View source for Fipronil

{{Use dmy dates|date=June 2023}}
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| Name           = Fipronil
| ImageFile1     = Fipronil.svg
| ImageName1     = 2D chemical structure of fipronil
| ImageFile2     = Fipronil-3D-balls.png
| ImageName2     = 3D chemical structure of fipronil
| ImageName      = Fipronil
| IUPACName      = 
| PIN            = 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethylsulfinyl)pyrazole-3-carbonitrile{{r|PubChem}}
| OtherNames     = Fipronil<br />Fluocyanobenpyrazole<br />Taurus<br />Termidor
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| KEGG = D01042
| InChI = 1/C12H4Cl2F6N4OS/c13-5-1-4(11(15,16)17)2-6(14)8(5)24-10(22)9(7(3-21)23-24)26(25)12(18,19)20/h1-2H,22H2
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| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 101326
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C12H4Cl2F6N4OS/c13-5-1-4(11(15,16)17)2-6(14)8(5)24-10(22)9(7(3-21)23-24)26(25)12(18,19)20/h1-2H,22H2
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| StdInChIKey = ZOCSXAVNDGMNBV-UHFFFAOYSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 120068-37-3
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| SMILES = FC(F)(F)S(=O)c2c(C#N)nn(c1c(Cl)cc(cc1Cl)C(F)(F)F)c2N
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| Section2       = {{Chembox Properties
| C=12|H=4|Cl=2|F=6|N=4|O=1|S=1
| Density = 1.477-1.626 g/cm<sup>3</sup>
| MeltingPtC = 200.5
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| Section6       = {{Chembox Pharmacology
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| Section7       = {{Chembox Hazards
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| NFPA-H = 2
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| NFPA_ref =<ref name="Santa Cruz Biotech 2019">{{cite web |url=https://datasheets.scbt.com/sds/aghs/en/sc-201546.pdf |title=Safety Date Sheet |id=SC-201546 - Fipronil |publisher=Santa Cruz Biotechnology, Inc. |date=23 April 2019 |access-date=30 Oct 2023}}</ref>
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| LD50 = 97 mg/kg (rat, oral)
| LDLo = 
| LC50 = 0.25 mg/L (rainbow trout, aquatic)
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'''Fipronil''' is a broad-spectrum [[insecticide]] that belongs to the [[phenylpyrazole]] chemical family. Fipronil disrupts the [[insect central nervous system]] by blocking the [[ligand-gated ion channel]] of the [[GABAA receptor|GABA<sub>A</sub> receptor]] and [[glutamate-gated chloride channel|glutamate-gated chloride (GluCl) channels]]. This causes hyperexcitation of contaminated insects' nerves and muscles. Fipronil's specificity towards insects is believed to be due to its greater [[Affinity (biochemistry)|binding affinity]] for the GABA<sub>A</sub> receptors of insects than to those of [[mammal]]s, and for its action on GluCl channels, which do not exist in mammals.<ref name="Raymond-Delpech 2005">{{Cite journal |last1=Raymond-Delpech |first1=Valérie |last2=Matsuda |first2=Kazuhiko |last3=Sattelle |first3=Benedict M. |last4=Rauh |first4=James J. |last5=Sattelle |first5=David B. |date=2005 |title=Ion channels: molecular targets of neuroactive insecticides |journal=Invertebrate Neuroscience |language=en |volume=5 |issue=3–4 |pages=119–133 |doi=10.1007/s10158-005-0004-9 |pmid=16172884 |s2cid=12654353 |issn=1354-2516}}</ref> {{As of|2017}}, there does not appear to be significant resistance among [[flea]]s to fipronil.<ref name="Todd-Jenkins 2017">{{cite journal |title=Perception Versus Reality: Insecticide Resistance in Fleas |url=https://www.americanveterinarian.com/journals/amvet/2017/june2017/perception-versus-reality-insecticide-resistance-in-fleas |archive-date=11 Apr 2020 |archive-url=https://web.archive.org/web/20200411171315/https://www.americanveterinarian.com/journals/amvet/2017/june2017/perception-versus-reality-insecticide-resistance-in-fleas |url-status=unfit |journal=American Veterinarian |date=18 Jun 2017 |last=Todd-Jenkins |first=Karen |volume=2 |issue=3}}</ref>

