Tricresyl phosphate

Many isomers of tricresyl phosphate exist and comprise typical samples of this compound. The World Health Organization stated in 1990 that "Because of considerable variation among individuals in sensitivity to TOCP, it is not possible to establish a safe level of exposure" and "TOCP are therefore considered major hazards to human health." The most toxic isomer is tri-ortho-cresyl phosphate, (TOCP). Strenuous efforts have been made to minimize the content of the ortho isomers in commercial TCP if there is a risk of human exposure. However other isomers present in synthetic jet engine oils do inhibit certain enzymes. ==Toxicity==

TCP has very low acute toxicity, but it is transformed in the body to a highly toxic metabolite. In humans, the first symptoms are weakness/paralysis of the hands and feet on both sides of the body due to damage to the peripheral nervous system (polyneuropathy) and a sensation of pins-and-needles (paresthesia). Onset typically occurs between 3–28 days from initial exposure. Exposure to TOCP has been characterized by a list of observations: Mammalian placental development were also negatively affected. This metabolite is able to inhibit neuropathy target esterase (NTE) and results in the classic organophosphate-induced delayed neuropathy (OPIDN). In tandem, TOCP exerts physical damage by causing axonal destruction and myelin disintegration within specialized cells that transmit nerve impulses (neurons). In addition to the formation of SCOTP, the interactions between TOCP and two different human cytochrome P450 complexes (1A2 and 3A4) can further produce 2-(ortho-cresyl)-4H-1,2,3-benzodioxaphosphoran-2-one (CBDP). This metabolite can bind to butyrylcholinesterase (BuChE) and/or acetylcholinesterase (AChE). Binding to BuChE results in no adverse effects, for its typical role is to covalently bind to organophosphate poisons and detoxify them by inactivation. The dangers in metabolizing TOCP to CBDP occur when its potential to bind to AChE become imminent, for inactivation of the enzyme in nerve synapses can be lethal. The enzyme plays a tantamount role in terminating nerve impulse transmission "by hydrolyzing the neurotransmitter acetylcholine." Upon inactivation, acetylcholine can no longer be broken down in the body and results in uncontrollable muscle spasms, paralyzed breathing (bradycardia), convulsions, and/or death. Luckily, TOCP is considered a weak AChE inhibitor. ==Health calamities from TCP==

The earliest known mass poisoning event by TOCP occurred in 1899 when six French hospital patients were given a medication containing this compound. Pharmacist Jules Brissonet had synthesized this compound in the hopes of treating tuberculosis, but soon after administration all six patients developed polyneuropathy. The original paper described this medication to be:A bland, limpid liquid, nearly tasteless and odourless, which is not irritating to the gastric mucous membranes. When creosote is combined with phosphoric acid the metabolic action produced is much more marked, and Phosote can be tolerated in larger doses and for a longer continuance than Creosote or Guaiacol. Dose of the preparation, one to two grammes three times a day. The greatest mass poisoning by TOCP occurred in 1930 when it was added as an adulterant to the popular drink Jamaica ginger, also known as Ginger Jake, during the United States Prohibition era. Up to 100,000 people were poisoned and 5,000 paralyzed when a manufacturer of Ginger Jake added Lindol—a compound that consisted mainly of TOCP—to their product. The reason for why TOCP was found in Ginger Jake is disputed; one source claims it was to further extract the Jamaica root, and yet another source claims it was a result of contamination from lubricating oils. Binges of Ginger Jake resulted in what was known to be a "Jake walk", in which patients experienced a highly irregular gait caused by numbness in the legs, followed by eventual paralysis of the wrists and feet. In medical journals it was described to have produced an organophosphate-induced delayed neuropathy (OPIDN) neurodegenerative syndrome, "characterized by distal axonal lesions, ataxia, and neuronal degeneration in the spinal cord and peripheral nervous systems." In 1932, 60 European women experienced TOCP poisoning due to the abortion-inducing (abortifacient) drug apiol, which was adulterated with TCP. Apiol was subsequently criticized by doctors, journalists, and activists until it was discontinued, citing that the dangers were too great and the number of poisonings was likely higher than accounted for. Other mass poisonings --> ==References==