Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Toxicity to reproduction

Currently viewing:

Administrative data

Endpoint:
fertility, other
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Data is from a study report.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2019
Report date:
2019

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Principles of method if other than guideline:
According to OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium iodide
EC Number:
231-679-3
EC Name:
Sodium iodide
Cas Number:
7681-82-5
Molecular formula:
INa
IUPAC Name:
sodium iodide
Test material form:
solid: crystalline
Details on test material:
Name: Sodium Iodide (as per study report)
Appearance: White colour crystalline powder
Purity (a.i.): 99.13% w/w
Storage conditions : Room Temperature (20 - 30˚C)
Molecular Weight: 149.89 g/mol
Molecular Formula: Na-I
SMILES: [Na+].[IH-]

Test animals

Species:
rat
Strain:
Wistar
Details on species / strain selection:
The Rat is a commonly used species for toxicity studies and is also recommended by the stated regulatory guidelines.
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Inbred animals of animal house facility, of the CRO were used after accuring CPCSEA approval.
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 6-7 weeks
- Weight at study initiation: Males: 206.20 g
Females: 203.60 g
- Fasting period before study: Yes.
- Housing: A total 2-3 rats were housed in each polycarbonate cage (size 37 [cm] x 21 [cm], height 20 [cm]). Cage rotation in every rack was carried weekly once. Sterilized corn-cob produced from pure corn, dried and free from dust, was used as bedding material. It was renewed as often as necessary to keep the animals dry and clean.
- Diet (e.g. ad libitum): A conventional laboratory pellet diet. was offered ad libitum. The copy of composition, microbial and chemical contaminant reports analysed periodically.
- Water (e.g. ad libitum): Aquaguard filtered drinking water in bottles was offered ad libitum. Samples of the drinking water were subjected periodically to bacteriological tests and to chemical contaminant analysis.
- Acclimation period: 7-8 days

DETAILS OF FOOD AND WATER QUALITY: No Data Available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.60 and 23.20°C
- Humidity (%): 40.60 to 66.10%
- Air changes (per hr): 12 times per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark.

IN-LIFE DATES: From: February 15, 2019
To: April 06, 2019

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
The oral route was selected for the dose administration and recommended by the regulatory guideline.
Details on mating procedure:
No Data Available
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
The concentration and homogeneity assessment of the dose formulation of Sodium Iodide (CAS No.: 7681-82-5) was performed on Day 01 and Day 22. The results of the analyzed formulation were 3.65, 7.34 and 14.72 mg/ml for Day 01 and 3.65, 7.26 and 14.48 mg/ml for Day 22 for low, mid and high dose respectively. Dose concentration verification were within the acceptance limits of ± 20% of the nominal concentrations for all the dose formulation analysis.
Duration of treatment / exposure:
28 days with 14 days recovery period
Frequency of treatment:
Once Daily
Details on study schedule:
No Data Available
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day
Remarks:
Control Group
Dose / conc.:
0 mg/kg bw/day
Remarks:
Control Group (Recovery)
Dose / conc.:
37.5 mg/kg bw/day
Remarks:
Low Dose Group
Dose / conc.:
75 mg/kg bw/day
Remarks:
Mid Dose Group
Dose / conc.:
150 mg/kg bw/day
Remarks:
High Dose Group
Dose / conc.:
150 mg/kg bw/day
Remarks:
High Dose Group (Recovery)
No. of animals per sex per dose:
G1 (Control Group): 5 males and 5 females
G2 (Low Dose Group): 5 males and 5 females
G3 (Mid Dose Group): 5 males and 5 females
G4 (High Dose Group): 5 males and 5 females
G1-R (Control Recovery Group): 5 males and 5 females
G4-R (High Dose Recovery Group): 5 males and 5 females
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: The doses were selected based upon previously performed Dose-Range FInding Study for the test chemical.
- Rationale for animal assignment (if not random): Prior to the first day of dosing, male and female animals were separately randomized into four different test groups, based on the most recent body weight, using validated software.
- Fasting period before blood sampling for clinical biochemistry: Animals were fasted overnight prior to blood collection.
- Rationale for selecting satellite groups: The satellite group was selected as per the requirement of regulatory guideline.
- Post-exposure recovery period in satellite groups: 2 weeks
- Section schedule rationale (if not random): N/A
- Other: N/A
Positive control:
No Data Available

Examinations

Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Once Daily, preferably at the same time.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: On treatment Day 1 and weekly thereafter during experimental period.

