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'''Fipronil''' is a broad-spectrum [[insecticide]] which belongs to the phenyl [[pyrazole]] chemical family. Fipronil disrupts the [[insect central nervous system]] by blocking [[gamma-Aminobutyric acid|GABA]]-gated chloride channels and [[glutamate-gated chloride channel|glutamate-gated chloride (GluCl) channels]]. This causes hyperexcitation of contaminated insects' nerves and muscles.
'''Fipronil''' is a broad-spectrum [[insecticide]] that belongs to the [[phenylpyrazole]] chemical family.''' '''Fipronil disrupts the [[insect central nervous system]] by blocking [[gamma-Aminobutyric acid|GABA]]-gated chloride channels 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 to the [[GABA receptor]] in insects relative to mammals and its effect on GluCl channels, which do not exist in mammals.<ref>Raymond-Delpech V, Matsuda K, Sattelle BM, Rauh JJ, Sattelle DB (2005) Ion channels: molecular targets of neuroactive insecticides. ''Invert Neurosci'': 1-15.</ref>


Fipronil is used as the active ingredient in [[Flea_treatments|flea control products]] for pets and home [[Roach_bait|roach traps]] 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. This includes ongoing observations on possible off-target harm to humans or ecosystems as well as the monitoring of [[Pesticide_resistance|resistance development]].<ref>{{Cite book
Because of its effectiveness on a large number of pests, Fipronil is used as the active ingredient in [[Flea_treatments|flea control products]] for pets and home [[Roach_bait|roach traps]] 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. This includes ongoing observations on possible off-target harm to humans or ecosystems as well as the monitoring of [[Pesticide_resistance|resistance development]].<ref>{{Cite book
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==Biochemistry==
==Effects==
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Fipronil is a slow-acting poison. When used on dogs and cats, it kills virtually all fleas in 24–48 hours.
Fipronil belongs to the [[phenylpyrazole]] chemical family.{{cn|date=August 2017}}


==Effects on insects==
When used as bait, it allows the poisoned insect time to return to the colony or harborage. In [[cockroach]]es, the feces and carcass can contain sufficient residual pesticide to kill others in the same nesting site. In [[ant]]s, the sharing of the bait among colony members assists in the spreading of the poison throughout the colony. With the cascading effect, the projected kill rate is about 95% in three days for ants and cockroaches. Fipronil serves as a good bait toxin not only because of its slow action, but also because most, if not all, of the target insects do not find it offensive or repulsive.{{citation needed|date=December 2013}}
When used as bait, it allows the poisoned insect time to return to the colony or harborage. In [[cockroach]]es, the feces and carcass can contain sufficient residual pesticide to kill others in the same nesting site. In [[ant]]s, the sharing of the bait among colony members assists in the spreading of the poison throughout the colony. With the cascading effect, the projected kill rate is about 95% in three days for ants and cockroaches. Fipronil serves as a good bait toxin not only because of its slow action, but also because most, if not all, of the target insects do not find it offensive or repulsive.{{citation needed|date=December 2013}}
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Fipronil is a slow-acting poison killing virtually all fleas when used on dogs and cats, itin 24–48 hours.{{cn|date=August 2017}}
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Toxic baiting with fipronil has also been shown to be extremely effective in locally eliminating [[German wasp]]s. All colonies within foraging range are completely eliminated within one week.<ref>{{cite web | url = http://anterior.inta.gov.ar/bariloche/ssd/nqn/ecologiadeinsectos/pdfs/Sackmann%20et%20al%202001.pdf |format=PDF| title = Successful Removal of German Yellowjackets (Hymenoptera: Vespidae) by Toxic Baiting. | author = Paula Sackmann, Mauricio Rabinovich and Juan Carlos Corley J.| pages = 811–816 | year = 2001 }}</ref><ref>{{cite journal | url = http://onlinelibrary.wiley.com/doi/10.1002/ps.3262/abstract | title = Short and long-term control of Vespula pensylvanica in Hawaii by fipronil baiting | doi=10.1002/ps.3262 | volume=68 | journal=Pest Management Science | pages=1026–1033}}</ref><ref name="New Zealand">{{cite web|url=http://www.doc.govt.nz/about-doc/news/newsletters/revive-rotoiti/autumn-2011/#wasp-warfare|title=Revive Rotoiti Autumn 2011|year=2011|publisher=New Zealand Department of Conservation|accessdate=11 April 2012}}</ref>{{failed verification|date=August 2017}}


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Toxic baiting with fipronil has also been shown to be extremely effective in locally eliminating [[German wasp]]s. All colonies within foraging range are completely eliminated within one week.<ref>{{cite web | url = http://anterior.inta.gov.ar/bariloche/ssd/nqn/ecologiadeinsectos/pdfs/Sackmann%20et%20al%202001.pdf |format=PDF| title = Successful Removal of German Yellowjackets (Hymenoptera: Vespidae) by Toxic Baiting. | author = Paula Sackmann, Mauricio Rabinovich and Juan Carlos Corley J.| pages = 811–816 | year = 2001 }}</ref><ref>{{cite journal | url = http://onlinelibrary.wiley.com/doi/10.1002/ps.3262/abstract | title = Short and long-term control of Vespula pensylvanica in Hawaii by fipronil baiting | doi=10.1002/ps.3262 | volume=68 | journal=Pest Management Science | pages=1026–1033}}</ref><ref name="New Zealand">{{cite web|url=http://www.doc.govt.nz/about-doc/news/newsletters/revive-rotoiti/autumn-2011/#wasp-warfare|title=Revive Rotoiti Autumn 2011|year=2011|publisher=Department of Conservation|accessdate=11 April 2012}}</ref>
Fipronil's specificity towards insects is believed to be due to its greater affinity to the [[GABA receptor]] in insects relative to mammals and its effect on GluCl channels, which do not exist in mammals.<ref>Raymond-Delpech V, Matsuda K, Sattelle BM, Rauh JJ, Sattelle DB (2005) Ion channels: molecular targets of neuroactive insecticides. ''Invert Neurosci'': 1-15.</ref>


