Summary

More active military service days have been lost to diseases—many of them transmitted by insects—than to combat. In the Vietnam War and the Persian Gulf War, disease casualties (caused mostly by insect bites) outnumbered combat casualties. U.S. military personnel deployed on field operations all over the world face an increased risk of mortality or morbidity from insect-borne diseases. More than 60 diseases are spread between humans and animals by arthropod vectors such as mosquitoes, ticks, flies, and mites. The insect-borne diseases most often encountered by U.S. overseas troops are malaria, scrub typhus, leishmaniasis, and Congo-Crimean hemorrhagic fever. Three tick-borne diseases—Lyme disease, Rocky Mountain spotted fever, and Colorado tick fever—are often encountered by U.S. military personnel in the United States during stateside training exercises.

U.S. military personnel deployed overseas to insect-infested areas usually have not acquired natural immunity to insect-borne diseases and, therefore, are at increased risk of developing those diseases. Some insect-borne diseases are fatal if not diagnosed and treated promptly, and traditional chemoprophylactic and therapeutic treatments for these diseases are often inadequate. Vaccines are not available against many of the insect-transmitted diseases. Vector-control procedures have been effective in reducing, but not eradicating, insect and other arthropod populations and slowing the transmission of disease. However, rapidly



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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms Summary More active military service days have been lost to diseases—many of them transmitted by insects—than to combat. In the Vietnam War and the Persian Gulf War, disease casualties (caused mostly by insect bites) outnumbered combat casualties. U.S. military personnel deployed on field operations all over the world face an increased risk of mortality or morbidity from insect-borne diseases. More than 60 diseases are spread between humans and animals by arthropod vectors such as mosquitoes, ticks, flies, and mites. The insect-borne diseases most often encountered by U.S. overseas troops are malaria, scrub typhus, leishmaniasis, and Congo-Crimean hemorrhagic fever. Three tick-borne diseases—Lyme disease, Rocky Mountain spotted fever, and Colorado tick fever—are often encountered by U.S. military personnel in the United States during stateside training exercises. U.S. military personnel deployed overseas to insect-infested areas usually have not acquired natural immunity to insect-borne diseases and, therefore, are at increased risk of developing those diseases. Some insect-borne diseases are fatal if not diagnosed and treated promptly, and traditional chemoprophylactic and therapeutic treatments for these diseases are often inadequate. Vaccines are not available against many of the insect-transmitted diseases. Vector-control procedures have been effective in reducing, but not eradicating, insect and other arthropod populations and slowing the transmission of disease. However, rapidly

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms moving military units cannot wait for pesticide programs to be completed, and spraying is impossible in areas under enemy control. Thus, personal protection methods are important alternatives for controlling insect-borne diseases. Such methods include the use of topical repellents and clothing impregnants to prevent contact with insects and other arthropods. Those products can be used separately or in combination to obtain up to 100% protection from biting arthropods. N, N-diethyl-m-toluamide (DEET), a topical insect repellent, has proved to be effective against insects. It provides protection, especially against mosquitoes, for up to 8 hr. However, DEET has several drawbacks—it has a distinctive odor, it washes off easily and needs to be reapplied frequently, and it damages plastics. Permethrin is a synthetic pyrethroid insecticide, used on vegetable and fruit crops for control of insects. Although highly toxic to insects and other arthropods, it is one of the least toxic insecticides to mammals. Controlled experiments in the laboratory and with human volunteers in the field show that clothing impregnated or sprayed with permethrin offers reliable protection against a wide range of vector insects and arthropods, such as mosquitoes, human body lice, tsetse flies, and ticks, including Ixodes dammini, the principal vector of Lyme disease and human babesiosis in the United States. Therefore, the U.S. Army has proposed using permethrin as a clothing impregnant in battle-dress uniforms (BDUs) to kill or repel insects, ticks, and mites. Efficacy tests conducted by the U.S. Department of Agriculture and the U.S. Department of Defense show that the wearing of permethrin-impregnated BDUs in conjunction with application of DEET to areas of skin not covered by BDUs provides nearly 100% protection against bites from most insect vectors. (BDUs, made from either 100% cotton fabric or 50% nylon and 50% cotton fabric, are used to camouflage soldiers.) Before introducing permethrin-impregnated BDUs for military personnel, the U.S. Army wanted a thorough and independent evaluation of the safety of wearing them or working with permethrin-impregnated fabric (as do garment workers) for long periods. Therefore, the Army requested that the National Research Council (NRC) review the toxicological and exposure data on permethrin to determine whether wearing BDUs impregnated with permethrin (at a concentration of 0.125 mg/cm2of fabric) 18 hr per day, 7 days per week, for up to 10 years is safe for sol-

