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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Comparison of toxicity induced by iodine and iodide in male and female rats
Author:
Sherer TT, Thrall KD, Bull RJ
Year:
1991
Bibliographic source:
J. Toxicol. Environ. Health: Curr. Iss. 32, 89

Materials and methods

Principles of method if other than guideline:
The subchronic study was conducted to evaluate the toxic effects of repeated administration of sodium iodide to Sprague-Dawley rats by the oral (drinking water) route.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Simonsen Laboratories(Gilroy, Calif.)
- Age at study initiation: 34-38 days
- Housing: 3 per cage
- Diet (e.g. ad libitum): Purina rodent chow, ad lib.
- Water (e.g. ad libitum): ad libitum

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

I

Administration / exposure

Route of administration:
oral: drinking water
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
100 days
Frequency of treatment:
Daily
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/L drinking water
Remarks:
Vehicle controls
Dose / conc.:
1 mg/L drinking water
Dose / conc.:
3 mg/L drinking water
Dose / conc.:
10 mg/L drinking water
Dose / conc.:
100 mg/L drinking water
No. of animals per sex per dose:
Controls: 12/sex/dose
Test groups: 6/sex/dose
Control animals:
yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:
BODY WEIGHT: Yes

HAEMATOLOGY: Yes
- Time schedule for collection of blood: day 10 and day 100, from tail vein (700 µL/animal, after warming under a heat lamp)
- Anaesthetic used for blood collection: Not specified
The following parameters were examined: hematocrit, total hemoglobin, blood urea nitrogen, triglycerides, alanine aminotransferase, aspartate aminotransferase, total cholesterol

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: day 10 and day 100
- Animals fasted: Not specified
The following parameters were examined: plasma T3 and T4 levels

OTHER: the following organ weights were determined: thyroid, brain, liver, kidney, heart, testes
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 specified
Mortality:
not specified
Body weight and weight changes:
no effects observed
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.
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
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.
Gross pathological findings:
not specified
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Effect levels

open allclose all
Key result
Dose descriptor:
NOAEL
Effect level:
10 mg/L drinking water
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical biochemistry
Key result
Dose descriptor:
LOAEL
Effect level:
100 mg/L drinking water
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical biochemistry

Target system / organ toxicity

Key result
Critical effects observed:
yes
Lowest effective dose / conc.:
100 mg/L drinking water
System:
endocrine system
Organ:
thyroid gland
Treatment related:
yes
Dose response relationship:
not specified
Relevant for humans:
yes

Any other information on results incl. tables

The study was performed with young rats, estimated average weight = 100 g. Based on an average water consumption of 18 ml/day[1](water consumption = 0.11 * (0.1)0.7872), the intake of the 10 mg/L group is estimated to correlate to appr. 0.18 mg sodium iodide. Thus, the intake for rats of 100 g is estimated at 1.8 mg/kg bw/ day NaI, which correlates to appr. 1.53 mg I-/ kg bw/ day.


[1]Calculation based on defaults reported in TNO report V98.390 (1998)

Applicant's summary and conclusion

Conclusions:
In the drinking water study with the test substance sodium iodide, following 100 days exposure, a significant increase of T4/T3 ratio was noted in female rats at the highest dose level of 100 mg/L drinking water. 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. Therefore the LOAEL for repeated dose toxicity study was considered to be 100 mg/L. The NOAEL was 10 mg/L drinking water, which was calculated to correspond to ca. 1.8 mg NaI/kg bw/day.
Executive summary:

The subchronic study was conducted to evaluate the toxic effects of repeated administration of sodium iodide to Sprague-Dawley rats by the oral (drinking water) route. Rats were treated with 0, 1, 3, 10, and 100 mg/l of sodium iodide in the drinking water for 100 days.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 day of treatment with sodium iodide.The results of this study indicate that sodium iodide affect thyroid hormone status in substantially different ways. The highest concentration level of 100 mg/L was considered to be a LOAEL based on the results of the study. The NOAEL was set at 10 mg/L, which was calculated to correspond to ca. 1.8 mg NaI/kg bw/day.