Incorporation of in vitro enzyme data into the physiologically-based pharmacokinetic (PB-PK) model for methylene chloride: implications for risk assessment

R H Reitz; A L Mendrala; C N Park; M E Andersen; F P Guengerich

doi:10.1016/0378-4274(88)90023-9

Incorporation of in vitro enzyme data into the physiologically-based pharmacokinetic (PB-PK) model for methylene chloride: implications for risk assessment

Toxicol Lett. 1988 Oct;43(1-3):97-116. doi: 10.1016/0378-4274(88)90023-9.

Authors

R H Reitz¹, A L Mendrala, C N Park, M E Andersen, F P Guengerich

Affiliation

¹ Dow Chemical Company, Health and Environmental Sciences, Midland, MI 48674.

PMID: 3176073
DOI: 10.1016/0378-4274(88)90023-9

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.

MeSH terms

Animals
Cricetinae
Cytosol / enzymology
Glutathione Transferase / metabolism
Humans
Hydrocarbons, Chlorinated / toxicity*
In Vitro Techniques
Liver / enzymology
Lung / enzymology
Methylene Chloride / pharmacokinetics
Methylene Chloride / toxicity*
Mice
Microsomes / enzymology
Mixed Function Oxygenases / metabolism
Models, Biological*
Neoplasms, Experimental / chemically induced
Rats
Risk Factors
Xenobiotics / toxicity

Substances

Hydrocarbons, Chlorinated
Xenobiotics
Methylene Chloride
Mixed Function Oxygenases
Glutathione Transferase