Wikipedia

Fipronil

Fipronilis a broad-spectruminsecticidethat belongs to thephenylpyrazolechemical family. Fipronil disrupts theinsect central nervous systemby blocking theligand-gated ion channelof theGABAAreceptorandglutamate-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 greaterbinding affinityfor the GABAAreceptors of insects than to those ofmammals,and for its action on GluCl channels, which do not exist in mammals.[3]As of 2017,there does not appear to be significant resistance amongfleasto fipronil.[4]

Fipronil
2D chemical structure of fipronil
3D chemical structure of fipronil
Names
Preferred IUPAC name
5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethylsulfinyl)pyrazole-3-carbonitrile[1]
Other names
Fipronil
Fluocyanobenpyrazole
Taurus
Termidor
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.102.312Edit this at Wikidata
KEGG
UNII
  • InChI=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,22H2checkY
    Key: ZOCSXAVNDGMNBV-UHFFFAOYSA-NcheckY
  • 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
    Key: ZOCSXAVNDGMNBV-UHFFFAOYAP
  • FC(F)(F)S(=O)c2c(C#N)nn(c1c(Cl)cc(cc1Cl)C(F)(F)F)c2N
Properties
C12H4Cl2F6N4OS
Molar mass 437.14g·mol−1
Density 1.477-1.626 g/cm3
Melting point 200.5 °C (392.9 °F; 473.6 K)
Pharmacology
QP53AX15(WHO)
Hazards
GHSlabelling:
GHS06: ToxicGHS08: Health hazardGHS09: Environmental hazard
Danger
NFPA 704(fire diamond)
[2]
NFPA 704 four-colored diamondHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
2
1
0
Lethal doseor concentration (LD, LC):
97 mg/kg (rat, oral)
0.25 mg/L (rainbow trout, aquatic)
Safety data sheet(SDS) Fipronil
Except where otherwise noted, data are given for materials in theirstandard state(at 25 °C [77 °F], 100 kPa).

Because of its effectiveness on various pests, fipronil is used as the active ingredient inflea controlproducts for pets and homeroach baitsas well as fieldpest controlfor 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 ofpesticide resistancedevelopment.[5]

Physical properties

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Fipronil (IUPAC name5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethylsulfinyl)pyrazole-3-carbonitrile[1]) is a white, solid powder with amoldyodor. It is degraded slightly by sunlight, stable at normal temperatures for one year, and is not stable in presence ofmetal ions.[6]

Use

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Fipronil is/was used against many different pests on different crops, it is used against majorlepidopteran(moth, butterfly, etc.) andorthopteran(grasshopper, locust, etc.) pests on a range of field andhorticulturalcrops and againstcoleopteran(beetle) larvae insoils.It is employed forcockroachandantcontrol as well as locust control and termite pest control. In theUnited States of America,fipronil was approved for use against theRasberry crazy antuntil 2022[7][needs update]in counties ofTexaswhere positive identification had been made by entomologists from theTexas Department of Agricultureand theEnvironmental Protection Agency.InNew Zealand,fipronil was used in trials to control wasps (Vespulaspp.), which are a threat to indigenousbiodiversity.[8]It is now being used by the Department of Conservation to attempt local eradication of wasps,[9][10][11]and is being recommended for control of the invasiveArgentine ant.[12]Fipronil is also the active ingredient in many commercialtickandfleatreatments forpets.[13]

Effects

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Toxicity

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Fipronil is classed as aWHOClass II moderately hazardous pesticide, and has aratacute oralLD50of 97 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 torabbits.[14]

ThephotodegradateMB46513 or desulfinylfipronil, appears to have a higheracute toxicityto mammals than fipronil itself by a factor of about 10.[15]

Symptoms of acute toxicity via ingestion includes sweating, nausea, vomiting, headache, abdominal pain, dizziness, agitation, weakness, andtonic-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. TheUnited States Environmental Protection Agencyhas classified fipronil as a group C (possible human)carcinogenbased on an increase inthyroid follicular cell tumorsin both sexes of the rat. However, as of 2011, no human data are available regarding thecarcinogeniceffects of fipronil.[16]

