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Cyfluthrin

Cyfluthrin is a synthetic pyrethroid insecticide with the molecular formula C₂₂H₁₈Cl₂FNO₃ and a molecular weight of 434.3 g/mol.^[1] Developed as a broad-spectrum contact and stomach poison, it targets the nervous systems of insects by disrupting sodium channels, leading to hyperexcitation, paralysis, and death.^[2] First registered for use in the United States by the Environmental Protection Agency in 1987, it appears in over 150 commercial products, including emulsifiable concentrates, granules, aerosols, and foggers.^[2] Cyfluthrin is applied in agricultural settings to protect crops such as cotton, corn, soybeans, fruits, vegetables, and hops from pests including cutworms, aphids, beetles, and weevils, with typical application rates ranging from 0.0125 to 0.05 pounds per acre.^[3] In non-agricultural uses, it controls household and structural pests like ants, cockroaches, termites, fleas, mosquitoes, and flies in homes, yards, livestock facilities, and public health programs, often via aerial spraying or cattle ear tags.^[2] Its low water solubility (approximately 0.003 mg/L at 20°C) and moderate persistence in soil (half-life of 2–56 days) contribute to its effectiveness, though it degrades faster in sunlight-exposed environments or high-organic soils.^[4]^[2] While less toxic to mammals due to rapid metabolism and excretion (98% within 1–2 days), cyfluthrin can cause moderate acute toxicity in humans, including nausea, headaches, and skin or eye irritation upon exposure, classifying it as EPA Toxicity Category II for most formulations.^[2] It poses significant ecological risks, being highly toxic to bees, fish, and aquatic invertebrates, with regulatory mitigations such as 25-foot vegetative buffer strips required to reduce runoff and drift.^[5] The EPA's 2020 interim registration review confirmed no unacceptable human health risks after refinements but mandated label updates for pollinator and aquatic protection.^[5]

Introduction

Definition and Classification

Cyfluthrin is a synthetic pyrethroid insecticide belonging to the type II subclass, designed as an analog of the naturally occurring pyrethrins extracted from chrysanthemum flowers.^[1]^[6] Pyrethroids, including cyfluthrin, replicate the neurotoxic effects of pyrethrins on insect nervous systems while providing improved environmental stability and persistence.^[5] As a non-systemic insecticide, cyfluthrin operates primarily through contact and stomach action, targeting the nervous system to disrupt sodium channel function in pests, resulting in rapid knockdown and prolonged residual activity.^[3]^[7] It is recognized as a broad-spectrum agent effective against a diverse array of insects, including those in agricultural, structural, and public health settings.^[8] The distinction between type I and type II pyrethroids lies in the presence of an alpha-cyano group in the latter, such as cyfluthrin, which enhances potency—particularly via ingestion—compared to type I variants that lack this structural feature and primarily induce repetitive nerve firing.^[8]^[9] Commercially, cyfluthrin is supplied as 10–25% liquid concentrates, which are diluted for application in pest control formulations.^[10]

History and Development

Cyfluthrin emerged as part of the broader evolution of synthetic pyrethroids, which originated from natural pyrethrins isolated from chrysanthemum flowers in the 19th century.^[11] Building on post-World War II advancements, such as the 1949 invention of allethrin by the U.S. Department of Agriculture, researchers in the 1970s sought to develop photostable analogs with enhanced insecticidal potency and residual activity compared to natural pyrethrins.^[12] In 1977, Bayer AG developed cyfluthrin through targeted modifications to existing pyrethroid structures, incorporating an alpha-cyano group at the 3-phenoxybenzyl alcohol moiety to increase efficacy against a range of pests while improving environmental stability.^[7] This innovation addressed limitations of earlier non-cyano pyrethroids like permethrin, resulting in a type II pyrethroid with prolonged sodium channel disruption in insect nerves for greater potency.^[12] The compound's key patent, DE 2709264, was filed on March 3, 1977, by inventors Rainer Fuchs, Ingeborg Hammann, Wolfgang Behrenz, and others, assigning rights to Bayer AG and describing its arthropodicidal esters.^[13] Cyfluthrin was introduced commercially in 1981 as a cotton insecticide under the trade name Baythroid, marking its market entry for agricultural applications.^[7] Initial testing demonstrated its efficacy against key cotton pests through contact and residual control. This launch positioned cyfluthrin as a significant advancement in pyrethroid chemistry, influencing subsequent formulations and isomer enrichments like beta-cyfluthrin.^[14]

Chemical Properties

Molecular Structure and Formula

Cyfluthrin is a synthetic pyrethroid insecticide with the molecular formula \ce{C22H18Cl2FNO3}.^[1] Its molecular weight is 434.29 g/mol.^[1] The molecule consists of an ester linkage between 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid and cyano(4-fluoro-3-phenoxyphenyl)methanol, forming the core pyrethroid skeleton characteristic of type II pyrethroids, which includes a cyclopropane ring substituted with a dichlorovinyl group and geminal methyl groups, connected via the ester to a benzyl alcohol derivative bearing a cyano group at the alpha position and a phenoxy substituent ortho to the fluoro group on the benzene ring.^[15] This structure mimics natural pyrethrins found in chrysanthemum flowers but incorporates synthetic modifications for enhanced stability.^[16] Cyfluthrin possesses three chiral centers—two on the cyclopropane ring (leading to cis-trans isomerism) and one at the benzylic carbon bearing the cyano group—resulting in eight possible stereoisomers that form four diastereomeric pairs, typically denoted as isomers I through IV based on chromatographic retention times.^[17] In the technical-grade product, these diastereoisomers are present in specific proportions: 23-27% isomer I, 17-21% isomer II, 32-36% isomer III, and 21-25% isomer IV.^[17]