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms diers, and whether handling permethrin-impregnated fabric is safe for garment workers. The Army also asked the NRC to identify gaps in the permethrin toxicity data and make recommendations for future research. In response to the Army's request, the NRC's Committee on Toxicology established the Subcommittee to Review Permethrin Toxicity from Military Uniforms, which prepared this report. The subcommittee based its evaluation of permethrin-impregnated BDUs on a detailed examination of current data on permethrin toxicity in animals and humans, pharmacokinetics, and potential exposure of military personnel and garment workers. EXPOSURE ASSESSMENT The subcommittee considered the dermal route to be the only significant route of exposure for soldiers wearing permethrin-impregnated BDUs. Because permethrin is solid at room temperature and has a relatively low vapor pressure, the subcommittee concluded that the inhalation route is probably insignificant and need not be considered. At present, there is no information to indicate that significant exposure to permethrin will occur by any route other than dermal absorption in soldiers wearing permethrin-impregnated BDUs. Several conversion factors were used to translate the proposed fabric-impregnation concentration, 0.125 mg/cm2, to an estimated internal dose for military personnel through dermal absorption. These factors were the time-weighted-average percentage of permethrin remaining in fabric through 50 washings (26%), percentage of permethrin migration from fabric to skin (0.49%/day), body-contact area (1.5 m2), dermal absorption rate (2%/day), and adult body weight (70 kg). To adjust for actual exposure conditions, it was assumed that military personnel would wear the permethrin-treated BDUs 18 hr per day for 10 years during a 75-year lifetime. Adjusting for the proportion of lifetime exposure resulted in a calculated average daily lifetime dose of 6.8 × 10−5 mg/kg per day. The only difference between field and nonfield military personnel is that field troops apply DEET topically to areas of the skin not normally covered by permethrin-treated BDUs. However, less than 5% of the skin would be expected to have overlapping exposure to

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms DEET and permethrin. Thus, no adjustment was made to distinguish between exposure patterns for military field personnel and nonfield personnel. The average daily lifetime internal dose for garment workers was calculated to be 3.0 × 10−5 mg/kg per day—less than half the daily dose calculated for military personnel. That dose is only for dermal exposure from direct contact with permethrin-treated cloth and does not include possible exposure to permethrin by inhalation of permethrin-impregnated airborne particles from cutting and sewing the treated fabric. The subcommittee recommends that studies should be conducted to collect data on representative permethrin exposure factors to produce a more complete and accurate risk characterization for garment workers. PHARMACOKINETICS Following absorption, permethrin is extensively and rapidly metabolized. The two major pathways for metabolism are hydrolysis, which essentially splits the permethrin molecule in two, and oxidation, which occurs at a number of carbon atoms throughout the molecule. Both of these metabolic processes make the resulting permethrin metabolite more water soluble and more likely to be excreted in the urine. Thus, metabolism can be viewed as an important detoxification pathway for permethrin, because only the parent chemical exerts toxic effects. Experiments with laboratory animals have shown that, upon absorption, permethrin is distributed throughout the body but appears to concentrate predominantly in fat. Solubility in fat might explain its high concentrations in brain and nervous tissue in comparison with other body organs. Because dermal penetration of many chemicals is enhanced by DEET, use of DEET in combination with permethrin might also facilitate dermal absorption of permethrin. Research specifically on the interaction of DEET and permethrin has not been conducted. Facilitated absorption of permethrin by DEET represents an area of uncertainty in assessing risk for military personnel who wear permethrin-treated BDUs and apply DEET to uncovered areas of skin. Because the potential area of skin with overlapping coverage is small, the effect of DEET on the facilitated

