This article is about the organic derivatives of the phosphate ion. For the inorganic ion, seephosphate. For all organic compound incorporating phosphorus, seeorganophosphorus chemistry.
General chemical structure of the organophosphatefunctional group
Like mostfunctional groups, organophosphates occur in a diverse range of forms,[2] with important examples including key biomolecules such asDNA,RNA andATP, as well as manyinsecticides,herbicides,nerve agents andflame retardants. OPEs have been widely used in various products as flame retardants,plasticizers, and performance additives to engine oil. The low cost of production and compatibility to diverse polymers made OPEs to be widely used in industry including textile, furniture, electronics as plasticizers and flame retardants. These compounds are added to the final product physically rather than by chemical bond.[3] Due to this, OPEs leak into the environment more readily through volatilization, leaching, and abrasion.[4] OPEs have been detected in diverse environmental compartments such as air, dust, water, sediment, soil and biota samples at higher frequency and concentration.[1][4]
The popularity of OPEs as flame retardants came as a substitution for the highly regulatedbrominated flame retardants.[5]
Organophosphates are a class of compounds encompassing a number of distinct but closely relatedfunction groups. These are primarily theesters ofphosphoric acid and can be mono‑esters, di‑esters or tri‑esters depending on the number of attachedorganic groups (abbreviated as 'R' in the image below). In general man‑made organophosphates are most often triesters, while biological organophosphates are usually mono- or di-esters. The hydrolysis of triesters can form diesters and monoesters.[6]
In the context of pesticides, derivatives of organophosphates such asorganothiophosphates (P=S) orphosphorodiamidates (P-N) are included as being organophosphates. The reason is that these compound are converted into organophosphates biologically.
In biology the esters ofdiphosphoric acid andtriphosphoric acid are generally included as organophosphates. The reason is again a practical one, as many cellular processes involve the mono-, di- and tri- phosphates of the same compound. For instance, the phosphates ofadenosine (AMP,ADP,ATP) play a key role in many metabolic processes.
When aliphatic alcohols are used the HCl by-product can react with the phosphate esters to giveorganochlorides and a lower ester.
O=P(OR)3 + HCl → O=P(OR)2OH + RCl
This reaction is usually undesirable and is exacerbated by high reaction temperatures. It can be inhibited by the use of a base or the removal of HCl throughsparging.
Esterifications ofphosphoric acid with alcohols proceed less readily than the more commoncarboxylic acid esterifications, with the reactions rarely proceeding much further than the phosphate mono-ester. The reaction requires high temperatures, under which the phosphoric acid can dehydrate to form poly-phosphoric acids. These are exceedingly viscous and their linear polymeric structure renders them less reactive than phosphoric acid.[7] Despite these limitations the reaction does see industrial use for the formation of monoalkyl phosphates, which are used assurfactants.[8] A major appeal of this route is the low cost of phosphoric acid compared to phosphorus oxychloride.
OP(OH)3 + ROH → OP(OH)2(OR) + H2O
P2O5 is the anhydride of phosphoric acid and acts similarly. The reaction yields equimolar amounts of di- and monoesters with no phosphoric acid. The process is mostly limited to primary alcohols, as secondary alcohols are prone to undesirable side reactions such as dehydration.[7]
Organophosphites can be easily oxidised to give organophosphates. This is not a common industrial route, however large quantities of organophosphites are manufactured as antioxidantstabilisers for plastics. The gradual oxidation of these generates organophosphates in the human environment.[9][10][11]
The formation of organophosphates is an important part of biochemistry and living systems achieve this using a variety ofenzymes. Phosphorylation is essential to the processes of bothanaerobic andaerobic respiration, which involve the production ofadenosine triphosphate (ATP), the "high-energy" exchange medium in the cell.Protein phosphorylation is the most abundantpost-translational modification in eukaryotes. Many enzymes and receptors are switched "on" or "off" by phosphorylation and dephosphorylation.
