Fipronil
- Molecular Formula C12H4Cl2F6N4OS
- Average mass 437.148 Da
APPROVED CDSCO INDIA 25.06.2018
Fipronil 50mg/134mg/268mg/402 mg spot on solution for cats and dogs , For treatment of flea and tick infestation in cats and dogs (for veterinary use only)
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]
Use
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.[3]
- 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.[3]
- It has been used under the trade name Adonis for locust control in Madagascar and Kazakhstan.[3]
- 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.[3]
- 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 Texascounties experiencing “confirmed infestations” of the newly discovered ant species.[4] 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.[citation needed]
- 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.[3]
- 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,[6].[7][8]
Effects
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.[9]
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 is available regarding the carcinogenic effects of fipronil.[10]
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.[3] Fipronil is not volatile, so the likelihood of humans being exposed to this compound in the air is low.[10]
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.[11]
Detection in body fluids
Fipronil may be quantitated in plasma by gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry to confirm a diagnosis of poisoning in hospitalised patients or to provide evidence in a medicolegal death investigation.[12]
Ecological toxicity
Fipronil is highly toxic for crustaceans, insects and zooplankton,[13] 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).[14]
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 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.[3] 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.[15] Toxic baiting with fipronil has been shown to be effective in locally eliminating German wasps. All colonies within foraging range were completely eliminated within one week.[16][17][5]
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.[18] 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.[19]
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.[20]
- Fipronil is toxic to bees and should not be applied to vegetation when bees are foraging.[20]
- 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.[21]
- 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).[21]
- Fipronil is very highly toxic to bluegill sunfish and highly toxic to rainbow trout on an acute basis.[21]
- 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.[21]
- An invertebrate lifecycle daphnia study showed that fipronil affects length in daphnids at concentrations greater than 9.8 ppb.[21]
- A lifecycle study in mysids shows fipronil affects reproduction, survival, and growth of mysids at concentrations less than 5 ppt.[21]
- 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).[21]
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.[22] A synergistic toxic effect of fipronil with the fungal pathogen Nosema ceranae was recently reported[23]. The functional basis for this toxic effect is now understood: the synergy between fipronil and the pathogenic fungus induces changes in male physiology leading to infertility[24] A 2013 report by the European 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 corn and sunflowers within the EU. The ban took effect at the end of 2013.”[25][26]
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.[27][28][29][30]
- 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.[31][32]
History
Fipronil was discovered and developed by Rhône-Poulenc between 1985 and 1987, and placed on the market in 1993 under the B2 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, BASF holds the patent rights for producing and selling fipronil-based products in many countries.
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. Chicken eggs were found to contain Fipronil and distributed to 15 European Union countries, Switzerland, and Hong Kong.[33][34] Approximately 700,000 eggs are thought to have reached shelves in the UK alone.[35] Eggs at 44 farms in Taiwan were also found with excessive Fipronil levels.[36]
SYN
SYN 2
SYN 3
SYN 4
PATENT
http://www.allindianpatents.com/patents/271132-a-process-for-the-synthesis-of-fipronil
5-Amino-l-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethyl
sulfinyl pyrazole or 5-Amino-[2,6-dichloro-4-(trif]uoromethyl)phenyl]-4-[-(1 (R,S)-trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile also known as Fipronil is a novel pesticide characterized by high efficiency, low toxicity and especially low residue.
There are various routes to synthesize Fipronil by oxidation of thiopyrazole with various other oxidizing agents in suitable solvents. Oxidation of sulfides is a very useful route for the preparation of sulfoxides. Literature is replete with the conversion of sulfides to sulfoxides and/or sulfones. However, most of the existing methods use expensive, toxic or rare oxidizing reagents, which are difficult to prepare, are very expensive and cannot be used on commercial scale. Many of these processes suffer from poor selectivity.
WO01/30760 describes oxidation of 5-amino-l-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylthio-pyrazole with trifluoro-acetic acid and hydrogen peroxide in the presence of boric acid. The quantity
of trifluoroacetic acid used is 14.5 molar equivalents. The patent also
discloses the preparation of 5-amino-1-(2,6-dichloro-4-trifluoromethyl
phenyl)-3-cyano-4-trifluoromethylthio-pyrazole from 5-amino-1-(2,6-
dichloro-4-trifluoromethyl phenyl)-3-cyano pyrazole-4-yl disulphide.
