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Environ Mol Mutagen. 2019 Nov 9. doi: 10.1002/em.22346. [Epub ahead of print]

Utility of a next generation framework for assessment of genomic damage: A case study using the industrial chemical benzene.

Author information

1
Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
2
The Dow Chemical Company, Horgen, Switzerland.
3
Burke, Virginia.
4
Center for Health Sciences, Exponent, Inc., Alexandria, Virginia.
5
Swansea University Medical School, Swansea University, Swansea, United Kingdom.
6
European Commission, Joint Research Centre (JRC), Ispra, Italy.
7
Health and Environmental Sciences Institute, Washington, District of Columbia.
8
Procter & Gamble, Mason, Ohio.
9
Corteva Agriscience, Newark, Delaware.
10
Centre for Safety of Substances and Products, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
11
Department of Biology, University of Ottawa, Ottawa, Ontario, Canada.

Abstract

We recently published a next generation framework for assessing the risk of genomic damage via exposure to chemical substances. The framework entails a systematic approach with the aim to quantify risk levels for substances that induce genomic damage contributing to human adverse health outcomes. Here, we evaluated the utility of the framework for assessing the risk for industrial chemicals, using the case of benzene. Benzene is a well-studied substance that is generally considered a genotoxic carcinogen and is known to cause leukemia. The case study limits its focus on occupational and general population health as it relates to benzene exposure. Using the framework as guidance, available data on benzene considered relevant for assessment of genetic damage were collected. Based on these data, we were able to conduct quantitative analyses for relevant data sets to estimate acceptable exposure levels and to characterize the risk of genetic damage. Key observations include the need for robust exposure assessments, the importance of information on toxicokinetic properties, and the benefits of cheminformatics. The framework points to the need for further improvement on understanding of the mechanism(s) of action involved, which would also provide support for the use of targeted tests rather than a prescribed set of assays. Overall, this case study demonstrates the utility of the next generation framework to quantitatively model human risk on the basis of genetic damage, thereby enabling a new, innovative risk assessment concept. Environ. Mol. Mutagen. 2019. © 2019 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.

KEYWORDS:

exposure; genotoxicity; human health risk assessment; mutagenicity; testing strategy

PMID:
31709603
DOI:
10.1002/em.22346

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