© 2000 CRC Press LLC Section II Pesticide profiles L1190 CH02 pgs Page 13 Friday, July 2, 1999 3:58 PM © 2000 CRC Press LLC chapter two Pyrethroids and other botanicals 2.1Class overview and general description Background Pyrethroids and other botanical pesticides are grouped together not because they have similar toxicological properties, like the organophosphates or carba- mates, but because they all have biological origins. Pesticides may be extracted from naturally occurring materials or they can be synthesized in commercial lab- oratories. The most common natural materials come from plants. Some plants have developed, over long periods of time, substances that deter plant-eating insects. The plants use these compounds as protection from insects. Researchers have isolated a number of compounds from plants that are effective insecticides or fungicides. Development of these botanical pesticides is one of the fastest growing areas in the pesticide industry. The World Health Organization, in 1967, stated that “all of the most poisonous materials so far known are, in fact, of natural origin” (1). Whether this is still true or not is unimportant; however, the comment points out that just because something is found in nature does not mean that it is harmless (1). Pesticides extracted from plants or synthesized to mimic compounds found in plants are powerful and effective control agents. Plant-derived pesticides fall into several different broad classifications. By far the largest group of such pesticides consists of pyrethrum and its related synthetic compounds, pyrethroids. Pyrethrum comes from chrysanthemums. There are cur- rently over 20 pyrethroids and they constitute the single largest group of natural insect chemical control agents in the world (2). Another class of botanicals is the rotenoids. They are found in several plants in the bean family. Rotenone is one of six compounds in this group. It is used as a fish poison. A third important category of botanicals, the nicotinoids, comes from tobacco and several other plants. Nicotine is the most commonly used compound in the group. The fourth group of botanicals includes the compounds strychnine and scilliroside. These and several other compounds in the group are used to control rodents. The latter three groups of botanicals will not be discussed in detail here, though they will be briefly described at the end of the overview in this chapter. Only the pyrethroids will be discussed at length in this chapter. The generalized structure of the pyrethroids is shown in Figure 2.1, and the various pyrethroids are listed in Table 2.1. L1190 CH02 pgs Page 15 Friday, July 2, 1999 3:58 PM © 2000 CRC Press LLC Uses of pyrethroids and other botanicals Currently, there are no estimates of the national or regional use patterns of botanically derived pesticides in the United States. Pyrethrum and pyrethroid mechanisms of toxicity This group of pesticides interferes with the balance of sodium ions in the nerve junctions of target and non-target organisms, rendering them inactive (2). The pes- ticide provides a “knockdown” dose to insects but is generally not strong enough to kill them. Compounds in this group are toxic to insects but not as toxic to mammals because of their ability to break down the pyrethroids into metabolite compounds that are easily excreted. Pyrethrins and pyrethroids are commonly combined with other insecticides to enhance their efficacy against insects. The synthetic pyrethroids are more potent than the natural compounds. Acute toxicity Pyrethroids are slightly to moderately toxic to animals. The LD 50 of allethrin is 1100 mg/kg in male rats and 370 mg/kg in mice (2). Cypermethrin is moderately toxic, with an LD 50 of 187 to 326 mg/kg in male rats (2). Exposure to high doses of pyrethroids can be fatal. There was one instance when a man died after eating a meal cooked in 10% cypermethrin concentrate mistakenly used for cooking oil. He had symptoms of nausea that progressed to stomach pains, Figure 2.1 Generic pyrethroid structure. Table 2.1 Pyrethroids Allethrin* Fenfluthrin Barthrin Fenvalerate Bioallethrin Flucythrinate* Bioresmethrin Fluorocyphenothrin Cismethrin Fluvalinate* Cyphenothrin Kadethrin Cyflurthin Permethrin* Cyhalothrin Pyrethrin I Cypermethrin* Pyrethrin II Deltamethrin Resmethrin* Esfenvalerate* Tetramethrin Fenproponate Note: * indicates that a profile for this compound is included in this chapter. L1190 CH02 pgs Page 16 Friday, July 2, 1999 3:58 PM © 2000 CRC