Morpholine, 4-[(triethoxysilyl)methyl]-

Endpoint summary

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

100 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Additional information

In a 28 days oral administration test with (N-Morpholinomethyl)triethoxysilane groups of 5 male and female rats (HsdRccHan : WIST) were exposed to 0, 20, 150 and 1000 mg/kg bw/day by gavage with corn oil as the vehicle. No mortality occurred during the study period. The mean body weight development in all male dose groups was almost unaffected when compared to the standard growth curve for this strain. Females showed higher weight gain to the corresponding control group, reaching statistically significance at 1000 mg/kg bw/d. Food consumption was found slightly, but statistically significant, reduced for all female dose groups compared to the corresponding controls. No differences were observed concerning functional and behavioural examination prior to application and during the last week of dosing, respectively. Responses to reflex testing were normal in all groups. The values for haematology were in normal ranges without significant deviations. For a small number of clinical biochemistry parameters the differences between control and test groups attained a degree of statistical significance. However, these differences were all within the range of the historical control data for this rat strain, so no toxicological significance was attached to these findings. No test substance-related differences in urinalysis parameters were noted when compared with the control values. There were no changes in organ weights, macroscopic and microscopic examination that were considered to be an effect of treatment. Based on the results of the study, 1000 mg/kg bw/day is considered to be the no-observed-adverse-effect-level (NOAEL) and the no-observed-effect-level (NOEL) for the test substance in animals of both sexes.

In a 90-day repeated oral dose toxicity study with the test item (N-Morpholinomethyl)triethoxysilan groups of 10 male and female Wistar rats were exposed to 0, 100, 300 and 1000 mg/kg bw/day by gavage with corn oil as the vehicle.

Histopathological findings directly attributed to the test item were seen in the kidney of males treated at 1000 and 300 mg/kg/day.

At 300 mg/kg/day, one surviving male rat showed also kidney lesions considered test item-related, and another male died spontaneously of severe renal pathology with secondary myocarditis. Renal lesions were partially reversible after 28 days. A minimally increased myeloid:erythroid ratio of the bone marrow was considered indicative of increased myelopoiesis in individuals presenting prominent renal lesions, and was therefore considered indirectly test item-related. It was not reversible after 28 days. The significance of some minor pulmonary lesions seen in males at 1000 mg/kg/day could not be elucidated, a test item relationship cannot be excluded. Pulmonary lesions had resolved after 28 days without treatment.

Further associated findings in the HD group were: macroscopic findings in the kidney, slightly higher kidney weight and increase in blood urea and creatinine in male animals. Finally, overall body weight gain was slightly attenuated in male animals.

On the basis of these findings, the kidney can be considered the major target organ of (N-Morpholinomethyl)triethoxysilan.

A reproduction toxicological effect of (N-Morpholinomethyl)triethoxysilan was not found in this study.

A slightly lower weight in adrenal glands of female animals of all dose groups and a slightly higher spleen weight in female animals of the MD and HD group cannot not be elucidated but was absent at the end of the recovery period. A relation to the test item is unclear.

The dose level of 100 mg/kg/day marks the NOAEL in this study.

Justification for classification or non-classification

Based on the NOAEL of 100 mg/kg bw/day in the 90-day oral gavage study (N-Morpholinomethyl)triethoxysilane is not classified as harmful after repeated exposure.