European Patent publication No.295117 describes the preparation of 5-amino-l-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylsulphinyl pyrazole starting from 2,6-Dichloro-4-trifluoromethylaniline to give an intermediate 5-amino-l-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylthiopyrazole which is oxidized with meta-chloroperbenzoic acid in chloroform to give desired product.
Oxidizing agents such as perbenzoic acids do not provide effective and regioselective oxidation of electron deficient sulfides such as trifluoromethylsulphides which are less readily oxidized than other sulfides. Trifluoroacetic acid and trichloroacetic acid are found to be very efficient and regioselective oxidation medium for oxidation of 5-amino-l-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylthio-pyrazole in presence of hydrogen peroxide. Trichloroacetic acid can not be used alone due to higher melting point. Trifluoroacetic acid on the other hand is very regioselective with respect to conversion and low by-products formation. However, it is expensive, water miscible, corrosive to metal as well as glass, comparatively lower boiling and it’s recovery (in anhydrous form) is complex in nature.
W000/35851/2000 talks about synthesis of 2,6-Dichloro-4-trifluoromethylaniline starting from 3,4,5-trichloro-benzotrifluoride in the presence of alkaline fluorides like lithium fluoride and ammonia in the
presence of N-methylpyrrolidone at 250°C to give 97% conversion and 87% selectivity. The main drawback of the above process is the synthesis of 3,4,5-trichlorobenzotrifluoride in high yield and purity. Chlorination of p-chlorobenzotrifluoride gives a mixture of 3,4,5-trichlorobenzotrifluoride in 72% GLC conversions, 3,4-dichloro and tetrachlorobenzotrifluoride. The process to get pure 3,4,5-isomer from this mixture by fractionation followed by crystallization is very tedious. Moreover in-spite of using very pure intermediates, substantial amount of an undesired isomer (3-amino-4,5-dichlorobenzotrifluoride) is also obtained.
Another approach to generate 3,4,5-trichlorobenzotrifluoride with high yield and purity is to perform denitrochlorination of 4-chloro-3,5-dinitrobenzotrifluoride in the presence of a catalyst as described in GB Patent 2154581A. Even though the process produces 3,4,5-trichlorobenzotrifluoide in high yield and purity, the reaction conditions are too drastic to be employed for an industrial process.
The known commercial processes for the manufacture of Fipronil uses corrosive and expensive chemical such as trifluoroaceticacid, hydrogen peroxide and m-chloroperbenzoicacid Trifluoroacetic acid is expensive and generally not used in large quantities, as well as of m-chloroperbenzoic acid is difficult to handle at commercial scale due to its un-stability and detonating effect. Also the raw material used such as 2,6-Dichloro-4-trifluoromethylaniline are not easily available or made. The overall process for the Fipronil as disclosed above is found to be unsatisfactory in one respect or the other.
Thus, there is felt a need for preparing Fipronil from easily available raw materials in a simple and economical manner at an industrial level, with high yields and purity.
PATENT
https://patents.google.com/patent/US20130030190A1/en
-
5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethyl sulfinyl pyrazole or 5-Amino-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[-(1(R,S)-trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile also known as Fipronil is a novel pesticide characterized by high efficiency, low toxicity and especially low residue.
- [0005]
There are various routes to synthesize Fipronil by oxidation of thiopyrazole with various other oxidizing agents in suitable solvents. Oxidation of sulfides is a very useful route for the preparation of sulfoxides. Literature is replete with the conversion of sulfides to sulfoxides and/or sulfones. However, most of the existing methods use expensive, toxic or rare oxidizing reagents, which are difficult to prepare, are very expensive and cannot be used on commercial scale. Many of these processes suffer from poor selectivity.
- [0006]
WO01/30760 describes oxidation of 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylthio-pyrazole with trifluoro-acetic acid and hydrogen peroxide in the presence of boric acid. The quantity of trifluoroacetic acid used is 14.5 molar equivalents. The patent also discloses the preparation of 5-amino-1-(2,6-dichloro-4-trifluoromethyl phenyl)-3-cyano-4-trifluoromethylthio-pyrazole from 5-amino-1-(2,6-dichloro-4-trifluoromethyl phenyl)-3-cyano pyrazole-4-yl disulphide.
