Chronic toxicity of metrifonate.

From chronic toxicity studies with metrifonate (identical with trichlorfon) on different animal species, the following conclusion can be reached: 1. There is no conclusive evidence that trichlorfon has a carcinogenic effect. 2. There is no indication that trichlorfon has a significant cumulative toxic effect. 3. There is no confirmation that trichlorfon has a specific effect on liver, blood and haematopoietic organs. 4. The toxicological profile of trichlorfon in the chronic toxicity study consists, on the one hand, in a depression of cholinesterase activity whereby the different animal species differed in their sensitivity. In rats, cholinesterase activity was depressed in serum at dietary levels of 500 p.p.m. and above and also in erythrocytes at a dietary concentration of 1000 p.p.m. In dogs, cholinesterase activity was depressed in serum and erythrocytes at a dietary level of only 200 p.p.m. The Rhesus monkey seemingly is very sensitive because erythrocyte cholinesterase activity is possibly reduced at a daily dose of 0.2 mg/kg per os. On the other hand, induction of an inhibition of spermatogenesis in rats and dogs at a high dose level is discussed, an effect which seemingly is morphologically detectable but nonetheless seems not to affect function as animal experiments have demonstrated.