Fipronil is a broad-spectrum insecticide that belongs to the phenylpyrazole chemical family. Fipronil disrupts the

insect central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

by blocking the

ligand-gated ion channel Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in res ...

of the GABA_A receptor 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

binding affinity In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usually a m ...

to the GABA_A receptors of insects, than to those of mammals, and to its action on GluCl channels, which do not exist in mammals. , there did not appear to be significant resistance among fleas to fipronil. Because of its effectiveness on various pests, fipronil is used as the active ingredient in flea control products for pets and home roach traps as well as field

pest control Pest control is the regulation or management of a species defined as a pest; any animal, plant or fungus that impacts adversely on human activities or environment. The human response depends on the importance of the damage done and will range ...

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.

Use

Fipronil is or has been used in: *Under the

trade name A trade name, trading name, or business name, is a pseudonym used by companies that do not operate under their registered company name. The term for this type of alternative name is a "fictitious" business name. Registering the fictitious name w ...

Regent, it is used against major lepidopteran (moth, butterfly, etc.) and orthopteran (grasshopper, locust, etc.) pests on a wide range of field and

horticultural Horticulture is the branch of agriculture that deals with the art, science, technology, and business of plant cultivation. It includes the cultivation of fruits, vegetables, nuts, seeds, herbs, sprouts, mushrooms, algae, flowers, seaweeds and no ...

crops and against

coleopteran Beetles are insects that form the order Coleoptera (), in the superorder Endopterygota. Their front pair of wings are hardened into wing-cases, elytra, distinguishing them from most other insects. The Coleoptera, with about 400,000 described ...

(beetle) larvae in

soil Soil, also commonly referred to as earth or dirt Dirt is an unclean matter, especially when in contact with a person's clothes, skin, or possessions. In such cases, they are said to become dirty. Common types of dirt include: * Debri ...

s. 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. *Under the trade names Goliath and Nexa, it is employed for

cockroach Cockroaches (or roaches) are a Paraphyly, paraphyletic group of insects belonging to Blattodea, containing all members of the group except termites. About 30 cockroach species out of 4,600 are associated with human habitats. Some species are we ...

and

ant Ants are eusocial insects of the family Formicidae and, along with the related wasps and bees, belong to the order Hymenoptera. Ants evolved from vespoid wasp ancestors in the Cretaceous period. More than 13,800 of an estimated total of ...

control, including in the United States. It is also used against pests of field corn, golf courses, and commercial lawn care under the trade name Chipco Choice. *It has been used under the trade name Adonis for

locust Locusts (derived from the Vulgar Latin ''locusta'', meaning grasshopper) are various species of short-horned grasshoppers in the family Acrididae that have a swarming phase. These insects are usually solitary, but under certain circumstanc ...

control in Madagascar and Kazakhstan. *Marketed under the names Termidor, Ultrathor, Fipforce and Taurus in Africa and Australia, fipronil effectively controls

termite Termites are small insects that live in colonies and have distinct castes (eusocial) and feed on wood or other dead plant matter. Termites comprise the infraorder Isoptera, or alternatively the epifamily Termitoidae, within the order Blatto ...

pests, and was shown to be effective in field trials in these countries. *Under the trade name Termidor, fipronil is approved for use against the

Rasberry crazy ant The tawny crazy ant or Rasberry crazy ant, ''Nylanderia fulva'', is an ant originating in South America. Like the longhorn crazy ant (''Paratrechina longicornis''), this species is called "crazy ant" because of its quick, unpredictable movemen ...

until 2022 in counties where positive identification had been made by entomologists from the

Texas Department of Agriculture The Texas Department of Agriculture (TDA) is a state agency within the state of Texas, which is responsible for matters pertaining to agriculture, rural community affairs, and related matters. It is currently headed by Agriculture Commissioner ...

and the Environmental Protection Agency. 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. *In Australia, it is marketed under numerous trade names, including Combat Ant-Rid, Anthem, Clearout (used together with Pyriproxyfen in the Clearout PLUS version as an aerosol spray to control ants, cockroach and flies), Fipforce, Radiate and Termidor, and as generic fipronil. *In the United Kingdom, provisional approval for five years has been granted for fipronil use as a public hygiene insecticide. *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) in the USA and Frontline Tri-Act for Dogs, Plus (Dog), Plus (Cat), Spot-On (Dog) and Spot-On (Cat) in the UK; these treatments are used in fighting

tick Ticks (order Ixodida) are parasitic arachnids that are part of the mite superorder Parasitiformes. Adult ticks are approximately 3 to 5 mm in length depending on age, sex, species, and "fullness". Ticks are external parasites, living by ...

and

flea Flea, the common name for the order Siphonaptera, includes 2,500 species of small flightless insects that live as external parasites of mammals and birds. Fleas live by ingesting the blood of their hosts. Adult fleas grow to about long, a ...

infestations in dogs and cats. *In New Zealand, fipronil was used in trials to control wasps (''

Vespula ''Vespula'' is a small genus of social wasps, widely distributed in the Northern Hemisphere. Along with members of their sister genus ''Dolichovespula'', they are collectively known by the common name yellowjackets (or yellow jackets) in Nor ...

