Disease relevance of TRICRESYL PHOSPHATE

• Effects of neuropathic and non-neuropathic isomers of tricresyl phosphate and their microsomal activation on the production of axon-like processes by differentiating mouse N2a neuroblastoma cells [1].
• The adduct pattern after in vivo treatment with tri-o-tolyl phosphate was identical with that found in bacteria and hepatoma cells treated with 2-phenoxy-4H-1,3,2-benzo-dioxaphosphorin 2-oxide, the major adduct being N3-(o-hydroxybenzyl)deoxycytidine 3' monophosphate and the minor N3-(o-hydroxybenzyl)deoxyuridine 3' monophosphate [2].
• The toxicity of T-2 toxin in mice was enhanced by pre-treatment with tri-o-cresyl phosphate (TOCP), a specific carboxylesterase inhibitor [3].
• This condition is characterized by ataxia that progresses to paralysis concurrent with a central-peripheral distal axonopathy after a delay period of 1-2 weeks following exposure to an organophosphorus compound causing delayed neurotoxicity, such as tri-o-cresyl phosphate (TOCP) [4].
• We have investigated the genotoxicity of this saligenin phosphate and the structure of adducts formed by incubation of 2-phenoxy-4H-1,3,2-benzodioxaphosphorin 2-oxide with nucleosides and DNA. o-Tolyl phosphate was mutagenic in the Ames test (695 revertants/mumol, Salmonella typhimurium TA 100) only with metabolic activation [5].

High impact information on TRICRESYL PHOSPHATE

• Calcium and calmodulin-enhanced in vitro phosphorylation of hen brain cold-stable microtubules and spinal cord neurofilament triplet proteins after a single oral dose of tri-o-cresyl phosphate [6].
• The effect of a single 750-mg/kg oral dose of tri-o-cresyl phosphate (TOCP) on the endogenous phosphorylation of brain microtubule preparations and spinal cord neurofilaments was assessed in hens after the development of delayed neurotoxicity [6].
• In the past the isomer tri-o-cresyl phosphate (TOCP) was thought to be the component primarily responsible for OPIDN [7].
• Axonal transport of these nerves was faster than of their opposite side and of those simply treated by TOCP [8].
• The aim of this work was to investigate the sublethal neuropathic effects of tricresyl phosphate (TCP: mixed isomers), triorthocresyl phosphate (TO:CP) and triparacresyl phosphate (TP:CP) on differentiating mouse N2a neuroblastoma cells [1].

Chemical compound and disease context of TRICRESYL PHOSPHATE

• In the present study we compare DNA adduct formation using 32P-post-labelling assays in 2-phenoxy-4H-1,3,2-benzodioxaphosphorin 2-oxide-treated bacteria (S.typhimurium TA100) and hepatoma cells with DNA adducts formed in liver, kidney, lung and heart of tri-o-tolyl phosphate-exposed Fischer 344 male rats [2].

Biological context of TRICRESYL PHOSPHATE

• 2-Phenoxy-4H-1,3,2-benzodioxaphosphorin 2-oxide, which is a cyclization product similar to those expected from o-tolyl phosphate, was a potent mutagen in bacteria (1452 revertants/mumol, S. typhimurium TA 100) which did not require metabolic activation [5].
• Pretreatment of rabbits with an ip injection of tri-o-tolyl phosphate eliminated more than 95% of the paraoxon binding sites [9].
• The evidence is interpreted as a distal axonopathy in chicks treated with TOCP during late embryonic development [10].
• The results suggest that tricresyl phosphate has a selective effect on neuronal cell differentiation, which involves impaired axon outgrowth, reduced levels of the neurofilament heavy chain and disruption of the neurofilament network [11].
• With respect to its IC50, TCP was at least an order of magnitude more potent in its antiproliferative activity than both TPP and POX [12].

