chemicalWATCH Factsheet SYNTHETIC PYRETHROIDS
Pesticide products containing pyrethroids properties. They are not easily absorbed nasal stuffiness, headache, nausea, incoor- are often described by pest control opera- through the skin, but are absorbed through dination, tremors, convulsions, facial flush- tors and community mosquito management the gut and pulmonary membrane. Tests of ing and swelling, and burning and itching bureaus as safe as chrysanthemum flow- some pyrethroids on laboratory animals re- sensations. The most severe poisonings ers. While pyrethroids are a synthetic ver- veal striking neurotoxicity when administered have been reported in infants, who are not sion of an extract from the chyrsanthemum, by injection or orally. Systemic toxicity by able to efficiently break down pyrethroids they were chemically designed to be more inhalation and dermal absorption is low. The (ETN, Pyrethroids, 1994). With orally in- toxic with longer breakdown times, and are acute toxicity, calculated by LD s, ranges 50 gested doses, nervous symptoms may oc- often formulated with synergists, increas- from low to high, depending on the specific cur, which include excitation and convulsions ing potency and compromising the human formulation. Low toxicity is attributed to two leading to paralysis, accompanied by mus- bodys ability to detoxify the pesticide. factors: limited absorption of some pyre- cular fibrillation and diarrhea (ETN, Pyre- throids, and rapid biodegradation by mam- throids, 1994). Death in these cases is due to What are Synthetic Pyrethroids? malian liver enzymes (ester hydrolysis and respiratory failure. Symptoms of acute expo- Synthetic pyrethroids are synthesized de- oxidation). Insects, without this liver func- sure last about 2 days. rivatives of naturally occurring pyrethrins, tion, exhibit greater susceptibility to the which are taken from pyrethrum, the oleo- chemicals (Reigart et al., 1999). Endocrine Disruption and Breast Cancer resin extract of dried chrysanthemum flow- Many pyrethroids have also been linked to ers. The insecticidal properties of pyrethrins Pyrethroids interfere with the ionic conduc- disruption of the endocrine system, which are derived from ketoalcoholic esters of tance of nerve membranes by prolonging the can adversely affect reproduction and sexual chrysanthemic and pyrethroic acids. These sodium current. This stimulates nerves to development, interfere with the immune sys- acids are strongly lipophilic and rapidly pen- discharge repeatedly causing hyper-excit- tem and increase chances of breast cancer. etrate many insects and paralyze their ner- ability in poisoned animals. The World Health Pyrethroids contain human-made, or vous system (Reigart et al., 1999). Both pyre- Organization explains that synthetic pyre- xenoestrogens, which can increase the thrins and synthetic pyrethroids are sold as throids are neuropoisons acting on the axons amount of estrogen in the body (Garey et al., commercial pesticides used to control pest in the peripheral and central nervous sys- 1998). When tested, certain pyrethroids dem- insects in agriculture, homes, communities, tems by interacting with sodium channels in onstrate significant estrogenicity and in- restaurants, hospitals, schools, and as a topi- mammals and/or insects. The main systems crease the levels of estrogen in breast can- cal head lice treatment. Various formulations for metabolism include breakage of the ester cer cells (Go et al., 1999). Because increased of these pesticides are often combined with bond by esterase action and oxidation at cell division enhances the chances for the other chemicals, known as synergists, to in- various parts of the molecule. Induction of formation of a malignant tumor in the breast, crease potency and persistence in the envi- liver microsomal enzymes has also been ob- artificial hormones, like those found in pyre- ronment. served (WHO, 1999). throids, may increase breast cancer risk (PCBR, 1996). Some pyrethroids are classi- While chemically and toxicologically similar, Signs and symptoms of poisoning by pyre- fied by EPA as possible human carcinogens. pyrethrins are extremely sensitive to light, throids may take several forms. Because of heat and moisture. In direct sunlight, half- the similarities to crude pyrethrum, pyre- Pyrethroids and the Environment lives that can be measured in hours. How- throids may act as dermal and respiratory