Sustainability and Social Justice
Document Type
Article
Abstract
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 life-stage-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.
Publication Title
Environmental Health Perspectives
Publication Date
4-1-2005
Volume
113
Issue
4
First Page
509
Last Page
516
ISSN
0091-6765
DOI
10.1289/ehp.7564
Keywords
carcinogenesis, fetal, mutagenic chemicals, risk assessment, susceptibility, uncertainties
Repository Citation
Hattis, Dale; Goble, Robert; and Chu, Margaret, "Age-Related Differences in Susceptibility to Carcinogenesis. II. Approaches for Application and uncertainty Analyses for Individual Genetically Acting Carcinogens" (2005). Sustainability and Social Justice. 175.
https://commons.clarku.edu/faculty_idce/175
Copyright Conditions
Published source must be acknowledged with citation. Hattis, Dale, Robert Goble, and Margaret Chu. "Age-related differences in susceptibility to carcinogenesis. II. Approaches for application and uncertainty analyses for individual genetically acting carcinogens." Environmental health perspectives 113.4 (2005): 509-516 Reproduced with permission from Environmental Health Perspectives.
