피프로닐

log Kow = 4.0

4

In water, 1.9 mg/L (pH 5), 2.4 mg/L (pH 9), 1.9 mg/L (distilled), all at 20 °C

In water, 2 mg/L

In organic solvents (g/L at 20 °C): acetone 545.9, dichloromethane 22.3, hexane 0.028, toluene 3.0

In acetone, >50%; corn oil >10,000 mg/L

Solubility in water: very poor

200-201 °C

201 °C

2.78X10-9 mm Hg at 25 °C

Vapor pressure at 20 °C: negligible

Solid;

WHITE POWDER.

178.1 Ų [M-H]- [CCS Type: DT; Buffer gas: N2; Ionization: ESI-; Dataset: TOXCAST; Source Identifier: DTXSID4034609]

178.83 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]；190.65 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

180.77 Ų [M+H]+ [CCS Type: TW]

181.45 Ų [M+H]+；177.61 Ų [M-H]-；194.16 Ų [M+Na]+

180.21 Ų [M+H]+ [CCS Type: TW; Buffer gas: N2; Ionization: GC-APCI+]

Danger

H301: Toxic if swallowed [Danger Acute toxicity, oral]；H311: Toxic in contact with skin [Danger Acute toxicity, dermal]；H331: Toxic if inhaled [Danger Acute toxicity, inhalation]；H372 *: Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]；H400: Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]；H410: Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]

P260, P261, P262, P264, P270, P271, P273, P280, P301+P316, P302+P352, P304+P340, P316, P319, P321, P330, P361+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

Danger

Regulation (EC) No 1107/2009 (amended)

Fipronil is listed in the dataset of EPA Human Health Benchmarks for Pesticides under the Safe Drinking Water Act (40 eCFR 141)

07/52/EC, 2010/21/EU, Reg (EU) 2015/408, Reg. (EU) 2016/2035, Reg. (EU) 2022/801, Reg. (EU) No 540/2011, Reg. (EU) No 781/2013

Status: No longer Valid Update: 10-11-2008 https://echa.europa.eu/registration-dossier/-/registered-dossier/4397

Fipronil: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.

Sold as Magforce roach killer bait containing 0.1% fipronil; This product may be irritating to the skin and eyes following prolonged contact but is not acutely toxic after ingestion or dermal exposure; Also sold as Chipco Choice Insecticide, containing 0.1% fipronil; This product may cause seizures after skin absorption, ingestion, or inhalation. A termiticide product contains 9.1% fipronil. Seizures are listed as possible effects from overexposure to this product. [MSDSonline] Causes seizures in high-dose animal studies; Technical (96.5%) fipronil is classified as moderate toxicity, and formulated products are classified as low toxicity. Formulated products may cause some skin irritation to pets, but are not absorbed through the skin; [NPIC]

Tolerances are established for combined residues of the insecticide fipronil (5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(1R,S)-(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile) and its metabolites 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl) sulfonyl]-1H-pyrazole-3-carbonitrile and 5-amino-1-[2,6-dichloro-4-(trifluoromethyl) phenyl]-4-[(trifluoromethyl)thio]-1H-pyrazole-3-carbonitrile and its photodegradate 5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(1R,S)-(trifluoromethyl)]-1H-pyrazole-3-carbonitrile in or on the following items at the levels specified:[Table#6680]

Time-limited tolerances are established for combined residues of the insecticide, fipronil, 5-amino-1-(2,6-dichloro-4-(trifluoromethyl) phenyl)-4-((1,R,S)-trifluoromethyl)sulfinyl)-1-H-pyrazole-3-carbonitrile and its 2 metabolites MB45950 (5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-[(trifluoromethyl)thio]-1H-pyrazole-3-carbonitrile) and MB46136 (5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-[(trifluoromethyl)sulfonyl]-1H-pyrazole-3-carbonitrile) and its photodegradate MB46513 (5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(1R,S)-(trifluoromethyl)]-1H-pyrazole-3-carbonitrile), in connection with use of the pesticide under Section 18 emergency exemptions granted by EPA. The tolerances expire and are revoked on the dates specified in the table for this paragraph.[Table#6681]

Tolerances are established for combined indirect or inadvertent residues of the insecticide fipronil and its metabolites and photodegradate in or on food commodities when present therein as a result of the application of fipronil to growing crops listed in paragraphs (a) and (b) of this section and other nonfood crops to read as follows:[Table#6682]

New Active Ingredients ... includes chemicals not previously registered as pesticides, as well as pesticide active ingredients initially registered after November 1, 1984 and that currently have active product registrations. By law, these pesticides must meet new safety standards, such as those described in the Food Quality Protection Act of 1996 and, if new safety standards are met, will be reviewed again on a 15-year cycle. Fipronil is designated by EPA as a New Pesticide Active Ingredient. Active Ingredient Number: 129121; Type of Pesticide: conventional - insecticide; Use Site: domestic use, pets, ornamentals, hospitals, eating establishments, etc.; Year: 1996.

