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ToxSci Advance Access published online on July 25, 2003
Toxicological Sciences, doi:10.1093/toxsci/kfg204
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
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Received May 12, 2003; accepted July 17, 2003
© 2003 Society of Toxicology

Review

Heterogeneity of Toxicant Response: Sources of Human Variability

Justin E. Aldridge 1, Jennifer A. Gibbons 1, Meghan M. Flaherty 2, Marisa L. Kreider 1, Jocelyn A. Romano 3, and Edward D. Levin 4*

1 Integrated Toxicology Program, Duke University Medical Center, Durham, NC 27710; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710
2 Integrated Toxicology Program, Duke University Medical Center, Durham, NC 27710; Biological Chemistry Program, Duke University Medical Center, Durham, NC 27710; Department of Chemistry, Duke University, Durham, NC 27708
3 Integrated Toxicology Program, Duke University Medical Center, Durham, NC 27710; Nicholas School of the Environment, Duke University Marine Laboratory, Beaufort, NC 28516
4 Integrated Toxicology Program, Duke University Medical Center, Durham, NC 27710; Department of Psychiatry, Duke University Medical Center, Durham, NC 27710

* To whom correspondence should be addressed. E-mail: edlevin{at}duke.edu.


  Abstract

While risk assessment models attempt to predict human risk to toxicant exposure, in many cases these models cannot account for the wide variety of human response. This review addresses several primary sources of heterogeneity that may affect individual response to drug or toxicant exposure. Consideration was given to genetic polymorphisms, age related factors during development and senescence, gender differences associated with hormonal function, and preexisting diseases influenced by toxicant exposure. These selected examples demonstrate the need for additional steps in risk assessment that are needed to more accurately predict human response to toxicants and drugs.


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