Because of its effectiveness on various pests, fipronil is used as the active ingredient in [[flea control]] products for pets and home [[roach bait]]s as well as field [[pest control]] for corn, golf courses, and commercial turf. Its widespread use makes its specific effects the subject of considerable attention. Observations on possible harm to humans or ecosystems are ongoing as well as the monitoring of [[pesticide resistance]] development.<ref name="Maddison p229">{{Cite book |title=Small Animal Clinical Pharmacology |last1=Maddison |first1=Jill E. |last2=Page |first2=Stephen W. |edition=2nd |year=2008 |page=229 |publisher=Elsevier Health Sciences |isbn=978-0-7020-2858-8}}</ref>

==Physical properties==
Fipronil ([[IUPAC name]] ''5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethylsulfinyl)pyrazole-3-carbonitrile''<ref name="PubChem">[https://pubchem.ncbi.nlm.nih.gov/compound/3303913 "Compound Summary {{!}} 5-Amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-1H-pyrazole-3-carbonitrile"]. ''PubChem''. Bethesda, Md.: National Library of Medicine. n.d.</ref>) is a white, solid powder with a [[mold]]y odor. It is degraded slightly by sunlight, stable at normal temperatures for one year, and is not stable in presence of [[metal ion]]s.<ref name="New  Pesticide Fact Sheet">{{cite web |author=<!--anonymous author(s)--> |title=New Pesticide Fact Sheet |url=https://nepis.epa.gov/Exe/ZyPURL.cgi?Dockey=P1001KCY.txt |publisher=Office of Pesticide Programs; Office of Prevention, Pesticides, and Toxic Substances; United States Environmental Protection Agency |access-date=30 October 2023 |date=May 1996 |id=EPA-737-F-96-005 |via=nepis.epa.gov}}</ref>

==Use==
Fipronil is/was used against many different pests on different crops, it is used against major [[lepidoptera]]n (moth, butterfly, etc.) and [[orthoptera]]n (grasshopper, locust, etc.) pests on a range of field and [[Horticulture|horticultural]] crops and against [[coleopteran]] (beetle) larvae in [[soil]]s. It is employed for [[cockroach]] and [[ant]] control as well as locust control and termite pest control. In the [[United States|United States of America]], fipronil was approved for use against the [[Rasberry crazy ant]] until 2022<ref name="Keigwin 2019">{{Cite letter|last=Keigwin|first=Richard C. Jr.|recipient=Texas Department of Agriculture|subject=Quarantine exemption under the provisions of Section 18 of the Federal Insecticide, Fungicide and Rodenticide Act|date=6 May 2019|publisher=United States Environmental Protection Agency|url=https://www.texasagriculture.gov/Portals/0/Publications/PEST/Sect18/19TX06_auth_crazy_ants.pdf|access-date=30 Oct 2023|via=Texasagriculture.gov}}</ref>{{Update after|2022}} in counties of [[Texas]] where positive identification had been made by entomologists from the [[Texas Department of Agriculture]] and the [[United States Environmental Protection Agency|Environmental Protection Agency]]. In [[New Zealand]], fipronil was used in trials to control wasps (''[[Vespula]]'' {{Abbr|spp.|species}}), which are a threat to indigenous [[biodiversity]].<ref name="Wasp Warfare 2011">{{cite magazine |date=Autumn 2011 |title=Wasp Warfare |url=https://www.doc.govt.nz/globalassets/documents/conservation/land-and-freshwater/land/revive-rotoiti/revive-rotoiti-issue24.pdf |magazine=Revive Rotoiti |location=St Arnaud |publisher=Department of Conservation; New Zealand Government |issue=24 |page=2 |access-date=30 Oct 2011}}</ref> It is now being used by the Department of Conservation to attempt local eradication of wasps,<ref name="Neal 2016">{{cite news |last1=Neal |first1=Tracy |date=10 February 2016 |title=War on wasps in Abel Tasman |work=RNZ |publisher=Radio New Zealand |url=https://www.rnz.co.nz/news/regional/296226/war-on-wasps-in-abel-tasman |access-date=30 October 2023}}</ref><ref>{{cite web |title=Vespex: Making wide-area wasp control a reality - WWF's Conservation Innovation Awards |url=https://wwf-nz.crowdicity.com/post/160207 |website=wwf-nz.crowdicity.com |access-date=5 March 2016 |archive-date=2 August 2017 |archive-url=https://web.archive.org/web/20170802204256/https://wwf-nz.crowdicity.com/post/160207 |url-status=dead }}</ref><ref name="Wasp Control Using Vespex">{{cite web |date=n.d. |title=Wasp control Using Vespex |url=http://www.doc.govt.nz/waspcontrol |access-date=30 Oct 2023 |publisher=Department of Conservation; New Zealand Government}}</ref> and is being recommended for control of the invasive [[Argentine ant]].<ref>{{Cite web |date=n.d. |title=Argentine Ants |url=https://www.doc.govt.nz/nature/pests-and-threats/animal-pests/argentine-ants/ |access-date=30 Oct 2023 |publisher=Department of Conservation; New Zealand Government}}</ref> Fipronil is also the active ingredient in many commercial [[tick]] and [[flea]] treatments for [[pet]]s.<ref>{{Cite web |title=Vet Strength Flea & Tick Treatments for Cats & Dogs &#124; FRONTLINE |url=https://uk.frontline.com/products |accessdate=26 June 2023 |website=uk.frontline.com}}</ref>

