Registration Dossier

Diss Factsheets

Administrative data

Description of key information

90-day oral NOAEL; study equivalent to OECD 408.  The mean absolute and body weight-related liver weight were significantly increased for males given 8 mg/kg/day and 16 mg/kg/day.  At the same dose levels, absolute and body weight-related kidney weights were increased for females. However, no associated histopathological changes were noted and no treatment macroscopic or microscopic findings were recorded.  Therefore, these effects were not considered adverse.  Based on these results the NOAEL was 16 mg/kg bw/day (highest dose tested) and the NOEL was established at 4 mg/kg bw/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
16 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Additional information

Male and female rats were exposed to the test substance via gavage at doses of 2, 4, 8, or 16 mg/kg/day for 13 weeks. No mortality was observed during the study. No treatment-related effects on clinical signs, body weight changes, food consumption, or ocular changes were observed. Increased mean absolute liver weights (≥8 mg/kg males) and body weight-related liver weights (16 mg/kg males) and increased mean absolute and body weight-related kidney weights (≥8 mg/kg females) were observed. As the increased body weight-related liver and kidney effects had no associated pathological changes (and are considered and adaptive response to dosing), they are not viewed as adverse. No effects were observed at 4 mg/kg/day.  Therefore, the no observed effect level (NOEL) for this study was 4 mg/kg/day and the NOAEL was 16 mg/kg/day.

Justification for classification or non-classification

R48/22 classification for the EU Directive 67/548/EEC and STOT Rep Cat 2 classification for the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 was precautionarily indicated because no data exists above 16 mg/kg bw. This classification deviates from that found in 67/548/EEC Annex I.

Categories Display