Acute Tox. 3 (100%)；Acute Tox. 3 (100%)；Acute Tox. 2 (92.3%)；STOT RE 1 (100%)；Aquatic Acute 1 (99.5%)；Aquatic Chronic 1 (100%)

Acute toxicity - category 3；Acute toxicity - category 3；Acute toxicity - category 3；Specific target organ toxicity (repeated exposure) - category 1；Hazardous to the aquatic environment (chronic) - category 1；Hazardous to the aquatic environment (acute) - category 1

Acute toxicity (Oral) - Category 3；Acute toxicity (Inhalation: Dusts and mists) - Category 3；Reproductive toxicity - Category 2；Specific target organ toxicity - Single exposure - Category 1 (nervous system)；Specific target organ toxicity - Repeated exposure - Category 1 (nervous system), Category 2 (thyroid, liver)；Hazardous to the aquatic environment (Acute) - Category 1；Hazardous to the aquatic environment (Long-term) - Category 1

Acute toxicity (Oral) - Category 3；Acute toxicity (Dermal) - Category 3；Acute toxicity (Inhalation: Dusts and mists) - Category 2；Carcinogenicity - Category 2；Reproductive toxicity - Category 2；Specific target organ toxicity - Single exposure - Category 1 (nervous system)；Specific target organ toxicity - Repeated exposure - Category 1 (central nervous system, thyroid, liver, kidney, haemal system)；Hazardous to the aquatic environment (Acute) - Category 1；Hazardous to the aquatic environment (Long-term) - Category 1

Acute Tox. 3 *；Acute Tox. 3 *；Acute Tox. 3 *；STOT RE 1；Aquatic Acute 1；Aquatic Chronic 1

M&B 46,030 (Fipronil, purity of 96.7%) was applied to a 1-inch gauze patch (0.5 g moistened with 0.5 mL corn oil) and placed on the right flank on the clipped area of skin (semi-occlusive dressing) of 3 New Zealand White Rabbits/sex for 4 hours. Minor to moderate erythema was reported in all 6 rabbits (one female had a score of 2, the remainder had a score of 1) at the 1 hour examination; during this period, mild transient edema was seen on 3 rabbits. The erythema subsided on 5 rabbits within 1 to 2 days, while the edema disappeared within 1 day. Only one rabbit showed mild (score of 1) erythema at 3 days and no effects were seen at 7 days.

M&B 46,030 (Fipronil, purity of 96.7% was applied at a volume of 0.1 mL (or approx. 90 mg) to the conjunctival sac of 6 New Zealand White rabbits (without washing). Minor corneal opacity (severity score of 1) was seen in 2 of 6 rabbits at the 1 hour examination; there were no indications of corneal opacity at 24 hour or later; minor inflammation of the iris (score of 1) in 5 of 6 rabbits and slight to moderate conjunctival irritation in all rabbits was seen at 1 hour. By Day 7, 3 of 6 rabbits showed no conjunctival irritation and the remaining 3 showed only slight redness.

Fresh air, rest. Refer for medical attention.

Remove contaminated clothes. Rinse and then wash skin with water and soap.

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

Give a slurry of activated charcoal in water to drink. Refer for medical attention .

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

Liquid formulations containing organic solvents may be flammable. Gives off irritating or toxic fumes (or gases) in a fire.

In case of fire in the surroundings, use appropriate extinguishing media.

Keep container tightly closed in a dry and well-ventilated place.

Store unused product in original container only, in cool, dry area out of reach of children. Do not transfer this product to another container for storage.

Seperated from food and feedstuffs.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

Personal protection: particulate filter respirator adapted to the airborne concentration of the substance. Do NOT let this chemical enter the environment. Sweep spilled substance into covered containers.

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber; Contaminated packaging: Dispose of as unused product.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.

Appropriate engineering controls: Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

For more Preventive Measures (Complete) data for Fipronil (7 total), please visit the HSDB record page.

Use of pesticides or insecticides can be highly toxic to aquatic life forms due to leaching and agricultural runoff, rains or flood. Fipronil(FP) is a GABA receptor inhibitor, while buprofezin (BPFN) is an insect growth regulator. Presently, we exposed groups of aquaria acclimated carp fish (Cyprinus carpio) for 96 hr to sub-lethal concentrations of fipronil (400 ug/L; 9.15 x 10(-7) mol/L) and buprofezin (BPFN, 100 mg/L; 1.072 x 10(-6) mol/L) singly or in combination. The extent of damage was assessed at biochemical, hematological, molecular biological and histopathological level. Results obtained in treated fish were compared statistically with those of control non-treated fish and also among treatment groups. Significance level was p<0.05. Compared to control, serum total protein and globulin concentrations decreased significantly (p<0.0001) in fish treated with FP; while albumin concentration remained unaltered with all treatments. Glucose concentration decreased significantly (p<0.002) in fish treated with FP. In contrast, combined FP+BPFN treatment and BPFN treatment caused insignificant elevation of glucose concentration. Hematological assessment demonstrated significant decrease in red blood cell and thrombocyte counts, hemoglobin concentration and hematocrit percent; while white blood cell count showed an increase in all treatment groups (p<0.0001). Blood smears from pesticide treated fish revealed aberrant erythrocyte morphologies which included necrosis, micronuclear formation and hyperchromatosis. DNA laddering assay carried out on whole blood demonstrated excessive smear formation in combined FP+BPFN and BPFN treatment groups but no smear formation was noticeable in FP treated fish. Compared to control, whole blood DNA content increased significantly in the combined FP+BPFN and BPFN treatment groups (p<0.001 and p<0.009). With all treatments histopathological changes observed in the gills were: epithelial uplifting and necrosis of lamellae, lamellar atro

The effects of fipronil and fluoride co-exposure were investigated on antioxidant status of buffalo calves. A total of 24 healthy male buffalo calves divided into 4 groups were treated for 98 consecutive days. Group I, receiving no treatment, served as the control. Animals of groups II and III were orally administered with fipronil at the dosage of 0.5 mg/kg/day and sodium fluoride (NaF) at the dosage of 6.67 mg/kg/day, respectively, for 98 days. Group IV was coadministered with fipronil and NaF at the same dosages as groups II and III. Administration of fipronil alone produced significant elevation in lipid peroxidation (LPO) and decrease in the levels of nonenzymatic antioxidant glutathione (GSH). However, it did not produce any significant effect on the activities of enzymatic antioxidants including glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). NaF exposure led to enhanced oxidative stress as shown by significant increase in the LPO and SOD activities while GPx and CAT activities and GSH levels were significantly decreased. Co-exposure to fipronil and NaF showed additive effects on LPO, GPx activity, and GSH levels.