While the development of the synthetic pyre- ever, the pyrethroids, the synthetic ana- allergens. Exposure to pyrethroids has re- throids was heralded with claims of selec- logues of naturally occurring pesticides, sulted in contact dermatitis and asthma-like tive toxicity to insects, both pyrethroids and were developed to capture the effective in- reactions. Persons, especially children, with pyrethrins are extremely toxic to aquatic or- secticidal activity of this botanical insecti- a history of allergies or asthma are particu- ganisms, including fish such as the bluegill cide, with increased stability in light, yield- larly sensitive, and a strong cross-reactivity and lake trout, with LC values less than 1.0 50 ing longer residence times (Gosselin et al., with ragweed pollen has been recognized. parts per billion. These levels are similar to 1984). Severe anaphylactic (allergic) reactions with those for mosquito, blackfly and tsetse fly peripheral vascular collapse and respiratory larvae, often the actual target of the pyre- Pyrethroids and Health Effects difficulty are rare. Other symptoms of acute throid application. Lobster, shrimp, mayfly Pyrethroids have irritant and/or sensitizing toxicity due to inhalation include sneezing, nymphs and zooplankton are the most Beyond Pesticides 701 E Street, S.E., Suite 200 Washington DC 20003 202-543-5450 (v) 202-543-4791 (f) [email protected] www.beyondpesticides.org susceptible non-target aquatic organisms cluding the active ingredients of pesticides. about 12 hours. A study on laboratory (Mueller-Beilschmidt, 1990). The nonlethal Specifically, it has been shown to inhibit he- mice shows that bifenthrin causes gene effects of pyrethroids on fish include dam- patic microsomal oxidase enzymes in labora- mutation in white blood cells (ETN, age to the gills and behavioral changes. tory rodents and interfere in humans. Be- Bifenthrin, 1995). EPA classifies bifenthrin cause these enzymes act to detoxify many as a Class C (possible human) carcinogen Pyrethroids are moderately toxic to birds, drugs and other chemicals, a heavy expo- (EPA, 1997). Of concern in the environ- with most LD values greater than 1000 mg/ sure to an insecticidal synergist may make a ment, bifenthrin is very highly toxic to fish, 50 kg. Birds can also be indirectly affected by person temporarily vulnerable to a variety crustaceans, other aquatic animals and pyrethroids, because of the threat to their of toxic insults that would normally be eas- bees, and is moderately toxic to birds. food supply. Waterfowl and small insectivo- ily tolerated. Symptoms of PBO poisoning Scientists are particularly concerned about rous birds are the most susceptible (Mueller- include anorexia, vomiting, diarrhea, intesti- possible bioaccumulation in birds. Beilschmidt, 1990). Because pyrethroids are nal inflammation, pulmonary hemorrhage and Cypermethrin (AmmoTM, CymbushTM, toxic to all insects, both beneficial insects perhaps mild central nervous system depres- DemonTM) and pests are affected by pyrethroid appli- sion. Repeated contact may cause slight skin Cypermethrin, one of a handful of light- cations. In some cases, predator insects may irritation. Chronic toxicity studies have stable synthetic pyrethroids, is registered be susceptible to a lower dose than the pest, shown increased liver weights, even at the to control cockroaches, fleas and other disrupting the predator-prey relationship. lowest doses, 30 mg/kg/day. While not con- indoor pests in homes, restaurants, sidered a carcinogen by EPA, animal studies hospitals, schools and food processing Pyrethroids Residues / Persistence have shown hepatocellular carcinomas, even plants, and also in agriculture to control As mentioned before, pyrethroids are de- treatments as low as 1.2% (Takahashi et al., pests on cotton, fruits and vegetables. signed to breakdown more slowly than the 1994). About 90% of the cypermthrin manufac- naturally occurring pyrethrins. While pyre- tured worldwide is used to combat pests thrins, extremely sensitive to light, heat and Bifenthrin (TalstarTM, BrigadeTM, feeding on cotton crops (WHO, 1989). moisture, break down in a few hours, the syn- CaptureTM) Depending on the specific product thetic pyrethroids are stable and persist in Bifenthrin is an off-white to pale tan waxy formulation, EPA classifies pesticides the environment much longer. As a general solid, characterized by its