The Lathyrus sativus neurotoxin: Resistance of the squirrel monkey to prolonged oral high doses

Abstract

Prolonged oral administration of the Lathyrus sativus neurotoxin, l-3-oxalylamino-2-aminopropionic acid (OAP), to three young male squirrel monkeys at dose rates of 0.6 to 6.0 mg/g body weight/day produced no neurologic signs and no adverse effects other than depressed activity and occasional foaming at the mouth. When the dose was increased to 8.0 to 8.5 mg/kg body weight/day in two animals, seizures and death occurred after 3 and 5 days. The signs were typical of acute OAP intoxication observed previously to occur in the squirrel monkey within an hour after a single ip dose (2 mg/g body weight) of OAP. Total cumulative dosage of OAP and duration of the experiments were as follows: Experiment 1, 9.5 g, 38 days; Experiment 2, 157 g, 178 days; Experiment 3, 64 g, 33 days. Histologic examination revealed no abnormalities in brain, spinal cord, or other organs. These experiments suggest that the adult squirrel monkey is highly resistant to chronic oral OAP intoxication. Under our experimental conditions, this species did not provide a satisfactory animal model for human neurolathyrism, a disease postulated to result from chronic OAP intoxication.