Fipronil is a relatively new insecticide of the phenpyrazole group. Fipronil-induced effects on antioxidant system and oxidative stress biomarkers are yet to be studied in vivo. The present study was undertaken to evaluate fipronil-induced alterations in the blood biochemical markers and tissue antioxidant enzymes after oral exposure in mice and to explore possible protective effect of pre-treatment of antioxidant vitamins against these alterations. Mice were divided into eight groups containing control, test and amelioration groups. Mice in the test groups were exposed to different doses of fipronil, i.e., 2.5, 5 and 10 mg/kg bw, respectively for 28 days. Mice in the amelioration groups were treated with vitamin E or vitamin C (each at 100 mg/kg) 2 hr prior to high dose (10 mg/kg) of fipronil. Fipronil exposure at three doses caused significant increase in the blood biochemical markers, lipid peroxidation and prominent histopathological alterations; while level of antioxidant enzymes was severely decreased both in kidney and brain tissues. Prior administration of vitamin E or vitamin C in the fipronil exposed mice led to decrease in lipid peroxidation and significant increase in activities of antioxidants, viz., glutathione, total thiol, superoxide dismutase and catalase. Vitamin E and vitamin C administration in fipronil exposed mice also improved histological architecture of the kidney and brain when compared with fipronil alone treated groups. Thus, results of the present study demonstrated that in vivo fipronil exposure induces oxidative stress and pre-treatment with vitamin E or C can protect mice against this oxidative insult.

LD50; Species; Anas platyrhynchos (Mallard duck) oral >2150 mg/kg

LC50; Species: Anas platyrhynchos (Mallard Duck) age 2 days; diet >5000 ppm for 22 days /95% purity/

LD50; Species: Anas platyrhynchos (Mallard Duck) age 26 weeks; oral via capsule 420 mg/kg (95% confidence interval: 298-581 mg/kg)

LD50; Species: Phasianus colchicus (Pheasant) oral 31 mg/kg

For more Ecotoxicity Values (Complete) data for Fipronil (35 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), Koc values of 825 to 6863(2-3), indicate that fipronil is expected to have low to no mobility in soil(SRC). Volatilization of fipronil from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 8.4X10-10 atm-cu m/mole(SRC), based upon its vapor pressure, 2.78X10-9 mm Hg(4), and water solubility, 1.9 mg/L(4). Fipronil is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(4). Photolytic half-lives in three soil types for fipronil were calculated as 147, 178 and 217 hours from experimental rate constants of 0.0047/hr, 0.0039/hr and 0.0032/hr, respectively(3). Fipronil is expected to biodegrade in soil based upon studies showing estimated degradation half-lives of 25.1 to 91.2 days in three sediments under aerobic conditions and 4.6 to 18.5 days for the same sediments under anaerobic conditions(5).

TERRESTRIAL FATE: The nitrile group of fipronil may undergo hydrolysis to the corresponding amide metabolite by chemical or biological processes(1). It has been reported that in acidic soil, the amide metabolite results more from biological activity rather than chemical hydrolysis(1). Oxidation of fipronil to the corresponding sulfone can result from biological or chemical processes; however, studies indicate that the major degradation process was probably a chemical transformation(1).

TERRESTRIAL FATE: Fipronil residues at two different application rates were studied in vineyards. The sum of fipronil residues in grape leaves, grape berries and in the soil were reported (mg/kg)(1). Fipronil concentration was below detection limit (0.01 mg/kg) at harvest time, 60 days after the last insecticide application, in leaves, grapes and in soil(1).；Table: Residues recovered (mg/kg) [Table#6679]

AQUATIC FATE: Based on a classification scheme(1), Koc values of 825 to 6863(2-3), indicate that fipronil is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 8.4X10-10 atm-cu m/mole(SRC), derived from its vapor pressure, 2.78X10-9 mm Hg(5), and water solubility, 1.9 mg/L(5). According to a classification scheme(6), a whole body BCF in bluegill of 321(7), suggests bioconcentration in aquatic organisms is high(SRC). Fipronil is stable to hydrolysis at pH 5.5 and pH 7, but has a hydrolysis half-life of 28 days at pH 9(5). An aqueous photolytic half-life for fipronil was calculated as 4.1 hours, from its experimental rate constant of 0.17/hr(3). Fipronil is expected to biodegrade in water based upon studies showing estimated degradation half-lives of 25.1 to 91.2 days in three sediments under aerobic conditions and 4.6 to 18.5 days for the same sediments under anaerobic conditions(8).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), fipronil, which has a vapor pressure of 2.78X10-9 mm Hg at 25 °C(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase fipronil may be removed from the air by wet and dry deposition(SRC).