==Toxicity==
===Toxicity===
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Fipronil is classed as a WHO Class II moderately hazardous pesticide, and has a rat acute oral {{LD50}} of 97&nbsp;mg/kg.{{cn|date=August 2017}}


⚫
Fipronil is classed as a WHO Class II moderately hazardous pesticide, and has a rat acute oral {{LD50}} of 97&nbsp;mg/kg.
It has moderate acute toxicity by the oral and inhalation routes in [[rat]]s. Dermal absorption in rats is less than 1% after 24 h and toxicity is considered to be low. It has been found to be very toxic to rabbits.{{cn|date=August 2017}} Fipronil is not absorbed substantially through the skin in contrast to [[neonicotinoid]]s, which are absorbed through the skin to some extent.<ref>{{cite web |url=https://www.pesticideresearch.com/site/?page_id=4843 |title=Cockroach Control |accessdate=August 10, 2016}}</ref> Fipronil is not [[volatility (chemistry)|volatile]], so the likelihood of humans being exposed to this compound in the air has been thought to below.<ref name="NPIC"/>
Symptoms of acute toxicity via ingestion includes sweating, nausea, vomiting, headache, abdominal pain, dizziness, agitation, weakness, and 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.<ref name="NPIC"/>


It has moderate acute toxicity by the oral and inhalation routes in [[rat]]s. Dermal absorption in rats is less than 1% after 24 h and toxicity is considered to be low. It has been found to be very toxic to rabbits.
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The [[Photodegradation|photodegradate]] MB46513 or desulfinylfipronil, has a higher acute toxicity to mammals than fipronil itself by a factor of about 10.<ref name="PNAS">{{Cite journal|url=http://www.pnas.org/content/93/23/12764.full|title=Fipronil insecticide: Novel photochemical desulfinylation with retention of neurotoxicity|doi=10.1073/pnas.93.23.12764 | volume=93|journal=Proceedings of the National Academy of Sciences|pages=12764–12767|date=20 August 1996}}</ref>


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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="PNAS">{{Cite journal|url=http://www.pnas.org/content/93/23/12764.full|title=Fipronil insecticide: Novel photochemical desulfinylation with retention of neurotoxicity|doi=10.1073/pnas.93.23.12764 | volume=93|journal=Proceedings of the National Academy of Sciences|pages=12764–12767}}</ref>
===Chronic toxicity, Carcinogenicity===
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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, in 1996, concerns were raised about human exposure to Frontline spray treatment leading to a denial of registration for the spray product. Commercial pet groomers and [[veterinarian]]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="PesticideNews1">{{cite journal|url= http://fluorideaction.org/wp-content/pesticides/fipronil.article.pest.news.htm|journal=Pesticides News|volume=48|year=2000|page=20|title=Fipronil|date=}}</ref>


The U.S. [[EPA]] 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 carcinogenic effects of fipronil.<ref name="NPIC">{{cite web|author=Jackson, D.; Cornell, C. B.; Luukinen, B.; Buhl, K.; Stone, D.|url=http://npic.orst.edu/factsheets/fipronil.html.|title=Fipronil General Fact Sheet|publisher= National Pesticide Information Center, Oregon State University Extension Services|date=2009.|accessdate=2015-12-07}}</ref>
Symptoms of acute toxicity via ingestion includes sweating, nausea, vomiting, headache, abdominal pain, dizziness, agitation, weakness, and 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 U.S. [[EPA]] 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 carcinogenic effects of fipronil.<ref name="NPIC">{{cite web|url=http://npic.orst.edu/factsheets/archive/fiptech.html|title=Fipronil Technical Fact Sheet, National Pesticide Information Center|date=|accessdate=2015-12-07}}</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 [[veterinarian]]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="PesticideNews1"/> Fipronil is not [[volatility (chemistry)|volatile]], so the likelihood of humans being exposed to this compound in the air is low.<ref name="NPIC"/>
Endocrine changes have been observed in rats: long-term exposure to fipronil in the diet can affect their fertility and it has been found to decrease thyroid hormone levels.<ref>[http://npic.orst.edu/factsheets/fipronil.html Fipronil General Fact Sheet] NPIC, retrieved 3 August 2017</ref>


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 |accessdate=August 10, 2016}}</ref>
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===Pharmacodynamics===


