Search tips
Search criteria 


Logo of brjindmedLink to Publisher's site
Br J Ind Med. 1960 July; 17(3): 190–200.
PMCID: PMC1039179

A Study on the Acute Toxicity of the Tri-aryl Phosphates Used as Plasticizers


Paralysis in man and the domestic fowl caused by “ToCP” (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 ortho-tolyl esters are toxic but we found that their removal does not make the mixture non-toxic. The meta- and para-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-ortho-ethylphenyl ester was non-toxic, but found the mono- and di-ortho-ethylphenyl phosphates to be highly toxic. We showed that TTP made from phenols with all the ortho-cresol and ortho-ethylphenol removed is non-toxic.

With TXP, however, elimination of all ortho-cresol and ortho-ethylphenol from the raw materials does not result in a non-toxic plasticizer. Tri-ortho-n-propylphenyl phosphate was shown to non-toxic but esters containing one or two ortho-propylphenyl groups are toxic.

The toxicity of the ortho-tolyl, ortho-ethylphenyl and ortho-propylphenyl groups is much reduced in the presence of the 3: 5-dimethylphenyl group. This influence is greatest in mono-ortho-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 ortho-cresol, ortho-ethylphenol and ortho-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-meta-ethylphenyl phosphate is non-toxic but tri-para-ethylphenyl phosphate is highly toxic. The mixture from which NTP is made contains 10% of para-ethylphenol. Based on chemical statistics the tri-para-ethylphenyl ester can be present only in minute quantities, and we have shown that esters containing one or two para-ethylphenyl groups are non-toxic. An ester with a methyl group in the ortho, and an ethyl group in the para position in the same benzene nucleus (tri-2-methyl-4-ethylphenyl phosphate) we showed, surprisingly, to be non-toxic.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.6M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • ALDRIDGE WN. Tricresyl phosphates and cholinesterase. Biochem J. 1954 Feb;56(2):185–189. [PubMed]
  • BARNES JM, DENZ FA. Experimental demyelination with organo-phosphorus compounds. J Pathol Bacteriol. 1953 Apr;65(2):597–605. [PubMed]
  • CAVANAGH JB. The toxic effects of triortho-cresyl phosphate on the nervous system; an experimental study in hens. J Neurol Neurosurg Psychiatry. 1954 Aug;17(3):163–172. [PMC free article] [PubMed]
  • CLOUGH M, COCK AG. Variability of inbred and incross chickens. Nature. 1957 May 18;179(4568):1030–1031. [PubMed]
  • EARL CJ, THOMPSON RHS. Cholinesterase levels in the nervous system in tri-ortho-cresyl phosphate poisoning. Br J Pharmacol Chemother. 1952 Dec;7(4):685–694. [PubMed]
  • HENSCHLER D. Die Trikresylphosphatvergiftung; experimentelle Klärung von Problemen der Atiologie und Pathogenese. Klin Wochenschr. 1958 Jul 15;36(14):663–674. [PubMed]
  • HENSCHLER D, BAYER HH. Toxikologische Untersuchungen über Triphenylphosphat, Trixylenylphosphate und Triarylphosphate aus Mischungen homologer Phenole. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1958;233(6):512–517. [PubMed]
  • HINE CH, DUNLAP MK, RICE EG, COURSEY MM, GROSS RM, ANDERSON HH. The neurotoxicity and anticholinesterase properties of some substituted phenyl phosphates. J Pharmacol Exp Ther. 1956 Feb;116(2):227–236. [PubMed]
  • POIRIER LJ, AYOTTE RA, GAUTHIER C. Modification of the Marchi technic. Stain Technol. 1954 Mar;29(2):71–75. [PubMed]
  • SMITH HV, SPALDING JM. Outbreak of paralysis in Morocco due to ortho-cresyl phosphate poisoning. Lancet. 1959 Dec 5;2(7110):1019–1021. [PubMed]
  • SUSSER M, STEIN Z. An outbreak of tri-ortho-cresyl phosphate (T.O.C.P.) poisoning in Durban. Br J Ind Med. 1957 Apr;14(2):111–120. [PMC free article] [PubMed]

Articles from British Journal of Industrial Medicine are provided here courtesy of BMJ Group