1 Introduction

In addition to being a nuisance, mosquitoes, ticks, biting flies, and other arthropods can be the bearers of disease—often debilitating, sometimes deadly. Throughout history, more active-soldier days have been lost to diseases—many of them transmitted by insects—than to combat. In the Vietnam War, disease casualties, mostly caused by insect bites, outnumbered combat casualties by more than two to one. In the United States and abroad, Lyme disease, vectored by deer ticks, is a serious concern for military and civilian populations. Public-health strategies rely on vector control to contain insect-borne diseases, but the military, because of its rapid deployment missions, must depend largely on personal protection methods, such as insect repellents. Recently, the U.S. Department of Defense (DOD) has focused on impregnating battle-dress uniforms (BDUs) with insect repellents to augment the protection provided by topically applied repellents. The most promising of the clothing treatments is the insecticide permethrin, a synthetic pyrethroid. Synthetic pyrethroids, such as permethrin, cypermethrin, and fenvalerate, are being considered as replacements for currently used insecticides (organochlorines, organophosphates, and methylcarbamates) because (1) they are more acutely toxic to target insects than other classes of available insecticides, and thus less insecticide is needed per application; and (2) they are less toxic than organochlorine, organophosphate, and methylcarbamate insecticides to mammals. Pyrethroids are more toxic to insects than mammals because of their more rapid absorp-



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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms 1 Introduction In addition to being a nuisance, mosquitoes, ticks, biting flies, and other arthropods can be the bearers of disease—often debilitating, sometimes deadly. Throughout history, more active-soldier days have been lost to diseases—many of them transmitted by insects—than to combat. In the Vietnam War, disease casualties, mostly caused by insect bites, outnumbered combat casualties by more than two to one. In the United States and abroad, Lyme disease, vectored by deer ticks, is a serious concern for military and civilian populations. Public-health strategies rely on vector control to contain insect-borne diseases, but the military, because of its rapid deployment missions, must depend largely on personal protection methods, such as insect repellents. Recently, the U.S. Department of Defense (DOD) has focused on impregnating battle-dress uniforms (BDUs) with insect repellents to augment the protection provided by topically applied repellents. The most promising of the clothing treatments is the insecticide permethrin, a synthetic pyrethroid. Synthetic pyrethroids, such as permethrin, cypermethrin, and fenvalerate, are being considered as replacements for currently used insecticides (organochlorines, organophosphates, and methylcarbamates) because (1) they are more acutely toxic to target insects than other classes of available insecticides, and thus less insecticide is needed per application; and (2) they are less toxic than organochlorine, organophosphate, and methylcarbamate insecticides to mammals. Pyrethroids are more toxic to insects than mammals because of their more rapid absorp-

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms tion, slower detoxification, and greater affinity for target sites in insects. Permethrin has insect-repellent as well as insecticidal properties. These insecticidal properties and those of other pyrethroids are due to their interference with the conductance of nerve impulses. Pyrethroid insecticides are registered as insect controls for fruits and vegetables. Permethrin is used extensively by agriculture for control of food-crop pests. Pyrethroids are also used in greenhouses for control of whitefly and in livestock buildings (beef barns, dairy barns, and poultry houses) and stables for control of house and stable flies. It is also the active ingredient (0.5%) in an aerosol spray formulation distributed for veterinary use and for human use in pediculocides (1%) and scabicides (5%) that have been approved by the Food and Drug Administration (FDA). The physical and chemical properties of permethrin are shown in the following list (CEPA, 1992). Common name: Permethrin Chemical name: 3-(phenoxyphenyl)methyl (±)-cis, trans-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate Tradenames: Permanone, Ambush, Pounce, Ectiban, FMC 33297, PP557, BW-21-Z, NRDC 143 CAS registry no.: 52645-53-1 Molecular weight: 391.3 Empirical formula: C21H20Cl2O3 Physical state: Clear liquid Color: Medium to dark amber Odor: Moderate aromatic Melting point: 55.7-56.3°C (cis) 45.7-46.3°C (trans)

