Chlorpyrifos: Difference between revisions

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| ImageFile = Chlorpyrifos.

| ImageFile1 = Chlorpyrifos-3D-vdW.png

| PIN = ''O'',''O''-Diethyl ''O''-(3,5,6-trichloropyridin-2-yl) phosphorothioate

| OtherNames = Brodan, Bolton insecticide, Chlorpyrifos-ethyl, Cobalt, Detmol UA, Dowco 179, Dursban, Empire, Eradex, Hatchet, Lorsban, Nufos, Paqeant, Piridane, Scout, Stipend, Tricel, Warhawk, others<ref>{{Cite web |title=California Department of Pestidicide Regulation – Chlorpyrifos Product List May 2015 |url=http://www.cdpr.ca.gov/docs/registration/reevaluation/chemicals/chlorpyrifos_list.pdf |url-status=dead |archive-url=https://web.archive.org/web/20190101111816/https://www.cdpr.ca.gov/docs/registration/reevaluation/chemicals/chlorpyrifos_list.pdf |archive-date=1 January 2019 |access-date=30 March 2017}}</ref>

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| C=9|H=11|Cl=3|N=1|O=3|P=1|S=1

| Appearance = Colorless crystals<ref name="agrochemicals" />

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| Density = 1.398 g/cm³ (43.5°C)

| MeltingPtC = 43

| MeltingPt_ref =<ref name="hand">{{Cite book |last=Lide |first=David R. |title=Handbook of Chemistry and Physics |publisher=CRC Press |year=2015–2016 |isbn=9781482208672 |edition=96 |location=Boca Raton, FL |pages=3–122 |chapter=Physical Constants of Organic Compounds}}</ref>

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| LogP=4.96 (octanol/water)<ref>Sangster J; LOGKOW Databank. Sangster Res. Lab., Montreal Quebec, Canada (1994)</ref>

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| LD50 = {{ubl|135 mg/kg (rat, oral)|202 mg/kg (rat, dermal)<ref>{{cite web |title=4Farmers Chlorpyrifos 500 Safety Data Sheet |url=https://4farmers.com.au/wp-content/uploads/2018/06/3_chlorpyrifos-500-ec_4FARMERS-CHLORPYRIFOS-500-INSECTICIDE.pdf |website=www.4farmers.com.au |publisher=4Farmers Australia |location=Perth, Australia |date=5 September 2016}}</ref>}}

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| PEL = none<ref name="PGCH">{{PGCH|0137}}</ref>

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| REL = TWA 0.2 mg/m³ ST 0.6 mg/m³ [skin]<ref name=PGCH/>

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'''Chlorpyrifos''' ('''CPS'''), also known as '''chlorpyrifos ethyl''', is an [[organophosphate pesticide]] that has been used on crops, and animals in buildings, and in other settings, to kill several [[pest (organism)|pest]]s, including insects and worms. It acts on the nervous systems of insects by [[acetylcholinesterase inhibitor|inhibiting the acetylcholinesterase enzyme]].<ref name="IRAC-MoA-2020">{{Cite web |date=2020-09-16 |title=Interactive MoA Classification |url=http://irac-online.org/modes-of-action/ |access-date=2021-04-01 |website=[[Insecticide Resistance Action Committee]]}}</ref><ref name="Sparks-et-al-2020">{{Cite journal |last1=Sparks |first1=Thomas C. |last2=Crossthwaite |first2=Andrew J. |last3=Nauen |first3=Ralf |last4=Banba |first4=Shinichi |last5=Cordova |first5=Daniel |last6=Earley |first6=Fergus |last7=Ebbinghaus-Kintscher |first7=Ulrich |last8=Fujioka |first8=Shinsuke |last9=Hirao |first9=Ayako |last10=Karmon |first10=Danny |last11=Kennedy |first11=Robert |last12=Nakao |first12=Toshifumi |last13=Popham |first13=Holly J.R. |last14=Salgado |first14=Vincent |last15=Watson |first15=Gerald B. |year=2020 |title=Insecticides, biologics and nematicides: Updates to IRAC's mode of action classification - a tool for resistance management |journal=Pesticide Biochemistry and Physiology |publisher=[[Elsevier]] |volume=167 |page=104587 |bibcode=2020PBioP.16704587S |doi=10.1016/j.pestbp.2020.104587 |issn=0048-3575 |pmid=32527435 |s2cid=218928832 |doi-access=free |last16=Wedel |first16=Barbara J. |last17=Wessels |first17=Frank J.}}</ref> Chlorpyrifos was patented in 1966 by [[Dow Chemical Company]].<ref>{{US Patent|3244586}}</ref>

Chlorpyrifos is considered moderately hazardous to humans (Class II) by the [[World Health Organization]] based on acute toxicity information dating to 1999.<ref>{{Cite report |url=https://www.who.int/publications/i/item/9789240005662 |title=The WHO Recommended Classification of Pesticides by Hazard and Guidelines to Classification 2019 |last=World Health Organization |date=2019 |publisher=World Health Organization}}</ref> Exposure surpassing recommended levels has been linked to neurological effects, persistent developmental disorders, and [[autoimmune disorder]]s. Exposure during pregnancy may harm the mental development of children.<ref name="sa">{{Cite journal |date=21 August 2012 |title=Common Insecticide May Harm Boys' Brains More Than Girls |url=http://www.scientificamerican.com/article.cfm?id=common-insecticide-may-harm-boys-brains-more-than-girls |journal=Scientific American |author-first=Brett |author-last=Israel}}</ref>

In the [[United Kingdom]], the use of chlorpyrifos was banned as of 1 April 2016 (with one minor exception).<ref name="Grainews">{{Cite news |date=March 30, 2016 |title=UK to ban sales and use of chlorpyrifos from April |url=https://news.agropages.com/News/NewsDetail---17532.htm |access-date=1 April 2022 |work=Grainews |language=en}}</ref>

As of 2020, chlorpyrifos and chlorpyrifos-methyl were banned throughout the [[European Union]], where they may no longer be used.

<ref name="Eurofins">{{Cite web |date=August 2020 |title=EU-Wide ban of Chlorpyrifos and Chlorpyrifos-methyl |url=https://www.eurofins.de/food-analysis/food-news/food-testing-news/eu-wide-ban-of-chlorpyrifos-and-chlorpyrifos-methyl/ |url-status=dead |archive-url=https://web.archive.org/web/20220616221450/https://www.eurofins.de/food-analysis/food-news/food-testing-news/eu-wide-ban-of-chlorpyrifos-and-chlorpyrifos-methyl/ |archive-date=16 June 2022 |access-date=31 March 2022 |website=Eurofins Scientific}}</ref> The EU also applied to have chlorpyrifos listed as a persistent organic pollutant under the [[Stockholm Convention on Persistent Organic Pollutants]].<ref name="Meshkat">{{Cite news |last=Meshkat |first=Nazanin |date=26 July 2021 |title=NGOs call on Health Canada to expedite ban on chlorpyrifos |url=https://www.theglobeandmail.com/canada/article-ngos-call-on-health-canada-for-quicker-ban-on-chlorpyrifos/ |access-date=1 April 2022 |work=The Globe and Mail |language=en-CA}}</ref>

As of August 18, 2021, the U.S. Environmental Protection Agency (EPA) announced a ban on the use of chlorpyrifos on food crops in the United States.<ref name="Trager">{{Cite news |last=Trager |first=Rebecca |date=27 August 2021 |title=US bans chlorpyrifos on all food crops |url=https://www.chemistryworld.com/news/us-bans-chlorpyrifos-on-all-food-crops/4014261.article |access-date=31 March 2022 |work=Chemistry World |language=en}}</ref><ref name="Solomon">{{Cite news |last=Solomon |first=Gina |date=August 24, 2021 |title=The EPA is banning chlorpyrifos, a pesticide widely used on food crops, after 14 years of pressure from environmental and labor groups |url=https://theconversation.com/the-epa-is-banning-chlorpyrifos-a-pesticide-widely-used-on-food-crops-after-14-years-of-pressure-from-environmental-and-labor-groups-166485 |access-date=1 April 2022 |work=The Conversation |language=en}}</ref><ref name="Romo">{{Cite news |last=Romo |first=Vanessa |date=18 August 2021 |title=EPA Will Ban A Farming Pesticide Linked To Health Problems In Children |url=https://www.npr.org/2021/08/18/1029144997/epa-will-ban-a-farming-pesticide-linked-to-health-problems-in-children |access-date=1 April 2022 |work=NPR |language=en}}</ref> Most home uses of chlorpyrifos had already been banned in the U.S. and Canada since 2001.<ref name=sa/><ref name="Canada">{{Cite news |date=19 May 2021 |title=Canada Quietly Bans Chlorpyrifos, While EPA's 60-Day Deadline For Action Rapidly Approaches |url=https://beyondpesticides.org/dailynewsblog/2021/05/canada-quietly-bans-chlorpyrifos-while-epas-60-day-deadline-for-action-rapidly-approaches/ |access-date=1 April 2022 |work=Beyond Pesticides Daily News Blog |language=en}}</ref>

It is banned in several other countries and jurisdictions as well. The chlorpyrifos ban on food crops is the result of a 1999 lawsuit filed by NRDC to force the EPA to take action on the riskiest pesticides, as well as five additional successful court orders obtained by Earthjustice to force the EPA to take action on a 2007 petition to ban chlorpyrifos filed by [[Natural Resources Defense Council]] and the [[Pesticide Action Network]] of North America (PANNA).<ref>{{Cite web |last1=April 20 |last2=Sass |first2=2022 Jennifer |date=20 April 2022 |title=EPA Bans Chlorpyrifos On Food Crops |url=https://www.nrdc.org/experts/jennifer-sass/epa-bans-chlorpyrifos-food-crops |access-date=2022-09-22 |website=NRDC |language=en}}</ref>

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== Synthesis ==

The industrial synthesis of chlorpyrifos ('''3''') is made by reacting [[3,5,6-trichloro-2-pyridinol]] (TCPy) ('''1''') with [[diethyl phosphorochloridothioate|''O'',''O''-diethyl phosphorochloridothioate]] ('''2'''):<ref>{{Cite book |last=Thomas A. Unger |title=Pesticide Synthesis Handbook |date=1996 |publisher=William Andrew |isbn=0-8155-1853-6 |page=313}}</ref>

[[File:Industrial synthesis of chlorpyrifos.svg|frameless|upright=3|center|Industrial synthesis of chlorpyrifos]]

== Uses ==

[[File:Chlorpyrifos USA 2011.png|thumb|Use in the USA]]

Chlorpyrifos was used in about 100 countries around the world to control insects in agricultural, residential, and commercial settings.<ref name="sf">{{Cite news |last=Bob Egelko |date=9 May 2019 |title=Newsom banning chemical on crops: Action outlaws pesticide Trump EPA wants to save |work=San Francisco Chronicle |page=A1}}</ref> Its use in residential applications is restricted in multiple countries. According to Dow, chlorpyrifos is registered for use in nearly 100 countries and is annually applied to approximately 8.5&nbsp;million crop acres.<ref>{{Cite web |last=The Dow Chemical Company |title=Chlorpyrifos and Responsible Use |url=http://www.chlorpyrifos.com/benefits-and-use/use/responsible-use.htm |url-status=dead |archive-url=https://web.archive.org/web/20140523101834/http://www.chlorpyrifos.com/benefits-and-use/use/responsible-use.htm |archive-date=23 May 2014 |access-date=24 July 2014}}</ref> The crops with the most usefulness include [[cotton]], [[Maize|corn]], [[almond]]s, and fruit trees, including oranges, bananas, and apples.<ref>{{Cite web |title=NASS Agricultural Chemical Database |url=http://www.pestmanagement.info/nass/app_usage.cfm |url-status=dead |archive-url=https://web.archive.org/web/20110927225357/http://www.pestmanagement.info/nass/app_usage.cfm |archive-date=27 September 2011 |access-date=20 November 2011 |publisher=Pestmanagement.info}}</ref>

Chlorpyrifos was first registered for use in the United States in 1965 for the control of [[foliage]] and soil-born insects.<ref name=":0" /> The chemical became widely used in residential settings, on golf course turf, as a structural termite control agent, and in agriculture. Most residential use of chlorpyrifos has been phased out in the United States; however, agricultural use remains common.<ref name=":0" />

EPA estimated that, between 1987 and 1998, about 21 million pounds of chlorpyrifos were used annually in the US.<ref name=":0">{{Cite web |last=U.S. EPA |date=2002 |title=Interim Reregistration Eligibility Decision for Chlorpyrifos |url=http://nepis.epa.gov/Exe/ZyPURL.cgi?Dockey=200008BM.TXT |archive-url=https://web.archive.org/web/20121119113014/http://www.epa.gov/oppsrrd1/REDs/chlorpyrifos_ired.pdf |archive-date=19 November 2012 |access-date=28 February 2016}}</ref> In 2001, chlorpyrifos ranked 15th among pesticides used in the United States, with an estimated 8 to 11 million pounds applied. In 2007, it ranked 14th among pesticide ingredients used in agriculture in the United States.<ref>{{Cite web |last1=Grube |first1=Arthur |last2=Donaldson |first2=David |last3=Kiely |first3=Timothy |last4=Wu |first4=La |date=2011 |title=Pesticide Industry Sales and Usage Report: 2006 and 2007 Market Estimates |url=http://www.epa.gov/opp00001/pestsales/07pestsales/market_estimates2007.pdf |archive-url=https://web.archive.org/web/20150318232514/http://www.epa.gov/opp00001/pestsales/07pestsales/market_estimates2007.pdf |archive-date=18 March 2015 |access-date=24 July 2014 |publisher=U.S. EPA}}</ref>

=== Application ===

Chlorpyrifos is normally supplied as a 23.5% or 50% liquid concentrate. The recommended concentration for direct-spray pin point application is 0.5% and for wide area application a 0.03–0.12% mix is recommended (US).<ref>{{Cite web |title=Dursban Pro specimen label |url=http://www.cdms.net/ldat/ld0AT004.pdf |archive-url=https://web.archive.org/web/20090824081746/http://www.cdms.net/ldat/ld0AT004.pdf |archive-date=24 August 2009}}</ref><ref>{{Cite web |title=Strike-Out 500WP label |url=http://www.farmoz.com.au/label/farmoz/STRIKE_OUT_500WP_16103844.pdf |archive-url=https://web.archive.org/web/20110311064523/http://www.farmoz.com.au/label/farmoz/STRIKE_OUT_500WP_16103844.pdf |archive-date=11 March 2011}}</ref>

