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Description of key information

28 day study:
The oral administration of the test material to rats by gavage, at a maximum dose level of 500 mg/kg/day for 28 days, resulted in adverse, treatment-related changes at 500 and 250 mg/kg/day. There were no treatment-related changes detected in the parameters measured among animals of either sex treated with 125 mg/kg/d. The NOAEL for systemic toxicity was therefore considered to be 125 mg/kg/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
125 mg/kg bw/day
Study duration:

Additional information

Justification for classification or non-classification

The oral repeat dose toxicity of this substance was evaluated in rats at levels up to 500 mg/kg/day according to OECD 407. Treatment-related deaths occurred at 500 mg/kg/day in both sexes. All of these animals had reddened adrenal and pituitary glands and yellow contents in the stomach. Microscopic examinations found edema and inflammation of the stomach in all 500 mg/kg/day group females and thickened mucosa in the nonglandular portion of the stomach in one male. In the 250 mg/kg/day group, one male also had edema and inflammation of the stomach. Clinical signs were toxicologically significant at 250 mg/kg/day and 500 mg/kg/day dose levels. The occurrence of soft stools, diarrhea, mucoid diarrhea, and a decrease in the general condition of the animals was greater than in the controls and lower dose. Significant decreases in body weight gain occurred only in the 500 mg/kg/day group males and females. Food consumption showed a slightly decrease in the 500 mg/kg/day groups although only the food consumption for females was significantly different from the controls. These findings are primary orsecondary effects dueto the local irritation via the experimental route of administration Treatment-related increases in mean absolute and relative adrenal gland weights occurred at the 250 and 500 mg/kg/day dose levels. However, no test article-related histopathological lesions were observed in the adrenal glands to account for the increases. Based on these findings, the No Adverse Effect Level NOAEL was determined to be 125 mg/kg/day.

In accordance to Directive 67/548/EEC and (Regulation (EC) No. 1272/2008) classification of this substance is not required for prolonged exposure.