IPCS framework for analyzing the relevance of a cancer mode of action for humans

被引:360
作者
Boobis, Alan R.
Cohen, Samuel M.
Dellarco, Vicki
McGregor, Douglas
Meek, M. E.
Vickers, Carolyn
Willcocks, Deborah
Farland, William
机构
[1] WHO, Int Programme Chem Safety, CH-1211 Geneva 27, Switzerland
[2] Univ London Imperial Coll Sci Technol & Med, Div Med, Sect Expt Med & Toxicol, London, England
[3] Univ Nebraska, Med Ctr, Omaha, NE 68182 USA
[4] US EPA, Off Pesticide Programs, Washington, DC 20460 USA
[5] Hlth Canada, Safe Environm Programme, Existing Subst Div, Ottawa, ON K1A 0L2, Canada
[6] Natl Ind Chem Notificat & Assessment Scheme, Sydney, NSW, Australia
[7] US EPA, Off Res & Dev, Washington, DC 20460 USA
关键词
animal-human concordance; DNA-reactive; carcinogens; human relevance framework for cancer; key events; mode of action; risk assessment;
D O I
10.1080/10408440600977677
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
The use of structured frameworks can be invaluable in promoting harmonization in the assessment of chemical risk. IPCS has therefore updated and extended its mode of action (MOA) framework for cancer to address the issue of human relevance of a carcinogenic response observed in an experimental study. The first stage is to determine whether it is possible to establish an MOA. This comprises a series of key events along the causal pathway to cancer, identified using a weight-of-evidence approach based on the Bradford Hill criteria. The key events are then compared first qualitatively and then quantitatively between the experimental animals and humans. Finally, a clear statement of confidence, analysis, and implications is produced. The IPCS human relevance framework for cancer provides an analytical tool to enable the transparent evaluation of the data, identification of key data gaps, and structured presentation of information that would be of value in the further risk assessment of the compound, even if relevancy cannot be excluded. This might include data on the shape of the dose-response curve, identification of any thresholds and recognition of potentially susceptible subgroups, for example, the basis of genetic or life-stage differences.
引用
收藏
页码:781 / 792
页数:12
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