== ==

Chlorpyrifos [[toxicokinetics|enters insects]] through several routes. Simon et al. 1998<ref>{{Cite journal |last1=Simon |first1=David |last2=Helliwell |first2=Stuart |last3=Robards |first3=Kevin |date=1998 |title=Analytical chemistry of chlorpyrifos and diuron in aquatic ecosystems |journal=Analytica Chimica Acta |language=en |volume=360 |issue=1–3 |pages=1–16 |bibcode=1998AcAC..360....1S |doi=10.1016/S0003-2670(97)00680-6}}</ref> report that insects are exposed to chlorpyrifos through ingesting treated [[insect herbivory|food plants]]. They also found it to enter through [[skin]] and [[biological membrane|membranes]] of the [[respiratory system (insect)|respiratory system]].<ref name="Chishti-et-al-2013">{{Cite journal |last1=Chishti |first1=Zia |last2=Hussain |first2=Sarfraz |last3=Arshad |first3=Khaliq R. |last4=Khalid |first4=Azeem |last5=Arshad |first5=Muhammad |year=2013 |title=Microbial degradation of chlorpyrifos in liquid media and soil |journal=[[Journal of Environmental Management]] |publisher=[[Elsevier]] |volume=114 |pages=372–380 |bibcode=2013JEnvM.114..372C |doi=10.1016/j.jenvman.2012.10.032 |issn=0301-4797 |pmid=23176983}}</ref>

=== Mechanism of action ===

Like other [[organophosphate pesticide]]s chlorpyrifos acts by [[acetylcholinesterase inhibitor|acetylcholinesterase inhibition]].<ref name="IRAC-MoA-2020" /><ref name="Sparks-et-al-2020" />

==Human toxicity==

Chlorpyrifos exposure may lead to [[acute toxicity]] at higher doses. [[Chronic condition|Persistent health effects]] follow acute poisoning or from long-term exposure to low doses, and [[developmental]] effects appear in [[fetuses]] and children even at very small doses.<ref>{{Cite journal |last1=Rauh |first1=Virginia A. |last2=Perera |first2=Frederica P. |last3=Horton |first3=Megan K. |last4=Whyatt |first4=Robin M. |last5=Bansal |first5=Ravi |last6=Hao |first6=Xuejun |last7=Liu |first7=Jun |last8=Barr |first8=Dana Boyd |last9=Slotkin |first9=Theodore A. |last10=Peterson |first10=Bradley S. |date=15 May 2012 |title=Brain anomalies in children exposed prenatally to a common organophosphate pesticide |journal=PNAS |volume=109 |issue=20 |pages=7871–7876 |bibcode=2012PNAS..109.7871R |doi=10.1073/pnas.1203396109 |pmc=3356641 |pmid=22547821 |doi-access=free}}</ref>

===Acute health effects===

For acute effects, the [[World Health Organization]] classifies chlorpyrifos as Class II: moderately hazardous.<ref>{{Cite report |url=https://www.who.int/ipcs/publications/pesticides_hazard/en/ |title=The WHO Recommended Classification of Pesticides by Hazard and Guidelines to Classifi³cation 2009 |last=World Health Organization |date=2010 |publisher=World Health Organization |access-date=9 July 2014 |archive-url=https://web.archive.org/web/20040708001948/http://www.who.int/ipcs/publications/pesticides_hazard/en/ |archive-date=8 July 2004 |url-status=dead}}</ref> The oral [[median lethal dose|LD50]] in experimental animals is 32 to 1000&nbsp;mg/kg. The dermal LD50 in rats is greater than 2000&nbsp;mg/kg and 1000 to 2000&nbsp;mg/kg in rabbits. The 4-hour inhalation of LC50 for chlorpyrifos in rats is greater than 200&nbsp;mg/m³.<ref>{{Cite web |title=Chlorpyrifos |url=http://pmep.cce.cornell.edu/profiles/extoxnet/carbaryl-dicrotophos/chlorpyrifos-ext.html |access-date=20 November 2011 |publisher=Pmep.cce.cornell.edu}}</ref>

====Symptoms of acute exposure====

Acute poisoning results mainly from interference with the [[acetylcholine]] [[neurotransmission]] pathway, leading to a range of [[neuromuscular]] symptoms. Relatively mild poisoning can result in eye-watering, increased saliva and sweating, nausea, and headache. Intermediate exposure may lead to muscle spasms or weakness, vomiting, or diarrhea, and impaired vision. Symptoms of severe poisoning include seizures, unconsciousness, paralysis, and suffocation from lung failure.<ref name="Christensen2009">{{Cite web |last1=Christensen |first1=K. |last2=Harper |first2=B. |last3=Luukinen |first3=B. |last4=Buhl |first4=K. |last5=Stone |first5=D. |date=2009 |title=Chlorpyrifos Technical Fact Sheet |url=http://npic.orst.edu/factsheets/archive/chlorptech.html#acute |access-date=3 July 2014 |publisher=National Pesticide Information Center}}</ref>

Children are more likely to experience muscle weakness rather than twitching; excessive saliva rather than sweat or tears; seizures; and sleepiness or coma.<ref name="Christensen2009" />

====Frequency of acute exposure====

Acute poisoning is probably most common in agricultural areas in Asia, where many small farmers are affected.<ref name="Eddleston2000">{{Cite journal |last=Eddleston |first=M. |date=1 November 2000 |title=Patterns and problems of deliberate self-poisoning in the developing world |journal=QJM |volume=93 |issue=11 |pages=715–731 |doi=10.1093/qjmed/93.11.715 |issn=1460-2725 |pmid=11077028 |doi-access=free}}</ref> Poisoning may be due to occupational or accidental exposure or intentional self-harm. Precise numbers of chlorpyrifos poisonings globally are not available.<ref name="Gunnell2007">{{Cite journal |last1=Gunnell |first1=David |last2=Eddleston |first2=Michael |last3=Phillips |first3=Michael R. |last4=Konradsen |first4=Flemming |date=21 December 2007 |title=The global distribution of fatal pesticide self-poisoning: Systematic review |journal=BMC Public Health |volume=7 |issue=1 |pages=357 |doi=10.1186/1471-2458-7-357 |issn=1471-2458 |pmc=2262093 |pmid=18154668 |doi-access=free}}</ref> Pesticides are used in an estimated 200,000+ suicides annually with tens of thousands due to chlorpyrifos. Organophosphates are thought to constitute two-thirds of ingested pesticides in rural Asia. Chlorpyrifos is among the commonly used pesticides used for self-harm.<ref name="Eddleston2000" /><ref name="Gunnell2007" /><ref>{{Cite journal |last1=Eddleston |first1=Michael |last2=Eyer |first2=Peter |last3=Worek |first3=Franz |last4=Mohamed |first4=Fahim |last5=Senarathna |first5=Lalith |last6=von Meyer |first6=Ludwig |last7=Juszczak |first7=Edmund |last8=Hittarage |first8=Ariyasena |last9=Azhar |first9=Shifa |last10=Dissanayake |first10=Wasantha |last11=Sheriff |first11=M. H. Rezvi |last12=Szinicz |first12=Ladislaus |last13=Dawson |first13=Andrew H. |last14=Buckley |first14=Nick A. |date=28 October 2005 |title=Differences between organophosphorus insecticides in human self-poisoning: a prospective cohort study |journal=The Lancet |volume=366 |issue=9495 |pages=1452–1459 |doi=10.1016/S0140-6736(05)67598-8 |issn=0140-6736 |pmid=16243090 |s2cid=13923877}}</ref>

In the US, the number of incidents of chlorpyrifos exposure reported to the US [[National Pesticide Information Center]] shrank sharply from over 200 in the year 2000 to less than 50 in 2003, following the residential ban.<ref>{{Cite journal |last1=Stone |first1=David L. |last2=Sudakin |first2=Daniel L. |last3=Jenkins |first3=Jeffrey J. |date=20 April 2009 |title=Longitudinal trends in organophosphate incidents reported to the National Pesticide Information Center, 1995–2007 |journal=Environmental Health |volume=8 |issue=1 |pages=18 |bibcode=2009EnvHe...8...18S |doi=10.1186/1476-069X-8-18 |issn=1476-069X |pmc=2673208 |pmid=19379510 |doi-access=free}}</ref>

====

Poisoning is treated with [[atropine]] and simultaneously with [[oxime]]s such as [[pralidoxime]].<ref name="Buckley2011">{{Cite journal |last1=Buckley |first1=Nick A. |last2=Eddleston |first2=Michael |last3=Li |first3=Yi |last4=Bevan |first4=Marc |last5=Robertson |first5=Jane |date=2011 |title=Oximes for acute organophosphate pesticide poisoning |journal=Cochrane Database of Systematic Reviews |publisher=John Wiley & Sons, Ltd |issue=2 |pages=CD005085 |doi=10.1002/14651858.CD005085.pub2 |pmid=21328273}}</ref> Atropine blocks [[acetylcholine]] from binding with [[muscarinic receptor]]s, which reduces the pesticide's impact. However, atropine does not affect acetylcholine at [[nicotinic receptor]]s and thus is a partial treatment. Pralidoxime is intended to reactivate [[acetylcholinesterase]], but the benefit of oxime treatment is questioned.<ref name="Buckley2011" /> A [[randomized controlled trial]] (RCT) supported the use of higher doses of pralidoxime rather than lower doses.<ref>{{Cite journal |last1=Pawar |first1=Kirti S |last2=Bhoite |first2=Ramesh R. |last3=Pillay |first3=Chandrakant P. |last4=Chavan |first4=Sujata C. |last5=Malshikare |first5=Dhananjay S. |last6=Garad |first6=Saraswati G. |date=22 December 2006 |title=Continuous pralidoxime infusion versus repeated bolus injection to treat organophosphorus pesticide poisoning: a randomised controlled trial |journal=The Lancet |volume=368 |issue=9553 |pages=2136–2141 |doi=10.1016/S0140-6736(06)69862-0 |issn=0140-6736 |pmid=17174705 |s2cid=10499125}}</ref> A subsequent double-blind RCT, that treated patients who self-poisoned, found no benefit of pralidoxime, including specifically in chlorpyrifos patients.<ref>{{Cite journal |last1=Eddleston |first1=Michael |last2=Eyer |first2=Peter |last3=Worek |first3=Franz |last4=Juszczak |first4=Edmund |last5=Alder |first5=Nicola |last6=Mohamed |first6=Fahim |last7=Senarathna |first7=Lalith |last8=Hittarage |first8=Ariyasena |last9=Azher |first9=Shifa |last10=Jeganathan |first10=K. |last11=Jayamanne |first11=Shaluka |last12=von Meyer |first12=Ludwig |last13=Dawson |first13=Andrew H. |last14=Sheriff |first14=Mohamed Hussain Rezvi |last15=Buckley |first15=Nick A. |date=June 2009 |title=Pralidoxime in acute organophosphorus insecticide poisoning—A randomised controlled trial |journal=PLOS Medicine |volume=6 |issue=6 |pages=e1000104 |doi=10.1371/journal.pmed.1000104 |issn=1549-1277 |pmc=2696321 |pmid=19564902 |doi-access=free}}</ref>

===Tourist deaths===

Chlorpyrifos poisoning was described by New Zealand scientists as the likely cause of death of several tourists in [[Chiang Mai]], Thailand who developed [[myocarditis]] in 2011.<ref>{{Cite web |title=Toxin 'likely' cause of Sarah Carter's death |url=http://www.stuff.co.nz/world/asia/4976814/Toxin-likely-cause-of-Sarah-Carters-death |access-date=8 May 2011 |publisher=stuff.co.nz}}</ref><ref>{{Cite news |title=Sarah Carter's likely cause of death – insecticide |url=http://www.3news.co.nz/Sarah-Carters-likely-cause-of-death---insecticide/tabid/423/articleID/210265/Default.aspx |url-status=dead |archive-url=https://web.archive.org/web/20110914020756/http://www.3news.co.nz/Sarah-Carters-likely-cause-of-death---insecticide/tabid/423/articleID/210265/Default.aspx |archive-date=14 September 2011 |access-date=8 May 2011 |work=3 News}}</ref><ref>{{Cite news |date=9 May 2011 |title=Thailand death cover-up suspected |url=http://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=10724455 |work=NZ Herald Online}}</ref> Thai investigators came to no conclusion on the subject,<ref>{{Cite news |last=Hayden Donnell |date=11 May 2011 |title=Thai experts: Bed bug spray didn't kill Kiwi tourist |url=http://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=10724871 |access-date=11 May 2011 |work=The New Zealand Herald}}</ref> but maintain that chlorpyrifos was not responsible and that the deaths were not linked.<ref>{{Cite news |date=26 May 2011 |title=Thais deny tourists' deaths linked |url=http://www.stuff.co.nz/dominion-post/news/5055760/Thais-deny-tourists-deaths-linked |access-date=26 May 2011 |work=Dominion Post}}</ref>

===Long term===

====Development====

Epidemiological and experimental animal studies suggest that infants and children are more susceptible than adults to the effects of low-dose exposure.<ref name="Flaskos2012">{{Cite journal |last=Flaskos |first=J. |date=25 February 2012 |title=The developmental neurotoxicity of organophosphorus insecticides: A direct role for the oxon metabolites |journal=Toxicology Letters |volume=209 |issue=1 |pages=86–93 |doi=10.1016/j.toxlet.2011.11.026 |issn=0378-4274 |pmid=22155227}}</ref><ref name="Timofeeva2010">{{Cite book |last1=Timofeeva |first1=Olga A. |title=Hayes' Handbook of Pesticide Toxicology |last2=Levin |first2=Edward D. |date=2010 |publisher=Academic Press |isbn=978-0-12-374367-1 |editor-last=R. Krieger |edition=Third |location=New York |pages=837–846 |chapter=Lasting Behavioral Consequences of Organophosphate Pesticide Exposure During Development |doi=10.1016/B978-0-12-374367-1.00033-1}}</ref> Chlorpyrifos has been suggested to have negative impacts on cognitive functions in the developing brain.<ref name=":1">{{Cite web |date=11 September 2015 |title=Chlorpyrifos {{!}} Pesticide Action Network |url=http://www.panna.org/resources/chlorpyrifos-facts |access-date=15 October 2018 |website=www.panna.org |language=en}}</ref> The young have a decreased capacity to detoxify chlorpyrifos and its [[metabolites]]. It is suggested that adolescents differ from adults in the metabolism of these compounds due to the maturation of organs in adolescents.<ref>{{Cite journal |last1=Smith |first1=Jordan Ned |last2=Hinderliter |first2=Paul M. |last3=Timchalk |first3=Charles |last4=Bartels |first4=Michael J. |last5=Poet |first5=Torka S. |date=1 August 2014 |title=A human life-stage physiologically based pharmacokinetic and pharmacodynamic model for chlorpyrifos: Development and validation |journal=Regulatory Toxicology and Pharmacology |language=en |volume=69 |issue=3 |pages=580–597 |doi=10.1016/j.yrtph.2013.10.005 |issn=0273-2300 |pmid=24200834}}</ref> This results in disruption in nervous system developmental processes, as observed in animal experiments.<ref name="Flaskos2012" /> There are several studies observed in animals that show that chlorpyrifos alters the expression of essential genes that assist in the development of the brain.<ref name=":1" />

