Registration Dossier

Administrative data

Description of key information

A 28 day study was available for an analogue substance suitable for read across (EC#224-235-5):
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.

90 day study:

A test proposal has been submitted for a category of substances of which this substance is a member. Multiple category members will be tested in a comprehensive intelligent testing strategy. Therefore, the read across to this substance will be based on multiple substances. See section 13 for category justification and test proposal.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

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

Additional information

Justification for classification or non-classification

The oral repeat dose toxicity of the test material was evaluated in rats at levels up to 500 mg/kg/day according to OECD 407 guidelines. 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 decline 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 or secondary effects due to the local irritation at the experimental route of administration and are not systemic in nature. 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.