slightly sweet containing cypermethrin as toxicity class II rule, pyrethroids break down most quickly smell. As a Restricted Use Pesticide, or III (I = most toxic, IV = least toxic) and in direct sunlight, usually just a few days bifenthrin may only be purchased or must display the word WARNING or after application, with a few exceptions. applied by certified applicators or persons CAUTION on the labels. Compared to However, in areas with limited sunlight, such under the direct supervision of a certified other pyrethroids, cypermethrin is rela- as grain silos and subway tunnels, pyre- applicator. EPA has registered bifenthrin tively stable, with a half-life of 8 16 days throids can persist for months. For more spe- for use on greenhouse ornamentals and in direct sunlight. In soil, studies have cific breakdown times see the sections be- cotton. Studies show bifenthrin to be shown the half-life to be as long as 8 low on resmethrin, permethrin and sumithrin. relatively insoluble in water. Its half-life in weeks, and in water as long as 100 days soil can range anywhere from 7 days to 8 (ETN, Cypermethrin, 1996). After treat- Synergists months depending on the soil type and the ments in the home, cypermethrin persists Both pyrethroids and pyrethrins are often amount of air in the soil (ETN, Bifenthrin, for about three months (Wright et al., formulated with oils or petroleum distillates 1995). Bifenthrin is one of a few synthetic 1993). and packaged in combination with syner- pyrethroids that are relatively stable in Cypermethrin is considered to be moder- gists, such as piperonyl butoxide (PBO) and direct sunlight. EPA has classified prod- ately toxic (oral male rat LD50 = 187 to 326 n-octyl bicycloheptene dicarboximide ucts containing bienthrin as toxicity class mg/kg, dermal rat LD50 = 1600 mg/kg) and (Gosselin et al., 1984). Synergists are added II (I = most toxic, IV = least toxic), and the like all pyrethroids, affects the central to increase the potency of the pesticide. A word WARNING must appear on all nervous system (ETN, Cypermethrin, range of products from repellants to foggers product labels. 1996). Symptoms of cypermethrin poison- to pediculicides (lice killers) to garden sprays Bifenthrin is moderately toxic to mammals ing in humans include numbness, burning, contain synergists. Many formulations of when ingested (oral rat LD50 = 54 to 70 loss of bladder control, vomiting, incoordi- permethrin, resmethrin and sumithrin, includ- mg/kg), and like all pyrethroids affects the nation, seizures, coma and death. In ing ScourgeTM and AnvilTM, used along the central nervous system. Symptoms of California, cypermethrin is the fourth most East Coast for mosquito control to combat poisoning include incoordination, tremor, common cause of pesticide-related illness the West Nile Virus, contain the synergist salivation, vomiting, diarrhea, and irritabil- in pest control operators. EPA classifies PBO. ity to sound and touch (ETN Bifenthrin, cypermethrin as a class C (possible 1995). Although bifenthrin does not cause human) carcinogen (EPA, 1997). Studies in PBO inhibits important liver enzymes re- inflammation or irritation on human skin, it laboratory animals have shown exposure sponsible for breakdown of some toxins, in- can cause a tingling sensation, lasting to cypermethrin to cause reproductive Beyond Pesticides 701 E Street, S.E., Suite 200 Washington DC 20003 202-543-5450 (v) 202-543-4791 (f) [email protected] www.beyondpesticides.org effects, including abnormal sperm and microsomal enzyme induction, irritability, is extremely toxic to bees and fish, and is disruption of sex hormones (Cox, 1996). peripheral vascular collapse, rhinorrhea, slightly toxic to birds. Cypermethrin should not be applied near serum alkaline phosphatase elevation, Permethrin (PounceTM, TorpedoTM, water, because it is very toxic to fish and tremors, vomiting and death due to DragnetTM) other aquatic organisms. respiratory failure. Deltamethrin is a Prior to 1978, permethrin was registered for Deltamethrin (ButoflinTM, ButossTM, suspected endocrine disruptor. use on cotton crops only. During the early CrackdownTM) Deltamethrin is also toxic to fish, aquatic 1980s registration was expanded to Deltamethrin is pyrethroid insecticide that organisms, amphibians and bees. include use on livestock and poultry, eggs, kills insects on contact and through Fenvalerate (Esfenvalerate, SumiflyTM, vegetables