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Current Opinion in Toxicology
Article . 2018 . Peer-reviewed
License: Elsevier TDM
Data sources: Crossref
image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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Genotoxicity in risk assessment: is it time to use a threshold approach?

Authors: Metruccio, Francesca; Moretto, Angelo;

Genotoxicity in risk assessment: is it time to use a threshold approach?

Abstract

Abstract Substances that act via a genotoxic mechanism are considered to follow a low dose linear relationship with the absence of a threshold. The discussion on the existence of a threshold for genotoxic (mutagenic and clastogenic) compounds appears sometimes more an academic exercise than of practical use in public health. However, pragmatically, determination of the PoD, i.e. the dose/concentration from which we derive acceptable exposure levels, should be the goal. This will include appropriate dose response data analysis, with statistically defensible methods and use of mechanistic data, and application of adequate uncertainty factors. The best and full use of the quantitative information can be used to analyse dose–response data, and dismiss the binary classification scheme for use in risk assessment and management. Certainly, in areas such as the relationship between the genotoxic and the carcinogenic effect, the appropriate BenchMark Response (BMR) to be used, the relation between effects in target tissues vs those observed in surrogate tissues, and the uncertainty of our measurements there is a need of more solid data. While the simple binary classification scheme can be of some help for screening and prioritization of substances that need further scrutiny, it is not an adequate tool to be used for risk management decisions. The final step of the assessment for guiding management decisions should be quantitative to the extent possible. Accepting the threshold approach on which to base the risk management decisions has significant beneficial economic and societal impact and implications.

Country
Italy
Related Organizations
Keywords

DNA adduct; DNA mutation; DNA repair; Dose-response; Metrics; Toxicology

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
3
Average
Average
Average
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