title: Overview: Using mode of action and life stage information to evaluate the human relevance of animal toxicity data.
abstract: A complete mode of action human relevance analysis--as distinct from mode of action (MOA) analysis alone--depends on robust information on the animal MOA, as well as systematic comparison of the animal data with corresponding information from humans. In November 2003, the International Life Sciences Institute's Risk Science Institute (ILSI RSI) published a 2-year study using animal and human MOA information to generate a four-part Human Relevance Framework (HRF) for systematic and transparent analysis of MOA data and information. Based mainly on non-DNA-reactive carcinogens, the HRF features a "concordance" analysis of MOA information from both animal and human sources, with a focus on determining the appropriate role for each MOA data set in human risk assessment. With MOA information increasingly available for risk assessment purposes, this article illustrates the further applicability of the HRF for reproductive, developmental, neurologic, and renal endpoints, as well as cancer. Based on qualitative and quantitative MOA considerations, the MOA/human relevance analysis also contributes to identifying data needs and issues essential for the dose-response and exposure assessment steps in the overall risk assessment.
authors.affiliation: US Environmental Protection Agency, Washington, DC, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Seed
authors.forename: Edward W
authors.initials: EW
authors.lastname: Carney
authors.forename: Richard A
authors.initials: RA
authors.lastname: Corley
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Crofton
authors.forename: John M
authors.initials: JM
authors.lastname: DeSesso
authors.forename: Paul M D
authors.initials: PM
authors.lastname: Foster
authors.forename: Robert
authors.initials: R
authors.lastname: Kavlock
authors.forename: Gary
authors.initials: G
authors.lastname: Kimmel
authors.forename: James
authors.initials: J
authors.lastname: Klaunig
authors.forename: M E
authors.initials: ME
authors.lastname: Meek
authors.forename: R Julian
authors.initials: RJ
authors.lastname: Preston
authors.forename: William
authors.initials: W
authors.lastname: Slikker
authors.forename: Sonia
authors.initials: S
authors.lastname: Tabacova
authors.forename: Gary M
authors.initials: GM
authors.lastname: Williams
authors.forename: Jeanette
authors.initials: J
authors.lastname: Wiltse
authors.forename: R Thomas
authors.initials: RT
authors.lastname: Zoeller
authors.forename: Penelope
authors.initials: P
authors.lastname: Fenner-Crisp
authors.forename: Dorothy E
authors.initials: DE
authors.lastname: Patton
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D006801:Humans; D013045:Species Specificity; D014116:Toxicology / Q000706:statistics & numerical data*
chemical_list: D002273:Carcinogens