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4213 
Book/Book Chapter 
Dose-route extrapolations in quantitative toxicology: Physiologically based pharmacokinetics and pharmacodynamics of chloroform 
Corley, RA; Reitz, RH 
1990 
Elsevier 
New York, NY 
Principles of route to route extrapolation for risk assessment : proceedings of the workshop held in South Carolina and North Carolina 
195-216 
English 
is a chapter of 4185786 Principles of route to route extrapolation for risk assessment : Proceedings of the workshop held in South Carolina and North Carolina
Prior chapters focused on the biology of the respiratory tract, gastrointestinal tract, and skin as each related to absorption of xenobiotics. Key parameters that were considered important for describing the uptake, disposition, and toxicity were addressed. The purpose of this paper is to apply some of the principles already discussed using a physiologically based pharmacokinetic (PB-PK)/ pharmacodynamic model developed for chloroform [1, 2]. This model was developed to provide a rational basis for risk assessment by incorporating available information on the disposition and mechanisms of action of chloroform as a function of dose, species, and route of administration.

A recent risk assessment for chloroform [3] was based on a National Cancer Institute bioassay where a high incidence of liver tumors was observed in B5C3F1 mice when chloroform was administered by gavage in corn oil [4]. The significance of this study for human cancer risk assessment is questionable, especially since a recent bioassay conducted in the same strain of mice by a more appropriate route of administration (drinking water) at daily dose levels of chloroform comparable to the National Cancer Institute study resulted in no liver tumors [SJ.

Since the results from a battery of mutagenicity tests with chloroform have been largely negative [6], Reitz et a/.[7] have proposed that chloroform induces tumors in laboratory animals without direct interaction of chloroform, or its reactive metabolites, with the genome. Rather, the carcinogenicity of chloroform appears to be correlated with recurrent cytotoxicity and compensatory cell regeneration, which results from the metabolic activation of chloroform. 
Gerrity, TR; Henry, CJ 
9780444015822 
Workshops on Principles of Route-to-Route Extrapolation for Risk Assessment 
Hilton Head, SC; Durham, NC 
March 19-21, 1990; July 10-11, 1990