title: Incorporation of in vitro enzyme data into the physiologically-based pharmacokinetic (PB-PK) model for methylene chloride: implications for risk assessment.
abstract: Physiologically-based pharmacokinetic (PB-PK) models provide a mechanism for reducing the uncertainty inherent in extrapolating the results of animal toxicity tests to man. This paper discusses a technique for incorporating data from in vitro studies of xenobiotic metabolism into in vivo PB-PK models. Methylene chloride is used as an example, and carcinogenic risk estimates incorporating PB-PK principles are presented.
authors.affiliation: Dow Chemical Company, Health and Environmental Sciences, Midland, MI 48674.
authors.forename: R H
authors.initials: RH
authors.lastname: Reitz
authors.forename: A L
authors.initials: AL
authors.lastname: Mendrala
authors.forename: C N
authors.initials: CN
authors.lastname: Park
authors.forename: M E
authors.initials: ME
authors.lastname: Andersen
authors.forename: F P
authors.initials: FP
authors.lastname: Guengerich
mesh_terms: D000818:Animals; D006224:Cricetinae; D003600:Cytosol / Q000201:enzymology; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008752:Methylene Chloride / Q000493:pharmacokinetics / Q000633:toxicity*; D051379:Mice; D008861:Microsomes / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D008954:Models, Biological; D009374:Neoplasms, Experimental / Q000139:chemically induced; D051381:Rats; D012307:Risk Factors; D015262:Xenobiotics / Q000633:toxicity
chemical_list: D006843:Hydrocarbons, Chlorinated; D015262:Xenobiotics; D008752:Methylene Chloride; D006899:Mixed Function Oxygenases; D005982:Glutathione Transferase