Pulmonary toxicity of 1,1-dichloroethylene: correlation of early changes with covalent binding.

Abstract

Administration of a single intraperitoneal dose of 1,1-dichloroethylene (125 mg/kg, 1,1-DCE) to mice resulted in bronchiolar injury with selective necrosis of Clara cells. Degenerative changes were manifest in Clara cells as early as 1 h following 1,1-DCE exposure, and were characterized by marked swelling of mitochondria and aggregation of chromatin against the nuclear membrane. Cell death was apparent at 2 h; by 8 h, areas of the bronchiolar epithelium were devoid of lining cells, and at 24 h, the majority of Clara cells were exfoliated. The residual epithelium consisted of flattened cells which formed a thin lining for the airway. Necrosis of Clara cells early in the course of 1,1-DCE exposure coincided with peak covalent binding of [14C]1,1-DCE and significant depression of components of the pulmonary mixed-function oxidase system; cytochrome P-450 and aryl hydrocarbon hydroxylase activity were markedly reduced but not depleted. Liver damage involving centrilobular hepatocytes was observed at 24 h in 30% of treated animals, and coincided with significant inhibition of aryl hydrocarbon hydroxylase activity; cytochrome P-450 content, however, remained unchanged. While changes in the liver evoked by 1,1-DCE were less striking, the results in lung demonstrate positive temporal correlations between structural damage, peak covalent binding and disturbances of monooxygenase enzymes.

• Authors: P G Forkert, V Stringer, K M Troughton
• Journal: Canadian journal of physiology and pharmacology (Can J Physiol Pharmacol) Vol. 64 Issue 2 Pg. 112-21 (Feb 1986) ISSN: 0008-4212 [Print] Canada
• PMID: 3697828 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carbon Radioisotopes
• Dichloroethylenes
• Hydrocarbons, Chlorinated
• Cytochrome P-450 Enzyme System
• Aryl Hydrocarbon Hydroxylases
• 1,2-dichloroethylene

Topics

• Animals
• Aryl Hydrocarbon Hydroxylases (metabolism)
• Carbon Radioisotopes
• Cytochrome P-450 Enzyme System (metabolism)
• Dichloroethylenes (metabolism, toxicity)
• Epithelium (ultrastructure)
• Hydrocarbons, Chlorinated (toxicity)
• Liver (drug effects, pathology)
• Lung (drug effects, metabolism, pathology)
• Male
• Mice
• Microscopy, Electron
• Microsomes (metabolism)
• Microsomes, Liver (metabolism)
• Tissue Distribution