Fipronil is a broad-spectrum insecticide which belongs to the phenyl pyrazole 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 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.
When used as 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. Fipronil serves as a good bait toxin not only because of its slow action, but also because most, if not all, of the target insects do not find it offensive or repulsive. Fipronil is a slow-acting poison killing virtually all fleas when used on dogs and cats, itin 24–48 hours. Toxic baiting with fipronil has also been shown to be extremely effective in locally eliminating German wasps. All colonies within foraging range are completely eliminated within one week. Fipronil’s specificity towards insects is believed to be due to its greater affinity to the GABA receptor in insects relative to mammals and its effect on GluCl channels, which do not exist in mammals.
Fipronil is highly toxic for crustaceans, insects and zooplankton, 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.
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 in 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.
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. Fipronil was used in a broad spraying to control locusts in Madagascar in a program that began in 1997.
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) = 1000 ppm) or quail (NOEC = 10 ppm). The metabolite MB 46136 is more toxic to the parent than avian species tested (very highly toxic to upland game birds and moderately toxic to waterfowl on an acute oral basis.
- Fipronil is very 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 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 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).
Acute Toxicity and Tolerance of Fipronil
- LD50 acute, rats, p.o. 97 mg/kg
- LD50 acute, dogs, p.o. 640 mg/kg
- LD50 acute, chicken, p.o. 11.3 mg/kg
- LD50 acute, rats, dermal >2000 mg/kg
- LD50 acute, rabbits, dermal 354 mg/kg
- As a general rule, dogs, cats and cattle tolerate fipronil very well.
- Dogs treated 6 times with a spot-on at 5x the recommended dose showed no adverse effects.
- Puppies treated twice with a spot-on at 2x the recommended dose showed no adverse effects.
- In a one-year study fipronil was administered daily to dogs in gelatin capsules at 0.2, 2, or 5 mg/kg. At doses of ≥2 mg/kg several neurotoxicity signs were recorded and one animal died. The NOAEL was 0.2 mg/kg/day.
Toxic Symptoms caused by Fipronil Poisoning
- The primary symptoms of intoxication with fipronil and other phenylpyrazoles affect mainly the Central Nervous System (CNS).
- Most frequent symptoms are:
- Ataxia (uncoordinated movements)
- Hyperreactivity (exaggerated reaction to stimuli)
- Tremor (uncoordinated trembling or shaking movements)
- Cramps (sudden, involuntary contractions of muscles)
- Abnormal gait
- Other symptoms reported after fipronil poisoning include twitching, nodding, aggression, sweating, nausea, lack of appetite, vomiting, headache, abdominal pain, dizziness, agitation and weakness.
- Symptoms appear a few hours after exposure, but depend strongly on the formulation, the dose and the kind of contact (skin, inhalation, ingestion etc).
- Sustained skin exposure can cause local dermatitis (skin irritation) with pruritus (itching) and erythema (red skin).
- In chronic toxicity studies in rats, liver, kidneys and thyroid gland were also affected.
- As a general rule, young animals are more sensitive to overdosing and react stronger.
- Besides erroneous dosing, overdosing can occur due to excessive licking after spot-on delivery to dogs and cats (particularly in cats due to intense grooming).
- A frequent administration error in dogs is partial administration to small dogs of spot-ons approved for large animals.
- A frequent administration error in cats is partial administration to cats of spot-ons approved only for dogs.
Fipronil Side Effects, Adverse Drug Reactions (ADRs) and Warnings
- Fipronil can be slightly irritant for the skin and the eyes.
- When using sprays or aerosols, excessive inhalation of some solvents (e.g. isopropanol) can cause serious problems in young or weak animals. This is not related to fipronil.
- Never use spot-ons for dogs in cats; never use spot-ons for large dogs in small dogs. It happens that some users want to save money buying large tablets or spot-ons for treating smaller dogs (or even cats!) twice or more times. The risk of overdosing is considerable, either due to erroneous calculations or to unskilled manipulation. In addition, dog medicines may sometimes contain other ingredients that are toxic to cats.
- Fipronil is not approved for use in livestock in many countries (e.g. US, EU, Australia) but is abundantly used in cattle in other countries (mainly in Latin America: Argentina, Brazil, Mexico, etc.), mainly in pour-ons. Most such products have withholding periods of 3-4 months for meat and are not approved for use in dairy cows. Unfortunately little is known about the target-animal safety of such pour-ons.
- Never use on rabbits or hedgehogs, particularly on young one, which seem to be particularly sensitive to fipronil.
- Never use on chickens and other poultry: they are much more sensitive to fipronil than mammals. However ducks and other aquatic birds tolerate fipronil better.
- Unless prescribed by a veterinary doctor, never use on dogs or cats products for livestock that are not explicitly approved for such use. There is a high risk of overdosing or of adverse drug reactions due to ingredients that are not tolerated by pets or are even toxic to them.
Antidote and Treatment of Fipronil Intoxication
- There exists no antidote for fipronil poisoning.
- Treatment consists in preventing further exposure together with supportive and symptomatic measures.
- In case of dermal exposure rinse the skin with abundant water and soft detergents.
- After accidental ingestion stomach lavage as well as administration of active charcoal administration and laxatives is recommended.