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Carcinogenicity

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Description of key information

There are no indications of a carcinogenic potential from the available in vitro and in vivo genotoxicity and repeated dose toxicity study results. No carcinogenic potential was revealed for the category member pentan-1-ol in a 24 week pulmonary tumor screening assay performed using intraperitoneal injections in mice.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
250 mg/kg bw/day
Study duration:
subchronic
Species:
mouse
Quality of whole database:
reliable publication

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The available data are considered reliable and suitable for classification purposes under Regulation (EC) No 1272/2008 (CLP).

As a result, the substance is not classified for carcinogenicity under Regulation (EC) No 1272/2008, as amended for the seventh time in Regulation No (EC) 1297/2014.

Additional information

Based on reliable in vitro and in vivo genetic toxicity tests with 2-methylbutan-1-ol and its structural analogues, these substances are not considered to be genotoxic. In addition, there is no indication from repeated dose studies that the substances are able to induce hyperplasia or pre-neoplastic lesions. Thus, there is not concern regarding carcinogenicity for these substances.

No adequate experimental animal data according to or equivalent to the OECD guidelines 451/452/453 are available and no epidemiological studies investigating the carcinogenicity of 2-methybutan-1-ol or its structural analogues were identified. However, carcinogenicity of the read-across substance pentan-1-ol was investigated in a 24 week pulmonary tumor assay, where 30 female A/He mice per dose received 24 intraperitoneal injections of 50 or 250 mg/kg bw pentan-1-ol over 8 weeks. Thereby, survival, body weights and results from gross pathological and histological examinations of the lungs were assessed. 24 weeks after the start of dosing, animals were sacrificed and liver, kidney, spleen, thymus, intestine and salivary and endocrine glands were examined for abnormalities at necropsy. Positive control groups consisting of animals treated with 2 dose levels of urethane (10 or 20 mg urethane/animal) were also maintained. An untreated control group of 50 mice per sex was included. Data on untreated animals represent the spontaneous lung tumor incidence in A/He mice and according to the authors, were in close accord with earlier data on mice of equivalent age. Positive controls treated with urethane showed a dose-related increase in pulmonary tumor incidence. The result of this study was clearly negative, as the lung tumor rate was found to be lower in pentan-1-ol treated groups as compared to the untreated control group (3 % in treated versus 17 % in untreated mice). Thus, under the conditions of this study, pentan-1-ol did not show any carcinogenic potential.

2 -methylbutan-1 -ol (CAS No. 123 -51 -3) was evaluated in an invalid and badly documented carcinogenicity study which was described in two publications (Gibel et al. 1974, 1975). In these studies, 19 Wistar rats were dosed orally twice a week with 0.2 mL/kg bw 2-methylbutan-1-ol corresponding to 163 mg/kg bw/dose whereas 24 animals received an subcutaneous injection of 0.05 mL/kg bw corresponding to 40.8 mg/kg bw/dose twice a week. The number of control animals was inconsistently reported as either 25 or 30. Postmortal examination after the average life time of 495 (oral) and 544 (s.c.) days included blood analysis as well as histopathological analysis of the organs, spinal segments and femurs. Severe chronic-toxic effects were reported. These were liver cirrhosis, myocard necrosis and effects on pancreas and haematopoietic organs. However, the number of affected animals was not given, nor could the effects be assigned to a specific dose group. The effects are especially surprising since no adverse effects were observed in two studies after daily treatment with a more than 10 times higher dose for 90 days, which leads to a higher cumulative dose (108 -119g/kg compared to 23g/kg p. o. and 6.3g/kg s. c.) in a much shorter time period. No tumours were seen in the control rats after two years, which is unlikely even considering the relatively low number of animals used. No historical control data were provided. A low overall number of tumours occured in the treated groups (3 after oral treatment, 8 after s.c. treatment) as single incidences of different tumour types in different organs, which are considered incidental. Due to severe deficits the study was disregarded for the assessment.


Justification for selection of carcinogenicity via oral route endpoint:
most reliable data available