Microsomal dechlorination of chloroethanes: structure-reactivity relationships

1. The dechlorination rates of six haloethanes were investigated in vitro, using liver microsomes derived from rats treated with Aroclor 1254. 2. The compounds studied were 1,1-dichloroethane, 1,2-dichloroethane, 1,1,1-trichloroethane, 1,1,2,2-tetrachloroethane, 1,1,1-trifluoro-2-chloroethane and hexachloroethane. 3. Dechlorination kinetics (Km and Vmax) were measured at various substrate concentrations. 4. Electron densities in the molecules for which dechlorination data are available were calculated by the MINDO/3 method. 5. A previously reported correlation between electronic parameters and dechlorination rate was not confirmed, but rather a separate relationship between these parameters for each of three structural classes (RCH2Cl, RCHCl2 and RCCl3) was observed. 6. On the basis of these observations, possible reaction mechanisms and their toxicological implications are discussed.