''Human studies'': In multiple [[epidemiology|epidemiological]] studies, chlorpyrifos exposure during gestation or childhood has been linked with lower [[birth weight]] and neurological changes such as slower motor development and attention problems.<ref name="Timofeeva2010" /><ref>{{Cite web |last=Rauh |first=Virginia |title=7-Year Neurodevelopmental Scores and Prenatal Exposure to Chlorpyrifos, a Common Agricultural Pesticide |url=http://ccceh.org/wp-content/uploads/2012/01/RauhEHPApril2011_2.pdf |url-status=dead |archive-url=https://wayback.archive-it.org/all/20160202224822/http://ccceh.org/wp-content/uploads/2012/01/RauhEHPApril2011_2.pdf |archive-date=2 February 2016 |access-date=8 April 2018 |website=ccceh.org |publisher=Columbia Center for Children's Environmental Health}}</ref> Children with prenatal exposure to chlorpyrifos have been shown to have lower IQs.<ref>{{Cite journal |last1=Bouchard |first1=Maryse F. |last2=Chevrier |first2=Jonathan |last3=Harley |first3=Kim G. |last4=Kogut |first4=Katherine |last5=Vedar |first5=Michelle |last6=Calderon |first6=Norma |last7=Trujillo |first7=Celina |last8=Johnson |first8=Caroline |last9=Bradman |first9=Asa |date=2011 |title=Prenatal Exposure to Organophosphate Pesticides and IQ in 7-Year-Old Children |journal=Environmental Health Perspectives |language=en |volume=119 |issue=8 |pages=1189–1195 |doi=10.1289/ehp.1003185 |issn=0091-6765 |pmc=3237357 |pmid=21507776|bibcode=2011EnvHP.119.1189B }}</ref> They have also been shown to have a higher chance of developing autism, attention deficit problems, and developmental disorders.<ref name="Rauh 2011 1196–1201">{{Cite journal |last1=Rauh |first1=Virginia |last2=Arunajadai |first2=Srikesh |last3=Horton |first3=Megan |last4=Perera |first4=Frederica |last5=Hoepner |first5=Lori |last6=Barr |first6=Dana B. |last7=Whyatt |first7=Robin |date=2011 |title=Seven-Year Neurodevelopmental Scores and Prenatal Exposure to Chlorpyrifos, a Common Agricultural Pesticide |journal=Environmental Health Perspectives |language=en |volume=119 |issue=8 |pages=1196–1201 |doi=10.1289/ehp.1003160 |issn=0091-6765 |pmc=3237355 |pmid=21507777|bibcode=2011EnvHP.119.1196R }}</ref> A cohort of 7-year-old children was studied for neurological damage from prenatal exposure to chlorpyrifos. The study determined that the exposed children had deficits in working memory and full scale intelligence quotient (IQ).<ref name="Rauh 2011 1196–1201" /> In a study on groups of Chinese infants, those exposed to chlorpyrifos showed significant decreases in motor functions such as reflexes, locomotion, and grasping at 9 months compared to those not exposed.<ref name=":2">{{Cite journal |last1=Silver |first1=Monica K. |last2=Shao |first2=Jie |last3=Zhu |first3=Binquan |last4=Chen |first4=Minjian |last5=Xia |first5=Yankai |last6=Kaciroti |first6=Niko |last7=Lozoff |first7=Betsy |last8=Meeker |first8=John D. |date=2017 |title=Prenatal naled and chlorpyrifos exposure is associated with deficits in infant motor function in a cohort of Chinese infants |journal=Environment International |volume=106 |pages=248–256 |bibcode=2017EnInt.106..248S |doi=10.1016/j.envint.2017.05.015 |issn=0160-4120 |pmc=5533622 |pmid=28602489}}</ref> Exposure to organophosphate pesticides in general has been increasingly associated with changes in children's cognitive, behavioral and motor performance.<ref name="Muñoz-Quezada2013">{{Cite journal |last1=Muñoz-Quezada |first1=Maria Teresa |last2=Lucero |first2=Boris A. |last3=Barr |first3=Dana B. |last4=Steenland |first4=Kyle |last5=Levy |first5=Karen |last6=Ryan |first6=P. Barry |last7=Iglesias |first7=Veronica |last8=Alvarado |first8=Sergio |last9=Concha |first9=Carlos |last10=Rojas |first10=Evelyn |last11=Vega |first11=Catalina |date=December 2013 |title=Neurodevelopmental effects in children associated with exposure to organophosphate pesticides: A systematic review |journal=NeuroToxicology |volume=39 |pages=158–168 |bibcode=2013NeuTx..39..158M |doi=10.1016/j.neuro.2013.09.003 |issn=0161-813X |pmc=3899350 |pmid=24121005}}</ref><ref name="NeuroToxicology 26 (2005) 573–587">{{Cite journal |last=Perera |first=FP |year=2005 |title=A Summary of Recent Findings on Birth Outcomes and Developmental Effects of Prenatal ETS, PAH, and Pesticide Exposures |journal=NeuroToxicology |volume=26 |issue=4 |pages=573–587 |bibcode=2005NeuTx..26..573P |doi=10.1016/j.neuro.2004.07.007 |pmid=16112323 |s2cid=16115200}}</ref> Infant girls were shown to be more susceptible to harmful effects from organophosphate insecticides than infant boys.<ref name=":2" />

''Animal experiments'': In experiments with rats, early, short-term low-dose exposure to chlorpyrifos resulted in lasting neurological changes, with larger effects on emotional processing and cognition than on motor skills.<ref name=Timofeeva2010/> Such rats exhibited behaviors consistent with depression and reduced [[anxiety]].<ref name=Timofeeva2010/> In rats, low-level exposure during development has its greatest neurotoxic effects during the period in which [[sexual differentiation|sex differences]] in the brain develop. Exposure leads to reductions or reversals of normal gender differences.<ref name="Connors2008">{{Cite journal |last1=Connors |first1=Susan L. |last2=Levitt |first2=Pat |last3=Matthews |first3=Stephen G. |last4=Slotkin |first4=Theodore A. |last5=Johnston |first5=Michael V. |last6=Kinney |first6=Hannah C. |last7=Johnson |first7=William G. |last8=Dailey |first8=Rosa M. |last9=Zimmerman |first9=Andrew W. |date=March 2008 |title=Fetal Mechanisms in Neurodevelopmental Disorders |journal=Pediatric Neurology |volume=38 |issue=3 |pages=163–176 |doi=10.1016/j.pediatrneurol.2007.10.009 |issn=0887-8994 |pmid=18279750}}</ref> Exposure to low levels of chlorpyrifos early in rat life or as adults also affects metabolism and body weight.<ref name="Slotkin2011">{{Cite journal |last=Slotkin |first=T. A. |date=April 2011 |title=Does early-life exposure to organophosphate insecticides lead to prediabetes and obesity? |journal=Reproductive Toxicology |series=Prenatal Programming and Toxicity II (PPTOX II): Role of Environmental Stressors in the Developmental Origins of Disease |volume=31 |issue=3 |pages=297–301 |bibcode=2011RepTx..31..297S |doi=10.1016/j.reprotox.2010.07.012 |issn=0890-6238 |pmc=3025269 |pmid=20850519}}</ref> These rats show increased body weight as well as changes in liver function and chemical indicators similar to prediabetes, likely associated with changes to the [[Cyclic adenosine monophosphate|cyclic AMP]] system.<ref name="Slotkin2011" /> Moreover, experiments with zebrafish showed significant detriments to survivability, reproductive processes, and motor function. Varying doses created a 30%–100% mortality rate of embryos after 90 days. Embryos were shown to have decreased mitosis, resulting in mortality or developmental dysfunctions. In the experiments where embryos did survive, spinal [[lordosis]] and lower motor functions were observed. The same study showed that chlorpyrifos had more severe morphological deformities and mortality in embryos than [[diazinon]], another commonly used organophosphate insecticide.<ref>{{Cite journal |last1=Cao |first1=Fangjie |last2=Souders |first2=Christopher L. |last3=Li |first3=Pengfei |last4=Pang |first4=Sen |last5=Qiu |first5=Lihong |last6=Martyniuk |first6=Christopher J. |date=2018 |title=Biological impacts of organophosphates chlorpyrifos and diazinon on development, mitochondrial bioenergetics, and locomotor activity in zebrafish (Danio rerio) |journal=Neurotoxicology and Teratology |volume=70 |pages=18–27 |bibcode=2018NTxT...70...18C |doi=10.1016/j.ntt.2018.10.001 |issn=0892-0362 |pmid=30290195 |s2cid=52925464}}</ref>

====Adulthood====

Adults may develop lingering health effects following acute exposure or repeated low-dose exposure. Among agricultural workers, chlorpyrifos has been associated with slightly increased risk of [[wheeze]], a whistling sound while breathing due to obstruction of the airways.<ref>{{Cite journal |last1=Hoppin |first1=Jane A. |last2=Umbach |first2=David M. |last3=London |first3=Stephanie J. |last4=Alavanja |first4=Michael C. R. |last5=Sandler |first5=Dale P. |date=1 March 2002 |title=Chemical predictors of wheeze among farmer pesticide applicators in the Agricultural Health Study |journal=American Journal of Respiratory and Critical Care Medicine |volume=165 |issue=5 |pages=683–689 |doi=10.1164/ajrccm.165.5.2106074 |issn=1073-449X |pmid=11874814}}</ref>

Among 50 farm pesticides studied, chlorpyrifos was associated with higher risks of lung cancer among frequent pesticide applicators than among infrequent or non-users. Pesticide applicators as a whole were found to have a 50% lower cancer risk than the general public, likely due to their nearly 50% lower smoking rate. However, chlorpyrifos applicators had a 15% lower cancer risk than the general public, which the study suggests indicates a link between chlorpyrifos application and lung cancer.<ref>{{Cite web |title=Lung Cancer in the Agricultural Health Study |url=http://aghealth.nci.nih.gov/pdfs/IALungCancer2006.pdf |url-status=dead |archive-url=https://web.archive.org/web/20111015061917/http://aghealth.nci.nih.gov/pdfs/IALungCancer2006.pdf |archive-date=15 October 2011}}</ref><ref>{{Cite journal |last1=Lee |first1=Won Jin |last2=Blair |first2=Aaron |last3=Hoppin |first3=Jane A. |last4=Lubin |first4=Jay H. |last5=Rusiecki |first5=Jennifer A. |last6=Sandler |first6=Dale P. |last7=Dosemeci |first7=Mustafa |last8=Alavanja |first8=Michael C. R. |date=1 December 2004 |title=Cancer incidence among pesticide applicators exposed to chlorpyrifos in the Agricultural Health Study |journal=Journal of the National Cancer Institute |volume=96 |issue=23 |pages=1781–1789 |doi=10.1093/jnci/djh324 |issn=0027-8874 |pmid=15572760 |doi-access=free}}</ref>

Twelve people who had been exposed to chlorpyrifos were studied over periods of 1 to 4.5 years. They were found to have a heightened immune responses to common allergens and increased antibiotic sensitivities, elevated CD26 cells, and a higher rate of autoimmunity, compared with control groups. Autoantibodies were directed toward smooth muscle, parietal cell, [[brush border]], thyroid gland, myelin, and the subjects also had more anti-nuclear antibodies.<ref>{{Cite journal |last1=Thrasher |first1=JD |last2=Madison |first2=R |last3=Broughton |first3=A |date=Mar–Apr 1993 |title=Immunologic abnormalities in humans exposed to chlorpyrifos: preliminary observations |journal=Archives of Environmental Health |volume=48 |issue=2 |pages=89–93 |doi=10.1080/00039896.1993.9938400 |pmid=7682805}}</ref>

==Chlorpyrifos methyl==

The Dow Chemical Company also developed '''Chlorpyrifos methyl''' in 1966, which had a lower acute toxicity (WHO class III), but this appears to be no longer in commercial use. The molecule is similar to Chlorpyrifos ethyl, but with a O,O dimethyl chain. Proposed applications included [[vector control]].<ref name="BCPC">Tomlin CDS (2000) ''The Pesticide Manual'' 12th Ed. British Crop Protection Council (BCPC)</ref>

==Mechanisms of toxicity==

===Acetylcholine neurotransmission===

[[File:Chlorpyrifos-oxon.svg|thumb|Structure of chlorpyrifos-oxon]]

Primarily, chlorpyrifos and other organophosphate pesticides interfere with signaling from the [[neurotransmitter]] acetylcholine.<ref name= Christensen2009/> One chlorpyrifos [[metabolite]], chlorpyrifos-oxon, binds permanently to the [[enzyme]] acetylcholinesterase, preventing this enzyme from deactivating acetylcholine in the [[synapse]].<ref name= Christensen2009/><ref name="Flaskos2012" /> By irreversibly [[acetylcholinesterase inhibitor|inhibiting acetylcholinesterase]], chlorpyrifos leads to a build-up of acetylcholine between [[neuron]]s and a stronger, longer-lasting signal to the next neuron. Only when new molecules of acetylcholinesterase have been synthesized can normal function return. Acute symptoms of chlorpyrifos poisoning only occur when more than 70% of acetylcholinesterase molecules are inhibited.<ref name=Connors2008/> This mechanism is well established for acute chlorpyrifos poisoning and also some lower-dose health impacts. It is also the primary insecticidal mechanism.{{citation needed|date=September 2021}}

===Non-cholinesterase mechanisms===

Chlorpyrifos may affect other neurotransmitters, enzymes and cell signaling pathways, potentially at doses below those that substantially inhibit acetylcholinesterase. The extent of and mechanisms for these effects remain to be fully characterized.<ref name="Costa2006">{{Cite journal |last=Costa |first=Lucio G. |date=April 2006 |title=Current issues in organophosphate toxicology |journal=Clinica Chimica Acta |volume=366 |issue=1–2 |pages=1–13 |doi=10.1016/j.cca.2005.10.008 |issn=0009-8981 |pmid=16337171}}</ref><ref name="Slotkin2004">{{Cite journal |last=Slotkin |first=T A |date=15 July 2004 |title=Cholinergic systems in brain development and disruption by neurotoxicants: nicotine, environmental tobacco smoke, organophosphates |journal=Toxicology and Applied Pharmacology |volume=198 |issue=2 |pages=132–151 |bibcode=2004ToxAP.198..132S |doi=10.1016/j.taap.2003.06.001 |issn=0041-008X |pmid=15236950}}</ref> Laboratory experiments in rats and cell cultures suggest that exposure to low doses of chlorpyrifos may alter [[serotonin]] signaling and increase rat symptoms of depression; change the expression or activity of several [[serine hydrolase]] enzymes, including [[neuropathy target esterase]] and several [[endocannabinoid]] enzymes; affect components of the [[cyclic AMP]] system; and influence other chemical pathways.<ref name="Connors2008" /><ref name="Slotkin2004" /><ref name="Casida2008">{{Cite journal |last1=Casida |first1=John E. |last2=Nomura |first2=Daniel K. |last3=Vose |first3=Sarah C. |last4=Fujioka |first4=Kazutoshi |date=25 September 2008 |title=Organophosphate-sensitive lipases modulate brain lysophospholipids, ether lipids and endocannabinoids |journal=Chemico-Biological Interactions |series=Proceedings of the IX International Meeting on Cholinesterases |volume=175 |issue=1–3 |pages=355–364 |bibcode=2008CBI...175..355C |doi=10.1016/j.cbi.2008.04.008 |issn=0009-2797 |pmc=2582404 |pmid=18495101}}</ref><ref name="Eaton2008">{{Cite journal |last1=Eaton |first1=David L. |last2=Daroff |first2=Robert B. |last3=Autrup |first3=Herman |last4=Bridges |first4=James |last5=Buffler |first5=Patricia |last6=Costa |first6=Lucio G. |last7=Coyle |first7=Joseph |last8=McKhann |first8=Guy |last9=Mobley |first9=William C. |author-link9=William C. Mobley |last10=Nadel |first10=Lynn |last11=Neubert |first11=Diether |last12=Schulte-Hermann |first12=Rolf |last13=Spencer |first13=Peter S. |date=January 2008 |title=Review of the toxicology of chlorpyrifos with an emphasis on human exposure and neurodevelopment. |journal=Critical Reviews in Toxicology |volume=38 Suppl 2 |issue=s2 |pages=1–125 |doi=10.1080/10408440802272158 |issn=1547-6898 |pmid=18726789 |s2cid=84162223}}</ref>

