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Administrative data

Description of key information

The test substance was administered to rats in a daily diet over a period of 28 days (according GLP and OECD guideline 407). Since no treatment related effects occurred during the study and during recovery period, the dosage level of 1000 mg/kg/day is considered to be the no-observed-effect level (NOEL) and the no-observed-adverse effect level (NOAEL) of the test substance. 

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

Procedure and observations

The purpose of the study was to evaluate the potential toxicity of the test material when administered orally, by gavage, to rats for 28 consecutive days followed by a 14-day recovery phase. The study design consisted of a control group and three treatment groups with ten animals per sex in the control and high-dose groups and five animals per sex in the low- and mid-dose groups. The test article in the vehicle was administered as a single daily dose at dosage levels of 100, 500 and 1000 mg/kg/day for 28 consecutive days.

Oral administration of the test article to rats did not produce any treatment-related mortalities. One control male was found dead on day 23 from bladder calculi. No treatment-related clinical abnormalities, bodyweight effects, food consumption abnormalities or ophthalmological findings were noted during the main or recovery phases of this study. Weekly neurotoxicological evaluations of the animals did not reveal any notable abnormalities. FOB examinations conducted prior to dosing were consistent between control and treated animals and no notable abnormalities were observed in any animal during the recovery phase.

No treatment-related abnormalities were observed in the clinical pathology parameters evaluated or organ weight data. In addition, there was no evidence of treatment-related effects on the organs or tissues as determined by histopathological evaluation.

 

Discussion

One male control animal was found to be dead on day 23. However, this death was not considered treatment-related since it occurred in a control animal and apparently was a result of renal failure that was secondary to the bladder calculi.

Since no treatment related effects occurred during the study and during recovery period, the dosage level of 1000 mg/kg/day is considered to be the no-observed-effect level (NOEL) and the no-observed-adverse effect level (NOAEL) of the test substance.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is notconsidered to be classified for repeated dose toxicity under Directive 67/548/EEC, as amended for the 30th time in Directive 2008/58/EC.

 

 

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for repeated dose toxicity under Regulation (EC) No. 1272/2008, as amended for the second time in Directive (EC 286/2011).