Various specialised methods have been developed on the laboratory-scale for scientific investigations. These are rarely employed in bulk manufacturing. Examples include theAtherton-Todd reaction, which converts adialkyl phosphite to a phosphoryl chloride. This can then react with an alcohol to give an organophosphate and HCl.
The bonding in organophosphates has been a matter of prolonged debate; the phosphorus atom is classicallyhypervalent, as it possesses more bonds than theoctet rule should allow.[12] The focus of debate is usually on the nature of thephosphoryl P=O bond, which displays (in spite of the common depiction) non-classical bonding, with abond order somewhere between 1 and 2. Early papers explained the hypervalence in terms of d-orbital hybridisation, with the energy penalty of promoting electrons into the higher energy orbitals being off-set by the stabilisation of additional bonding.[13] Later advances incomputational chemistry showed that d-orbitals played little significant role in bonding.[14][15] Current models rely on eithernegative hyperconjugation,[16] or a more complex arraignment with adative-type bond from P to O, combined with back-donation from an oxygen 2p orbital.[15][17] These models agree with the experimental observations of the phosphoryl as being shorter than P-OR bonds[18] and much more polarised. It has been argued that a more accurate depiction is dipolar (i.e. (RO)3P+-O−),[19] which is similar to the depiction ofphosphorus ylides such asmethylenetriphenylphosphorane. However in contrast to ylides, the phosphoryl group is unreactive and organophosphates are poor nucleophiles, despite the high concentration of charge on the phosphoryl oxygen. The polarisation accounts in part for the higher melting points of phosphates when compared to their correspondingphosphites. The bonding in penta-coordinatephosphoranes (i.e. P(OR)5) is entirely different and involvesthree-center four-electron bonds.
Phosphate esters bearing P-OH groups areacidic. The pKa of the first OH group is typically between 1-2, while the second OHdeprotonates at a pKa between 6-7.[20] As such, phosphate mono- and di-esters are negatively charged atphysiological pH.[21] This is of great practical importance, as it makes these compounds far more resistant to degradation by hydrolysis or other forms of nucleophilic attack, due to electrostatic repulsion between negative charges.[22] This effects nearly all organophosphate biomolecules, such as DNA and RNA and accounts in-part for their high stability.[22] The presence of this negative charge also makes these compounds much more water soluble.
The water solubility of organophosphates is an important characteristic in biological, industrial and environmental settings. The wide variety of substitutes used in organophosphate esters results in great variations in physical properties. OPEs exhibit a wide range of octanol/waterpartition coefficients where log Kow values range from -0.98 up to 10.6.[5] Mono- and di- esters are usually water soluble, particularity biomolecules. Tri-esters such as flame retardants and plasticisers have positive log Kow values ranging between 1.44 and 9.49, signifyinghydrophobicity.[5][23][4][24] Hydrophobic OPEs are more likely to be bioaccumulated and biomagnified in aquatic ecosystems.[3] Halogenated organophosphates tend to be denser than water and sink, causing them to accumulate in sediments.[25]
Malathion, one of the first organophosphate insecticides. It remains important as a Vector control agent.
Organophosphates are best known for their use as pesticides. The vast majority areinsecticides and are used either to protect crops, or asvector control agents to reduce the transmission of diseases spread by insects, such as mosquitoes. Health concerns have seen their use significantly decrease since the turn of the century.[26][27]Glyphosate is sometimes called an organophosphate, but is in-fact aphosphonate. Its chemistry, mechanism of toxicity and end-use as a herbicide are different from the organophosphate insecticides.