Anatomical context of TRICRESYL PHOSPHATE

• Biochemical changes in sciatic nerve of hens treated with tri-o-cresyl phosphate: increased phosphorylation of cytoskeletal proteins [4].
• Enhancement of endogenous kinase-dependent in vitro protein phosphorylation of subcellular fractions from brains and spinal cords of hens paralyzed 3 weeks after intoxication with tri-o-cresyl phosphate was correlated with the development of organophosphorus compound-induced delayed neurotoxicity (OPIDN) [13].
• Chick embryos were injected on incubation Day 14 with 62 microliter of triorthocresyl phosphate (TOCP)/kg egg [14].
• Tricresyl phosphate inhibits the formation of axon-like processes and disrupts neurofilaments in cultured mouse N2a and rat PC12 cells [11].
• The interaction of Sertoli and Leydig cells in the testicular toxicity of tri-o-cresyl phosphate [15].

Associations of TRICRESYL PHOSPHATE with other chemical compounds

• Triaryl phosphates including tricresyl phosphate (TCP) and butylated triphenyl phosphate (BTP) are organophosphates used in the commercial manufacture of plastics, lubricants, and hydraulic fluids [16].
• Chick embryos were treated with tri-o-cresyl phosphate (TOCP) or leptophos, organophosphorus compounds that cause delayed neurotoxicity [10].
• Three control groups consisted of hens left untreated, given a single, dermal dose of 500 mg/kg tri-o-cresyl phosphate (TOCP, positive control for organophophorous compound-induced delayed neurotoxicity), or 10 mg/kg O,O-diethyl O-4-nitrophenyl phosphorothioate (parathion, negative control) [17].
• The specific binding of [3H]clonidine to alpha 2-adrenoceptors on neural membranes isolated from various brain areas was determined with rats treated for 7-14 days with the cholinesterase inhibitors neostigmine, triorthocresyl phosphate (TOCP), diisopropylfluorophosphate (DFP) and paraoxon, or with vehicle [18].
• Pretreatment of rats with piperonyl butoxide or SKF 525A (cytochrome P-450 inhibitors) or tri-o-cresyl phosphate (TOCP) or paraoxon (carboxylesterase inhibitors) or methyl carbamate (competitive substrate) did not greatly alter the metabolism of EC to CO2 [19].

Gene context of TRICRESYL PHOSPHATE

• Male Fischer 344 rats were treated orally for 10 days with tri-o-tolyl phosphate (50 mg/kg/day) and DNA was isolated from liver, kidney, lung, heart, brain and testes 1, 4, 7 and 28 days after giving the last dose [2].
• In another experiment, to enhance minor metabolic pathways, rats were dosed with 0.25 mmol/kg of a carboxylesterase inhibitor, tri-o-tolyl phosphate, prior to 0.5 mmol/kg butyl [3-13C]acrylate [20].
• The effects of tri-o-cresyl phosphate and metabolites on rat Sertoli cell function in primary culture [21].
• Calcium and calmodulin stimulated in vitro phosphorylation of rooster brain tubulin and MAP-2 following a single oral dose of tri-o-cresyl phosphate [22].
• Tricresyl phosphate (1 microg/ml) inhibited the outgrowth of axon-like processes in mouse N2a neuroblastoma and rat PC12 pheochromocytoma cell lines induced to differentiate by serum withdrawal and nerve growth factor addition, respectively [11].

Analytical, diagnostic and therapeutic context of TRICRESYL PHOSPHATE

• Effect of oral administration of tri-o-cresyl phosphate on in vitro phosphorylation of membrane and cytosolic proteins from chicken brain [23].
• Western blots of neuronal cell extracts probed with the same antibody revealed decreased cross-reactivity after exposure to tricresyl phosphate [11].
• Gas chromatography of the tricresyl phosphate 5% pet. patch test material supplied from Trolab showed that it contained a mixture of a wide range of triaryl phosphates, including 0.08% triphenyl phosphate which is above the threshold for detecting triphenyl phosphate allergy in our patient [24].
• A single intraperitoneal injection of beta NF at 80 mg/kg body weight 48 h prior to administration of o-tolyl saligenin phosphate (TSP), the neuroactive metabolite of tri-o-tolyl phosphate (TOTP), caused a significant increase in hepatic microsomal cytochrome P-450 concentrations and aniline hydroxylase activities after 72 h in both strains [25].
• The refractive index matching polymer film, the refractive index of which was nearly equal to the prism and sensor chip material (a cover glass) of the SPR sensor, was prepared by casting a tetrahydrofuran solution of poly (vinyl chloride) (PVC) containing equal weights of dioctyl phthalate and tricresyl phosphate [26].

References