Pulmonary toxicity of trichloroethylene in mice. Covalent binding and morphological manifestations
Forkert, P.G.; Birch, D.W.
Drug Metabolism and Disposition the Biological Fate of Chemicals 17(1): 106-113
1989
ISSN/ISBN: 0090-9556 PMID: 2566461 Document Number: 346382
We examined the time course of trichloroethylene (TCE)-induced pulmonary injury and focused on morphological changes and covalent binding of [14C]TCE soon after administration of a single dose of TCE (2000 mg/kg) to CD-1 male mice. At 1 hr after chemical treatment, Clara cells of the bronchiolar epithelium exhibited necrotic changes involving the mitochondrial and endoplasmic reticulum. Diatation of the endoplasmic reticulum became more severe at 2 hr after TCE administration and, by 4 hr, distended cisternae coalesced to form small vacuoles within the cytoplasmic matrix of the Clara cell. The severity of cellular damage increased progressively between 8 and 12 hr and, by 24 hr, the majority of Clara cells within an airway were severely vacuolated. Covalent binding of [14C]TCE to lung macromolecules was evident at 1 hr, peaked at 4 hr, declined thereafter, and reached a plateau between 12 and 24 hr. Peak binding (142.6 .+-. 31.8 nmol/g of wet weight) represented approximately 205 of [14C]TCE distributed to the lung. Although the levels of binding in the liver were at all times greater than those in the lung, liver injury was relatively insignificant. The results demonstrate a positive correlation between the onset of Clara cell injury and the formation of reactive metabolites, as assessed by covalent binding of [14C]TCE.