Tri-ortho-cresyl phosphate

An organophosphate ester commonly used in hydraulic fluids, tricresyl phosphate (TCP), and tri-ortho-cresyl phosphate (TOCP), a possible contaminant of older formulations of TCP, have been shown to alter testicular morphology, testicular function, and reproductive function in rodents after oral exposure (Carlton et al. 1987 Chapin et al. 1988 NTP 1994 Somkuti et al. 1987a, 1987b). 

Inui K, Mitsumori K, Harada T, et al. 1993. Quantitative analysis of neuronal damage induced by tri-ortho-cresyl phosphate in Wistar rats. Fundam Appl Toxicol 20 111-119. 

Padilla S, Veronesi B. 1985. The relationship between neurological damage and neurotoxic esterase inhibition in rats acutely exposed to tri-ortho-cresyl phosphate. Toxicol Appl Pharmacol 78 78-87. 

Somkuti SG, Lapadula D, Chapin RM, et al. 1991. Light and electron microscopic evidence of tri-ortho-cresyl phosphate (TOCP)-mediated testicular toxicity in F344 rats. Toxicol Appl Pharmacol 107 35-46. 

Susser M, Stein Z An outbreak of tri-ortho-cresyl phosphate (TOCP) poisoning in Durban. Br J Ind Med 14 11-120, 1957... 

Polak, R.L., Cohen, E.M. (1969). The influence of tri-ortho-cresyl phosphate on the distribution of P in the body of the rat after the injection of P-sarin. Biochem. Pharmacol. 18 813-20. 

Tri-ortho-cresyl phosphate mass poisoning, Morocco, 1959... 

Other species, including rats, rabbits, guinea pigs, and hamsters, do not exhibit consistent delayed neurotoxic responses to the neuropathic organophosphorus compounds (e.g., tri-ortho cresyl phosphate). 

Axonal transport Tri-ortho-cresyl phosphate, carbon disulfide, colchicine, lead, some organophosphates... 

One of the main human health concerns about organophosphate esters is the potential for neurotoxicity reactions, in particular a condition known as organophosphate-induced delayed neurotoxicity (OPIDN). Tri-ort/20-cresyl phosphate (TOCP) has been identified as one of the more potent OPIDN neurotoxins in humans, and was formerly a constituent in some organophosphate ester hydraulic fluid products (Marino 1992 Marino and Placek 1994). Production processes now routinely remove virtually all the TOCP. For instance, tricresyl phosphate (TCP) products now typically are manufactured to contain over 98% meta and para isomers and virtually no TOCP (Marino and Placek 1994). Products containing these compounds associated with OPIDN have now entirely disappeared from commercial use, and the vast majority of the industrial organophosphate esters are based on triaryl phosphates with no halogenated components (Marino 1992). At waste disposal sites, however, site contaminants from older product formulations containing the ortho form may be encountered. 

Another mechanism of dearylation has been proven for tris(2-methylphen-yl) phosphate, and it is a pathway whose first step must be cytochrome P450 dependent. As shown in Fig. 9.10, the compound is hydroxylated at a Me group to yield the hydroxymethyl analogue 9.46. The latter then breaks down by intramolecular nucleophilic attack to form 2-(2-methylphenoxy)-4//-l,3,2A5-benzodioxaphosphinin-2-one (9.47, Fig. 9.10). This reaction of cy-clization occurs with loss of a ortho-cresyl moiety and is catalyzed by serum albumin [102], The cyclized product is a more potent inhibitor of esterases than tris(2-methylphenyl) phosphate, and it is also more toxic [100][101],... 

Synonyms Cresyl phosphate Phosphoric acid, tris (methylphenyl) ester Phosphoric acid, tritolyl ester TCP Tricresyl phosphate, with > 3% ortho isomer Tris (methylphenyl) phosphate Tris (tolyloxy) phosphine oxide Tritolyl phosphate Classification Aromatic phosphorus compd. 

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