==Effects==
===Toxicity===

Fipronil is classed as a [[WHO]] Class II moderately hazardous pesticide, and has a [[rat]] [[Acute oral toxicity|acute oral]] {{LD50}} of 97&nbsp;mg/kg.

It has moderate acute toxicity by the oral and inhalation routes in rats. Dermal absorption in rats is less than 1% after 24 hours exposure and toxicity is considered to be low.  It has been found to be very toxic to [[rabbit]]s.<ref>{{Cite web |title=Fipronil Toxicity: Keep Flea Products Away from Rabbits |url=https://vetmed.illinois.edu/pet-health-columns/rabbits-fipronil-toxic/ |access-date=2023-11-20 |website=Veterinary Medicine at Illinois |language=en-US}}</ref>

The [[Photodegradation|photodegradate]] MB46513 or desulfinylfipronil, appears to have a higher [[acute toxicity]] to mammals than fipronil itself by a factor of about 10.<ref name="Hainzl 1996">{{Cite journal |title=Fipronil insecticide: Novel photochemical desulfinylation with retention of neurotoxicity |doi=10.1073/pnas.93.23.12764 |pmid=8917493 |volume=93 |issue=23 |journal=Proceedings of the National Academy of Sciences |pages=12764–12767 |pmc=23994 |year=1996 |last1=Hainzl |first1=D. |last2=Casida |first2=J. E. |bibcode=1996PNAS...9312764H |doi-access=free}}</ref>

Symptoms of acute toxicity via ingestion includes sweating, nausea, vomiting, headache, abdominal pain, dizziness, agitation, weakness, and [[Generalized tonic–clonic seizure|tonic-clonic seizures]]. Clinical signs of exposure to fipronil are generally reversible and resolve spontaneously. As of 2011, no data were available regarding the chronic effects of fipronil on humans. The [[United States Environmental Protection Agency]] has classified fipronil as a group C (possible human) [[carcinogen]] based on an increase in [[Thyroid cancer|thyroid follicular cell tumors]] in both sexes of the rat. However, as of 2011, no human data are available regarding the [[carcinogen]]ic effects of fipronil.<ref name="Jackson 2009">{{cite web |last1=Jackson, D. |last2=Cornell, C. B. |last3=Luukinen, B. |last4=Buhl, K. |last5=Stone, D. |title=Fipronil Technical Fact Sheet |url=http://npic.orst.edu/factsheets/archive/fiptech.html |publisher=National Pesticide Information Center, Oregon State University Extension Services |access-date=30 October 2023 |date=2009}}</ref>

Two Frontline TopSpot products were determined by the [[New York State Department of Environmental Conservation]] to pose no significant exposure risks to workers applying the product. However, concerns were raised about human exposure to Frontline spray treatment in 1996, leading to a denial of registration for the spray product. Commercial pet groomers and [[veterinary physician]]s were considered to be at risk from chronic exposure via inhalation and dermal absorption during the application of the spray, assuming they may have to treat up to 20 large dogs per day.<ref name="Pesticides News 2000">{{cite magazine |year=2000 |title=Fipronil |journal=Pesticides News |publisher=Pesticides Trust |publication-place=London |volume=48 |page=20 |issn=0967-6597}}{{better source needed|date=October 2023}}</ref> Fipronil is not [[volatility (chemistry)|volatile]], so the likelihood of humans being exposed to this compound in the air is low.<ref name="Jackson 2009"/>