and fruit. Today uses also digestion. It works by paralyzing the SumiflowerTM) include lice treatments and urban/subur- insects nervous system and therefore Fenvalerate is registered for use on a wide ban pest control. Permethrin resembles giving a quick knock-down effect. It is array of crops including cotton, soybeans, pyrethrins chemically, but is chlorinated to used commonly to control caterpillars on corn, vegetables, apples, peaches, pears increase its stability. There are four apples, pears and hops, and for the control and nuts, as well as a termiticide and insect isomeric forms, two cis and two trans of of aphids, mealy bugs, scale insects, and repellent. Fenvalerate was first formulated technical permethrin. Although the acute whiteflies on glasshouse cucumbers, for agricultural use in 1974, but was toxicity of the mixture (oral rat LD50 > 5000 tomatoes, peppers, potted plants, and approved as a termiticide in 1987, as an mg/kg, oral mouse LD50 = 500) is less than ornamentals (ETN, Deltamethrin, 1995). It alternative to the voluntarily cancelled that of natural pyrethrins, the cis-isomer is is also registered for use on livestock and cyclodiene termiticides. During the late considerably more toxic (oral mouse LD50 for public health uses. Depending on the 1980s, fenvalerate received national press = 100), and in rats, the metabolites of the product formulation, deltamethrin pesti- coverage due to over 200 dog and cat cis-isomer are more persistent biologically. cides may range in toxicity from EPA poisonings, including 26 deaths, following (The cis and trans isomers differ in the toxicity class I to class III (I = most toxic, the use of BlockadeTM, a product contain- spatial arrangement of the atoms.) Product IV = least toxic), bearing the words ing fenvalerate in combination with DEET, formulations of permethrin can vary DANGER-POISON, WARNING or CAU- a common insect repellant. EPA classifies greatly in isomeric content. Compared to TION on the label (PANNA, 2000). fenvalerate products as toxicity class II (I = other pyrethroids, permethrin is very Deltamethrin products may be general or most toxic, IV = least toxic), and include stable, even when exposed to ultraviolet Restricted Use Pesticides. Most the word WARNING on all product labels. light. Permethrin is strongly absorbed to deltamethrin products persist from one to Some formulations are Restricted Use soil and other organic particles, with half- two weeks in the environment, with shorter Pesticides, and may only be purchased or lives in soil of up to 43 days. When used times in direct sunlight (ETN, Deltamethrin, applied by certified applicators or persons as a termiticide, permethrin can persist up 1995). under the direct supervision of a certified to 5 years. Deltamethrin produces different signs of applicator. The half-life of fenvalerate Permethrin receives an EPA toxicity class poisoning than other pyrethroids. When ranges from 15 days to 3 months in soil, 21 rating of II or III (I = most toxic, IV = least exposed to deltamethrin, mammals exhibit days in water and 2-4 weeks on vegetation. toxic), and carries either the word WARN- typical type II motor symptoms, which Fenvalerate is considered to be moderately ING or CAUTION on its label, depending include a writhing syndrome in rodents, as toxic (oral rat LD50 = 486 mg/kg). Symp- on the formulation. While it is not ex- well as copious salivation. The acute oral toms of poisoning through direct contact tremely toxic to humans, there are numer- LD in male rats has been reported as low include dizziness, burning and itching ous reports of transient skin, eye and 50 as 128 mg/kg to greater than 5,000 mg/kg (which is worsened by sweating and respiratory irritation. Like all pyrethroids, depending on the carrier and conditions of washing), blurred vision, tightness in the permethrin is a central nervous system the study (ETN, Deltamethrin, 1995). Some chest, and convulsions. When ingested by poison. Workers and researchers report studies have shown deltamethrin to cause laboratory animals, symptoms of poison- tingling in face and hands, and some skin irritation. Especially characteristic of ing include muscle incoordination, tremors, report allergic reactions. Based on studies deltamethrin poisoning is rolling convul- convulsions, nerve damage, and weight demonstrating carcinogenicity, EPA ranks sions. The sequence of the signs of