Concordance between rats and mice in bioassays for carcinogenesis

被引:12
作者
Freedman, DA
Gold, LS
Lin, TH
机构
[1] UNIV CALIF BERKELEY, LAWRENCE BERKELEY LAB, DIV BIOCHEM & MOL BIOL, BERKELEY, CA 94720 USA
[2] UNIV CALIF BERKELEY, LAWRENCE BERKELEY LAB, DIV LIFE SCI, BERKELEY, CA 94720 USA
关键词
D O I
10.1006/rtph.1996.0046
中图分类号
DF [法律]; D9 [法律]; R [医药、卫生];
学科分类号
0301 ; 10 ;
摘要
According to current policy, chemicals are evaluated for possible cancer risk to humans at low dose by testing in bioassays in which high doses of the chemical are given to rodents. Thus, risk: is extrapolated from high dose in rodents to low dose in humans. The accuracy of these extrapolations is generally unverifiable because data on humans are limited However, it is feasible to examine the accuracy of extrapolations from mice to rats. If mice and rats are similar with respect to carcinogenesis, this provides some evidence in favor of interspecies extrapolations; conversely, if mice and rats are different, this casts doubt on the validity of extrapolations from mice to humans. One measure of interspecies agreement is concordance, the percentage of chemicals that are classified the same way as to carcinogenicity in mice and rats. Observed concordance in National Cancer Institute/National Toxicology Program bioassays is about 75%, which may seem on the low side because mice and rats are closely related species tested under the same experimental conditions. However, observed concordance could underestimate true concordance due to measurement error in the bioassays-a possibility demonstrated by Piegorsch ct al. (Risk Anal. 12, 115-121, 1992). Expanding on this work, we show that the bias in observed concordance can be either positive or negative: an observed concordance of 75% can arise if the true concordance is anything between 20 and 100%. In particular, observed concordance can seriously overestimate-true concordance. (C) 1996 Academic Press, Inc.
引用
收藏
页码:225 / 232
页数:8
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