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ToxSci Advance Access originally published online on July 25, 2003
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Toxicological Sciences 76, 3-20 (2003)
Copyright © 2003 by the Society of Toxicology

REVIEW

Heterogeneity of Toxicant Response: Sources of Human Variability

Justin E. Aldridge*,{dagger}, Jennifer A. Gibbons*,{dagger}, Meghan M. Flaherty*,{ddagger},§, Marisa L. Kreider*,{dagger}, Jocelyn A. Romano*,¶ and Edward D. Levin*,||,1

* Integrated Toxicology Program, {dagger} Departments of Pharmacology and Cancer Biology, {ddagger} Biological Chemistry Program, and || Department of Psychiatry, Duke University Medical Center, Durham, North Carolina 27710; § Department of Chemistry, Duke University, Durham, North Carolina 27708; and Nicholas School of the Environment, Duke University Marine Laboratory, Beaufort, North Carolina 28516

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 responses. This review addresses several primary sources of heterogeneity that may affect individual responses 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 responses to toxicants and drugs.


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