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| Names | |
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| Other names
tricresylphosphate, tri-o-cresyl phosphate, TOCP, tritolyl phosphate, tolyl phosphate, tri-o-tolyl ester of phosphoric acid
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| Identifiers | |
3D model (JSmol)
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| ChemSpider | |
| UNII | |
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| Properties | |
| C21H21O4P | |
| Molar mass | 368.37 g/mole |
| Appearance | colourless liquid |
| Melting point | −40 °C (−40 °F; 233 K) |
| Boiling point | 255 °C (491 °F; 528 K) (10 mmHg) |
| Hazards | |
| Flash point | > 225 °C (437 °F; 498 K) |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Tricresyl phosphate, abbreviated TCP, is an organophosphate compound that is used as a plasticizer and diverse other applications. It is a toxic substance that causes neuropathy through injestion, and has been the cause of several mass poisonings in history. It is a colourless, viscous liquid, although commercial samples are typically yellow. It is virtually insoluble in water.
Production edit
Tricresyl phosphate is manufactured by reaction of cresols with phosphorus oxychloride:
- OPCl3 + 3 HOC6H4CH3 → OP(OC6H4CH3)3 + 3 HCl
The cresol is a mixture of three isomers (ortho, meta, and para). The fact that tricresyl phosphate is derived from a mixture and itself is a mixture ensures that it remains liquid over a wide span of temperatures.
Symptoms edit
Tri-o-cresyl Phosphate poisoning is characterized by numbness of the legs and hands accompanied by weakness or paralysis of these regions, though all symptoms usually only occur after a latency period of 2-3 days. If the dose is substantial, gastrointestinal distress may occur immediately, and the latency period may be shortened. 10 to 40 days after the onset of numbness, there is a potential for abrupt flaccid paralysis of the toes, feet, and lower parts of the leg, which may be followed by paralysis of the fingers and hands after 4 to 5 additional days. Fatalities are rare, but there is potential for permanent paralysis, due to death of nerve cells and damage to myelin sheaths[1].
Toxicity edit
Of the three tricresyl phosphate isomers, only the ortho isomer demonstrates high toxicity, though this toxicity has been demonstrated to be caused by a metabolite that is made from tri-ortho-cresyl phosphate (TOCP). This metabolite is 2-(ortho-cresyl)-4H-1,3,2-benzodioxaphosphoran-2-one (CBDP) and is an irreversible inhibitor of human butyrylcholinesterase (BChE) and human acetylcholinesterase (AChE). CBDP ultimately binds to the BChE and AChE at a serine residue in the active site after two consecutive dealkyalation reactions (aging). Though CBDP readily inhibits BChE and AChE, BChE has a sensitivity to CBDP that is nearly one order of magnitude greater than that of AChE[2]. The inhibition of cholinesterases causes a build up in cholines that would have been broken down by the esterase. The build up of cholines causes an over-activity of neurons, ultimately causing them to function abnormally, or not at all.
Major Cases edit
The earliest major poisoning by TOCP was in France, in 1898 where 6 of 41 people treated with phospho-creosote for tuberculosis developed polyneuropathy, later to be determined to be caused by TOCP[3].
In 1930, 50,000 cases of paralysis broke out in the mid-western and south-western US. This was attributed to the consumption of a medicine called Jamaica Ginger, which had been adulterated with TOCP. TOCP had been mixed into the alcoholic medicine so that the drink would pass inspection by prohibition officers without making the alcohol taste as bitter as other adulterants. This caused partial paralysis of many of its consumers, characterized by an awkward, high-kneed walk, dubbed Jake Walk[4].
Another large outbreak of TOCP poisoning occurred in Meknes, Morocco in the 1960's. Of the 10,000 cases, nearly all of them were Arab and middle class, with the majority being women. The condition was found to be caused by the adulteration of cooking oil with lubricating oil used in jet engines which contained 3% mixed cresyl phosphates[5].
The most recent incident of large scale poisoning by TOCP was in Sri Lanka, where over 20 woman suffered from acute polyneuropathy in 1977. This poisoning was determined to be caused by contamination of cooking oil that was transported in barrels that had previously stored mineral oil[6].