Physical and Chemical Characteristics

Cyfluthrin appears as a viscous amber to brown liquid or partly crystalline oil, though it may present as brown crystals with a characteristic odor depending on purity and isomer composition.^[17]^[4] Its melting point is 60°C (140°F), above which it transitions from a solid to a liquid state.^[18]^[4] Cyfluthrin exhibits very low solubility in water, approximately 2–3 μg/L at 20°C and pH 7, rendering it practically insoluble and limiting its mobility in aqueous environments.^[17]^[18]^[4] In contrast, it is highly soluble in organic solvents, such as acetone (>250 g/L at 20°C), n-hexane (10 g/L at 20°C), and dichloromethane (200 g/L at 20°C), facilitating its formulation and application.^[18]^[19] The compound remains stable under neutral and acidic conditions but undergoes hydrolysis in alkaline media, with a half-life of 33–42 hours at pH 9 and 20°C.^[17] It is photostable under normal conditions yet degrades gradually upon extended exposure to sunlight.^[10]^[20] Cyfluthrin has a low vapor pressure of approximately 3 × 10^{-7} Pa at 20°C, signifying minimal volatility and reduced risk of airborne dispersion during handling.^[18] Its octanol-water partition coefficient is log K_{ow} = 6.0 at 20°C and pH 7, reflecting high lipophilicity that enhances partitioning into lipid phases.^[18]^[17] This property contributes to its potential for bioaccumulation in fatty tissues.^[18]

Production

Synthesis Methods

Cyfluthrin is synthesized through a multi-step process typical of pyrethroid esters, involving the coupling of a cyclopropanecarboxylic acid derivative with a fluorinated benzyl cyanohydrin alcohol.^[21] The primary reaction is esterification, where 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid (or its acid chloride) is reacted with 2-hydroxy-2-(4-fluoro-3-phenoxyphenyl)acetonitrile under acidic conditions, often in a hydrocarbon solvent like toluene at reflux temperatures of 75–115°C, to form the ester linkage.^[14] This step proceeds without an acid acceptor to minimize epimerization and preserve the stereochemistry of the starting materials, yielding 87–99% based on the limiting reactant.^[14] Key preparatory steps focus on constructing the acid and alcohol components. For the acid moiety, halogenation introduces the dichlorovinyl group via dehydrohalogenation of 4,6,6,6-tetrahalo-2,2-dimethylhexanoates or stereoselective cyclopropanation followed by Wittig olefination with dichloromethylenetriphenylphosphorane, starting from chrysanthemic acid analogs.^[22] ^[23] The alcohol component involves fluorination of the benzene ring at the 4-position, typically from 2-fluoro-5-nitrophenol etherified with phenylboronic acid derivatives, followed by reduction to the aniline and diazotization, then cyano group addition via condensation of the resulting 4-fluoro-3-phenoxybenzaldehyde with hydrogen cyanide or sodium cyanide in the presence of acid, forming the cyanohydrin.^[24] ^[21] Standard synthesis employs dehalogenation precursors for the vinyl group, while labeled variants (e.g., for research) use noble metal catalysts like palladium for deuteration or tritium incorporation during selective reductions.^[25] A major challenge is controlling stereochemistry across the three chiral centers—the cyclopropane ring and the cyanohydrin carbon—resulting in eight possible isomers; this is achieved by using enantiopure or diastereomer-enriched precursors, such as (1R,3R)-acid chlorides, to favor bioactive cis/trans ratios like 51.8:48.2.^[14] ^[25] Purification typically involves washing with aqueous base (e.g., sodium carbonate) to remove impurities, followed by solvent evaporation and column chromatography to isolate desired diastereomers, with overall yields for multi-step routes ranging from 52–87% depending on stereoselectivity.^[14] ^[24]

Commercial Formulations and Isomers

Cyfluthrin is commercially available as a technical-grade active ingredient with a minimum purity of 920 g/kg, consisting of a mixture of four diastereoisomers in specified proportions to ensure consistent efficacy.^[17] The diastereoisomer composition includes 23-27% diastereoisomer I, 17-21% diastereoisomer II, 32-36% diastereoisomer III, and 21-25% diastereoisomer IV, as defined by FAO specifications to meet regulatory standards for pesticide quality and performance.^[17] These proportions are verified through methods such as normal-phase high-performance liquid chromatography (HPLC) to confirm the material's identity and isomer balance in both technical and formulated products.^[17] A key variant, beta-cyfluthrin, is an enriched form of cyfluthrin with a higher concentration of the biologically more active diastereoisomers II and IV, achieving a technical-grade purity of at least 965 g/kg.^[26] In beta-cyfluthrin, diastereoisomer II comprises 30-40% and diastereoisomer IV 57-67%, while isomers I and III are minimized to ≤2-3%, enhancing potency against target pests compared to the full isomer mix in standard cyfluthrin.^[26] This enrichment, analyzed via HPLC, allows for lower application rates while maintaining or improving insecticidal effectiveness, and beta-cyfluthrin is treated as a distinct compound in regulatory evaluations.^[21] Commercial formulations of cyfluthrin and beta-cyfluthrin are designed for diverse applications, including emulsifiable concentrates (ECs) typically containing 10-25% active ingredient, wettable powders (WPs), suspension concentrates (SCs), emulsion in water (EW), ultra-low volume (UL) liquids, granules, and aerosols.^[17] Notable examples include Baythroid XL, an EC formulation of beta-cyfluthrin (12.7% active ingredient) used in crop protection, and Tempo SC Ultra, an SC with 11.8% beta-cyfluthrin for structural pest control.^[27]^[28] These formulations must adhere to FAO tolerances, such as ±10-15% for declared active ingredient content and stability tests under storage conditions like 0°C and 54°C, ensuring emulsification and suspensibility for practical use.^[26] Isomer-specific activity varies, with diastereoisomers II and IV in beta-cyfluthrin demonstrating the highest potency against a broad spectrum of insects, including lepidopterans and sucking pests, due to their enhanced binding to sodium channels in neuronal membranes.^[21] Regulatory specifications, such as those from the FAO, mandate the 23-27% proportion for isomer I in technical cyfluthrin to balance overall efficacy and minimize less active components, while beta-cyfluthrin formulations prioritize the enriched active isomers for optimized performance.^[17] Global production of cyfluthrin, originally developed by Bayer, is now supplemented by generic manufacturers, with output scaled to meet regional demands for pest management in agriculture and public health, contributing to a market valued at approximately USD 343 million in 2024.^[29]

