Registration Dossier

Administrative data

Description of key information

The key study (Brown, 1981) was conducted in a way similar to the OECD 453 guideline. Although the study predates the guideline and deviates from it in minor ways the study was considered to be of sufficient reliability (reliability score of 2 according to the criteria of Klimisch et al, 1997) to fulfil the regulatory requirement and be used as a basis for classification and labelling. The study was conducted on the mouse (male and female) using a feeding methodology with concentrations present in feed to obtain 1, 3 and 10 mg/kg bw/day dose levels. In addition to test groups a negative control group (plain diet) was used to verify the validity of the study result.
Animals were dosed for 100 weeks after which all animals were subject to gross necropsy. Unscheduled deaths during the study period were also subject to gross necropsy. In addition to this animals were also observed for appearance, behaviour, general observations, bodyweight, food consumption, water consumption, opthalmology, haematology, blood chemistry and urine analysis during the study period and histological examination of tissues after termination.
Treatment affected body weight changes in females, and resulted in opthalmological effects during the test period. Although an increased incidence of hepatocellular tumours was observed in treated female mice, this was considered to not be a carcinogenic response because no increased incidence was noted in males; neoplasms in females were only observed in the terminal stage of the study (week 96 onwards) and there was no evidence of any early significant mortality associated with neoplasia; a zero incidence, a relatively unusual event in the majority of chronic mouse studies at the performing laboratory, was recorded in control females; no dose-relationship was apparent; and no pre-neoplastic lesions were noted.
Based upon these effects the NOAEL for carcinogenicity was set at 10mg/kg bw/day, the highest dose level tested.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Dose descriptor:
10 mg/kg bw/day

Additional information

The available data was considered to be adequate to fulfil the regulatory requirement and to be used as a basis for classification and labelling.

Carcinogenicity: via oral route (target organ): cardiovascular / hematological: lymph nodes; digestive: liver; respiratory: lung

Justification for classification or non-classification

Dinoseb was considered not to be carcinogenic in mice.