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Mode of action-based risk assessment of genotoxic carcinogens

Hartwig, Andrea; Arand, Michael; Epe, Bernd; Guth, Sabine; Jahnke, Gunnar; Lampen, Alfonso; Martus, Hans-Jörg; Monien, Bernhard; Rietjens, Ivonne M. C. M.; Schmitz-Spanke, Simone; Schriever-Schwemmer, Gerlinde; Steinberg, Pablo; Eisenbrand, Gerhard

Abstract:
The risk assessment of chemical carcinogens is one major task in toxicology. Even though exposure has been mitigated effectively during the last decades, low levels of carcinogenic substances in food and at the workplace are still present and often not completely avoidable. The distinction between genotoxic and non-genotoxic carcinogens has traditionally been regarded as particularly relevant for risk assessment, with the assumption of the existence of no-effect concentrations (threshold levels) in case of the latter group. In contrast, genotoxic carcinogens, their metabolic precursors and DNA reactive metabolites are considered to represent risk factors at all concentrations since even one or a few DNA lesions may in principle result in mutations and, thus, increase tumour risk. Within the current document, an updated risk evaluation for genotoxic carcinogens is proposed, based on mechanistic knowledge regarding the substance (group) under investigation, and taking into account recent improvements in analytical techniques used to quantify DNA lesions and mutations as well as “omics” approaches. Furthermore, wherever possible and appropriate, special attention is given to the integration of background levels of the same or comparable DNA lesions. ... mehr

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Verlagsausgabe §
DOI: 10.5445/IR/1000121452
Veröffentlicht am 20.07.2020
Originalveröffentlichung
DOI: 10.1007/s00204-020-02733-2
Scopus
Zitationen: 18
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Zitationen: 22
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Angewandte Biowissenschaften (IAB)
Publikationstyp Zeitschriftenaufsatz
Publikationsmonat/-jahr 06.2020
Sprache Englisch
Identifikator ISSN: 0340-5761, 1432-0738
KITopen-ID: 1000121452
Erschienen in Archives of toxicology
Verlag Springer
Band 94
Heft 6
Seiten 1787–1877
Vorab online veröffentlicht am 15.06.2020
Schlagwörter Genotoxicity, Carcinogens, Mutagens, Risk assessment, Mode of action, Endogenous exposure, Exogenous exposure, Toxicogenomics, Biomarker dosimetry
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