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Administrative data

Description of key information

The endpoint conclusion was derived after evaluation of all data available on analogues. The worst case was selected for the endpoint conclusion. A summary of the evaluation is included in Section 13.

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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
The rationale to read across the data is attached in Section 13.
Reason / purpose:
read-across source
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
Key result
Dose descriptor:
NOAEL
Effect level:
6.7 mg/kg bw/day (actual dose received)
Based on:
test mat.
Remarks:
Recalculated dose based on iodide content (see any other information on results").
Sex:
male/female
Basis for effect level:
clinical biochemistry
Key result
Critical effects observed:
yes
Lowest effective dose / conc.:
67 mg/kg bw/day (actual dose received)
System:
endocrine system
Organ:
thyroid gland
Treatment related:
yes
Dose response relationship:
not specified
Relevant for humans:
yes
Conclusions:
In the drinking water study with the read-across analogue 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, corresponding to 1.8 mg sodium iodide/kg bw/day, or 1.53 mg I-/kg bw/day. These results can be read across to bismuth oxy-iodide bromide, applying a correction for molecular weight. The corresponding NOAEL for BiOI0.6Br0.4 was calculated to be 6.7 mg/kg bw/day.
Executive summary:

The subchronic study was conducted to evaluate the toxic effects of repeated administration of the read-across analogue test substance 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, corresponding to 1.8 mg sodium iodide/kg bw/day, or 1.53 mg I-/kg bw/day. These results can be read across to bismuth oxy-iodide bromide, applying a correction for molecular weight. The corresponding NOAEL for BiOI0.6Br0.4 was calculated to be 6.7 mg/kg bw/day.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
6.7 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Sufficient studies on analogues are available.
System:
endocrine system
Organ:
thyroid gland

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on the available data, bismuth oxy-iodide bromide is not classified for effects after repeated dose exposure according to Regulation (EC) No 1272/2008.