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Biological Basis for Interspecies Extrapolations of Halogenated Solvents and of 1,3-Butadiene

  • Hermann M. Bolt
  • Reinhold J. Laib

Abstract

It is well established that species differences in toxicity and carcinogenicity of xenobiotics are often based on species-specific metabolism. Hence, the use of pharmacokinetic models considering relevant metabolic routes may considerably improve risk assessment procedures (Bolt, 1987; Travis, 1987). The biological basis for an appropriate interspecies extrapolation is knowledge of the biochemical mode of action and of the toxicologically relevant metabolic pathways. This will be exemplified by a discussion of major halogenated industrial solvents and of 1,3-butadiene. Long-term animal bioassays with these compounds have demonstrated considerable differences between the two most widely used animal species, mice and rats. This review will not consider 1,1,1trichloroethane. This solvent is metabolized in man and in experimental animals to a very low extent only (up to 5–10% of the inhaled dose), and no positive carcinogenicity data have hitherto been obtained. However, the closely related compounds 1,1,2-trichloroethane and 1,1,2,2-tetrachloroethane which are extensively metabolized have produced liver tumors in mice (Baseman et al., 1984).

Keywords

Covalent Binding Inhalation Exposure Chloroacetic Acid Dichloroacetic Acid Decline Curve 
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Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Hermann M. Bolt
    • 1
  • Reinhold J. Laib
    • 1
  1. 1.Institut für ArbeitsphysiologieUniversität DortmundDortmund 1Germany

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