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Fipronil acts by binding to [[allosteric regulation|allosteric]] sites of [[GABAA receptor|GABA<sub>A</sub> receptors]] and GluCl receptors (of insects) as an antagonist (a form of 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>{{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 | url = http://www.sciencedirect.com/science/article/pii/S0048357583710357 | journal = Pestic. Biochem. Physiol | volume = 46 | issue = | pages = 47–54 | doi=10.1006/pest.1993.1035}}</ref><ref>{{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 | url = | journal = Toxicol. Lett | volume = 122 | issue = | pages = 215–222 | pmid = 11489356 | doi=10.1016/s0378-4274(01)00366-6}}</ref><ref>WHO. [http://www.inchem.org/documents/jmpr/jmpmono/v097pr09.htm Pesticide Residues in Food - 1997: Fipronil; International Programme on Chemical Safety], World Health Organization: Lyon, 1997.</ref><ref name="isbn0-397-51820-X">{{cite book |vauthors=Olsen RW, DeLorey TM |veditors=Siegel GJ, Agranoff BW, Fisher SK, Albers RW, Uhler MD | title = Basic neurochemistry: molecular, cellular, and medical aspects | edition = Sixth | language = | publisher = Lippincott-Raven | location = Philadelphia | year = 1999 | origyear = | pages = | quote = | isbn = 0-397-51820-X | oclc = | url = http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=bnchm.section.1181 | chapter = Chapter 16: GABA and Glycine }}</ref>

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

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In animals and humans, fipronil poisoning is characterized by vomiting, agitation, and seizures, and can usually be managed through supportive care and early treatment of seizures, generally with [[benzodiazepine]] use.<ref>{{cite book | url = https://books.google.com/?id=NgMX__L3q40C&pg=PA503&lpg=PA503&dq=fipronil+bioaccumulate+dogs | title = Veterinary Toxicology | author = Ramesh C. Gupta | year = 2007 | pages = 502–503 | isbn = 978-0-12-370467-2 }}</ref><ref>Mohamed F, Senarathna L, Percy A, Abeyewardene M, Eaglesham G, Cheng R, Azher S, Hittarage A, Dissanayake W, Sheriff MH, Davies W, Buckley NA, Eddleston M., Acute human self-poisoning with the N-phenylpyrazole insecticide fipronil--a GABAA-gated chloride channel blocker, J Toxicol Clin Toxicol. 2004;42(7):955-63.</ref>
===Ecological toxicity===
===Ecological toxicity===
<!-- Water and soil -->
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*Fipronils half-life in soil is four months to one year. Its halflife is much less on soil surface, because it is more sensitive to degradation by light ([[photolysis]]) than to degradation water ([[hydrolysis]].<ref>{{cite web|url=http://cdpr.ca.gov/docs/emon/pubs/fatememo/fipronilrev.pdf|title=Environmental Fate of Fipronil|date=March 5, 2007|lastauthoramp=yes|author1=Amrith S. Gunasekara|author2=Tresca Troung|accessdate=April 16, 2016}}</ref>)


Fipronil is highly toxic for [[crustaceans]], [[insects]] and [[zooplankton]],<ref>{{cite web|url=http://www.pesticideinfo.org/Detail_Chemical.jsp?Rec_Id=PC35768#Ecotoxicity|title=Ecotoxicity for Fipronil|date=|accessdate=2010-05-03}}</ref> as well as [[bee]]s, [[termite]]s, [[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.
<!-- aquatic toxicity -->
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Notable results from [[wildlife]] studies include:
⚫
* Fipronil binds to sediments and is highly [[aquatic toxicity|toxic]] to [[zooplankton]], [[crustaceans]], aquatic invertebrates, the [[fringe-toed lizard]], and many fish species. Its low water solubility may reduce the potential hazard to aquatic wildlife.<ref name="Fipronil">{{cite web|title=Fipronil|url=http://www.livingwithbugs.com/PDFiles/fipronil.pdf|publisher=National Pesticides Telecommunication Network|date=1997|accessdate=19 June 2012|page=3}}</ref>


⚫
Its half-life in soil is four months to one year, but much less on soil surface because it is more sensitive to light ([[photolysis]]) than water ([[hydrolysis]].<ref>{{cite web|url=http://cdpr.ca.gov/docs/emon/pubs/fatememo/fipronilrev.pdf|title=Environmental Fate of Fipronil|date=March 5, 2007|lastauthoramp=yes|author1=Amrith S. Gunasekara|author2=Tresca Troung|accessdate=April 16, 2016}}</ref>).
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* Fipronil is very highly toxic to [[bluegill sunfish]] and highly toxic to rainbow trout on an acute basis.<ref name=":0" /> 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).
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An invertebrate lifecycle study on [[daphnia]] showed that fipronil affects length in daphnids at concentrations greater than 9.8 ppb.Based on studies using its metabolites, fipronil is characterized as highly toxic to aquatic invertebrates.<ref name=":0" />
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A lifecycle study in mysids shows fipronil affects reproduction, survival, and growth of mysids at concentrations less than 5 ppt.<ref name=":0" />
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Acute studies of estuarine animals showed 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).<ref name=":0">{{cite web | url=https://nepis.epa.gov/Exe/ZyPURL.cgi?Dockey=P1001KCY.txt | title = Fipronil. May 1996. New Pesticide Fact Sheet. US EPA Office of Prevention, Pesticides and Toxic Substances. | author = United States Environmental Protection Agency Office of Prevention, Pesticides and Toxic Substances| year = 1996}}</ref>