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms Boiling point: 220°C at 0.05 mm Hg Density: 1.0138 at 25°C Solubility: 0.07 mg/L at 25°C in water Mixable with most organic solvents Vapor pressure: 2.15 × 10−8 mm Hg at 25°C (cis) 0.69 × 10−8 mm Hg at 25°C (trans) Hydrolysis: Stable under acidic or slightly acidic conditions (pH 3-6) at 25-45 °C, but hydrolyzes slowly at pH 9, increasing with temperature (t1/2 = 3 days at 45°C). The cis isomer is more stable. Photolysis: Degrades slowly in sterile water (pH 5) and soil with exposure to xenon arc lamp at 25°C (60-86% remained intact after 32-35 days) Permethrin has been registered by the U.S. Environmental Protection Agency (EPA) as a clothing treatment to repel disease-transmitting and nuisance insects and other arthropods. Many studies have shown that permethrin-impregnated fabric is effective in repelling insects, ticks, and other arthropods (Schreck et al., 1978, 1980a,b, 1982a,b,c, 1984, 1986; Breeden et al., 1982; Mount and Snoddy, 1983; Dees et al., 1986; U.S. Army Natick Research, Development, and Engineering Center, 1987; Lillie et al., 1988; Sholdt et al., 1988, 1989; U.S. Army Environmental Hygiene Agency, 1988; Schreck and Kline, 1989; Schreck and McGovern, 1989; Evans et al., 1990). Studies have also shown that permethrin impregnation of BDUs at the concentration of 0.125 mg/cm2 of cloth along with application of the insect repellent N,N-diethyl-m-toluamide (DEET) to exposed skin provides nearly 100% protection against bites of insects and other arthropods. Treatment at the approved dosage remains effective through 35 launderings of the uniform (i.e., beyond the combat life of the uniform) but can be removed by dry cleaning (U.S. Army, 1993). A kit method and 2-gallon-sprayer method for permethrin impregna-

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms tion of BDUs have already been field tested, but both are more expensive than factory impregnation and require soldiers to perform the treatment. Short-notice deployments can result in units deploying without treated uniforms. According to the U.S. Army, application of permethrin to the BDU cloth at the time of manufacturing provides the most consistent treatment at the approved dosage and will relieve soldiers from the burden of treating BDUs. EPA-registered aerosol cans of 0.5% permethrin are used by all services. Initial spraying of a BDU with the aerosol formulation provides a permethrin dosage approximately equal to that of an impregnated uniform that has been washed 25 times. However, pressurized cans in a combat environment are a potential problem. The Army Clothing and Equipment Board has recommended factory permethrin treatment of all desert BDUs, which are worn by soldiers in such deployments as the Gulf War or by field units in rapid deployments. Permethrin-impregnated BDUs are recommended to be worn in garrison or nondeployment situations as well as in deployments. However, there is concern that long-term exposure to permethrin might result in adverse health effects, such as neurotoxicity or carcinogenicity. In response to those concerns, the U.S. Army requested that the National Research Council's Board on Environmental Studies and Toxicology (BEST) review the toxicological and exposure data for permethrin and make recommendations regarding long-term exposure to permethrin. In response to the Army's request, this project was assigned to BEST 's Committee on Toxicology. The Subcommittee on Permethrin Toxicity from Military Uniforms was established to review the current permethrin toxicity and exposure data and the appropriateness of long-term exposure to permethrin-impregnated BDUs. This report is the result of the subcommittee's detailed evaluation of possible adverse health effects associated with wearing permethrin-impregnated BDUs. The report examines the data on exposure assessment of permethrin in Chapter 2, pharmacokinetics in Chapter 3, acute toxicity in humans and animals in Chapter 4, dermal or ocular toxicity in Chapter 5, neurotoxicity in Chapter 6, liver and other organ toxicity in Chapter 7, immunotoxicity in Chapter 8, reproductive and developmental toxicity in Chapter 9, genotoxicity in Chapter 10, and carcinogenicity

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms in Chapter 11. Chapter 12 provides a summary of the subcommittee's conclusions and recommendations.

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