IDENTIFICATION AND USE: Fipronil is a solid. Fipronil is a pyrazole acaricide and insecticide that may be used for insect, tick, lice, and mite control on pets. HUMAN STUDIES: Most cases of exposure (89%) had mild, temporary health effects. Neurological symptoms (50%) such as headache, dizziness, and paresthesia were the most common, followed by ocular (44%), gastrointestinal (28%), respiratory (27%), and dermal (21%) symptoms. Exposures usually occurred from inadvertent spray/splash/spill of products or inadequate ventilation of the treated area before re-entry. Fipronil was tested in an in vitro cytogenetics assay using human lymphocyte cultures. No increase in chromosome aberrations was reported at any dose level. However, in an alkaline comet assay fipronil induced DNA damage in human peripheral blood lymphocytes in vitro. ANIMAL STUDIES: No skin irritation was observed in rabbits. In studies with female rats, the clinical signs of toxicity did not reach their peak until 2 days after treatment in some animals, and deaths did not occur until 4 days after treatment. Some signs of toxicity and body-weight loss were still evident when the observation period ended at day 7 after treatment. Since these findings suggested that bioaccumulation of the test material could occur, a 5-day study with cumulative treatment was performed in which groups of 4 female rats were given fipronil at 75 mg/kg bw/day orally for up to 5 days. Clinical signs of neurotoxicity were seen after administration of 2 doses, and 3 of 4 rats died after admin of 3 or 4 doses. In the only rat that survived the study, abnormal behavioral responses persisted until 6 days after administration of the final dose, at which time it had regained most of its pretreatment weight. A commercial product that contains fipronil was administered orally to pregnant Wistar rats at dosages of 0.1, 1.0, or 10.0 mg/kg/day from the 6th to the 20th day of gestation. The fipronil caused a disturbance of the maternal aggre

Fipronil blocks the passage of chloride ions through the GABA-regulated chloride channel, disrupting CNS activity. (T10) Organic nitriles decompose into cyanide ions both in vivo and in vitro. Consequently the primary mechanism of toxicity for organic nitriles is their production of toxic cyanide ions or hydrogen cyanide. Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected. Cyanide is also known produce some of its toxic effects by binding to catalase, glutathione peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, succinic dehydrogenase, and Cu/Zn superoxide dismutase. Cyanide binds to the ferric ion of methemoglobin to form inactive cyanmethemoglobin. (L97)

/BIRDS and MAMMALS/ Fipronil is an insecticide commonly used in agriculture, but there are growing concerns over its environmental impacts (e.g., harmful effects on pollinators). Fipronil-treated seed ingestion might threaten granivorous farmland birds, in particular, Gallinaceous birds that are particularly sensitive to this insecticide. We report here on exposure risk and effects in a game bird of high socioeconomic importance, the red-legged partridge (Alectoris rufa). We fed captive birds with untreated maize (controls) or with a mixture of untreated-treated maize (ratio 80:20; exposed birds) during 10 days at the beginning of the breeding period (n = 12 pairs in each group). We first show that exposed partridges did not reject treated seeds but reduced food intake and lost body condition. We further studied the effects of treated seed ingestion on adult survival, oxidative balance, plasma biochemistry, carotenoid-based coloration, cellular immune response, steroid hormone levels, and reproduction. Fipronil exposure altered blood biochemistry and sexual hormone levels and reduced cellular immune response, antioxidant levels, and carotenoid-based coloration. Exposed pairs also had reduced egg fecundation rate and produced eggs with fewer antioxidants and offspring that had reduced cellular immune response. These negative effects on adult partridges, their reproductive performance, and offspring quality highlight that fipronil-treated seed ingestion is a significant threat to wild birds.

/BIRDS and MAMMALS/ Two studies were carried out to examine the impact of maternal fipronil exposure on embryonic and offspring development. In the first study, breeding female zebra finches were orally dosed with single sublethal levels of fipronil (1, 5, and 10 mg/kg body weight) to determine behavioral and developmental consequences on chicks following maternal pesticide exposure. Significant levels of fipronil and fipronil-sulfone residues were detected in eggs laid by females in all dosed groups, however, these were undetectable in eggs laid 13 days after treatment. The level of sulfone detected in eggs was consistently higher than that of the parent fipronil compound. Of the seven eggs laid in the treatment groups, only one (14%) chick hatched and this was from the lowest dose group. This chick was severely underdeveloped at 10 days of age in comparison to control chicks and fiproles were detected in brain, liver, and adipose tissues collected following euthanasia of this individual. In contrast, there was 100% hatchability of control group eggs and all chicks fledged nests on schedule. In the second study, domestic chicken eggs were injected with 5.5, 17.5, and 37.5 mg/kg egg weight of fipronil directly into the yolk sac on day 12 of incubation. Treatment did not affect hatching success, however, behavioral and developmental abnormalities were observed in hatchlings from the highest dose group. These chicks also demonstrated reduced feeding rates, as indicated by reduced body mass at 48 hr period post hatch. Both fipronil and fipronil-sulfone residues were detected in brain and liver tissue of hatchlings at all pesticide dose levels tested.

/BIRDS and MAMMALS/ ... /Investigators/ examined the effects of a single oral dose of fipronil in northern bobwhite quail, the most fipronil-sensitive species tested to date, in respect to signs of intoxication and the metabolic fate of fipronil. Fipronil-treated birds did not eat or drink following pesticide administration, and as a result lost a significant amount of body mass. Treated birds also appeared withdrawn and did not respond to disturbance within the first hour after treatment. Identifiable signs of fipronil toxicity were not observed until at least 2 days after treatment. Chemical analyses indicated a difference between fipronil and fipronil-sulfone residue distribution and bioaccumulation, with significantly higher (30- to 1000-fold) tissue concentrations of the sulfone detected at all time points from 8 to 96 hr post-dose in brain, liver and adipose tissues. Tissue sulfone concentrations increased significantly in fipronil-treated birds, peaking at 72 hr post-dose. Body mass decreased at all time points in dosed birds. The coincidence of the particular intoxication symptoms with the time course of rise in brain sulfone levels after fipronil dosing gives insight into possible mechanisms of toxicity in this highly sensitive species.

