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Carcinogenic risk assessment with time-dependent exposure patterns.
Previous applications of carcinogenic risk assessment using mathematical models of carcinogenesis have focused largely on the case where the level of exposure remains constant over time. In many situations, however, the dose of the carcinogen varies with time. In this paper, we discuss both the classical Armitage-Doll multistage model and the Moolgavkar-Venzon-Knudson two-stage birth-death-mutation model with time-dependent dosing regimens. Bounds on the degree of underestimation of risk that can occur through the use of a simple time-weighted average dose are derived by means of comparison with an equivalent constant dose corresponding to the actual risk under the time-dependent dosing regimen.
Authors
- Murdoch, D J, Murdoch DJ, Health Protection Branch, Health and Welfare Canada, Ottawa, Ontario
- Krewski, D, Krewski D,
YEAR OF PUBLICATION: 1988
SOURCE: Risk Anal. 1988 Dec;8(4):521-30. doi: 10.1111/j.1539-6924.1988.tb01192.x.
JOURNAL TITLE ABBREVIATION: Risk Anal
JOURNAL TITLE: Risk analysis : an official publication of the Society for Risk Analysis
ISSN: 0272-4332 (Print) 0272-4332 (Linking)
VOLUME: 8
ISSUE: 4
PAGES: 521-30
PLACE OF PUBLICATION: United States
ABSTRACT:
Previous applications of carcinogenic risk assessment using mathematical models of carcinogenesis have focused largely on the case where the level of exposure remains constant over time. In many situations, however, the dose of the carcinogen varies with time. In this paper, we discuss both the classical Armitage-Doll multistage model and the Moolgavkar-Venzon-Knudson two-stage birth-death-mutation model with time-dependent dosing regimens. Bounds on the degree of underestimation of risk that can occur through the use of a simple time-weighted average dose are derived by means of comparison with an equivalent constant dose corresponding to the actual risk under the time-dependent dosing regimen.
Previous applications of carcinogenic risk assessment using mathematical models of carcinogenesis have focused largely on the case where the level of exposure remains constant over time. In many situations, however, the dose of the carcinogen varies with time. In this paper, we discuss both the classical Armitage-Doll multistage model and the Moolgavkar-Venzon-Knudson two-stage birth-death-mutation model with time-dependent dosing regimens. Bounds on the degree of underestimation of risk that can occur through the use of a simple time-weighted average dose are derived by means of comparison with an equivalent constant dose corresponding to the actual risk under the time-dependent dosing regimen.
LANGUAGE: eng
DATE OF PUBLICATION: 1988 Dec
DATE COMPLETED: 19890601
DATE REVISED: 20191022
MESH DATE: 1988/12/01 00:01
EDAT: 1988/12/01 00:00
STATUS: MEDLINE
PUBLICATION STATUS: ppublish
OWNER: NLM
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Chief Risk Scientist
Dr. Daniel Krewski is Chief Risk Scientist and co-founder of Risk Sciences International (RSI), a firm established in 2006 to bring evidence-based, multidisciplinary expertise to the challenge of understanding, managing, and communicating risk. As RSI’s inaugural CEO and long-time scientific...