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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. Also, adverse effects in 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]]).
<!-- birds -->
* Fipronil is highly toxic for certain groups of [[galliformes|gallinaceous birds]]. It appears to reduce the [[longevity]] and [[fecundity]] of female [[Braconidae|braconid parasitoids]]. Conversely, the substance is relatively innocuous to [[passerines]], [[wildfowl]], and [[earthworm]]s.<ref>{{cite web|url=http://www.pesticideinfo.org/Detail_Chemical.jsp?Rec_Id=PC35768#Ecotoxicity|title=Ecotoxicity for Fipronil|date=|accessdate=2010-05-03}}</ref>
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Fipronil is highly toxic to upland game birds 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=":0" />
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Chronic (avian reproduction) studies showed no effects at the highest levels tested in mallards (NOEC) = 1000 ppm) or quail (NOEC = 10 ppm). The metabolite MB 46136 is more toxic to the parent than avian species tested (very highly toxic to upland game birds and moderately toxic to waterfowl on an acute oral basis).<ref name=":0" />


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Nontarget effects on some insects (predatory and 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 ecology of the habitat remain unknown, but appear unlikely to be severe.<ref name="PesticideNews1"/> 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="Fipronil 69–72">{{cite journal|last=Jacob|first=CRO|author2=Hellen Maria Soares|author3=Stephen Malfitano Carvalho|author4=Roberta Cornélio Ferreira Nocelli|author5=Osmar Malspina|title=Acute Toxicity of Fipronil to the Stingless Bee Scaptotrigona postica Latreille|journal=Bulletin of Environmental Contamination and Toxicology|year=2013|volume=90|issue=1|pages=69–72|url=http://link.springer.com/article/10.1007%2Fs00128-012-0892-4|accessdate=23 September 2015|doi=10.1007/s00128-012-0892-4}}</ref>
<!-- insects -->
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*Studies of the impact from emergency applications of fipronil as barrier sprays for locust control in Madagascar showed adverse impacts of fipronil on [[termite]]s, which appear to be very severe and long-lived, and, adverse effects on several other invertebrate groups, one species of lizard (''[[Trachylepis elegans]]''), and several species of birds (including the [[Olive Bee-eater|Madagascar bee-eater]]) were seen.

Nontarget effects on sinsects like [[beetle]]s, [[termite]]s, some [[wasps]] and bees were found in field trials of fipronil for desert locust control in [[Mauritania]]. 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.<ref name="PesticideNews1"/> Fipronil is [[Bees and toxic chemicals|toxic to bees]] and should not be applied to vegetation when bees are foraging.<ref name="Fipronil"/>


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>{{cite web | 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=Elise Kissling |author2=BASF SE | year = 2003 }}</ref> The seed treatment involved has since been banned.{{Citation needed|date=November 2007}} Fipronil was used in a broad spraying to control locusts in Madagascar in a program that began in 1997.<ref>June 2000 BBC News story [http://news.bbc.co.uk/2/hi/science/nature/806641.stm "Anti-locust drive 'created havoc'"].</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>{{cite web | 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=Elise Kissling |author2=BASF SE | year = 2003 }}</ref> The seed treatment involved has since been banned.{{Citation needed|date=November 2007}} Fipronil was used in a broad spraying to control locusts in Madagascar in a program that began in 1997.<ref>June 2000 BBC News story [http://news.bbc.co.uk/2/hi/science/nature/806641.stm "Anti-locust drive 'created havoc'"].</ref>
⚫
Fipronil was found to be highly toxic for bee species when used in Brazil: studies on the stingless bee ''[[Scaptotrigona postica]]'' have shown adverse reactions, 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="Fipronil 69–72">{{cite journal|last=Jacob|first=CRO|author2=Hellen Maria Soares|author3=Stephen Malfitano Carvalho|author4=Roberta Cornélio Ferreira Nocelli|author5=Osmar Malspina|title=Acute Toxicity of Fipronil to the Stingless Bee Scaptotrigona postica Latreille|journal=Bulletin of Environmental Contamination and Toxicology|year=2013|volume=90|issue=1|pages=69–72|url=http://link.springer.com/article/10.1007%2Fs00128-012-0892-4|accessdate=23 September 2015|doi=10.1007/s00128-012-0892-4}}</ref>


⚫
Notable results from wildlife studies include:
⚫
* Fipronil is highly [[aquatic toxicity|toxic to fish]] and aquatic invertebrates. Its tendency to bind to sediments and its low water solubility may reduce the potential hazard to aquatic wildlife.<ref name="Fipronil">{{cite web|title=Fipronil|url=http://www.livingwithbugs.com/PDFiles/fipronil.pdf|publisher=National Pesticides Communication Network|accessdate=19 June 2012|page=3}}</ref>
* Fipronil is [[Bees and toxic chemicals|toxic to bees]] and should not be applied to vegetation when bees are foraging.<ref name="Fipronil"/>
⚫
* Based on ecological effects, fipronil is highly toxic to upland game birds 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=":0" />
⚫
* Chronic (avian reproduction) studies show no effects at the highest levels tested in mallards (NOEC) = 1000 ppm) or quail (NOEC = 10 ppm). The metabolite MB 46136 is more toxic to the parent than avian species tested (very highly toxic to upland game birds and moderately toxic to waterfowl on an acute oral basis).<ref name=":0" />
* Fipronil is very highly toxic to bluegill sunfish and highly toxic to rainbow trout on an acute basis.<ref name=":0" />
⚫
* 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=":0" />
⚫
* An invertebrate lifecycle daphnia study showed that fipronil affects length in daphnids at concentrations greater than 9.8 ppb.<ref name=":0" />
⚫
* A lifecycle study in mysids shows fipronil affects reproduction, survival, and growth of mysids at concentrations less than 5 ppt.<ref name=":0" />
⚫
* Acute studies of estuarine animals using oysters, mysids, and sheepshead minnows 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).<ref name=":0">{{cite web | url=https://nepis.epa.gov/Exe/ZyPURL.cgi?Dockey=P1001KCY.txt | title = Fipronil. May 1996. New Pesticide Fact Sheet. US EPA Office of Prevention, Pesticides and Toxic Substances. | author = United States Environmental Protection Agency Office of Prevention, Pesticides and Toxic Substances| year = 1996}}</ref>


