Incorporation of in vitro enzyme data into the physiologically-based pharmacokinetic (PB-PK) model for methylene chloride: implications for risk assessment.
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.
Reitz
R H
RH
Dow Chemical Company, Health and Environmental Sciences, Midland, MI 48674.
Mendrala
A L
AL
Park
C N
CN
Andersen
M E
ME
Guengerich
F P
FP
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
D006843:Hydrocarbons, Chlorinated; D015262:Xenobiotics; D008752:Methylene Chloride; D006899:Mixed Function Oxygenases; D005982:Glutathione Transferase