p-[(2-chloroethyl)ethylamino]benzaldehyde

Endpoint summary

Description of key information

The oral administration of N-Chlorethyl,N-Ethyl-4-Aminobenzaldehyde by gavage over a period of 4 weeks caused incipient signs of general systemic toxicity at dose levels of 10 mg/kg bw/d in female animals (clinicochemical parameters) and 40 mg/kg bw/d in both genders. Therefore, the NOAEL was 2.5 mg/kg bw/d in female and 10 mg/kg bw/d in male Wistar rats.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

2.5 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

A repeated dose 28-day toxicity study in Wistar rats according to OECD TG 407 in compliance with GLP was assigned as key study for short-term repeated dose toxicity (BASF SE, 2010). In this study, the test substance was administered for 4 weeks daily by gavage to male and female Wistar rats at dose levels of 2.5, 10 and 40 mg/kg bw/d (test groups 1-3).

Regarding clinical examinations, signs of general systemic toxicity were only observed at a dose level of 40 mg/kg bw/d as there were lower body weights in male animals at the end of the study accompanied with reduced body weight gain. In addition, food consumption was slightly lower during the second half of the administration period. In male animals of test groups 1 and 2 (2.5 and 10 mg/kg bw/d) as well as in female animals of all test groups no impairment of these parameters were observed during clinical examinations. Salivation was seen after dosing nearly all rats of test group 3 (40 mg/kg bw/d) and. From the temporary, short appearance immediately after dosing it is likely, that this finding was induced by a bad taste of the test substance or local affection of the upper digestive tract. This finding was not considered to be an adverse and toxicologically relevant effect. All other clinical parameters as well as FOB and MA did not reveal any treatment-related effects.

Regarding clinical pathology, the common alteration in rats of both sexes of test group 3 (40 mg/kg bw/d) was the decrease of globulin levels. This may include globulin transport proteins because their reduction led to decreased calcium levels in females of test groups 2 and 3 (10 and 40 mg/kg bw/d) and to decreased cholesterol and triglyceride levels in males of test group 3 (40 mg/kg bw/d). The reduced creatinine levels in combination with the decreased globulin levels in females might be due to a decreased formation of skeletal muscles. The reason for the higher potassium levels in males of the test group 3 (40 mg/kg bw/d) could not be elucidated, but a compound-related effect could not be excluded.

Regarding pathology, males and females of test group 3 (40 mg/kg bw/d) showed a decrease in terminal body weight, which was regarded to be a treatment-related effect. In addition, significant increases of absolute and relative liver weights were observed in females of this test group but no histopathological correlate was found for the liver weight increase. Therefore, a treatment-related effect cannot be completely ruled out.

In conclusion, the oral administration of N-Chlorethyl,N-Ethyl-4-Aminobenzaldehyde by gavage over a period of 4 weeks caused incipient signs of general systemic toxicity at dose levels of 10 mg/kg bw/d in female animals (clinicochemical parameters) and 40 mg/kg bw/d in both genders. Therefore, the NOAEL was determined to be 2.5 mg/kg bw/d in female and 10 mg/kg bw/d in male Wistar rats.

Justification for classification or non-classification

EU classification according to Annex VI of the Directive 67/548/EEC:

- Toxic: Danger of serious damage to health by prolonged exposure if swallowed, R48/25

GHS classification according toAnnex I 1272/2008 CLP (EU GHS):

- STOT repeated Cat. 1