===Paraoxonase activity===

The enzyme [[paraoxonase 1]] (PON1) detoxifies chlorpyrifos oxon, the more toxic metabolite of chlorpyrifos, via [[hydrolyze|hydrolysis]]. In laboratory animals, additional PON1 protects against chlorpyrifos toxicity while individuals that do not produce PON1 are particularly susceptible.<ref name="Costa2012">{{Cite journal |last1=Costa |first1=Lucio G. |last2=Giordano |first2=Gennaro |last3=Cole |first3=Toby B. |last4=Marsillach |first4=Judit |last5=Furlong |first5=Clement E. |date=10 May 2013 |title=Paraoxonase 1 (PON1) as a genetic determinant of susceptibility to organophosphate toxicity |journal=Toxicology |series=Emerging health issues from chronic pesticide exposure: Innovative methodologies and effects on molecular cell and tissue level |volume=307 |pages=115–122 |bibcode=2013Toxgy.307..115C |doi=10.1016/j.tox.2012.07.011 |issn=0300-483X |pmc=3516631 |pmid=22884923}}</ref> In humans, studies about the effect of PON1 activity on the toxicity of chlorpyrifos and other organophosphates are mixed, with modest yet inconclusive evidence that higher levels of PON1 activity may protect against chlorpyrifos exposure in adults; PON1 activity may be most likely to offer protection from low-level chronic doses.<ref name="Costa2012" /> Human populations have [[genetic variation]] in the sequence of PON1 and its [[promoter region]] that may influence the effectiveness of PON1 at detoxifying chlorpyrifos oxon and the amount of PON1 available to do so.<ref name="Costa2012" /> Some evidence indicates that children born to women with low PON1 may be particularly susceptible to chlorpyrifos exposure. Further, infants produce low levels of PON1 until six months to several years after birth, likely increasing the risk from chlorpyrifos exposure early in life.<ref name="Costa2012" />

===Combined exposures===

Several studies have examined the effects of combined exposure to chlorpyrifos and other chemical agents, and these combined exposures can result in different effects during development. Female rats exposed first to [[dexamethasone]], a treatment for [[premature labor]], for three days in utero and then to low levels of chlorpyrifos for four days after birth experienced additional damage to the acetylcholine system upstream of the synapse that was not observed with either exposure alone.<ref>{{Cite journal |last1=Slotkin |first1=Theodore A. |last2=Card |first2=Jennifer |last3=Infante |first3=Alice |last4=Seidler |first4=Frederic J. |date=May 2013 |title=Prenatal dexamethasone augments the sex-selective developmental neurotoxicity of chlorpyrifos: Implications for vulnerability after pharmacotherapy for preterm labor |journal=Neurotoxicology and Teratology |volume=37 |pages=1–12 |bibcode=2013NTxT...37....1S |doi=10.1016/j.ntt.2013.02.002 |issn=0892-0362 |pmc=3669256 |pmid=23416428}}</ref> In both male and female rats, combined exposures to dexamethasone and chlorpyrifos decreased serotonin turnover in the synapse, for female rats with a greater-than-additive result.<ref>{{Cite journal |last1=Slotkin |first1=Theodore A. |last2=Card |first2=Jennifer |last3=Seidler |first3=Frederic J. |date=January 2014 |title=Prenatal dexamethasone, as used in preterm labor, worsens the impact of postnatal chlorpyrifos exposure on serotonergic pathways |journal=Brain Research Bulletin |volume=100 |pages=44–54 |doi=10.1016/j.brainresbull.2013.10.014 |issn=0361-9230 |pmc=3891922 |pmid=24280657}}</ref> Rats that were co-exposed to dexamethasone and chlorpyrifos also exhibited complex behavioral differences from exposure to either chemical alone, including lessening or reversing normal sex differences in behavior.<ref>{{Cite journal |last1=Levin |first1=Edward D. |last2=Cauley |first2=Marty |last3=Johnson |first3=Joshua E. |last4=Cooper |first4=Ellen M. |last5=Stapleton |first5=Heather M. |last6=Ferguson |first6=P. Lee |last7=Seidler |first7=Frederic J. |last8=Slotkin |first8=Theodore A. |date=January 2014 |title=Prenatal dexamethasone augments the neurobehavioral teratology of chlorpyrifos: Significance for maternal stress and preterm labor |journal=Neurotoxicology and Teratology |volume=41 |pages=35–42 |bibcode=2014NTxT...41...35L |doi=10.1016/j.ntt.2013.10.004 |issn=0892-0362 |pmc=3943881 |pmid=24177596}}</ref> In the lab, in rats and neural cells co-exposed to both [[nicotine]] and chlorpyrifos, nicotine appears to protect against chlorpyrifos acetylcholinesterase inhibition and reduce its effects on neurodevelopment.<ref name="Lee2010">{{Cite journal |last1=Lee |first1=Sookwang |last2=Poet |first2=Torka S. |last3=Smith |first3=Jordan N. |last4=Busby-Hjerpe |first4=Andrea L. |last5=Timchalk |first5=Charles |date=30 March 2010 |title=Effect of in vivo nicotine exposure on chlorpyrifos pharmacokinetics and pharmacodynamics in rats |url=https://zenodo.org/record/1258824 |journal=Chemico-Biological Interactions |volume=184 |issue=3 |pages=449–457 |bibcode=2010CBI...184..449L |doi=10.1016/j.cbi.2010.01.024 |issn=0009-2797 |pmid=20097188}}</ref><ref>{{Cite journal |last1=Billauer-Haimovitch |first1=Hana |last2=Slotkin |first2=Theodore A. |last3=Dotan |first3=Sharon |last4=Langford |first4=Rachel |last5=Pinkas |first5=Adi |last6=Yanai |first6=Joseph |date=28 December 2009 |title=Reversal of chlorpyrifos neurobehavioral teratogenicity in mice by nicotine administration and neural stem cell transplantation |journal=Behavioural Brain Research |volume=205 |issue=2 |pages=499–504 |doi=10.1016/j.bbr.2009.08.006 |issn=0166-4328 |pmc=2782724 |pmid=19682500}}</ref><ref>{{Cite journal |last1=Qiao |first1=Dan |last2=Seidler |first2=Frederic J. |last3=Violin |first3=Jonathan D. |last4=Slotkin |first4=Theodore A. |date=30 December 2003 |title=Nicotine is a developmental neurotoxicant and neuroprotectant: stage-selective inhibition of DNA synthesis coincident with shielding from effects of chlorpyrifos |journal=Developmental Brain Research |series=Role of Prenatal Drugs of Abuse on Neuronal Development |volume=147 |issue=1–2 |pages=183–190 |doi=10.1016/S0165-3806(03)00222-0 |issn=0165-3806 |pmid=14741763}}</ref> In at least one study, nicotine appeared to enhance chlorpyrifos detoxification.<ref name= Lee2010/>

==Human exposure==

In 2011, EPA estimated that, in the general US population, people consume 0.009 micrograms of chlorpyrifos per kilogram of their body weight per day directly from food residue.<ref name="EPA2011">{{Cite report |url=http://www.epa.gov/oppsrrd1/registration_review/chlorpyrifos/EPA-HQ-OPP-2008-0850-DRAFT-0024%5B1%5D.pdf |title=Chlorpyrifos Preliminary Human Health Risk Assessment for Registration Review |last=U.S. EPA |date=30 June 2011 |access-date=24 July 2014}}</ref> Children are estimated to consume a greater quantity of chlorpyrifos per unit of body weight from food residue, with toddlers the highest at 0.025 micrograms of chlorpyrifos per kilogram of their body weight per day. People may also ingest chlorpyrifos from drinking water or from residue in food handling establishments. The EPA's [[Reference dose|acceptable daily dose]] is 0.3 micrograms/kg/day.<ref name="EPA2011" /> However, as of 2016, EPA scientists had not been able to find any level of exposure to the pesticide that was safe.<ref name="The New York Times">{{Cite news |last=Rabin |first=Roni Caryn |date=16 May 2017 |title=A Strong Case Against a Pesticide Does Not Faze E.P.A. Under Trump |url=https://www.nytimes.com/2017/05/15/health/pesticides-epa-chlorpyrifos-scott-pruitt.html |access-date=28 March 2018 |work=The New York Times |page=D1}}</ref> The EPA 2016 report states in part "... this assessment indicates that dietary risks from food alone are of concern&nbsp;..." The report also states that previous published risk assessments for "chlorpyrifos may not provide a sufficiently health protective human health risk assessment given the potential for neurodevelopmental outcomes."<ref name="EPA-HQ-OPP-2015-0653">{{Cite web |last=Drew |first=Danette |title=Chlorpyrifos Revised Human Health Risk Assessment (2016) |url=https://www.regulations.gov/contentStreamer?documentId=EPA-HQ-OPP-2015-0653-0454&contentType=pdf |access-date=8 April 2018 |website=Regulations.gov |publisher=EPA}}</ref>

Humans can be exposed to chlorpyrifos by way of ingestion (e.g., residue on treated produce, drinking water), inhalation (especially of indoor air), or absorption (i.e., through the skin). However, compared to other organophosphates, chlorpyrifos degrades relatively quickly once released into the environment. According to the National Institutes of Health, the half-life for chlorpyrifos (i.e., the period of time that it takes for the active amount of the chemical to decrease by 50%) "can typically range from 33–56 days for soil incorporated applications and 7–15 days for surface applications"; in water, the half-life is about 25 days, and in the air, the half-life can range from four to ten days.<ref>{{Cite web |title=TOXNET |url=https://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs%20hsdb:@term%20@DOCNO%20389 |access-date=15 October 2018 |website=toxnet.nlm.nih.gov |language=en}}</ref>

Children of agricultural workers are more likely to come into contact with chlorpyrifos. A study done in an agricultural community in Washington State showed that children who lived in closer proximity to farmlands had higher levels of chlorpyrifos residues from house dust.<ref name=":3">{{Cite journal |last1=Fenske |first1=Richard A. |last2=Lu |first2=Chensheng |last3=Barr |first3=Dana |last4=Needham |first4=Larry |date=5 April 2002 |title=Children's Exposure to Chlorpyrifos and Parathion in an Agricultural Community in Central Washington State |journal=Environmental Health Perspectives |volume=110 |issue=5 |pages=549–553 |doi=10.1289/ehp.02110549 |issn=0091-6765 |pmc=1240847 |pmid=12003762|bibcode=2002EnvHP.110..549F }}</ref> Chlorpyrifos residues were also found on work boots and children's hands, showing that agricultural families could take home these residues from their jobs.<ref name=":3" /> Urban and suburban children get most of their chlorpyrifos exposure from fruits and vegetables.<ref>{{Cite journal |last1=Lu |first1=Chensheng |last2=Barr |first2=Dana B. |last3=Pearson |first3=Melanie A. |last4=Waller |first4=Lance A. |date=2008 |title=Dietary Intake and Its Contribution to Longitudinal Organophosphorus Pesticide Exposure in Urban/Suburban Children |journal=Environmental Health Perspectives |language=en |volume=116 |issue=4 |pages=537–542 |doi=10.1289/ehp.10912 |issn=0091-6765 |pmc=2290988 |pmid=18414640|bibcode=2008EnvHP.116..537L }}</ref> A study done in North Carolina on children's exposure showed that chlorpyrifos was detected in 50% of the food, dust, and air samples in both their homes and daycare, with the main route of exposure being through ingestion.<ref>{{Cite journal |last1=Morgan |first1=Marsha |last2=Wilson |first2=Nancy |last3=Chuang |first3=Jane |last4=Morgan |first4=Marsha K. |last5=Wilson |first5=Nancy K. |last6=Chuang |first6=Jane C. |date=3 April 2014 |title=Exposures of 129 Preschool Children to Organochlorines, Organophosphates, Pyrethroids, and Acid Herbicides at Their Homes and Daycares in North Carolina |journal=International Journal of Environmental Research and Public Health |language=en |volume=11 |issue=4 |pages=3743–3764 |doi=10.3390/ijerph110403743 |pmc=4025031 |pmid=24705361 |doi-access=free}}</ref> Certain other populations with higher likely exposure to chlorpyrifos, such as people who apply pesticides, work on farms, or live in agricultural communities, have been measured in the US to excrete TCPy in their urine at levels that are 5 to 10 times greater than levels in the general population.<ref>{{Cite journal |last1=Thomas |first1=Kent W. |last2=Dosemeci |first2=Mustafa |last3=Hoppin |first3=Jane A. |last4=Sheldon |first4=Linda S. |last5=Croghan |first5=Carry W. |last6=Gordon |first6=Sydney M. |last7=Jones |first7=Martin L. |last8=Reynolds |first8=Stephen J. |last9=Raymer |first9=James H. |last10=Akland |first10=Gerald G. |last11=Lynch |first11=Charles F. |last12=Knott |first12=Charles E. |last13=Sandler |first13=Dale P. |last14=Blair |first14=Aaron E. |last15=Alavanja |first15=Michael C. |date=March 2010 |title=Urinary biomarker, dermal, and air measurement results for 2,4-D and chlorpyrifos farm applicators in the Agricultural Health Study |journal=Journal of Exposure Science and Environmental Epidemiology |volume=20 |issue=2 |pages=119–134 |doi=10.1038/jes.2009.6 |issn=1559-0631 |pmc=3633453 |pmid=19240759|bibcode=2010JESEE..20..119T }}</ref><ref>{{Cite journal |last1=Curwin |first1=Brian D. |last2=Hein |first2=Misty J. |last3=Sanderson |first3=Wayne T. |last4=Striley |first4=Cynthia |last5=Heederik |first5=Dick |last6=Kromhout |first6=Hans |last7=Reynolds |first7=Stephen J. |last8=Alavanja |first8=Michael C. |date=1 January 2007 |title=Urinary pesticide concentrations among children, mothers and fathers living in farm and non-farm households in Iowa |journal=Annals of Occupational Hygiene |volume=51 |issue=1 |pages=53–65 |doi=10.1093/annhyg/mel062 |issn=0003-4878 |pmid=16984946 |doi-access=free}}</ref><ref>{{Cite journal |last1=Egeghy |first1=Peter P. |last2=Cohen Hubal |first2=Elaine A. |last3=Tulve |first3=Nicolle S. |last4=Melnyk |first4=Lisa J. |last5=Morgan |first5=Marsha K. |last6=Fortmann |first6=Roy C. |last7=Sheldon |first7=Linda S. |date=24 May 2011 |title=Review of pesticide urinary biomarker measurements from selected US EPA children's observational exposure studies |journal=International Journal of Environmental Research and Public Health |volume=8 |issue=5 |pages=1727–1754 |doi=10.3390/ijerph8051727 |pmc=3108137 |pmid=21655147 |doi-access=free}}</ref>