The development of organophosphate insecticides dates back to the 1930s and is generally credited toGerhard Schrader.[28] At the time pesticides were largely limited to arsenic salts (calcium arsenate,lead arsenate andParis green)[29] orpyrethrin plant extracts, all of which had major problems.[30] Schrader was seeking more effective agents, however while some organophosphates were found to be far more dangerous to insects than higher animals,[31] the potential effectiveness of others aschemical weapons did not go unnoticed. The development of organophosphate insecticides and the earliestnerve agents was conjoined, with Schrader also developing the nerve agentstabun andsarin. Organophosphate pesticides were not commercialised until after WWII.Parathion was among the first marketed, followed bymalathion andazinphosmethyl . Although organophosphates were used in considerable qualities they were originally less important thanorganochlorine insecticides such asDDT,dieldrin, andheptachlor. When many of the organochlorines were banned in the 1970s, following the publishing ofSilent Spring, organophosphates became the most important class of insecticides globally. Nearly 100 were commercialised, with the following being a varied selection:
Organophosphate insecticides areacetylcholinesterase inhibitors, which disrupt the transmission of nerve signals in exposed organisms, with fatal results. The risk of human death throughorganophosphate poisoning[32] was obvious from the start and led to efforts to lower toxicity against mammals while not reducing efficacy against insects.[33][34]
The majority of organophosphate insecticides areorganothiophosphates (P=S) orphosphorodiamidates (P-N), both of which are significantly weaker acetylcholinesterase inhibitors than the corresponding phosphates (P=O). They are 'activated' biologically by the exposed organism, via oxidative conversion of P=S to P=O,[35] hydroxylation,[36][37] or other related process which see them transformed into organophosphates. In mammals these transformations occur almost exclusively in the liver,[38] while in insects they take place in the gut andfat body.[39][40][41] As the transformations are handled by differentenzymes in different classes of organism it is possible to find compounds which activate more rapidly and completely in insects, and thus display more targeted lethal action.
This selectivity is far from perfect and organophosphate insecticides remainacutely toxic to humans, with many thousands estimated to be killed each year due to intentional (suicide)[42] or unintentional poisoning. Beyond their acute toxicity, long-term exposure to organophosphates is associated with a number of heath risks, includingorganophosphate-induced delayed neuropathy (muscle weakness) and developmentalneurotoxicity.[28][43][44] There is limited evidence that certain compounds cause cancer, includingmalathion anddiazinon.[45] Children[46] and farmworkers[47] are considered to be at greater risk.
Pesticide regulation in the United States and theregulation of pesticides in the European Union have both been increasing restrictions on organophosphate pesticides since the 1990s, particularly when used for crop protection. The use of organophosphates has decreased considerably since that time, having been replaced bypyrethroids andneonicotinoids, which are effective a much lower levels.[26] Reported cases of organophosphate poisoning in the US have reduced during this period.[48][49] Regulation in the global south can be less extensive.[50][51]
In 2015, only 3 of the 50 most common crop-specific pesticides used in the US were organophosphates (Chlorpyrifos,Bensulide,Acephate).[52] No new organophosphate pesticides have been commercialised in the 21st century.[53] The situation invector control is fairly similar, despite different risk trade-offs,[54] with the global use of organophosphate insecticides falling by nearly half between 2010 and 2019.[27]Pirimiphos-methyl,Malathion andTemefos are still important, primarily for the control ofmalaria in the Asia-Pacific region.[27] The continued use of these agents is being challenged by the emergence ofinsecticide resistance.[55]
Flame retardants are added to materials to prevent combustion and to delay the spread of fire after ignition. Organophosphate flame retardants are part of a wider family of phosphorus-based agents which include organicphosphonate andphosphinate esters, in addition to inorganic salts.[56][57] When some prominentbrominated flame retardant were banned in the early 2000s phosphorus-based agents were promoted as safer replacements. This has led to a large increase in their use, with an estimated 1 million tonnes of organophosphate flame retardants produced in 2018.[58] Safety concerns have subsequently been raised about some of these reagents,[59][60] with several under regulatory scrutiny.[61][62]
Organophosphate flame retardants were first developed in the first half of the twentieth century in the from oftriphenyl phosphate,tricresyl phosphate andtributyl phosphate for use in plastics likecellulose nitrate andcellulose acetate.[63] Use in cellulose products is still significant, but the largest area of application is now in plasticized vinyl polymers, primarilyPVC. The more modern organophosphate flame retardants come in 2 major types;chlorinated aliphatic compounds or aromatic diphosphates.[56] The chlorinated compoundsTDCPP,TCPP andTCEP are all involatile liquids, of which TCPP is perhaps the most important. They are used inpolyurethane (insulation, soft furnishings),PVC (wire and cable)phenolic resins andepoxy resins (varnishes, coatings and adhesives). The most important of the diphosphates isbisphenol-A bis(diphenyl phosphate), with related analogues based aroundresorcinol andhydroquinone. These are used inpolymer blends ofengineering plastics, such asPPO/HIPS andPC/ABS,[64] which are commonly used to make casing for electrical items like TVs, computers and home appliances.