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms absorption of permethrin is probably of minor importance and can be investigated easily. The subcommittee recommends that military personnel consider minimizing areas of skin that are covered by both DEET and permethrin-treated uniforms to reduce potential interactive effects of DEET on permethrin absorption. The subcommittee also recommends that the Army conduct a human pharmacokinetic study with combined exposure to permethrin and DEET to determine whether this exposure increases the absorption of permethrin. ACUTE TOXICITY Although permethrin is highly toxic to insects and other arthropods, it is one of the least toxic insecticides to mammals. Its acute toxicity has been studied in several animal species and has been found to be more toxic by the oral route than by the dermal or inhalation routes. The oral LD50 (acute oral lethal dose for 50% of the subjects) of technical-grade permethrin in experimental animals is in the range of 0.5-5 g/kg of body weight. Aqueous suspensions of permethrin usually produced the least toxicity, with LD50 values ranging from 3 to 4 g/kg of body weight. Permethrin in corn oil suspensions yielded LD50 values of approximately 0.5 g/kg in most of the studies involving oral administration to rats and mice. The cis/trans isomer ratio also affects the toxicity, the cis isomer being more toxic than the trans isomer. Permethrin in BDU fabric would contain 60% cis isomer and 40% trans isomer. The clinical signs of acute poisoning become evident within 2 hr of exposure to permethrin and are targeted to the central nervous system; symptoms are uncoordination, ataxia, hyperactivity, convulsions, and, finally, prostration, paralysis, and death. SUBCHRONIC TOXICITY The no-observed-effect level (NOEL) for permethrin in rats in 3-and 6-month feeding studies ranged from 20 to 1,500 mg/kg. Rats and mice have survived permethrin exposures as high as 10,000 mg/kg (in feed)

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms for 2-26 weeks, although clinical signs of toxicity were clearly evident. NOELs in dogs administered permethrin orally in gelatin capsules ranged from 5 mg/kg in a 3-month study to 250 mg/kg in a 6-month study. The primary target organ in subchronic toxicity studies in rodents is the liver (see section on liver toxicity). The lowest NOEL from subchronic toxicity studies of permethrin was estimated to be 5 mg/kg per day in dogs. That NOEL and the daily exposure to permethrin of 6.8 × 10−5 mg/kg per day from wearing permethrin-impregnated BDUs provide a margin of safety (MOS) of approximately 74,000, as shown in the following equation: Because the daily lifetime permethrin dose for garment workers (3 × 10−5 mg/kg per day) is less than the daily dose for military personnel (6.8 × 10−5 mg/kg per day), the MOS for garment workers is even higher—approximately 168,000. Therefore, subchronic toxicity of permethrin should not be of concern when permethrin-treated BDUs are worn or permethrin-treated fabric is handled. DERMAL TOXICITY The dermal toxicity of permethrin has been studied in animals and humans. Single dermal application of permethrin failed to produce skin irritation in rabbits. Repeated dermal exposure to permethrin in rabbits has been shown to produce slight erythema. When cotton cloth impregnated with permethrin was applied to the clipped skin of rabbits for 21 days to mimic occupational exposure, no adverse effects were reported. Experiments with guinea pigs showed that permethrin might be a skin sensitizer at high doses. In photochemical irritation studies, permethrin did not cause phototoxicity in experimental animals. In a study with 184 human subjects, a 21-day repeat patch test with a 40% permethrin solution did not cause any skin sensitization. However, several subjects described a transient burning, stinging, or itching sensation (subjective irritation). In a Swedish study of 87 plant nursery workers who were exposed to permethrin, itching and burning skin were re-

