Appendix A



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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms Appendix A

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms This page in the original is blank.

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms Quantitative Risk Assessment Permethrin-Impregnated Battle Dress Uniform October 1989 REFERENCES. See . . . list of references cited in this assessment. BACKGROUND AND INTRODUCTION. The following describes the procedures used to quantify the potential carcinogenic risks from wearing the permethrin-impregnated Battle Dress Uniform (BDU). A risk assessment is an attempt to describe potential health risks resulting from specific exposure scenario to a given contaminant. For the present assessment, we proceeded in stages as recommended in reference 1. Hazard Evaluation. This is the process of gathering and evaluating all data that may reveal the type of adverse effects produced by a substance. This can include animal as well as human toxicity data. Dose Response Evaluation. In this step, the dose response relationships are described for each biological response. This step also includes extrapolation of animal data to humans, if required. Human Exposure Evaluation. Qualitative and quantitative descriptions of each potential exposure route are detailed. Populations at risk and sensitive subgroups should also be identified. Risk Characterization. This involves combining the analyses in the above steps to provide a measure of the potential risks. PERMETHRIN RISK ASSESSMENT. Hazard Evaluation. Several recent reviews have summarized the toxicity of permethrin (references 2 and 3) and these should be consulted

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms for more complete information. In this assessment, we will focus on potential carcinogenic risks. Seven long term carcinogen bioassays have been performed with permethrin. Of these, only one (FMC Mouse II) showed a statistically significant dose-related increase in cancer. In this study, female mice exhibited an increased incidence of alveolar cell adenomas and carcinomas. These animals also tended to have a dose-related increase in liver adenomas and carcinomas. This study was used by the Environmental Protection Agency (EPA) as the basis for classifying permethrin as a Category C compound (possible human carcinogen). Dose Response Extrapolation. A key toxicity value in quantifying potential carcinogenic risk is the carcinogen potency factor. This value represents the slope of the upper 95% confidence interval of the extrapolated dose response curve. A published potency factor was not available for permethrin, so we derived a value based on the positive female mouse data. This process involved extrapolation of the bioassay data from high doses to low doses and then to humans. We used the Linearized Multistage Model for dose extrapolation. This model is relatively conservative and results in a plausible upper bound estimate of risk (reference 4). This is also the model used by the EPA for most of their published potency factors. As recommended in reference 5, alveolar cell adenomas were combined with carcinomas for use in the dose response extrapolation. Animal doses were converted to human dose levels using a surface area correction as described in reference 4. Table 1 summarizes the data and results of the dose response extrapolation. Exposure Assessment. The current exposure assessment addresses potential human exposures resulting from wearing a permethrin-impregnated BDU. It is anticipated that this treatment process will be utilized by military personnel, deployed to areas posing a recognized threat from insect-borne diseases. Two potential exposure routes should be addressed: inhalation of vapor volatilizing from the fabric and dermal exposures. Inhalation. Since permethrin is a solid at room temperature and has a relatively low vapor pressure (10 torr at 50° C), the inhalation route is probably insignificant and will not be considered further.

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms TABLE 1. Data Summary and Dose Response Extrapolation Concentration in Food (ppm) Daily Dose * (mg/kg/day) Human Equivalent** Dose (mg/kg/day) Tumor Incidence 0 0 0 15/74 20 2.7 0.2 24/74 2500 333 25 35/75 5000 667 50 44/65 Oral Potency Factor: 0.016 (mg/kg/day)−1 * Based on animal weight of 30 grams and 4 grams food per day. ** Human equivalent Dose = Animal Dose / (70 kg / 0/03 kg)1/3 Dermal. A preliminary exposure assessment was previously published (reference 6). The predicted exposure of approximately 0.005 mg/kg/day was based on continuous wear of a uniform impregnated with permethrin at a target concentration of 0.125 mg/cm2. Skin area exposed to contaminant was assumed to be 2.2 m2 with a dermal penetration of 2%. Although field operations may require soldiers to wear the BDU on a continual basis, this seems an unlikely scenario for more than a few days. Similarly, estimates of carcinogenic risk are typically based on a lifetime exposure; however, no one will spend an entire lifetime in the military. Finally, laundering of the BDUs removes a portion of the impregnant with each wash as does migration of the compound out of the fabric during wear. We therefore have adjusted the predicted exposure factors to account for these differences: Initial Treatment Level - 0.125 mg/cm2 Adjustment Factor - 26 % Time-weighted average of permethrin remaining in impregnated 100% cotton and NYCO BDU fabrics through 50 wash-