Organophosphates act multifunctionally to retard fire in both the gas phase and condensed (solid) phase. Halogenated organophosphates are more active overall as their degradation products interfere with combustion directly in the gas phase. All organophosphates have activity in the condensed phase, by forming phosphorus acids which promotechar formation, insulating the surface from heat and air.
Organophosphates were originally thought to be a safe replacements for brominated flame retardants, however many are now coming under regulatory pressure due to their apparent health risks.[62][59][60] The chlorinated organophosphates may be carcinogenic, while others such astricresyl phosphate have necrotoxic properties.[65] Bisphenol-A bis(diphenyl phosphate) can hydrolyse to formBisphenol-A which is under significant scrutiny as potentialendocrine-disrupting chemical. Although their names imply that they are a single chemical, some (but not all) are produced as complex mixtures. For instance, commercial grade TCPP can contain 7 differentisomers,[66] whiletricresyl phosphate can contain up to 10.[67] This makes their safety profiles harder to ascertain, as material from different producers can have different compositions.[68]
Plasticisers are added to polymers and plastics to improve their flexibility and processability, giving a softer more easily deformable material. In this way brittle polymers can be made more durable. The most frequently plasticised polymers are the vinyls (PVC,PVB,PVA andPVCA), as well as cellulose plastics (cellulose acetate,nitrocellulose andcellulose acetate butyrate).[69] PVC dominates the market, consuming 80-90% of global plasticiser production.[69][70] PVC can accept large amounts of plasticiser; it is common for products to be 0-50% plasticiser by mass, but loadings can be as high as 70-80% in the case ofplastisols.[71]
Pure PVC is more than 60% chlorine by mass and is difficult to burn, but its flammability increases the more it is plasticised.[72] Organophosphates find use because they are multifunctional; primarily plasticising but also imparting flame resistance. Compounds are typically triaryl or alkyl diaryl phosphates, withcresyl diphenyl phosphate and2-ethylhexyl diphenyl phosphate being important examples respectively.[73] These are both liquids with high boiling points. Organophosphates are more expensive than traditional plasticisers and so tend be used in combination with other plasticisers and flame retardants.[74]
Similar to their use as plastisiers, organophosphates are well suited to use ashydraulic fluids due to their low freezing points and high boiling points, fire-resistance, non-corrosiveness, excellent boundary lubrication properties and good general chemical stability. The triaryl phosphates are the most important group, with tricresyl phosphate being the first to be commercialised in the 1940s, withtrixylyl phosphate following shortly after. Butylphenyl diphenyl phosphate and propylphenyl diphenyl phosphate became available after 1960.[75]
Mono- and di- phosphate esters of alcohols (or alcoholethoxylates) act assurfactants (detergents).[82] Although they are very common in biology asphospholipids, their industrial use is largely limited to certain niche areas. Compared to the more common sulfur-based anionic surfactants (such asLAS orSLES), phosphate ester surfactants are more expensive and generate less foam.[82] Benefits include high stability at extremes of pH, low skin irritation and a high tolerance to dissolved salts.[7]In agricultural settings monoesters of fatty alcohol ethoxylates are used, which are able to disperse poorly miscible or insoluble pesticides into water. As they are low-foaming these mixtures can be sprayed effectively onto fields, while a high salt tolerance allows co-spraying of pesticides and inorganic fertilisers.[83]Low-levels of phosphate mono-esters, such aspotassium cetyl phosphate, find use in cosmetic creams and lotions.[84] These in oil-in-water formulations are primarily based on non-ionic surfactants, with the anionic phosphate acting as emulsion-stabilisers. Phosphate tri-esters such astributyl phosphate are used asanti-foaming agent in paints and concrete.