Applications

Agricultural Uses

Cyfluthrin is widely used in agriculture as a broad-spectrum pyrethroid insecticide for foliar applications to protect various crops from chewing and sucking pests.^[5] Primary crops include cotton, corn, soybeans, vegetables such as tomatoes and peppers, fruits like citrus and grapes, and grains like wheat and sunflowers.^[2] In cotton production, it effectively targets bollworms, tobacco budworms, plant bugs, and stink bugs, while in vegetables, it controls caterpillars, aphids, and leafhoppers.^[30] For fruits and tree nuts, applications address mites, beetles, and lygus bugs, and in grains, it manages weevils, armyworms, and grasshoppers.^[5]^[31] Application rates typically range from 0.01 to 0.05 kg active ingredient per hectare, often delivered as emulsifiable concentrates via ground, aerial, or chemigation methods for contact and stomach action.^[5] For example, in corn, rates of 0.8–2.8 fl oz/acre (approximately 0.007–0.025 kg ai/ha) control European corn borers and cutworms, with similar dosages used for soybean aphids and sunflower seed weevils in respective crops.^[31] Pre-harvest intervals are generally short, ranging from 0 to 7 days for many vegetables and cotton, allowing flexibility in harvest scheduling, though longer intervals like 21–45 days apply to grains and soybeans.^[30] Cyfluthrin provides rapid knockdown of pests within hours through nerve paralysis, offering immediate protection during vulnerable crop stages.^[2] It delivers residual control on treated foliage for up to 7 days, reducing the need for frequent reapplication while supporting resistance management when rotated with other insecticide classes.^[2]^[5] Its compatibility with integrated pest management (IPM) programs stems from targeted efficacy against key pests like tobacco budworms in tobacco and weevils in stored grains, minimizing disruption to beneficial insects when applied with proper timing and drift mitigation.^[31]

Household and Public Health Uses

Cyfluthrin is employed in household pest management to control a range of indoor insects, including ants, cockroaches, silverfish, fleas, and bed bugs, through targeted applications that minimize exposure in living spaces.^[32] Common methods include crack-and-crevice treatments and aerosol sprays, which deliver the insecticide directly to pest harborages such as baseboards, voids, and entry points.^[5] Ready-to-use liquid formulations, typically at 0.05% active ingredient, allow for spot treatments on surfaces like floors and walls, providing residual efficacy against crawling pests for several weeks.^[5] In structural protection, cyfluthrin targets termites and other wood-infesting insects around homes via perimeter barrier sprays applied to foundations and soil, creating a protective zone up to 7 feet wide.^[32] Reapplication is recommended every 3 to 6 months to maintain residual activity, depending on environmental factors and pest pressure.^[5] For public health applications, cyfluthrin serves in vector control programs to manage mosquitoes, flies, and ticks that transmit diseases, often through outdoor barrier sprays around residential and public structures.^[32] Mosquito control districts apply ultra-low volume (ULV) formulations via aerial or ground methods, exempt from certain buffer zones to facilitate rapid response in disease outbreaks.^[5] It demonstrates efficacy against houseflies at WHO-recommended doses of 0.03 g active ingredient per square meter, achieving high mortality rates in resistance monitoring.^[33] In malaria-endemic areas, pyrethroids like cyfluthrin contribute to integrated vector management, including indoor residual spraying and space treatments, though resistance patterns necessitate rotation with other classes.^[34] Professional products, such as controlled-release microencapsulated sprays, ensure knockdown of flying insects within 24 to 48 hours while providing extended protection.^[5]

Mechanism of Action

Insecticidal Effects

Cyfluthrin exhibits rapid knockdown effects on target insects, inducing paralysis through overstimulation of the nervous system, often within minutes to hours of exposure. This initial response manifests as constant muscle spasms, leading to immobilization that prevents feeding and movement. The compound's contact and stomach poison action facilitates quick penetration, making it particularly effective against both chewing pests, such as beetles and caterpillars, and sucking pests, like aphids and mosquitoes.^[2]^[5] Following knockdown, lethal effects result in insect death as paralysis progresses to starvation or direct neurotoxic failure. This process is observed in various studies on stored-product and agricultural pests. Cyfluthrin's efficacy ties briefly to its disruption of sodium channels in insect nerves, amplifying the overstimulation that culminates in fatality.^[5]^[7] The insecticide demonstrates a broad spectrum of activity, with high efficacy against orders such as Lepidoptera (e.g., moths and butterflies), Coleoptera (e.g., beetles and weevils), and Diptera (e.g., flies and mosquitoes). It controls a range of pests in field and structural settings, though effectiveness may be reduced in strains exhibiting resistance due to repeated exposure. Residual persistence on treated surfaces varies by formulation and environmental factors, generally lasting several days to weeks and allowing sustained control against reinfestation.^[2]^[5]^[35]

