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DTIC ADA499675: A Probabilistic Risk Assessment for Deployed Military Personnel After the Implementation of the Leishmaniasis Control Program at Tallil Air Base, Iraq PDF

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Preview DTIC ADA499675: A Probabilistic Risk Assessment for Deployed Military Personnel After the Implementation of the Leishmaniasis Control Program at Tallil Air Base, Iraq

MODELING/GIS,RISKASSESSMENT,ECONOMICIMPACT A Probabilistic Risk Assessment for Deployed Military Personnel After the Implementation of the “Leishmaniasis Control Program” at Tallil Air Base, Iraq JEROMEJ.SCHLEIER,III,1,2RYANS.DAVIS,3LORENM.BARBER,1PAULAA.MACEDO,4 ANDROBERTK.D.PETERSON1 J.Med.Entomol.46(3):693Ð702(2009) ABSTRACT LeishmaniasishasbeenofconcerntotheU.S.militaryandhasre-emergedinimpor- tancebecauseofrecentdeploymentstotheMiddleEast.Weconductedaretrospectiveprobabilistic riskassessmentformilitarypersonnelpotentiallyexposedtoinsecticidesduringthe“Leishmaniasis ControlPlan”(LCP)undertakenin2003atTallilAirBase,Iraq.Weestimatedacuteandsubchronic risksfromresmethrin,malathion,piperonylbutoxide(PBO),andpyrethrinsappliedusingatruck- mountedultra-low-volume(ULV)sprayerandlambda-cyhalothrin,cyßuthrin,bifenthrin,chlorpyr- ifos,andcypermethrinusedforresidualsprays.Weusedtheriskquotient(RQ)methodforourrisk assessment (estimated environmental exposure/toxic endpoint) and set the RQ level of concern (LOC)at1.0.AcuteRQsfortruck-mountedULVandresidualspraysrangedfrom0.00007to33.3at the95thpercentile.Acuteexposuretolambda-cyhalothrin,bifenthrin,andchlorpyrifosexceededthe RQLOC.SubchronicRQsfortruck-mountedULVandresidualspraysrangedfrom0.00008to32.8 atthe95thpercentile.Subchronicexposurestolambda-cyhalothrinandchlorpyrifosexceededthe LOC. However, estimated exposures to lambda-cyhalothrin, bifenthrin, and chlorpyrifos did not exceedtheirrespectivenoobservedadverseeffectlevels. KEYWORDS organophosphate,pyrethroid,sandßy,Phlebotomus,Leishmania Leishmaniasis has been of concern to U.S. military pendingontheregionandthestrain(Seamanetal. personnelinthe20thcenturyandhasre-emergedin 1996).MucosalleishmaniasisisgenerallyaNewWorld importance because of recent deployments to the diseaseandisrelativelyrare(Kenneretal.1999).In MiddleEast(Magilletal.1993,AFPMB1999,Weina 1990and1991,therewere20casesofcutaneousleish- etal.2004).Althoughleishmaniasisisnotconsidered maniasisand12casesofvisceralleishmaniasisinsol- adiseaseofstrategicmilitarysigniÞcance,itmaypose diersdeployedtotheArabianPeninsuladuringOp- a signiÞcant threat to mission objectives (AFPMB erationsDesertShieldandStorm(AFPMB1999).The 1999).Leishmaniasisisadiseasecomplexcausedby majorityofcasesinIraqsincethebeginningofOp- 17Ð20 species of protozoan parasites of the genus eration Iraqi Freedom in 2003 are associated with Leishmania,whicharevectoredbyphlebotominesand increasedexposuretoinfectedsandßies(Colemanet ßies(Croftetal.2006).Therearethreeclinicalsub- al. 2006). The increased exposure is caused by in- types of leishmaniasis: cutaneous, mucocutaneous, creasednumbersofbreedingsitesbecauseofthede- andvisceral.Themostcommonsubtypeiscutaneous structionofwaterandsanitationsystems,shortageof leishmaniasis,with1.5Ð2millioncasesperyearworld- insecticides,equipment,accumulationofgarbage,and wide, and the more serious subtype, visceral leish- the increase in the numbers of dogs in the streets maniasis, infects 500,000 people per year worldwide (Jassimetal.2006). (Herwaldt1999,Croftetal.2006,Ameen2007).Cu- In 2003 and 2004, the annual incidence rates of taneousleishmaniasisalonenormallydoesnotcause leishmaniasisintheU.S.militarywere40.9and24.4per death,althoughsecondaryinfectionsbybacteriacan 100,000 person-years (Lay 2004), respectively, al- befatal(PiscopoandMallia2006).Untreatedvisceral though the rate could be as high as 10% of soldiers