Press LLC to diarrhea, to convulsions, to unconsciousness, and then to coma. Death then occurred due to respiratory failure (2). For humans, dermal contact with large amounts of these compounds, such as deltamethrin, may result in numbness, burning and itching of the skin, and intoxi- cation (2). Chronic toxicity Long-term studies of pyrethroids showed that several of them can cause liver effects (2). In a chronic feeding study with rats, doses of 125 mg/kg/day of resmethrin produced some pathological liver changes in addition to increased liver weights (3). Rats fed large doses of pyrethrins over two years showed liver damage (2). Reproductive effects In laboratory animal studies on about half of the pyrethroids, there were no significant reproductive effects. However, in experiments with two pyrethroids, per- methrin and resmethrin, there were some reproductive effects. High oral doses of 250 mg/kg/day of permethrin during days 6 to 15 of pregnancy reduced the fertility of female rats (2). A three-generation rat study using resmethrin showed slight increases in premature stillbirths and a decrease in pup weight at the 25-mg/kg/day dose (2). Therefore, botanical compounds at low doses are unlikely to cause reproductive effects in humans. Teratogenic effects Available evidence suggests that pyrethroids will be unlikely to cause teratogenic effects. No developmental effects were seen in the offspring of rats given doses of allethrin as high as 195 mg/kg/day (2). Also, no birth defects were observed in the offspring of rabbits given doses of resmethrin as high as 100 mg/kg/day (4). Mutagenic effects Laboratory animal experiments with various pyrethroids (compounds such as esfenvalerate, permethrin, and resmethrin) showed no mutagenic effects (5,6). Carcinogenic effects The majority of pyrethroids have been shown through animal experiments to be unlikely to produce carcinogenic effects (2,3). However, there is one exception: the U.S. Environmental Protection Agency has classified cypermethrin as a possible human carcinogen since there was evidence of some benign lung tumors in female mice exposed to very high doses of this pyreth- noid (8). Organ toxicity As stated earlier in the chronic toxicity section, at high doses, pyrethroids may cause adverse effects on the central nervous system (CNS) and also adverse changes in the liver (9). L1190 CH02 pgs Page 17 Friday, July 2, 1999 3:58 PM © 2000 CRC Press LLC Fate in humans and animals Pyrethroid compounds are metabolized and excreted rapidly in animals. For example, rats eliminated over 99% of cypermethrin within a few hours (2). Also, when an oral dose of 10 mg/kg resmethrin was given to laying hens, 90% of the dose was eliminated via urine and feces within 24 hours (10). Humans also eliminate pyrethroid compounds such as cypermethrin relatively quickly. The “urinary excretion of cypermethrin metabolites was complete 48 hours after the last of five daily tracer doses of 1.5 mg” (2). Ecological effects Effects on birds The majority of the pyrethroid compounds are practically nontoxic to birds. The LD 50 of allethrin in mallard ducks is 2000 mg/kg and the LD 50 of cypermethrin in mallard ducks is 4640 mg/kg (7,8). Effects on aquatic organisms Pyrethroid compounds are very highly toxic to fish and aquatic invertebrates. The LC 50 of bioallethrin in coho salmon is 0.0026 mg/L, and the 96-hour LC 50 of cypermethrin in rainbow trout is 0.00082 mg/L (7). Also, the acute LC 50 for Daphnia magna, a small freshwater crustacean, is 0.0002 mg/L (8). In addition, pyrethroid compounds tend to bioaccumulate in fish. A bioconcentration factor of 1200 × was determined in a flow-through study investigating the accumulation of cypermethrin in rainbow trout (8). In another study, the bioaccumulation factor of esfenvalerate in rainbow trout was found to be about 400 × (11). Effects on other organisms (non-target species) The majority of pyrethroids are highly toxic to bees (8,12). Environmental fate Breakdown in soil and groundwater Pyrethroid compounds have a strong tendency to adsorb to soil particles and are moderately persistent. For example, permethrin has a half-life of 3 to 6 weeks (13) and esfenvalerate has a half-life ranging from 15 days to 3 months (11). However, one of the pyrethroids, cypermethrin, has low persistence in sunlight inasmuch as it photodegrades rapidly with a half-life of 8 to 16 days (8). Because of the pyrethroid compounds’ tendency to bind to soil, they are unlikely to cause