Evaluating the human relevance of chemically induced animal tumors

被引:119
作者
Cohen, SM
Klaunig, J
Meek, E
Hill, RN
Pastoor, T
Lehman-McKeeman, L
Bucher, J
Longfellow, DG
Seed, J
Dellarco, V
Fenner-Crisp, P
Patton, D
机构
[1] Univ Nebraska, Med Ctr, Dept Pathol Microbiol, ILSI RSI Steering Comm, Omaha, NE 69198 USA
[2] Indiana Univ, Sch Med, Indianapolis, IN 46202 USA
[3] Hlth Canada, Ottawa, ON K1A 0L2, Canada
[4] US EPA, Washington, DC 20460 USA
[5] Syngenta Crop Protect, Greensboro, NC 27419 USA
[6] Bristol Myers Squibb Co, Princeton, NJ 08543 USA
[7] NIEHS, Res Triangle Pk, NC 27709 USA
[8] NCI, NIH, Bethesda, MD 20892 USA
[9] Int Life Sci Inst, Washington, DC 20005 USA
关键词
carcinogenic mode of action; human relevance of animal tumors; risk assessment; PPAR alpha agonists;
D O I
10.1093/toxsci/kfh073
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Defining the mode(s) of action by which chemicals induce tumors in laboratory animals has become a key to judgments about the relevance of such tumor data for human risk assessment. Frameworks for analyzing mode of action information appear in recent U.S. EPA and IPCS publications relating to cancer risk assessment. This FORUM paper emphasizes that mode of action analytical frameworks depend on both qualitative and quantitative evaluations of relevant data and information: (1) presenting key events in the animal mode of action, (2) developing a "concordance" table for side-by-side comparison of key events as defined in animal studies with comparable information from human systems, and (3) using data and information from mode of action analyses, as well as information on relative sensitivity and exposure, to make weight-of-evidence judgments about the relevance of animal tumors for human cancer assessments. The paper features a systematic analysis for using mode of action information from animal and human studies, based in part on case examples involving environmental chemicals and pharmaceuticals.
引用
收藏
页码:181 / 186
页数:6
相关论文
共 6 条
  • [1] The human relevance of information on carcinogenic modes of action: Overview
    Cohen, SM
    Meek, ME
    Klaunig, JE
    Patton, DE
    Fenner-Crisp, PA
    [J]. CRITICAL REVIEWS IN TOXICOLOGY, 2003, 33 (06) : 581 - 589
  • [2] ENVIRONMENT AND DISEASE - ASSOCIATION OR CAUSATION
    HILL, AB
    [J]. PROCEEDINGS OF THE ROYAL SOCIETY OF MEDICINE-LONDON, 1965, 58 (05): : 295 - +
  • [3] PPARα agonist-induced rodent tumors:: Modes of action and human relevance
    Klaunig, JE
    Babich, MA
    Baetcke, KP
    Cook, JC
    Corton, JC
    David, RM
    DeLuca, JG
    Lai, DY
    McKee, RH
    Peters, JM
    Roberts, RA
    Fenner-Crisp, PA
    [J]. CRITICAL REVIEWS IN TOXICOLOGY, 2003, 33 (06) : 655 - 780
  • [4] A framework for human relevance analysis of information on carcinogenic modes of action
    Meek, ME
    Bucher, JR
    Cohen, SM
    Dellarco, V
    Hill, RN
    Lehman-McKeeman, LD
    Longfellow, DG
    Pastoor, T
    Seed, J
    Patton, DE
    [J]. CRITICAL REVIEWS IN TOXICOLOGY, 2003, 33 (06) : 591 - 653
  • [5] IPCS conceptual framework for evaluating a mode of action for chemical carcinogenesis
    Sonich-Mullin, C
    Fielder, R
    Wiltse, J
    Baetcke, K
    Dempsey, J
    Fenner-Crisp, R
    Grant, D
    Hartley, M
    Knaap, A
    Kroese, D
    Mangelsdorf, I
    Meek, E
    Rice, JM
    Younes, M
    [J]. REGULATORY TOXICOLOGY AND PHARMACOLOGY, 2001, 34 (02) : 146 - 152
  • [6] *US EPA, 1999, GUID CARC RISK ASS R