Acute toxicological studies on paraquat: pathological findings in beagle dogs following single subcutaneous injections
Nagata, T.; Kono, I.; Masaoka, T.; Akahori, F.
Veterinary and Human Toxicology 34(2): 105-112
1992
ISSN/ISBN: 0145-6296 PMID: 1509667 Document Number: 394111
Groups of 4 Beagles, each of 2 males and 2 females, were injected s.c. with 1, 3, 5 or 7 mg paraquat/kg. The dogs were observed for 2 weeks after dosing when all the dying and surviving dogs were examined pathologically. The LD was calculated as 1.8 (1.0-6.1) in males and 3.5 (2.4-10.1) mg/kg in females. Clinical tests showed increases in segmented neutrophils and monocytes, decreases in lymphocytes, slight decreases in chloride, moderate increases in BUN, transaminases and phospholipids, slight increases in uric acid, total protein, creatine, total cholesterol and total bilirubin, and prolonged prothrombin times. Marked oedema, congestion and haemorrhage of lungs, as well as slight congestion in various organs, were observed grossly. In histopathological examination, marked pulmonary haemorrhage and congestion, fibroblast-like cells in alveolar septa, breakdown of alveolar walls, thickening of alveolar walls and pleura, mild congestion and degeneration of the liver, and mild degeneration of renal tubules were observed. The cause of death was respiratory distress and renal failure. The surviving animals had mild atelectasis of the lungs. Electronmicroscopic examination of the surviving animals showed the appearance of spindle-shaped cells, proliferation of type II alveolar cells and fibroblasts, mitosis of fibroblasts, and abundant collagen fibre in the lung, calcium deposition, stratification and thickening of basement membranes, and localized necrotic epithelial cells in the proximal tubules of kidneys, and stratification of intramitochondrial cristae of the liver. Pulmonary fibrosis in the switchover stage was present with participation from type II alveolar cells, fibroblasts and myofibroblasts.