leishmaniasishasacase-mortalityrateof30Ð60%,de- stationedinthePersianGulf(Pehousheketal.2004). From January 2003 to November 2004, there were 1,178casesofleishmaniasisinservicemembersofthe 1Department of Land Resources and Environmental Sciences, Montana State University, 334 Leon Johnson Hall, Bozeman, MT U.S.military,witharateof51.4casespermonth.Most 59717. oftheaffectedsoldiersservedinIraqand/orKuwait 2Correspondingauthor,e-mail:[email protected]. (Lay2004).In2003,theestimatedcaserateforsol- 3ElectricalConsultantsInc.,3521GabelRoad,Billings,MT59102. diersstationedneartheIraqÐIranboarderwas(cid:1)200 4Sacramento-Yolo Mosquito and Vector Control District, 8631 BondRd.,ElkGrove,CA95624. per 1,000 deployed persons (Aronson 2007a). From 0022-2585/09/0693Ð0702$04.00/0(cid:1)2009EntomologicalSocietyofAmerica Report Documentation Page Form Approved OMB No. 0704-0188 Public reporting burden for the collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden, to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to a penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. 1. REPORT DATE 3. DATES COVERED 2009 2. REPORT TYPE 00-00-2009 to 00-00-2009 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER A Probabilistic Risk Assessment for Deployed Military Personnel After 5b. GRANT NUMBER the Implementation of the ’Leishmaniasis Control Program’ at Tallil Air Base, Iraq 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION Montana State University,Department of Land Resources and REPORT NUMBER Environmental Sciences,334 Leon Johnson Hall,Bozeman,MT,59717 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM(S) 11. SPONSOR/MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION/AVAILABILITY STATEMENT Approved for public release; distribution unlimited 13. SUPPLEMENTARY NOTES U.S. Government or Federal Rights License 14. ABSTRACT see report 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF 18. NUMBER 19a. NAME OF ABSTRACT OF PAGES RESPONSIBLE PERSON a. REPORT b. ABSTRACT c. THIS PAGE Same as 10 unclassified unclassified unclassified Report (SAR) Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 694 JOURNALOFMEDICALENTOMOLOGY Vol.46,no.3 2001to2006,theincidencerateinIraqandAfghan- ULVandindoorresidualsprays)usedforsandßiesat istanwas2.31casesper1,000person-yearsofservice, TallilAirBaseduringtheLCP. with the largest numbers of leishmaniasis cases oc- curring in late summer and fall of 2003 (Aronson MaterialsandMethods 2007b). Therehasbeenasharpreductioninleishmaniasis ProblemFormulation.Weperformedareasonable casesinIraq/Afghanistan,mostlikelybecauseofim- worst-caseprobabilisticriskassessmentofacuteand provementsintentsandbuildings,aswellasemphasis subchronic human exposures after the LCP was on personal protective measures (PPMs) (Aronson adoptedduringOperationIraqiFreedomtoprotectall 2007b).Ofthe1,287casesofleishmaniasisdiagnosed coalitionforcesinthevicinityofTallilAirBase.Risk from2001to2006,only4havebeenvisceral(Aronson assessment is the formalized basis for the objective 2007b).DuringOperationsDesertShieldandStorm, evaluationofriskinwhichallassumptionsanduncer- theestimatedcostofleishmaniasistotheU.S.military tainties are clearly considered and presented (NRC wasapproximately$18,000and92lostdutydaysper 1983).Reasonableworst-caseriskassessmentserron patient(Grogletal.1993,GambelandAronson1997, thesideofsafetythroughdeliberateoverestimationof Martinetal.1998,AFPMB1999).Assumingthe2003 theriskstohumansandtheenvironment.Probabilistic and 2004 incidence rates of leishmaniasis, the esti- analysisincorporatessamplingfromthestatisticaldis- mated overall cost of treatment and lost duty days tributionofeachinputvariableandpropagateseach variable into output of estimated exposures. Acute wouldbe$867,000to$918,000permonth. exposures were deÞned in this study as single-day Topreventsandßybites,theU.S.militaryprovides exposuresafterasingleinsecticideapplication.Sub- PPMs to military personnel, including