Registration Dossier

Administrative data

Description of key information

90-day oral toxicity study in rats, No Effect Level = 500 mg/kg/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
500 mg/kg bw/day

Additional information

A repeated dose toxicity study was conducted by Istituto Di Recherche Biomediche "Antoine Marxer" RBM S.p.a., Italy, on behalf of Enichem Synthesis S.p.a., Italy, to assess the repeated dose toxicity by the oral route of administration of the test substance DMC. The study was conducted according to OECD test guideline 408, and in compliance with GLP.

The test material was administered by oral gavage to groups of rats (15 males and 15 females per group) for 13 weeks; at the end of the dosing period, 10 rats/sex/dose level were sacrificed for pathology examination, while 5 rats/sex/dose level were retained without treatment for a 4 -week recovery period. Dose groups were 0 (vehicle control), 1, 5, 50, and 500 mg/kg/day.

No deaths related to the test substance were seen, nor were any clinical signs during the dosing or recovery periods, and no compound-related changes were seen in post-mortem examinations.

In conclusion, on the basis of the overall results obtained in this study, oral administration of the test article DMC daily for 13 consecutive weeks to rats was well tolerated up to and including the highest dosage of 500 mg/kg/day and therefore this dose level is considered the NEL both in male and female rats.

Justification for classification or non-classification

According to Directive 67/548/EEC, classification as "R48 Danger of serious damage to health by prolonged exposure" applies when an effect is seen in rats by oral administration at up to 50 mg/kg bodyweight/day during a 90 -day study. In the test, no effects were seen up to 500 mg/kg/day, and so classification is not required on the basis of this result.