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Description of key information

There are two repeated dose toxicity studies by oral exposure route; the 28-day study in rats in which the doses of 1000, 150 and 15 mg/kg/day were administered and the reproduction / developmental toxicity screening study in rats in which the doses of 750, 150 and 30 mg/kg/day were administered.
In the 28-day study, there was a sign of adverse effects at the dose of 1000 mg/kg in males/females and the NOAEL of 150 mg/kg/day was derived from the study results. Whereas no adverse effects were observed at any doses tested in the reproduction / developmental toxicity screening study therefore the NOAEL of 750 mg/kg/day was derived from the study results.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

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

Mode of Action Analysis / Human Relevance Framework

Additional information

There are two repeated dose toxicity data by oral exposure route; the 28-day study and reproduction / developmental toxicity screening test. In the 28-day study, the doses of 1000, 150 and 15 mg/kg/day were administered in rats and the adverse effects were observed at the highest dose. Therefore the NOAEL has been determined to be 1000 mg/kg.day in this study. In the screening study, the doses of 750, 150 and 30 mg/day were administered and no adverse effects were observed at any doses tested. Therefore the NOAEL of 750 mg/kg/day was derived from this study. The design of 28 -day studies are more relevant to examine the systemic effects of the tested animals at this endpoint. In adidtion to this, the worst case has to be considered for the hazard / risk assessment for the substance under REACH. For this respect, the NOAEL of 150 mg/kg/day derived from the 28 -day study results is used for the calculation of DNEL in repeated dose toxicity.

The repeated dose toxicity tests described above meet the requirements of OECD Test Guidelines and are assigned to be reliability 1 data according to the scoring system of Klimisch et al (Klimisch et al., 1997). This ranking was deemed appropriate because the studies were conducted the GLP certified laboratory and were in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.

Justification for classification or non-classification

The test substance does not meet the criteria for classification according to EU classification system (Council Directive 67/548/EEC and Regulation (EC) No 1272/2008) with respect to repeated dose toxicity: oral.