A microscopic and ultrastructural evaluation of dibasic esters (DBE) toxicity in rat nasal explants.
Dibasic esters (DBE) solvent has been demonstrated to induce a mild degeneration of the olfactory, but not the respiratory epithelium of the rat nasal cavity following a 90-day inhalation exposure. Previous work has demonstrated that acid phosphatase release is a reliable index of DBE-induced cytotoxicity in an in vitro system of rat nasal explants. In the present study, rat nasal explants were examined microscopically and ultrastructurally following incubation in varying concentrations of a representative DBE, dimethyl adipate (DMA). DMA-induced microscopic and ultrastructural changes in rat nasal explants correlated well with biochemical perturbations associated with DBE exposure in a previous study. In both studies, olfactory epithelium was more susceptible to DMA-induced toxicity than respiratory epithelium and DMA-induced nasal toxicity was attenuated by pretreatment with a carboxylesterase inhibitor. The results of this study support the hypothesis that DBE and potentially other inhaled organic esters induce nasal toxicity via a common mechanism, carboxylesterase-mediated production of toxic acid metabolites. It was established that carboxylesterase-rich sustentacular cells are the primary target cells for DBE toxicity in rat nasal explants. It was proposed that degeneration of nasal olfactory sensory cells observed in rats following 90-day inhalation exposure to DBE may be secondary to necrosis and loss of sustentacular cells.
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E. I. du Pont de Nemours and Company, Haskell Laboratory for Toxicology and Industrial Medicine, Newark, Delaware 19714.
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D000135:Acid Phosphatase / Q000378:metabolism; D000272:Adipates / Q000633:toxicity; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D004952:Esters / Q000633:toxicity*; D005260:Female; D008854:Microscopy, Electron; D009296:Nasal Cavity / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure*; D051381:Rats; D013997:Time Factors
D000272:Adipates; D004952:Esters; C067354:dimethyladipate; D000135:Acid Phosphatase