Toxicologic Information About Insecticides
Used for Eradicating Mosquitoes
(West Nile Virus Control)
April 2005
Permethrin is a synthetic pyrethriod that is used mostly for agricultural purposes. It has potential application in the protection of stored grain and it has been used in aerial application for forest protection and vector control, for the control of noxious insects in the household and on cattle, for the control of body lice, and in mosquito nets (WHO 1990). Permethrin is the most frequently used pyrethroid in the United States (ATSDR 2001).
Section 1. Environmental Factors
In laboratory studies, permethrin has been shown to degrade in soil with a half-life of 28 days or less. Studies to investigate the leaching potential of permethrin and its degradates showed that very little downward movement occurs in soil. Permethrin deposited on plants degrades with a half-life of approximately 10 days. In water and on soil surfaces permethrin is photodegraded by sun-light. In general, the degradative processes which occur in the environment lead to less toxic products. Permethrin disappears rapidly from the environment, in 6-24 hours from ponds and streams, 7 days from pond sediment, and 58 days from foliage and soil in a forest. From cotton leaves in a field, 30% of the compound was lost within 1 week. Under aerobic conditions in soil, permethrin degrades with a half-life of 28 days. There is very little movement of permethrin in the environment, and it is unlikely that it will attain significant levels in the environment (WHO 1990).
Direct releases to water are expected to be low for pyrethroids because these compounds are primarily applied aerially or from ground-based sprayers directly to crops and vegetation. Spray drift after application of these compounds, however, can contaminate nearby waters. Pyrethroids such as permethrin, which often is used in mosquito control, is prohibited from being applied to open water or within 100 feet of lakes, rivers, and streams because of its high toxicity to fish (EPA 2000). In addition, permethrin is highly toxic to bees.
Section 2. Potential for Exposure
Occupational exposure to phenothrin may occur through inhalation and dermal contact with this compound at workplaces where phenothrin is produced or used. Crop workers may be exposed during application and from contact with treated foliage. The general population may be exposed to permethrin via inhalation of ambient air after use, ingestion of food, and with the household use of insecticides containing permethrin (HSDB 2003). Exposure of the general population to permethrin is mainly via dietary residues. However, residue levels in crops grown according to good agricultural practice are generally low and the resulting exposure of the general population is expected to be low (WHO 1990).
Section 3. Health Effects/Toxicity
Almost all systemic effects resulting from exposures to pyrethroids are related to their action on the nervous system. These chemicals exert their profound effect by prolonging the open phase of the sodium channel gates when a nerve cell is excited. In rodents, effects such as tremors are induced if the open state is prolonged for brief periods; effects such as sinuous writhing (choreoathetosis) and salivation occur if the open state is prolonged for longer periods. Neurologic signs typically result from acute toxicity. Low-level chronic exposures to pyrethroids usually do not cause neurologic signs in mammals, largely because of rapid metabolism and elimination. Data from animal studies do not indicate that pyrethroids significantly affect end points other than the nervous system, although changes in liver weight and metabolism of chemicals sometimes have been used as an index of adverse effect levels for pyrethroids. A few recent animal studies indicate the potential for adverse neurodevelopmental, reproductive, and immunologic effects at exposure levels below those expected to result in overt signs of neurotoxicity. Data do not indicate that pyrethroids should be considered a carcinogenic concern to humans. No data in humans are available regarding the potential for pyrethroids to cross the placental barrier and enter a developing fetus. Limited data from animals indicate that transfer of pyrethroids across the placenta to the fetus may result in persistent effects on neurotransmitters later in life. Although pyrethroids have not been identified in human breast milk, very low levels of pyrethroids (<1% of an orally administered dose) are excreted into milk of lactating animals (ATSDR 2001).
Permethrin has been used for many years, with no human poisoning cases reported. No indication exists that permethrin has a significant adverse effect on humans when used as recommended. It has induced skin sensations and paraesthesia in exposed workers, but these effects disappeared within 24 hours. Transient numbness, itching, tingling, and burning sensations have been reported in a small percentage of humans after dermal exposure to permethrin when it was used to treat head lice (WHO 1990).
Studies of laboratory animals exposed to permethrin are summarized in Table 2, with NOAELs and LOAELs indicated. Permethrin caused mild primary irritation of intact or abraded skin in rabbits. The dermal LD50 is >4,000 mg/kg for rats, >2,000 mg/kg for rabbits, and >2,500 mg/kg for mice (HSDB 2003).
A 4-hour inhalation LC50 for permethrin in rats is >23.5 mg/L (Extoxnet 2003), and oral LD50 values for permethrin in rats range from 410 to 6,000 mg/kg (HSDB 2003). The oral LD50 for mice ranges from 250 to >4,000 mg/kg. Mortality also was observed during a 90-day oral exposure to permethrin in the diets of rats (DOD 1977). All 10 male and female rats in the projected 850 mg/kg/day exposure groups died during the study; actual doses were 505 and 870 mg/kg/day in males and females, respectively.