loss. Fenvalerate is a strong eye irritant permethrin as a class C, or possible human poisoning is clearly defined, progressing and a suspected endocrine disruptor carcinogen (U.S. EPA, 1997). Other studies from chewing, salivation, and pawing to (PANNA, 2000). Sweden has banned the have shown effects on the immune system, rolling convulsions, tonic seizures, and chemical for use in forestry following enlarged livers and at high doses, de- death (ETN, Deltamethrin, 1995). In health related complaints from workers. creased female fertility and endocrine humans, symptoms of poisoning include Studies have found that immediate disruption. Permethrin is extremely toxic to ataxia, convulsions leading to muscle application of vitamin E to exposed areas aquatic life, bees and other wildlife. It fibrillation and paralysis, dermatitis, edema, can lessen the painful effects. Fenvalerate should not be applied in crops or weeds diarrhea, dyspnea, headache, hepatic
Beyond Pesticides 701 E Street, S.E., Suite 200 Washington DC 20003 202-543-5450 (v) 202-543-4791 (f) [email protected] www.beyondpesticides.org where foraging may occur (ETN, toxic to fish, other aquatic life and bees. is an endocrine disruptor, demonstrating Permethrin, 1996). The domestic manufacturer of resmethrin, significant estrogenicity and increases the Resmethrin (ScourgeTM, Raid Flying Penick Company, will not identify the inert level of estrogen in breast cancer cell, Insect KillerTM) ingredients in its product, but recommends suggesting that sumithrin may increase the Resmethrin is used for control of flying that it is not sprayed on paint, plastic or risk of breast cancer (Go et al., 1999). and crawling insects in homes, green- varnished surfaces, and that treatment of Sumithrin houses, processing plants, commercial living areas or areas with large amounts of (AnvilTM, d-Phenothrin) kitchens, airplanes and for public mosquito textiles be avoided. Sumithrin has been registered for use since control. Resmethrin is considered slightly Sumithrin (AnvilTM, d-Phenothrin) 1975. It is used to control adult mosquitoes toxic to humans and is rated EPA toxicity Sumithrin has been registered for use since and as an insecticide in transport vehicles, class III (I = most toxic, IV = least toxic), 1975. It is used to control adult mosquitoes commercial, industrial and institutional non- bearing the word CAUTION on its label. and as an insecticide in transport vehicles, food areas, in homes, gardens, greenhouses The oral rat LD50 is about 2500 mg/kg. commercial, industrial and institutional and on pets. Chemically, it is an ester of Although resmethrin has a very short half- non-food areas, in homes, gardens, chrysanthemic acid and alcohol. It is a com- life (under an hour in direct sunlight), it greenhouses and on pets. Chemically, it is bination of two cis and two trans isomers. persists much longer in soil with a half-life an ester of chrysanthemic acid and Sumithrin is slightly toxic and is rated EPA of 30 days (ETN, Resmethrin, 1996). alcohol. It is a combination of two cis and toxicity class IV bearing the word CAUTION Resmethrin breaks down into a smelly two trans isomers. Sumithrin is slightly on its label. The oral rat LD is greater than 50 byproduct, phenylacetic acid, which binds toxic and is rated EPA toxicity class IV (I = 5,000 mg/kg, and the LC for inhalation is 50 strongly to textiles and dissipates slowly, most toxic, IV = least toxic) bearing the greater than 1210 mg/m3. Sumithrin degrades smelling of urine. word CAUTION on its label. The oral rat rapidly, with a half-life of 1-2 days under dry, Resmethrin is absorbed rapidly and LD50 is greater than 5,000 mg/kg, and the sunny conditions. Under flooded conditions, distributed to all tissues including the LC50 for inhalation is greater than 1210 the half-life increases to 2-4 weeks for the brain. Skin absorption is low, although it mg/m3. Sumithrin degrades rapidly, with a trans isomer and 1-2 months for the cis iso- should be noted that some individuals half-life of 1-2 days under dry, sunny mer. In grain silos, with no sunlight and little manifest allergic responses including conditions. Under flooded conditions, the air circulation, most of the product still re- dermatitis, asthma, runny nose and watery half-life increases to 2-4 weeks for the mains after one year (WHO, 1990). eyes after initial contact. In laboratory trans isomer and 1-2 months