@article{1a16fb8ccd8049dbb73df237558a9323,
title = "Chemical carcinogenicity revisited 3: Risk assessment of carcinogenic potential based on the current state of knowledge of carcinogenesis in humans",
abstract = "Over 50 years, we have learned a great deal about the biology that underpins cancer but our approach to testing chemicals for carcinogenic potential has not kept up. Only a small number of chemicals has been tested in animal-intensive, time consuming, and expensive long-term bioassays in rodents. We now recommend a transition from the bioassay to a decision-tree matrix that can be applied to a broader range of chemicals, with better predictivity, based on the premise that cancer is the consequence of DNA coding errors that arise either directly from mutagenic events or indirectly from sustained cell proliferation. The first step is in silico and in vitro assessment for mutagenic (DNA reactive) activity. If mutagenic, it is assumed to be carcinogenic unless evidence indicates otherwise. If the chemical does not show mutagenic potential, the next step is assessment of potential human exposure compared to the threshold for toxicological concern (TTC). If potential human exposure exceeds the TTC, then testing is done to look for effects associated with the key characteristics that are precursors to the carcinogenic process, such as increased cell proliferation, immunosuppression, or significant estrogenic activity. Protection of human health is achieved by limiting exposures to below NOEALs for these precursor effects. The decision tree matrix is animal-sparing, cost effective, and in step with our growing knowledge of the process of cancer formation.",
keywords = "Carcinogenicity, Decision tree-matrix, Mode of action, Risk assessment",
author = "Cohen, {Samuel M.} and Boobis, {Alan R.} and Dellarco, {Vicki L.} and Doe, {John E.} and Fenner-Crisp, {Penelope A.} and Angelo Moretto and Pastoor, {Timothy P.} and Schoeny, {Rita S.} and Seed, {Jennifer G.} and Wolf, {Douglas C.}",
note = "Funding Information: This work did not receive any specific support from funding agencies in the public, commercial, or not-for-profit sectors. The authors' affiliations are as shown on the cover page. The authors had sole responsibility for the writing and content of the paper. The views and opinions expressed in the paper are those of the authors, and do not necessarily reflect the views or policies of the authors' current or former employers. The authors have served as members of the following panels or committees and/or for the following organizations: Council of Canadian Academies (VD); European Food Safety Authority (AB, AM); European Centre for Ecotoxicology and Toxicology of Chemicals (AB, JD); EU Scientific Committee on Occupational Exposure Limit Values (AM); European Medicines Agency (AB); Health Canada (PF C); International Agency for Research on Cancer (SC, DW); International Life Science Institute (AB, SC, JD, VD, PF-C, AM, JS, RS, DW); Joint WHO/FAO Meeting on Pesticides Residues (AB, VD, PF-C, AM); Italian Committee on Pesticides (AM); Joint WHO/FAO Expert Committee on Food Additives (Residues of Veterinary Drugs) (AB); National Institutes of Health (SC); National Academy of Sciences (SC, PF-C, RS); National Institute of Environmental Health Sciences (SC, DW); National Toxicology Program (SC, VD, PF-C, JS, DW); Organization for Economic Cooperation and Development (VD, PF-C, JS, RS); Swiss Centre for Applied Human Toxicology (AB, AM); UK Advisory Committee on Pesticides (AB); United Kingdom Committee on Carcinogenicity (AB, JD); UK Committee on the Medical Effects of Air Pollutants (AB); UK Committee on Residues of Veterinary Drugs (AB); UK Committee on Toxicity (AB); United States Environmental Protection Agency (SC, VD, PF-C, JS, RS, DW); United States Food and Drug Administration (SC, PF-C); World Health Organization International Program on Chemical Safety (AB, SC, JD, VD, PF-C, AM, JS, RS). VD, JS and RS are retired from the US Environmental Protection Agency. PF-C is retired from the US Environmental Protection Agency and the International Life Sciences Institute. The authors would like to thank Dr Brian Berridge and Dr David Geter for review and comments. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = apr,
doi = "10.1016/j.yrtph.2019.01.017",
language = "English (US)",
volume = "103",
pages = "100--105",
journal = "Regulatory Toxicology and Pharmacology",
issn = "0273-2300",
publisher = "Academic Press Inc.",
}