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Carcinogenicity

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Description of key information

There are no bioassays or chronic studies available to assess the carcinogenic potential of o-cresol.
From tumour promotion studies in mice there are some indications that cresol may act as promotor (Boutwell and Bosch 1959). In cell transformation assays in vitro the transforming activity of o-cresol was evaluated as inconclusive in the presence of a metabolic activation system (CMA 1989) whereas without a metabolic activation system no activity was detected (Pepper, Hamilton and Scheetz 1981).

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

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

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.

Additional information

There are no bioassays or chronic studies available to assess the carcinogenic potential of o-cresol.

From tumour promotion studies in mice there are some indications that cresol may act as promotor (Boutwell and Bosch 1959). Due to limited information on materials and methods, insufficient characterisation of test compond, benzene as solvent and acute toxicity of the applied doses, the study is not assignable. In cell transformation assays in vitro the transforming activity of o-cresol was evaluated as inconclusive in the presence of a metabolic activation system (CMA 1989) whereas without a metabolic activation system no activity was detected (Pepper, Hamilton and Scheetz 1981).

The tumor-promoting ability of o-cresol using the mouse skin-painting model was investigated (Boutwell & Bosch, 1959). Both the average number of skin papillomas per mouse and the percentage of exposed mice with at least one papilloma were increased by treatment with o-cresol. No carcinomas were observed. It should be noted that the vehicle used was benzene, a known carcinogen. The presence of benzene did not appear to affect the results, however, since no papillomas were observed in benzene treated controls. This study suggests cresols may act as promoters (OECD SIDS o-Cresol, CAS NĀ°: 95-48-7, UNEP publication).

Cresols have not been evaluated for ability to induce cancer when applied to the skin of animals. However, a study of skin tumor promotion by cresols was located (Boutwell and Bosch 1959). 27 to 29 mice were given a single dermal application of 9,10-dimethyl-1,2-benzanthracene (DMBA), a cancer initiator, followed by application of 20% solutions of o-, p-, or m-cresol in benzene twice a week for 12 weeks. This level of cresols exposure proved to be acutely toxic, producing relatively high nontumor-related mortality. Consequently, all tumor results were based on number of survivors (14ā€“20 per group). Promotion with cresols led to increases in the average number of skin papillomas per mouse and the percentage of exposed mice with at least one papilloma. o-Cresol was the most potent isomer, and p-cresol the least. Carcinomas were not observed following cresols exposure, although the observed papillomas have the potential to develop into carcinomas. A problem with the study was use of benzene, a known carcinogen, as the solvent for the cresols. However, benzene controls in the cresols experiment did not develop papillomas, and neither did benzene controls in four parallel series of experiments (a few papillomas were observed in a fifth benzene control group). Therefore, the results of this study showing that all three cresol isomers are capable of promoting skin tumors initiated by DMBA appear to be valid (U.S. DEPART- MENT OF HEALTH AND HUMAN SERVICES, Public Health Service, Agency for Toxic Substances and Disease RegistrySeptember 2008).

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