Recent developments in carcinogenic risk assessment.
In this paper, recent developments in the quantitative assessment of carcinogenic risks based on toxicological and epidemiological data are reviewed. In particular, model-free approaches to low-dose risk assessment which involve only the assumption of low-dose linearity are considered. Measures of carcinogenic potency which avoid the need to extrapolate to low doses are also described. The allometric bases for converting risk estimates between species are then discussed. Pharmacokinetic models for determining the dose delivered to the target tissue are examined, and the implications of using such models in extrapolating between doses, of exposure, and species are examined. The application of these concepts in chemical and radiation carcinogenesis is illustrated by means of brief case studies of methylene chloride and Rn. Biologically motivated cancer models based on the initiation-promotion-progression theory of carcinogenesis are discussed and compared with the classical multistage model. The estimation of risks with time-dependent exposure patterns is considered, and conditions under which the use of a time-weighted average dose is appropriate are identified. Finally, the estimation of carcinogenic risks posed by exposure to complex mixtures is explored.
Krewski
D
D
Health Protection Branch, Health & Welfare Canada, Ottawa, Ontario.
Murdoch
D
D
Withey
J R
JR
D000818:Animals; D006801:Humans; D008752:Methylene Chloride; D008954:Models, Biological; D009369:Neoplasms / Q000139:chemically induced*; D009374:Neoplasms, Experimental / Q000139:chemically induced; D009381:Neoplasms, Radiation-Induced; D011886:Radon; D012306:Risk
D008752:Methylene Chloride; D011886:Radon