Fipronil

Fipronil
File:(±)-Fipronil enantiomers structural formulae.png
File:Fipronil-3D-sticks.png
IUPAC name (RS)-5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4- (trifluoromethylsulfinyl)-1H-pyrazole-3-carbonitrile
Other names Fipronil Fluocyanobenpyrazole Termidor
style="background: #F8EABA; text-align: center;" colspan="2" | Identifiers
CAS number	120068-37-3 Y
PubChem	3352
ATCvet code	QP53AX15
SMILES
style="background: #F8EABA; text-align: center;" colspan="2" | Properties
Molecular formula	C12H4Cl2F6N4OS
Molar mass	437.15 g/mol
Density	1.477-1.626 g/cm³
Melting point	200.5 °C
Y (what is this?)  (verify) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Fipronil is a broad spectrum insecticide that disrupts the insect central nervous system by blocking the passage of chloride ions through the GABA receptor and glutamate-gated chloride channels (GluCl), components of the central nervous system. This causes hyperexcitation of contaminated insects' nerves and muscles. Insect specificity of fipronil may come from a better efficacy on GABA receptor but also on the fact that GluCl does not exist in mammals.

Fipronil is a slow acting poison. When mixed with a 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 3 days for ants and cockroaches.

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.

Wildlife impacts include the following:

• 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.
• Fipronil has been found to be highly toxic to upland game birds, but is practically non-toxic to waterfowl and other bird species (2,4). One of the metabolites of fipronil has a higher toxicity to birds than the parent compound itself.

Fipronil is used as the active ingredient in Effipro, Frontline Top Spot (Merial) at about 9.8% concentration. Fipronil is also used together with (S)-methoprene (8.8%) in Frontline Plus (Merial), a topical flea and tick control commonly used on dogs and cats. It kills adult fleas before they lay eggs (within 24 hours). It is also the active ingredient in GardenTech's Over N Out season-long fire ant control product.

After a local application of Effipro/Frontline, fipronil is slightly absorbed (approx. 15%) through the skin. Low levels of fipronil may be detected in the plasma, with a very high variability between dogs.

It is also the active ingredient of Regent, now marketed by BASF, which also sells Fipronil under the brand name Termidor for use as a conventional barrier treatment for termites and also as a dust to be blown into termite tunnels. In the US, ant Fipronil based gels are sold under the MaxForce brand (mfg. Bayer), and under the Combat brand (mfg. Dial Corp). Both brands carry .001% Fipronil by weight as the active ingredient. Agricultural products include Chipco Choice for use against pests of field corn, golf courses and commercial turf.

It acts by binding to an allosteric site of GABAA receptors and GluCl receptor (of the insect), a form of non-competitive inhibition.

Acute oral LD50 (rat) 97 mg/kg

Acute dermal LD50 (rat) >2000 mg/kg

In animals and humans, fipronil poisoning is characterized by vomiting, agitation, and seizures, and can usually be managed through supportive care and early treatment of seizures. This risk may be associated with the withdrawal of the MaxForce tick management product.

In May 2003, the DGAL (Direction Générale de l'Alimentation du ministère de l'Agriculture ) indicated a case of bee mortality observed in Southern France related to Fipronil acute toxicity. Intoxication was linked to defective seed treatment, which generated dust. In February 2003, the French Ministry of Agriculture decided to temporarily suspend the sale of BASF crop protection products containing fipronil in France. The seed treatment involved has since been forbidden. Fipronil was used in a broad spraying to control locusts in Madagascar in a program that began in 1997 .

Fipronil was first developed by Rhone-Poulenc and patented under the US Patent No. US 5,232,940 B2. Since 2003, BASF holds the patent rights for producing and selling Fipronil based products in many countries.

Historical use

Fipronil was discovered and developed by Rhône-Poulenc between 1985–87 and placed on the market in 1993. 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.

Fipronil as marketed under the name Regent is used against major lepidopterous and orthopterous pests on a wide range of field and horticultural crops and against coleopterous larvae in soils. It is also employed for cockroach and ant control under the trade names Goliath and Nexa including in the US, where it is also used against pests of field corn, golf courses and commercial turf (trade name Chipco Choice). It has been used under the trade name Adonis for locust control in Madagascar and in Kazakhstan.

Fipronil controls effectively termite pests and was shown to be effective in field trials in Africa and Australia where it is marketed under the name Termidor.

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. In the UK, provisional approval for five years has been granted for fipronil use as a public hygiene insecticide.

Fipronil is also the main active ingredient of Frontline, a treatment used in fighting ticks and fleas infestations in dogs and cats.

Ecological toxicity

Fipronil is highly toxic to certain groups of gallinaceous birds, while being relatively innocuous to passerines and wildfowl. It is also highly toxic for the fringe-toed lizard. It is highly toxic to bees and termites. It appears to reduce the longevity and fecundity of female braconid parasitoids. It is virtually non-toxic to earthworms.

Fipronil is very highly toxic for crustaceans, insects and zooplankton. It is highly toxic to fish and toxicity to fish varies with species as it is very highly toxic to bluegill sunfish, highly toxic to rainbow trout and highly toxic to European carp. It is also very highly toxic to one of the African tilapia.

Few studies of effects on wildlife have been carried out, but studies of the non-target 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. There were also indications of adverse effects in the short-term on several other invertebrate groups, one species of lizard (Mabuya elegans) and several species of birds (including the Madagascar bee-eater).

Non-target 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 non-target insects comparable with 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.

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.

Toxicity

Fipronil is classed as a WHO Class II moderately hazardous pesticide and has a rat acute oral LD50 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. In contrast, it is of moderate dermal toxicity to rabbits.

The photodegradate MB46513 appears to have a higher acute toxicity to mammals than fipronil itself by a factor of about 10.

Toxicity on humans has been tested in few studies, more commonly involving human cells which were used in carcinogenicity studies but with no adverse effects. Yet, fipronil has been classified as a Group C (Possible Human) Carcinogen based on an increase in thyroid follicular cell tumors in both sexes of the rat. Still, fipronil is considered slightly irritating to the skin, while moderately irritating to the eyes in both humans and animals and there is no evidence suggesting that it may cause birth defects.

Two Top Spot 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 veterinarians were considered to be at risk from chronic exposure via inhalation and dermal absorption during the application of the spray, assuming that they may have to treat up to 20 large dogs per day. Fipronil is not volatile so there is little likelihood of humans being exposed to this compound in the air.

External links

• Fipronil Fact Sheet - National Pesticide Information Center
• Fipronil Toxicity & Regulatory Info - PANNA PesticideInfo database

cs:Fipronil pt:Fipronil