Biochemical Interactions

Cyfluthrin, a synthetic pyrethroid insecticide, primarily targets voltage-gated sodium channels (VGSCs) in the nerve axons of insects, binding to specific receptor sites on the alpha subunit of these channels. This interaction modifies the gating kinetics of the VGSCs, preventing their transition from the open to the inactivated state and thereby prolonging sodium influx during membrane depolarization. As a result, the channels remain open longer than normal, leading to repetitive nerve firing and eventual disruption of nerve impulse transmission, which causes hyperexcitation and paralysis in the target insects.^[36]^[7] As a Type II pyrethroid, cyfluthrin possesses an alpha-cyano group attached to the alpha-carbon of the alcohol moiety, which distinguishes it from Type I pyrethroids and enhances its binding affinity to VGSCs. This structural feature increases the potency of the insecticide by stabilizing the open state of the channel more effectively, producing a characteristic prolonged sodium tail current and promoting greater neurotoxicity through sustained depolarization without initial repetitive discharges. The alpha-cyano group also slows the rate of ester hydrolysis, further contributing to its prolonged action on insect nervous systems.^[7]^[37] The selectivity of cyfluthrin for insects over mammals arises partly from differences in detoxification metabolism; insects possess less efficient carboxylesterases and cytochrome P450 enzymes, which results in slower hydrolysis of the ester bond in pyrethroids compared to mammals, where rapid hepatic metabolism converts cyfluthrin to inactive, water-soluble metabolites. Additionally, insect VGSCs exhibit higher sensitivity to pyrethroids due to subtle amino acid differences, such as methionine at position 918 versus isoleucine in mammals, making insect channels approximately 10 to 100 times more susceptible to modification.^[7]^[38]^[39] Resistance to cyfluthrin in insect populations often develops through knock-on mutations in the voltage-gated sodium channel genes, such as the knockdown resistance (kdr) mutation L1014F or the super-kdr mutation M918T (also known as M918L), which alter the channel's structure and reduce the binding affinity of the insecticide. These point mutations, particularly in the S6 segments of domains II and III, sterically hinder pyrethroid access to the binding site, thereby decreasing the prolongation of channel opening and conferring varying levels of resistance across species like mosquitoes and agricultural pests.^[36]^[40]

Toxicology and Safety

Human Health Effects

Cyfluthrin exposure in humans primarily occurs through dermal contact or inhalation during occupational handling of pesticide formulations, with rare instances of oral ingestion from accidental contamination. Due to its rapid metabolism in mammals, systemic effects are uncommon, as the compound is quickly hydrolyzed in the liver to inactive metabolites, with about 40% excreted in urine within 48 hours.^[7]^[2] Acute dermal exposure often results in transient skin paresthesia, characterized by tingling, numbness, itching, or burning sensations on contact areas, which typically resolve within 1-2 days but may persist for weeks in severe cases; these symptoms are exacerbated by heat or moisture.^[2]^[7] Inhalation of cyfluthrin aerosols or dust can cause respiratory irritation, including coughing, sneezing, and mild shortness of breath, along with systemic symptoms such as nausea, vomiting, headache, and dizziness.^[2]^[7] Acute oral ingestion exhibits low toxicity, with rat LD50 values exceeding 500 mg/kg depending on the vehicle, though high doses may induce neurotoxic symptoms like tremors, muscle fasciculations, and fatigue.^[17]^[9]^[2] Chronic exposure to cyfluthrin has been associated with potential neurotoxic effects, including possible cognitive impairments or neurological symptoms in pesticide applicators, though no permanent sensory nerve damage has been documented.^[41] Organ inflammation may occur with prolonged exposure, as indicated by animal studies showing effects on multiple systems, but human data remain limited.^[42] Standard tests indicate no carcinogenicity or reproductive toxicity in humans, with the U.S. EPA classifying cyfluthrin as "not likely to be carcinogenic" based on rodent studies, and minimal impact on fertility or development.^[43]^[2] The EPA's 2020 interim registration review confirmed the existing toxicology profile with no unacceptable human health risks.^[5] Overall, cyfluthrin demonstrates lower acute toxicity to humans compared to aquatic species.^[2]

Mammalian Toxicity Data

Cyfluthrin exhibits moderate acute toxicity via the oral route in mammals, with reported LD50 values in rats ranging from 590 to 869 mg/kg in males and 1189 to 1271 mg/kg in females when administered in polyethylene glycol vehicle.^[44] The dermal LD50 in rats exceeds 5000 mg/kg, indicating low acute dermal toxicity.^[45] For inhalation, the 4-hour LC50 in rats is greater than 0.96 mg/L, classifying it as moderately toxic by this route.^[3] In subchronic and chronic exposure studies, the no-observed-adverse-effect level (NOAEL) for cyfluthrin was established at 9.5 mg/kg/day (125 ppm) in a 13-week dietary rat study, based on the absence of significant effects at this dose.^[44] At higher doses, such as 38 mg/kg/day, effects included reduced body weight gain and neurobehavioral changes like decreased motor activity.^[45] In a 2-year chronic dietary study in rats, the NOAEL was 6.2 mg/kg/day, with body weight reductions observed at 12.4 mg/kg/day.^[44] Developmental toxicity studies in rats and rabbits showed no evidence of teratogenicity across tested doses.^[44] The NOAEL for developmental effects was 10 mg/kg/day in rats and 20 mg/kg/day in rabbits, with slight maternal toxicity, including reduced body weight gain, noted at higher doses such as 42 mg/kg/day in rats and 60 mg/kg/day in rabbits.^[45] Reproductive toxicity assessments in rats identified a NOAEL of 34.7 mg/kg/day, with no adverse effects on fertility or offspring viability at the highest tested dose.^[44] Key mammalian toxicity evaluations by the U.S. Environmental Protection Agency highlight neurotoxic potential, including functional observational battery changes in rats at doses above 2 mg/kg/day in acute studies.^[45] EPA assessments also reference neurotoxicity studies in hens showing symptoms of intoxication at high doses (e.g., 500 mg/kg bw) but no evidence of delayed neuropathy or nerve fiber degeneration.^[43] These animal data align with observed neurobehavioral symptoms in human exposure cases, such as tremors and ataxia.^[11]

