Age-Related Differences in Susceptibility to Carcinogenesis. Ii Approaches for Application and Uncertainty Analyses for Individual Genetically Acting Carcinogens

By Hattis, Dale

Book Id: WPLBN0000070878
Format Type: PDF eBook
File Size: 0.2 MB
Reproduction Date: 2005

Title:	Age-Related Differences in Susceptibility to Carcinogenesis. Ii Approaches for Application and Uncertainty Analyses for Individual Genetically Acting Carcinogens
Author:	Hattis, Dale
Volume:
Language:	English
Subject:	Government publications, United Nations., United Nations. Office for Disarmament Affairs
Collections:	Government Library Collection, Disarmament Documents
Historic Publication Date:
Publisher:	United Nations- Office for Disarmament Affairs (Unoda)


Citation APA MLA Chicago Hattis, D. (n.d.). Age-Related Differences in Susceptibility to Carcinogenesis. Ii Approaches for Application and Uncertainty Analyses for Individual Genetically Acting Carcinogens. Retrieved from http://gutenberg.cc/

Description
Government Reference Publication

Excerpt
Excerpt: In an earlier report we developed a quantitative likelihood-based analysis of the differences in sensitivity of rodents to mutagenic carcinogens across three life stages (fetal, birth to weaning, and weaning to 60 days) relative to exposures in adult life. Here we draw implications for assessing human risks for full lifetime exposures, taking into account three types of uncertainties in making projections from the rodent data: uncertainty in the central estimates of the life-stage?specific sensitivity factors estimated earlier, uncertainty from chemical-to-chemical differences in lifestage? specific sensitivities for carcinogenesis, and uncertainty in the mapping of rodent life stages to human ages/exposure periods. Among the uncertainties analyzed, the mapping of rodent life stages to human ages/exposure periods is most important quantitatively (a range of several-fold in estimates of the duration of the human equivalent of the highest sensitivity ?birth to weaning? period in rodents). The combined effects of these uncertainties are estimated with Monte Carlo analyses. Overall, the estimated population arithmetic mean risk from lifetime exposures at a constant milligrams per kilogram body weight level to a generic mutagenic carcinogen is about 2.8-fold larger than expected from adult-only exposure with 5?95% confidence limits of 1.5- to 6-fold. The mean estimates for the 0- to 2-year and 2- to 15-year periods are about 35?55% larger than the 10- and 3-fold sensitivity factor adjustments recently proposed by the U.S. Environmental Protection Agency. The present results are based on data for only nine chemicals, including five mutagens. Risk inferences will be altered as data become available for other chemicals. Key words: carcinogenesis, fetal, mutagenic chemicals, risk assessment, susceptibility, uncertainties.