===Colony collapse disorder===
Fipronil is one of the main chemical causes blamed for the spread of [[colony collapse disorder]] among bees. 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 hive, resulting in large numbers of forager bees lost with every pollen-finding expedition.<ref>{{cite web|url=http://revistagloborural.globo.com/GloboRural/0,6993,EEC1707683-5809,00.html|title=Colony Collapse Disorder linked to Fipronil|date=|accessdate=2010-06-17}}</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 corn and sunflowers within the EU. The ban took effect at the end of 2013."<ref>{{cite web|url=http://www.efsa.europa.eu/en/press/news/130527.htm|title=EFSA assesses risks to bees from fipronil|date=27 May 2013|accessdate=29 May 2013}}</ref><ref>{{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>
Fipronil is one of the main chemical causes blamed for the spread of [[colony collapse disorder]] among bees. 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 hive, resulting in large numbers of forager bees lost with every pollen-finding expedition.<ref>{{cite web|url=http://revistagloborural.globo.com/GloboRural/0,6993,EEC1707683-5809,00.html|title=Colony Collapse Disorder linked to Fipronil|date=|accessdate=2010-06-17}}</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 corn and sunflowers within the EU. The ban took effect at the end of 2013."<ref>{{cite web|url=http://www.efsa.europa.eu/en/press/news/130527.htm|title=EFSA assesses risks to bees from fipronil|date=27 May 2013|accessdate=29 May 2013}}</ref><ref>{{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 antagonist (a form of 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>{{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 | url = http://www.sciencedirect.com/science/article/pii/S0048357583710357 | journal = Pestic. Biochem. Physiol | volume = 46 | issue = | pages = 47–54 | doi=10.1006/pest.1993.1035}}</ref><ref>{{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 | url = | journal = Toxicol. Lett | volume = 122 | issue = | pages = 215–222 | pmid = 11489356 | doi=10.1016/s0378-4274(01)00366-6}}</ref><ref>WHO. [http://www.inchem.org/documents/jmpr/jmpmono/v097pr09.htm Pesticide Residues in Food - 1997: Fipronil; International Programme on Chemical Safety], World Health Organization: Lyon, 1997.</ref><ref name="isbn0-397-51820-X">{{cite book |vauthors=Olsen RW, DeLorey TM |veditors=Siegel GJ, Agranoff BW, Fisher SK, Albers RW, Uhler MD | title = Basic neurochemistry: molecular, cellular, and medical aspects | edition = Sixth | language = | publisher = Lippincott-Raven | location = Philadelphia | year = 1999 | origyear = | pages = | quote = | isbn = 0-397-51820-X | oclc = | url = http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=bnchm.section.1181 | chapter = Chapter 16: GABA and Glycine }}</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 animals and humans, fipronil poisoning is characterized by vomiting, agitation, and seizures, and can usually be managed through supportive care and early treatment of seizures, generally with [[benzodiazepine]] use.<ref>{{cite book | url = https://books.google.com/?id=NgMX__L3q40C&pg=PA503&lpg=PA503&dq=fipronil+bioaccumulate+dogs | title = Veterinary Toxicology | author = Ramesh C. Gupta | year = 2007 | pages = 502–503 | isbn = 978-0-12-370467-2 }}</ref><ref>Mohamed F, Senarathna L, Percy A, Abeyewardene M, Eaglesham G, Cheng R, Azher S, Hittarage A, Dissanayake W, Sheriff MH, Davies W, Buckley NA, Eddleston M., Acute human self-poisoning with the N-phenylpyrazole insecticide fipronil--a GABAA-gated chloride channel blocker, J Toxicol Clin Toxicol. 2004;42(7):955-63.</ref>


==Discovery and use==
==Discovery and use==
Fipronil was discovered and developed by [[Rhône-Poulenc]] between 1985 and 1987, and placed on the market in 1993 under the US Patent No. US 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.{{cn|date=August 2017}}
Fipronil was discovered and developed by [[Rhône-Poulenc]] between 1985 and 1987, and placed on the market in 1993 under the US Patent No. US 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.

Fipronil is or has been used in:


⚫
*Under the [[trade name]] [[Regent (insecticide)|Regent]], it is used against major [[lepidoptera]]n (moth, butterfly, etc.) and [[orthoptera]]n (grasshopper, locust, etc.) pests on a wide range of field and [[horticultural]] crops and against coleopteran (beetle) larvae in [[soils]]. In 1999, 400,000 hectares were treated with Regent. It became the leading imported product in the area of [[rice]] [[insecticide]]s, the second-biggest crop protection market after [[cotton]] in [[China]].<ref name="PesticideNews1">{{cite journal|journal=Pesticides News|volume=48|year=2000|page=20|title=Fipronil|date=}}</ref>
===Trade names===
*Under the trade names Goliath and Nexa, it is employed for [[cockroach]] and [[ant]] control, including in the US. It is also used against pests of [[field corn]], [[golf courses]], and commercial [[lawn care]] under the trade name Chipco Choice.<ref name="PesticideNews1"/>
Fipronil is or has been used under many [[trade name]]s:<ref>[http://npic.orst.edu/NPRO/ National Pesticide Information Center] Oregon State University and the U.S. Environmental Protection Agency, retrieved 3 August 2017</ref>
*It has been used under the trade name Adonis for [[locust]] control in [[Madagascar]] and [[Kazakhstan]].<ref name="PesticideNews1"/>
⚫
*[[Regent (insecticide)|Regent]] has been used against major [[lepidoptera]]n (moth, butterfly, etc.) and [[orthoptera]]n (grasshopper, locust, etc.) pests on a wide range of field and [[horticultural]] crops and against coleopteran (beetle) larvae in [[soils]]. In 1999, 400,000 hectares were treated with Regent. It became the leading imported product in the area of [[rice]] [[insecticide]]s, the second-biggest crop protection market after [[cotton]] in [[China]].<ref name="PesticideNews1"/>
*Under the trade names Goliath and Nexa, it has been employed for [[cockroach]] and [[ant]] control, including in the US. Under the trade name Chipco Choice it has also been used against pests of [[field corn]], [[golf courses]], and commercial [[lawn care]] .<ref name="PesticideNews1"/>
*Marketed under the names Termidor, Ultrathor, and Taurus in Africa and Australia, fipronil effectively controls [[termite]] pests, and was shown to be effective in field trials in these countries.<ref name="PesticideNews1"/>
⚫
*Termidor has been approved for use against the [[Rasberry crazy ant]] in the [[Houston, Texas]], area, under a special "crisis exemption" from the [[Texas Department of Agriculture]] and the [[United States Environmental Protection Agency|Environmental Protection Agency]]. The chemical is only approved for use in [[Texas]] counties experiencing "confirmed infestations" of the newly discovered ant species.<ref>{{cite web|title=Rasberry Crazy Ant|date=2008-04-12|accessdate=2012-08-06|publisher=Texas A&M|url=http://urbanentomology.tamu.edu/ants/exotic_tx.cfm}}</ref> Use of Termidor is restricted to certified pest control operators in the following states: Alaska, Connecticut, Nebraska, South Carolina, Massachusetts, Indiana, New York, and Washington State.<ref>{{cite web|url=http://www.pestproductsonline.com/products/Termidor-SC-14.html|title=Termidor SC|accessdate=2012-08-06}}</ref>
⚫
*Frontline TopSpot, Fiproguard, Flevox, PetArmor and Sergeant contain Fipronil as the main active ingredient, and along with [[Methoprene|S-methoprene]] in the 'Plus' versions of these products in fighting [[tick]] and [[flea]] infestations in dogs and cats.{{cn|date=August 2017}}
⚫
*In Australia, it is marketed under numerous trade names, including Combat Ant-Rid, Radiate and Termidor, and as generic fipronil
⚫
*Termidor has been approved for use against the [[Rasberry crazy ant]] in the [[Houston, Texas]], area, under a special "crisis exemption" from the [[Texas Department of Agriculture]] and the [[United States Environmental Protection Agency|Environmental Protection Agency]]. The chemical is only approved for use in Texas counties experiencing "confirmed infestations" of the newly discovered ant species.<ref>{{cite web|title=Rasberry Crazy Ant| date=2008-04-12| accessdate=2012-08-06| publisher=Texas A&M|url=http://urbanentomology.tamu.edu/ants/exotic_tx.cfm}}</ref> Use of Termidor is restricted to certified pest control operators in the following states: Alaska, Connecticut, Nebraska, South Carolina, Massachusetts, Indiana, New York, and Washington State.<ref>{{cite web|url=http://www.pestproductsonline.com/products/Termidor-SC-14.html|title=Termidor SC|accessdate=2012-08-06}}</ref>{{dead link|date=August 2017}}
*Under the trade name Adonis it has been used for [[locust]] control in [[Madagascar]] and [[Kazakhstan]].<ref name="PesticideNews1"/>
*In the UK, provisional approval for five years has been granted for fipronil use as a public hygiene insecticide.<ref name="PesticideNews1"/>
⚫
*Fipronil is the main active ingredient of Frontline TopSpot, Fiproguard, Flevox, and PetArmor (used along with [[Methoprene|S-methoprene]] in the 'Plus' versions of these products); these treatments are used in fighting [[tick]] and [[flea]] infestations in dogs and cats.
*Marketed under the names Termidor, Ultrathor, and Taurus in Africa and Australia, fipronil is used against [[termite]]s, and was shown to be effective in field trials in these countries.<ref name="PesticideNews1"/>
⚫
*In New Zealand, fipronil was used in trials to control wasps (''Vespula'' spp.), which are a threat to indigenous [[biodiversity]].<ref name="New Zealand" /> It is now being used by the Department of Conservation to attempt local eradication of wasps,<ref>{{cite web|url=http://www.radionz.co.nz/news/regional/296226/war-on-wasps-in-abel-tasman|title=War on wasps in Abel Tasman|date=10 February 2016|publisher=}}</ref> and is available to the public in an award-winning protein-based bait designed to avoid attracting honey bees.<ref>{{cite web|url=https://wwf-nz.crowdicity.com/post/160207|title=Vespex: Making wide-area wasp control a reality - WWF's Conservation Innovation Awards|website=wwf-nz.crowdicity.com}}</ref><ref>{{cite web|url=http://www.doc.govt.nz/waspcontrol|title=Wasp control using Vespex|first=corporatename = New Zealand Department of Conservation|last=(DOC)|website=www.doc.govt.nz}}</ref>
⚫
*Under numerous trade names, including Combat Ant-Rid, Radiate and Termidor and as generic fipronil it has been marketed in Australia.{{cn|date=August 2017}}
*In the UK, provisional approval for five years has been granted{{when|date=August 2017}} for fipronil use as a public hygiene insecticide.<ref name="PesticideNews1"/>
⚫
*In New Zealand, fipronil was used in trials to control wasps (''Vespula'' spp.), which are a threat to indigenous [[biodiversity]].<ref name="New Zealand" /> As of 2016 it has been used by the Department of Conservation to attempt local eradication of wasps,<ref>{{cite web|url=http://www.radionz.co.nz/news/regional/296226/war-on-wasps-in-abel-tasman|title=War on wasps in Abel Tasman|date=10 February 2016|publisher=}}</ref> and has been available to the public in a protein-based bait designed to avoid attracting honey bees.<ref>{{cite web|url=https://wwf-nz.crowdicity.com/post/160207|title=Vespex: Making wide-area wasp control a reality - WWF's Conservation Innovation Awards|publisher=WWF New Zealand|website=wwf-nz.crowdicity.com|author=Richard Toft | date=25 September 2015}}</ref><ref>{{cite web| url=http://www.doc.govt.nz/waspcontrol| title=Wasp control using Vespex| first=corporatename = New Zealand Department of Conservation|last=(DOC)| website=www.doc.govt.nz}}</ref>