Two Frontline TopSpot products were determined by theNew York State Department of Environmental Conservationto 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 andveterinary physicianswere 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.[17]Fipronil is notvolatile,so the likelihood of humans being exposed to this compound in the air is low.[16]

In contrast toneonicotinoidssuch asacetamiprid,clothianidin,imidacloprid,andthiamethoxam,which are absorbed through the skin to some extent, fipronil is not absorbed substantially through the skin.[18]

Drinking water contamination

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In 2021, the US EPA put fipronil on the Draft Fifth Contaminant Candidate List (CCL 5) which can lead to future regulation under theSafe Drinking Water Act.[19]

Detection in body fluids

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Fipronil may be quantitated in plasma bygas chromatography-mass spectrometryorliquid chromatography-mass spectrometryto confirm a diagnosis ofpoisoningin hospitalized patients or to provide evidence in a medicolegal death investigation.[20]

Ecological toxicity

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Further information:Pesticide toxicity to bees

Fipronil is highly toxic tocrustaceans,insects(includingbeesandtermites) andzooplankton,as well asrabbits,thefringe-toed lizard,and certain groups ofgallinaceous birds.It appears to reduce thelongevityandfecundityof femalebraconid parasitoids.It is also highly toxic to manyfish,though its toxicity varies with species. Conversely, the substance is relatively innocuous topasserines,wildfowl,andearthworms.

Itshalf-lifein 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).[21]

Few studies of effects onwildlifehave 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.[22]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 theMadagascar bee-eater).

Nontarget effects on some insects (predatory anddetritivorousbeetles,some parasitic wasps and bees) were also found in field trials of fipronil for desert locust control inMauritania,and very low doses (0.6-2.0 g a.i./ha) used againstgrasshoppersinNigercaused 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.[17]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 beeScaptotrigona posticahave shown adverse reactions to the pesticide, including seizures,paralysis,and death with a lethal dose of.54 ng a.i./bee and a lethal concentration of.24 ng a.i./μl diet. These values are highly toxic inScaptotrigona posticaand bees in general.[23]Toxic baiting with fipronil has been shown to be effective in locally eliminatingGerman wasps.All colonies within foraging range were eliminated within one week.[24][25]

In May 2003, the French Directorate-General of Food at the Ministry of Agriculture determined that a case of mass bee mortality observed insouthern Francewas related to acute fipronil toxicity. Toxicity was linked to defectiveseed treatment,which generated dust. In February 2003, the ministry decided to temporarily suspend the sale of BASF crop protection products containing fipronil in France.[26]The seed treatment involved has since been banned.[citation needed]

Notable results from wildlife studies include:

  • Fipronil is highlytoxic to fishandaquatic invertebrates.Its tendency to bind tosedimentsand its low water solubility may reduce the potential hazard to aquatic wildlife.[27]
  • Fipronil istoxic to beesand should not be applied tovegetationwhen bees are foraging.[27]
  • Based on ecological effects, fipronil is highly toxic toupland game birdson 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.[6]
  • Chronic (avian reproduction) studies show no effects at the highest levels tested inmallards(NOEC= 1000 ppm) orquail(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).[6]
  • Fipronil is highly toxic tobluegillsunfish and highly toxic torainbow trouton an acute basis.[6]
  • An early-lifestage toxicity study inrainbow troutfound 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 tofreshwater fish(6.3 times more toxic to rainbow trout and 3.3 times more toxic to bluegill sunfish). Based on an acutedaphniastudy using fipronil and three supplemental studies using its metabolites, fipronil is characterized as highly toxic to aquatic invertebrates.[6]
  • An invertebrate lifecycledaphniastudy showed that fipronil affects length in daphnids at concentrations greater than 9.8 ppb.[6]
  • A lifecycle study inmysidsshows fipronil affects reproduction, survival, and growth of mysids at concentrations less than 5 ppt.[6]
  • Acute studies of estuarine animals usingoysters,mysids, andsheepshead minnowsshow 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).[6]