In contrast to [[neonicotinoid]]s such as [[acetamiprid]], [[clothianidin]], [[imidacloprid]], and [[thiamethoxam]], which are absorbed through the skin to some extent, fipronil is not absorbed substantially through the skin.<ref>{{cite web |url=https://www.pesticideresearch.com/site/?page_id=4843 |title=Cockroach Control |website=Pesticideresearch.com |access-date=August 10, 2016 |date=2013-03-31 |archive-date=12 August 2017 |archive-url=https://web.archive.org/web/20170812022459/http://www.pesticideresearch.com/site/?page_id=4843 |url-status=dead }}{{better source needed|date=October 2023}}</ref>

===Drinking water contamination===
In 2021, the US EPA put fipronil on the Draft Fifth Contaminant Candidate List (CCL 5) which can lead to future regulation under the [[Safe Drinking Water Act]].<ref name="Contaminant Candidate List 5">{{cite web |title=Contaminant Candidate List 5{{dash}}CCL 5 |date=n.d. |url=https://www.epa.gov/ccl/contaminant-candidate-list-5-ccl-5 |publisher=United States Environmental Protection Agency |access-date=30 Oct 2023}}</ref>

===Detection in body fluids===
Fipronil may be quantitated in plasma by [[Gas chromatography–mass spectrometry|gas chromatography-mass spectrometry]] or [[Liquid chromatography–mass spectrometry|liquid chromatography-mass spectrometry]] to confirm a diagnosis of [[poisoning]] in hospitalized patients or to provide evidence in a medicolegal death investigation.<ref name="Baselt p894">{{cite book |last1=Baselt |first1=Randall C. |title=Disposition of Toxic Drugs and Chemicals in Man |date=2017 |publisher=Biomedical Publications |location=Seal Beach, California |isbn=978-0-692-77499-1 |pages=894–895 |edition=Eleventh}}</ref>

===Ecological toxicity===
{{further|Pesticide toxicity to bees}}
Fipronil is highly toxic to [[crustaceans]], [[insects]] (including [[bee]]s and [[termite]]s) and [[zooplankton]], as well as [[rabbit]]s, the [[fringe-toed lizard]], and certain groups of [[galliformes|gallinaceous birds]]. It appears to reduce the [[longevity]] and [[fecundity]] of female [[Braconidae|braconid parasitoids]]. It is also highly toxic to many [[fish]], though its toxicity varies with species. Conversely, the substance is relatively innocuous to [[passerines]], [[wildfowl]], and [[earthworm]]s.

Its [[half-life]] in soil is four months to one year, but much less on the soil surface because it is more sensitive to light ([[photolysis]]) than water ([[hydrolysis]]).<ref name="Gunasekara 2007">{{cite journal |last1=Gunasekara |first1=Amrith S. |last2=Truong |first2=Tresca |last3=Goh |first3=Kean S. |last4=Spurlock |first4=Frank |last5=Tjeerdema |first5=Ronald S. |title=Environmental fate and toxicology of fipronil |journal=Journal of Pesticide Science |url=https://www.jstage.jst.go.jp/article/jpestics/32/3/32_3_189/_article |access-date=30 October 2023 |date=2007 |volume=32 |issue=3 |pages=189–199 |doi=10.1584/jpestics.R07-02 |doi-access=free |format=PDF |issn=1349-0923}}</ref>

Few studies of effects on [[wildlife]] have been conducted, but studies of the nontarget impact from emergency applications of fipronil as barrier sprays for locust control in Madagascar showed adverse impacts of fipronil on termites, which appear to be very severe and long-lived.<ref name="Kirby 2000">{{cite news |last1=Kirby |first1=Alex |title=Anti-locust drive 'created havoc' |url=http://news.bbc.co.uk/2/hi/science/nature/806641.stm |access-date=30 October 2023 |work=BBC News |department=Sci/Tech |date=27 June 2000}}</ref> Also, adverse effects were indicated in the short term on several other invertebrate groups, one species of lizard (''[[Trachylepis elegans]]''), and several species of birds (including the [[Olive Bee-eater|Madagascar bee-eater]]).

