Organophosphate

{{biology}}
'''Organophosphates''' (OPs) are chemically esters of phosphoric acid<ref name=wpop>{{wpa|Organophosphate}}</ref>. Many are used as insecticides (killing insects), anthelmintics   (killing parasitic worms), and nerve agents (killing human beings). They also have other uses in chemical engineering and manufacture, but it is their use in agriculture that is particularly controversial today. Health risks from direct exposure are now well-known, particularly for agricultural workers, but there are also worries about safe levels in food and the effects of aerial spraying. They have been implicated in a variety of public health and environmental issues from [[ADHD]] to [[colony collapse disorder]].

The good news is that OPs are often used to combat insects which act as disease vectors, such as mosquitos, as well as to combat agricultural pests. They became popular as a safer and less environmentally damaging alternative to organochlorine insecticides like [[DDT]] at a time when there were concerns about DDT poisoning the environment.

Organophosphate pesticides go by names such as parathion, malathion, methyl parathion, chlorpyrifos, diazinon, dichlorvos, phosmet, fenitrothion, tetrachlorvinphos, azamethiphos, azinphos-methyl, and naled. Other OPs include trichlorfon aka {{wpl|Metrifonate}} (formerly used to treat {{wpl|helminth}} infections), and echothiophate and isoflurophate (used in opthalmology to treat glaucoma).

==How they work==
Organophosphates work by destroying nerve function in insects, humans, and other things you want to kill. Specifically, they deactivate acetylcholinesterase (ACHE or AChE), which catalyses the breakdown of certain neurotransmitters and thereby terminates synaptic transmissions. Deactivation of ACHE causes an accumulation of acetylcholine (ACh), a chemical which carries stimulating signals across synapses between neurones. An accumulation of ACh means that instead of the normal rapid pattern of stimulation and destimulation of neurones that allows rapid messages to be sent, there is overstimulation and signalling between neurones is knocked out of balance.<ref>[http://pmep.cce.cornell.edu/profiles/extoxnet/TIB/cholinesterase.html Cholinesterase Inhibition], Toxicology Information Brief, Cornell Extension Toxicology Network</ref>

In humans this results in symptoms including anxiety, headaches, convulsions, ataxia, lowered respiration and heart rate, general weakness, diarrhoeia, vomiting, visual disturbance, bronchoconstriction, bronchorrhea, convulsions, seizures, paralysis, and coma. The end result can be respiratory failure and death. They are also associated with psychological effects such as anxiety, memory impairment, irritability, and psychosis.<ref name=medscape/>

OPs can enter the body through ingestion, inhalation, or contact with skin or open wounds.<ref name=idph/> Treatment is limited, using drugs such as atrophine, which blocks the action of ACh. However the efficacy is not great and even with treatment permanent brain damage can result.<ref>{{wpa|Organophosphate poisoning}}</ref> There is no vaccine.<ref name=idph>[http://www.idph.state.il.us/bioterrorism/factsheets/organophosphate.htm Organophosphate], Illinois Department of Public Health</ref>

==Risk to humans==
===General===
There is evidence that they are harmful to brain development in fetuses, babies, and young children, which poses a particular risk to children growing up in agricultural environments where OPs are used. Research on animals suggests it is plausible that OP exposure may cause respiratory problems in children.<ref>Eskenazi B, Bradman A, Castorina R. Exposures of children to organophosphate pesticides and their potential adverse health effects. Environmental Health Perspectives. 1999;107(Suppl 3):409-419.</ref> Tests on rats suggest parathion is particularly dangerous.<ref>[http://www.ncbi.nlm.nih.gov/pubmed/16675431 Comparative developmental neurotoxicity of organophosphate insecticides: effects on brain development are separable from systemic toxicity], Slotkin TA, Levin ED, Seidler FJ, Environ Health Perspect. 2006 May;114(5):746-51.</ref> Another study found that exposure to chlorpyrifos, formerly used for indoor pest control, resulted in lower IQs in children in New York City.<ref>[http://scienceblogs.com/thepumphandle/2012/09/13/organic-shcmorganic-unless-its-your-childs-ability-to-learn-thats-impaired-by-pesticides/ "Organic, schmorganic" – unless it’s your child’s ability to learn that’s impaired by pesticides], The Pump Handle, Science Blogs, 2012</ref> However a 2013 study looking at levels of OP metabolites found no evidence of negative effects on neurobehaviour from low-level exposure (it also found that the highest levels of metabolites were in well-educated, white, married women, who presumably ate the most vegetables).<ref>[https://ehjournal.biomedcentral.com/articles/10.1186/1476-069X-12-79 Impact of low-level gestational exposure to organophosphate pesticides on neurobehavior in early infancy: a prospective study], Kimberly Yolton, Yingying Xu, Heidi Sucharew, Paul Succop, Mekibib Altaye, Ann Popelar, M Angela Montesano, Antonia M Calafat and Jane C Khoury, Environmental Health 2013 12:79 DOI: 10.1186/1476-069X-12-79</ref>