Environmental Impact

Fate in the Environment

Cyfluthrin exhibits moderate persistence in soil, where it primarily undergoes aerobic microbial degradation with a typical half-life of 33 days under laboratory conditions, though values can range from 7 to 90 days depending on soil type, temperature, and microbial activity. Anaerobic conditions extend this half-life significantly, with studies showing only gradual decline over 140 days in heavy clay soils. The compound binds strongly to soil organic matter, with organic carbon-water partition coefficients (Koc) ranging from 73,000 to 180,000 mL/g, which greatly limits its mobility and potential for leaching into groundwater.^[18]^[11]^[46] In aquatic environments, cyfluthrin's low water solubility (approximately 0.0066 mg/L at pH 7 and 20°C) further restricts its dissolution and transport, minimizing leaching risks from soil applications. It hydrolyzes slowly under neutral conditions, with a degradation time for 50% (DT50) of about 215 days at pH 7 and 20°C, though this accelerates to 1.6 days at pH 9. Photodegradation in water is more rapid, achieving a DT50 of 1 day at pH 7 in the presence of sunlight, primarily through cleavage of the ester bond. In water-sediment systems, overall DT50 is around 8 days, with faster dissipation in the water phase due to combined microbial and photolytic processes.^[18]^[11]^[47] Cyfluthrin has low volatility due to its vapor pressure of about 2 × 10^{-9} mm Hg at 25°C, reducing atmospheric transport, though any airborne residues degrade quickly via photolysis with a half-life of 1–2 days under sunlight exposure. Bioaccumulation potential is moderate to high in aquatic organisms, evidenced by a bioconcentration factor (BCF) of 506 in fish, but rapid metabolism and depuration (CT50 of 9 days) limit long-term buildup in tissues. Primary degradation pathways involve microbial ester hydrolysis in soil and water, yielding key metabolites such as 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid and 4-fluoro-3-phenoxybenzoic acid, which are less persistent and further mineralized to carbon dioxide.^[18]^[11]^[47]

Ecotoxicity to Non-Target Organisms

Cyfluthrin exhibits extremely high toxicity to aquatic organisms, posing significant risks to freshwater ecosystems through direct exposure or runoff. For instance, the 96-hour LC50 for rainbow trout (Oncorhynchus mykiss) is reported as 0.68 μg/L in static tests, indicating acute lethality at very low concentrations. Similarly, the 48-hour LC50 for the water flea (Daphnia magna) is 0.00014 μg/L (0.14 ng/L), classifying cyfluthrin as one of the most potent pyrethroids against aquatic invertebrates.^[3] These values underscore its potential to disrupt aquatic food webs, with sublethal effects such as impaired reproduction and locomotion observed in surviving populations.^[48] Pollinators, particularly honey bees (Apis mellifera), face severe threats from cyfluthrin due to its high contact toxicity, with an acute LD50 of 0.025 μg/bee, leading to rapid mortality and potential colony disruption through foraging exposure.^[49] This toxicity extends to non-target insects beneficial in integrated pest management (IPM), such as ladybugs (Coccinellidae) and predatory mites, where cyfluthrin causes broad-spectrum mortality that reduces natural pest control efficacy.^[2] In contrast, cyfluthrin shows low acute toxicity to birds, with avian oral LD50 values exceeding 2000 mg/kg in species like bobwhite quail and mallard ducks, suggesting minimal direct risk to avian populations from ingestion.^[50] Earthworms (Eisenia fetida) experience moderate toxicity from cyfluthrin, with a contact LC50 of 0.5 μg/cm² in filter paper assays, which can reduce soil biodiversity and affect nutrient cycling in treated fields.^[51] Field studies on agricultural runoff have detected cyfluthrin in sediments at concentrations exceeding U.S. EPA aquatic life benchmarks by factors of 10 to 100 times, particularly following storm events in urban and cropland watersheds, amplifying exposure to benthic organisms.^[52]^[53] This sediment contamination, often linked to its moderate persistence in soils, prolongs ecological risks in receiving waters.^[5]

Regulation and Legal Status

Approvals and Restrictions

Cyfluthrin was unconditionally registered by the United States Environmental Protection Agency (EPA) on December 30, 1987, for use as an insecticide in agricultural and non-agricultural settings.^[50] The EPA has established tolerances for cyfluthrin residues in over 50 raw agricultural commodities under 40 CFR 180.436, with maximum levels ranging from 0.01 ppm (e.g., in processed foods) to 12 ppm (e.g., in grass forage), including 0.2 ppm for cotton, undelinted seed.^[54] To protect aquatic environments, EPA restrictions prohibit direct applications to water bodies or areas where surface water is present, and labels require no aerial applications over aquatic habitats; for ultra-low volume (ULV) aerial applications, no applications within 450 feet of such areas; for other aerial applications, within 150 feet; and for ground applications, within 25 feet, to prevent drift and runoff.^[5]^[55] In the European Union, cyfluthrin is no longer approved as an active substance for plant protection products under Regulation (EC) No 1107/2009, with the approval expiring on April 30, 2014, following a non-renewal decision.^[56] Current maximum residue levels (MRLs) for cyfluthrin have been reduced to the default value of 0.01 mg/kg for most food commodities, reflecting its non-approved status, though higher levels up to 0.5 mg/kg apply in specific cases like certain animal products.^[57]^[58] Prior to expiration, risk mitigation measures included mandatory buffer zones near water bodies to minimize spray drift and protect non-target aquatic organisms.^[59] Health Canada's Pest Management Regulatory Agency (PMRA) completed a re-evaluation of cyfluthrin in 2018 (Re-evaluation Decision RVD2018-35), confirming its continued registration for agricultural uses but imposing limits on non-agricultural applications to reduce human exposure risks.^[60] These include restrictions to spot or crack-and-crevice treatments only, with no broadcast sprays or space sprays permitted indoors, and ventilation requirements post-application.^[61] Cyfluthrin pesticide labels in the US and Canada generally require the signal word "Caution" due to its moderate acute toxicity profile.^[42] Handlers must wear personal protective equipment (PPE), including long-sleeved shirts, long pants, shoes, socks, and chemical-resistant gloves, with additional respiratory protection for certain mixing/loading activities.^[5] The restricted-entry interval (REI) is 12 hours in the US, during which treated areas must not be entered without appropriate PPE, while Canadian labels specify a 6-hour re-entry period for people and pets after application dries.^[61]

