N,N-bis(trimethylsilyl)aminopropylmethyldiethoxysilane

Endpoint summary

Description of key information

In the key 28-day repeated dose oral toxicity study, conducted according to OECD 407 and GLP, the reported NOAEL value was 150 mg/kg bw/day based on post-dose clinical signs in both sexes and reduced motor activity seen in females dosed at 650 mg/kg bw/day (Huntingdon, 2003).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

150 mg/kg bw/day

Study duration:

subacute

Species:

rat

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

In the key 28-day repeated dose oral toxicity study, conducted according to OECD 407 and GLP, the reported NOAEL value was 150 mg/kg bw/day post-dose clinical signs in both sexes and the reduced motor activity seen in females dosed at 650 mg/kg bw/day (Huntingdon, 2003).

Following daily oral gavage administration of 15, 150 and 650 mg/kg bw/day of test substance in dry corn oil for 28 days to three groups of 5 male and 5 female rats, no mortality occurred during the study period. Reduced body tone, abnormal gait, underactivity, limited use of limbs, hunched posture, pre and post-dose salivation, unresponsive behaviour and partially closed eyelids were observed in animals dosed at 650 mg/kg bw/day. Each day the animals fully recovered from the post-dose clinical signs. Neurobehavioural screening revealed lower motor activity in females dosed at 650 mg/kg bw/day. The lower motor activity in females was considered to be likely associated with the post-dose reduced body tone and abnormal gait. The post-dose clinical signs in both sexes and the lower motor activity seen in females were considered to represent toxicity, likely to be associated with a transient effect on the nervous system.

No treatment-related effects were observed on body weights. The overall mean food consumption for females at 650 mg/kg bw/day was lower than the control. Food efficiency values for all treated animals were comparable to the controls.

The microscopic examinations revealed treatment-related hyaline droplets in the kidneys of most of the treated males. These lesions were considered to be associated with the slightly higher than control mean creatinine levels seen for all treated male groups. Dose-response relationship was seen in the increased creatinine levels, however the magnitude of the differences were minimal and considered not to be of toxicological importance. The presence of hyaline droplets in the cortical tubule cells of the kidneys in male rats is likely to have occurred by the hydrocarbon based origin of the test material. Similar effects due to hydrocarbons have not been shown to occur in human kidneys, nor in female rats. Therefore, the incidence of these findings were considered to be attributable to treatment, but of no toxicological importance with regard to health risk to humans.

Lower platelet count and higher aspartate aminotransferase values were observed in males dosed at 650 mg/kg bw/day when compared to controls. These differences from control were slight and although possibly related to treatment, were not associated with any corroborative findings including histopathological lesions. Therefore, the changes in platelet and aspartate aminotransferase values noted in males dosed at 650 mg/kg bw/day were considered to be of no toxicological importance.

Justification for classification or non-classification

Based on the available data for N,N-bis(trimethylsilyl)aminopropylmethyldiethoxysilane, no classification is required for specific organ toxicity following repeated exposures according to Regulation (EC) No. 1272/2008