Although the first phosphorus compounds observed to act as cholinesterase inhibitors were organophosphates,[85] the vast majority of nerve agents are insteadphosphonates containing a P-C bond. Only a handful of organophosphate nerve agents were developed between the 1930s and 1960s, includingdiisopropylfluorophosphate,VG andNPF. Between 1971 and 1993 theSoviet Union developed many new potential nerve agents, commonly known as theNovichok agents.[86] Some of these can be considered organophosphates (in a broad sense), being derivatives offluorophosphoric acid. Examples includeA-232,A-234,A-262,C01-A035 andC01-A039. The most notable of these is A-234, which was claimed to be responsible for thepoisoning of Sergei and Yulia Skripal in Salisbury (UK) 2018.[87]
The detection of OPEs in the air as far away as Antarctica at concentrations around 1 ng/m3 suggests their persistence in air, and their potential for long-range transport.[24] OPEs were measured in high frequency in air and water and widely distributed in northern hemisphere.[88][89] The chlorinated OPEs (TCEP, TCIPP, TDCIPP) in urban sampling sites and non-halogenated like TBOEP in rural areas respectively were frequently measured in the environment across multiple sites. In the Laurentian Great Lakes total OPEs concentrations were found to be 2–3 orders of magnitude higher than concentrations of brominated flame retardants measured in similar air.[89] Waters from rivers in Germany, Austria, and Spain have been consistently recorded for TBOEP and TCIPP at highest concentrations.[24] From these studies, it is clear that OPE concentrations in both air and water samples are often orders of magnitude higher than other flame retardants, and that concentrations are largely dependent on sampling location, with higher concentrations in more urban, polluted locations.
^abcArora, Pinklesh; Singh, Rakhi; Seshadri, Geetha; Tyagi, Ajay Kumar (16 July 2018). "Synthesis, Properties and Applications of Anionic Phosphate Ester Surfactants: A Review".Tenside Surfactants Detergents.55 (4):266–272.doi:10.3139/113.110570.S2CID105424570.
^Tracy, David J.; Reierson, Robert L. (April 2002). "Commercial synthesis of monoalkyl phosphates".Journal of Surfactants and Detergents.5 (2):169–172.doi:10.1007/s11743-002-0218-9.S2CID96234775.
^Liu, Runzeng; Mabury, Scott A. (19 February 2019). "Organophosphite Antioxidants in Indoor Dust Represent an Indirect Source of Organophosphate Esters".Environmental Science & Technology.53 (4):1805–1811.doi:10.1021/acs.est.8b05545.PMID30657667.S2CID58665691.
^Gong, Xinying; Zhang, Wenjun; Zhang, Shuyi; Wang, Yu; Zhang, Xinyi; Lu, Yuan; Sun, Hongwen; Wang, Lei (1 June 2021). "Organophosphite Antioxidants in Mulch Films Are Important Sources of Organophosphate Pollutants in Farmlands".Environmental Science & Technology.55 (11):7398–7406.doi:10.1021/acs.est.0c08741.PMID33754709.
^Fugel, Malte; Malaspina, Lorraine A.; Pal, Rumpa; Thomas, Sajesh P.; Shi, Ming W.; Spackman, Mark A.; Sugimoto, Kunihisa; Grabowsky, Simon (7 May 2019). "Revisiting a Historical Concept by Using Quantum Crystallography: Are Phosphate, Sulfate and Perchlorate Anions Hypervalent?".Chemistry – A European Journal.25 (26):6523–6532.doi:10.1002/chem.201806247.PMID30759315.S2CID73451989.
