Registration Dossier

Administrative data

Description of key information

Oral administration of the test item to rats for a period of forty-two days for males and up to fifty-four days for females at dose levels of up to 1000 mg/kg/day resulted in treatment-related effects in males treated with 1000 and 350 mg/kg/day. No toxicologically significant effects were detected in females from any treatment groups. No clinically observable signs of toxicity were observed during the daily clinical observations and no toxicologically significant effects were observed during the weekly open field arena observations, the haematological parameters, or the blood chemical parameters. The effects detected in this study were considered not to represent an adverse health effect, therefore a NOAEL and a suitable high dose level for use on a twenty-eight day study was considered to be 1000 mg/kg/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat

Additional information

Oral administration of the test item to rats for a period of forty-two days for males and up to fifty-four days for females at dose levels of up to 1000 mg/kg/day resulted in treatment-related effects in males treated with 1000 and 350 mg/kg/day. No toxicologically significant effects were detected in females from any treatment groups. No clinically observable signs of toxicity were observed during the daily clinical observations and no toxicologically significant effects were observed during the weekly open field arena observations, the haematological parameters, or the blood chemical parameters.

 

Macroscopic findings did not reveal any effects considered to be attributable to treatment. Organ weight data however revealed increases in absolute and relative liver and kidney weight for males treated with 1000 and 350 mg/kg/day and microscopic examinations revealed treatment related effects in the liver and kidney for males treated with 1000 mg/kg/day. Centrilobular hepatocyte enlargement was evident however this is commonly observed in the rodent liver following the administration of xenobiotics and, in the absence of associated inflammatory or degenerative changes, is generally considered to be adaptive in nature.

A higher incidence of globular accumulations of eosinophilic material in the tubular epithelium was also detected. Accumulations of globular eosinophilic material in the tubular epithelium is a well documented effect and are peculiar to the male rat, which occurs in response to treatment with certain hydrocarbons. Female rats and other species do not develop “hydrocarbon nephropathy” and for this reason, the effect is not indicative of a hazard to human health.
Centrilobular hepatocyte enlargement was seen in relation to treatment for males only treated with 1000 mg/kg/day. Hepatocyte enlargement is commonly observed in the rodent liver following the administration of xenobiotics and, in the absence of associated inflammatory or degenerative changes, is generally considered to be adaptive in nature.

The effects detected in this study were considered not to represent an adverse health effect, therefore a NOAEL and a suitable high dose level for use on a twenty-eight day study was considered to be 1000 mg/kg/day.

Justification for classification or non-classification

There are conclusive and sufficient data for classification of the substance with regard to repeated dose toxicity.

The test item is not classified for this endpoint in accordance to Directive 67/548/EEC or to the CLP Regulation (EC) No 1272/2008.