- [0007]
European Patent publication No. 295117 describes the preparation of 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylsulphinyl pyrazole starting from 2,6-Dichloro-4-trifluoromethylaniline to give an intermediate 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylthiopyrazole which is oxidized with meta-chloroperbenzoic acid in chloroform to give desired product.
- [0008]
Oxidizing agents such as perbenzoic acids do not provide effective and regioselective oxidation of electron deficient sulfides such as trifluoromethylsulphides which are less readily oxidized than other sulfides. Trifluoroacetic acid and trichloroacetic acid are found to be very efficient and regioselective oxidation medium for oxidation of 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylthio-pyrazole in presence of hydrogen peroxide. Trichloroacetic acid can not be used alone due to higher melting point. Trifluoroacetic acid on the other hand is very regioselective with respect to conversion and low by-products formation. However, it is expensive, water miscible, corrosive to metal as well as glass, comparatively lower boiling and it’s recovery (in anhydrous form) is complex in nature.
- [0009]
WO00/35851/2000 talks about synthesis of 2,6-Dichloro-4-trifluoromethylaniline starting from 3,4,5-trichloro-benzotrifluoride in the presence of alkaline fluorides like lithium fluoride and ammonia in the presence of N-methylpyrrolidone at 250° C. to give 97% conversion and 87% selectivity. The main drawback of the above process is the synthesis of 3,4,5-trichlorobenzotrifluoride in high yield and purity. Chlorination of p-chlorobenzotrifluoride gives a mixture of 3,4,5-trichlorobenzotrifluoride in 72% GLC conversions, 3,4-dichloro and tetrachlorobenzotrifluoride. The process to get pure 3,4,5-isomer from this mixture by fractionation followed by crystallization is very tedious. Moreover in-spite of using very pure intermediates, substantial amount of an undesired isomer (3-amino-4,5-dichlorobenzotrifluoride) is also obtained.
- [0010]
Another approach to generate 3,4,5-trichlorobenzotrifluoride with high yield and purity is to perform denitrochlorination of 4-chloro-3,5-dinitrobenzotrifluoride in the presence of a catalyst as described in GB Patent 2154581A. Even though the process produces 3,4,5-trichlorobenzotrifluoide in high yield and purity, the reaction conditions are too drastic to be employed for an industrial process.
- [0011]
The known commercial processes for the manufacture of Fipronil uses corrosive and expensive chemical such as trifluoroaceticacid, hydrogen peroxide and m-chloroperbenzoicacid Trifluoroacetic acid is expensive and generally not used in large quantities, as well as of m-chloroperbenzoic acid is difficult to handle at commercial scale due to its un-stability and detonating effect. Also the raw material used such as 2,6-Dichloro-4-trifluoromethylaniline are not easily available or made. The overall process for the Fipronil as disclosed above is found to be unsatisfactory in one respect or the other.
- [0012]
Thus, there is felt a need for preparing Fipronil from easily available raw materials in a simple and economical manner at an industrial level, with high yields and purity.
-
- Example 18
- [0081]
A mixture of 700 g of dichloroacetic acid and trichloroacetic acid was taken along with 300 g of chlorobenzene, 2 g of boric acid and 280 g of 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethyl thiopyrazole, the content were cooled to 15-20° C. Aqueous H202 (44.2 g, 50%) was added and mass was stirred for 20 hrs. The mass was then processed and Fipronil was isolated by filtration. After work up as above, 269 g of Fipronil of purity 94% was obtained. The filtered Fipronil was then purified using chlorobenzene (5 ml/g) followed by mixture (1 ml/g, 80:20 v/v) of ethylacetate and chlorobenzene to get 232 g of Fipronil of greater than 97% purity.
- [0081]
Example 19 Purification of Fipronil
- [0082]
The fipronil prepared in example 18 of purity 97% was treated with a mixture (232 ml) of ethylacetate & chlorobenzene (80:20 v/v). This reaction mixture was heated to 85-90° C. & maintained for 1 hr. It was further cooled up to 30° C. in stages & filtered. Fipronil thus obtained had a purity of 98%. This cycle was repeated to obtain fipronil of above 98% purity.
- [0083]
The useful constituents from various streams of crystallization, leaching as above were reused and recycled, fipronil was isolated in 80-85% yield with purity of above 98%.
PATENT
CN 101250158 [2008 to Hunan Res Inst of of chemical Ind.]
