title: Moving forward in human cancer risk assessment.
abstract: BACKGROUND
  The current safety paradigm for assessing carcinogenic properties of drugs, cosmetics, industrial chemicals, and environmental exposures relies mainly on in vitro genotoxicity testing followed by 2-year rodent bioassays. This testing battery is extremely sensitive but has low specificity. Furthermore, rodent bioassays are associated with high costs, high animal burden, and limited predictive value for human risks.
  
  
  OBJECTIVE
  We provide a response to a growing appeal for a paradigm change in human cancer risk assessment.
  
  
  METHODS
  To facilitate development of a road map for this needed paradigm change in carcinogenicity testing, a workshop titled "Genomics in Cancer Risk Assessment" brought together toxicologists from academia and industry and government regulators and risk assessors from the United States and the European Union. Participants discussed the state-of-the-art in developing alternative testing strategies for carcinogenicity, with emphasis on potential contributions from omics technologies.
  
  
  CONCLUSIONS
  The goal of human risk assessment is to decide whether a given exposure to an agent is acceptable to human health and to provide risk management measures based on evaluating and predicting the effects of exposures on human health. Although exciting progress is being made using genomics approaches, a new paradigm that uses these methods and human material when possible would provide mechanistic insights that may inform new predictive approaches (e.g., in vitro assays) and facilitate the development of genomics-derived biomarkers. Regulators appear to be willing to accept such approaches where use is clearly defined, evidence is strong, and approaches are qualified for regulatory use.
authors.affiliation: National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA. paules@niehs.nih.gov
authors.forename: Richard S
authors.initials: RS
authors.lastname: Paules
authors.forename: Jiri
authors.initials: J
authors.lastname: Aubrecht
authors.forename: Raffaella
authors.initials: R
authors.lastname: Corvi
authors.forename: Bernward
authors.initials: B
authors.lastname: Garthoff
authors.forename: Jos C
authors.initials: JC
authors.lastname: Kleinjans
mesh_terms: D015197:Carcinogenicity Tests / Q000379:methods* / Q000592:standards; D002273:Carcinogens / Q000633:toxicity*; D005062:European Union; D023281:Genomics / Q000379:methods; D006801:Humans; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology*; D018570:Risk Assessment / Q000379:methods* / Q000592:standards; D014481:United States
chemical_list: D002273:Carcinogens