Developments in the understanding of the etiology of cancer have undermined the 1970s concept that chemicals are either “carcinogens” or “non-carcinogens”. The capacity to induce cancer should not be classified in an inflexible binary manner as present (carcinogen) or absent (non-carcinogen). Chemicals may induce cancer by three categories of mode of action: direct interaction with DNA or DNA replication including DNA repair and epigenetics; receptor-mediated induction of cell division; and non-specific induction of cell division. The long-term rodent bioassay is neither appropriate nor efficient to evaluate carcinogenic potential for humans and to inform risk management decisions. It is of questionable predicitiveness, expensive, time consuming, and uses hundreds of animals. Although it has been embedded in practice for over 50 years, it has only been used to evaluate less than 5% of chemicals that are in use. Furthermore, it is not reproducible because of the probabilisitic nature of the process it is evaluating combined with dose limiting toxicity, dose selection, and study design. The modes of action that lead to the induction of tumors are already considered under other hazardous property categories in classification (Mutagenicity/Genotoxicity and Target Organ Toxicity); a separate category for Carcinogenicity is not required and provides no additional public health protection.

Chemical carcinogenicity revisited 2 : current knowledge of carcinogenesis shows that categorization as a carcinogen or non-carcinogen is not scientifically credible / J.E. Doe, A.R. Boobis, V. Dellarco, P.A. Fenner-Crisp, A. Moretto, T.P. Pastoor, R.S. Schoeny, J.G. Seed, D.C. Wolf. - In: REGULATORY TOXICOLOGY AND PHARMACOLOGY. - ISSN 0273-2300. - 103(2019 Apr), pp. 124-129. [10.1016/j.yrtph.2019.01.024]

Chemical carcinogenicity revisited 2 : current knowledge of carcinogenesis shows that categorization as a carcinogen or non-carcinogen is not scientifically credible

A. Moretto;
2019-04

Abstract

Developments in the understanding of the etiology of cancer have undermined the 1970s concept that chemicals are either “carcinogens” or “non-carcinogens”. The capacity to induce cancer should not be classified in an inflexible binary manner as present (carcinogen) or absent (non-carcinogen). Chemicals may induce cancer by three categories of mode of action: direct interaction with DNA or DNA replication including DNA repair and epigenetics; receptor-mediated induction of cell division; and non-specific induction of cell division. The long-term rodent bioassay is neither appropriate nor efficient to evaluate carcinogenic potential for humans and to inform risk management decisions. It is of questionable predicitiveness, expensive, time consuming, and uses hundreds of animals. Although it has been embedded in practice for over 50 years, it has only been used to evaluate less than 5% of chemicals that are in use. Furthermore, it is not reproducible because of the probabilisitic nature of the process it is evaluating combined with dose limiting toxicity, dose selection, and study design. The modes of action that lead to the induction of tumors are already considered under other hazardous property categories in classification (Mutagenicity/Genotoxicity and Target Organ Toxicity); a separate category for Carcinogenicity is not required and provides no additional public health protection.
Carcinogenicity; Classification; Long term bioassay; Mode of action; Risk assessment; Toxicology
Settore MED/44 - Medicina del Lavoro
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/621121
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