WO2005/44806 A1, ; Page/Page column 7-8; 12 ;
WO2009/77853 A1, ; Page/Page column 28-29 ;
US 5,618,945 [1995, to Rhone-Poulenc]
CN 102060774
IN 178903 [1997, to Rallis India Ltd.]
WO 2009/077,853 [2009 to Vetoquinol SA ]
BG 109983 [2008 to BASF Agro B V]
US 8,507,693 [2013, to Gharda]
US 5,618,945 [1995, to Rhone-Poulenc]
WO 2007/122,440 [ 2007 to Gharda Chemicals Ltd.]
FR 2,925,493 [2009 to to Vetoquinol SA ]
CN 1176078 [ 2002 to Jiangsu Prov Inst of Pesticide]
EP 0,374,061 [ 1990 to Rhone Poulenc Agrochimie]
US 5,232,940 [1993, to May and Baker]
PAPER
Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), , # 24 p. 3371 – 3376
Synthesis 2008, 11, 1682-1684
Synthesis 2007, 22, 3507-3511
Tetrahedron Letters, , 2007, 48(48), 8518-8520
Tetrahedron Letters 2008 ,49. 3463-3465
References
- Jump up^ Raymond-Delpech, Valérie; Matsuda, Kazuhiko; Sattelle, Benedict M.; Rauh, James J.; Sattelle, David B. (2005-09-20). “Ion channels: molecular targets of neuroactive insecticides”. Invertebrate Neuroscience. 5 (3-4): 119–133. doi:10.1007/s10158-005-0004-9. ISSN 1354-2516.
- Jump up^ Maddison, Jill E.; Page, Stephen W. (2008). Small Animal Clinical Pharmacology(Second ed.). Elsevier Health Sciences. p. 229. ISBN 9780702028588.
- ^ Jump up to:a b c d e f g “Fipronil”. Pesticides News. 48: 20. 2000.
- Jump up^ “Rasberry Crazy Ant”. Texas A&M. 2008-04-12. Archived from the original on 2007-07-14. Retrieved 2012-08-06.
- ^ Jump up to:a b “Revive Rotoiti Autumn 2011”. Department of Conservation. 2011. Retrieved 11 April2012.
- Jump up^ “War on wasps in Abel Tasman”. 10 February 2016.
- Jump up^ “Vespex: Making wide-area wasp control a reality – WWF’s Conservation Innovation Awards”. wwf-nz.crowdicity.com.
- Jump up^ (DOC), corporatename = New Zealand Department of Conservation. “Wasp control using Vespex”. http://www.doc.govt.nz.
- Jump up^ “Fipronil insecticide: Novel photochemical desulfinylation with retention of neurotoxicity”. Proceedings of the National Academy of Sciences. 93: 12764–12767. doi:10.1073/pnas.93.23.12764. PMC 23994
![Freely accessible]( "Freely accessible")
. - ^ Jump up to:a b “Fipronil Technical Fact Sheet, National Pesticide Information Center”. Retrieved 2015-12-07.
- Jump up^ “Cockroach Control”. Retrieved August 10, 2016.
- Jump up^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 11th edition, Biomedical Publications, Seal Beach, CA, 2017, pp. 894-895. ISBN 978-0-692-77499-1
- Jump up^ “Ecotoxicity for Fipronil”. Retrieved 2010-05-03.
- Jump up^ Amrith S. Gunasekara & Tresca Troung (March 5, 2007). “Environmental Fate of Fipronil” (PDF). Retrieved April 16, 2016.
- Jump up^ 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.
- Jump up^ Paula Sackmann, Mauricio Rabinovich and Juan Carlos Corley J. (2001). “Successful Removal of German Yellowjackets (Hymenoptera: Vespidae) by Toxic Baiting” (PDF). pp. 811–816.
- Jump up^ “Short and long-term control of Vespula pensylvanica in Hawaii by fipronil baiting”. Pest Management Science. 68: 1026–1033. doi:10.1002/ps.3262.
- Jump up^ Elise Kissling; BASF SE (2003). “BASF statement regarding temporary suspension of sales of crop protection products containing fipronil in France”.
- Jump up^ June 2000 BBC News story “Anti-locust drive ‘created havoc'”.
- ^ Jump up to:a b “Fipronil” (PDF). National Pesticides Communication Network. p. 3. Retrieved 19 June 2012.