Uses edit
Tricresyl phosphate is used as a plasticizer in nitrocellulose, acrylate lacquers, varnishes, and in polyvinyl chloride. It is a flame retardant in plastics and rubbers. It is used as a gasoline additive as a lead scavenger for tetraethyllead.[7] It is a hydraulic fluid and a heat exchange medium. It is also used by the U.S. Navy in its pure form as a lubricant in cryogenic liquid pumps. Exploiting its hydrophobic properties, it is used for the waterproofing of materials. It is a solvent for extractions, a solvent for nitrocellulose and other polymers. It is used as an antiwear and extreme pressure additive in lubricants and hydraulic fluids.[8][9]
Safety edit
TCP is used as an additive in turbine engine oil and can potentially get into the airliner cabins via a bleed air "fume event". Aerotoxic syndrome is the name given to the alleged health ill-effects (with symptoms including memory loss, depression and schizophrenia) caused by exposure to engine chemicals although UK industry-funded studies have not yet made a link between TCP and long-term health issues.[10] The most dangerous isomers are considered to be those containing ortho isomers, such as tri-ortho-cresyl phosphate, TOCP. The World Health Organisation 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."[11] Therefore, strenuous efforts have been made to reduce the content of the ortho isomers in commercial TCP if there is a risk of human exposure. Nevertheless, actual measurements of TOCP concentrations in airliner cabin air show a much higher level than expected.[12] Researchers at the University of Washington found that non-ortho TCP isomers present in synthetic jet engine oils do inhibit certain enzymes.[13]
TCP is combustible, although less so than typical organic compounds.
References edit
- ^ "TRI-O-CRESYL PHOSPHATE - National Library of Medicine HSDB Database". toxnet.nlm.nih.gov.
- ^ Carletti, Eugenie (2011). "Reaction of Cresyl Saligenin Phosphate, the Organophosphorus Agent Implicated in Aerotoxic Syndrome, with Human Cholinesterases: Mechanistic Studies Employing Kinetics, Mass Spectrometry, and X-ray Structure Analysis". Chemical Research in Toxicology. 24 (6): 797–808. doi:10.1021/tx100447k. PMID 21438623. S2CID 24147948.
- ^ "Tricresyl phosphate (EHC 110, 1990)". www.inchem.org.
- ^ Baum, Dan. "Annals of Epidemiology: Jake Leg". archives.newyorker.com. The New Yorker.
- ^ Travers PR (1962). "The Results of Intoxication with Orthocresyl Phosphate Absorbed from Contaminated Cooking Oil, as seen in 4,029 Patients in Morocco". Proceedings of the Royal Society of Medicine. 55 (1): 57–60. doi:10.1177/003591576205500116. S2CID 255018.
- ^ Rege, Rekha S. Singhal ; Pushpa R. Kulkarni ; Dinanath V. (1997). Handbook of indices of food quality and authenticity ([1st publ.]. ed.). Cambridge: Woodhead. ISBN 9781855732995.
{{cite book}}: CS1 maint: multiple names: authors list (link) - ^ Marvel & other solutions to the lead problem, checked 2009-06-18.
- ^ Jürgen Svara, Norbert Weferling, Thomas Hofmann "Phosphorus Compounds, Organic" in Ullmann's Encyclopedia of Industrial Chemistry 2006, Wiley-VCH: Wienheim. doi:10.1002/14356007.a19_545.pub2
- ^ Solbu, K.; Thorud, S.; Hersson, M.; Ovrebø, S.; Ellingsen, G.; Lundanes, E.; Molander, P. (Aug 2007). "Determination of airborne trialkyl and triaryl organophosphates originating from hydraulic fluids by gas chromatography-mass spectrometry. Development of methodology for combined aerosol and vapor sampling". Journal of Chromatography A. 1161 (1–2): 275–283. doi:10.1016/j.chroma.2007.05.087. ISSN 0021-9673. PMID 17574560.
- ^ UK Parliament: Elements of healthy cabin air
- ^ Tricresyl Phosphate Environmental Health Criteria A110. International Programme On Chemical Safety (IPCS) WHO Geneva 1990
- ^ J.J. Ramsden (2013). "On the proportion of ortho isomers in the tricresyl phosphates contained in jet oil". Journal of Biological Physics and Chemistry. 13 (2): 69–72. doi:10.4024/03RA13L.jbpc.13.02.
- ^ Baker P., Cole T et al., Identifying safer anti-wear triaryl phosphate additives for jet engine lubricants. Chemico-Biological Interactions. Volume 203, Issue 1, 25 March 2013, Pages 257–264