@article{454f07c889684e7ba9e20b217ac24e5e,
title = "Human carcinogenic risk evaluation: An alternative approach to the two-year rodent bioassay",
abstract = "An approach to the evaluation of carcinogenic risk resulting from exposure to a given chemical is presented in place of a reliance on two-year rodent bioassays. An emphasis is placed on evaluation of the potential DNA reactivity or increased cell proliferation that can be produced by a chemical. The special cases of immunosuppressive and estrogenic chemicals are considered. These evaluations are proposed to involve a combination of in vitro assays, computerized models, and short-term (up to 13 weeks) bioassays in rodents. The emphasis is on mechanistic understanding and evaluation of the dose response and relevance to humans.",
keywords = "Cell proliferation, DNA reactive, Estrogen, Immunosuppressive, Mechanism, Non-genotoxic",
author = "Cohen, {Samuel M.}",
note = "Funding Information: Several examples have been identified for which the animal MOA is not relevant to humans. Most well known is the example of a2u-globulin-related induction of male rat kidney tumors, based on interaction of the administered chemical (or metabolite) with a2u-globulin, ingestion, impaired digestion and accumulation in the renal tubular cells leading to cell death, regeneration, and eventually renal cell tumors. No comparable protein is present in humans, and therefore, this MOA cannot occur in humans. Similarly, formation of calcium phosphate-containing urinary precipitate following administration of high doses of sodium salts to rats, such as saccharin or ascorbate, occurs by a mechanism that does not occur in humans. This lack of human relevance led to the down classification of saccharin by the International Agency for Research on Cancer (IARC) and delisting from the National Toxicology Program List of Carcinogens.",
year = "2004",
month = aug,
doi = "10.1093/toxsci/kfh159",
language = "English (US)",
volume = "80",
pages = "225--229",
journal = "Toxicological Sciences",
issn = "1096-6080",
publisher = "Oxford University Press",
number = "2",
}