groundwater con- tamination. Breakdown in water Pyrethroid compounds are relatively insoluble in water. They readily adsorb to sediment and soils and, therefore, concentrations of pyrethroids in silty water decrease rapidly. Breakdown in vegetation For many of the pyrethroid compounds, there is no information available regard- ing their fate in vegetation. In one study, a 4.5 ml/100 L solution of Cymbush 250 L1190 CH02 pgs Page 18 Friday, July 2, 1999 3:58 PM © 2000 CRC Press LLC EC (cypermethrin) was applied to strawberry plants. Results revealed that 40% of the applied cypermethrin remained after 1 day, 12% remained after three days, and 0.5% remained after 7 days (14). In another study, permethrin was neither phytotoxic nor poisonous to most plants when used directly. However, some injury occurred on certain ornamental plants (15). General properties of other botanicals Rotenoids The rotenoids are extracted mainly from two species, Derris and Lonchocarpus, members of the bean family. These compounds are found in over 65 species of legumes. Rotenoids are found in leaves, stems, roots, and seeds of these plants. Parts of the plant may contain up to 40% of the compound (2). Rotenoids are highly toxic to fish and some insects; however, they are only moderately toxic to mammals (16). Refer to the rotenone profile for further informa- tion. Nicotinoids Three compounds make up the bulk of this category: nicotine, nornicotine, and anabasine. Nicotine is by far the most widely used of the group and is also the most potent. The active compounds in this group have been extracted from five different families of plants (2). Nicotine is extracted with steam or water from the different plants, though most commonly from tobacco. It is a moderately to highly toxic compound with an acute oral LD 50 of 50 to 60 mg/kg (17). The compound affects the nerve’s ability to function properly, much like the organo- phosphate and carbamate insecticides, resulting in similar symptoms. Nicotine can cause twitching and difficulties with breathing, convulsions, and death. The use of nicotinoids has been declining. They are being replaced with equally effective synthetic insecticides. Additionally, they are nonpersistent, and are ineffective in cold weather (16). Botanical rodenticides Three compounds are found in this group: strychnine, scilliroside, and ricin. Strychnine comes from the plant Strychnos nux-vomica, scilliroside comes from the red squill bulb, and ricin comes from castor beans. 2.2Individual profiles 2.2.1 Allethrin Figure 2.2 Allethrin. L1190 CH02 pgs Page 19 Friday, July 2, 1999 3:58 PM © 2000 CRC Press LLC Trade or other names Trade names for allethrin include Alleviate, Pynamin, d-allethrin, d-cisallethrin, Bioallethrin, Esbiothrin, Pyresin, Pyrexcel, Pyrocide, and trans -allethrin. Regulatory status Pesticides containing allethrin are toxicity class III — slightly toxic, and bear the Signal Word CAUTION on the product label. Containers of technical grade d- trans - allethrin bear the Signal Word WARNING. Allethrin is a General Use Pesticide (GUP). Introduction Allethrin is a nonsystemic insecticide that is used almost exclusively in homes and gardens for control of flies and mosquitoes, and in combination with other pesticides to control flying or crawling insects. Another structural form, the d- trans - isomer of allethrin, is more toxic to insects and is used to control crawling insects in homes and restaurants. It is often used to control parasites living within animal systems. It is available as mosquito coils, mats, oil formulations, and as an aerosol spray. Allethrin is a pyrethroid, a synthetic compound that duplicates the activity of the pyrethrin plant. It has stomach and respiratory action and paralyzes insects before killing them. Unless stated otherwise, information in this profile refers to unpurified allethrin. Toxicological effects Acute toxicity Allethrin is slightly toxic by dermal absorption and ingestion. Short-term dermal exposure to allethrin may cause itching, burning, tingling, numbness, or a feeling of warmth, but not dermatitis (2). Exposure to large doses by any route may lead to nausea, vomiting, diarrhea, hyperexcitability, incoordination, tremors, convulsive twitching, convulsions, bloody tears, incontinence, muscular paralysis, prostration, and coma. Allethrin is a central nervous system stimulant. Heavy respiratory exposure caused incoordination and loss of bladder control in mice and rats (2). The toxicity of allethrin