== See also ==
== See also ==

Revision as of 13:39, 3 August 2017

Fipronil
2D chemical structure of fipronil
3D chemical structure of fipronil
Names
IUPAC name
(RS)-5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethylsulfinyl)pyrazole-3-carbonitrile
Other names
Fipronil
Fluocyanobenpyrazole
Termidor
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.102.312 Edit 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,22H2 checkY
    Key: ZOCSXAVNDGMNBV-UHFFFAOYSA-N checkY
  • 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 437.14 g·mol−1
Density 1.477-1.626 g/cm3
Melting point 200.5 °C (392.9 °F; 473.6 K)
Pharmacology
QP53AX15 (WHO)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Fipronil is a broad-spectrum insecticide that belongs to the phenylpyrazole chemical family. Fipronil disrupts the insect central nervous system by blocking GABA-gated chloride channels and 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 to the GABA receptor in insects relative to mammals and its effect on GluCl channels, which do not exist in mammals.[1]

Because of its effectiveness on a large number of pests, Fipronil is used as the active ingredient in flea control products for pets and home roach traps 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. This includes ongoing observations on possible off-target harm to humans or ecosystems as well as the monitoring of resistance development.[2]

Effects

Fipronil is a slow-acting poison. When used on dogs and cats, it kills virtually all fleas in 24–48 hours.

When used as bait, it allows the poisoned insect time to return to the colony or harborage. In cockroaches, the feces and carcass can contain sufficient residual pesticide to kill others in the same nesting site. In ants, the sharing of the bait among colony members assists in the spreading of the poison throughout the colony. With the cascading effect, the projected kill rate is about 95% in three days for ants and cockroaches. Fipronil serves as a good bait toxin not only because of its slow action, but also because most, if not all, of the target insects do not find it offensive or repulsive.[citation needed]

Toxic baiting with fipronil has also been shown to be extremely effective in locally eliminating German wasps. All colonies within foraging range are completely eliminated within one week.[3][4][5]

Toxicity

Fipronil is classed as a WHO Class II moderately hazardous pesticide, and has a rat acute oral LD50 of 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 h and toxicity is considered to be low. It has been found to be very toxic to rabbits.

The photodegradate MB46513 or desulfinylfipronil, appears to have a higher acute toxicity to mammals than fipronil itself by a factor of about 10.[6]

Symptoms of acute toxicity via ingestion includes sweating, nausea, vomiting, headache, abdominal pain, dizziness, agitation, weakness, and 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 U.S. EPA has classified fipronil as a group C (possible human) carcinogen based on an increase in thyroid follicular cell tumors in both sexes of the rat. However, as of 2011, no human data are available regarding the carcinogenic effects of fipronil.[7]

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 veterinarians 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.[8] Fipronil is not volatile, so the likelihood of humans being exposed to this compound in the air is low.[7]

In contrast to neonicotinoids such as acetamiprid, clothianidin, imidacloprid, and thiamethoxam, which are absorbed through the skin to some extent, fipronil is not absorbed substantially through the skin.[9]

Ecological toxicity

Fipronil is highly toxic for crustaceans, insects and zooplankton,[10] as well as bees, termites, rabbits, the fringe-toed lizard, and certain groups of gallinaceous birds. It appears to reduce the longevity and fecundity of female 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 earthworms.

Its half-life in soil is four months to one year, but much less on soil surface because it is more sensitive to light (photolysis) than water (hydrolysis.[11]).

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. Also, adverse effects in were indicated in the short term on several other invertebrate groups, one species of lizard (Trachylepis elegans), and several species of birds (including the Madagascar bee-eater).