/BIRDS and MAMMALS/ ... Fipronil /was/ administered via the diet to male red-winged blackbirds (Agelaius phoeniceus L), male and female brownheaded cowbirds, and female boat-tailed grackles (Quiscalus major Viellot). Fipronil was added to a rice seed medium at 0, 325, and 500 mg a.i./kg. Birds were allowed to feed at will from open cups of the treated diet. No adverse toxicological effects were noted and no reduction in food consumption (p>0.05) was noted for any species and any dose group.

For more Ecotoxicity Excerpts (Complete) data for Fipronil (43 total), please visit the HSDB record page.

Convulsions. Tremor.

See Inhalation.

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of August 9, 2018: http://actor.epa.gov/dashboard/]

The following link will take the user to the National Toxicology Program (NTP) Test Status of Agents Search page, which tabulates the results and current status of tests such as "Short-Term Toxicity Studies", "Long-term Carcinogenicity Studies", "Developmental Studies", "Genetic Toxicology Studies", etc., performed with this chemical. Testing status for fipronil is available.[Available from, as of August 9, 2018: https://ntpsearch.niehs.nih.gov/?e=True&ContentType=Testing+Status]

The substance is very toxic to aquatic organisms. This substance may be hazardous to the environment. Special attention should be given to birds and bees. This substance does enter the environment under normal use. Great care, however, should be taken to avoid any additional release, for example through inappropriate disposal.

Regulation (EC) No 1107/2009 (amended)

Fipronil is listed in the dataset of EPA Human Health Benchmarks for Pesticides under the Safe Drinking Water Act (40 eCFR 141)

07/52/EC, 2010/21/EU, Reg (EU) 2015/408, Reg. (EU) 2016/2035, Reg. (EU) 2022/801, Reg. (EU) No 540/2011, Reg. (EU) No 781/2013

Status: No longer Valid Update: 10-11-2008 https://echa.europa.eu/registration-dossier/-/registered-dossier/4397

Fipronil: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.

Tolerances are established for combined residues of the insecticide fipronil (5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(1R,S)-(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile) and its metabolites 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl) sulfonyl]-1H-pyrazole-3-carbonitrile and 5-amino-1-[2,6-dichloro-4-(trifluoromethyl) phenyl]-4-[(trifluoromethyl)thio]-1H-pyrazole-3-carbonitrile and its photodegradate 5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(1R,S)-(trifluoromethyl)]-1H-pyrazole-3-carbonitrile in or on the following items at the levels specified:[Table#6680]

Time-limited tolerances are established for combined residues of the insecticide, fipronil, 5-amino-1-(2,6-dichloro-4-(trifluoromethyl) phenyl)-4-((1,R,S)-trifluoromethyl)sulfinyl)-1-H-pyrazole-3-carbonitrile and its 2 metabolites MB45950 (5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-[(trifluoromethyl)thio]-1H-pyrazole-3-carbonitrile) and MB46136 (5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-[(trifluoromethyl)sulfonyl]-1H-pyrazole-3-carbonitrile) and its photodegradate MB46513 (5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(1R,S)-(trifluoromethyl)]-1H-pyrazole-3-carbonitrile), in connection with use of the pesticide under Section 18 emergency exemptions granted by EPA. The tolerances expire and are revoked on the dates specified in the table for this paragraph.[Table#6681]

Tolerances are established for combined indirect or inadvertent residues of the insecticide fipronil and its metabolites and photodegradate in or on food commodities when present therein as a result of the application of fipronil to growing crops listed in paragraphs (a) and (b) of this section and other nonfood crops to read as follows:[Table#6682]

New Active Ingredients ... includes chemicals not previously registered as pesticides, as well as pesticide active ingredients initially registered after November 1, 1984 and that currently have active product registrations. By law, these pesticides must meet new safety standards, such as those described in the Food Quality Protection Act of 1996 and, if new safety standards are met, will be reviewed again on a 15-year cycle. Fipronil is designated by EPA as a New Pesticide Active Ingredient. Active Ingredient Number: 129121; Type of Pesticide: conventional - insecticide; Use Site: domestic use, pets, ornamentals, hospitals, eating establishments, etc.; Year: 1996.

QP - Antiparasitic products, insecticides and repellents；QP53 - Ectoparasiticides, insecticides and repellents；QP53A - Ectoparasiticides for topical use, incl. insecticides；QP53AX - Other ectoparasiticides for topical use；QP53AX15 - Fipronil

Fipronil is a second-generation phenilpirazol insecticide that is used in agriculture and veterinary medicine for protection against fleas, ticks, ants, cockroaches and other pests. The insecticide blocks the chloride channels associated with the gamma-amino butyric acid (GABA) receptors in mammals and the chloride channels associated with the GABA and glutamate (Glu) receptors in insects.

GABA-gated chloride channel antagonists.