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms ported. Among 17 human volunteers exposed to 1% permethrin with skin patches for up to 9 days, two complained of mild erythema and skin irritation. Among 10 male volunteer soldiers who wore uniforms impregnated with an aqueous solution of 0.2% permethrin, none complained of skin irritation. Permethrin preparations are the treatment of choice for insect-transmitted diseases such as crab lice and scabies. In studies of 1% permethrin cream rinse to treat head lice and 5% permethrin cream to treat scabies in humans, mild skin irritation occurred in a small percentage of those treated. The subcommittee estimated a MOS of 126,000 based on the studies that used 5% permethrin cream to treat scabies in humans. The weight of evidence shows that permethrin is unlikely to be a skin irritant or skin sensitizer for military personnel who are exposed to it dermally from wearing permethrin-impregnated BDUs or for garment workers who sew permethrin-impregnated BDUs. A few persons, however, might be hypersensitive to permethrin-treated BDUs and thus develop skin sensitization. Therefore, the subcommittee recommends that the Army should monitor for hypersensitivity when it begins to use permethrin-treated BDUs on a regular basis. OCULAR TOXICITY Several investigators have tested ocular toxicity of permethrin in rabbits. In one study, no eye irritation was observed when 0.1 mL of undiluted technical permethrin was instilled in the eyes of Japanese White rabbits. In other similar studies, minimal ocular effects were observed. The weight of evidence from ocular studies conducted to date suggests that permethrin is mildly irritating to the eyes only when high concentrations of permethrin are instilled in the eyes; therefore, wearing permethrin-treated BDUs or working with permethrin-impregnated fabric is not expected to produce eye irritation. NEUROTOXICITY Permethrin is neurotoxic at high doses. It produces a variety of neu-

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms rotoxic effects in animals. Some of these effects are tremors, salivation, paresthesia, splayed gait, depressed reflexes, and tiptoe gait; reversible axonal injury occurs at very high doses. In one study, rats fed permethrin in diet at 6,000 mg/kg for 14 days showed fragmented and swollen sciatic nerve axons and myelin degeneration. In another study, rats fed permethrin at up to 9,000 mg/kg developed severe trembling but exhibited no consistent histological effects in nerve tissues. In other studies of neurotoxicity in rats, lesions caused by high concentrations of permethrin included swelling and increased vesiculation of unmyelinated nerves, hypertrophy of Schwann cells, fragmentation of myelinated axons, and demyelination of sciatic nerves. In other studies, repeated oral administration of permethrin at doses of up to 9,000 mg/kg for 3 weeks or longer was not found to be neurotoxic in hens. A few studies on the effect of permethrin on neurobehavior of animals showed that permethrin exposure might have a weak effect on neurobehavior, but nerve conduction studies in 23 permethrin workers showed no evidence of nerve impairment associated with permethrin exposure. Animal data show that permethrin is neurotoxic at high doses, but similar human data to verify that evidence are lacking. The estimated no-observed-adverse-effect level (NOAEL) for neurotoxicity by the dermal route in rats is 200 mg/kg. Based on that NOAEL from available neurotoxicity data, the MOS associated with daily human exposure from permethrin-treated BDUs at a level of 6.8 × 10−5 mg/kg per day is approximately 3 million. Because the daily dose for garment workers (3 × 10−5 mg/kg per day) is lower than that for military personnel, the MOS for garment workers is approximately 6.8 million. Therefore, neurotoxicity from wearing permethrin-impregnated BDUs or working with permethrin-treated fabric should not be a concern. Although animal data clearly demonstrate the neurotoxic properties of high doses of permethrin, human data are needed to place these data in perspective. Therefore, the subcommittee recommends that data on neurotoxicity of permethrin in humans be collected from epidemiological studies of workers or from accidental human exposures.