Colony collapse disorder

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Main article:Colony collapse disorder

Fipronil is one of the main chemical causes blamed for the spread ofcolony collapse disorderamong bees[citation needed].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 theirhive,resulting in large numbers offoragerbees lost with every pollen-finding expedition.[28]A synergistic toxic effect of fipronil with the fungal pathogenNosema ceranaewas recently reported.[29]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.[30] A 2013 report by theEuropean Food Safety Authorityidentified 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.[31][32]

Pharmacodynamics

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Fipronil acts by binding toallostericsites ofGABAAreceptorsand GluCl receptors (of insects) as anantagonist(a form ofnoncompetitive inhibition). This prevents the opening of chloride ion channels normally encouraged by GABA, reducing the chloride ions' ability to lower aneuron'smembrane potential.This results in an overabundance of neurons reachingaction potentialand likewise CNS toxicity via overstimulation.[33][34][35]

Acute oralLD50(rat) 97 mg/kg
Acute dermal LD50(rat) >2000 mg/kg

In mammals (including humans) fipronil overdose is characterized by vomiting, agitation, and seizures. Intravenous or intramuscularbenzodiazepinesare a useful antidote.[36][37]

History

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Development

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Fipronil was discovered and developed byRhône-Poulencbetween 1985 and 1987, and placed on the market in 1993 under theB2 U.S. 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,BASFholds the patent rights for producing and selling fipronil-based products in many countries.

2017 fipronil eggs contamination

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Main article:2017 fipronil eggs contamination

The 2017 fipronil eggs contamination is an incident in Europe and South Korea involving the spread ofinsecticidecontaminated eggs and egg products.Chicken eggswere found to contain fipronil and distributed to 15European Unioncountries,Switzerland,andHong Kong.[38][39]Approximately 700,000 eggs are thought to have reached shelves in the UK alone.[40] Eggs at 44 farms inTaiwanwere also found with excessive fipronil levels.[41]

