Fipronil

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 GABAA 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:
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 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.
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.
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 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. 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 wasps. 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:
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. A synergistic toxic effect of fipronil with the fungal pathogen "Nosema ceranae" 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 physiology leading to infertility. 
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."
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.
In animals and humans, fipronil overdose is characterized by vomiting, agitation, and seizures, and can usually be managed through use of benzodiazepines
History.
Fipronil was discovered and developed by Rhône-Poulenc 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 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. 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.