^Cundari, Thomas R. (2013). "Chemical bonding involving d-orbitals".Chemical Communications.49 (83):9521–9525.doi:10.1039/c3cc45204b.PMID24013652.
^Magnusson, Eric (October 1990). "Hypercoordinate molecules of second-row elements: d functions or d orbitals?".Journal of the American Chemical Society.112 (22):7940–7951.doi:10.1021/ja00178a014.
^abGamoke, Benjamin; Neff, Diane; Simons, Jack (14 May 2009). "Nature of PO Bonds in Phosphates".The Journal of Physical Chemistry A.113 (19):5677–5684.doi:10.1021/jp810014s.PMID19378976.
^Rajani, Puchakayala; Gopakumar, Gopinadhanpillai; Nagarajan, Sivaraman; Brahmmananda Rao, Cherukuri Venkata Siva (July 2021). "Does the basicity of phosphoryl oxygen change with alkyl chain length in phosphate ligands?".Chemical Physics Letters.775: 138641.doi:10.1016/j.cplett.2021.138641.S2CID234836388.
^Chesnut, D. B. (1 May 2003). "Atoms-in-Molecules and Electron Localization Function Study of the Phosphoryl Bond".The Journal of Physical Chemistry A.107 (21):4307–4313.doi:10.1021/jp022292r.
^Corbridge, Derek E. C. (1971). "The structural chemistry of phosphates".Bulletin de la Société française de Minéralogie et de Cristallographie.94 (3):271–299.doi:10.3406/bulmi.1971.6534.
^Rai, Uma S.; Symons, Martyn C. R. (1994). "EPR data do not support the P=O representation for trialkyl phosphates and phosphine oxides or sulfides".J. Chem. Soc., Faraday Trans.90 (18):2649–2652.doi:10.1039/FT9949002649.
^Kumler, W. D.; Eiler, John J. (December 1943). "The Acid Strength of Mono and Diesters of Phosphoric Acid. The n-Alkyl Esters from Methyl to Butyl, the Esters of Biological Importance, and the Natural Guanidine Phosphoric Acids".Journal of the American Chemical Society.65 (12):2355–2361.doi:10.1021/ja01252a028.
^abcGreaves, Alana K.; Letcher, Robert J. (January 2017). "A Review of Organophosphate Esters in the Environment from Biological Effects to Distribution and Fate".Bulletin of Environmental Contamination and Toxicology.98 (1):2–7.doi:10.1007/s00128-016-1898-0.PMID27510993.S2CID19824807.
^ab"Status and Trends of Pesticide Use".United Nations Environment Programme. World Health Organization, & Food and Agriculture Organization of the United Nations. 2022.
^Richmond, Martha (2021). "Discovery and Commercial Introduction and Mode of Action of Parathion, Malathion, Diazinon, Tetrachlorvinphos, and Glyphosate".Cancer Hazards: Parathion, Malathion, Diazinon, Tetrachlorvinphos and Glyphosate. AESS Interdisciplinary Environmental Studies and Sciences Series. pp. 3–11.doi:10.1007/978-3-030-81953-8_1.ISBN978-3-030-81952-1.
^O’Brien, R. D.; Thorn, G. D.; Fisher, R. W. (1 October 1958). "New Organophosphate Insecticides Developed on Rational Principles1".Journal of Economic Entomology.51 (5):714–718.doi:10.1093/jee/51.5.714.
^Salgado, Vincent L; David, Michael D (April 2017). "Chance and design in proinsecticide discovery".Pest Management Science.73 (4):723–730.doi:10.1002/ps.4502.PMID27976502.
^"The decomposition of some organophosphorus insecticides and related compounds in plants".Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences.239 (663):191–214. 22 December 1955.doi:10.1098/rstb.1955.0009.S2CID84496732.
