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.

Genotoxicity in risk assessment : is it time to use a threshold approach? / F. Metruccio, A. Moretto. - In: CURRENT OPINION IN TOXICOLOGY. - ISSN 2468-2020. - 11-12(2018 Nov 30), pp. 21-26.

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

A. Moretto
2018-11-30

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.
DNA adduct; DNA mutation; DNA repair; Dose-response; Metrics; Toxicology
Settore MED/44 - Medicina del Lavoro
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/621125
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