In acute and intermediate studies of oral toxicity in animals, permethrin caused tremors, weight loss, and increased liver and kidney weights at levels starting at 185 mg/kg/day. NOAELs in these studies ranged from 92 to 210 mg/kg/day (DOD 1977). Chronic studies on permethrin also showed increased liver weights in rats at levels starting at 25 mg/kg/day, with NOAELs at 5 mg/kg/day. One threegeneration rat study showed hepatic effects in the offspring at doses of 25 mg/kg/day (FMC Corp. 1978), whereas another three-generation rat study showed no reproductive effects at 180 mg/kg/day (James 1979). No teratogenicity was seen in rats at doses up to 225 mg/kg (McGregor and Wickramaratne 1976). In another study, parent rats fed 50 mg/kg showed ataxia, tremor, and slight reduction in body weight, but no teratogenic effects were noted (Kohda et al. 1976). No oncogenicity was observed in rats and mice. Permethrin was not mutagenic in an Ames test and was negative in two reverse mutation tests in Escherichia coli (HSDB 2003).
Table 1. Health Effect Levels of Permethrin in Laboratory Animals
(PDF Version 67k)
On the basis of the results of a study in which plasma permethrin concentrations were measured in an adult male who ingested permethrin in a suicide attempt, permethrin appears to follow a twocompartment model, with distribution half-times for the trans and cis compounds of 5.08 and 4.82 hours, respectively (Gotoh at el. 1998). After dermal application of permethrin to patients for treatment of scabies, the estimated absorption of permethrin was 0.5% of the applied dose, based on the urinary excretion of permethrin metabolites (van der Rhee et al. 1989). Urinary excretion of metabolites persisted for 7–10 days after one dermal application. A study using an in vitro preparation of human skin indicated that only a small fraction (approximately 0.7%) of a topically applied dose of permethrin fully penetrated the skin after a 48-hour exposure, with small amounts of permethrin identified in the epidermal and dermal layers (Franz et al. 1996).
Permethrin administered to mammals was rapidly metabolized and almost completely excreted in urine and feces within a short period of time. In rats, permethrin was distributed rapidly to nervous tissues after administration of an oral dose, with a distribution half-time of 4.85 hours (Anadón et al. 1991b). Concentrations of permethrin metabolites (m-phenoxy-benzyl alcohol and mphenoxybenzoic acid) in nerve tissues were lower than those observed for the parent compound (Anadón et al. 1991a, 1991b). 14C-permethrin or its metabolites also are distributed rapidly to the kidney after oral administration to rats, with levels in the kidney peaking approximately 4 hours after dosing (Miyamoto et al. 1968). After oral exposure, permethrin or its metabolites also have been detected in fat of cows and rats up to 12 days after dosing (Gaughan et al. 1977, 1978). In rats exposed to single dermal doses of permethrin, >90% of the absorbed dose was excreted in urine and feces, with a urine-to-fecal ratio of approximately 4:1 (Shah et al. 1987). Percutaneous absorption of permethrin was also demonstrated in guinea pigs in vivo after a dermal application (Franz et al. 1996). The concentration of permethrin measured in brain tissue 24 hours after dosing was sevenfold higher than that of plasma. In this study, absorption was 20-fold greater than that measured in a preparation of human skin.
Section 5. Standards and Guidelines for Protecting Human Health
Regulatory standards and guidance values are summarized in Table 2.
EPA has established an oral RfD for permethrin of 0.05 mg/kg/day based on a 2-year rat feeding study (FMC Corp. 1977), in which a NOAEL of 100 ppm (5 mg/kg/day) and a LOAEL of 500 ppm (25 mg/kg/day) for liver weight increases were identified. An uncertainty factor of 100 was used to account for interspecies and intraspecies differences (IRIS 2003).
The only other standards and regulations available are a World Health Organization (WHO) drinking water guideline for permethrin of 20 µg/L (WHO 2001) and a Food and Agriculture Organization/WHO accepted daily intake for permethrin of 0.05 mg/kg (HSDB 2003).
April 2005 Tolerances are established for residues of permethrin and the sum total of its metabolites in or on the following animal commodities: cattle fat—3.0 ppm; cattle meat—0.25 ppm; cattle meat byproducts —2.0 ppm; eggs—1.0 ppm; goat fat—3.0 ppm; goat meat—0.25 ppm; goat meat byproducts —2.0 ppm; hog fat—3.0 ppm; hog meat—0.25 ppm; hog meat by-products—3.0 ppm; horse fat—3.0 ppm; horse meat—0.25 ppm; horse meat by-products—2.0 ppm; milk fat (reflecting 0.25 ppm in whole milk)—6.25 ppm: poultry fat—0.15 ppm; poultry meat—0.05 ppm; poultry meat byproducts —0.25 ppm; sheep fat—3.0 ppm; sheep meat—0.25 ppm; and sheep meat by-products—2.0 ppm (HSDB 2003).
| Table 2. Regulatory Standards and Guidance Values for Permethrin | ||
| Standard/Guidance | Value | Reference |
| World Health Organization (WHO) drinking water guideline | 20 µg/L | WHO 2001 |
| Food and Agriculture Organization/WHO accepted daily intake (ADI) | 0.05 mg/kg | HSDB 2003 |
| Environmental Protection Agency Reference Dose (RfD) | 0.05 mg/kg/day | IRIS 2003 |
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