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Carcinogenicity

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Description of key information

In vitro cell transformation and tumour promotion in mouse cells: inconclusive (o-cresol)
In vivo 2 year feeding study with rat and mouse: only equivocal evidence of carcingenicity (p-/m-cresol mixture)

Key value for chemical safety assessment

Additional information

There is no carcinogenicity bioassay or other chronic study available to assess the carcinogenic potential of cresols.

From tumour promotion studies in mice there are some indications that cresols 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).

In 2007, US Health and Human Services published a Toxicity and Carcinogenicity Study in which only male rats or only female mice were fed m/p-cresol mixture (60:40) over a period of two years without interim kill (US Department of Health and Human services, 2007). Neither absolute/relative organ weights nor blood biochemistry data were reported so far. The report contains only histopathological data.

In the two studies, that were performed with rats, male F344/N rats received 0, 1500, 5000, and 15000 ppm m-/p-cresol daily for 105 weeks in the diet. Under the condition of these 2-year studies, there was equivocal evidence of carcinogenic activity on m-/p-cresol based on the 4/50 male rats with renal tubular adenomas. The incidence of these neoplasms was not significant but exceeded the historical control data of the laboratory for feeding studies (1/297).

In the mouse study female B6C3F1 mice received in 0, 1000, 3000, 10000 ppm of the m-/p-cresol mixture for 106-107 weeks in the diet. Under the conditions of these 2-year studies there was some evidence of carcinogenic activity of m-/p-cresol mixture based on the increased incidence of fore stomach squamous cell papillomas. However, there is no human counterpart for the rodent fore stomach (Proctor 2007). Therefore, the fore stomach squamous cell paplillomas are of minor significance for the human situation. In addition, due to the corrosive property of cresols, chronic irritation is expected to be the mode of action.

Justification for classification or non-classification

Carcingenicity of cresols can not undisputable be evaluated, because there are only inconclusive and equivocal study results available.