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms ings (reference 7). Body Contact area - 1.5 m2 EPA has established that the average body surface area for a 70 kg man is 1.9 m2. This value is adjusted to 1.5 m2 when the area for hands, feet, head and neck (not contacted by the impregnated cloth) is subtracted (reference 8). Dermal Absorption - 2 % / day Value is reported for man (reference 9). Migration - 0.49 % / day Permethrin migrating from treated fabrics to the skin surface. Collective experimental data for 7-day exposures in animals (references 6 and 10). Body Weight - 70 kg. The EPA uses 60 kg (132 lbs.) as the average body weight. Seventy kg (154 lbs.) is more realistic for military combat personnel. Daily Wear - 16 hrs / day While soldiers may sleep in clothing, 16 hours per day is the maximum predicted contact time when averaged over a 6-year exposure period. Time Worn (Exposed) - 6 years Initial assignment of 3 years is typically followed by a 3-year reenlistment. Lifetime - 75 years

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms From EPA guidelines (reference 8). The Exposure Dose (ED) is derived by multiplying the values (a) through (f); the value for (f) being 1/70. Exposure Dose = 6.8 × 10−4 mg/kg/day. The Chronic Daily Intake (CDI) is derived by modifying the ED by the predicted exposure period: Chronic Daily Intake = 6.8 × 10−4 mg/kg/day × (16/24) × (6/75) = 3.6 × 10−5 mg/kg/day Risk Characterization. An estimate of carcinogenic risk can be calculated using the potency factor and CDI values derived above. This calculation is shown in the following expression: RISK = (CDI) × (Potency Factor) = (3.6 × 10−5 mg/kg/day) × (1.6 × 10−2 mg/kg/day) =6 × 10−7 This value represents an upper bound estimate of carcinogenic risk under the exposure conditions outlined above. Under the assumed conditions, an individual faces a probability of less than 1 chance in 1,000,000 of developing cancer as a result of permethrin exposure. In terms of populations, we would expect 1 excess cancer to develop in 2,000,000 exposed individuals as a result of permethrin. These calculations are based upon very conservative assumptions, and in all likelihood, actual risks will be less than this value. Uncertainties. Toxicological Assessment/Dose Extrapolation. As discussed in

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms reference 4, there are many uncertainties in the low dose extrapolation and animal to human extrapolation which could affect the actual risk to exposed humans. There are important species differences in contaminant uptake, distribution and metabolism as well as target organ susceptibility for which we have no information. Our potency factor derivation is also based on summaries of animal data and not the original literature. We were forced to estimate animal dose levels based on estimated body weights and food consumption rates. Human Exposure. In the exposure dose assessment, the 6.8 × 10−4 mg/kg/day estimated dose was based in part on a daily migration rate from fabric to skin of 0.49%. This value was determined experimentally in animal studies and represents the maximum rate measured over the first seven days of continuous wear. Subsequent weeks showed a much smaller transfer of contaminant (reference 11). Laundering of these garments would be expected to reduce the migration rate even further. The dermal penetration rate is a second critical value which could dramatically affect estimated risks. The 2% penetration value was taken from a literature summary (reference 9) and represents the maximum absorption seen in human volunteers. Average values were approximately half this value. Finally, the effects of weathering on the permethrin content of treated BDUs were not considered. It is likely that these factors, particularly photodynamic, may significantly accelerate degradation of the substance. REFERENCES 1. National Academy of Sciences, 1983. Risk Assessment in the Federal Government: Managing the Process. National Academy of Sciences, National Academy Press, Washington, D.C. 2. Paynter, O.E., E.R. Budd and B.D. Litt, 1982. Permethrin, Assessment of Chronic and Oncogenic Effects, A Summary . Toxicology Branch, Hazard Evaluation Division, Office of Pesticide Programs, USEPA.

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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms 3. EER, 1989. Draft Report: Permethrin Toxicity. Engineering and Economics Research, Inc., Vienna, VA. 4. Federal Register, 1986. Guidelines for Carcinogenic Risk Assessment, 51 CFR 33992. 5. McConnell, E.E., H.A. Solleveld, J.A. Swenberg and G.A. Boorman, 1986. Guidelines for Combining Neoplasms for Evaluation of Rodent Carcinogenesis Studies. J. Natl. Cancer Inst. 20:282-288. 6. Snodgrass, H.L. and P.A. McGreal, 1988. Phase 2, Migration of Permethrin From Military Fabrics Under Varying Environmental Conditions. Study No. 75-52-0687-88. USAEHA Technical Report. 7. McNally, B.F., 1987. Interim Report on Contract for Further Investigation of the Application of Permethrin to Battle Dress Uniforms, MER Report No. 8868, NRDEC Technical Report. 8. EPA, July 1989. Exposure Factors Handbook, USEPA, Office of Health and Environmental Assessment. EPA/600/8-89/043. 9. Taplin, D. and T.L. Meinking, 1987. Pyrethrins and Pyrethroids for the Treatment of Scabies and Pediculosis . Seminars in Dermatology 6(2): 125-135. 10. Snodgrass, H.L. 1988. Final Phase, The Effects of Laundering on the Permethrin Content of Impregnated Military Fabrics, Study No. 75-52-0687-88. USAEHA Technical Report. 11. Snodgrass, H.L., 1982. Interim Report, Migration of 14C Permethrin from Impregnated Military Fabric. Study No. 75-51-0351-82. USAEHA Technical Report.