varies with the amounts of different isomers present. The oral LD 50 for allethrin is 1100 mg/kg in male rats, 685 mg/kg in female rats, 480 mg/kg in mice, and 4290 mg/kg in rabbits (7,12). For d-allethrin, the oral LD 50 is 1320 mg/kg in rats. The dermal LD 50 is greater than 2500 mg/kg in rats (12,19). Chronic toxicity Reproductive effects No data are currently available. Teratogenic effects No developmental defects were seen in the offspring of rats given doses as high as 195 mg/kg/day (7). L1190 CH02 pgs Page 20 Friday, July 2, 1999 3:58 PM © 2000 CRC Press LLC Mutagenic effects Allethrin has been found to be mutagenic under certain conditions in strains of the bacterium Salmonella typhinurium (18). However, tests of d-allethrin (bioallethrin) for DNA damage and mutation were negative (19). Thus, allethrin appears to have little or no mutagenic activity. Carcinogenic effects Rats fed very high doses of d-allethrin for 2 years did not develop cancer (19). Organ toxicity Rats fed 75 mg/kg/day of d-allethrin exhibited decreased body weight gain, increased liver weights, and, in females only, increased levels of serum liver enzymes (19). A 6-month study with dogs fed d-allethrin (bioallethrin) showed effects on the liver at 5 mg/kg/day (19). A dose of 50 mg/kg/day allethrin for 2 years produced no detectable effect in dogs (19). Fate in humans and animals Following oral administration, allethrin is readily absorbed and metabolized in mammalian systems to less toxic compounds that may be more easily eliminated by the body (12). Ecological effects Effects on birds Allethrin is practically nontoxic to birds. The oral LD 50 for allethrin is 2030 mg/kg in bobwhite quail and greater than 2000 mg/kg in mallards (12,19). The dietary LD 50 is 5620 ppm for d-allethrin in mallards and bobwhite quail (19). Effects on aquatic organisms The pyrethroid insecticides, including allethrin, are toxic to fish. Fish sensitivity to the pyrethroids may be explained by their relatively slow metabolism and elim- ination of these compounds. The half-lives for elimination of several pyrethroids by trout are all greater than 48 hours (20,21). Generally, the lethality of pyrethroids to fish increases with increasing ability to dissolve in fat (22). The LC 50 (96-hour) for channel catfish is 30 mg/L. The toxicity of allethrin compounds ranges from an LC 50 of 0.0026 mg/L for d-allethrin in coho salmon to an LC 50 of 0.08 mg/L for s-bioallethrin in fathead minnows (19). Effects on other organisms (non-target species) Allethrin is slightly toxic to bees (19). Its LD 50 is 0.003 to 0.009 mg per bee (19). Environmental fate Breakdown in soil and groundwater No data are currently available. L1190 CH02 pgs Page 21 Friday, July 2, 1999 3:58 PM © 2000 CRC Press LLC Breakdown in water In pond waters and in laboratory degradation studies, pyrethroid concentrations decrease rapidly due to sorption to sediment, suspended particles and plants. Micro- bial and photodegradation also occur (19). Breakdown in Vegetation No data are currently available. Physical properties Allethrin is a yellow to amber colored viscous liquid with a mild or slightly aromatic odor (12). It may decompose when exposed to heat or light. Chemical name: 2-methyl-4-oxo-3-(2-propenyl)-2-cyclopenten-1-yl 2,2-dimethyl- 3-(2-methyl-l-propenyl)cyclopropanecarboxylate (12) CAS #: 584-79-2 (allethrin); 42534-61-2 (d-allethrin) Molecular weight: 302.4 (12) Solubility in water: Allethrin and d-allethrin are insoluble in water (12) Solubility in other solvents: alcohol v.s.; hexane v.s.; xylene v.s., petroleum ether v.s. (12). Melting point: 4 ° C (12) Vapor pressure: 16 mPa @ 30 ° C (12) Partition coefficient (octanol/water): 91,300 (12) Adsorption coefficient: Not available Exposure guidelines ADI: Not available HA: Not available RfD: Not available PEL: Not available Basic manufacturer Sumitomo Chemical Co., Ltd. 5–33, Kitahama 4-chome Chuo-ku Osaka 541 Japan Telephone:81-6-220-3693 FAX: 81-6-220-3492 Telex: 522–7541 SUMIKA J 2.2.2 Cypermethrin Figure 2.3 Cypermethrin. L1190 CH02 pgs Page 22 Friday, July 2, 1999 3:58 PM © 2000 CRC Press LLC Trade or other names Trade names include Ammo, Arrivo, Barricade, Basathrin, CCN52, Cymbush, Cymperator, Cynoff, Cypercopal, Cyperguard 25EC, Cyperhard Tech, Cyperkill, Cypermar, Demon, Flectron, Fligene CI, Folcord, Kafil Super, NRDC 149, Polytrin, PP 383, Ripcord, Siperin, Stockade, and Super. Regulatory status Many products containing cypermethrin are classified as Restricted