BODY WEIGHT: Yes
- Time schedule for examinations: At start of treatment and weekly (± 2 days) thereafter, till the end of experimental period.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes, at start of treatment and weekly (± 2 days) thereafter, till the end of experimental period.
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Not specified
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Not specified

FOOD EFFICIENCY: Not Specified
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Not specified

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not specified
- Time schedule for examinations: Not Specified

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: During week 4th for main group animals.
- Dose groups that were examined: High dose and control group animals for main group.

HAEMATOLOGY: Yes
- Time schedule for collection of blood: On the termination day, just prior to necropsy.
- Anaesthetic used for blood collection: Not specified
- Animals fasted: Yes
- How many animals: All animals were subjected to blood collection.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: On the termination day, just prior to necropsy.
- Animals fasted: Yes
- How many animals: All animals were subjected to blood collection.

URINALYSIS: Yes
- Time schedule for collection of urine: At the last week of the treatment and recovery periods, all surviving rats of main groups and recovery groups were housed in metabolic cages overnight for collection of urine.
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes

NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: Functional Observation Battery/ Neurobehavioral Observation, sensory reactivity to stimuli, assessment of grip strength, hind limb foot splay and motor activity assessment was performed in week 4th for main group animals and in week 6th for recovery group animals.
- Dose groups that were examined: All animals were subjected to Neurobehavioural examinations.
- Battery of functions tested: sensory activity / grip strength / motor activity / other: hind limb foot splay

IMMUNOLOGY: No
- Time schedule for examinations: N/A
- How many animals: N/A
- Dose groups that were examined: N/A

OTHER:
Oestrus Cycle: At termination, the oestrus cycle of all females were determined by taking vaginal smears.
Bone Marrow Smear Examination: Bone marrow smear (from femur) were prepared at the time of necropsy.
Oestrous cyclicity (parental animals):
At termination, the oestrus cycle of all females were determined by taking vaginal smears.
Sperm parameters (parental animals):
No Data Available
Litter observations:
No Data Available
Postmortem examinations (parental animals):
GROSS PATHOLOGY: Yes, all surviving animals from main group were sacrificed on Day 29 and from recovery group were sacrificed on recovery Day 15. All surviving animals (main and recovery groups) were subjected to necropsy and detailed gross pathology evaluation. Animals were fasted overnight before necropsy. Animals were weighed, euthanized by CO2 asphyxiation and examined externally. All orifices and the cranial, thoracic and visceral cavities were opened and examined macroscopically.

HISTOPATHOLOGY: Yes, full histopathology was carried out on the preserved organs and tissues of all animals in the control and high dose groups. Histopathology was not extended to lower dose groups and recovery group, as there is no test item related lesions observed in control and high dose groups.
Postmortem examinations (offspring):
No Data Available
Statistics:
Raw Data were processed using Statistical Software Sigma Plot 14.0. The mean and Standard Deviation were calculated using the software and all data were summarized in tabular form. All continuous data (body weight, percent change in body weight with respect to day 1, feed consumption, functional observation battery/neurobehavioral observation, foot splay record, grip strength, motor activity, haematology, clinical chemistry, absolute and relative organ weights, etc.) were checked for their normality and for homogeneity, and analysed using one-way ANOVA for comparison of means. Heterogneous data was analysed using Dunnett’s test. In case of recovery groups, means were compared using t-test for homogeneous data and Mann Whitney’s test for heterogeneous data. The significane threshold for all tests (p value) was set at 0.05. Significant differences obtained from the statistical analysis have been indicated at the relevant places in this report.
Reproductive indices:
No Data Available
Offspring viability indices:
No Data Available

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Description (incidence and severity):
No treatment related clinical signs were noted upto 150.0 mg/kg body weight in either sex.
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Description (incidence):
No morbidity or mortality were detected in animals of any of the experimental groups throughout the duration of the experiment.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Males: Treatment related mean body weight and body weight gain (percent change in body weight with respect to Day 1) decrease were noted in males at 150.0 mg/kg when compared to concurrent control animals on Day 8, 15, 22 and 28 in all the groups. . Statistically (P<0.05) significant decrease in percent change in body weight with respect to Day 1 was noted in males on Day 8 (-42% at 150.0 mg/kg), on Day 15 (upto -44% at 37.5, 75.0 and 150.0 mg/kg), on Day 22 (upto -34% at 37.5, 75.0 and 150.0 mg/kg) when compared to concurrent control animals. In recovery males statistically (P<0.05) significant decrease in percent change in body weight with respect to Day 1 was noted on Day 8 (-60% at 150.0 mg/kg), Day 15 (-32% at 150.0 mg/kg) and on Day 28 (-28% at 150.0 mg/kg) when compared to concurrent recovery control animals.

