Variability of safe dose estimates when using complicated models of the carcinogenic process. A case study: methylene chloride.
Advances in understanding carcinogenesis have led to the development of mathematical models that have biologically interpretable parameters. These models utilize more of the available scientific data than the empirical models routinely employed for quantifying carcinogenic risk. They also require consideration of sources of uncertainty in risk estimates that were previously ignored, such as animal-to-animal variability of physiological and pharmacological constants. A numerical technique is proposed for studying the consequences of incorporating the intrapopulation variability of biologically interpretable parameters into the risk assessment process. To demonstrate the technique, the variability of safe dose estimates for exposure to methylene chloride is considered. The results suggest that intrapopulation variability of the model parameters can increase the variability of safe dose estimates an appreciable amount.
Portier
C J
CJ
Statistics and Biomathematics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Kaplan
N L
NL
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D002273:Carcinogens; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D007700:Kinetics; D008297:Male; D008752:Methylene Chloride / Q000633:toxicity*; D051379:Mice; D008815:Mice, Inbred Strains; D008954:Models, Biological; D009010:Monte Carlo Method; D014481:United States; D014484:United States Environmental Protection Agency
D002273:Carcinogens; D006843:Hydrocarbons, Chlorinated; D008752:Methylene Chloride