Biologically motivated models for chemical risk assessment.
Assessing the risk associated with human exposure to environmental chemicals depends to a large extent on the ability to extrapolate from a particular range of exposure conditions in the test animal species to a very different range of exposure conditions in the human. One of the more promising tools for accomplishing this extrapolation is the biologically motivated pharmacokinetic/pharmacodynamic model. In a biologically motivated model, the structure is based on the physiological and biochemical structure of the animal system being described. This paper provides an overview of the biologically motivated modeling approach. Examples of models for styrene and methylene chloride are discussed in relation to their ability to predict human kinetics for these chemicals and their use in estimating the risk of chemicals to exposed humans. Finally, the use of a biologically motivated model to analyze the mechanistic basis of chemical carcinogenesis is discussed.
Clewell
H J
HJ
Toxic Hazards Division, Harry G. Armstrong Aerospace, Medical Research Laboratory (AAMRL/TH), Wright-Patterson Air Force Base, OH 45433-6573.
Andersen
M E
ME
D000818:Animals; D004785:Environmental Pollutants / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000633:toxicity; D005260:Female; D006801:Humans; D008297:Male; D008752:Methylene Chloride / Q000009:adverse effects / Q000493:pharmacokinetics / Q000633:toxicity; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000139:chemically induced; D009374:Neoplasms, Experimental / Q000139:chemically induced; D051381:Rats; D012306:Risk; D020058:Styrene; D013343:Styrenes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000633:toxicity
D004785:Environmental Pollutants; D013343:Styrenes; D020058:Styrene; D008752:Methylene Chloride