MicroRNAs (miRNAs), which are a class of small noncoding RNAs, can modulate the expression of many protein-coding genes when an organism is exposed to an environmental chemical. We previously demonstrated that miR-155 was significantly downregulated in adult zebrafish (Danio rerio) in response to fipronil (5-amino-1-[2,6-dichloro-4-(trifluoromethyl) phenyl]-4-[(trifluoromethyl) sulphinyl]-1H-pyrazole-3-carbonitrile) exposure. However, the regulation of this miRNA's predicted target gene cyb561d2, which is a member of the cytochrome b561 (cyt b561) family involved in electron transfer, cell defence, and chemical stress, has not been experimentally validated to date. In this study, we evaluated the effects of fipronil on miR-155 and cyb561d2 in zebrafish. The expression of miR-155 was downregulated, whereas cyb561d2 was upregulated in both mRNA and protein level in a dose-dependent manner upon stimulation of fipronil. The dual luciferase report assay demonstrated that miR-155 interacted with cyb561d2 3'-untranslated regions (3'-UTR). The expression of cyb561d2 was reduced in both mRNA and protein levels when ZF4 cells were transfected with an miR-155 mimic, whereas its expression levels of both mRNA and protein were increased when endogenous miR-155 was inhibited by transfection with an miR-155 inhibitor. The results improved our understanding of molecular mechanism of toxicity upon fipronil exposure, and presents miR-155 as a potential novel toxicological biomarker for chemical exposure.

Fipronil is the first phenylpyrazole insecticide widely used in controlling pests, including pyrethroid, organophosphate and carbamate insecticides. It is generally accepted that fipronil elicits neurotoxicity via interactions with GABA and glutamate receptors, although alternative mechanisms have recently been proposed. This study evaluates the genotoxicity of fipronil and its likely mode of action in Drosophila S2 cells, as an in vitro model. Fipronil administrated the concentration- and time-dependent S2 cell proliferation. Intracellular biochemical assays showed that fipronil-induced S2 cell apoptosis coincided with a decrease in the mitochondrial membrane potential and an increase reactive oxygen species generation, a significant decrease of Bcl-2 and DIAP1, and a marked augmentation of Cyt c and caspase-3. Because caspase-3 is the major executioner caspase downstream of caspase-9 in Drosophila, enzyme activity assays were used to determine the activities of caspase-3 and caspase-9. Our results indicated that fipronil effectively induced apoptosis in Drosophila S2 cells through caspase-dependent mitochondrial pathways.

For more Mechanism of Action (Complete) data for Fipronil (7 total), please visit the HSDB record page.

Female rabbits, rats and mice were dosed orally by gavage with M&B 46,030 (fipronil technical) (purity: 95.4% (based upon information provided under record no. 261658)) for 14 days. Two groups of rabbits received 0.4 or 1.2 mg/kg/day and two groups each of rats and mice were dosed with 0.4 or 4.0 mg/kg/day of the test material (study data for the rabbits is presented in record no. 261658). ... The predominant metabolite which was recovered was M&B 46136. ... For the rabbit, the study authors estimated the elimination half-lives for M&B 46136 to be 11 and 10 days for blood and fat, respectively. For the rodents, the values were 5 and 6 to 7 days, respectively. The brain half-lives ranged from 4 (mouse) to 9 days (rat) for the 3 species. The liver half-life values for the metabolite ranged between 3 and 5 days. The half-life in the thyroid of the rodents was 5 days. For the rabbit, the concentrations of M&B 46030 in the thyroid were too variable to calculate an elimination half-life.

Male and female CD rats were dosed orally by gavage with 4 or 40 mg/kg of Fipronil- (U-[(14)C] phenyl) (radiochemical purity > 99%). The specific activities of the dosing preparations were adjusted as required using unlabeled Fipronil (purity 99.4%). ... Elimination t1/2 estimates were 135 and 171 hours for 40 mg/kg males and females, compared to 183 and 245 hours for 4 mg/kg males and females.

Two female New Zealand white rabbits, 5 female Sprague-Dawley rats and 10 female CD1 mice were dosed orally with 5 mg/kg of M&B 46030- [phenyl-U-(14)C] (radiochemical purity: 98.7%, specific activity: 45.1 uCi/mg). The specific activity of the dosing preparations was adjusted to approximately 5.8 to 5.9 uCi/mg, using unlabeled M&B 46030 (purity: 99.3%). Urine and feces were collected up to 168 hours post-dose. Blood was drawn from each animal at specified intervals up to 168 hours post-dose. ... For the pharmacokinetic parameters, the Cmax values in the blood were 0.31, 0.64 and 0.58 ug/g for the rabbit, rat, and mouse, respectively. The tmax times were 12, 9 and 4 hours post-dose for the rabbit, rat, and mouse, respectively. The reported t1/2 times were 14, 3, and 3 days for the rabbit, rat and mouse, respectively.

Female rabbits, rats and mice were dosed orally by gavage with M&B 46,030 (fipronil technical) (purity: 95.4% (based upon information provided under record no. 261658)) for 14 days. Two groups of rabbits received 0.4 or 1.2 mg/kg/day and two groups each of rats and mice were dosed with 0.4 or 4.0 mg/kg/day of the test material (study data for the rabbits is presented in record no. 261658). ... For the rabbit, the study authors estimated the elimination half-lives for M&B 46136 to be 11 and 10 days for blood and fat, respectively. For the rodents, the values were 5 and 6 to 7 days, respectively. The brain half-lives ranged from 4 (mouse) to 9 days (rat) for the 3 species. The liver half-life values for the metabolite ranged between 3 and 5 days. The half-life in the thyroid of the rodents was 5 days. For the rabbit, the concentrations of M&B 46030 in the thyroid were too variable to calculate an elimination half-life.

Pharmacokinetic investigations showed that the whole-blood half-life at the single low dose was 149-200 hr in male and female rats /administered (14)C-fipronil (labelled uniformly at the phenyl ring; radiochemical purity, >97%)/... .

