Pentan-1-ol

Carcinogenicity

Description of key information

Carcinogenicity is no endpoint of concern since their are no indications from the available in vitro and in vivo genotoxicity and repeated dose toxicity stuy results. No carcinogenic potential was revealed in a 24 week pulmonary tumor 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 considered to be classified for carcinogenicity under Regulation (EC) No 1272/2008, as amended for the seventh time in Regulation No (EC) 1297/2014.

Additional information

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 pentan-1-ol or its structural analogues were identified. However, there are experimental data that can be taken into consideration for the assessment of carcinogenicity of pentan-1-ol and its analogues.

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

This assumption is supported by study results presented in a publication (Stoner et al. 1973). Carcinogenicity of pentan-1-ol was investigated in a 24 week pulmonary tumour 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 tumour 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 tumour incidence. The result of this study was clearly negative, as the lung tumour 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.

 

Furthermore, the carcinogenicity of the structural analogue 3-methylbutan-1-ol (CAS No. 123-51-3) was evaluated in a study which was described in two publications (Gibel et al. 1974, 1975). In these studies, 15 Wistar rats were dosed orally twice a week with 0.1 mL/kg bw 3-methylbutan-1-ol corresponding to 80.8 mg/kg bw/dose whereas 24 animals received an subcutaneous injection of 0.04 mLkg bw corresponding to 32.3 mg/kg bw/dose once a week. Postmortal examination after the average life time of 527 days included blood analysis as well as histopathological analysis of the organs, spinal segments and femurs. As result, severe chronic-toxic effects were reported, as liver cirrhosis, myocard necrosis and effects on pancreas and haematopoietic organs. However, in both studies, only one dose was administered and the MTD was exceeded as the animals were reported to show overt chronic-toxic effects. The number of control animals was not consistent in both applications and no discrimination between male and female animals was made. Additionally, the number of animals per dose or control group was insufficient, only 15-25 animals per group were tested. Due to these reasons, the relevance of the tumours distributed in different tissues of the treated animals is ambiguous. Thus, the studies showed serious deficits so that they cannot be taken into account for assessment.

 

 

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