Chlorinated Paraffins: Effect of some Microsomal Enzyme Inducers and Inhibitors on the Degradation of 1‐14C‐Chlorododecanes to14CO2in Mice

The degradation of 1-14C-chlorododecanes to 14CO2 in C57BL mice was studied. 1-14C-Chlorododecane-injected mice were transferred to an all-glass metabolism cage and the exhaled air was monitored for 14CO2. Pretreatment with cytochrome P-450 inhibitors resulted in a marked decrease in the rate of 14CO2-formation, when measured as peak 14CO2-exhalation rate (PER): After piperonyl butoxide pretreatment the degradation rate of a high-chlorinated 14C-dodecane (PCDD II; 68% Cl w/w) to 14CO2 was 16% of control, and after metyrapone pretreatment 40%. It was also shown that piperonyl butoxide pretreatment decreased the rate of 14CO2-formation, and the amount of 14CO2 formed, in proportion to the chlorine content of four differently chlorinated dodecanes. The cytochrome P-450 inducer phenobarbital moderately (PER 152%) increased the rate of 14CO2-formation from PCDD II, whereas 3-methylcholanthrene and several technical grade chlorinated paraffins generally gave less or no inductive effects. Also the cumulative 14CO2-exhalation, measured during six hours (CE-6), was inhibited and induced after the above pretreatments. The results indicate a cytochrome P-450-dependent degradation of C12-chloroalkanes to 14CO2 in vivo. The degradation via cytochrome P-450 seems to be relatively more important for higher chlorinated alkanes.