Bismuth bromide iodide oxide

Repeated dose toxicity: oral

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

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

Test material form:

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 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 / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/L drinking water

Remarks:

Vehicle controls

Doses / concentrations 2

Dose / conc.:

1 mg/L drinking water

Doses / concentrations 3

Dose / conc.:

3 mg/L drinking water

Doses / concentrations 4

Dose / conc.:

10 mg/L drinking water

Doses / concentrations 5

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

1

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

2

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.