Nontarget effects on some insects (predatory and detritivorous beetles, 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 grasshoppers 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 ecology of the habitat remain unknown, but appear unlikely to be severe.[8] 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 ng a.i./bee and a lethal concentration of .24 ng a.i./μl diet. These values are highly toxic in Scaptotrigona postica and bees in general.[12]

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.[13] The seed treatment involved has since been banned.[citation needed] Fipronil was used in a broad spraying to control locusts in Madagascar in a program that began in 1997.[14]

Notable results from wildlife studies include:

  • Fipronil is highly toxic to fish and aquatic invertebrates. Its tendency to bind to sediments and its low water solubility may reduce the potential hazard to aquatic wildlife.[15]
  • Fipronil is toxic to bees and should not be applied to vegetation when bees are foraging.[15]
  • Based on ecological effects, fipronil is highly toxic to upland game birds 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.[16]
  • Chronic (avian reproduction) studies show no effects at the highest levels tested in mallards (NOEC) = 1000 ppm) or quail (NOEC = 10 ppm). The metabolite MB 46136 is more toxic to the parent than avian species tested (very highly toxic to upland game birds and moderately toxic to waterfowl on an acute oral basis).[16]
  • Fipronil is very highly toxic to bluegill sunfish and highly toxic to rainbow trout on an acute basis.[16]
  • 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.[16]
  • An invertebrate lifecycle daphnia study showed that fipronil affects length in daphnids at concentrations greater than 9.8 ppb.[16]
  • A lifecycle study in mysids shows fipronil affects reproduction, survival, and growth of mysids at concentrations less than 5 ppt.[16]
  • Acute studies of estuarine animals using oysters, mysids, and sheepshead minnows 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).[16]

Colony collapse disorder

Fipronil is one of the main chemical causes blamed for the spread of colony collapse disorder among bees. 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 hive, resulting in large numbers of forager bees lost with every pollen-finding expedition.[17] 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 corn and sunflowers within the EU. The ban took effect at the end of 2013."[18][19]

Pharmacodynamics

Fipronil acts by binding to allosteric sites of GABAA receptors and GluCl receptors (of insects) as an antagonist (a form of 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.[20][21][22][23]

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

In animals and humans, fipronil poisoning is characterized by vomiting, agitation, and seizures, and can usually be managed through supportive care and early treatment of seizures, generally with benzodiazepine use.[24][25]

Discovery and use

Fipronil was discovered and developed by Rhône-Poulenc between 1985 and 1987, and placed on the market in 1993 under the US Patent No. US 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.

Fipronil is or has been used in:

  • Under the trade name Regent, it is used against major lepidopteran (moth, butterfly, etc.) and orthopteran (grasshopper, locust, etc.) pests on a wide range of field and horticultural crops and against coleopteran (beetle) larvae in soils. In 1999, 400,000 hectares were treated with Regent. It became the leading imported product in the area of rice insecticides, the second-biggest crop protection market after cotton in China.[8]
  • Under the trade names Goliath and Nexa, it is employed for cockroach and ant control, including in the US. It is also used against pests of field corn, golf courses, and commercial lawn care under the trade name Chipco Choice.[8]
  • It has been used under the trade name Adonis for locust control in Madagascar and Kazakhstan.[8]
  • Marketed under the names Termidor, Ultrathor, and Taurus in Africa and Australia, fipronil effectively controls termite pests, and was shown to be effective in field trials in these countries.[8]
  • Termidor has been approved for use against the Rasberry crazy ant in the Houston, Texas, area, under a special "crisis exemption" from the Texas Department of Agriculture and the Environmental Protection Agency. The chemical is only approved for use in Texas counties experiencing "confirmed infestations" of the newly discovered ant species.[26] Use of Termidor is restricted to certified pest control operators in the following states: Alaska, Connecticut, Nebraska, South Carolina, Massachusetts, Indiana, New York, and Washington State.[27]
  • In Australia, it is marketed under numerous trade names, including Combat Ant-Rid, Radiate and Termidor, and as generic fipronil
  • In the UK, provisional approval for five years has been granted for fipronil use as a public hygiene insecticide.[8]
  • Fipronil is the main active ingredient of Frontline TopSpot, Fiproguard, Flevox, and PetArmor (used along with S-methoprene in the 'Plus' versions of these products); these treatments are used in fighting tick and flea infestations in dogs and cats.
  • In New Zealand, fipronil was used in trials to control wasps (Vespula spp.), which are a threat to indigenous biodiversity.[5] It is now being used by the Department of Conservation to attempt local eradication of wasps,[28] and is available to the public in an award-winning protein-based bait designed to avoid attracting honey bees.[29][30]

See also

References

  1. ^ Raymond-Delpech V, Matsuda K, Sattelle BM, Rauh JJ, Sattelle DB (2005) Ion channels: molecular targets of neuroactive insecticides. Invert Neurosci: 1-15.
  2. ^ Maddison, Jill E.; Page, Stephen W. (2008). Small Animal Clinical Pharmacology (Second ed.). Elsevier Health Sciences. p. 229. ISBN 9780702028588. {{cite book}}: Cite has empty unknown parameters: |editorn-first= and |editorn-last= (help)
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  12. ^ Jacob, CRO; Hellen Maria Soares; Stephen Malfitano Carvalho; Roberta Cornélio Ferreira Nocelli; Osmar Malspina (2013). "Acute Toxicity of Fipronil to the Stingless Bee Scaptotrigona postica Latreille". Bulletin of Environmental Contamination and Toxicology. 90 (1): 69–72. doi:10.1007/s00128-012-0892-4. Retrieved 23 September 2015.
  13. ^ Elise Kissling; BASF SE (2003). "BASF statement regarding temporary suspension of sales of crop protection products containing fipronil in France".
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External links

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