Nontarget effects on some insects (predatory and [[Detritivore|detritivorous]] [[beetle]]s, some parasitic wasps and bees) were also found in field trials of fipronil for desert locust control in [[Mauritania]], and very low doses (0.6-2.0 g a.i./ha) used against [[grasshopper]]s in [[Niger]] caused impacts on nontarget insects comparable to those found with other insecticides used in grasshopper control. The implications of this for other wildlife and the ecology of the habitat remain unknown, but appear unlikely to be severe.<ref name="Pesticides News 2000"/> Unfortunately, this lack of severity was not observed in bee species in South America. Fipronil is also used in Brazil and studies on the stingless bee ''[[Scaptotrigona postica]]'' have shown adverse reactions to the pesticide, including seizures, [[paralysis]], and death with a lethal dose of .54&nbsp;ng a.i./bee and a lethal concentration of .24&nbsp;ng a.i./μl diet. These values are highly toxic in ''[[Scaptotrigona postica]]'' and bees in general.<ref name="Jacob 2013">{{cite journal |last1=Jacob |first1=Cynthia Renata Oliveira |last2=Soares |first2=Hellen Maria |last3=Carvalho |first3=Stephan Malfitano |last4=Nocelli |first4=Roberta Cornélio Ferreira |last5=Malaspina |first5=Osmar |title=Acute Toxicity of Fipronil to the Stingless Bee Scaptotrigona postica Latreille |journal=Bulletin of Environmental Contamination and Toxicology |date=2013 |volume=90 |issue=1 |pages=69–72 |doi=10.1007/s00128-012-0892-4 |pmid=23179165 |bibcode=2013BuECT..90...69J |s2cid=35297535 |issn=1432-0800}}</ref> Toxic baiting with fipronil has been shown to be effective in locally eliminating [[German wasp]]s. All colonies within foraging range were eliminated within one week.<ref name="Sackmann 2001">{{cite journal |last1=Sackmann |first1=Paula |last2=Rabinovich |first2=Mauricio |last3=Corley |first3=Juan Carlos |title=Successful Removal of German Yellowjackets (Hymenoptera: Vespidae) by Toxic Baiting |journal=Journal of Economic Entomology |date=2001 |volume=94 |issue=4 |pages=811–816 |doi=10.1603/0022-0493-94.4.811 |pmid=11561837 |issn=1938-291X}}</ref><ref name="Hanna 2012">{{cite journal |title=Short and long-term control of Vespula pensylvanica in Hawaii by fipronil baiting |doi=10.1002/ps.3262 |pmid=22392920 |volume=68 |issue=7 |journal=Pest Management Science |pages=1026–1033 |date=2012 |last1=Hanna |first1=Cause |last2=Foote |first2=David |last3=Kremen |first3=Claire}}</ref>

In May 2003, the French Directorate-General of Food at the Ministry of Agriculture determined that a case of mass bee mortality observed in [[southern France]] was related to acute fipronil toxicity. Toxicity was linked to defective [[seed treatment]], which generated dust. In February 2003, the ministry decided to temporarily suspend the sale of BASF crop protection products containing fipronil in France.<ref name="Kissling 2003">{{cite press release |url=http://www.agro.basf.com/agr/AP-Internet/en/content/news_room/news/basf-fipronil-temporary-suspension-in-france-statement |title=BASF statement regarding temporary suspension of sales of crop protection products containing fipronil in France |author1=Kissling, Elise |author2=BASF SE |year=2003}}{{dead link|date=October 2023}}</ref> The seed treatment involved has since been banned.{{Citation needed|date=November 2007}}

Notable results from wildlife studies include:
* Fipronil is highly [[aquatic toxicity|toxic to fish]] and [[Marine invertebrates|aquatic invertebrates]]. Its tendency to bind to [[sediment]]s and its low water solubility may reduce the potential hazard to aquatic wildlife.<ref name="NPTN p3">{{cite web |title=Fipronil |date=n.d. |url=http://www.livingwithbugs.com/PDFiles/fipronil.pdf |publisher=National Pesticide Telecommunications Network; Oregon State University |access-date=30 Oct 2023 |page=3 |via=Livingwithbugs.com}}</ref>
* Fipronil is [[Bees and toxic chemicals|toxic to bees]] and should not be applied to [[vegetation]] when bees are foraging.<ref name="NPTN p3"/>
* Based on ecological effects, fipronil is highly toxic to [[upland game bird]]s on an acute oral basis and very highly toxic on a subacute dietary basis, but is practically nontoxic to waterfowl on both acute and subacute bases.<ref name="New  Pesticide Fact Sheet" /> 
* Chronic ([[avian reproduction]]) studies show no effects at the highest levels tested in [[mallard]]s ([[NOEC]] = 1000 ppm) or [[quail]] (NOEC = 10 ppm). The metabolite MB 46136 is more toxic than the parent to avian species tested (very highly toxic to upland game birds and moderately toxic to waterfowl on an acute oral basis).<ref name="New  Pesticide Fact Sheet" /> 
* Fipronil is highly toxic to [[bluegill]] sunfish and highly toxic to [[rainbow trout]] on an acute basis.<ref name="New  Pesticide Fact Sheet" /> 
* An early-lifestage toxicity study in [[rainbow trout]] found that fipronil affects larval growth with a NOEC of 0.0066 ppm and an LOEC of 0.015 ppm. The metabolite MB 46136 is more toxic than the parent to [[freshwater fish]] (6.3 times more toxic to rainbow trout and 3.3 times more toxic to bluegill sunfish). Based on an acute [[daphnia]] study using fipronil and three supplemental studies using its metabolites, fipronil is characterized as highly toxic to aquatic invertebrates.<ref name="New  Pesticide Fact Sheet" /> 
* An invertebrate lifecycle [[daphnia]] study showed that fipronil affects length in daphnids at concentrations greater than 9.8 ppb.<ref name="New  Pesticide Fact Sheet" /> 
* A lifecycle study in [[Mysida|mysids]] shows fipronil affects reproduction, survival, and growth of mysids at concentrations less than 5 ppt.<ref name="New  Pesticide Fact Sheet" /> 
* Acute studies of estuarine animals using [[oyster]]s, mysids, and [[sheepshead minnow]]s show that fipronil is highly acutely toxic to oysters and sheepshead minnows, and very highly toxic to mysids. Metabolites MB 46136 and MB 45950 are more toxic than the parent to freshwater invertebrates (MB 46136 is 6.6 times more toxic and MB 45950 is 1.9 times more toxic to freshwater invertebrates).{{r|New Pesticide Fact Sheet}}

