of treatment:

Daily

Duration of test:

From breeding to day 21 of suckling

Remarks:

Doses / Concentrations:
0,150 mg/kg bw (2500 ppm)
Basis:

No. of animals per sex per dose:

27 females

Control animals:

yes, concurrent vehicle

Details on study design:

No Data Available

Maternal examinations:

Observations were made for length of parturition time and number of young born dead and those born live. Periodic observations were made through the lactation period for mothering instinct, evidence of lactation and survival of young.

Ovaries and uterine content:

No Data Available

Fetal examinations:

All surviving young from each female in the control and experimental groups were permitted to nurse through the normal suckling period.

Statistics:

The statistical data was analyzed by using Analysis of Variance (ANOVA).

Indices:

Pups Viability Index.

Historical control data:

No Data Available

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality:

not specified

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

Voluntary feed intake of rats fed with the test chemical was about 6 to 7% less than that of control rats and this reduced feed intake

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Number of abortions:

not specified

Pre- and post-implantation loss:

not specified

Total litter losses by resorption:

not specified

Early or late resorptions:

not specified

Dead fetuses:

effects observed, treatment-related

Description (incidence and severity):

An increased incidence of death in the neonates, with <10% of the young surviving for 3 days.

Changes in pregnancy duration:

no effects observed

Description (incidence and severity):

Gestation time for rats was not affected by the test chemical.
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): no effects observed
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.DescriptionIncidenceAndSeverityEffectsOnPregnancyDuration): Gestation time for rats was not affected by the test chemical.

Changes in number of pregnant:

not specified

Other effects:

not specified

Details on maternal toxic effects:

Prolonged parturition was observed in rats.No signs of the beginning of lactation were observed.

Dose descriptor:

LOAEL

Effect level:

150 other: mg/kg bw

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Abnormalities:

not specified

Fetal body weight changes:

effects observed, treatment-related

Description (incidence and severity):

Weaning weight was significantly less than that of controls.
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.DescriptionIncidenceAndSeverityFetalPupBodyWeightChanges): Survival of the young and body weights at weaning were equal to those of controls.

Reduction in number of live offspring:

not specified

Changes in sex ratio:

not specified

Changes in litter size and weights:

not specified

Changes in postnatal survival:

not specified

External malformations:

not specified

Skeletal malformations:

not specified

Visceral malformations:

not specified

Other effects:

not specified

Dose descriptor:

LOAEL

Effect level:

150 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

fetal/pup body weight changes

Abnormalities:

not specified

Developmental effects observed:

not specified

Conclusions:

Based on all the observations, it was concluded that the LOAEL for the test chemical was found to be 150 mg/kg bw after analyzing the effects on developmental parameters of the Long-Evans Rats.

Executive summary:

A study was conducted with rats to determine the effects of intake of the test chemical. A total of 27 animals were used in this study. Females were bred to normal males, wherein the test chemical was added to the diet during the latter portion of gestation and the females were permitted to litter normally. The effect of the treatment on gestation period, lactation and survival of the young was observed.It was observed that, gestation time for rats was not affected ; however, prolonged parturition was observed in rats. In fetal parameters, average mortality was slightly greater of young from those fed with the test chemical, while the weaning weight was significantly less than that of controls.In other experiment, the female rats were re-bred after removal of dietary intake of the test chemical. It was observed that the females gave birth and nursed litters normally. Thus, from all the above observations,LOAEL was found to be150 mg/kg bw and it is likely to be regarded that there is no reproductive and developmental toxicity at concentrations lower than150 mg/kg bw when administered orally.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LOAEL

150 mg/kg bw/day

Study duration:

chronic

Species:

rat

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

Developmental toxicity study:

Data available from different studies were reviewed to determine the developmental toxicity of test chemical.The studies are as mentioned below:

Developmental Toxicity Study 1:

A study was conducted with rats to determine the effects of intake of the test chemical. A total of 27 animals were used in this study. Females were bred to normal males, wherein the test chemical was added to the diet during the latter portion of gestation and the females were permitted to litter normally. The effect of the treatment on gestation period, lactation and survival of the young was observed.It was observed that, gestation time for rats was not affected ; however, prolonged parturition was observed in rats. In fetal parameters, average mortality was slightly greater of young from those fed with the test chemical, while the weaning weight was significantly less than that of controls.In other experiment, the female rats were re-bred after removal of dietary intake of the test chemical. It was observed that the females gave birth and nursed litters normally. Thus, from all the above observations,LOAEL was found to be150 mg/kg bw andit is likely to be regarded that there is no reproductive and developmental toxicity at concentrations lower than150 mg/kg bwwhen administered orally.

Developmental Toxicity Study 2:

The above experiment was performed to study the effect of ingestion of the test chemical by parental examinations on the behavioural competence of developing animals is studied.The test chemicalwas administered in diet to male and female Sprague-Dawley rats before and during breeding, to females only during gestation and lactation, at levels of 0, about 23,45 and 90 mg/kg bw [0, 0.025, 0.05 or 0.1% (w/w)]. Dams in a positive control group were given 4 mg/kg ip of the anti-mitotic/cytotoxic drug 5-azacytidine on day 17 of gestation.The LOAEL value for the test chemical in rats is found to be about 90 mg/kg/day (0.1%). At this dose level, the test chemical did not produce any significant reduction in parental body weight or food consumption, though it significantly reduced litter size and increased offspring mortality.The LOAEL value for the test chemical is found to be about 45 mg/kg/day (0.05%) for the F1 generation based on the effect of decreased pre-weaning body weights in the offspring, delay in auditory startle and delayed olfactory orientation from the home-cage scent.Overall, the data in this experiment support the view that the test chemical at doses of up to 0.1% in the diet of growing rats produces evidence of developmental toxicity.

Developmental Toxicity Study 3:

A one-generation study was conducted on Syrian hamsters to determine the effects of excess of the test chemical intake.Females were bred with normal males while the test chemical (2500 ppm per day or 160 mg/kg bw) was added to their diet during the latter portion of gestation and the females were permitted to litter normally. The effect of the treatment on gestation period, lactation and survival of the young was observed. After all the observations were performed, it was found that, in maternal animals, the mortality among nursing hamsters from females fed with the test chemical was high. Also, voluntary feed intake of the diets containing added test chemical by the pregnant and lactating hamsters was approximately 10% less than that of the controls. However, these cases were considered as sporadic. In fetal parameters, mortality of the young was high but approximately equal in both the experimental and control groups, however, the cause of high mortality is not known. In some cases, some cases of “wet tail” and evidence of dehydration were observed in both control and treated animals.Since there was an absence of specific effects upon reproduction and lactation in pregnant female hamsters, or no increased levels of mortality of the young compared to control, NOAEL of both the parental generation and the F1 generation was considered to be 2500 ppm per day of the test chemical.

Justification for classification or non-classification

From data of all the above studies, the test chemical does not exhibit toxicity to the reproductive system as well as developmental toxicity within the doses mentioned in the various end points.