As of 2016, chlorpyrifos was the most used conventional insecticide in the US and was used in over 40 states; the top five states (in total pounds applied) are California, North Dakota, Minnesota, Iowa, and Texas. It was used on over 50 crops, with the top five crops (in total pounds applied) being soybeans, corn, alfalfa, oranges, and almonds. Additionally, crops with 30% or more of the crop treated (compared to total acres grown) include apples, asparagus, walnuts, table grapes, cherries, cauliflower, broccoli, and onions.<ref>{{Cite web |last=Vogel |first=Dana |date=2016 |title=Chlorpyrifos Status Update |url=https://www.epa.gov/sites/production/files/2016-05/documents/session-2-chlorpyrifos-human-health-risk-assessment-approach.pdf&usg=AOvVaw3X8n4d1SWotVW_GS5MQJi3 |access-date=15 October 2018 |website=EPA |language=en}}{{dead link|date=October 2019|bot=medic}}{{cbignore|bot=medic}}</ref>

Air monitoring studies conducted by the [[California Air Resources Board]] (CARB) documented chlorpyrifos in the air of California communities.<ref>{{Cite web |title=CARB Chlorpyrifos Monitoring Studies |url=http://www.cdpr.ca.gov/docs/empm/pubs/tac/chlrpfs.htm |url-status=dead |archive-url=https://web.archive.org/web/20070720005752/http://www.cdpr.ca.gov/docs/empm/pubs/tac/chlrpfs.htm |archive-date=20 July 2007 |access-date=20 November 2011 |publisher=Cdpr.ca.gov}}</ref> Analyses indicate that children living in areas of high chlorpyrifos use are often exposed to levels that exceed EPA dosages.<ref>{{Cite journal |last1=Lee |first1=S |last2=McLaughlin |first2=R |last3=Harnly |first3=M |last4=Gunier |first4=R |last5=Kreutzer |first5=R |date=December 2002 |title=Community Exposures to Airborne Agricultural Pesticides in California: Ranking of Inhalation Risks |journal=Environmental Health Perspectives |volume=110 |issue=12 |pages=1175–84 |doi=10.1289/ehp.021101175 |pmc=1241103 |pmid=12460795|bibcode=2002EnvHP.110.1175L }}</ref><ref>{{Cite web |title=S Kegley et al., "Secondhand Pesticides", Pesticide Action Network North America, 2003 |url=http://www.panna.org/campaigns/docsDrift/SecondhandPs.pdf |url-status=dead |archive-url=https://web.archive.org/web/20060421162206/http://www.panna.org/campaigns/docsDrift/SecondhandPs.pdf |archive-date=21 April 2006}}</ref> A study done in Washington state using passive air samplers showed that households who lived less than 250 meters from a fruit tree field had higher levels of chlorpyrifos concentrations in the air than households that were further away.<ref>{{Cite journal |last1=Gibbs |first1=Jenna L. |last2=Yost |first2=Michael G. |last3=Negrete |first3=Maria |last4=Fenske |first4=Richard A. |date=2017 |title=Passive Sampling for Indoor and Outdoor Exposures to Chlorpyrifos, Azinphos-Methyl, and Oxygen Analogs in a Rural Agricultural Community |journal=Environmental Health Perspectives |language=en |volume=125 |issue=3 |pages=333–341 |doi=10.1289/ehp425 |issn=0091-6765 |pmc=5332193 |pmid=27517732|bibcode=2017EnvHP.125..333G }}</ref> Advocacy groups monitored air samples in [[Washington (state)|Washington]] and [[Lindsay, California]], in 2006 with comparable results.<ref>{{Cite report |url=http://www.biobased.us/poison-winds/FWPP-CP-12-14-06.pdf |title=Air Monitoring for Chlorpyrifos in the Yakima Valley, Washington, April 2006 |last1=Kegley |first1=Susan |last2=Tupper |first2=Karl |date=December 2006 |publisher=Pesticide Action Network North America |last3=Wangand |first3=Andrew |access-date=5 August 2014 |archive-url=https://web.archive.org/web/20140810102136/http://www.biobased.us/poison-winds/FWPP-CP-12-14-06.pdf |archive-date=10 August 2014 |url-status=dead}}</ref><ref>{{Cite web |last=Californians for Pesticide Reform |title=Airborne Poisons: Pesticides in Our Air and in Our Bodies |url=http://pesticidereform.org/downloads/Biodrift-Summary-Eng.pdf |url-status=dead |archive-url=https://web.archive.org/web/20130607010856/http://pesticidereform.org/downloads/Biodrift-Summary-Eng.pdf |archive-date=7 June 2013 |access-date=5 August 2014}}</ref> Grower and pesticide industry groups argued that the air levels documented in these studies are not high enough to cause significant exposure or adverse effects.<ref>{{Cite news |last=Hansen |first=Heather |date=18 January 2007 |title=Heather Hansen, "Proper Pest Management Keeps Washington Fruit Crop Healthy", Seattle Post Intellegencer, Jan 19, 2007 |url=http://www.seattlepi.com/opinion/300312_foodrebut19.html |access-date=20 November 2011 |work=Seattle Post-Intelligencer |publisher=Seattlepi.com}}</ref> A follow-up [[biomonitoring]] study in Lindsay also showed that people there display above-normal chlorpyrifos levels.<ref>{{Cite web |date=16 May 2007 |title=Douglas Fischer, "Toxins permeate Central Valley town", ''Tri-Valley Herald'', May 15th, 2007 |url=http://origin.insidebayarea.com/trivalleyherald/localnews/ci_5907782 |url-status=dead |archive-url=https://web.archive.org/web/20160108062004/http://origin.insidebayarea.com/trivalleyherald/localnews/ci_5907782 |archive-date=8 January 2016 |access-date=20 November 2011 |publisher=Origin.insidebayarea.com}}</ref><ref>{{Cite web |title=Californians For Pesticide Reform, ''Airborne Poisons: Pesticides in Our Air, and in Our Bodies'', May 16th, 2007. |url=http://pesticidereform.org/downloads/Biodrift-Summary-Eng.pdf |url-status=dead |archive-url=https://web.archive.org/web/20130607010856/http://pesticidereform.org/downloads/Biodrift-Summary-Eng.pdf |archive-date=7 June 2013 |access-date=20 November 2011}}</ref>

==Effects on wildlife==

===Aquatic life===

Among freshwater aquatic organisms, [[crustacean]]s and insects appear to be more sensitive to acute exposure than fish.<ref name="Giddings2014">{{Cite book |last1=Giddings |first1=Jeffrey M. |chapter-url=http://link.springer.com/10.1007/978-3-319-03865-0_5 |title=Ecological Risk Assessment for Chlorpyrifos in Terrestrial and Aquatic Systems in the United States |last2=Williams |first2=W. Martin |last3=Solomon |first3=Keith R. |last4=Giesy |first4=John P. |date=2014 |publisher=Springer International Publishing |isbn=978-3-319-03864-3 |editor-last=Giesy |editor-first=John P. |series=Reviews of Environmental Contamination and Toxicology, Continuation of Residue Reviews |volume=231 |location=Cham |pages=119–162 |chapter=Risks to Aquatic Organisms from Use of Chlorpyrifos in the United States |doi=10.1007/978-3-319-03865-0_5 |pmid=24723135 |editor-last2=Solomon |editor-first2=Keith R.}}</ref> Aquatic insects and animals appear to absorb chlorpyrifos directly from water rather than ingesting it with their [[food|diet]] or through [[sediment]] exposure.<ref name="Giddings2014" />

Concentrated chlorpyrifos released into rivers killed insects, shrimp and fish. In Britain, the rivers [[River Roding|Roding]] (1985), [[River Ouse, Sussex|Ouse]] (2001), Wey (2002 & 2003), and [[River Kennet|Kennet]] (2013) all experienced insect, shrimp, or fish kills as a result of small releases of concentrated chlorpyrifos.<ref>{{Cite news |date=28 August 2013 |title=Ban on domestic sale of insecticide welcomed by fisheries groups |url=https://www.fishupdate.com/ban-on-domestic-sale-of-insecticide-welcomed-by-fisheries-groups-fishupdate-com/ |url-status=dead |archive-url=https://web.archive.org/web/20180412001042/https://www.fishupdate.com/ban-on-domestic-sale-of-insecticide-welcomed-by-fisheries-groups-fishupdate-com/ |archive-date=12 April 2018 |access-date=11 April 2018 |publisher=FishUpdate.com}}</ref> The July 2013 release along the River Kennet poisoned insect life and shrimp along 15&nbsp;km of the river, likely from a half a cup of concentrated chlorpyrifos washed down a drain.<ref>{{Cite news |last=Case |first=Philip |date=1 October 2013 |title=Domestic source 'likely' cause of Kennet pollution |url=http://www.fwi.co.uk/articles/01/10/2013/141331/domestic-source-39likely39-cause-of-kennet-pollution.htm |url-status=dead |archive-url=https://web.archive.org/web/20140810041826/http://www.fwi.co.uk/articles/01/10/2013/141331/domestic-source-39likely39-cause-of-kennet-pollution.htm |archive-date=10 August 2014 |access-date=5 August 2014 |publisher=Farmers Weekly}}</ref>

===Bees===

{{Main|Pesticide toxicity to bees}}

Acute exposure to chlorpyrifos can be toxic to [[bees]], with an oral LD50 of 360&nbsp;ng/bee and a contact LD50 of 70&nbsp;ng/bee.<ref name="Christensen2009" /> Guidelines for Washington state recommend that chlorpyrifos products should not be applied to flowering plants such as fruit trees within 4–6 days of blossoming to prevent bees from directly contacting the residue.<ref>{{Cite web |last=Washington State Department of Agriculture |title=Bee Kill Prevention for Tree Fruits |url=http://agr.wa.gov/Pestfert/Pesticides/docs/BeeKillPreventionTreeFruits.pdf |url-status=dead |archive-url=https://web.archive.org/web/20141030180739/http://agr.wa.gov/PestFert/Pesticides/docs/BeeKillPreventionTreeFruits.pdf |archive-date=30 October 2014 |access-date=5 August 2014}}</ref>

Risk assessments have primarily considered acute exposure, but more recently researchers have begun to investigate the effects of chronic, low-level exposure through [[Pesticide residue|residue]] in pollen and components of bee hives.<ref name="Sanchez-Bayo2014">{{Cite journal |last1=Sanchez-Bayo |first1=Francisco |last2=Goka |first2=Koichi |date=9 April 2014 |title=Pesticide Residues and Bees – A Risk Assessment |journal=PLOS ONE |volume=9 |issue=4 |pages=–94482 |bibcode=2014PLoSO...994482S |doi=10.1371/journal.pone.0094482 |pmc=3981812 |pmid=24718419 |doi-access=free}}</ref> A review of US studies, several European countries, Brazil and India found chlorpyrifos in nearly 15% of hive pollen samples and just over 20% of honey samples. Because of its high toxicity and prevalence in pollen and honey, bees are considered to have higher risk from chlorpyrifos exposure via their diet than from many other pesticides.<ref name="Sanchez-Bayo2014" />

When exposed in the laboratory to chlorpyrifos at levels roughly estimated from measurements in hives, bee larvae experienced 60% mortality over 6 days, compared with 15% mortality in controls.<ref>{{Cite journal |last1=Zhu |first1=Wanyi |last2=Schmehl |first2=Daniel R. |last3=Mullin |first3=Christopher A. |last4=Frazier |first4=James L. |date=2014 |title=Four common pesticides, their mixtures and a formulation solvent in the hive environment have high oral toxicity to honey bee larvae |journal=PLOS ONE |volume=9 |issue=1 |pages=–77547 |bibcode=2014PLoSO...977547Z |doi=10.1371/journal.pone.0077547 |issn=1932-6203 |pmc=3885384 |pmid=24416121 |doi-access=free}}</ref> Adult bees exposed to sub-lethal effects of chlorpyrifos (0.46&nbsp;ng/bee) exhibited altered behaviors: less walking; more grooming, particularly of the head; more difficulty righting themselves; and unusual abdominal spasms.<ref name="Williamson2013">{{Cite journal |last1=Williamson |first1=Sally M. |last2=Moffat |first2=Christopher |last3=Gomersall |first3=Martha A. E. |last4=Saranzewa |first4=Nastja |last5=Connolly |first5=Christopher N. |last6=Wright |first6=Geraldine A. |date=2013 |title=Exposure to acetylcholinesterase inhibitors alters the physiology and motor function of honeybees |journal=Frontiers in Physiology |volume=4 |pages=13 |doi=10.3389/fphys.2013.00013 |pmc=3564010 |pmid=23386834 |doi-access=free}}</ref> Chlorpyrifos oxon appears to particularly inhibit acetylcholinesterase in bee gut tissue as opposed to head tissue.<ref name="Williamson2013" /> Other organophosphate pesticides impaired bee learning and memory of smells in the laboratory.<ref>{{Cite journal |last1=Williamson |first1=Sally M. |last2=Wright |first2=Geraldine A. |author-link2=Geraldine Wright |date=15 May 2013 |title=Exposure to multiple cholinergic pesticides impairs olfactory learning and memory in honeybees |journal=The Journal of Experimental Biology |volume=216 |issue=10 |pages=1799–1807 |doi=10.1242/jeb.083931 |issn=0022-0949 |pmc=3641805 |pmid=23393272}}</ref>