Some OPs may cause [[cancer]]. The International Agency for Research on Cancer (IARC) rates malathion and diazinon as "probably carcinogenic to humans" (Group 2A) and tetrachlorvinphos and parathion as "possibly carcinogenic to humans" (Group 2B - which is actually not a classification that requires a lot of hard evidence of risk).<ref>[https://www.iarc.fr/en/media-centre/iarcnews/pdf/MonographVolume112.pdf IARC Monographs Volume 112: evaluation of five organophosphate insecticides and herbicides], IARC press release</ref> The US Environmental Protection Agency also says parathion may be a carcinogen.<ref name=wpop/>

Because of the risk of domestic poisoning, the EPA has called for their elimination in pesticides for domestic use<ref name=natgeo>[http://news.nationalgeographic.com/news/2013/07/130718-organophosphates-pesticides-indian-food-poisoning/ Organophosphates: A Common But Deadly Pesticide], National Geographic, 2013</ref>, though there are no plans to end their use in agriculture.

There have been a number of cases of multiple deaths resulting from acute OP poisoning: 20 people in Sierra Leone died in 1986 after eating bread contaminated by OPs during transit; 25 children died in India in 2013 from eating free school meels apparently with dangerously high levels of OPs.<ref name=natgeo/> Because they are toxic they are also sometimes used for suicide.<ref>Satoh T, Hosokawa M. [http://www.ncbi.nlm.nih.gov/pubmed/10794404 Organophosphates and their impact on the global environment.] Neurotoxicology. 2000 Feb-Apr;21(1-2):223-7.</ref>

===Occupational risks===
Many people involved in agriculture, sheep dipping, and pest control work with OPs, and this has produced concerns about health risks.<ref>PG Blain, [http://oem.bmj.com/content/58/11/689.full Adverse health effects after low level exposure to organophosphates] (editorial), Occup Environ Med 2001;58:689-690 doi:10.1136/oem.58.11.689</ref> Symptoms of chronic occupational exposure include "difficulties in executive functions, psychomotor speed, verbal, memory, attention, processing speed, visual-spatial functioning, and coordination".<ref name=medscape>Kenneth D Katz, [http://emedicine.medscape.com/article/167726-overview Organophosphate Toxicity], Medscape</ref> Working with OPs is associated with an increased risk of Alzheimer's.<ref>[http://www.medscape.com/viewarticle/722040 Repeated Exposure to Pesticides Increases Alzheimer's Disease Risk], Fran Lowry, Medscape, 2010</ref>

Davies et al describe an Irish farmer suffering from chronic exposure: "His mood became markedly unstable with brief swings into both tearful depression and extreme irritability. These periods generally lasted for hours only, although against a background from time to time of more protracted periods of low-grade depression of mood. He also experienced several episodes of impulsive suicidal thinking and on one occasion 'came to' in his yard holding a loaded shotgun to his mouth." He also suffered from memory problems, hypersensitivity to perfumes, deteriorating handwriting, and other difficulties with muscular activity; he later committed suicide.<ref>Robert Davies, Ghouse Ahmed & Tegwedd Freer, [http://apt.rcpsych.org/content/aptrcpsych/6/3/187.full.pdf Chronic exposure to organophosphates: background and clinical picture], Advances in Psychiatric Treatment (2000), vol. 6, pp. 187–192</ref>

===Residue in food===
The chief advantage of OPs over other pesticides is that they degrade rapidly in the environment, which means that soon after use they break down into harmless compounds, and thus won't hang around forever to kill your children and your children's children.

But although they degrade, they do not disappear completely, and small amounts are permitted as residue on crops.<ref name=natgeo/> Levels from residue on food are far less than the amount a farmer will be exposed to during food production.

Research has linked OP exposure from pesticides to reduced [[IQ]]s in children. Foods particularly at risk include green beans (snap beans), watermelon, and raw tomatoes, with toddlers particularly at risk - and even though some developed nations impose tight limits on OP usage, many foods are imported from countries with less strict regulations.<ref>[https://www.sciencenews.org/blog/science-public/because-some-foods-carry-organophosphate-residues Because some foods carry organophosphate residues], Science News, 2011</ref>

Organophosphates are prohibited by [[organic farming]] standards.

===ADHD===
OPs act on acetylcholinesterase in the nervous system, and acetylcholinesterase is closely related to processes implicated in ADHD.

A 2010 study showed that levels in children's urine of dialkyl phosphates, a breakdown product of OPs, correlated with ADHD. The study concluded: "These findings support the hypothesis that organophosphate exposure, at levels common among US children, may contribute to ADHD prevalence. Prospective studies are needed to establish whether this association is causal."<ref>[http://pediatrics.aappublications.org/content/early/2010/05/17/peds.2009-3058 Attention-Deficit/Hyperactivity Disorder and Urinary Metabolites of Organophosphate Pesticides]. Maryse F. Bouchard, David C. Bellinger, Robert O. Wright, Marc G. Weisskopf, Pediatrics May 2010, peds.2009-3058; DOI: 10.1542/peds.2009-3058</ref>

==Nerve agents==
Because of how they work, OPs can also be used as a chemical weapon, uses pioneered by the Germans and British before and during [[World War Two]]. Sarin, Tabun, Soman, and VX are examples of OP nerve agents (the first 3 are German, VX is Britain's contribution).

