Because of its effectiveness on various pests, fipronil is used as the active ingredient in flea control products for pets and home roach baits 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. Observations on possible harm to humans or ecosystems are ongoing as well as the monitoring of pesticide resistance development.[5]
Physical properties
Fipronil (IUPAC name5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethylsulfinyl)pyrazole-3-carbonitrile[1]) is a white, solid powder with a moldy odor. It is degraded slightly by sunlight, stable at normal temperatures for one year, and is not stable in presence of metal ions.[6]
Fipronil is classed as a WHO Class II moderately hazardous pesticide, and has a ratacute oralLD50 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.[14]
The photodegradate MB46513 or desulfinylfipronil, appears to have a higher acute toxicity to mammals than fipronil itself by a factor of about 10.[15]
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.[16]
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.[17] Fipronil is not volatile, so the likelihood of humans being exposed to this compound in the air is low.[16]
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.[19]
Its half-life in soil is four months to one year, but much less on the soil surface because it is more sensitive to light (photolysis) than water (hydrolysis).[21]
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.[22] 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 detritivorousbeetles, 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 the ecology of the habitat remain unknown, but appear unlikely to be severe.[17] 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.[23] Toxic baiting with fipronil has been shown to be effective in locally eliminating German wasps. All colonies within foraging range were eliminated within one week.[24][25]
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.[26] The seed treatment involved has since been banned.[citation needed]
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.[6]
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 than the parent to avian species tested (very highly toxic to upland game birds and moderately toxic to waterfowl on an acute oral basis).[6]
Fipronil is highly toxic to bluegill sunfish and highly toxic to rainbow trout on an acute basis.[6]
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.[6]
An invertebrate lifecycle daphnia study showed that fipronil affects length in daphnids at concentrations greater than 9.8 ppb.[6]
A lifecycle study in mysids shows fipronil affects reproduction, survival, and growth of mysids at concentrations less than 5 ppt.[6]
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).[6]
Fipronil is one of the main chemical causes blamed for the spread of colony collapse disorder among bees[citation needed]. 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.[28] A synergistic toxic effect of fipronil with the fungal pathogen Nosema ceranae was recently reported.[29] 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.[30]
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 maize and sunflowers within the EU. The ban took effect at the end of 2013.[31][32]
In mammals (including humans) fipronil overdose is characterized by vomiting, agitation, and seizures. Intravenous or intramuscular benzodiazepines are a useful antidote.[37][38]
History
Development
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.
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.[39][40] Approximately 700,000 eggs are thought to have reached shelves in the UK alone.[41]
Eggs at 44 farms in Taiwan were also found with excessive fipronil levels.[42]
^Maddison, Jill E.; Page, Stephen W. (2008). Small Animal Clinical Pharmacology (2nd ed.). Elsevier Health Sciences. p. 229. ISBN978-0-7020-2858-8.
^ abcdefgh"New Pesticide Fact Sheet". Office of Pesticide Programs; Office of Prevention, Pesticides, and Toxic Substances; United States Environmental Protection Agency. May 1996. EPA-737-F-96-005. Retrieved 30 October 2023 – via nepis.epa.gov.
^"Wasp Warfare"(PDF). Revive Rotoiti. No. 24. St Arnaud: Department of Conservation; New Zealand Government. Autumn 2011. p. 2. Retrieved 30 October 2011.
^ abJackson, D.; Cornell, C. B.; Luukinen, B.; Buhl, K.; Stone, D. (2009). "Fipronil Technical Fact Sheet". National Pesticide Information Center, Oregon State University Extension Services. Retrieved 30 October 2023.
^Baselt, Randall C. (2017). Disposition of Toxic Drugs and Chemicals in Man (Eleventh ed.). Seal Beach, California: Biomedical Publications. pp. 894–895. ISBN978-0-692-77499-1.
^Jacob, Cynthia Renata Oliveira; Soares, Hellen Maria; Carvalho, Stephan Malfitano; Nocelli, Roberta Cornélio Ferreira; Malaspina, Osmar (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. ISSN1432-0800. PMID23179165. S2CID35297535.
^Sackmann, Paula; Rabinovich, Mauricio; Corley, Juan Carlos (2001). "Successful Removal of German Yellowjackets (Hymenoptera: Vespidae) by Toxic Baiting". Journal of Economic Entomology. 94 (4): 811–816. doi:10.1603/0022-0493-94.4.811. ISSN1938-291X. PMID11561837.
^Hanna, Cause; Foote, David; Kremen, Claire (2012). "Short and long-term control of Vespula pensylvanica in Hawaii by fipronil baiting". Pest Management Science. 68 (7): 1026–1033. doi:10.1002/ps.3262. PMID22392920.
^ ab"Fipronil"(PDF). National Pesticide Telecommunications Network; Oregon State University. n.d. p. 3. Retrieved 30 October 2023 – via Livingwithbugs.com.
^Cole, L. M.; Nicholson, R. A.; Casida, J. E. (1993). "Action of Phenylpyrazole Insecticides at the GABA-Gated Chloride Channel". Pesticide Biochemistry and Physiology. 46: 47–54. doi:10.1006/pest.1993.1035.
^Ratra, G. S.; Casida, J. E. (2001). "GABA receptor subunit composition relative to insecticide potency and selectivity". Toxicol. Lett. 122 (3): 215–222. doi:10.1016/s0378-4274(01)00366-6. PMID11489356.
^Olsen, Richard W.; DeLorey, Timothy M. (1999). "GABA Receptor Physiology and Pharmacology". In Siegel, G. J.; Agranoff, B. W.; Fisher, S. K.; Albers, R. W.; Uhler, M. D. (eds.). Basic Neurochemistry: Molecular, Cellular and Medical Aspects (6th ed.). Philadelphia: Lippincott-Raven. ISBN978-0-397-51820-3.
^"4.15 Fipronil (T)*". Pesticide Residues in Food – 1997: Report of the Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Core Assessment Group on Pesticide Residues: Lyons, France: 22 September - 1 October 1997, Part 1. FAO Plant Production and Protection Paper 145. Rome: Food and Agriculture Organization of the United Nations; World Health Organization. 1998. ISBN978-92-5-104116-1. ISSN0259-2517. M-84.
^Gupta, Ramesh C. (2007). Veterinary Toxicology: Basic and Clinical Principles. New York: Academic Press. pp. 502–503. ISBN978-0-12-370467-2.
