A study on the acute toxicity of the tri-aryl phosphates used as plasticizers.

Paralysis in man and the domestic fowl caused by “TCP” (tri-cresyl phosphate, tri-tolyl phosphate or TTP) is reviewed, and the search for a non-toxic plasticizer derived either from TTP or tri-xylenyl phosphate (tri-dimethylphenyl phosphate or TXP) is described. It had been previously shown that the -tolyl esters are toxic but we found that their removal does not make the mixture non-toxic. The - and -tolyl esters were known to be free from toxic effects and the 2: 4 and 2: 5 dimethylphenyl esters were equally shown to be non-toxic except in massive doses. We confirmed that the tri--ethylphenyl ester was non-toxic, but found the mono- and di--ethylphenyl phosphates to be highly toxic. We showed that TTP made from phenols with all the -cresol and -ethylphenol removed is non-toxic. With TXP, however, elimination of all -cresol and -ethylphenol from the raw materials does not result in a non-toxic plasticizer. Tri---propylphenyl phosphate was shown to non-toxic but esters containing one or two -propylphenyl groups are toxic. The toxicity of the -tolyl, -ethylphenyl and -propylphenyl groups is much reduced in the presence of the 3: 5-dimethylphenyl group. This influence is greatest in mono--propylphenyl-di-3: 5-dimethylphenyl phosphate which is non-toxic in five consecutive daily doses of 500 mg./kg. body weight. The removal of all -cresol, -ethylphenol and -propylphenol from the raw material results in a non-toxic product which we termed non-toxic plasticizer “NTP”. This has been fed in various doses to a variety of mammals and a large number of chickens in short term tests without toxic effects. Our experiments showed that tri--ethylphenyl phosphate is non-toxic but tri--ethylphenyl phosphate is highly toxic. The mixture from which NTP is made contains 10% of -ethylphenol. Based on chemical statistics the tri--ethylphenyl ester can be present only in minute quantities, and we have shown that esters containing one or two -ethylphenyl groups are non-toxic. An ester with a methyl group in the , and an ethyl group in the position in the same benzene nucleus (tri-2-methyl-4-ethylphenyl phosphate) we showed, surprisingly, to be non-toxic.