Registration Dossier

Administrative data

Description of key information

Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test: OECD 422: NOEL, males: 316 mg/kg body weight, NOEL,females: 870 mg/kg body weight. NOAEL, males and females: 870 mg/kg body weight.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
870 mg/kg bw/day
Study duration:
subacute
Species:
rat

Additional information

Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: stomach

Justification for classification or non-classification

The No-observed-effect-level (NOEL) of the test item was at 100 mg per kg body weight and day for males and at 870 mg/kg for females. The NOAEL was at 870 mg per kg body weight and day for both sexes.

Only local effects were noted (minimal irritation on the mucous membranes of the stomach noted by a proliferation of the limiting ridge). In the livers of the high dosed males a centrolobular cytoplasmatic basophilia of the hepatocytes is interpreted as indicator of an induction of metabolizing enzymes. As the liver weight was not affected, the amount of enzyme induction is assumed to be rather low. Enzyme induction is not taken as an adverse effect, but as an adaptive response.

According to EU-Directive 2001/59/EC, the application of "R48" is not considered as necessary for the test item, as no severe toxic effects were noted at doses of up to 316 mg/kg.