Clinical Signs Of Intoxication Research Articles

A comparative study of paraquat intoxication in rats, guinea pigs and monkeys

The purpose of this study was to characterize and compare the toxicity, clinical syndrome, and pathology of paraquat in rats, guinea pigs, and monkeys. The LD 50 of oral paraquat was 126, 22, and 50 mg/kg in the three species, respectively. Clinical signs of intoxication were anorexia, adipsia, diarrhea, hyperpnea, dyspnea, and tachycardia. All animals were hypoxic. Monkeys which received greater than 63 mg/kg of paraquat died within 1–2 days. Death was preceded by convulsive seizures. Monkeys that received paraquat dosages of 50–53 mg/kg showed signs of dyspnea prior to death while those monkeys given 30–40 mg/kg paraquat showed signs of dyspnea for 1–5 days and subsequently developed pulmonary fibrosis. Focal necrosis was noted in liver, kidney, and the gastrointestinal tract but the primary lesion occurred in the lungs of all species. Animals that died in less than 7 days showed pulmonary hemorrhage, edema, and congestion. Rats and monkeys but not guinea pigs developed interstitial fibrosis of the lung after 7–10 days. Monkeys did not have liver and kidney dysfunction. It was concluded that the paraquat-induced pulmonary fibrosis in humans could be duplicated in monkeys and rats.

Maximal tolerated daily doses of dicophane.

Dicophane was given by intragastric cannula to young male albino rats in daily doses of from 43 to 250 mg/kg for 100 days or until 90 % of the animals had died. The LDO (100 days) or maximal dose which killed no animals when given daily for 100 days was 42.8 ± 1.6 mg/kg/day, the LD50 (100 days) was 64.8 ± 1.4 mg/kg/day and the minimal LD100 (100 days) was 97.1 ± 2.8 mg/kg/day. The 100‐day LD50 index, or the LD50 (100 days) expressed as a percentage of the acute, oral LD50 (1 dose) was 17.6 ± 0.4. During the first 21 days of administration, the clinical signs of intoxication were similar to those recorded in studies on acute toxicity with single lethal doses. Clinical signs in 21 day‐survivors were limited to polydipsia, diuresis, aciduria, and some loss of body weight. Autopsy at 100 days revealed degenerative changes in the kidneys, liver and testes, a stress reaction, hypertrophy of the liver and gastrointestinal organs, and capillary congestion and loss of weight (with variable changes in water content) of many body organs. The 100‐day multiposal (subacute, chronic) toxicity of dicophane was similar to that of non‐narcotic analgesics such as aspirin, phenacetin and paracetamol.

Acute oral toxicity of cottonseed oil

Cottonseed oil given intragastrically to young, male albino rats in amounts over 70–80 ml/kg in one dose was immediately evacuated through the anus. When the total dose was divided into 4 equal parts, each part given daily for 4 days to segregated animals, deaths occurred on days 3 and 4. The LD50 (4 doses) ± SE of cottonseed oil so given was found to be 275 ± 22 ml/kg, the maximal LD0 was estimated at 203 and the minimal LD100 at 347 ml/kg. The clinical signs of intoxication were pallor, listlessness, diarrhea, cyanosis, epistaxis, ataxia, dyspnea, anorexia, loss of body weight, hypothermia, oligodypsia, oliguria and aciduria. At autopsy there was found a fulminating congestion of the brain associated with generalized capillary-venous congestion, lysis of the red blood cells, capillary hemorrhage, dehydration, loss of organ dry weight, and widespread deposits of oil droplets in tissues. The syndrome was accompanied by a stress reaction, large cell-infiltrated ulcers in the cardiac stomach, and degenerative changes in the renal tubules, skeletal muscle, and salivary glands.

Lindane toxicity and protein-deficient diet.

The median lethal dose (LD50) ± SE of gamma benzene hexachloride (lindane) given orally to young, male, albino rats was 157 ± 37 mg/kg. The clinical signs of intoxication were anorexia, diarrhea, sialorrhea, occasionally dacryorrhea, epistaxis, oligodipsia, hypothermia, loss of body weight, diuresis, proteinuria, and aciduria. Death occurred at from one to 25 hours from respiratory failure, usually following convulsions. At autopsy on animals which died early, the main histopathological finding was capillary-venous congestion of the brain, meninges, and many other organs. When death was delayed, degenerative changes appeared in the gastrointestinal tract, kidneys, liver, striated muscle, testes, and thymus gland. Many organs had lost weight sometimes due to loss of water. Cachectic rats whose growth had been stunted by the feeding of a low protein (casein) diet from the time of weaning were found to be twice as susceptible to the toxic effects of lindane. The results suggest the possibility that lindane should be used as an insecticide with caution in countries where the diet is deficient in protein.

The acute oral toxicity of phenacetin

Phenacetin given orally in doses of 1 and 2 g per kilogram body weight produced vomiting in cats and dogs. Further toxicity studies were confined to albino rats in which the oral LD 50 ± S.E. was found to be 1.65 ± 0.35 g per kilogram body weight. Clinical signs of intoxication were lethargy, hyporeflexia, ataxia, exophthalmos, dacryorrhea, sialorrhea, bradycardia, hypopnea, hypothermia, anorexia, adipsia, oliguria or anuria, and death due to respiratory failure in marked hypothermia at 22.8 ± 17.7 (mean ± S.D.) hours. Survivors had diarrhea and dark-colored urine. At autopsy there were found a fulminating gastroenteritis, hepatitis, pancreatitis, nephritis, pulmonary edema, capillary and venous congestion of the mesentery, heart, thymus gland, ovaries, lymph nodes, and spleen, and evidence of minor toxic changes in cardiac muscle, skeletal muscle, and the adrenal glands.