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms LIVER TOXICITY Extensive medical investigations of workers exposed to permethrin have not revealed any clinical chemistry changes that would suggest liver toxicity. The most significant toxicological effect of permethrin involves the liver in rodents. It is characterized by an increase in absolute and relative liver weight in rodents. The weight increase requires several repeated high-dose exposures to become evident, and recovery is manifested after permethrin exposure is stopped. A significant increase in liver weight occurred in rats following ingestion of permethrin at 100 mg/kg per day for 26 weeks, the lowest dose that has been reported to cause such an effect. The increase in liver weight in rats exposed to high doses of permethrin is due to hepatocellular hypertrophy. Necrotic foci, vacuolization, and increased eosinophilia also have been observed. Hepatocellular hypertrophy is characterized ultrastructurally by an increase in endoplasmic reticulum, which is functionally associated with an increase in microsomal activity and an increase in cytochrome-P-450-mediated enzymes. These changes are largely reversible after exposure to permethrin is stopped. Dogs did not show morphological changes in the liver even when exposed to 2,000 mg/kg per day for 3 months. No significant toxic effects were seen in the liver in rabbits or cows administered high concentrations of permethrin for 10 or 28 days, respectively. The NOAEL for hepatocellular hypertrophy in rats has been estimated to be 10 mg/kg per day. The subcommittee concluded that the NOAEL of 10 mg/kg per day from the available liver toxicity data and the daily exposure to permethrin at a level of 6.8 × 10−5 mg/kg per day from wearing treated BDUs provide a MOS of approximately 150,000 for liver toxicity. The MOS for garment workers is approximately 340,000. Therefore, liver toxicity from wearing permethrin-impregnated BDUs or working with treated fabric should not be a concern.

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms IMMUNOTOXICITY No data are available to evaluate the immunotoxic potential of permethrin in humans. Only two laboratory studies are reported in the literature —an in vitro study of mouse lymphocytes and a study of chicks; both are inconclusive regarding the immunotoxological effects of permethrin. The subcommittee recommends that immunotoxicological investigations be performed in laboratory animals to ascertain the immunotoxic properties, if any, of permethrin in mammalian species. The research should follow the guidelines presented in the 1992 NRC report Biologic Markers in Immunotoxicology. REPRODUCTIVE AND DEVELOPMENTAL TOXICITY Data on reproductive and developmental toxicity of orally administered permethrin suggest that there are few toxic effects, and those tend to be limited to high doses. No reproductive or developmental toxicity data are available from dermal exposure studies, but dermal absorption is poor, and oral dosing would be expected to maximize any effects. Some studies involving oral exposures have reported reproductive or developmental toxicity effects, but the effects have not been confirmed in other similar studies. Also, there is disagreement among the studies regarding the doses at which such toxicity occurs. There were some differences in the strain of rat used in the studies, and the cis/trans ratio was not always specified; these factors might explain, in part, the inconsistencies in the data. In studies of prenatal exposure only, NOAELs from the mouse and rabbit studies (400 mg/kg per day and 600 mg/kg per day, respectively) were much higher than those from the rat studies (20-50 mg/kg per day). In a three-generation reproductive toxicity study of permethrin, small increases in buphthalmos and persistent papillary membrane were observed in weanling rats following continuous exposure to permethrin at 1,000 and 2,500 ppm in diet (actual amounts of permethrin consumed were 50 and 125 mg/kg per day); the NOAEL was estimated to be 25 mg/kg per day. In contrast, another study reported no effects from

