Pharmacokinetics of Halogenated Ethylenes
The present discussion of toxic effects of vinyl chloride raises the question of interpretation of toxicological data. Evidently, biochemical and mechanistic concepts of action of halogenated ethylenes can only be correlated with toxicities observed in vivo, if differences in pharmacokinetics are taken into account. This consideration led to the present investigation. Rats were exposed in a closed system to atmospheric concentrations of fluoroethylene (vinyl fluoride) 1,1-difluoroethylene (vinylidene fluoride), chloroethylene (vinyl chloride), 1,1-dichloroethylene (vinylidene chloride), trans- and cis-1,2-dichloroethylene, trichloroethylene, and bromoethylene (vinyl bromide). Pharmacokinetic analysis was done as previously described (Toxicology 7, 179, 1977). The following principles could be derived. (1) “Non-linear” (dose-dependent) pharmacokinetics may apply if the organism is exposed to higher concentrations of halogenated ethylenes. This is constsient with the concept of Watanabe, Young & Gehring (J.Env.Path.Tox. 1, 1977). In the case of vinyl chloride, it refers to atmospheric concentrations higher than 250 ppm. (2) The equilibrium constant of distribution of the non-metabolised compound (concentration in the animal/concentration in the gas phase) increases from vinyl fluoride to vinyl bromide. (3) The rate of metabolism depends on the structural properties of the individual compound. Trans-1,2-dichloroethylene and vinylidene fluoride are extremely slowly metabolised, comparable to the rate of metabolism of 1,1,1-trichloroethane (methyl chloroform) which was used as a reference compound.