Long-term morphologic and biochemical changes induced by O,O,S-trimethyl phosphorothioate in the rat lung

The long-term pulmonary morphologic and biochemical changes induced by a single, sublethal dose of O,O,S-trimethyl phosphorothioate (OOS-TMP), an impurity present in organophosphorus insecticides, was examined in female WAG/Rij rats. Animals received either corn oil or a corn oil solution of OOS-TMP at a dose of 40 mg/kg body weight by gavage and were studied at the following time intervals after treatment: 10 days, 30 days, 90 days, 6 months, and 1 year. No control or OOS-TMP-treated animal died spontaneously. Significant increases in wet and dry lung weights occurred at all times examined in OOS-TMP-treated rats compared to those in age-matched controls. No difference was observed in percentage lung water content between treated and control rats. OOS-TMP treatment resulted in hypertrophy and hyperplasia of type II alveolar epithelial cells having morphologic alterations in the size and number of osmiophilic lamellar bodies. Interstitial changes were characterized as increased numbers of fibroblasts accompanied by increased amounts of collagen fibrils and basement membrane alterations. There was also a significant increase in pulmonary hydroxyproline content in OOS-TMP-treated animals compared to that in controls at all time periods. Collagen deposition was predominantly associated with the interalveolar septa rather than being oriented around airways. The results of this study indicate that a single, sublethal dose of OOS-TMP induces long-term structural and biochemical changes in the rat lung.