References

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  1. ^ab"Compound Summary | 5-Amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-1H-pyrazole-3-carbonitrile".PubChem.Bethesda, Md.: National Library of Medicine. n.d.
  2. ^"Safety Date Sheet"(PDF).Santa Cruz Biotechnology, Inc. 23 April 2019. SC-201546 - Fipronil.Retrieved30 October2023.
  3. ^Raymond-Delpech, Valérie; Matsuda, Kazuhiko; Sattelle, Benedict M.; Rauh, James J.; Sattelle, David B. (2005). "Ion channels: molecular targets of neuroactive insecticides".Invertebrate Neuroscience.5(3–4): 119–133.doi:10.1007/s10158-005-0004-9.ISSN1354-2516.PMID16172884.S2CID12654353.
  4. ^Todd-Jenkins, Karen (18 June 2017)."Perception Versus Reality: Insecticide Resistance in Fleas".American Veterinarian.2(3). Archived from the original on 11 April 2020.{{cite journal}}:CS1 maint: unfit URL (link)
  5. ^Maddison, Jill E.; Page, Stephen W. (2008).Small Animal Clinical Pharmacology(2nd ed.). Elsevier Health Sciences. p. 229.ISBN978-0-7020-2858-8.
  6. ^abcdefgh"New Pesticide Fact Sheet".Office of Pesticide Programs; Office of Prevention, Pesticides, and Toxic Substances; United States Environmental Protection Agency. May 1996. EPA-737-F-96-005.Retrieved30 October2023– via nepis.epa.gov.
  7. ^Keigwin, Richard C. Jr. (6 May 2019)."Quarantine exemption under the provisions of Section 18 of the Federal Insecticide, Fungicide and Rodenticide Act"(PDF).Letter to Texas Department of Agriculture. United States Environmental Protection Agency.Retrieved30 October2023– via Texasagriculture.gov.
  8. ^"Wasp Warfare"(PDF).Revive Rotoiti.No. 24. St Arnaud: Department of Conservation; New Zealand Government. Autumn 2011. p. 2.Retrieved30 October2011.
  9. ^Neal, Tracy (10 February 2016)."War on wasps in Abel Tasman".RNZ.Radio New Zealand.Retrieved30 October2023.
  10. ^"Vespex: Making wide-area wasp control a reality - WWF's Conservation Innovation Awards".wwf-nz.crowdicity.com.Archived fromthe originalon 2 August 2017.Retrieved5 March2016.
  11. ^"Wasp control Using Vespex".Department of Conservation; New Zealand Government. n.d.Retrieved30 October2023.
  12. ^"Argentine Ants".Department of Conservation; New Zealand Government. n.d.Retrieved30 October2023.
  13. ^"Vet Strength Flea & Tick Treatments for Cats & Dogs | FRONTLINE".uk.frontline.com.Retrieved26 June2023.
  14. ^"Fipronil Toxicity: Keep Flea Products Away from Rabbits".Veterinary Medicine at Illinois.Retrieved20 November2023.
  15. ^Hainzl, D.; Casida, J. E. (1996)."Fipronil insecticide: Novel photochemical desulfinylation with retention of neurotoxicity".Proceedings of the National Academy of Sciences.93(23): 12764–12767.Bibcode:1996PNAS...9312764H.doi:10.1073/pnas.93.23.12764.PMC23994.PMID8917493.
  16. ^abJackson, D.; Cornell, C. B.; Luukinen, B.; Buhl, K.; Stone, D. (2009)."Fipronil Technical Fact Sheet".National Pesticide Information Center, Oregon State University Extension Services.Retrieved30 October2023.
  17. ^ab"Fipronil".Pesticides News.Vol. 48. London: Pesticides Trust. 2000. p. 20.ISSN0967-6597.[better source needed]
  18. ^"Cockroach Control".Pesticideresearch.com.31 March 2013. Archived fromthe originalon 12 August 2017.Retrieved10 August2016.[better source needed]
  19. ^"Contaminant Candidate List 5 – CCL 5".United States Environmental Protection Agency. n.d.Retrieved30 October2023.
  20. ^Baselt, Randall C. (2017).Disposition of Toxic Drugs and Chemicals in Man(Eleventh ed.). Seal Beach, California: Biomedical Publications. pp. 894–895.ISBN978-0-692-77499-1.
  21. ^Gunasekara, Amrith S.; Truong, Tresca; Goh, Kean S.; Spurlock, Frank; Tjeerdema, Ronald S. (2007)."Environmental fate and toxicology of fipronil"(PDF).Journal of Pesticide Science.32(3): 189–199.doi:10.1584/jpestics.R07-02.ISSN1349-0923.Retrieved30 October2023.
  22. ^Kirby, Alex (27 June 2000)."Anti-locust drive 'created havoc'".Sci/Tech.BBC News.Retrieved30 October2023.
