Studies on the distribution and covalent binding of 1,1-dichloroethylene in the mouse. Effect of various pretreatments on covalent binding in vivo.
The distribution and covalent binding of a single dose of [1,2-14C] 1,1-dichloroethylene (DCE; 125 mg/kg, i.p.) was studied in male C57Bl/6N mice. Total radioactivity was distributed in whole homogenates of all tissues studied, with peak levels occurring within 6 hr. Covalent binding of radioactive material peaked at 6-12 hr in all tissues, and highest levels were found in kidney, liver, and lung with smaller amounts in skeletal muscle, heart, spleen, and gut. Covalent binding in kidney, liver, and lung fell to 50% of peak levels in about 4 days. Between 12 hr and 4 days after DCE administration, 70-100% of total radioactivity present in homogenates of kidney, liver, and lung was covalently bound. The three tissues showed a similar spread in total radioactivity in subcellular fractions 24 hr after exposure to DCE; most of the radioactivity was covalently bound (60-100%) and distributed fairly uniformly with a slight tendency to concentrate in the mitochondrial fraction. Phenobarbital (PB) and 3-methylcholanthrene (3-MC) pretreatments increased the covalent binding in the liver and lung but had no effect in the kidney. Piperonyl butoxide and SKF-525A decreased the covalent binding in liver and lung, but the latter increased binding in the kidney while the former decreased it. Diethylmaleate administration increased the covalent binding (2- to 3-fold) in all three tissues as well as increasing lethal toxicity. These results are consistent with the view that DCE is metabolized to some reactive intermediate(s) which may be detoxified by conjugation with glutathione.
D000818:Animals; D002250:Carbon Radioisotopes; D004000:Dichloroethylenes / Q000378:metabolism* / Q000633:toxicity; D004790:Enzyme Induction; D005978:Glutathione / Q000502:physiology; D006843:Hydrocarbons, Chlorinated / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010634:Phenobarbital / Q000494:pharmacology; D011335:Proadifen / Q000494:pharmacology; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D004000:Dichloroethylenes; D006843:Hydrocarbons, Chlorinated; C029297:vinylidene chloride; D011335:Proadifen; D005978:Glutathione; D010634:Phenobarbital