Sodium iodide

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

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 peer reviewed publication

Data source

Reference

Reference Type:

publication

Title:

Repeated dose oral toxicity study of the test chemical

Author:

Sherer et al

Year:

1991

Bibliographic source:

Journal of Toxicology and Environmental Health

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

The subchronic study was conducted to evaluate the toxic effects of repeated administration of the test chemical to sprague-dawley rats by the oral (drinking water) route.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

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

Details on test material:

- Name of test material:Sodium iodide
- Molecular formula:INa
- Molecular weight:149.89427
- Substance type:Inorganic
- Physical state:Solid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:Simonsen Laboratories(Gilroy, Calif.)
- Age at study initiation: 34-38 d
- Diet (e.g. ad libitum): Purina rodent chow ad lib.
- Water (e.g. ad libitum): ad libitum
- Housing: Animals were housed 3 per cage.

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12-h light/dark cycle

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

100 days

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 1, 3, 10, and 100 mg/l (0, 0.05, 0.15, 0.5 or 5 mg/Kg/day)
Basis:

No. of animals per sex per dose:

120 Sprague-Dawley rats

Control group
0 mg/l : Twelve female and 12 male rats

Treatment group
1, 3, 10, and 100 mg/l : 6 males and 6 females

Control animals:

yes, concurrent vehicle

Details on study design:

No data

Positive control:

No data

Examinations

Observations and examinations performed and frequency:

BODY WEIGHT: Yes

HAEMATOLOGY: Yes
-Blood samples were taken from the tail vein (700 µl/animal, after warming under a heat lamp) at d 10 and from the inferior vena cava upon termination of the study (d 100).

-Following Hematological Parameters were examined :
Hematocrit
Total Hemoglobin
Blood Urea Nitrogen (BUN)
Triglycerides
Alanine Aminotransferase
Aspartate Aminotransferase
Total Cholesterol

CLINICAL CHEMISTRY: Yes
Plasma T3 and T4 levels were determined at d 10 as well as at d 100.

ORGAN WEIGHT: Yes
Thyroid, brain,liver, kidney, heart, and testes weights were determined.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Statistics:

The data were subjected to statistical analysis, using the 95% confidence level. The methods used included a one-way analysis of variance (ANOVA),Tukey's multiple range test for thyroid hormone levels and two-sample t-test for all others.

Results and discussion

Results of examinations

Clinical signs:

not examined

Mortality:

not examined

Body weight and weight changes:

no effects observed

Description (incidence and severity):

No effects observed on body weights.

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Description (incidence and severity):

Hematocrit, hemoglobin, and blood urea nitrogen (BUN) values were relatively constant and did not vary with treatment. There were no significant differences in AST, ALT, cholesterol, and triglyceride values.

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

Significant increase in T4/T3 ratios in female rats after 100 d of treatment with sodium iodide was observed. There were variations in AST, ALT, cholesterol, and triglyceride values between treatment groups, but there are no consistent treatment-related effects.

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

Treatment had no effect on kideneys, liver, brain, or heart weights in either sex, or on testes weights in male rats. In male Sprague-Dawley rats thyroid weights increased with an increasing concentration of test chemical in the drinking water. The increase was statistically significant using a one-way ANOVA (p < .05 with a one-tailed test). When thyroid weights were corrected for body weight, this ratio was significantly increased at the 10 and 100 ppm levels in male rats. In contrast, thyroid weight was
decreased in female rats at the highest dose of iodide treatment.

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

Histological exmination of the thyroid sections stained revealed no pathological alterations that were treatment related

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Effect levels

Dose descriptor:

LOAEL

Effect level:

100 mg/L drinking water

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Effects were observed on modifications of thyroid function.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The repeated dose toxicity of the test chemical to rats by the oral route was observed at a dose concentration of 100 mg/l (5 mg/Kg/day) in a 100 days study period. Effects were observed on modifications of thyroid functions. Therefore the “ Lowest observed adverse effect level (LOAEL)” for repeated dose toxicity study was considered to be 100 mg/l (5 mg/Kg/day).

Executive summary:

The subchronic study was conducted to evaluate the toxic effects of repeated administration of the test chemical to sprague-dawley rats by the oral (drinking water) route. Rats were treated with 0, 1, 3, 10, and 100 mg/l ( (0, 0.05, 0.15, 0.5 or 5 mg/Kg/day)) of the test chemical in the drinking water for 100 d. Treatment had no effect on body, brain, or heart weights in either sex, or on testes weights in male rats. Although differences in kidney and liver weights were noted, they did not appear to be treatment related. Thyroid weight in male rats was significantly increased with an increasing concentration of sodium iodide in the water. In contrast, thyroid weight decreased at the highest dose of sodium iodide in female rats. Hematocrit, hemoglobin, and blood urea nitrogen (BUN) values were relatively constant and did not vary with treatment. There were no significant differences in AST, ALT, cholesterol, and triglyceride values.Also there was a significant increase in T4/T3 ratios in female rats after 100 d of treatment with sodium iodide.The results of this study indicate that sodium iodide affect thyroid hormone status in substantially different ways. Based on the observations made, the the “ Lowest observed adverse effect level (LOAEL)” for repeated dose toxicity study was considered to be 100 mg/l (5 mg/Kg/day).