The Human Relevance of Information on Carcinogenic Modes of Action: Overview

Samuel Monroe Cohen, M. E. Meek, James E. Klaunig, Dorothy E. Patton, Penelope A. Fenner-Crisp

Research output: Contribution to journalReview article

74 Citations (Scopus)

Abstract

Risk assessment policies and practice place increasing reliance on mode of action (MOA) data to inform conclusions about the human relevance of animal tumors. In June 2001, the Risk Science Institute of the International Life Sciences Institute formed a workgroup to study this issue. The workgroup divided into two subgroups, one developing and testing a "framework" for MOA relevance analysis and the other conducting an in-depth analysis of peroxisome proliferation-activated receptor (PPAR)α activation as the MOA for some animal carcinogens. This special issue of Critical Reviews in Toxicology presents the scientific reports emerging from this activity. These reports serve several purposes. For risk assessors in and out of government, they offer a new human relevance framework (HRF) that complements and extends existing guidance from other organizations. Regarding the specific MOA for peroxisome proliferating chemicals, these reports offer a state-of-the-science review of this important MOA and its role in tumorigenesis in three different tissues (liver, testis, and pancreas). The case studies in these reports present models for using MOA information to evaluate the hazard potential for humans. The cases also illustrate the substantial impact of a complete human relevance analysis, as distinct from an animal MOA analysis alone, on the nature and scope of risk assessment.

Original languageEnglish (US)
Pages (from-to)581-589
Number of pages9
JournalCritical reviews in toxicology
Volume33
Issue number6
DOIs
StatePublished - Jan 1 2003

Fingerprint

Animals
Risk assessment
Peroxisomes
Carcinogens
Liver
Biological Science Disciplines
Tumors
Hazards
Chemical activation
Toxicology
Tissue
Testis
Pancreas
Carcinogenesis
Testing
Organizations
Neoplasms

Keywords

  • Carcinogenic mode of action
  • Human relevance of animal tumors
  • PPARα agonists
  • Peroxisome proliferation
  • Risk assessment

ASJC Scopus subject areas

  • Toxicology

Cite this

The Human Relevance of Information on Carcinogenic Modes of Action : Overview. / Cohen, Samuel Monroe; Meek, M. E.; Klaunig, James E.; Patton, Dorothy E.; Fenner-Crisp, Penelope A.

In: Critical reviews in toxicology, Vol. 33, No. 6, 01.01.2003, p. 581-589.

Research output: Contribution to journalReview article

Cohen, Samuel Monroe ; Meek, M. E. ; Klaunig, James E. ; Patton, Dorothy E. ; Fenner-Crisp, Penelope A. / The Human Relevance of Information on Carcinogenic Modes of Action : Overview. In: Critical reviews in toxicology. 2003 ; Vol. 33, No. 6. pp. 581-589.
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