==Regulation==

{{Update|section|date=March 2022}}

{{globalize|section|date=June 2019}}

===International law===

Chlorpyrifos is not regulated under international law or treaty. Organizations such as [[Pesticide Action Network|PANNA]] and the [[Natural Resources Defense Council|NRDC]] state that chlorpyrifos meets the four criteria (persistence, [[bioaccumulation]], long-range transport, and toxicity) in Annex D of the [[Stockholm Convention on Persistent Organic Pollutants]] and should be restricted.<ref>{{Cite journal |last=Watts |first=Meriel |date=2012 |title=Chlorpyrifos as a possible global POP |url=http://w.rapaluruguay.org/agrotoxicos/Chlorpyrifos_as_POP.pdf |url-status=dead |journal=Pesticide Action Network North America, Oakland, CA. WWW. Pan-europe. Info/News/PR/121009_Chlorpyrifos_as_POP_final. PDF |archive-url=https://web.archive.org/web/20140822120922/http://w.rapaluruguay.org/agrotoxicos/Chlorpyrifos_as_POP.pdf |archive-date=22 August 2014 |access-date=21 July 2014}}</ref> In 2021, the European Union submitted a proposal to list chlorpyrifos in Annex A to the Stockholm Convention.<ref>{{Cite web |title=UNEP/POPS/POPRC.17/5 – Proposal to list chlorpyrifos in Annex A to the Stockholm Convention on Persistent Organic Pollutants |url=http://chm.pops.int/theconvention/popsreviewcommittee/meetings/poprc17/overview/tabid/8900/ |access-date=2021-11-02 |website=pops.int}}</ref>

===National regulations===

Chlorpyrifos was used to control insect infestations of homes and commercial buildings in Europe until it was banned from sale in 2008.<ref>[http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:1998:123:0001:0063:EN:PDF Directive 98/8/EC] of the European parliament and of the council of 16 February 1998, concerning the placing of biocidal products on the market. Published in the Official Journal of the European Communities, 24 April 1998</ref> Chlorpyrifos is restricted from [[termite]] control in Singapore as of 2009.<ref>{{Cite web |last=Yong |first=Koh Chin |date=1 January 2009 |title=Prohibition on the use of chlorpyrifos in Singapore |url=http://app2.nea.gov.sg/docs/default-source/anti-pollution-radiation-protection/chemical-pollution/prohibition-on-the-use-of-chlorpyrifos-in-singapore.pdf?sfvrsn=0 |url-status=dead |archive-url=https://web.archive.org/web/20140821034224/http://app2.nea.gov.sg/docs/default-source/anti-pollution-radiation-protection/chemical-pollution/prohibition-on-the-use-of-chlorpyrifos-in-singapore.pdf?sfvrsn=0 |archive-date=21 August 2014 |access-date=14 August 2014 |website=National Environment Agency |format=PDF}}</ref> It was banned from residential use in South Africa as of 2010.<ref>{{Cite web |title=Harmful pesticide banned in SA – South Africa |url=http://www.iol.co.za/news/south-africa/harmful-pesticide-banned-in-sa-1.485733#.U-VBFPldV9w |access-date=8 August 2014 |website=IOL News}}</ref> It has been banned in the United Kingdom in 2016 apart from a limited use in drenching seedlings.<ref>{{Cite web |title=Changes to authorisations for products containing chlorpyrifos |url=http://www.hse.gov.uk/pesticides/news/information-update-0316.htm |url-status=dead |archive-url=https://web.archive.org/web/20210808121455/https://www.hse.gov.uk/pesticides/news/information-update-0316.htm |archive-date=8 August 2021 |access-date=7 November 2019 |publisher=Health and Safety Executive}}</ref>

Chlorpyrifos has not been permitted for agricultural use in Sweden at all<ref>{{Cite journal |last1=Norén |first1=Erika |last2=Lindh |first2=Christian |last3=Rylander |first3=Lars |last4=Glynn |first4=Anders |last5=Axelsson |first5=Jonatan |last6=Littorin |first6=Margareta |last7=Faniband |first7=Moosa |last8=Larsson |first8=Estelle |last9=Nielsen |first9=Christel |display-authors=2 |date=2020-07-01 |title=Concentrations and temporal trends in pesticide biomarkers in urine of Swedish adolescents, 2000–2017 |journal=Journal of Exposure Science & Environmental Epidemiology |language=en |volume=30 |issue=4 |pages=756–767 |doi=10.1038/s41370-020-0212-8 |issn=1559-064X |pmc=8075908 |pmid=32094458 |quote=... , as chlorpyrifos has never been approved for plant protection in Sweden. |doi-access=free|bibcode=2020JESEE..30..756N }}</ref>

====United States====

{{See Also|Pesticide regulation in the United States}}

In the United States, several laws directly or indirectly regulate the use of pesticides. These laws, which are implemented by the [[EPA]], [[NIOSH]], [[USDA]] and [[FDA]], include: the [[Clean Water Act]] (CWA); the [[Endangered Species Act]] (ESA); the Federal Insecticide, Fungicide, and Rodenticide Act ([[FIFRA]]); the Federal Food, Drug, and Cosmetic Act ([[FFDCA]]); the Comprehensive Environmental Response, Compensation, and Liability Act ([[CERCLA]]); and the Emergency Planning and Community Right-to-Know Act ([[EPCRA]]). As a pesticide, chlorpyrifos is not regulated under the Toxic Substances Control Act ([[TSCA]]).<ref>{{Cite web |last=U.S. EPA |date=22 February 2013 |title=Summary of the Toxic Substances Control Act |url=http://www2.epa.gov/laws-regulations/summary-toxic-substances-control-act |url-status=dead |archive-url=https://web.archive.org/web/20140821043236/http://www2.epa.gov/laws-regulations/summary-toxic-substances-control-act |archive-date=21 August 2014 |access-date=11 August 2014 |format=Overviews and Factsheets}}</ref>

Chlorpyrifos is sold in restricted-use products for certified pesticide applicators to use in agriculture and other settings, such as golf courses or for [[mosquito]] control.<ref>{{Cite web |last=U.S. EPA, Office of Pesticide Programs |date=February 2002 |title=Chlorpyrifos Facts |url=http://www.epa.gov/oppsrrd1/REDs/factsheets/chlorpyrifos_fs.htm |access-date=21 July 2014}}</ref> It may also be sold in ant and [[Cockroach|roach]] baits with childproof packaging.<ref>{{Cite web |last=U.S. EPA |date=27 June 2001 |title=Chlorpyrifos; Receipt of Requests For End-Use Product Amendments and Cancellations |url=https://www.federalregister.gov/articles/2001/06/27/01-16125/chlorpyrifos-receipt-of-requests-for-end-use-product-amendments-and-cancellations |access-date=23 July 2014 |website=Federal Register}}</ref> In 2000, manufacturers reached an agreement with the EPA to voluntarily restrict the use of chlorpyrifos in places where children may be exposed, including homes, schools and day care centers.<ref>{{Cite news |last=Revkin |first=Andrew C. |date=9 June 2000 |title=E.P.A., Citing Risks to Children, Signs Accord to Limit Insecticide |url=https://www.nytimes.com/2000/06/09/us/epa-citing-risks-to-children-signs-accord-to-limit-insecticide.html |access-date=20 August 2014 |work=The New York Times |issn=0362-4331}}</ref><ref>{{Cite news |last=Beckerman |first=Josh |date=31 October 2015 |title=EPA Proposes Ending Use of Certain Pesticide on Foods, Citing Risk to Water |url=https://www.wsj.com/articles/epa-proposes-ending-use-of-certain-pesticide-on-foods-citing-risk-to-water-1446250171 |access-date=31 October 2015 |work=Wall Street Journal}}</ref>

In 2007 [[Pesticide Action Network North America]] and [[Natural Resources Defense Council]] (collectively, PANNA) submitted an administrative petition requesting a chlorpyrifos ban, citing harm to the brains of developing children.<ref name=":5">{{Cite web |last=Erickson |first=Britt E. |date=2023-11-06 |title=Chlorpyrifos returns to the US market |url=https://cen.acs.org/environment/pesticides/Chlorpyrifos-returns-US-market/101/web/2023/11 |access-date=2023-11-08 |website=[[Chemical & Engineering News]] |language=en}}</ref> On 10 August 2015, the [[Ninth Circuit Court of Appeals]] in PANNA v. EPA ordered the EPA to respond to PANNA's petition by "revok[ing] all tolerances for the insecticide chlorpyrifos", den[ying] the Petition or [issuing] a "proposed or final tolerance revocation" no later than 31 October 2015.<ref>{{Cite web |title=Pesticide Action Network v. U.S. Environmental Protection Agency |url=http://cdn.ca9.uscourts.gov/datastore/opinions/2015/08/10/14-72794.pdf |access-date=14 August 2015 |format=WebContent}}</ref><ref name="federalregister_2015" /> The EPA was "unable to conclude that the risk from aggregate exposure from the use of chlorpyrifos [met] the safety standard of section 408(b)(2) of the Federal Food, Drug, and Cosmetic Act (FFDCA)" and therefore proposed "to revoke all tolerances for chlorpyrifos."<ref name="federalregister_2015">{{Citation |title=Chlorpyrifos Tolerance Revocations: A Proposed Rule by the Environmental Protection Agency |date=6 November 2015 |url=https://www.federalregister.gov/documents/2015/11/06/2015-28083/chlorpyrifos-tolerance-revocations |access-date=30 March 2015}} Docket number EPA-HQ-OPP-2015-0653. This report is no longer available on the EPA website</ref>

In an 30 October 2015 statement Dow AgroSciences disagreed with the EPA's proposed revocation and "remain[ed] confident that authorized uses of chlorpyrifos products, as directed, offer wide margins of protection for human health and safety." In a November 2016 press release, DOW argued that chlorpyrifos was "a critical tool for growers of more than 50 different types of crops in the United States" with limited or no viable alternatives."<ref name="dowagro_2016">{{Citation |title=Dow AgroSciences, U.S. Farmers Disagree with U.S. EPA Proposal to Revoke Chlorpyrifos Tolerances |date=10 November 2016 |url=https://www.dowagro.com/en-us/newsroom/pressreleases/2016/11/dow-agrosciences-us-farmers-disagree-with-us-epa-proposal--to-revoke-chlorpyrifos-tolerances#.WN2KCmjysdU |access-date=30 March 2017 |publisher=Dow AgroSciences}}</ref> The ''Environment News Service'' quoted the Dow AgroSciences' statement disagreeing with the EPA findings.<ref name="ENS_2015">{{Citation |title=EPA Urged to Ban Widely-Used Pesticide Chlorpyrifos |date=5 January 2016 |url=http://ens-newswire.com/2016/01/05/epa-urged-to-ban-widely-used-pesticide-chlorpyrifos/ |access-date=30 March 2017 |publisher=Environment News Service}}</ref>

{{blockquote|Chlorpyrifos is one of the most widely used pest control products in the world. It is authorized for use in about 100 nations, including the U.S., Canada, the United Kingdom, Spain, France, Italy, Japan, Australia and New Zealand, where it is registered for protection of essentially every crop now under cultivation. No other pesticide has been more thoroughly tested.|Statement Dow AgroSciences October 30, 2015}}

In November 2016, the EPA reassessed its ban proposal after taking into consideration recommendations made by the agency's Science Advisory Panel which had rejected the EPA's methodology in quantifying the risk posed by chlorpyrifos. Using a different methodology as suggested by the panel, the EPA retained its decision to completely ban chlorpyrifos. The EPA concluded that, while "uncertainties" remain, a number of studies provide "sufficient evidence" that children experience neurodevelopment effects even at low levels of chlorpyrifos exposure.<ref name="The New York Times" /><ref name="EPA-HQ-OPP-2015-0653" /><ref>{{Cite web |date=27 April 2017 |title=The Facts on Chlorpyrifos |url=http://www.factcheck.org/2017/04/the-facts-on-chlorpyrifos/ |access-date=2 July 2017 |website=Fact Check.Org}}</ref>

On 29 March 2017, EPA Administrator [[Scott Pruitt]], appointed by the Trump administration, overturned the 2015 EPA revocation and denied the administrative petition by the Natural Resources Defense Council and the Pesticide Action Network North America to ban chlorpyrifos.<ref name="reuters_2017_epa">{{Citation |title=U.S. EPA denies petition to ban pesticide chlorpyrifos |date=29 March 2017 |work=[[Reuters]] |url=https://www.reuters.com/article/us-usa-pesticide-epa-idUSKBN17039F |access-date=30 March 2017}}</ref><ref>{{Cite news |date=9 August 2018 |title=Federal appeals court orders EPA to ban pesticide |url=https://www.washingtonexaminer.com/policy/energy/federal-appeals-court-orders-epa-to-ban-pesticide |access-date=9 August 2018 |work=Washington Examiner |language=en}}</ref><ref name="The Hill">{{Cite news |date=24 September 2018 |title=Trump admin appeals ruling ordering EPA to ban pesticide |url=https://thehill.com/policy/energy-environment/408173-trump-admin-appeals-ruling-ordering-epa-to-ban-pesticide?amp |access-date=24 January 2019 |work=The Hill |language=en}}</ref><ref name="Samet">{{Cite journal |last1=Samet |first1=Jonathan M. |last2=Burke |first2=Thomas A. |date=2 April 2020 |title=Deregulation and the Assault on Science and the Environment |journal=Annual Review of Public Health |volume=41 |issue=1 |pages=347–361 |doi=10.1146/annurev-publhealth-040119-094056 |issn=0163-7525 |pmid=31905321 |s2cid=210042328 |doi-access=free}}</ref>

The [[American Academy of Pediatrics]] responded to the administration's decision saying they are "deeply alarmed" by Pruitt's decision to allow the pesticide's continued use. "There is a wealth of science demonstrating the detrimental effects of chlorpyrifos exposure to developing fetuses, infants, children and pregnant women. The risk to infant and children's health and development is unambiguous."<ref name="latimes.com">{{Cite web |date=27 June 2017 |title=EPA chief met with Dow Chemical CEO before deciding not to ban toxic pesticide |url=http://www.latimes.com/business/la-fi-epa-pesticide-dow-20170627-story.html |access-date=2 July 2017 |website=Los Angeles Times}}</ref>

Asked in April whether Pruitt had met with Dow Chemical Company executives or lobbyists before his decision, an EPA spokesman replied: "We have had no meetings with Dow on this topic." In June, after several [[Freedom of Information Act (United States)|Freedom of Information Act]] requests, the EPA released a copy of Pruitt's March meeting schedule which showed that a meeting had been scheduled between Pruitt and Dow CEO [[Andrew Liveris]] at a hotel in Houston, Texas, on 9 March.<ref name="latimes.com" /> Both men were featured speakers at an energy conference. An EPA spokesperson reported that the meeting was brief and the pesticide was not discussed.<ref>{{Cite web |title=Scott Pruitt, Trump's EPA chief met with Dow Chemical exec before rolling back a ban on pesticides |url=http://www.businessinsider.com/scott-pruitt-trumps-epa-chief-met-with-dow-chemical-exec-before-rolling-back-a-ban-on-pesticides-2017-6?IR=T |access-date=6 August 2017 |website=Business Insider}}</ref>