^Spencer, E. Y.; O'Brien, R. D.; White, R. W. (February 1957). "Metabolism of Insecticides, Permanganate Oxidation Products of Schradan".Journal of Agricultural and Food Chemistry.5 (2):123–127.doi:10.1021/jf60072a004.
^Metcalf, Robert L.; March, Ralph B. (1 March 1953). "Further Studies1 on the Mode of Action of Organic Thionophosphate Insecticides".Annals of the Entomological Society of America.46 (1):63–74.doi:10.1093/aesa/46.1.63.
^Spencer, E. Y.; O'Brien, R. D. (August 1953). "Schradan, Enhancement of Anticholinesterase Activity in Octamethylpyrophosphoramide by Chlorine".Journal of Agricultural and Food Chemistry.1 (11):716–720.doi:10.1021/jf60011a003.
^Mew, Emma J.; Padmanathan, Prianka; Konradsen, Flemming; Eddleston, Michael; Chang, Shu-Sen; Phillips, Michael R.; Gunnell, David (September 2017). "The global burden of fatal self-poisoning with pesticides 2006-15: Systematic review".Journal of Affective Disorders.219:93–104.doi:10.1016/j.jad.2017.05.002.hdl:20.500.11820/0c890816-28a1-438e-8260-95dcd13ee57e.PMID28535450.
^Jokanović, Milan; Oleksak, Patrik; Kuca, Kamil (January 2023). "Multiple neurological effects associated with exposure to organophosphorus pesticides in man".Toxicology.484: 153407.doi:10.1016/j.tox.2022.153407.PMID36543276.S2CID254871617.
^IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (2017). "Some Organophosphate Insecticides and Herbicides".IARC Monographs on the Evaluation of Carcinogenic Risks to Humans.12.International Agency for Research on Cancer: 464.PMID31829533.
^Souza, Marília Cristina Oliveira; Cruz, Jonas Carneiro; Cesila, Cibele Aparecida; Gonzalez, Neus; Rocha, Bruno Alves; Adeyemi, Joseph A.; Nadal, Marti; Domingo, José L.; Barbosa, Fernando (July 2023). "Recent trends in pesticides in crops: A critical review of the duality of risks-benefits and the Brazilian legislation issue".Environmental Research.228: 115811.doi:10.1016/j.envres.2023.115811.PMID37030406.S2CID258033572.
^Gray, George M.; Hammitt, James K. (October 2000). "Risk/Risk Trade-offs in Pesticide Regulation: An Exploratory Analysis of the Public Health Effects of a Ban on Organophosphate and Carbamate Pesticides".Risk Analysis.20 (5):665–680.doi:10.1111/0272-4332.205060.PMID11110213.S2CID10379060.
^Siegfried, Blair D.; Scharf, Michael E. (2001). "Mechanisms of Organophosphate Resistance in Insects".Biochemical Sites of Insecticide Action and Resistance. pp. 269–291.doi:10.1007/978-3-642-59549-3_13.ISBN978-3-540-67625-6.
^Schmitt, Elmar (May 2007). "Phosphorus-based flame retardants for thermoplastics".Plastics, Additives and Compounding.9 (3):26–30.doi:10.1016/S1464-391X(07)70067-3.
^He, Huan; Gao, Zhanqi; Zhu, Donglin; Guo, Jiehong; Yang, Shaogui; Li, Shiyin; Zhang, Limin; Sun, Cheng (December 2017). "Assessing bioaccessibility and bioavailability of chlorinated organophosphorus flame retardants in sediments".Chemosphere.189:239–246.doi:10.1016/j.chemosphere.2017.09.017.PMID28942249.
^Pawlowski, Kristin H; Schartel, Bernhard (November 2007). "Flame retardancy mechanisms of triphenyl phosphate, resorcinol bis(diphenyl phosphate) and bisphenol A bis(diphenyl phosphate) in polycarbonate/acrylonitrile–butadiene–styrene blends".Polymer International.56 (11):1404–1414.doi:10.1002/pi.2290.