Females: No treatment related changes were noted in females in mean body weight and percent change in body weight with respect to Day 1 upto 150.0 mg/kg
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
No treatment related effect on food consumption was noted up to 150.0 mg/kg
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
no effects observed
Description (incidence and severity):
No ophthalmological abnormalities were detected in the control (G1) and high-dose (G4) groups at week 4 in either sex.
Haematological findings:
effects observed, non-treatment-related
Description (incidence and severity):
Statistically significant increase were noted in RBC, Hematocrit and Hemoglobin of males in G3 and G4 groups, while whereas statistically significant decrease in levels of MCH in males of G2 and G3 group, MCHC in G2 males and WBC in females of G4 group. when compared to concurrent control animals. In recovery animals, statistically significant increase were noted in MCV and MCH (Female: G4-R at 150 mg/kg body weight) while statistically significant decrease were noted in RBC and Platelets (Female: G4-R at 150 mg/kg body weight) when compared to concurrent recovery control animals. The observed variations in hematology parameters at the end of treatment and treatment free period, considered as an inconsistence with dose related response in either sex, reversed in recovery group, minimal in nature and it was further not evidenced by histopathological observations.
Clinical biochemistry findings:
effects observed, non-treatment-related
Description (incidence and severity):
Statistically significant increase were noted in Creatinine in males of G2 groups, Glucose in males of G3 and G4 group, Globulin of females in G2 group when compared to concurrent control animals. In recovery animals, statistically significant increase were noted in ALT and Cholesterol in males of high dose recovery group, while statistically significanct decreased was noted in Phosphorus in males of high dose recovery group, when compared to concurrent recovery control animals. The observed variations in biochemical parameters at the end of treatment and treatment free period, considered as an inconsistence with dose related response in either sex, reversed in recovery group, minimal in nature and it was further not evidenced by histopathological observations.
Urinalysis findings:
no effects observed
Description (incidence and severity):
No treatment related changes were noted in urine analysis upto 150 mg/kg body weight in either sex of treated and treatment free groups.
Behaviour (functional findings):
effects observed, non-treatment-related
Description (incidence and severity):
No treatment-related changes were noted in functional observational battery/neurobehavioral observation upto 150.0 mg/kg. Mean foot splay of all dose groups was also found comparable to the control mean. Motor activity measurements revealed statistically significant decreases in Horizontal Count (HC) and in Ambulatory Count (AC) at 150.0 mg/kg in female. This changes were not related to treatment, as it was inconsistent, not dose dependent manner and observed only in single sex.
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
effects observed, non-treatment-related
Histopathological findings: non-neoplastic:
effects observed, non-treatment-related
Description (incidence and severity):
No treatment related histopathological findings were observed in vehicle control group and in high dose group animals. Microscopic examination revealed varying degree of different pathological changes in various organs belonging to control and treatment groups as follows:
Liver: focal to multifocal minimal perivascular lymphocytic infiltrate (Male: G4: 2/5; Female: G1: 2/5; G4: 2/5);
Kidneys (Unilateral): focal mild lymphocytic infiltrate (Male: G1: 1/5; Female: G1: 1/5; G4: 1/5) ;
Thyroid: Congenital cyst (Male: G1: 1/5, G4: 2/5; Female: G1:1/5, G4:: 1/5)
Testes(Unilateral): focal minimal to diffuse moderate multinucleated giant cell ( G1: 1/5, G4:1/5);
Epididymis(Unilateral): focal mild sperm stasis ( G4:2/5).
All the other histopathological changes observed during the study were considered as spontaneous and incidental to Wistar Rats
Histopathological findings: neoplastic:
not specified
Other effects:
no effects observed
Description (incidence and severity):
Bone Marrow smear did not show any adverse effects or deviation as compared to controls.

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Description (incidence and severity):
No abnormalities detected in the oestrus cycle in any of the treatment group at termination.
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified

Details on results (P0)

The test chemical did not cause any systemic toxicity to the animals. However, significant differences in the body weights were observed even in recovery periods. The test chemical also had effects on the weight of organs especially epididymides in males, wherein reduction of organ weight was observed. However, in absence of any histopathological evidence, the effect was considered as non-significant and inconsistent. However, reduction of body weight was considered to be related to the treatment of the test chemical, Sodium Iodide.

