Registration Dossier

Administrative data

Description of key information

No carcinogenic potential

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
823 mg/kg bw/day
Study duration:
Quality of whole database:
The available information comprises an adequate and reliable study.

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

A 2 -year carcinogenicity study was performed according to OECD 451 in rats (Kuwahara, 2007). Groups of 51 male and female animals were orally administered 0, 2000, 6000 and 20000 ppm of the test substance in food, equivalent to 0, 79.2, 242 and 823 mg/kg bw/d (males) and 0, 105, 311 and 1052 mg/kg bw/d (females). At terminal sacrifice, the adverse effects seen in the 6000 ppm group (males) and 20000 ppm groups (both sexes) were a dose-related bronchiolisation of the alveolar wall, which was more pronounced in males; as well as decreased body weight and body weight gain in the 20000 ppm group. Hyperplasia of the forestomach was observed in both sexes at all dose levels, including the 2000 ppm group, in statistically significant higher numbers than in the control groups. As humans do not have a forestomach, this effect is not toxicologically relevant to humans. A statistically significant increase in the incidence of chronic nephropathy was observed in all female treatment groups. In males, the increase was statistically significant in the 6000 ppm group and the severity of the lesion increased with dose level in the 6000 and 20000 ppm groups. Therefore, no NOAEL can be established and the LOAEL is considered to be 105 mg/kg bw/d for females and 79.2 mg/kg bw/d for males.

Incidental neoplastic lesions were observed, but none showed a statistically significant or dose-dependent increase. One male in the high dose group had a squamous cell carcinoma in the forestomach. The tumour developed in the more central portion of the stomach than the limiting ridge, where the hyperplastic lesions were generally observed and is thus not considered to be related to the forestomach lesions. One male and two females in the high dose group had squamous cell carcinoma in the nasal cavity. As neoplastic lesions occurred randomly in single animals in the low- or mid-dose group of one sex in other tissues, the lesions in the high dose group are considered to be incidental occurrences. No other toxicologically relevant neoplastic lesions were observed. The test substance did therefore not have a carcinogenic potential under the conditions of the study.

Justification for selection of carcinogenicity via oral route endpoint:
The reliable GLP compliant OECD Guideline study was chosen.

Justification for classification or non-classification

The available data are conclusive but not sufficient for classification according to the criteria of DSD (67/548/EEC) and CLP (1272/2008/EC).