Risk Assessments for Exposure of Deployed Military Personnel to Insecticides used for Personal Protection and Disease-Vector Management Robert K. D. Peterson Montana State University Bozeman, Montana

Problem Because of the lack of vaccines and therapeutic drugs, vector management, including the use of personal protective measures, is the best tool that deployed military personnel have against most vector-borne pathogens that cause disease In preparation for military operations and force-health protection, the health risks from vector-borne pathogens that cause disease and vector management tactics need to be understood

Problem Due to long-standing perceptions of risk from pesticides, the use of insecticides may raise concerns about their potential adverse health effects on military personnel The uncertainties about exposure of the troops to pesticides led the DOD to investigate the use and management of pesticides during the Gulf War and to raise concerns about the potential health effects of pesticide exposures to service members in general

Objective To use risk assessment methodologies to evaluate health risks to deployed U.S. military personnel from insect-vector management tactics © 2004 RKD Peterson

Risk Assessment Risk assessment is a formalized basis for the objective evaluation of risk in which assumptions and uncertainties are clearly considered and presented.

Hazard Identification Dose-Response Relationships Exposure Assessment Risk Characterization Risk Assessment Paradigm Problem Formulation

Risk Assessment Extremely conservative assumptions to screen out negligible risks Reasonable worst-case scenarios Tier I Tier II Tier III Tier IV Most refined assessment

Methodology Acute Exposure: Single-day exposures after a single application or use of the chemicalSingle-day exposures after a single application or use of the chemical Subchronic Exposure: The exposure per day over 180 days with multiple spray eventsThe exposure per day over 180 days with multiple spray events Chronic Exposure: The exposure per day over 250 days per year for 10 yearsThe exposure per day over 250 days per year for 10 years

Methodology Hazard Identification: permethrin, resmethrin, sumithrin Outdoor Space Sprays BDU, Bednet Synergist piperonyl butoxide cyfluthrin, lambda-cyhalothrin, alpha-cypermethrin, sumithrin permethrin, deltamethrin, lambda-cyhalothrin, alpha-cypermethrin, cyfluthrin Indoor/Outdoor Residual

Insecticide-Impregnated BDU’s Worn 18 hr/day Permethrin Only Dermal Exposure Only Briefs and undershirt Arms, hands, and legs No wash-off or degradation

Insecticide-Impregnated Bednet 8 hr/night permethrin, deltamethrin, lambda-cyhalothrin, alpha- cypermethrin, cyfluthrin Inhalation Exposure Dermal Exposure 50% of head, trunk, arms, legs, hands, feet No wash-off or degradation

Surface Residual and Indoor Space Applications Surface residuals: cyfluthrin, cypermethrin, cyhalothrin Indoor space spray: sumithrin Dermal Exposure Only 50% of head, trunk, arms, and hands Subchronic = 6 apps/180 days Chronic = 9 apps/yr AFPMB Image Database

Outdoor ULV Exposure Inhalation: moderate activity Dermal: no clothing 1-hr peak aerial concentration

Subchronic/Chronic Outdoor ULV Exposure Inhalation: moderate activity Dermal: no clothing Inhalation from re-suspended soil particles Dermal exposures from contact with soil Dermal exposures from contact with outdoor surfaces 30 spray events in 250 days

Surface-Residual Spray (cyfluthrin, alpha- cypermethrin, lambda-cyhalothrin) Indoor Space Spray (d-phenothrin) Outdoor ULV Space Spray (permethrin, resmethrin, d- phenothrin, piperonyl butoxide) Insecticide- Impregnated Battle Dress Uniforms (BDUs) (permethrin) Insecticide- Impregnated Bednets (permethrin, cyfluthrin, lambda- cyhalothrin, deltamethrin, alpha- cypermethrin) Dermal contact with sprayed surface Inhalation from spray particles Dermal contact with spray particles Inhalation exposures from re- suspended outdoor soil particles Dermal exposures from contact with soil Dermal exposures from contact with outdoor surfaces Dermal contact with BDU Dermal contact with bednet Inhalation from bednet Application Type Exposure Pathways, Routes, and Durations (acute, subchronic, chronic) (subchronic, chronic)