===Colony collapse disorder===
{{main|Colony collapse disorder}}
Fipronil is one of the main chemical causes blamed for the spread of [[colony collapse disorder]] among bees{{citation needed|date=July 2021}}. It has been found by the Minutes-Association for Technical Coordination Fund in France that even at very low nonlethal doses for bees, the pesticide still impairs their ability to locate their [[Beehive|hive]], resulting in large numbers of [[forager]] bees lost with every pollen-finding expedition.<ref name="Lima 2007">{{cite web |last=Lima |first=Pedro |work=Globo Rural |date=n.d. |title=Abelhas com microchip |language=pt |url=http://revistagloborural.globo.com/GloboRural/0,6993,EEC1707683-5809,00.html |archive-url=https://web.archive.org/web/20100112092243/http://revistagloborural.globo.com/GloboRural/0,6993,EEC1707683-5809,00.html |archive-date=2010-01-12 |url-status=dead}}</ref> A synergistic toxic effect of fipronil with the fungal pathogen ''[[Nosema ceranae]]'' was recently reported.<ref name="Aufauvre 2012">{{cite journal |display-authors=3 |last1=Aufauvre |first1=Julie |last2=Biron |first2=David G. |last3=Vidau |first3=Cyril |last4=Fontbonne |first4=Régis |last5=Roudel |first5=Mathieu |last6=Diogon |first6=Marie |last7=Viguès |first7=Bernard |last8=Belzunces |first8=Luc P. |last9=Delbac |first9=Frédéric |last10=Blot |first10=Nicolas |title=Parasite-insecticide interactions: a case study of Nosema ceranae and fipronil synergy on honeybee |journal=Scientific Reports |date=2012 |volume=2 |page=326 |id=Article number: 326 |doi=10.1038/srep00326 |doi-access=free |pmid=22442753 |pmc=3310228|bibcode=2012NatSR...2E.326A }}</ref> The functional basis for this toxic effect is now understood: the synergy between fipronil and the pathogenic fungus induces changes in male bee physiology leading to infertility.<ref name="Kairo 2017">{{cite journal |display-authors=3 |last1=Kairo |first1=Guillaume |last2=Biron |first2=David G. |last3=Ben Abdelkader |first3=Faten |last4=Bonnet |first4=Marc |last5=Tchamitchian |first5=Sylvie |last6=Cousin |first6=Marianne |last7=Dussaubat |first7=Claudia |last8=Benoit |first8=Boris |last9=Kretzschmar |first9=André |last10=Belzunces |first10=Luc P. |last11=Brunet |first11=Jean-Luc |title=Nosema ceranae, Fipronil and their combination compromise honey bee reproduction via changes in male physiology |journal=Scientific Reports |date=2017 |volume=7 |issue=1 |page=8556 |id=Article number: 8556 |doi=10.1038/s41598-017-08380-5 |doi-access=free |pmid=28819220 |pmc=5561069|bibcode=2017NatSR...7.8556K }}</ref> 
A 2013 report by the [[European Food Safety Authority]] identified fipronil as "a high acute risk to honeybees when used as a seed treatment for maize" and on July 16, 2013, the EU voted to ban the use of fipronil on maize and sunflowers within the EU. The ban took effect at the end of 2013.<ref name="EFSA Assesses Risks">{{cite press release |author=<!--anonymous author(s)--> |publisher=European Food Safety Authority |url=http://www.efsa.europa.eu/en/press/news/130527 |title=EFSA assesses risks to bees from fipronil |date=27 May 2013 |access-date=30 Oct 2023}}</ref><ref name="Carrington 2013">{{cite news |url=https://www.theguardian.com/environment/2013/jul/16/eu-fipronil-ban-bees |title=EU to ban fipronil to protect honeybees |date=16 July 2013 |location=London |work=The Guardian |first=Damian |last=Carrington}}</ref>