International Variations

The World Health Organization (WHO) classifies cyfluthrin as moderately hazardous (Class II) based on its acute oral toxicity profile.^[9] It recommends cyfluthrin for vector control in tropical regions, particularly for indoor residual spraying against malaria vectors, with precautions to mitigate risks to applicators and non-target organisms. In Australia and New Zealand, cyfluthrin is approved for agricultural and public health uses similar to those in other regions, including pest control in crops and households. However, maximum residue limits (MRLs) are generally stricter; if no specific MRL is established, residues above 0.01 mg/kg (limit of quantification) are not permitted, with specific values such as 0.2 mg/kg for tomatoes.^[63] Beta-cyfluthrin, an isomer-enriched variant, is often preferred in formulations due to its enhanced efficacy and stability.^[64] In developing countries across Africa and Asia, cyfluthrin is widely employed for malaria vector control through indoor spraying and treated materials, contributing to reduced transmission in endemic areas.^[65] For instance, studies in Tanzania demonstrate its effectiveness in impregnated nets for lowering malaria incidence.^[65] However, import and use restrictions exist in parts of India due to widespread insecticide resistance in vectors like Anopheles culicifacies.^[66] Regulatory differences are notable globally: the European Union does not approve cyfluthrin for plant protection products following the expiration of its authorization in 2014, leading to lowered MRLs (often 0.01 mg/kg as the limit of quantification) and bans on certain emulsifiable concentrate formulations to protect aquatic environments near water bodies.^[67] No full global bans exist, though phase-outs occur in organic farming systems that prohibit synthetic insecticides. Ongoing re-assessments, such as the U.S. EPA's 2020 interim registration review (which as of March 2025 remains ongoing with no final decision), evaluate risks to support continued use with mitigation measures.^[5]^[68] International trade is facilitated by Codex Alimentarius MRLs, which harmonize standards; for example, 0.05 mg/kg applies to bananas and certain spice fruits, aiding export compliance across borders.^[69]

