Fipronil
IUPAC name (RS)-5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4- (trifluoromethylsulfinyl)-1H-pyrazole-3-carbonitrile
Other names Fipronil Fluocyanobenpyrazole Termidor
Identifiers
CAS number	120068-37-3 Y
PubChem	3352
ChemSpider	3235 Y
UNII	QGH063955F Y
KEGG	D01042 Y
ChEBI	CHEBI:5063 Y
ChEMBL	CHEMBL101326 Y
ATCvet code	QP53AX15
Jmol-3D images	Image 1
SMILES FC(F)(F)S(=O)c2c(C#N)nn(c1c(Cl)cc(cc1Cl)C(F)(F)F)c2N
InChI 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 Y Key: ZOCSXAVNDGMNBV-UHFFFAOYSA-N Y 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
Properties
Molecular formula	C12H4Cl2F6N4OS
Molar mass	437.15 g/mol
Density	1.477-1.626 g/cm³
Melting point	200.5 °C
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Fipronil is a broad spectrum insecticide that disrupts the insect central nervous system by blocking the passage of chloride ions through the GABA receptor and glutamate-gated chloride (GluCl) channels, components of the central nervous system. This causes hyperexcitation of contaminated insects' nerves and muscles. Specificity of fipronil on insects may come from a better efficacy on GABA receptor, but also because GluCl channels do not exist in mammals.^[1]

Effects[link]

Fipronil is a slow acting poison. When mixed with a 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.^{[citation needed]}

Toxic baiting with fipronil has also been shown to be extremely effective in locally eliminating German wasps (commonly called yellowjackets in North America). All colonies within foraging range are completely eliminated within one week.^{[2] [3] [4]}

Wildlife impacts include the following:

• 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.^{[citation needed]}
• Fipronil is toxic to bees and should not be applied to vegetation when bees are foraging.^{[citation needed]}
• Fipronil has been found to be highly toxic to upland game birds, but is practically nontoxic to waterfowl and other bird species. One of the metabolites of fipronil has a higher toxicity to birds than the parent compound itself.^[5]

Fipronil is also used as the active ingredient in flea control products for pets, field pest control for corn, golf courses and commercial turf.

It acts by binding to an allosteric site of GABA_A receptors and GluCl receptor (of the insect), a form of noncompetitive inhibition.

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 benzodiazepine use.^[6][7]

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.^[8] The seed treatment involved has since been forbidden.^{[citation needed]} Fipronil was used in a broad spraying to control locusts in Madagascar in a program that began in 1997.^[9]

Discovery and use[link]

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.

Current use of fipronil is as follows:

• Under the trade name Regent, it is used against major lepidopteran and orthopteran pests on a wide range of field and horticultural crops and against coleopteran 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.^[10]

• 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 in commercial lawn care under the trade name Chipco Choice.^[10]

• It has been used under the trade name Adonis for locust control in Madagascar and in Kazakhstan.^[10]

• 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.^[10]

• In the UK, provisional approval for five years has been granted for fipronil use as a public hygiene insecticide.^[10]

• Fipronil is the main active ingredient of Frontline 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.^[11]

• In New Zealand fipronil is has been used in a trial to control wasps, which are a threat to indigenous biodiversity.^[4]

Ecological toxicity[link]

Fipronil is highly toxic for crustaceans, insects and zooplankton^[12], 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.

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. There were also indications of adverse effects in the short term on several other invertebrate groups, one species of lizard (Mabuya 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.^[10]

Colony collapse disorder[link]

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.^[13]

Toxicity[link]

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 appears to have a higher acute toxicity to mammals than fipronil itself by a factor of about 10.^{[citation needed]}

Toxicity on humans has been tested in few studies, more commonly involving human cells which were used in carcinogenicity studies, but with no adverse effects. Yet, fipronil has been classified as a Group C (possible human) carcinogen based on an increase in thyroid follicular cell tumors in both sexes of the rat. Furthermore, fipronil is considered slightly irritating to the skin, while moderately irritating to the eyes in both humans and animals, and there is no evidence suggesting it may cause birth defects.^[14]

Two Top Spot 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.^[10] Fipronil is not volatile, so there is little likelihood of humans being exposed to this compound in the air.^[14]

See also[link]

• Imidacloprid
• Insecticide
• Pesticide toxicity to bees

References[link]

External links[link]

• Fipronil Fact Sheet - National Pesticide Information Center
• Fipronil Toxicity & Regulatory Info - PANNA PesticideInfo database