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms permethrin doses as high as 180 mg/kg per day given in the diet, but such effects might not have been observed because these changes are subtle and have a very low incidence. No histopathological examinations were conducted or organ weights measured in any of the three-generation reproductive studies performed to determine the effect of permethrin on male reproductive function. Among the chronic exposure studies, one study in mice did note an effect on testis weight and testicular hypoplasia at permethrin doses of 75 and 300 mg/kg per day (NOAEL of 3 mg/kg per day). However, in other studies, no such effects were noted in rats or mice at permethrin doses of up to 250 mg/kg per day. Thus, information on male reproductive effects is minimal at best, and the most conservative NOAEL is 3 mg/kg per day. The NOAEL of 3 mg/kg per day based on testicular effects and the permethrin intake of 6.8 × 10−5 mg/kg per day from wearing permethrin-impregnated BDUs provide a MOS of approximately 44,000. The MOS for garment workers is even higher—approximately 100,000. Given the lack of effects in most of the reproductive and developmental toxicity studies on permethrin and a MOS of approximately 44,000 from the most sensitive end point (decreased testicular weight), the possibility of male reproductive effects or other reproductive and developmental effects occurring from wearing permethrin-impregnated BDUs or working with permethrin-treated fabric is remote. GENOTOXICITY Studies conducted to determine the potential of permethrin to produce gene mutations were all negative. These studies included tests for gene mutations in microbial systems (Ames Salmonella reverse mutation assay, forward mutation assay using Escherichia coli WP2, and Drosophila sex-linked recessive lethal test) and gene mutations in mammalian cells in culture (mouse lymphoma L5178Y cells and V79 Chinese hamster ovary cells).

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms Studies conducted to determine the potential of permethrin to produce chromosomal damage provided an array of results. Some were positive, some negative, and others deficient in information needed to draw a definitive conclusion. Of the two in vivo studies conducted in the micronucleus assay, one was negative and the other was inadequate because an insufficient number of animals were used and only one dose was tested. Three in vitro studies in which clastogenicity of permethrin was investigated provided evidence of potential clastogenicity of permethrin. Small statistically significant elevations in sister chomatid exchanges, micronuclei, and chromosomal aberrations in human lymphocyte cultures were reported. Chromosomal aberrations were also reported in Chinese hamster ovary cells. All three in vitro studies were performed in one laboratory by the same investigators. Two studies were conducted with the dominant lethal test; both were considered deficient. In one study, there was no explanation of the deaths of at least 5% of the female animals, and the number of pregnant animals was insufficient. In the other study, only one dose was tested. Other genotoxicity tests of permethrin (E. coli pol A assay, Bacillus subtilis rec assay, Saccharomyces cerevisiae D3 mitotic recombination assay, and unscheduled DNA synthesis assays) were negative. The subcommittee believes that the weight of evidence suggests that permethrin does not produce gene mutations but is a potential clastogen in certain in vitro systems. Three in vitro studies from one laboratory showed small statistically significant increases in clastogenic effects of permethrin. These results have not been independently confirmed by other investigators. The subcommittee recommends that these studies be repeated by other investigators to determine if the positive findings of permethrin 's clastogenicity can be confirmed. If these findings are confirmed, the clastogenicity of permethrin should also be studied in vivo with an adequate number of animals and dosages of permethrin. CARCINOGENICITY There is no information in the literature on carcinogenic effects of permethrin in humans. Evidence of permethrin's possible carcinogenic-

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms ity in humans is derived from bioassays in rodents. Permethrin has been tested in seven chronic exposure studies in which permethrin was administered in the diet to rats in three studies and to mice in four studies. The three rat studies were negative for carcinogenicity; however, permethrin concentrations were not high enough to adequately assess the oncogenic potential of permethrin. In spite of some deficiencies in the mouse studies, two showed evidence of carcinogenicity. In a 24-month study, permethrin was administered to male and female CD-1 mice. Permethrin doses were 0, 20, 500, and 2,000 ppm for males and 0, 20, 2,500 and 5,000 ppm for females. The primary findings were as follows: In males, statistically significant increases in liver adenomas at all doses were observed, as was a statistically significant dose-related trend. In females, statistically significant increases in lung adenomas and carcinomas combined were observed at mid and high doses, and the dose-related trend was also statistically significant. In addition, lung adenomas and carcinomas occurring separately showed statistically significant dose-related trends. In a 92-week study, permethrin was administered in the diet to male and female CFLP mice at doses of 0, 10, 50, and 250 mg/kg per day. There was a statistically significant increase in lung tumors in females at the highest dose, as well as a statistically significant dose-related trend. Permethrin was also tested in the Shimkin mouse lung bioassay to determine if permethrin is a tumor promoter. This assay did not show any evidence that permethrin promoted lung tumors; however, the Shimkin assay is not a definitive mouse oncogenicity assay. Based on the weight of evidence from animal studies, the subcommittee concludes that permethrin is a possible human carcinogen. The subcommittee based its quantitative cancer risk assessment for permethrin on the 24-month chronic feeding study in CD-1 mice as described above. The oral carcinogenic potency factor (upper 95% confidence limit) was calculated on the basis of combined adenomas and carcinomas of the lungs in female mice. The subcommittee calculated a human-equivalent carcinogenic potency factor of 0.016 mg/kg per day, using the linearized multistage procedure, and extrapolated to humans on the basis of body weight to the 2/3 power. An upper bound on the lifetime carcinogenic risk was estimated by multiplying the carcinogenic potency factor by the estimated average daily lifetime dose. For military personnel wearing permethrin-impreg-

