EXPERIMENTAL STUDIES ON THE TOXICITY OF ORGANIC PHOSPHITES

Abstract

In spite of many efforts in studies on the toxicity of organic phosphates, which have been well known as agricultural insecticides, no attempts have been made to obtain an understanding of the effects which the organic phosphite might have on man and domestic animals. Organic phosphites are about to be used as antioxidants and stabilizers of resin or transparency promoters of alkyd resin paints. Investigations on the effects of organic phosphites upon living bodies should be made before their industrial use. For this reason we have attempted to make experimental studies of the toxicity of organic phosphites in vitro or in vivo. Organic phosphites we used were tridecyl-, phenyldidecyl-, diphenyldecyl-, and triphenyl-phos-phite. We have studied the peroral LD₅₀, the rate of organ weight, and the inhibitory action of cholinesterase activity in the red blood cells and the plasma, and still more, have attempted to elucidate whether the triphenyl phosphite has the same toxic effects as triphenyl phosphate. The results obtained were: 1. Peroral LD₅₀ in mice of tridecyl-, phenyldidecyl-, diphenyldecyl-, and triphenyl-phosphite were 13.9, 13.1, 16.0 and 3.1 grams per kilogram body weight respectively. According to the classification of Hodge et al., the former three compounds are harmless and the latter, triphenyl phosphite, is slightly toxic. 2. The rate of the organ weight to the body weight at the 8 th day following the single peroral administration in mice was higher in the heart, spleen, kidney and testis as compared respectively with those of normal mice. Lung weight of mice treated subcutaneously with triphenyl phosphite increased more than that of mice treated perorally. 3. Subcutaneous LD₅₀ in mice of triphenyl phosphite and triphenyl phosphate were 0.47 and 1.05 gram per kilogram body weight respectively. The toxicity expressed by LD₅₀ of triphenyl phosphite was approximately three times higher as compared with that of triphenyl phosphate. 4. When triphenyl phosphite was administered subcutaneously to rabbits in a dose of 30 mg/kg a day for consecutive 20 days, slight anemia appeared and inhibitions of the activity of cholinesterase of the blood cells and the plasma occured. 5. Triphebnyl phosphite or triphenyl phosphate showed an extreme inhibition of the cholinesterase activity in the blood plasma from 12 to 24 hours after the injection and recovered after 2 or 3 days, but no remarkable inhibitory action was found in the cholinesterase activity of the red blood cells in the case of single subcutaneous injections in rabbits. 6. When triphenyl pshophite or triphenyl phosphate were added to human blood cell suspension and plasma in vitro, the cholinesterase activity was more inhibited in the plasma than in the red blood cells.