===Pharmacodynamics===

Fipronil acts by binding to [[allosteric regulation|allosteric]] sites of [[GABAA receptor|GABA<sub>A</sub> receptors]] and GluCl receptors (of insects) as an [[Antagonism (chemistry)|antagonist]] (a form of [[Non-competitive inhibition|noncompetitive inhibition]]). This prevents the opening of chloride ion channels normally encouraged by GABA, reducing the chloride ions' ability to lower a [[neuron]]'s [[membrane potential]]. This results in an overabundance of neurons reaching [[action potential]] and likewise CNS toxicity via overstimulation.<ref name="Cole 1993">{{cite journal |last1=Cole |first1=L. M. |last2=Nicholson |first2=R. A. |last3=Casida |first3=J. E. |year=1993 |title=Action of Phenylpyrazole Insecticides at the GABA-Gated Chloride Channel |journal=Pesticide Biochemistry and Physiology |volume=46 |issue=1 |pages=47–54 |doi=10.1006/pest.1993.1035|bibcode=1993PBioP..46...47C }}</ref><ref name="Ratra 2001">{{cite journal |last1=Ratra |first1=G. S. |last2=Casida |first2=J. E. |year=2001 |title=GABA receptor subunit composition relative to insecticide potency and selectivity |journal=Toxicol. Lett. |volume=122 |issue=3 |pages=215–222 |pmid=11489356 |doi=10.1016/s0378-4274(01)00366-6}}</ref><ref name="Olsen 1999">{{cite book |last1=Olsen |first1=Richard W. |last2=DeLorey |first2=Timothy M. |editor1=Siegel, G. J. |editor2=Agranoff, B. W. |editor3=Fisher, S. K. |editor4=Albers, R. W. |editor5=Uhler, M. D. |title=Basic Neurochemistry: Molecular, Cellular and Medical Aspects |edition=6th |publisher=Lippincott-Raven |location=Philadelphia |date=1999 |isbn=978-0-397-51820-3 |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK28090/ |chapter=GABA Receptor Physiology and Pharmacology}}</ref><ref name="Pesticide Residues in Food">{{cite book |title=Pesticide Residues in Food{{dash}}1997: Report of the Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Core Assessment Group on Pesticide Residues: Lyons, France: 22 September - 1 October 1997, Part 1 |date=1998 |series=FAO Plant Production and Protection Paper 145 |id=M-84 |publisher=Food and Agriculture Organization of the United Nations; World Health Organization |location=Rome |isbn=978-92-5-104116-1 |issn=0259-2517 |chapter-url=https://www.fao.org/3/w8141e/w8141e0s.htm#4.15%20fipronil%20(t)* |chapter=4.15 Fipronil (T)*}}</ref>

:Acute oral {{LD50}} (rat) 97 mg/kg
:Acute dermal LD<span style="font-size:100%;"><sub>50</sub></span> (rat) >2000 mg/kg

In mammals (including humans) fipronil overdose is characterized by vomiting, agitation, and seizures. Intravenous or intramuscular [[benzodiazepine]]s are a useful antidote.<ref name="Gupta p502">{{cite book |title=Veterinary Toxicology: Basic and Clinical Principles |last=Gupta |first=Ramesh C. |year=2007 |pages=502–503 |publisher= Academic Press |location=New York |isbn=978-0-12-370467-2}}</ref><ref name="Mohamed 2004">{{cite journal |display-authors=3 |last1=Mohamed |first1=Fahim |last2=Senarathna |first2=Lalith |last3=Percy |first3=Adrian |last4=Abeyewardene |first4=Manel |last5=Eaglesham |first5=Geoffrey |last6=Cheng |first6=Ron |last7=Azher |first7=Shifa |last8=Hittarage |first8=Ariyasena |last9=Dissanayake |first9=Wasantha |last10=Sheriff |first10=M.H. Rezvi |last11=Davies |first11=Willie |last12=Buckley |first12=Nick A. |last13=Eddleston |first13=Michael |title=Acute Human Self-Poisoning with the N -Phenylpyrazole Insecticide Fipronil—a GABA A -Gated Chloride Channel Blocker |journal=Journal of Toxicology: Clinical Toxicology |date=2004 |volume=42 |issue=7 |pages=955–963 |doi=10.1081/clt-200041784 |pmid=15641641 |pmc=1351141}}</ref>

