Frontline (product)

Fipronil is a broad-spectrum insecticide that belongs to the phenylpyrazole chemical family. Fipronil disrupts the insect central nervous system by blocking the ligand-gated ion channel 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 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 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 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.
*Under the trade names Goliath and Nexa, it is employed for cockroach and ant 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 control in Madagascar and Kazakhstan.
*Marketed under the names Termidor, Ultrathor, Fipforce and Taurus in Africa and Australia, fipronil effectively controls termite 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 until 2022 in counties where positive identification had been made by entomologists from the Texas Department of Agriculture 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 and flea infestations in dogs and cats.
*In New Zealand, fipronil was used in trials to control wasps (''Vespula'' ), which are a threat to indigenous biodiversity. 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.
*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.

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 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 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.

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 physicians 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 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.

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.

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, insects (including bees and termites) and zooplankton, as well as 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).

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

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