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Description of key information

Key value for chemical safety assessment

Additional information

No specific study was performed on the absorption/distribution/metabolism/excretion (ADME) of this substance (BMI) but data are currently available from the in vivo toxicology studies.

 

Absorption

Oral route

During acute oral studies in rats all behavioural, clinical and physiological responses after administration were considered normal. The oral LD50for BMI was >2000 mg/kg body weight in female rats. Without pharmacokinetic data it is difficult to say if absorption occurred in these studies.

 

In a repeat dose (28-day) study no toxicologically significant adverse systemic effects were noted and there was no effect of treatment on reproductive performance, including mating performance, fertility and offspring survival and development up to Day 7 of age. The presence of vacuolated macrophages in the mesenteric lymph nodes may be an indication of accumulation of the test material, following adsorption through the gastro-intestinal tract.

 

Dermal route

An acute dermal study was not performed as this was not considered to be an appropriate route of exposure. 

A M+K guinea pig sensitiser study showed BMI to be a moderate sensitiser, however, as no effects were noted in the control animals this is not indicative of adsorption.

 

Inhalation route

An acute inhalation toxicity study was performed where rats were subjected to a single 4-hour snout-only exposure with the test substance at target concentrations of 2.0, 1.0 or 0.5 mg/L, and a target Mass median aerodynamic diameter (MMAD) of 4 µm, in a stepwise fashion. Following exposure the rats were monitored for 15 days or until death or sacrifice if determined as necessary on justification of animal welfare concerns. After 15 days the surviving animals were sacrificed and subject to a macroscopic examination, all animals that died during the course of the study were also subject to a macroscopic examination. During the course of the study several rats died prematurely and many clinical signs, mainly associated with the lungs, were noted, however, it is considered that all mortalities were a result of localised toxicity to the respiratory tract. There is no evidence, therefore, that adsorption of the test material occurred during this study.

 

 

Distribution

The findings from the combined repeat dose and reproductive screening study did not provide evidence that BMI was distributed systemically following oral administration.It was concluded that oral administration of BMI to Crl: CD (SD) rats for at least 5 weeks at doses of 100, 300 and 1000 mg/kg/day was well tolerated with no toxicologically significant adverse systemic effects and there was no effect of treatment on reproductive performance, including mating performance, fertility and offspring survival and development up to Day 7 of age. It was considered that the presence of vacuolated macrophages in the mesenteric lymph nodes might be an indication of accumulation of test material, following adsorption through the GI tract but this has not been proven.

 

Metabolism

No data are available on metabolism in the existing toxicity studies. The clinical signs seen in the acute inhalation study wereconsidered to be a result of localised toxicity to the respiratory tract.

 

Excretion

No data are available on excretion in the existing toxicity studies.

 

 

Conclusion

From the data available so far there is no evidence that the test substance is absorbed via the gastrointestinal tract following oral (or inhalation) administration or via the skin following dermal administration.