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.