A paradigm shift is required for the risk assessment of potential human health after exposure to low level chemical exposures: a response to the toxicity testing in the 21st century report

International Journal of Toxicology
J E Trosko, Brad L Upham

Abstract

Chemicals are known to be associated with birth defects, cancer, cardiovascular diseases, immunological, reproductive, and neurological disorders. In response to recent reviews of limitations of current concepts and techniques for toxicity testing, this commentary challenges the paradigm that chemicals are directly responsible for DNA damage in the genomic-nuclear DNA in relevant cells of the human body. This challenge is not that mutations do not play roles in human-inherited or somatic diseases but that chemical exposures bring about disease end points by epigenetic mechanisms or by alterations in adult stem cell numbers in utero (ie, the Barker hypothesis) or postnatally, by selecting preexisting mutated cells. Classic concepts, that is, multistage, multimechanism process of carcinogenesis, stem cell theory of cancer, and newer and ignored concepts, such as cancer stem cells and cell-cell communication, will be used to support the view that the toxic effect of chemicals is mediated by nonmutagenic mechanisms at human relevant exposures.

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Citations

Oct 10, 2013·Expert Opinion on Drug Metabolism & Toxicology·David Canovas-JordaSusanne Bremer
Dec 27, 2011·Preventive Medicine·Se-Ran YangKyung-Sun Kang
Jun 25, 2015·Carcinogenesis·Kannan Badri NarayananHyun Ho Park
Oct 18, 2011·Biochimica Et Biophysica Acta·Ilaria PotolicchioPaolo Meda
Jul 31, 2019·Environmental Science and Pollution Research International·Panithi SaktrakulklaKeri C Hornbuckle
Jun 21, 2021·Archives of Toxicology·Carr J SmithAnthony Dayan

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transgenic

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