OP nerve agents were used by [[Saddam Hussein]] in the 1980s and in the Syrian civil war in the 2010s. Sarin was also used by [[Aum Shinrikyo]] in their 1995 Tokyo subway attack.

==Environmental risk==
Many OPs are highly toxic to birds, fish, and bees.<ref>[http://edis.ifas.ufl.edu/pi087 Pesticide Toxicity Profile: Organophosphate Pesticides], University of Florida Electronic Data Information Source</ref>

Although another group of pesticides, nicotinoids, is most strongly associated with [[colony collapse disorder]] (dead bees), some OP pesticides are also toxic to bees.<ref>{{wpa|Pesticide toxicity to bees}}</ref> Ironically, nicotinoids were introduced as replacements to OPs because they were believed to be less toxic to wildlife.<ref>[http://www.forbes.com/sites/jonentine/2013/04/11/science-collapse-disorder-the-real-story-behind-neonics-and-mass-bee-deaths/#5846fee9591e Science Collapse Disorder -- The Real Story Behind Neonics And Mass Bee Deaths], Jon Entine, Forbes, 2013</ref> But as yet there's no evidence to implicate OPs in the recent decline in bee populations.

===Zika===
This issue has reached new levels of controversy with the use of organophosphate spraying to combat the [[Zika]] virus, particularly when done in the USA (other countries with greater prevalence of mosquito-borne diseases face different cost-benefit trade-offs). For this purpose the American CDC in some cases recommends aerial spraying with temephos against larval mosquitos and chlorpyrifos, malathion, and naled against adult mosquitos, as part of a strategy that also involves physically removing breeding sites (stagnant water) and testing for insecticide resistance prior to use.<ref>[http://www.cdc.gov/zika/public-health-partners/vector-control-us.html Interim CDC Recommendations for Zika Vector Control in the Continental United States], CDC</ref> ''Aedes aegypti'', the mosquito which spreads Zika and many other diseases, is hard to combat because it can breed in almost any small pool or vessel of stagnant water, so targetting waterways from the ground is ineffective.<ref name=mechanic>[http://www.motherjones.com/politics/2016/05/stop-freaking-out-zika-olympics-aedes-aegypti Should Americans Be Panicking About Zika?], Michael Mechanic, Mother Jones, May 31, 2016</ref>

In Florida, spraying has involved a variety of pesticides including the organophosphate naled.<ref>[http://www.reuters.com/article/us-health-zika-insecticide-idUSKCN10E06Q Florida to begin aerial spraying of insecticides to control Zika], Reuters, Aug 3, 2016</ref> Inevitably critics of organophosphates have been getting very angry, using studies of risks from sustained agricultural pesticide use to argue against spraying against mosquitos, despite the considerable differences in pesticide levels and length of exposure (remember, organophosphates break down quickly after use), and without any attempt to compare risks from OPs against risks from Zika.<ref name=rappaport>[https://jonrappoport.wordpress.com/2016/08/13/bombshell-zika-fraud-leads-to-mosquito-spraying-and-autism/ Bombshell: Zika fraud leads to mosquito spraying and autism], Jon Rappaport, Aug 13, 2016</ref> The EPA states that there is no danger from naled spraying even if it is used multiple times and a toddler eats some grass or soil afterwards.<ref>[https://www.epa.gov/mosquitocontrol/naled-mosquito-control Naled for Mosquito Control], US EPA</ref> On the other hand, it's by no means clear that Zika is a significant public health hazard in the USA because Americans spend a lot of time indoors and public health officials tend to clamp down quickly on any outbreaks that do occur, so regardless of the danger of organophosphates, widespread spraying may not be necessary.<ref name=mechanic/>

==Conclusion==
Any pesticide is likely to be somewhat toxic, because that's what they do. Pesticides are necessary when growing vegetables, even in [[organic farming]] where supposedly more wholesome organic pesticides are used. Eating vegetables is good for you and for the vast number of livestock who depend on fodder crops for most of their diet. Killing insects which spread diseases is also a good thing. So balance is required. And today, OPs are increasingly being taken off the market and replaced by nicotinoids, which appear less damaging to the environment although still not entirely benign: pesticide manufacturers and agronomists are always looking for better pesticides.

The evidence seems clear that exposure to high level of organophosphates is dangerous, particularly over a long period of time: this can occur in agriculture, when using them as domestic pesticides, or where poor regulation means large amounts are present in food. There is not sufficient evidence to say that there is a risk from exposure to the very small levels found in food grown in those countries that control the use of organophosphates and impose limits on residue, although the single study showing a link to ADHD needs further investigation.

==References==
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