Thresholds in genotoxicity responses

It has been commonly accepted that risk assessments of genotoxic chemicals are based on linear extrapolation methods. However, there is substantial evidence that some chemicals may be genotoxic only at high doses by mechanisms that do not occur at low doses, or only under specific conditions in geno...

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Bibliographic Details
Published in:Mutation research. Genetic toxicology and environmental mutagenesis 2000-01, Vol.464 (1), p.123-128
Main Authors: Henderson, Leigh, Albertini, Silvio, Aardema, Marilyn
Format: Article
Language:English
Subjects:
Aneuploidy
Biological and medical sciences
Chemical mutagenesis
Fundamental and applied biological sciences. Psychology
Homeostatic overload
In vitro artefacts
Medical sciences
Molecular and cellular biology
Molecular genetics
Mutagenesis. Repair
Risk assessment of genotoxins
Threshold mechanisms in genotoxicity
Toxicology
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Summary:It has been commonly accepted that risk assessments of genotoxic chemicals are based on linear extrapolation methods. However, there is substantial evidence that some chemicals may be genotoxic only at high doses by mechanisms that do not occur at low doses, or only under specific conditions in genotoxicity assays, but are inactive at concentrations within the range of human exposure levels. There are a variety of possible mechanisms of thresholded genotoxicity, including disruption of cell division and chromosome segregation, inhibition of DNA synthesis, overloading of oxidative defence mechanisms, metabolism or plasma binding capacity, disturbances of metal homeostasis, cytotoxicity and physiological perturbations in in vivo assays. The degrees of evidence supporting the proposed mechanisms are variable and not all are sufficiently robust to be universally accepted as yet by the scientific community. However, a survey of industrial companies indicated that data have been accepted by some regulatory authorities indicating thresholds contributing to genotoxicity responses.
ISSN:1383-5718
1879-3592
DOI:10.1016/S1383-5718(99)00173-4