  23. ^Jacob, Cynthia Renata Oliveira; Soares, Hellen Maria; Carvalho, Stephan Malfitano; Nocelli, Roberta Cornélio Ferreira; Malaspina, Osmar (2013). "Acute Toxicity of Fipronil to the Stingless Bee Scaptotrigona postica Latreille".Bulletin of Environmental Contamination and Toxicology.90(1): 69–72.Bibcode:2013BuECT..90...69J.doi:10.1007/s00128-012-0892-4.ISSN1432-0800.PMID23179165.S2CID35297535.
  24. ^Sackmann, Paula; Rabinovich, Mauricio; Corley, Juan Carlos (2001). "Successful Removal of German Yellowjackets (Hymenoptera: Vespidae) by Toxic Baiting".Journal of Economic Entomology.94(4): 811–816.doi:10.1603/0022-0493-94.4.811.ISSN1938-291X.PMID11561837.
  25. ^Hanna, Cause; Foote, David; Kremen, Claire (2012). "Short and long-term control of Vespula pensylvanica in Hawaii by fipronil baiting".Pest Management Science.68(7): 1026–1033.doi:10.1002/ps.3262.PMID22392920.
  26. ^Kissling, Elise; BASF SE (2003)."BASF statement regarding temporary suspension of sales of crop protection products containing fipronil in France"(Press release).[dead link‍]
  27. ^ab"Fipronil"(PDF).National Pesticide Telecommunications Network; Oregon State University. n.d. p. 3.Retrieved30 October2023– via Livingwithbugs.com.
  28. ^Lima, Pedro (n.d.)."Abelhas com microchip".Globo Rural(in Portuguese). Archived fromthe originalon 12 January 2010.
  29. ^Aufauvre, Julie; Biron, David G.; Vidau, Cyril; et al. (2012)."Parasite-insecticide interactions: a case study of Nosema ceranae and fipronil synergy on honeybee".Scientific Reports.2:326.Bibcode:2012NatSR...2E.326A.doi:10.1038/srep00326.PMC3310228.PMID22442753.Article number: 326.
  30. ^Kairo, Guillaume; Biron, David G.; Ben Abdelkader, Faten; et al. (2017)."Nosema ceranae, Fipronil and their combination compromise honey bee reproduction via changes in male physiology".Scientific Reports.7(1): 8556.Bibcode:2017NatSR...7.8556K.doi:10.1038/s41598-017-08380-5.PMC5561069.PMID28819220.Article number: 8556.
  31. ^"EFSA assesses risks to bees from fipronil"(Press release). European Food Safety Authority. 27 May 2013.Retrieved30 October2023.
  32. ^Carrington, Damian (16 July 2013)."EU to ban fipronil to protect honeybees".The Guardian.London.
  33. ^Cole, L. M.; Nicholson, R. A.; Casida, J. E. (1993). "Action of Phenylpyrazole Insecticides at the GABA-Gated Chloride Channel".Pesticide Biochemistry and Physiology.46(1): 47–54.Bibcode:1993PBioP..46...47C.doi:10.1006/pest.1993.1035.
  34. ^"4.15 Fipronil (T)*".Pesticide Residues in Food – 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.FAO Plant Production and Protection Paper 145. Rome: Food and Agriculture Organization of the United Nations; World Health Organization. 1998.ISBN978-92-5-104116-1.ISSN0259-2517.M-84.
  35. ^Wang, Xu; Martínez, María Aránzazu; Wu, Qinghua; Ares, Irma; Martínez-Larrañaga, María Rosa; Anadón, Arturo; Yuan, Zonghui (2016)."Fipronil insecticide toxicology: Oxidative stress and metabolism"(PDF).Critical Reviews in Toxicology.46(10): 876–899.doi:10.1080/10408444.2016.1223014.PMID27643517.
  36. ^Gupta, Ramesh C. (2007).Veterinary Toxicology: Basic and Clinical Principles.New York: Academic Press. pp. 502–503.ISBN978-0-12-370467-2.
  37. ^Mohamed, Fahim; Senarathna, Lalith; Percy, Adrian; et al. (2004)."Acute Human Self-Poisoning with the N -Phenylpyrazole Insecticide Fipronil—a GABA A -Gated Chloride Channel Blocker".Journal of Toxicology: Clinical Toxicology.42(7): 955–963.doi:10.1081/clt-200041784.PMC1351141.PMID15641641.
  38. ^"Eggs containing fipronil found in 15 EU countries and Hong Kong".BBC News.11 August 2017.Retrieved30 October2023.
  39. ^"EU: 17 nations get tainted eggs, products in growing scandal".ABC News.Associated Press. Archived fromthe originalon 11 August 2017.
  40. ^Boffey, Daniel (11 August 2017)."Egg contamination scandal widens as 15 EU states, Switzerland and Hong Kong affected".The Guardian.Retrieved11 August2017.
  41. ^"Eggs at 44 farms in Taiwan found with excessive insecticide levels".Taiwan News.26 August 2017. Archived fromthe originalon 26 August 2017.Retrieved26 August2017.

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