- ^ Jump up to:a b c d e f g United States Environmental Protection Agency Office of Prevention, Pesticides and Toxic Substances (1996). “Fipronil. May 1996. New Pesticide Fact Sheet. US EPA Office of Prevention, Pesticides and Toxic Substances”.
- Jump up^ “Colony Collapse Disorder linked to Fipronil”. Retrieved 2010-06-17.
- Jump up^ Aufavure J., Biron D. G., Vidau C., Fontbonne R., Roudel M., Diogon M., Viguès B., Belzunces L. P., Delbac F., Blot N. (2012) Parasite – insecticide interactions: a case study of Nosema ceranae and fipronil synergy on honeybee. Scientific Reports 2:326 – DOI: 10.1038/srep00326
- Jump up^ Kairo G, Biron D.G, Ben A.F, Bonnet M, Tchamitchian S, Cousin M, … & Brunet J.L (2017) Nosema ceranae, Fipronil and their combination compromise honey bee reproduction via changes in male physiology]. Scientific reports, 7(1), 8556.
- Jump up^ “EFSA assesses risks to bees from fipronil”. 27 May 2013. Retrieved 29 May 2013.
- Jump up^ Carrington, Damian (16 July 2013). “EU to ban fipronil to protect honeybees”. The Guardian. London.
- Jump up^ Cole, L. M.; Nicholson, R. A.; Casida, J. E. (1993). “Action of Phenylpyrazole Insecticides at the GABA-Gated Chloride Channel”. Pestic. Biochem. Physiol. 46: 47–54. doi:10.1006/pest.1993.1035.
- Jump up^ Ratra, G. S.; Casida, J. E. (2001). “GABA receptor subunit composition relative to insecticide potency and selectivity”. Toxicol. Lett. 122: 215–222. doi:10.1016/s0378-4274(01)00366-6. PMID 11489356.
- Jump up^ WHO. Pesticide Residues in Food – 1997: Fipronil; International Programme on Chemical Safety, World Health Organization: Lyon, 1997.
- Jump up^ Olsen RW, DeLorey TM (1999). “Chapter 16: GABA and Glycine”. In Siegel GJ, Agranoff BW, Fisher SK, Albers RW, Uhler MD. Basic neurochemistry: molecular, cellular, and medical aspects (Sixth ed.). Philadelphia: Lippincott-Raven. ISBN 0-397-51820-X.
- Jump up^ Ramesh C. Gupta (2007). Veterinary Toxicology. pp. 502–503. ISBN 978-0-12-370467-2.
- Jump up^ 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.
- Jump up^ “Eggs containing fipronil found in 15 EU countries and Hong Kong”. BBC News. 2017-08-11. Retrieved 2017-08-11.
- Jump up^ News, ABC. “EU: 17 nations get tainted eggs, products in growing scandal”. ABC News. Archived from the original on 2017-08-11. Retrieved 2017-08-11.
- Jump up^ Boffey, Daniel (11 August 2017). “Egg contamination scandal widens as 15 EU states, Switzerland and Hong Kong affected”. The Guardian. Retrieved 11 August 2017.
- Jump up^ “Eggs at 44 farms in Taiwan found with excessive insecticide levels”. Taiwan News. 26 August 2017. Retrieved 26 August 2017.
External links
- Fipronil Fact Sheet – National Pesticide Information Center
- Fipronil Toxicity & Regulatory Info – PANNA PesticideInfo database
- Fipronil in the Pesticide Properties DataBase (PPDB)
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| Names | |
|---|---|
| IUPAC name
(RS)-5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethylsulfinyl)pyrazole-3-carbonitrile
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| Other names
Fipronil
Fluocyanobenpyrazole Termidor |
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| Identifiers | |
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3D model (JSmol)
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| ChEBI | |
| ChEMBL | |
| ChemSpider | |
| ECHA InfoCard | 100.102.312 |
| KEGG | |
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PubChem CID
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| UNII | |
| 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) | |
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Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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/////////////Fipronil, INDIA 2018, フィプロニル , HSDB 7051, RM 1601, veterinary, ind 2018
C1=C(C=C(C(=C1Cl)N2C(=C(C(=N2)C#N)S(=O)C(F)(F)F)N)Cl)C(F)(F)F
“ DRUG APPROVALS INTERNATIONAL” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent