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Aromatic amines: mechanisms of carcinogenesis and implications for risk assessment
Hans-Guenter Neumann1
1
Department of Toxicology, University of Wuerzburg, Germany. hg-neumann@t-online.de
DOI: 10.2741/3665 Volume 15 Issue 3, pp.1119-1130
Published: 01 June 2010
(This article belongs to the Special Issue Arylamine induced carcinogenesis)
Abstract

Carcinogenic aromatic amines are widespread and need to be regulated. Genotoxic and non-genotoxic effects are both necessary for tumor development. The common mode of action includes metabolic activation, the reaction of metabolites with nucleic acids and cellular macromolecules as well as toxic effects. The dose-response relationship of irreversible DNA damage is linear down to background concentrations and a no-effect level (NEL) cannot be defined. The dose-response relationships of reversible toxic effects are often non-linear and have been used to derive no-observed adverse effect levels (NOAEL). However, this procedure does not account for background exposure, the activity of structurally related, and those structurally unrelated chemicals which compete for the same biochemical systems. Fixed limit values for acceptable risk are therefore unacceptably uncertain. The perspective should change from "risk" to the "contribution to risk". The ALARA principle (as low as reasonably achievable) is part of such an approach. It does not say how much exposure is acceptable. Scientific risk assessment and risk management should be kept distinct and the input of scientific data and expert judgement documented.

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Hans-Guenter Neumann. Aromatic amines: mechanisms of carcinogenesis and implications for risk assessment. Frontiers in Bioscience-Landmark. 2010. 15(3); 1119-1130.