^Barth, Mary L.; Craig, Peter H. (October 1999). "Evaluation of the hazards of industrial exposure to tricresyl phosphate:a review and interpretation of the literature".Journal of Toxicology and Environmental Health, Part B.2 (4):281–300.doi:10.1080/109374099281142.PMID10596299.
^Truong, Jimmy W.; Diamond, Miriam L.; Helm, Paul A.; Jantunen, Liisa M. (December 2017). "Isomers of tris(chloropropyl) phosphate (TCPP) in technical mixtures and environmental samples".Analytical and Bioanalytical Chemistry.409 (30):6989–6997.doi:10.1007/s00216-017-0572-7.PMID29147747.S2CID24611076.
^Rahman, M; Brazel, C (December 2004). "The plasticizer market: an assessment of traditional plasticizers and research trends to meet new challenges".Progress in Polymer Science.29 (12):1223–1248.doi:10.1016/j.progpolymsci.2004.10.001.
^Krauskopf LG (2009). "3.13 Plasticizers".Plastics additives handbook (6. ed.). Munich: Carl Hanser Verlag. pp. 485–511.ISBN978-3-446-40801-2.
^William Coaker, A. (September 2003). "Fire and flame retardants for PVC".Journal of Vinyl and Additive Technology.9 (3):108–115.doi:10.1002/vnl.10072.S2CID247663661.
^Grossman, Richard F (2008-05-02).Handbook of Vinyl Formulating. John Wiley & Sons. p. 289.ISBN978-0-470-25354-0.
^Levchik, Sergei V.; Weil, Edward D. (October 2005). "Overview of the recent literature on flame retardancy and smoke suppression in PVC".Polymers for Advanced Technologies.16 (10):707–716.doi:10.1002/pat.645.
^Guan, Bihan; Pochopien, Bernadeta A.; Wright, Dominic S. (August 2016). "The chemistry, mechanism and function of tricresyl phosphate (TCP) as an anti-wear lubricant additive".Lubrication Science.28 (5):257–265.doi:10.1002/ls.1327.S2CID93027894.
^Li, Haogang; Zhang, Yanbin; Li, Changhe; Zhou, Zongming; Nie, Xiaolin; Chen, Yun; Cao, Huajun; Liu, Bo; Zhang, Naiqing; Said, Zafar; Debnath, Sujan; Jamil, Muhammad; Ali, Hafiz Muhammad; Sharma, Shubham (May 2022). "Extreme pressure and antiwear additives for lubricant: academic insights and perspectives".The International Journal of Advanced Manufacturing Technology.120 (1–2):1–27.doi:10.1007/s00170-021-08614-x.S2CID246434462.
^Hidayah, Nur Nadiatul; Abidin, Sumaiya Zainal (June 2018). "The evolution of mineral processing in extraction of rare earth elements using liquid-liquid extraction: A review".Minerals Engineering.121:146–157.doi:10.1016/j.mineng.2018.03.018.S2CID104245067.
^Paiva, A. P.; Malik, P. (2004). "Recent advances on the chemistry of solvent extraction applied to the reprocessing of spent nuclear fuels and radioactive wastes".Journal of Radioanalytical and Nuclear Chemistry.261 (2):485–496.doi:10.1023/B:JRNC.0000034890.23325.b5.S2CID94173845.
^Miller, Dennis; Wiener, Eva-Maria; Turowski, Angelika; Thunig, Christine; Hoffmann, Heinz (July 1999). "O/W emulsions for cosmetics products stabilized by alkyl phosphates — rheology and storage tests".Colloids and Surfaces A: Physicochemical and Engineering Aspects.152 (1–2):155–160.doi:10.1016/S0927-7757(98)00630-X.
^Petroianu, G. A. (2010-10-01). "Toxicity of phosphor esters: Willy Lange (1900-1976) and Gerda von Krueger (1907-after 1970)".Die Pharmazie.65 (10):776–780.ISSN0031-7144.PMID21105582.
