Sodium iodide

Endpoint summary

Description of key information

Repeated dose toxicity: Oral

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).

Repeated dose toxicity: Inhalation

According to column 2 of Annex VIII, exposure by inhalation route is negligible due to the very low vapour pressure of NaI (which is found to be 0.9 mm Hg as mentioned in the relevant end point) on account of high boiling points (as has been informed in the boiling point end point that is 1304 °C).

Repeated dose toxicity: Dermal

The acute dermal toxicity value for Sodium iodide (CAS no. 7681-82-5) (as provided in section 7.2.3) is >2000 mg/kg body weight. Considering this, the end point for repeated dermal toxicity is considered as waiver.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

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

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

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

Route of administration:

oral: drinking water

Vehicle:

water

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

100 days

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

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.

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

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.

Critical effects observed:

not specified

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).

 

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LOAEL

5 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Data is from peer reviewed publication

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Critical effects observed:

not specified

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Waiver

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Critical effects observed:

not specified

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Waiver

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Data available for the target chemical was reviewed to determine the toxic nature of the test chemical upon repeated exposure. The studies are as mentioned below:

Repeated dose toxicity: Oral

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).

Another subacute study was conducted to evaluate the toxic effects of repeated administration of the test chemical to wistar rats by the oral route. Thirty six rats were given the test chemical by oral route on a daily basis for 21 days. Body weight of the TPTX rats were decreased , the intake of I with the drink increased I concentrations in plasma (+ 114%), kidney (+ 100%), liver (+50%), and heart (+ 200%), but there was no increase in the brain. Levels of thyroxine were decreased in the plasma of TPTX rats. The concentrations of I were much higher in plasma than in the other tissues.whereas TPTX did not induce any change in the concentration of I in the tissues tested. Based on the observations made, the low observed adverse effect level (LOAEL) for repeated dose toxicity study is therefore considered to be 0.5 µmol/kg/d.

In yet another study, subchronic study was conducted to evaluate the toxic effects of repeated administration of the test chemical to Walter Reed strain albino rats by the oral route. Fifty four rats were given 0, 500 mg/kg bw and 4000 mg/kg bw sodium iodide by oral (feed) route for 28 days. Submaxillary gland sialadenitis has been produced in rats on diets containing 500 mg/kg bw and 4000 mg/kg bw. This inflammatory and metaplastic process selectively involves distal ductular structures and is modified by concomitant administration of 2000 mg/kg bw sulfaguanidine. Based on the observations made, the low observed adverse effect level (LOAEL) for repeated dose toxicity study is therefore considered to be 500 mg/kg

Repeated dose toxicity: Inhalation

According to column 2 of Annex VIII, exposure by inhalation route is negligible due to the very low vapour pressure of NaI (which is found to be 0.9 mm Hg as mentioned in the relevant end point) on account of high boiling points (as has been informed in the boiling point end point that is 1304 °C).

Repeated dose toxicity: Dermal

The acute dermal toxicity value for Sodium iodide (CAS no. 7681-82-5) (as provided in section 7.2.3) is >2000 mg/kg body weight. Considering this, the end point for repeated dermal toxicity is considered as waiver.

Based on the data available, the test chemical is likely to be toxic upon repeated exposure by oral route and hence it can be categorized as STOT RE 1.

Justification for classification or non-classification

Based on the data available, the test chemical is likely to be toxic upon repeated exposure by oral route and hence it can be categorized as STOT RE 1.