'' ), which are a threat to indigenous

biodiversity Biodiversity or biological diversity is the variety and variability of life on Earth. Biodiversity is a measure of variation at the genetic (''genetic variability''), species (''species diversity''), and ecosystem (''ecosystem diversity'') l ...

. It is now being used by the Department of Conservation to attempt local eradication of wasps, and is being recommended for control of the invasive

Argentine ant The Argentine ant (''Linepithema humile''), formerly ''Iridomyrmex humilis'', is an ant native to northern Argentina, Uruguay, Paraguay, Bolivia and southern Brazil. It is an invasive species that has been established in many Mediterranean c ...

. *In Iran it's used in different forms including a gel formed roach bait named Bersuda which is popular due to minimal footprint, granularity and stickiness that is claimed to spread the contamination by infected roach to other members of the nest. It is reportedly used for

Integrated Pest Management Integrated pest management (IPM), also known as integrated pest control (IPC) is a broad-based approach that integrates both chemical and non-chemical practices for economic control of pests. IPM aims to suppress pest populations below the econ ...

Effects

Toxicity

Fipronil is classed as a WHO Class II moderately hazardous pesticide, and has a rat acute oral 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 hours exposure 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 Acute toxicity describes the adverse effects of a substance that result either from a single exposure or from multiple exposures in a short period of time (usually less than 24 hours). To be described as ''acute'' toxicity, the adverse effect ...

to mammals than fipronil itself by a factor of about 10. 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

United States Environmental Protection Agency The Environmental Protection Agency (EPA) is an independent executive agency of the United States federal government tasked with environmental protection matters. President Richard Nixon proposed the establishment of EPA on July 9, 1970; it ...

has classified fipronil as a group C (possible human)

carcinogen A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive subs ...

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. Two Frontline TopSpot products were determined by the New York State Department of Environmental Conservation to pose no significant exposure risks to workers applying the product. However, concerns were raised about human exposure to Frontline spray treatment in 1996, leading to a denial of registration for the spray product. Commercial pet groomers and

veterinary physician A veterinarian (vet), also known as a veterinary surgeon or veterinary physician, is a medical professional who practices veterinary medicine. They manage a wide range of health conditions and injuries in non-human animals. Along with this, vet ...

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. Fipronil is not volatile, so the likelihood of humans being exposed to this compound in the air is low. In contrast to

neonicotinoid Neonicotinoids (sometimes shortened to neonics ) are a class of neuro-active insecticides chemically similar to nicotine, developed by scientists at Shell and Bayer in the 1980s. The neonicotinoid family includes acetamiprid, clothianidin, din ...

s such as

acetamiprid Acetamiprid is an organic compound with the chemical formula C10H11ClN4. It is an odorless neonicotinoid insecticide produced under the trade names Assail, and Chipco by Aventis CropSciences. It is systemic and intended to control sucking insects ...

clothianidin Clothianidin is an insecticide developed by Takeda Chemical Industries and Bayer AG. Similar to thiamethoxam and imidacloprid, it is a neonicotinoid. Neonicotinoids are a class of insecticides that are chemically similar to nicotine, which has be ...

imidacloprid Imidacloprid is a systemic insecticide belonging to a class of chemicals called the neonicotinoids which act on the central nervous system of insects. The chemical works by interfering with the transmission of stimuli in the insect nervous system ...

, and

thiamethoxam Thiamethoxam is the ISO common name for a mixture of ''cis-trans'' isomers used as a systemic insecticide of the neonicotinoid class. It has a broad spectrum of activity against many types of insects and can be used as a seed dressing. History ...

, which are absorbed through the skin to some extent, fipronil is not absorbed substantially through the skin.

Drinking water contamination

In 2021, the US EPA put fipronil on the Draft Fifth Contaminant Candidate List (CCL 5) which can lead to future regulation under the

Safe Drinking Water Act The Safe Drinking Water Act (SDWA) is the principal federal law in the United States intended to ensure safe drinking water for the public. Pursuant to the act, the Environmental Protection Agency (EPA) is required to set standards for drinking wa ...

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.

Ecological toxicity

Fipronil is highly toxic for

crustaceans Crustaceans (Crustacea, ) form a large, diverse arthropod taxon which includes such animals as decapods, seed shrimp, branchiopods, fish lice, krill, remipedes, isopods, barnacles, copepods, amphipods and mantis shrimp. The crustacean gro ...

insects Insects (from Latin ') are pancrustacean hexapod invertebrates of the class Insecta. They are the largest group within the arthropod phylum. Insects have a chitinous exoskeleton, a three-part body (head, thorax and abdomen), three pairs of j ...

