ACUTE TOXICOLOGICAL STUDIES ON PARAQUAT - PATHOLOGICAL FINDINGS IN BEAGLE DOGS FOLLOWING SINGLE SUBCUTANEOUS INJECTIONS

Sixteen beagles were allocated into 4 groups, each group consisting of 2 males and 2 females, which were injected sc with 1,3,5, or 7 mg par aquat/kg. The beagles were observed for 2 w after the administration. At the end of the observation period all the dying and surviving dogs were studied pathologically. The LD50 was calculated as 1.8 (1.0-6.1) in males and 3.5 (2.4-10.1) mg/kg in females. Clinical laboratory test s showed increases in segmented neutrophils and monocytes, decreases i n lymphocytes, slight decreases in chloride, moderate increases in BUN , GOT, GPT and phospholipids, slight increases in uric acid, total pro tein, creatine, total cholesterol and total bilirubin, and prolonged p rothrombin times. Marked edema, congestion and hemorrhage of lungs, as well as slight congestion in various organs, were observed grossly. I n histopathological examination, marked pulmonary hemorrhage and conge stion, fibroblast-like cells in alveolar septa, breakdown of alveolar walls, thickening of alveolar walls and pleura, mild congestion and de generation of the liver, and mild degeneration of renal tubules were o bserved. The cause of death was respiratory distress and renal failure . The surviving animals had mild atelectasis of the lungs. Electromicr oscopic examination on the surviving animals revealed the appearance o f spindle-shaped cells, proliferation of type II alveolar cells and fi broblasts, mitosis of fibroblasts, and abundant collagen fiber in the lung, calcium deposition, stratification and thickening of basement me mbranes, and localized necrotic epithelial cells in the proximal tubul es of kidneys, and stratification of intramitochondrial cristae of the liver. Pulmonary fibrosis in the switchover stage was present with pa rticipation from type II alveolar cells, fibroblasts and myofibroblast s.