References

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The WHO Recommended Classification of Pesticides by Hazard identifies Cyfluthrin and beta-Cyfluthrin (technical grade) as Class II: moderately hazardous; Main ...
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Cyfluthrin is used to control pests like ants, silverfish, cockroaches, termites, weevils, fleas, mosquitoes and flies.
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EXTOXNET PIP - CYFLUTHRIN - Oregon State University
Water Solubility: 0.002 mg/ml @ 20 degrees C. Solubility in Other Solvents: > 200 g/l in dichloromethane and toluene, 10-20 g/l hexane, 20-50 g/l propan-2-ol. ...
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Melting point: 60°C Solubility in water, mg/l at 20°C: 0.003. Density (at 20°C): 1.27 g/cm³. Octanol/water partition coefficient as log Pow: 5.9. Vapour ...
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Sep 30, 2020 · This document is the Environmental Protection Agency's (EPA or the Agency) Interim. Registration Review Decision (ID) for cyfluthrin and ...
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The pyrethroids are synthetic analogs and derivatives of the original pyrethrins and represent a diverse group of over 1,000 powerful insecticides.
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Cyfluthrin is effective against many pests. It has a rapid knockdown effect and long-lasting residual activity (Pesticide Manual, 1997).Missing: broad- spectrum stomach
[8]
Cyfluthrin; Pesticide Tolerance - Federal Register
Sep 13, 2005 · Cyfluthrin is a member of the pyrethroid class of pesticides. EPA is not currently following a cumulative risk approach based on a common ...Missing: properties | Show results with:properties
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891. Cyfluthrin (WHO Food Additives Series 39) - INCHEM
EXPLANATION Cyfluthrin (Figure 1) is a synthetic cyano-containing pyrethroid insecticide. ... type-II pyrethroid poisoning. After oral administration, the ...
[10]
Cyfluthrin - an overview | ScienceDirect Topics
It is generally supplied as a 10–25% liquid concentrate for commercial use. View chapterExplore book · Read full chapter. URL: https://www.sciencedirect.com ...
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[PDF] ATSDR Pyrethrins and Pyrethroids Tox Profile
Other case studies of interest include Reproductive and Developmental. Hazards; Skin Lesions and Environmental Exposures; Cholinesterase-Inhibiting Pesticide.
[12]
The history of extensive structural modifications of pyrethroids - PMC
Nov 20, 2019 · The first synthetic pyrethroid, allethrin, was invented at the United States Department of Agriculture (USDA) in 1949, and its patent was opened ...<|control11|><|separator|>
[13]
US5028731A - Preparation of mixtures of cypermethrin or cyfluthrin ...
Preparation of mixtures of cypermethrin or cyfluthrin isomers enriched in more active species.
[14]
Cyfluthrin - the NIST WebBook
Cyfluthrin · Formula: C22H18Cl2FNO · Molecular weight: 434.288 · IUPAC Standard InChI: InChI=1S/C22H18Cl2FNO3/c1-22(2)15(11-19(23)24)20(22)21(27)29-18(12-26)13-8-9 ...
[15]
Cyfluthrin | 68359-37-5 - ChemicalBook
ChEBI: A carboxylic ester obtained by formal condensation between 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid and (4-fluoro-3-phenoxyphenyl)( ...
[16]
[PDF] fao specifications and evaluations
Melting point and temperature of decomposition. Melting ... Chemical composition and physico-chemical properties of cyfluthrin technical material (TC).
[17]
Cyfluthrin (Ref: OMS 2012) - AERU - University of Hertfordshire
Cyfluthrin is a pyrethroid insecticide. It has a low aqueous solubility and is non-volatile. It may be moderately persistent in some soil systems.
[18]
[PDF] TECHNICAL DATA SHEET - Endura
Nov 13, 2013 · Solubility in other solvents. Xylene: > 250 g/l at 20 °C. Solubility in other solvents. Acetone: > 250 g/l at 20 °C. Viscosity, kinematic ca ...
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Cyfluthrin - Endura
CYFLUTHRIN is an effective photostable synthetic pyrethroid insecticide with killing effect on a broad spectrum of insects such as flies, mosquitoes ...Missing: photostability | Show results with:photostability
[20]
[PDF] cyfluthrin (157)/beta-cyfluthrin (228)
Beta-cyfluthrin is an enriched isomeric form of the two biologically active diastereoisomeric pairs of isomers of cyfluthrin. It is considered a new compound ...
[21]
Stereochemical and chiral aspects in the synthesis of 3‐(2,2 ...
The synthesis of (1RS)-cis,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid by dehydrohalogenation of 4,6,6,6-tetrahalohexanoates has been ...
[22]
Stereoselective synthesis of cis-3-(2,2-dichlorovinyl)
Stereoselective synthesis of cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid ... ChemInform Abstract: Stereoselective Synthesis of cis‐3 ...
[23]
Cyfluthrin hapten compound, its synthesis method and use
Wash with water, add 30ml of ethyl acetate to dilute, first extract with 5% NaOH (30ml×3), combine, wash the lye with ether (20ml×3), then adjust the pH value ...
[24]
Synthesis of optically active cis-3-(2,2-dichlorovinyl)
Jul 1, 1987 · Synthesis of optically active cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid via intramolecular alkylation of a chiral ...
[25]
[PDF] fao specifications and evaluations
The material shall consist of technical beta-cyfluthrin, complying with the requirements of FAO specification 482/TC (August 2016), dissolved in suitable ...
[26]
Baythroid XL Insecticide - Bayer Crop Science
Baythroid XL insecticide is the complete pyrethroid for many crops and provides fast, effective control of labeled primary and secondary pests.Missing: introduction 1981
[27]
[PDF] Health Questions and Answers for Tempo Insecticidal Products
Q: What is Tempo®? A: Tempo® is a line of pesticide products containing the active ingredient beta-cyfluthrin, which is in the pyrethroid family of ...
[28]
Cyfluthrin Market 2025 Forecast to 2032 - 24ChemicalResearch
Rating 4.9 (3,567) Nov 1, 2025 · Global Cyfluthrin market was valued at USD 342.7 million in 2024 and is projected to reach USD 412.8 million by 2032, at a CAGR of 2.4% ...Missing: generics | Show results with:generics
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[PDF] 2025 Insect Control Guide for Agronomic Crops
Successful, economical control of cotton insect pests requires using a variety of control methods instead of only one, such as scheduled insecticide use. This ...
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None
Below is a merged summary of the agricultural uses of cyfluthrin extracted from the NDSU Insect Management Guide E1143-22. To retain all information in a dense and organized format, I’ve used tables in CSV-style text for key details (crops, pests, application rates, and PHI). Additional notes, efficacy details, examples, and URLs are provided in a narrative format following the tables.
[31]
[PDF] CYFLUTHRIN | National Pesticide Information Center
What is cyfluthrin. Cyfluthrin is in a group of man-made insecticides called pyrethroids.1 It was first registered in the US in 1987.
[32]
Evaluation of Cyfluthrin and Etofenprox Resistance in House Fly ...
Sep 26, 2024 · ... molecular weight: 376.49 g/mol) and cyfluthrin (C22H18Cl2NO3, CAS number: 68359-37-5, molecular weight: 434.29 g/mol), purchased from Sigma ...
[33]
[PDF] WHO Guidelines for malaria - 16 February 2021
Feb 16, 2021 · cyhalothrin, etofenprox, bifenthrin, cyfluthrin ... Larval source management: a supplementary measure for malaria vector control.
[34]
Beta-cyfluthrin, a synthetic pyrethroid for mosquito control - PubMed
Residual efficacy at 50 mg(ai)/m2 was more persistent (for 14-25 weeks) on thatch and asbestos among the four treated surfaces. This compound also elicited ...
