Advancing chemical risk assessment decision-making with population variability data: challenges and opportunities

Advancing chemical risk assessment decision-making with population variability data: challenges... Characterizing population variability, including identifying susceptible populations and quantifying their increased susceptibility, is an important aspect of chemical risk assessment, but one that is challenging with traditional experimental models and risk assessment methods. New models and methods to address population variability can be used to advance the human health assessments of chemicals in three key areas. First, with respect to hazard identification, evaluating toxicity using population-based in vitro and in vivo models can potentially reduce both false positive and false negative signals. Second, with respect to evaluating mechanisms of toxicity, enhanced ability to do genetic mapping using these models allows for the identification of key biological pathways and mechanisms that may be involved in toxicity and/or susceptibility. Third, with respect to dose–response assessment, population-based toxicity data can serve as a surrogate for human variability, and thus be used to quantitatively estimate the degree of human toxicokinetic/toxicodynamic variability and thereby increase confidence in setting health-protective exposure limits. A number of case studies have been published that demonstrate the potential opportunities for improving risk assessment and decision-making, and include studies using Collaborative Cross and Diversity Outbred mice, as well as populations of human cell lines from the 1000 Genomes project. Key challenges include the need to apply more sophisticated computational and statistical models analyzing population-based toxicity data, and the need to integrate these more complex analyses into risk assessments and decision-making. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Mammalian Genome Springer Journals

Advancing chemical risk assessment decision-making with population variability data: challenges and opportunities

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Publisher
Springer US
Copyright
Copyright © 2018 by Springer Science+Business Media, LLC, part of Springer Nature
Subject
Life Sciences; Cell Biology; Animal Genetics and Genomics; Human Genetics
ISSN
0938-8990
eISSN
1432-1777
D.O.I.
10.1007/s00335-017-9731-6
Publisher site
See Article on Publisher Site

Abstract

Characterizing population variability, including identifying susceptible populations and quantifying their increased susceptibility, is an important aspect of chemical risk assessment, but one that is challenging with traditional experimental models and risk assessment methods. New models and methods to address population variability can be used to advance the human health assessments of chemicals in three key areas. First, with respect to hazard identification, evaluating toxicity using population-based in vitro and in vivo models can potentially reduce both false positive and false negative signals. Second, with respect to evaluating mechanisms of toxicity, enhanced ability to do genetic mapping using these models allows for the identification of key biological pathways and mechanisms that may be involved in toxicity and/or susceptibility. Third, with respect to dose–response assessment, population-based toxicity data can serve as a surrogate for human variability, and thus be used to quantitatively estimate the degree of human toxicokinetic/toxicodynamic variability and thereby increase confidence in setting health-protective exposure limits. A number of case studies have been published that demonstrate the potential opportunities for improving risk assessment and decision-making, and include studies using Collaborative Cross and Diversity Outbred mice, as well as populations of human cell lines from the 1000 Genomes project. Key challenges include the need to apply more sophisticated computational and statistical models analyzing population-based toxicity data, and the need to integrate these more complex analyses into risk assessments and decision-making.

Journal

Mammalian GenomeSpringer Journals

Published: Jan 3, 2018

References

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