The toxicity of Escherichia coli L-asparaginase.

Abstract

Summary l-Asparaginase-containing extracts from Escherichia coli have undergone toxicologic evaluation in mice, guinea pigs, rabbits, beagle dogs, and Rhesus monkeys. The preparation elicited acute anaphylaxis in sensitized guinea pigs and produced precipitating antibodies in one of six rabbits. In five of nine batches, temperature elevations of one degree Fahrenheit or more, associated with leukocytosis, were observed in the monkey. With continued treatment the monkey demonstrated varying degrees of weight loss, colitis, leukopenia, and abnormal liver function and histology, which could not be directly correlated with dose or specific activity of the enzyme preparation. The dog was resistant to all toxic effects other than a reversible anemia. Measurement of plasma enzyme concentration after dosing revealed that the monkey maintained significantly higher peak levels than the dog one hour after injection. Both the monkey and dog maintained high plasma activity for the eight hours after the first injection of a twice-daily schedule, and in the monkey the enzyme remained at detectable levels for at least 18 hours. The role that contaminating bacterial endotoxin may be contributing to the overall toxicity is discussed.