In August, it was revealed that in fact Pruitt and other EPA officials had met with industry representatives on dozens of occasions in the weeks immediately prior to the March decision, promising them that it was "a new day" and assuring them that their wish to continue using chlorpyrifos had been heard. Ryan Jackson, Pruitt's chief of staff, said in an 8 March email that he had "scared" career staff into going along with the political decision to deny the ban, adding "[T]hey know where this is headed and they are documenting it well."<ref>{{Cite news |last1=Lipton |first1=Eric |last2=Rabin |first2=Roni Caryn |date=18 August 2017 |title=E.P.A. Promised 'a New Day' for the Agriculture Industry, Documents Reveal |url=https://www.nytimes.com/2017/08/18/us/politics/epa-agriculture-industry.html |access-date=28 August 2017 |work=The New York Times |language=en-US |issn=0362-4331}}</ref>

On 9 August 2018 the U.S. 9th Circuit court of Appeals ruled that the EPA must ban chlorpyrifos within 60 days from that date. A spokesman for Dow DuPont stated that "all appellate options" would be considered. In contrast, Marisa Ordonia, a lawyer for [[Earthjustice]], the organization that had conducted much of the legal work on the case, hailed the decision.<ref>{{Cite news |last=Lipton |first=Eric |date=9 August 2018 |title=Court Orders E.P.A. To Ban Chlorpyrifos, Pesticide Tied to Children's Health Problems |url=https://www.nytimes.com/2018/08/09/us/politics/chlorpyrifos-pesticide-ban-epa-court.html |work=The New York Times}}</ref><ref>{{Cite web |date=10 August 2018 |title=What is the Insecticide Chlorpyrifos? |url=https://www.nationalgeographic.com/environment/2018/08/chlorpyrifos-insecticides-pesticides-epa-organophosphates/ |url-status=dead |archive-url=https://web.archive.org/web/20180811134420/https://www.nationalgeographic.com/environment/2018/08/chlorpyrifos-insecticides-pesticides-epa-organophosphates/ |archive-date=11 August 2018 |website=[[National Geographic Society]]}}</ref> The ruling was almost immediately appealed by Trump administration lawyers.<ref name="The Hill" />

On August 18, 2021 the U.S. Environmental Protection Agency (EPA) announced a ban on the use of chlorpyrifos on food crops in the United States.<ref name="Trager" /><ref name="Solomon" /><ref name="Romo" />

On February 25, 2022 the EPA released a statement upholding its decision to revoke all tolerance standards on chlorpyrifos use, and sent letters to registered chlorpyrifos food producers confirming the ban to be in effect as of February 28, 2022.<ref name="epaInfo">{{Cite web |date=29 December 2014 |title=Chlorpyriphos l US EPA |url=https://www.epa.gov/ingredients-used-pesticide-products/chlorpyrifos |access-date=30 May 2023}}</ref>

On 14 December, 2022 the EPA filed a Notice of Intent to Cancel (NOIC) for three chlorpyrifos pesticide products because they bear labeling for use on food, despite the ban.<ref>{{Cite web |date=14 December 2022 |title=EPA Continues Work to Reduce Chlorpyrifos Exposure |url=https://www.epa.gov/pesticides/epa-continues-work-reduce-chlorpyrifos-exposure |access-date=30 May 2023}}</ref>{{update after|2022}}<!-- did EPA get beyond "intent", and actually promulgate new regulations? -->

However, on November 2, 2023 the [[United States Court of Appeals for the Eighth Circuit]] nixed a 2021 rule issued by the [[Environmental Protection Agency]] banning all neurotoxic insecticide on all food crops. The court concluded, that by deciding to ban all uses of chlorpyrifos on food plants, the EPA ignored the long standing American practice and prior court orders to evaluate each crop group on its own merits and "to keep a set of high-benefit uses in place." The court ordered the EPA to reevaluate whether "chlorpyrifos can be safely used on crops like sugar beets, soybeans, and certain fruits and vegetables".<ref name=":5" />

Some states, including California, Hawaii, Maryland, New York, and Oregon, have banned chlorpyrifos on food grown and sold in their jurisdictions. Those bans remain in effect.

===== Residue =====

The use of chlorpyrifos in agriculture can leave chemical [[pesticide residue|residue]] on food commodities. The FFDCA requires EPA to set limits, known as tolerances, for pesticide residue in human food and animal feed products based on risk quotients for acute and chronic exposure from food in humans.<ref>{{Cite web |last=US EPA Office of Pesticide Programs |date=20 August 2015 |title=EPA sets limits on the amount of pesticides that may remain in foods |url=http://www.epa.gov/pesticides/regulating/tolerances.htm |access-date=23 July 2014}}</ref><ref name="EPA2006">{{Cite report |url=http://www.epa.gov/oppsrrd1/reregistration/REDs/chlorpyrifos_red.pdf |title=US Environmental Protection Agency Office of Pesticide Programs Reregistration Eligibility Decision for Chlorpyrifos |date=2006 |access-date=23 July 2014 |archive-url=https://web.archive.org/web/20080520204436/http://www.epa.gov/oppsrrd1/reregistration/REDs/chlorpyrifos_red.pdf |archive-date=May 20, 2008 |url-status=dead}}</ref> These tolerances limit the amount of chlorpyrifos that can be applied to crops. FDA enforces EPA's pesticide tolerances and determines "action levels" for the unintended [[pesticide drift|drift of pesticide]] residues onto crops without tolerances.<ref>{{Cite web |title=Compliance Policy Guides – CPG Sec. 575.100 Pesticide Residues in Food and Feed – Enforcement Criteria |url=https://www.fda.gov/iceci/compliancemanuals/compliancepolicyguidancemanual/ucm123236.htm |access-date=23 July 2014 |website=[[Food and Drug Administration]] |format=WebContent}}</ref>

After years of research without a conclusion and cognizant of the court order to issue a final ruling, the EPA proposed to eliminate all tolerances for chlorpyrifos ("Because tolerances are the maximum residue of a pesticide that can be in or on food, this proposed rule revoking all chlorpyrifos tolerances means that if this approach is finalized, all agricultural uses of chlorpyrifos would cease."), and then solicited comments.<ref>{{Cite web |last=US Environmental Protection Agency |title=Proposal to Revoke Chlorpyrifos Food Residue Tolerances |url=https://www.epa.gov/ingredients-used-pesticide-products/proposal-revoke-chlorpyrifos-food-residue-tolerances#revocation |access-date=4 February 2017 |format=WebContent}}</ref>

The Dow Chemical Company is actively opposed to tolerance restrictions on chlorpyrifos and is currently lobbying the White House to, among other goals, pressure EPA to reverse its proposal to revoke chlorpyrifos food residue tolerances.<ref>{{Cite web |last=Lerner |first=Sharon |date=14 January 2017 |title=POISON FRUIT: Dow Chemical Wants Farmers to Keep Using a Pesticide Linked to Autism and ADHD |url=https://theintercept.com/2017/01/14/dow-chemical-wants-farmers-to-keep-using-a-pesticide-linked-to-autism-and-adhd/ |access-date=4 February 2017}}</ref>

The EPA has not updated the approximately 112 tolerances pertaining to food products and supplies since 2006.<ref name="EPA2006" /><ref name="Code of Federal Regulations">{{Cite web |last=Code of Federal Regulations |date=1 July 2010 |title=Section 180.342 – Chlorpyrifos; tolerances for residues. |url=http://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol23/xml/CFR-2010-title40-vol23-sec180-342.xml |access-date=23 July 2014}}</ref> However, in a 2016 report, EPA scientists had not been able to find any level of exposure to the pesticide that was safe.<ref name="The New York Times" /> The EPA 2016 report states in part "... this assessment indicates that dietary risks from food alone are of concern&nbsp;..." the report also states that previous published risk assessments for "chlorpyrifos may not provide a [sufficient]&nbsp;... human health risk assessment given the potential for neurodevelopmental outcomes."<ref name="EPA-HQ-OPP-2015-0653" />

″The&nbsp;... [food only] exposures for chlorpyrifos are of risk concern&nbsp;... for all population subgroups analyzed. Children (1–2 years old) is the population subgroup with the highest risk estimate at 14,000% of the ssPADfood.″<ref name="EPA-HQ-OPP-2015-0653" /> (This acronym refers to the steady-state population-adjusted dose for food, which is considered the maximum safe oral dose.)

Based on 2006 EPA rules, chlorpyrifos has a tolerance of 0.1 part per million (ppm) residue on all food items unless a different tolerance has been set for that item or chlorpyrifos is not registered for use on that crop.<ref>{{Cite web |title=Chlorpyrifos – PubChem |url=https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2730 |access-date=23 July 2014}}</ref> EPA set approximately 112 tolerances pertaining to food products and supplies.<ref name="EPA2006" /><ref name="Code of Federal Regulations" /> In 2006, to reduce childhood exposure, the EPA amended its chlorpyrifos tolerance on apples, grapes and tomatoes, reducing the grape and apple tolerances to 0.01 ppm and eliminating the tolerance on tomatoes.<ref name="EPA2006" /> Chlorpyrifos is not allowed on crops such as spinach, squash, carrots, and tomatoes; any chlorpyrifos residue on these crops normally represents chlorpyrifos misuse or spray drift.<ref name="EPA2006" />

Food handling establishments (places where food products are held, processed, prepared or served) are included in the food tolerance of 0.1 ppm for chlorpyrifos. Food handling establishments may use a 0.5% solution of chlorpyrifos solely for spot and/or crack and crevice treatments.<ref name="Code of Federal Regulations" /> Food items are to be removed or protected during treatment. Food handling establishment tolerances may be modified or exempted under FFDCA sec. 408.<ref>{{Cite web |title=Tolerances and Exemptions for Pesticide Chemical Residues in Food [ 40 CFR 180 ] : (Protection of Environment [ 40 CFR ]) |url=http://cfr.regstoday.com/40cfr180.aspx#40_CFR_180p7 |url-status=dead |archive-url=https://web.archive.org/web/20140729113305/http://cfr.regstoday.com/40cfr180.aspx#40_CFR_180p7 |archive-date=29 July 2014 |access-date=23 July 2014 |website=Code of Federal Regulations}}</ref>

=====Water=====

Chlorpyrifos in waterways is regulated as a hazardous substance under section 311(b)(2)(A) of the [[Federal Water Pollution Control Act]] and falls under the CWA amendments of 1977 and 1978.<ref>{{Cite web |title=Designation of Hazardous Substances [ 40 CFR 116 ] : (Protection of Environment [ 40 CFR ]) |url=http://cfr.regstoday.com/40cfr116.aspx |url-status=dead |archive-url=https://web.archive.org/web/20140729090102/http://cfr.regstoday.com/40cfr116.aspx |archive-date=29 July 2014 |access-date=23 July 2014}}</ref> The regulation is inclusive of all chlorpyrifos [[isomer]]s and [[hydrate]]s in any solution or mixture. EPA has not set a [[drinking water quality standards|drinking water regulatory standard]] for chlorpyrifos, but has established a drinking water guideline of 2&nbsp;ug/L.<ref name="toxnet">{{Cite web |last=GCF |date=10 January 2008 |title=Hazardous Substances Data Bank: Chlorpyrifos |url=http://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+iris:@term+@DOCNO+IRIS0026 |website=U.S National Library of Medicine TOXNET |format=Reference Resources}}</ref>

In 2009, to protect threatened [[salmon]] and [[Rainbow trout|steelhead]] under CWA and ESA, EPA and [[National Marine Fisheries Service]] (NMFS) recommended limits on the use of chlorpyrifos in California, Idaho, Oregon and Washington and requested that manufacturers voluntarily add [[buffer strip|buffer zones]], application limits and fish toxicity to the standard labeling requirements for all chlorpyrifos-based products.<ref>{{Cite web |date=11 September 2009 |title=New Limits on Pesticide Uses Will Protect Salmon |url=http://yosemite.epa.gov/opa/admpress.nsf/eeffe922a687433c85257359003f5340/cd1f6f9dbe3db7d68525762e004f693a!OpenDocument |access-date=23 July 2014}}</ref> Manufacturers rejected the request.<ref>{{Cite web |date=7 May 2010 |title=Registrants' Response to EPA's April 29, 2010 Letter: Implementation of Chlorpyrifos, Diazinon and Malathion Salmonid BiOp-Davids letter |url=http://www.epa.gov/espp/litstatus/wtc/davids-letter.pdf |access-date=15 August 2014}}</ref> In February 2013 in Dow AgroSciences vs NMFS, the [[United States Court of Appeals for the Fourth Circuit|Fourth Circuit Court of Appeals]] vacated EPA's order for these labeling requirements.<ref>{{Cite web |date=25 February 2013 |title=Regulatory Developments: Court of Appeals Issues Landmark Ruling Vacating Biological Opinion Concerning Effects of Three Pesticides on Salmon Species |url=http://www.lawbc.com/regulatory-developments/entry/court-of-appeals-issues-landmark-ruling-vacating-biological-opinion-concern/ |access-date=18 August 2014 |website=Bergeson & Campbell}}</ref> In August 2014, in the settlement of a suit brought by environmental and fisheries advocacy groups against EPA in the [[United States District Court for the Western District of Washington|U.S. District Court for the Western District of Washington]], EPA agreed to re-instate no-spray stream buffer zones in California, Oregon and Washington, restricting aerial spraying (300&nbsp;ft.) and ground-based applications (60&nbsp;ft.) near salmon populations.<ref>{{Cite web |title=ODA Pesticides Interim court ordered pesticide buffers |url=http://www.oregon.gov/ODA/PEST/pages/buffers.aspx |access-date=18 August 2014}}</ref> These buffers will remain until EPA makes a permanent decision in consultation with NMFS.<ref>{{Cite web |last=McLernon |first=Sean |title=EPA Settlement Creates Pesticide-Free Zones For Salmon – Law360 |url=http://www.law360.com/articles/566999/epa-settlement-creates-pesticide-free-zones-for-salmon |access-date=18 August 2014}}</ref>

=====Reporting =====

EPCRA designates the chemicals that facilities must report to the [[Toxics Release Inventory]] (TRI), based on EPA assessments. Chlorpyrifos is not on the reporting list. It is on the list of hazardous substances under CERCLA (aka the [[Superfund]] Act). In the event of an environmental release above its reportable quantity of 1&nbsp;lb or 0.454&nbsp;kg, facilities are required to immediately notify the [[National Response Center]] (NRC).<ref>{{Cite web |title=Chlorpyrifos – CERCLA Quantities |url=http://webwiser.nlm.nih.gov/getSubstanceData.do?substanceId=280&displaySubstanceName=Danusban&STCCID=&UNNAID=&selectedDataMenuItemID=77 |access-date=23 July 2014 |website=NIH U.S National Library of Medicine WebWISER}}</ref>