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms nated BDUs, the upper bound on lifetime carcinogenic risk is estimated to be 1.6 × 10−6. That same value applies to nonfield and field personnel and assumes that topically applied DEET does not enhance dermal absorption of permethrin. As stated earlier, less than 5% of the skin would have overlapping exposure to DEET and permethrin. If the recommended pharmacokinetic studies are done and the results of those studies indicate an enhanced absorption of permethrin from simultaneous exposure to DEET and permethrin, that would mean that soldiers wearing permethrin-impregnated BDUs and applying DEET to skin areas not covered by BDUs are exposed to higher concentrations of permethrin. In that case, carcinogenic risk should be reevaluated to determine if the revised carcinogenic risk is acceptable. The estimated upper-bound lifetime carcinogenic risk to garment workers, 6.9 × 10−7, is less than half the calculated upper-bound risk to military personnel. That value does not reflect the possibility of workers being exposed to permethrin from airborne particles of permethrin-impregnated fabric, and it might not represent a true upper bound on the overall carcinogenic risk to garment workers. However, assuming that appropriate safety precautions are taken, it seems unlikely that the exposure of garment workers to airborne particles of permethrin-treated cloth would increase their overall exposure and thus their risk to the same level as military personnel. The carcinogenic risk to field or nonfield military personnel or to garment workers from exposure to permethrin-impregnated fabric is very small—of the order of 10−6 or less. Therefore, the subcommittee concludes that premethrin-impregnation of BDUs is not a serious carcinogenic risk to field or nonfield military personnel or to garment workers. CONCLUSIONS The subcommittee analyzed the risk of adverse health effects to soldiers who wear permethrin-impregnated BDUs and the risk to garment workers who handle permethrin-treated fabric. Based on the review of the toxicity data on permethrin, the subcommittee concludes that soldiers who wear permethrin-impregnated BDUs are unlikely to experience ad-

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms verse health effects at the suggested permethrin exposure levels (fabric impregnation concentration of 0.125 mg/cm2). The risk of adverse health effects in garment workers who handle permethrin-impregnated fabric is even smaller because their exposure to permethrin is estimated to be less than that of soldiers. Permethrin-impregnated BDUs are effective in preventing insect-borne diseases in military personnel in insect-infested field areas. The most beneficial use of permethrin-impregnated BDUs will be in overseas field settings, where exposure to disease-bearing insects is substantial. The risk of vector-borne disease in the United States is considerably less but not zero. Military personnel wearing permethrin-impregnated BDUs in field operations in the United States will benefit from protection from tick and mosquito bites, which, in turn, will protect them from endemic diseases, such as Lyme disease, Rocky Mountain spotted fever, and viral encephalitis. They will also be protected from other routine insect bites that often become infected and require medical treatment. The subcommittee notes that in situations where soldiers are in protected environments, such as offices, where insect contact is remote, there is no tangible benefit from wearing impregnated BDUs.

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