Frontline Plus For Cats Side Effects

- 02.26

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Fipronil is a broad-use insecticide that belongs to the phenylpyrazole chemical family. Fipronil is a broad-spectrum insecticide that disrupts the insect central nervous system by blocking GABA-gated chloride channels and glutamate-gated chloride (GluCl) channels, resulting in central nervous system toxicity. This causes hyperexcitation of contaminated insects' nerves and muscles. Specificity of fipronil on insects may come from a better efficacy on GABA receptor, but also because GluCl channels do not exist in mammals.


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Effects

Fipronil is a slow acting poison. When used on dogs and cats, it kills virtually all fleas in 24-48 hours.

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.

Toxic baiting with fipronil has also been shown to be extremely effective in locally eliminating German wasps (commonly called yellow jackets in North America). 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.
  • The ecological effects data show that fipronil is highly toxic to upland game birds on an acute oral basis, very highly toxic on a subacute dietary basis, and is practically non-toxic to waterfowl on both an acute and subacute basis. The 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). Fipronil is very highly toxic to bluegill sunfish and highly toxic to rainbow trout on an acute basis. The results of a fish early life-stage toxicity study in rainbow trout show 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 life cycle daphnia study showed that fipronil affects length in daphnids at concentrations greater than 9.8 ppb. A life cycle study in mysids shows fipronil affects reproduction, survival and growth of mysids at concentrations less than 5 pptr. Acute studies of estuarine animals using oysters, mysids, and sheepshead minnows shows 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).

Fipronil is also used as the active ingredient in flea control products for pets, field pest control for corn, golf courses and commercial turf, although flea populations appear to be developing a genetic resistance to its effects.

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 over-stimulation.

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, generally with benzodiazepine use.


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Discovery and use

Fipronil was discovered and developed by Rhône-Poulenc between 1985 and 1987, and placed on the market in 1993 under the US Patent No. US 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.

Fipronil is or has been used in these manners:

  • 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 US. It is also used against pests of field corn, golf courses in commercial lawn care under the trade name Chipco Choice.
  • It has been used under the trade name Adonis for locust control in Madagascar and in Kazakhstan.
  • Marketed under the names Termidor, Ultrathor, and Taurus in Africa and Australia, fipronil effectively controls termite pests, and was shown to be effective in field trials in these countries.
  • Termidor has been approved for use against the Rasberry crazy ant in the Houston, Texas area, under a special "crisis exemption" from the Texas Department of Agriculture and the Environmental Protection Agency. The chemical is only approved for use in Texas counties experiencing "confirmed infestations" of the newly discovered ant species. 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 State.
  • In Australia, marketed under numerous trade names, including Combat Ant-Rid, Termidor, and as generic fipronil
  • In the UK, 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); 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 spp.), 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 available to the public in an award winning protein-based bait designed to avoid attracting honey bees.

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Ecological toxicity

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. There were also indications of adverse effects 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 utilized 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./?L diet. These values are highly toxic in both 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.

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 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."


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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. 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 human. The U.S. EPA 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 is 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 veterinarians 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 there is little likelihood of humans being exposed to this compound in the air.

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.

Source of the article : Wikipedia



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