Methodology Toxicity Endpoints: Chosen based on EPA regulatory endpoints Inhalation and dermal toxicity endpoints used for respective exposure route and duration No-Observed-Adverse-Effect-Level (NOAEL) compared to estimated exposures

Methodology Toxicity Endpoints: Permethrin Example: Inhalation NOAEL = 11 mg/kg body weight (BW) Dermal NOAEL = 500 mg/kg BW

Risk Characterization Integration of toxicity and exposure Margin of Exposure Method (MOE) NOAELExposure If MOE > 100, then it is typically below level of concern (LOC) MOE =

Results Surface Residual and Indoor Space ChemicalApplication rate SubgroupAcuteSubchronicChronic MOE Cyfluthrin215.8 mg/m 2 Adult male1394,1731,434,203 Adult female1474,4201,519,148 Lambda- cyhalothrin mg/m 2 Adult male ,416 Adult female ,255 Alpha-cypermethrin125.9 mg/m 2 Adult male2,02130,30812,291,542 Adult female2,14032,10313,019,541 Sumithrin2.15 mg/m 2 Adult male295,7968,873,87521,293,191 Adult female313,3159,399,45322,554,336

Results Outdoor ULV Space Spray ChemicalApplication rate SubgroupAcuteSubchronicChronicCancer MOE Risk PBO kg/haAdult male2,198,386116,94641,328,113N/A Adult female1,837,09297,72734,572,845N/A Permethrin kg/haAdult male4,30715,33721, X Adult female4,40715,71422, X Resmethrin kg/haAdult male42,690123,2751,839, X Adult female35,674125,6301,886, X Sumithrin0.004 kg/haAdult male1,357,058495,9617,456N/A Adult female1,134,032504,4597,618N/A

Results BDU’s and Bednetting ChemicalTarget doseSubgroupAcuteSubchronicChronicCancer MOE Risk Permethrin (BDUs) mg/cm 2 Adult male7,587 11, X Adult female7,594 11, X Permethrin (bednets) 500 mg/m 2 Adult male2,8308,49712, X Adult female2,8788,64212, X Permethrin (bednets) mg/m 2 Adult male23,20870,422102, X Adult female23,55071,621104, X Deltamethrin (bednets) 25 mg/m 2 Adult male88,601328,495479,602N/A Adult female86,052331,671484,239N/A Lambda- cyhalothrin (bednets) 20 mg/m 2 Adult male6772,1133,085N/A Adult female6832,1463,134N/A Alpha- cypermethrin (bednets) 40 mg/m 2 Adult male27,58742,41874,292N/A Adult female27,90543,12475,525N/A Cyfluthrin (bednets) 50 mg/m 2 Adult male2,6648,01811,906N/A Adult female2,7078,15412,107N/A

Discussion Our risk assessments were sufficiently conservative and indicate that health risks to military personnel from exposures to vector- control insecticides and personal protective measures would be lowOur risk assessments were sufficiently conservative and indicate that health risks to military personnel from exposures to vector- control insecticides and personal protective measures would be low

Discussion Our results most likely do not warrant significant refinements for regulatory decision- making, but data on actual use patterns, timing and areas treated, and data on actual air concentrations and deposition rates would better characterize risksOur results most likely do not warrant significant refinements for regulatory decision- making, but data on actual use patterns, timing and areas treated, and data on actual air concentrations and deposition rates would better characterize risks

Discussion Approach allows for the comparison of risks between vector-borne diseases and vector management strategies

Acknowledgments U.S. Armed Forces Pest Management Board's Deployed War Fighter Protection Research Program Montana Agricultural Experiment Station, MSU

Thank You