International Development, Community, and Environment

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

Included in

Sociology Commons

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.