Effect levels (P0)

open allclose all
Dose descriptor:
NOAEL
Effect level:
75 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
body weight and weight gain
food consumption and compound intake
ophthalmological examination
haematology
clinical biochemistry
urinalysis
organ weights and organ / body weight ratios
gross pathology
histopathology: non-neoplastic
reproductive function (oestrous cycle)
other: No adverse effect during bone marrow smear examinations were observed in both males and females.
Remarks on result:
not determinable due to absence of adverse toxic effects
Dose descriptor:
LOAEL
Effect level:
150 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
Remarks on result:
not determinable due to absence of adverse toxic effects

Target system / organ toxicity (P0)

Critical effects observed:
no

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
not specified
Body weight and weight changes:
not specified
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
Anogenital distance (AGD):
not specified
Nipple retention in male pups:
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

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Effect levels (F1)

Remarks on result:
not measured/tested

Target system / organ toxicity (F1)

Critical effects observed:
not specified

Overall reproductive toxicity

Reproductive effects observed:
no
Treatment related:
no

Applicant's summary and conclusion

Conclusions:
Based on all the available data, and from the observations and conclusion, the NOAEL and LOAEL for the test chemical, Sodium Iodide (CAS No. 7681-82-5) was found to be 75 mg/kg bw/day and 150 mg/kg bw/day, respectively.
Executive summary:

A 28 days repeated dose toxicity study was performed using the test chemical, Sodium Iodide (CAS No. 7681-82-5). Wistar rats were used as animals of choice, wherein the test chemical was dosed to the rats for 28 days with 14 days recovery period. A total number of 60 Wistar rats (30 males and 30 females) were randomly allocated to six different dose groups of 5 animals/sex/group. The animals allocated to Group G2, G3 and G4/G4-R received 37.5, 75.0and 150.0mg/kg body weight of Sodium Iodide (CAS No.: 7681-82-5) respectively, whereas the animals of Group G1/G1-R, received vehicle alone [Distilled Water] for 28 consecutive days. Observations comprised of mortality/morbidity, clinical signs, detailed clinical observation, body weight, body weight gain, feed consumption, ophthalmoscopic examination, functional observational battery/neurobehavioral observation, hematology, clinical biochemistry, urinalysis, gross pathology and histopathology (vehicle control group and high dose group). No treatment related mortality/morbidity were noted in either sex up to 150.0 mg/kg body weight. No treatment related clinical signs were noted up to 150.0 mg/kg body weight in either sex. No abnormalities were detected during ophthalmological examination at 150.0 mg/kg body weight in either sex, when compared with control group. Treatment related mean body weight and body weight gain (percent change in body weight with respect to Day 1) decrease were noted in males at 150.0 mg/kg when compared to concurrent control animals on Day 8, 15, 22 and 28 in all the groups. Moreover statistically (P<0.05) significant decreases in mean body weight were noted in males on Day 22 (up to -14% at 37.5, 75.0 and 150.0 mg/kg) and on Day 15 (-15% at 75.0 mg/kg) when compared to concurrent control animals. Statistically (P<0.05) significant decrease in percent change in body weight with respect to Day 1 was noted in males on Day 8 (-42% at 150.0 mg/kg), on Day 15 (up to -44% at 37.5, 75.0 and 150.0 mg/kg), on Day 22 (up to -34% at 37.5, 75.0 and 150.0 mg/kg) when compared to concurrent control animals. In recovery males statistically (P<0.05) significant decrease in percent change in body weight with respect to Day 1 was noted on Day 8 (-60% at 150.0 mg/kg), Day 15 (-32% at 150.0 mg/kg) and on Day 28 (-28% at 150.0 mg/kg) when compared to concurrent recovery control animals. No treatment related changes were noted in feed consumption up to 150.0 mg/kg body weight in either sex. No treatment related changes were noted in functional observational battery/ neurobehavioral observation, foot splay, grip strength and motor activity assessment up to 150.0 mg/kg body weight in either sex. No treatment related changes were noted in hematological and clinical chemistry parameters up to 150.0 mg/kg body weight in either sex. No treatment related changes were noted in urine analysis up to 150.0 mg/kg body weight in either sex. No any abnormalities detected in the oestrus cycle in any of the treatment group at termination. No treatment related gross (external and internal) pathological changes were noted up to 150.0 mg/kg body weight in either sex. No treatment related histopathological examination were noted in any of the tissue/organ at 150.0 mg/kg body weight in either sex. Based on all the above data, and from the observations and conclusion, the NOAEL and LOAEL for the test chemical, Sodium Iodide (CAS No. 7681-82-5) was found to be 75 mg/kg bw/day and 150 mg/kg bw/day, respectively.