[35]
Voltage-gated sodium channels as targets for pyrethroid insecticides
Jan 9, 2017 · The mode of action of pyrethroids is known to be via interactions with the voltage-gated sodium channel.
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Biomarkers of Type II Synthetic Pyrethroid Pesticides in Freshwater ...
Mar 31, 2014 · Type II synthetic pyrethroids contain an alpha-cyano group which renders them more neurotoxic than their noncyano type I counterparts.
[37]
Characterization of pyrethroid hydrolysis by the human liver ...
Differences in the activities of carboxylesterases and P450s between mammals and insects contribute to the low mammalian toxicity of pyrethroids (i.e., ...
[38]
Pyrethroids: mammalian metabolism and toxicity - PubMed
Apr 13, 2011 · They showed that ester hydrolysis and oxidation play predominant roles in mammalian metabolism of pyrethroids and that rapid metabolism leads to low mammalian ...
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Sodium Channel Mutations and Pyrethroid Resistance in Aedes ...
Oct 31, 2016 · Mutations in the sodium channel have been shown to be responsible for pyrethroid resistance, known as knockdown resistance (kdr), in various insects including ...
[40]
Neurotoxicity of Pesticides - PMC - PubMed Central
Neurological effects, including cognitive impairment, have been observed following pyrethroid exposure of pesticide applicators and their families [96, 136].
[41]
[PDF] Cyfluthrin C hemicalWatch Factsheet - Beyond Pesticides
CAS Registry Number: 68359-37-5. Chemical Class: Synthetic pyrethroid. Use: Broad spectrum insecticide for a variety of agri- cultural crops.
[42]
Cyfluthrin; Pesticide Tolerance - Federal Register
Sep 27, 2002 · iii. Cancer. Cyfluthrin has been classified as “not likely to be carcinogenic in humans” based on the results of a carcinogenicity study in ...Missing: inflammation | Show results with:inflammation
[43]
[PDF] (Pesticide residues in food \227 2006: Toxicological evaluations)
For cyfluthrin, the specifications were established by the FAO/WHO Joint Meeting on Pesticide ... containing technical-grade cyfluthrin (purity, 95.5%–96.2%) at a ...
[44]
[PDF] UNITED STATES ENVIRONMENTAL PROTECTION AGENCY ...
Jun 14, 2025 · agricultural uses of cyfluthrin and beta-cyfluthrin, assuming baseline clothing and no PPE. The inhalation risk estimates for scenarios that ...
[45]
US EPA-Pesticides; Cyfluthrin
It is noted, however, that Koc values for cyfluthrin vary considerably (73,500 mL/g – 180,300 mL/g.-OC) which likely reflect differences in organic carbon ...
[46]
[PDF] Literature Review for Candidate Chemical Control Agents for ...
Hyatt (2004) reported even more rapid degradation with significant chemical losses within an hour after application. Photodegradation and sedi- ment binding ...
[47]
Role of Sediments in Insecticide Runoff from Urban Surfaces
Jul 11, 2018 · Insecticides, such as pyrethroids, have frequently been detected in runoff from urban areas, and their offsite transport can cause aquatic ...
[48]
[PDF] FAO SPECIFICATIONS AND EVALUATIONS FOR PLANT ...
The material shall consist of technical beta-cyfluthrin, complying with the requirements of FAO specification 482/TC (1999), dissolved in suitable solvents, ...
[49]
Pesticide Fact Sheet: Cyfluthrin - epa nepis
... Registration Date Issued: December 30, 1987 Fact Sheet Number: 164 ... Sufficient data are available to characterize cyfluthrin from an environmental fate and ...
[50]
The potential acute and chronic toxicity of cyfluthrin on the soil ...
Aug 6, 2025 · ... earthworm progeny. Li et al. (2017) also showed that applying cyfluthrin at more than 20 mg/kg considerably reduced the number of cocoons ...
[51]
[PDF] attachment_3.pdf - Regulations.gov
Jul 31, 2012 · most of the fipronil sulfone and cyfluthrin detections were above their lowest US EPA aquatic benchmark. ... pesticide runoff studies with changes ...
[52]
Storm-event-transport of urban-use pesticides to streams likely ...
Multiple U.S. EPA benchmark or criterion exceedances occurred in 40 % of urban streams sampled. Bed sediment concentrations of bifenthrin were highly correlated ...
[53]
40 CFR 180.436 -- Cyfluthrin and the isomer beta-cyfluthrin - eCFR
40 CFR 180.436 establishes tolerances for cyfluthrin and beta-cyfluthrin residues in raw agricultural commodities, such as alfalfa (5.0 ppm) and barley grain ( ...Missing: crops | Show results with:crops
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[PDF] Updated Spray Drift Language for Pyrethroid Agricultural Use Products
Do not apply within 450 feet of aquatic habitats (such as, but not limited to, lakes, reservoirs, rivers, streams, marshes, ponds, estuaries, and commercial ...<|separator|>
[55]
Review of the existing maximum residue levels for Beta‐cyfluthrin ...
Sep 23, 2021 · EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substances Beta‐cyfluthrin and Cyfluthrin.
[56]
Review of the existing maximum residue levels for Beta‐cyfluthrin ...
Sep 23, 2021 · EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substances Beta‐cyfluthrin and Cyfluthrin.
[57]
Maximum residue levels for cyfluthrin - AGRINFO Platform
Feb 6, 2023 · The EU has lowered MRLs for cyfluthrin to the lowest limit of analytical detection (LOD: 0.01 – 0.05 mg/kg), on certain fruits.
[58]
[PDF] commission implementing regulation (eu) 2020/968
Jul 3, 2020 · e.g. no-spray buffer zones and/or spray drift reduction, to achieve a low risk for sediment-dwelling organisms and aquatic organisms. As ...
[59]
[PDF] Re-evaluation Decision RVD2018-35 - à www.publications.gc.ca
Oct 31, 2018 · 1.1 Toxicology Assessment for Cyfluthrin. The initial toxicological assessment for cyfluthrin was presented in the Proposed Re-evaluation.Missing: efficacy boll weevils
[60]
Changes to the cyfluthrin pesticides registration (non-agricultural uses)
Jan 19, 2024 · Domestic products are for indoor use against household pests such as ants, earwigs, cockroaches and spiders.Missing: fleas | Show results with:fleas
[61]
Mandatory Intervals Between Application, Reentry, Harvest ... - UC IPM
Mandatory Intervals Between Application, Reentry, Harvest, and Hazards to Bees ; cyfluthrin, Tombstone, 12, 0, 3A ; diflubenzuron, Micromite 80WGS and 2L, 12, 7 ...Missing: PPE | Show results with:PPE
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[PDF] Food Notice: Maximum Residue Levels for Agricultural Compounds
Jul 31, 2025 · The purpose of the Food Act 2014 (the Act) includes achieving the safety and suitability of food for sale, maintaining and improving confidence ...
[63]
[PDF] Cyflu hrin & Beta-cyfluthrin - EPA
This document provides a review of the appropriate studies for cyfluthrin and beta-cyfluthrin to determine their Global Harmonised System (GHS)/EPA hazard ...Missing: fact | Show results with:fact
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Impact of cyfluthrin (Solfac EW050) impregnated bed nets on ...
Jan 11, 2013 · Conclusion. The study confirms the effectiveness of cyfluthrin impregnated nets in reducing malaria transmission. Lessons from this study could ...
[65]
Insecticide resistance status of malaria vectors in ... - PubMed Central
Nov 26, 2022 · An. fluviatilis was susceptible to malathion, cyfluthrin, and deltamethrin in the two tribal districts (mortality – 98–100%) but possible ...
[66]
Review of the existing maximum residue levels for Beta‐cyfluthrin ...
Sep 23, 2021 · EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substances Beta-cyfluthrin and Cyfluthrin.
[67]
Pesticide Detail | CODEXALIMENTARIUS FAO-WHO
Commodity name. 157 - Cyfluthrin/beta-cyfluthrin. Functional class ... Spices, fruits and berries, 0.03 mg/Kg, 2011. Spices, roots and rhizomes, 0.05 mg/Kg ...