(including bees and

s) and

zooplankton Zooplankton are the animal component of the planktonic community ("zoo" comes from the Greek word for ''animal''). Plankton are aquatic organisms that are unable to swim effectively against currents, and consequently drift or are carried along by ...

, as well as rabbits, the

fringe-toed lizard Fringe-toed lizards are lizards of the genus ''Uma'' in the family Phrynosomatidae, native to deserts of North America. They are adapted for life in sandy deserts with fringe-like scales on their hind toes hence their common name. Description ...

, and certain groups of

gallinaceous birds Galliformes is an order of heavy-bodied ground-feeding birds that includes turkeys, chickens, quail, and other landfowl. Gallinaceous birds, as they are called, are important in their ecosystems as seed dispersers and predators, and are often ...

. It appears to reduce the longevity and

fecundity Fecundity is defined in two ways; in human demography, it is the potential for reproduction of a recorded population as opposed to a sole organism, while in population biology, it is considered similar to fertility, the natural capability to pr ...

of female braconid parasitoids. It is also highly toxic to many

fish Fish are aquatic, craniate, gill-bearing animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish as well as various extinct related groups. Approximately 95% of ...

, though its toxicity varies with species. Conversely, the substance is relatively innocuous to

passerines A passerine () is any bird of the order Passeriformes (; from Latin 'sparrow' and '-shaped'), which includes more than half of all bird species. Sometimes known as perching birds, passerines are distinguished from other orders of birds by th ...

wildfowl The Anatidae are the biological family of water birds that includes ducks, geese, and swans. The family has a cosmopolitan distribution, occurring on all the world's continents except Antarctica. These birds are adapted for swimming, floating on ...

, and

earthworm An earthworm is a terrestrial invertebrate that belongs to the phylum Annelida. They exhibit a tube-within-a-tube body plan; they are externally segmented with corresponding internal segmentation; and they usually have setae on all segments. T ...

s. 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 Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolys ...

). Few studies of effects on

wildlife Wildlife refers to undomesticated animal species, but has come to include all organisms that grow or live wild in an area without being introduced by humans. Wildlife was also synonymous to game: those birds and mammals that were hunted ...

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 The olive bee-eater or Madagascar bee-eater (''Merops superciliosus'') is a near passerine bee-eater species in the genus ''Merops''. It is native to the southern half of Africa where it is present in Angola; Botswana; Burundi; Comoros; Democrat ...

). Nontarget effects on some insects (predatory and detritivorous

beetle Beetles are insects that form the order Coleoptera (), in the superorder Endopterygota. Their front pair of wings are hardened into wing-cases, elytra, distinguishing them from most other insects. The Coleoptera, with about 400,000 describ ...

s, some parasitic

wasps A wasp is any insect of the narrow-waisted suborder Apocrita of the order Hymenoptera which is neither a bee nor an ant; this excludes the broad-waisted sawflies (Symphyta), which look somewhat like wasps, but are in a separate suborder. ...

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 ) , official_languages = , languages_type = National languages 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. Toxic baiting with fipronil has been shown to be effective in locally eliminating

German wasp ''Vespula germanica'', the European wasp, German wasp, or German yellowjacket, is a species of wasp found in much of the Northern Hemisphere, native to Europe, Northern Africa, and temperate Asia. It has spread and become well-established in ma ...

s. All colonies within foraging range were completely eliminated within one week. 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. The seed treatment involved has since been banned. 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. * Fipronil is toxic to bees and should not be applied to vegetation when bees are foraging. * 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. * Chronic (avian reproduction) studies show no effects at the highest levels tested in mallards (

NOEC Measures of pollutant concentration are used to determine risk assessment in public health. Industry is continually synthesizing new chemicals, the regulation of which requires evaluation of the potential danger for human health and the environm ...

= 1000 ppm) or

quail Quail is a collective name for several genera of mid-sized birds generally placed in the order Galliformes. The collective noun for a group of quail is a flock, covey, or bevy. Old World quail are placed in the family Phasianidae, and New ...