for the cis Symptoms of acute sumithrin poisoning in- animals, chronic toxicity studies have isomer. In grain silos, with no sunlight and clude hyperexcitability, prostration, slow res- shown hypertrophy of the liver, prolifera- little air circulation, most of the product piration, salivation, tremor, ataxia and paraly- tive hyperplasia and benign and cancerous still remains after one year (WHO, 1990). sis. Chronic feeding studies resulted in in- liver tumors. EPA reviewers noted slight, Symptoms of acute sumithrin poisoning creased liver weights in both males and fe- but significant, increases in the number of include hyperexcitability, prostration, slow males. In rat studies, sumithrin was com- offspring born dead and decreased respiration, salivation, tremor, ataxia and pletely excreted in 3-7 days (WHO, 1990). viability, which they thought might be paralysis. Chronic feeding studies resulted Studies have shown that sumithrin demon- secondary to trans placental toxicity. Tests in increased liver weights in both males strates significant estrogenicity and in- for neurotoxicity have been negative, but it and females. In rat studies, sumithrin was creases the level of estrogen in breast can- is a suspected endocrine disruptor completely excreted in 3-7 days (WHO, cer cell, suggesting that sumithrin may in- (PANNA, 2000). Resmethrin is extremely 1990). Studies have shown that sumithrin crease the risk of breast cancer (Go et al., 1999).
Synthetic Pyrethroids chemicalWATCH Factsheet References
Cassagrande, R.A. 1989. Considerations ace.orst.edu/cgi-bin/mfs/01/pips/ Information Profiles. Beyond Pesticides 701 E Street, S.E., Suite 200 Washington DC 20003 202-543-5450 (v) 202-543-4791 (f) [email protected] www.beyondpesticides.org Synthetic Pyrethroids chemicalWATCH Factsheet References continued MCF-7 Human Breast Carcinoma Occupational exposure to some rats: induction of hepatocellular Cell Line. Environmental Health synthetic pyrethroids (permethrin carcinoma. Fund. Appl. Toxicol. 22: Perspectives. 107:3 and fenvalerate). Arch. Toxicol. 293-303. Gosselin, R.E. 1984. Clinical Toxicology of 50:27-33. Thomson, W.T. 1984. Agricultural Commercial Products. Williams Mueller-Beilschmidt, Doria. 1990. Chemicals: Insecticides. Thompson and Wilkins. Baltimore, MD. Toxicology and Environmental Fate Publications, Fresno, CA. Hallenbeck, W.H. and K.M. Cunningham- of Sythetic Pyrethrois. Journal of U.S. EPA. 1979. Environmental Fate Review Burns. Pesticides and Human Health. Pesticide Reform. 10 (3):32-37. of Permethrin (activated sludge Springer-Verlag, New York, NY. National Research Council. 1987. metabolism study). November 29. Hayes, W.H., Pesticides Studied in Man, Regulating Pesticides in Food: The Office of Pesticide Programs. Williams & Wilkins. Baltimore, Delaney Paradox. National Academy Washington, DC. MD. 1982. Press, Washington, DC. U.S. EPA. 2000. For Your Information, Hormonal and Environmental Factors Olkowski, W. 1989. Natural and synthetic Synthetic Pyrethroids for Mosquito Affecting Cell proliferation and pyrethrum insecticides: Finding your Control. Washington, DC. May. Neoplasia in the Mammary Gland. way through the maze. Common U.S. EPA. 1997. Office of Pesticide Progress in Clinical and Biological Sense Pest Quarterly. 5(1):8-12. Programs list of chemicals evaluated Research (PCBR). 394:211-53, 1996. Reigart, J., M.D. et al., Recognition and for carcinogenic potential. Memo from Kaloyanova, F. and S. Tarkowski, eds, Management of Pesticide Poisonings, W.L. Burnman, HED, to HED branch Toxicology of Pesticides - Interm EPA, 1999. chiefs. Washington, DC. February 19. Document 9, World Health Scourge Insecticide Product Label with World Health Organization (WHO). 1990. Organization, Copenhagen, 1982. SBP-1382/Piperonyl Butoxide 18% + d-Phenothrin. Environmental Health Klaassen, C.D. et al., eds, Casarett and 54% MF. U.S. EPA Reg. No. 432-667. Criteria. Geneva. Doulls Toxicology, Macmillan AgrEvo, montvale, NJ. Wright, C., et al. 1981. Insecticides in the Publishing Co., New York, NY. Takahashi, O., et al., 1994. Chronic toxicity ambient air of rooms following their Kolmodin-Hedman, B., et al. 1982. studies of piperonyl butoxide in F344 application of control of pests. Bull. Environ. Contam. Toxicol. 26:548-553. Beyond Pesticides 701 E Street, S.E., Suite 200 Washington DC 20003 202-543-5450 (v) 202-543-4791 (f) [email protected] www.beyondpesticides.org