Fipronil gives effective control of early shoot borer and termites in sugarcane. The persistence and metabolism of fipronil in sugarcane leaves and juice were studied following application of fipronil (Regent 0.3 G) at 75 and 300 g a.i./ha. Samples of sugarcane leaves were collected at various time intervals. Samples of sugarcane juice were collected at harvest. Residues of fipronil and its metabolites were quantified by gas liquid chromatograph. The limit of quantification of fipronil and its metabolites was 0.01 mg/kg for sugarcane leaves and juice. Total residues of fipronil and its metabolites in sugarcane leaves after 7 days of its application at 75 and 300 g a.i./ha were 0.26 and 0.66 mg/kg, respectively. Residues could not be detected after 60 and 90 following fipronil application at either concentration. In sugarcane leaves, fipronil was found to be the main constituent, followed by its metabolites amide, desulfinyl, sulfone and sulfide. Samples of sugarcane juice did not reveal the presence of fipronil or its metabolites following its application at both the dosages at harvest.

The enantioselective bioaccumulation and elimination of fipronil in Anodonta woodiana (A. woodiana) were studied and the main metabolites fipronil desulfinyl, fipronil sulfide and fipronil sulfone were determined. The acute toxicity of the enantiomers of fipronil and the three metabolites were also investigated. In the bioaccumulation process, fipronil in A. woodiana reached equilibrium after 11 days with BCF value of 0.2, and the enantiomeric fraction (EF) values showed that the bioaccumulation was enantioselective with enantioenrichment of S-fipronil. The degradation of fipronil in A. woodiana fitted first-order kinetics model with half-lives of the enantiomers were 5.8 d for R-fipronil and 7.6 d for S-fipronil, and the EF values decreasing from 0.5 gradually indicating the R-enantiomer was preferentially degraded. The degradation of single enantiomers was also performed and the results revealed a fast conversion of R-fipronil to S-fipronil by A. woodiana. The three metabolites were all detected in A. woodiana-water system, in which fipronil sulfone and fipronil sulfide had higher concentration levels. According to the 72-hr LC50 values, S-fipronil was much more toxic than the racemate and R-fipronil. Moreover, the metabolites were more toxic than the parent fipronil. The results suggested the individual enantiomers of chiral pollutants and the metabolites should be considered in the risk assessments.

Fipronil is a phenylpyrazole insecticide commonly used in residential and agricultural applications. To understand more about the potential risks for human exposure associated with fipronil, urine and serum from dosed Long Evans adult rats (5 and 10 mg/kg bw) were analyzed to identify metabolites as potential biomarkers for use in human biomonitoring studies. Urine from treated rats was found to contain seven unique metabolites, two of which had not been previously reported-M4 and M7 which were putatively identified as a nitroso compound and an imine, respectively. Fipronil sulfone was confirmed to be the primary metabolite in rat serum. The fipronil metabolites identified in the respective matrices were then evaluated in matched human urine (n=84) and serum (n=96) samples from volunteers with no known pesticide exposures. Although no fipronil or metabolites were detected in human urine, fipronilsulfone was present in the serum of approximately 25% of the individuals at concentrations ranging from 0.1 to 4 ng/mL. These results indicate that many fipronil metabolites are produced following exposures in rats and that fipronil sulfone is a useful biomarker in human serum. Furthermore, human exposure to fipronil may occur regularly and require more extensive characterization.

... In this study, the tissue distribution, the metabolic fate, and the elimination of fipronil was investigated in rats using radiolabeled fipronil. When a single oral dose of (14)C-fipronil (10 mg/kg b.w.) was given to rats, the proportion of dose eliminated in urine and feces 72 hr after dosing was ca 4% for each route. At the end of the experiment the highest levels of radioactivity were found in adipose tissue and adrenals. The main part of the radioactivity present in investigated tissues (adipose tissue, adrenals, liver, kidney, testes) was due to fipronil-sulfone. Five additional metabolites, isolated from urine were characterized by LC-MS/MS. Most of them are formed by the loss of the trifluoromethylsulphinyl group and subsequent hydroxylation and/or conjugation to glucuronic acid or sulfate. In conclusion, the retention of the metabolite fipronil sulfone in tissues following fipronil administration raises the question of the potential toxicity of this insecticide.

For more Metabolism/Metabolites (Complete) data for Fipronil (15 total), please visit the HSDB record page.

Organic nitriles are converted into cyanide ions through the action of cytochrome P450 enzymes in the liver. Cyanide is rapidly absorbed and distributed throughout the body. Cyanide is mainly metabolized into thiocyanate by either rhodanese or 3-mercaptopyruvate sulfur transferase. Cyanide metabolites are excreted in the urine. (L96)

Drugs used to treat or prevent parasitic infections.

Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics.

... In this study, the tissue distribution, the metabolic fate, and the elimination of fipronil was investigated in rats using radiolabeled fipronil. When a single oral dose of (14)C-fipronil (10 mg/kg b.w.) was given to rats, the proportion of dose eliminated in urine and feces 72 hr after dosing was ca 4% for each route. At the end of the experiment the highest levels of radioactivity were found in adipose tissue and adrenals. The main part of the radioactivity present in investigated tissues (adipose tissue, adrenals, liver, kidney, testes) was due to fipronil-sulfone. Five additional metabolites, isolated from urine were characterized by LC-MS/MS. Most of them are formed by the loss of the trifluoromethylsulphinyl group and subsequent hydroxylation and/or conjugation to glucuronic acid or sulfate. In conclusion, the retention of the metabolite fipronil sulfone in tissues following fipronil administration raises the question of the potential toxicity of this insecticide.