(NOEC = 10 ppm). The metabolite MB 46136 is more toxic than the parent to avian species tested (very highly toxic to upland game birds and moderately toxic to waterfowl on an acute oral basis). * Fipronil is highly toxic to bluegill sunfish and highly toxic to rainbow trout on an acute basis. * 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 ''Daphnia'' is a genus of small planktonic crustaceans, in length. ''Daphnia'' are members of the order Anomopoda, and are one of the several small aquatic crustaceans commonly called water fleas because their saltatory swimming style resembl ...

study using fipronil and three supplemental studies using its metabolites, fipronil is characterized as highly toxic to aquatic invertebrates. * An invertebrate lifecycle daphnia study showed that fipronil affects length in daphnids at concentrations greater than 9.8 ppb. * A lifecycle study in mysids shows fipronil affects reproduction, survival, and growth of mysids at concentrations less than 5 ppt. * Acute studies of estuarine animals using

oyster Oyster is the common name for a number of different families of salt-water bivalve molluscs that live in marine or brackish habitats. In some species, the valves are highly calcified, and many are somewhat irregular in shape. Many, but not ...

mysid Mysida is an order of small, shrimp-like crustaceans in the malacostracan superorder Peracarida. Their common name opossum shrimps stems from the presence of a brood pouch or "marsupium" in females. The fact that the larvae are reared in ...

s, and

sheepshead minnow The sheepshead minnow or sheepshead pupfish (''Cyprinodon variegatus'') is a species of ray-finned fish in the family Cyprinodontidae, the pupfishes. It is found in salt marsh and estuary environments and is native to the eastern coasts of Nort ...

s show that fipronil is highly acutely toxic to oysters and sheepshead minnows, and very highly toxic to mysids. Metabolites MB 46136 and MB 45950 are more toxic than the parent to freshwater invertebrates (MB 46136 is 6.6 times more toxic and MB 45950 is 1.9 times more toxic to freshwater invertebrates).

Colony collapse disorder

Fipronil is one of the main chemical causes blamed for the spread of

colony collapse disorder Colony collapse disorder (CCD) is an abnormal phenomenon that occurs when the majority of worker bees in a honey bee colony disappear, leaving behind a queen, plenty of food, and a few nurse bees to care for the remaining immature bees. While s ...

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. A synergistic toxic effect of fipronil with the fungal pathogen ''

Nosema ceranae ''Nosema ceranae'' is a microsporidian, a small, unicellular parasite that mainly affects ''Apis cerana'', the Asiatic honey bee. Along with '' Nosema apis'', it causes the disease nosemosis, the most widespread of the diseases of adult honey b ...

'' was recently reported. The functional basis for this toxic effect is now understood: the synergy between fipronil and the pathogenic fungus induces changes in male bee physiology leading to infertility. A 2013 report by the

European Food Safety Authority The European Food Safety Authority (EFSA) is the agency of the European Union (EU) that provides independent scientific advice and communicates on existing and emerging risks associated with the food chain. EFSA was established in February 2002, ...

identified fipronil as "a high acute risk to honeybees when used as a seed treatment for maize" and on July 16, 2013 the EU voted to ban the use of fipronil on maize and sunflowers within the EU. The ban took effect at the end of 2013.

Pharmacodynamics

Fipronil acts by binding to allosteric sites of GABA_A 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. :Acute oral (rat) 97 mg/kg :Acute dermal LD₅₀ (rat) >2000 mg/kg In

mammals Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur o ...

(including humans) fipronil overdose is characterized by vomiting, agitation, and seizures. Intravenous or intramuscular benzodiazepines are a useful antidote.

History

Development

Fipronil was discovered and developed by

Rhône-Poulenc Rhône-Poulenc () was a French chemical and pharmaceutical company founded in 1928. In 1999 it merged with Hoechst AG to form Aventis. As of 2015, the pharmaceutical operations of Rhône-Poulenc are part of Sanofi and the chemicals divisions a ...

between 1985 and 1987, and placed on the market in 1993 under the . 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 BASF SE () is a German multinational chemical company and the largest chemical producer in the world. Its headquarters is located in Ludwigshafen, Germany. The BASF Group comprises subsidiaries and joint ventures in more than 80 countries ...

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 Humans and human ancestors have scavenged and eaten animal eggs for millions of years. Humans in Southeast Asia had domesticated chickens and harvested their eggs for food by 1,500 BCE. The most widely consumed eggs are those of fowl, especia ...

were found to contain fipronil and distributed to 15

European Union The European Union (EU) is a supranational political and economic union of member states that are located primarily in Europe. The union has a total area of and an estimated total population of about 447million. The EU has often been de ...

countries, Switzerland, and

Hong Kong Hong Kong ( (US) or (UK); , ), officially the Hong Kong Special Administrative Region of the People's Republic of China (abbr. Hong Kong SAR or HKSAR), is a city and special administrative region of China on the eastern Pearl River Delta i ...

. Approximately 700,000 eggs are thought to have reached shelves in the UK alone. Eggs at 44 farms in Taiwan were also found with excessive fipronil levels.

References

External links

Fipronil Fact Sheet - National Pesticide Information Center
* {{Convulsants Chloroarenes Convulsants Endocrine disruptors GABAA receptor negative allosteric modulators Insecticides Nitriles Trifluoromethyl compounds Pyrazoles Sulfoxides Chloride channel blockers Neurotoxins Synthetic insecticides French inventions

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