Use Pesti- cides (RUPs) by the EPA because of cypermethrin’s toxicity to fish. RUPs may be purchased and used only by certified applicators. Cypermethrin is classified toxicity class II — moderately toxic. Some formulations are toxicity class III — slightly toxic. Pesticides containing cypermethrin bear the Signal Word WARNING or CAUTION on the product label, depending on the particular formulation. Introduction Cypermethrin is a synthetic pyrethroid insecticide used to control many pests, including moth pests of cotton, fruit, and vegetable crops. It is also used for crack, crevice, and spot treatment to control insect pests in stores, warehouses, industrial buildings, houses, apartment buildings, greenhouses, laboratories, and on ships, railcars, buses, trucks, and aircraft. It may also be used in non-food areas in schools, nursing homes, hospitals, restaurants, and hotels, in food processing plants, and as a barrier treatment insect repellent for horses. Technical cypermethrin is a mixture of eight different isomers, each of which may have its own chemical and biological properties. Cypermethrin is light stable. It is available as an emulsifiable concentrate or wettable powder. Toxicological effects Acute toxicity Cypermethrin is a moderately toxic material by dermal absorption or ingestion (2,8). Symptoms of high dermal exposure include numbness, tingling, itching, burn- ing sensation, loss of bladder control, incoordination, seizures, and possible death (2,8). Pyrethroids like cypermethrin may adversely affect the central nervous system (2,8). Symptoms of high-dose ingestion include nausea, prolonged vomiting, stomach pains, and diarrhea that progresses to convulsions, unconsciousness, and coma. Cypermethrin is a slight skin or eye irritant, and may cause allergic skin reactions (8). The oral LD 50 for cypermethrin in rats is 250 mg/kg (in corn oil) or 4123 mg/kg (in water) (2,8). The EPA reports an oral LD 50 of 187 to 326 mg/kg in male rats and 150 to 500 mg/kg in female rats (8). The oral LD 50 varies from 367 to 2000 mg/kg in female rats, and from 82 to 779 mg/kg in mice, depending on the ratio of cis/trans - isomers present (2). This wide variation in toxicity may reflect different mixtures of isomers in the materials tested. The dermal LD 50 in rats is 1600 mg/kg, and in rabbits is greater than 2000 mg/kg (2,8). Chronic toxicity Reproductive effects No adverse effects on reproduction were observed in a three-generation study with rats given doses of 37.5 mg/kg/day, the highest dose tested (8). L1190 CH02 pgs Page 23 Friday, July 2, 1999 3:58 PM [...]... Chemical name: (R,S)-alpha-cyano-3-phenoxybenzyl(1RS)-cis,trans- 3-( 2, 2dichlorovinyl ) -2 , 2- dimethylcyclopropane-carboxylate ( 12) CAS #: 523 1 5-0 7-8 Molecular weight: 416.3 ( 12) Solubility in water: 0.01 mg/L @ 20 °C; insoluble in water ( 12) Solubility in other solvents: methanol v.s.; acetone v.s.; xylene v.s ( 12) Melting point: 60–80°C (pure isomers) ( 12, 2) Vapor pressure: 5.1 × 10–7 nPa @ 70°C ( 12) Partition... name: (RS)-alpha-cyano-3-phenoxybenzyl-(S ) -2 -( 4-difluoromethoxyphenyl )-3 -methylbutyrate ( 12) CAS #: 70 12 4-7 7-5 Molecular weight: 451.4 ( 12) Solubility in water: 0.5 mg/L @ 21 °C ( 12) , insoluble in water Solubility in other solvents: s in acetone, xylene, isopropanol, and most organic solvents ( 12) Melting point: Not available Vapor pressure: 0.00 12 mPa @ 25 °C ( 12) Partition coefficient (octanol/water ): 120 ... viscous, yellow oil ( 12) Chemical name: (RS)-alpha-cyano-3-phenoxybenzyl N- ( 2- chloro-a,a,a-trifluorop-tolyl)-D-valinate ( 12) CAS #: 1 028 5 1-0 6-9 Molecular weight: 5 02. 93 ( 12) Solubility in water: 0.0 02 mg/L ( 12) , insoluble in water Solubility in other solvents: v.s in organic solvents and aromatic hydrocarbons; s.s in hexane ( 12) Melting point: Not available Vapor pressure: . ( 12) . It may decompose when exposed to heat or light. Chemical name: 2- methyl-4-oxo- 3-( 2- propenyl ) -2 -cyclopenten-1-yl 2, 2-dimethyl- 3-( 2- methyl-l-propenyl)cyclopropanecarboxylate ( 12) CAS #:. liquid (2, 12) . Chemical name: (R,S)-alpha-cyano-3-phenoxybenzyl(1RS)-cis,trans- 3-( 2, 2- dichlorovinyl ) -2 , 2- dimethylcyclopropane-carboxylate ( 12) CAS #: 523 1 5-0 7-8 Molecular weight: 416.3 ( 12) Solubility. odor. Chemical name: (RS)-alpha-cyano-3-phenoxybenzyl-(S ) -2 -( 4-difluoromethox- yphenyl )-3 -methylbutyrate ( 12) CAS #: 70 12 4-7 7-5 Molecular weight: 451.4 ( 12) Solubility in water: 0.5 mg/L @ 21 °C ( 12) , insoluble