To investigate the localization of fipronil in dog skin, (14)C-fipronil was topically applied to a male beagle dog (spot-on administration) at the therapeutic dose of 10 mg/kg. By means of autohistoradiography, the radioactivity was precisely detected in the skin and appendages at various intervals after application. Radioactivity was predominantly observed within the stratum corneum, the viable epidermis, and in the pilo-sebaceous units (mainly in the sebaceous glands and epithelial layers). (14)C-fipronil was significantly detected in these structures up to 56 days post-treatment, in the application zone (neck) but also in the lumbar zone, thus indicating the mechanical displacement of fipronil. No radioactivity was detected in either the dermal or the hypodermal layers, confirming the low percutaneous passage of fipronil.

Absorption of (14)C-fipronil through epidermal membranes of humans, rabbits, and rats was measured in vitro in horizontal glass diffusion cells. ... The epidermal membranes were set up as a barrier between the two halves of the diffusion cells, and the absorption rates of a neat suspension of fipronil (200 g/L) as a formulation in EP60145A (a formulation base) and of two aqueous dilutions of the formulation containing 0.2 and 4 g/L of fipronil suspended in EP 60145A were determined ... . Fipronil at doses of 4 and 200 g/L penetrated rabbit and rat epidermal membranes to a greater extent than those of humans, whereas at 0.2 g/L the extent of penetration was similar through human and rat skin. The extent of penetration increased with time across species. The % of the applied dose that had penetrated the different membranes after 8 hr was 0.08% through rat epidermal membranes, 0.07% through rabbit membranes, and 0.01% through human membranes for the neat formulation; 0.14, 0.67, and 0.07% of the dose of 4.0 g/L active ingredient; and 0.9, 13.9, and 0.9% of the dose of 0.2 g/L active ingredient, respectively. At the dose of 4.0 g/L, fipronil penetrated the skin of all three species more slowly than either testosterone or hydrocortisone. These two reference permeants were selected because their intrinsic rates of dermal penetration differ by two orders of magnitude, that of testosterone being faster. On the basis of the results for these two compounds, fipronil was considered to be a slow penetrant when applied as a formulation in EP 60145A.

In a study of the absorption, distribution, metabolism, and excretion of fipronil in ruminants, [phenyl(U)-14C]-fipronil (19.2 mCi/mmol) was administered orally by capsule twice daily before feeding to three lactating goats at a dose of 0.05, 2, or 10 ppm for 7 days; assuming a daily intake of 2.0 kg dry matter, these doses are approx equivalent to nominal daily doses of 0.1, 4, and 20 mg, respectively. Milk was collected twice daily. The animals were killed about 24 hr after admin of the final dose and tissues obtained for analysis. The recovery of radiolabel in urine, milk, and tissues indicated that the min absorption of test material was about 19% at 0.05 ppm, 33% at 2 ppm, and 15% at 10 ppm. Of the administered radiolabel, 18-64% was recovered in feces, 1-5% in the milk, and 8-25% in the tissues. Total recovery was similar at the low (83%) and high doses (77%) but was somewhat lower at the intermediate dose (50%). The greatest contributor to the difference in recovery between the animals at the low and high doses and those at the intermediate dose was the amount of radiolabel excreted in the feces: 18% of the total radiolabel administered at 2 ppm, 64% at 0.05 ppm, and 61% at 10 ppm. The reason for this difference is not clear. The greatest total tissue residues were observed in omental and renal fat (about 1.9 ppm at the 10 ppm dose), followed by liver (0.86 ppm) and much lower concns in kidney, milk (0.17 ppm), and skeletal muscle.

For more Absorption, Distribution and Excretion (Complete) data for Fipronil (15 total), please visit the HSDB record page.

Used to kill mole crickets, fire ants, fleas, ticks, termites, and roaches; [MSDSonline] Used in turf granules, flea and tick sprays, and roach and ant baits; [NPIC]

Farming (Pesticides) [Category: Industry]

For fipronil (USEPA/OPP Pesticide Code: 129121) ACTIVE products with label matches. /SRP: Registered for use in the USA but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

Attractant/pheromone, insecticide, seed treatment/protectant.

Pesticide

MEDICATION (VET)

Fipronil can be produced by treatment of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl) pyrazole with trifluoromethylsulfenyl chloride.

Preparation: I.G. Buntain et al., European Patent Office patent 295117 (1988 to May & Baker); L.R. Hatton et al., United States of America patent 5232940 (1993).

The National Pesticide Information Retrieval System (NPIRS) identifies 34 companies with active labels for products containing the chemical fipronil. To view the complete list of companies, product names and percent fipronil in formulated products click the following url and enter the CAS Registry number in the Active Ingredient field.

Yellow Jacket Killer! (2 Star Solution Inc): Active ingredient: fipronil 9.1%.

MCW 437 Technical (Adama Makhteshim Ltd.): Active ingredient: fipronil 96.5%.

Fipronil 80DF TC (Albaugh, LLC): Active ingredient: fipronil 80.0%.

For more Formulations/Preparations (Complete) data for Fipronil (30 total), please visit the HSDB record page.

Pesticides -> Insecticides -> Pyrazole insecticides -> Phenylpyrazole insecticides

Environmental transformation -> Pesticides (parent, predecessor)

Insecticides

Registration Notes: Outside USA: Standak in Europe.

The WHO Recommended Classification of Pesticides by Hazard identifies fipronil (technical grade) as Class II: moderately hazardous; Main Use: insecticide.