title: Heterogeneity of toxicant response: sources of human variability.
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.
authors.affiliation: Integrated Toxicology Program, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Justin E
authors.initials: JE
authors.lastname: Aldridge
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Gibbons
authors.forename: Meghan M
authors.initials: MM
authors.lastname: Flaherty
authors.forename: Marisa L
authors.initials: ML
authors.lastname: Kreider
authors.forename: Jocelyn A
authors.initials: JA
authors.lastname: Romano
authors.forename: Edward D
authors.initials: ED
authors.lastname: Levin
mesh_terms: D000367:Age Factors; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D004785:Environmental Pollutants / Q000009:adverse effects*; D020022:Genetic Predisposition to Disease; D006801:Humans; D018570:Risk Assessment; D012737:Sex Factors
chemical_list: D004785:Environmental Pollutants; D003577:Cytochrome P-450 Enzyme System