In 1995, Dow paid a $732,000 EPA penalty for not forwarding reports it had received on 249 chlorpyrifos poisoning incidents.<ref>{{Cite web |last=Fried |first=John J. |date=20 March 1996 |title=The Pesticide Puzzle |url=https://www.chicagotribune.com/1996/03/20/the-pesticide-puzzle/ |access-date=19 August 2014 |website=Chicago Tribune}}</ref>

=====Occupational exposure=====

In 1989, OSHA established a workplace [[permissible exposure limit]] (PEL) of 0.2&nbsp;mg/m3 for chlorpyrifos, based on an 8-hour time weighted average (TWA) exposure. However, the rule was remanded by the [[United States Court of Appeals|U.S. Circuit Court of Appeals]] and no PELs are in place presently.<ref>{{Cite web |date=1988 |title=OSHA PEL Project Documentation: Chlorpyrifos |url=https://www.cdc.gov/niosh/pel88/2921-88.html |access-date=10 July 2014 |website=CDC- NIOSH}}</ref>

EPA's [[Worker Protection Standard]] requires owners and operators of agricultural businesses to comply with safety protocols for agricultural workers and pesticide handlers (those who mix, load and apply pesticides). For example, in 2005, the EPA filed an administrative complaint against JSH Farms, Inc. (Wapato, Washington) with proposed penalties of $1,680 for using chlorpyrifos in 2004 without proper equipment. An adjacent property was contaminated with chlorpyrifos due to pesticide drift and the property owner suffered from eye and skin irritation.<ref>{{Cite web |last=U.S. EPA |date=22 February 2005 |title=Three Companies Penalized for Pesticide Violations on Yakama Reservation |url=http://yosemite.epa.gov/opa/admpress.nsf/d96f984dfb3ff7718525735900400c29/ebc25ff3231b9548852570cb0075e2cb!OpenDocument&Highlight=2,pesticide |access-date=15 August 2014}}</ref>

=====State laws=====

Additional laws and guidelines may apply for individual US states. California, Hawaii, Maryland, New York, and Oregon, have banned chlorpyrifos on food grown and sold in their jurisdictions. These State bans remain in effect regardless whether chlorpyrifos is allowed on the federal level or not.<ref name=":5" />

[[Oregon Department of Environmental Quality|Oregon's Department of Environmental Quality]] added chlorpyrifos to the list of targeted reductions in the [[Clackamas, Oregon|Clackamas]] Subbasin as part of the Columbia River National Strategic Plan, which is based on EPA'S 2006–11 National Strategic Plan.<ref>{{Cite web |title=Water Quality Total Maximum Daily Loads (TMDLs) Program |url=http://www.deq.state.or.us/WQ/TMDLs/columbia.htm |url-status=dead |archive-url=https://web.archive.org/web/20140821095331/http://www.deq.state.or.us/WQ/TMDLs/columbia.htm |archive-date=21 August 2014 |access-date=20 August 2014 |website=Oregon Department of Environmental Quality}}</ref>

In 2017, chlorpyrifos was included [[California Proposition 65 (1986)|California's Proposition 65]].<ref>{{Cite web |title=Chemicals Considered or Listed Under Proposition 65 - Chlorpyrifos |url=https://oehha.ca.gov/proposition-65/chemicals/chlorpyrifos |publisher=OEHHA}}</ref>

California included regulation limits for chlorpyrifos in [[waterway]]s and established maximum and continuous concentration limits of 0.025 ppb and 0.015 ppb, respectively.<ref>{{Cite conference |last=California |date=11 July 2013 |title=Total Maximum Daily Loads for Chlorpyrifos and Diazinon for the Pajaro River Watershed Monterey, Santa Clara, Santa Cruz, and San Benito Counties, California |location=895 Aerovista Place, Suite 101, San Luis Obispo, California 93401 |publisher=CALIFORNIA REGIONAL WATER QUALITY CONTROL BOARD CENTRAL COAST REGION |pages=65}}</ref><ref>{{Cite news |last=Elias |first=Tom |date=27 August 2019 |title=The end in sight for a perilous pesticide in California |url=https://www.vcstar.com/story/opinion/columnists/2019/08/26/end-sight-perilous-pesticide-california/2120380001/ |access-date=28 August 2019 |work=Ventura County Star |language=en}}</ref> Sale and possession of chlorpyrifos have been largely banned in California, as of 6 February – 31 December 2020, respectively. The California ban has an exception that, "a few products that apply chlorpyrifos in granular form, representing less than one percent of agricultural use of chlorpyrifos, will be allowed to remain on the market."<ref name=":4">{{Cite web |title=Agreement Reached to End Sale of Chlorpyrifos in California by February 2020 |url=https://www.cdpr.ca.gov/docs/pressrls/2019/100919.htm |access-date=2021-04-26 |website=www.cdpr.ca.gov}}</ref>

In Hawaii, a 2018 law introduced a complete ban on products containing chlorpyrifos, which went into effect on January 1, 2023. Before that, starting in 2019, the law mandated temporary application permits and annual reporting as well as mandating a 100-foot buffer around schools during school hours.<ref>{{Cite web |date=14 June 2018 |title=Hawaii to ban pesticides containing chlorpyrifos |url=https://www.hawaii247.com/2018/06/13/hawaii-to-ban-pesticides-containing-chlorpyrifos/ |access-date=14 June 2018 |website=Hawaii 24/7}}</ref><ref>{{Cite web |date=14 June 2018 |title=New Hawaii law bans use of pesticide |url=http://www.khon2.com/news/local-news/new-hawaii-law-bans-use-of-pesticide/1237801215 |access-date=14 June 2018 |website=KHON}}</ref><ref>{{Cite web |title=New Requirements Under Act 45 |url=https://hdoa.hawaii.gov/pi/main/act45/ |access-date=2023-06-11 |website=hdoa.hawaii.gov |language=en}}</ref>

Florida did not ban chlorpyrifos completely, but introduced a concentration limit of 21&nbsp;ug/L in drinking water.<ref name="toxnet" />

In 2003, Dow agreed to pay $2&nbsp;million to New York state, in response to a lawsuit to end Dow's advertising of Dursban as "safe".<ref>{{Cite web |date=15 December 2003 |title=Dow AgroSciences agrees to pay $2M to state over pesticide ads |url=http://www.bizjournals.com/albany/stories/2003/12/15/daily3.html?page=all |access-date=20 August 2014 |website=Albany Business Review}}</ref>

==== Australia ====

Chlorpyrifos is used agriculturally in Australia but household use was restricted to low strength solutions in 2001 and banned in 2020.<ref>{{Cite web |title=Chlorpyrifos |url=https://www.apvma.gov.au/resources/chemicals-news/chlorpyrifos |access-date=5 August 2024 |publisher=Australian Pesticides and Veterinary Medicines Authority}}</ref> There are 49 registered chlorpyrifos insecticide products, mostly as 500 g/L [[Pesticide formulation|emulsifiable concentrates]].<ref>{{Cite web |url=https://portal.apvma.gov.au/pubcris?p_auth=Q9sPGlVn&p_p_id=pubcrisportlet_WAR_pubcrisportlet&p_p_lifecycle=1&p_p_state=normal&p_p_mode=view&p_p_col_id=column-1&p_p_col_pos=2&p_p_col_count=4&_pubcrisportlet_WAR_pubcrisportlet_javax.portlet.action=search |access-date=5 August 2024 |website=Public Chemical Registration Information System Search |publisher=Australian Pesticides and Veterinary Medicines Authority|title=APVMA PubCRIS database search}}</ref>

The Australian Pesticides and Veterinary Medicine Authority's Chlorpyrifos Chemical Review, began July 2015,<ref>{{Cite web |date=27 May 2014 |title=Chlorpyrifos Chemical Review |url=http://apvma.gov.au/node/12451 |website=The Australian Pesticides and Veterinary Medicine Authority}}</ref> made the final decision in September 2024. Chlorpyrifos will continue to be used, though many uses of it are banned. The minimum technical grade chlorpyrifos purity is raised from 94% to 97% by weight.<ref>{{cite web |title=Special Gazette, 3 October 2024 |url=https://www.apvma.gov.au/news-and-publications/publications/gazette/special-gazette-3-oct-24 |website=Australian Pesticides and Veterinary Medicines Authority |access-date=21 October 2024}}</ref><ref>{{cite news |title=APVMA releases chlorpyrifos final regulatory decision |url=https://news.agropages.com/News/NewsDetail---51666.htm |work=Grainews |language=en}}</ref>

==== Denmark ====

Chlorpyrifos was never approved for use in Denmark, except on [[ornamental plant]]s grown in greenhouses. This use was banned in 2012.<ref>{{Cite web |last=Hecklen |first=Alexander |date=6 August 2019 |title=Fødevaremyndighed: Frygtet sprøjtegift skader børns udvikling og skal forbydes |url=https://www.dr.dk/nyheder/penge/foedevaremyndighed-frygtet-sproejtegift-skader-boerns-udvikling-og-skal-forbydes |access-date=6 August 2019 |website=dr.dk |publisher=Danmarks Radio |language=da}}</ref>

==== European Union ====

On 6 December 2019, the European Union (EU) announced that it will no longer permit sales of chlorpyrifos after 31 January 2020.<ref>{{Cite web |title=Search &#124; The National Law Review |url=https://www.natlawreview.com/nlr-legal-analysis-and-news-database-search?qnlr=Chlorpyrifos#gsc.tab=0&gsc.q=Chlorpyrifos&gsc.page=1 |website=www.natlawreview.com}}</ref>

The [[European Food Safety Authority]] released a statement in July 2019 which concluded that the approval criteria for chlorpyrifos which apply to human health are not met.<ref>{{Cite web |date=31 July 2019 |title=Statement on the available outcomes of the human health assessment in the context of the pesticides peer review of the active substance chlorpyrifos |url=https://www.efsa.europa.eu/sites/default/files/scientific_output/5809-chlorpyrifos.pdf |access-date=31 July 2019 |website=dr.dk |publisher=European Food Safety Authority Journal |language=en}}</ref> Their literature review concluded that there is no evidence for reproductive toxicity in rats, but that chlorpyrifos is potentially genotoxic. The report stated that chlorpyrifos is clearly a potent [[acetylcholinesterase inhibitor]], that it can be absorbed by ingestion, inhalation, and through the skin, and that epidemiological evidence supports the hypothesis that it is a human developmental neurotoxin that can cause early cognitive and behavioral deficits through prenatal exposure.

==== India ====

The FSSAI ([[Food Safety and Standards Authority of India]]) did not set a usage limits for chlorpyrifos.<ref>{{Cite news |title=വിഷത്തിൽ മുങ്ങിക്കുളിച്ച് മുളകും ചീരയും |url=https://www.manoramaonline.com/health/healthy-food/poisonous-countrygreen.html |work=ManoramaOnline |language=ml}}</ref> In 2010, India barred Dow from commercial activity for 5 years<ref>{{Cite news |last=Kumar |first=Devesh |date=18 September 2010 |title=Dow AgroSciences Blacklisted for Bribing |url=http://economictimes.indiatimes.com//articleshow/6575870.cms |access-date=19 August 2014 |work=The Economic Times}}</ref> after India's Central Bureau of Investigation found Dow guilty of bribing Indian officials in 2007 to allow the sale of chlorpyrifos.<ref>{{Cite web |date=21 August 2007 |title=Dow raided by CBI: profited $330,000 by bribing officials to license Dursban |url=http://www.bhopal.net/dow-raided-by-cbi-profited-330000-by-bribing-officials-to-license-dursban/ |access-date=19 August 2014 |website=International Campaign for Justice in Bhopal}}</ref> In 2020, the Indian government had published a draft bill to ban 27 pesticides including chlorpyrifos.<ref>{{Cite web |title=PRD Live - 27 കീടനാശിനികളുടെ നിരോധനത്തെ പിന്തുണച്ച് സംസ്ഥാനം |url=https://prdlive.kerala.gov.in/news/92594 |language=ml}}</ref>

==== New Zealand ====

Chlorpyrifos is currently approved in New Zealand for commercial use in crops, as a veterinary medicine, and as a timber treatment chemical.<ref>{{Cite web |title=First step towards reassessing controversial insecticide |url=https://www.epa.govt.nz/news-and-alerts/latest-news/first-step-towards-reassessing-controversial-insecticide/ |access-date=2023-07-07 |website=Environmental Protection Authority}}</ref>

==== Thailand ====

Chlorpyrifos was banned under Thai law effective from 1 June 2020. Farmers were given 270 days to destroy their stock, while a 90-day deadline was also given to farmers to return the [[chemical]]s for destruction, as their possession is considered illegal by the Department of Agriculture. After deadline, any person who possesses the illegal [[agrochemical]]s will be fined one million baht, jailed for 10 years, or both.<ref>{{Cite news |last=APINYA WIPATAYOTIN |date=29 May 2020 |title=Farmers given 90 days to hand in chemicals |url=https://www.bangkokpost.com/thailand/general/1925892/farmers-given-90-days-to-hand-in-chemicals |access-date=30 May 2020 |work=[[Bangkok Post]]}}</ref>

==== Malaysia ====

Chlorpyrifos was banned under by Department of Agriculture for use in farming and agriculture with effective from year 2023. However it is still permitted for general use other than agriculture purpose. <ref>{{Cite web |date=19 February 2024 |title=Chlorpyrifos &#124; Banned for use in Malaysia &#124; Health hazards |url=https://msianpestcontrol.com/chlorpyrifos-banned-insecticides/}}</ref>

==Manufacture==

Chlorpyrifos is produced via a multistep synthesis from [[3-Methylpyridine|3-methylpyridine]], eventually reacting 3,5,6-trichloro-2-pyridinol with diethylthiophosphoryl chloride.<ref name="agrochemicals">{{Cite book |title=Agrochemicals: Composition, Production, Toxicology, Applications |publisher=Wiley-VCH |year=2000 |isbn=978-3-527-29852-5 |editor-last=Muller, Franz |location=Toronto |page=541}}</ref>

*[[Organophosphate poisoning]]

{{Reflist}}

*[http://npic.orst.edu//. Chlorpyrifos Fact Sheet]

*[http://npic.orst.edu/factsheets/chlorpgen.pdf National Pesticide Information Center

* [https://web.archive.org/web/20130918183531/http://npic.orst.edu/factsheets/chlorptech.pdf Chlorpyrifos Technical Fact Sheet] (archived version) – National Pesticide Information Center

* [http://extoxnet.orst.edu/pips/chlorpyr.htm Chlorpyrifos Pesticide Information Profile – Extension Toxicology Network]

*[://www..// 's Chlorpyrifos Page]

* [https://www.cdc.gov/niosh/npg/npgd0137.html CDC – NIOSH Pocket Guide to Chemical Hazards – Chlorpyrifos]

{{Insecticides}}

{{Acetylcholine metabolism and transport modulators}}

{{Consumer Food Safety}}

[[Category:Acetylcholinesterase inhibitors]]

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[[Category:]]

[[Category:]]

[[Category:Suspected fetotoxicants]]

[[Category:Ethyl esters]]