==History==
===Development===
Fipronil was discovered and developed by [[Rhône-Poulenc]] between 1985 and 1987, and placed on the market in 1993 under the {{US Patent|5,232,940 B2}}.  Between 1987 and 1996, fipronil was evaluated on more than 250 insect pests on 60 crops worldwide, and crop protection accounted for about 39% of total fipronil production in 1997. Since 2003, [[BASF]] holds the patent rights for producing and selling fipronil-based products in many countries.

=== 2017 fipronil eggs contamination ===
{{main article|2017 fipronil eggs contamination}}
The 2017 fipronil eggs contamination is an incident in Europe and South Korea involving the spread of [[insecticide]] contaminated eggs and egg products. [[Egg as food|Chicken eggs]] were found to contain fipronil and distributed to 15 [[European Union]] countries, [[Switzerland]], and [[Hong Kong]].<ref name="15 EU Countries and Hong Kong">{{Cite news |author=<!--anonymous author(s)--> |url=https://www.bbc.com/news/world-europe-40896899 |title=Eggs containing fipronil found in 15 EU countries and Hong Kong |date=2017-08-11 |work=BBC News |access-date=30 Oct 2023 |language=en-GB}}</ref><ref name="17 Nations Get Tainted Eggs">{{Cite news |author=<!--anonymous author(s)--> |url=https://abcnews.go.com/Health/wireStory/danes-imported-20-tons-eggs-tainted-scandal-49152254 |title=EU: 17 nations get tainted eggs, products in growing scandal |work=ABC News |agency=Associated Press |language=en |url-status=dead |archive-url=https://web.archive.org/web/20170811130403/https://abcnews.go.com/Health/wireStory/danes-imported-20-tons-eggs-tainted-scandal-49152254 |archive-date=2017-08-11}}</ref> Approximately 700,000 eggs are thought to have reached shelves in the UK alone.<ref name="Boffey 2017">{{cite web |url=https://www.theguardian.com/world/2017/aug/11/tainted-eggs-found-in-hong-kong-switzerland-and-15-eu-countries |title=Egg contamination scandal widens as 15 EU states, Switzerland and Hong Kong affected |last=Boffey |first=Daniel |date=11 August 2017 |work=The Guardian |access-date=11 August 2017}}</ref>
Eggs at 44 farms in [[Taiwan]] were also found with excessive fipronil levels.<ref name="Eggs at 44 Farms">{{cite web |url=https://www.taiwannews.com.tw/en/news/3239808 |title=Eggs at 44 farms in Taiwan found with excessive insecticide levels |date=26 August 2017 |work=Taiwan News |access-date=26 August 2017 |archive-date=26 August 2017 |archive-url=https://web.archive.org/web/20170826063622/https://www.taiwannews.com.tw/en/news/3239808 |url-status=dead }}</ref>

== See also ==
*[[Imidacloprid]]
*[[Insecticide]]
*[[Merial]]
*[[Pesticide toxicity to bees]]

==References==
{{Reflist}}

==External links==
*[http://npic.orst.edu/factsheets/archive/fiptech.pdf Fipronil Fact Sheet - National Pesticide Information Center]
* {{PPDB|316}}

{{Commons category}}

{{Insecticides}}
{{GABAergics}}
{{Neurotoxins}}
{{Convulsants}}

[[Category:Chloroarenes]]
[[Category:Convulsants]]
[[Category:Endocrine disruptors]]
[[Category:GABAA receptor negative allosteric modulators]]
[[Category:Insecticides]]
[[Category:Nitriles]]
[[Category:Trifluoromethyl compounds]]
[[Category:Pyrazoles]]
[[Category:Sulfoxides]]
[[Category:Chloride channel blockers]]
[[Category:Neurotoxins]]
[[Category:Synthetic insecticides]]
[[Category:French inventions]]