insect repel- chronicexposurestoinsecticidesweredeÞnedasthe lents (DEET), insecticide treated bednets, and per- exposuretoinsecticidesperdayover165dthatthe methrin-impregnated battle dress uniforms (BDUs) LCPwasinstituted,duringandaftertruck-mounted (Martinetal.1998,AFPMB1999,Colemanetal.2006). ULVandresidualsprayevents(Colemanetal.2006). However,whenPPMswereavailabletoU.S.military Exposures to two population groups, adult men and personnelatTallilAirBase,Iraq,only31%ofmenand adultwomen(18Ð65yrofage),wereestimatedfor 12%ofwomenusedthesemeasures.Userateswere eachscenario,chemical,route,andpathway. lowbecauseoftheintenseheat,blowingsand,anda HazardIdentification.Weassessedthethreeactive lackofknowledgeabouthowtousethem(Coleman ingredientsresmethrin,malathion,andpyrethrinsand etal.2006). thesynergistpiperonylbutoxide(PBO)usedforthe AtTallilAirBasein2003,theU.S.militaryadopted truck-mounted ULV applications. We also assessed the “Leishmaniasis Control Plan” (LCP) to reduce the Þve active ingredients lambda-cyhalothrin, cy- sand ßy populations. During the LCP, the military ßuthrin, bifenthrin, chlorpyrifos, and cypermethrin used truck-mounted ultra-low-volume (ULV) insec- usedforresidualapplications. ticides and residual sprays in and around tents, as ToxicityandDose–ResponseRelationships.DoseÐ well rodent and canine control (Coleman et al. response information for each compound was re- 2006). The U.S. Armed Forces Pest Management viewed, and endpoints were chosen based on acute Board (AFPMB) recommends each of the control and subchronic exposures. The toxicity thresholds measuresundertakenatTallilAirBaseaswellasthe usedinthisassessmentwereingestionreferencedoses useofPPMsforthecontrolandpreventionofsandßy (RfDs), which are established by the U.S. Environ- bites(AFPMB1999,2008).However,littleornoim- mentalProtectionAgency(U.S.EPA).IngestionRfDs pactonsandßypopulationswasseenaftertheexten- were based on the no observed adverse effect level sivecontrolactivitiesatTallilAirBase(Colemanetal. (NOAEL)witha100-foldsafetyfactorforintra-and 2006). interspecies extrapolation uncertainties. The acute Macedoetal.(2007)performedareasonableworst- oralRfDsforresmethrin,malathion,PBO,pyrethrins, case, deterministic human-health risk assessment of lambda-cyhalothrin,cyßuthrin,bifenthrin,chlorpyri- acute, subchronic, and chronic risks after truck- fos, and cypermethrin are 0.1, 0.14, 6.3, 0.07, 0.0025, mounted ULV, indoor space sprays, surface-residual 0.02,0.01,0.005,and0.1mg/kgbodyweight(BW)/d, sprays, insecticide-impregnated BDUs, and insecti- respectively (U.S. EPA 1998a, 2000b, 2002, 2004a, cide-impregnatedbednets,usedforthemanagement 2005a,2006a,b,c,2008).ThesubchronicoralRfDsfor ofmosquitoes.Theyshowedthattheriskstomilitary resmethrin, malathion, PBO, pyrethrins, lambda-cy- personnel exposed to PPMs and mosquito manage- halothrin, cyßuthrin, bifenthrin, chlorpyrifos, and ment tactics are most likely negligible. The vector cypermethrin are 0.1, 0.07, 0.16, 0.044, 0.001, 0.024, controlmeasuresevaluatedbyMacedoetal.(2007) 0.015,0.0003,and0.06mg/kgBW/d,respectively(U.S. are similar to those used at Tallil Air Base for the EPA 1998a, 2000b, 2002, 2004a, 2005a, 2006a, b, c, controlofsandßies.However,themosquitomanage- 2008). menttacticsdifferfromthetacticsusedatTallilAir EstimationofEnvironmentalConcentrations.We Baseforthecontrolofsandßiesinnumberofappli- usedAERMODtier-1airdispersionmodel(U.S.EPA cations, environment, and target vector. Therefore, 1999)inconjunctionwithBEESTsoftware(Version weperformedaretrospectiveprobabilisticriskassess- 9.65; Oris Solutions, Austin, TX) to predict the air ment on the management tactics (truck-mounted concentrations and surface deposition for the three May2009 SCHLEIERETAL.:TALLILAIRBASELCP 695 Table1. Inputdistributionsforspraydepositionandaerialconcentrationsforeachchemicalusedfortruck-mountedultra-low-volume applications Input Distributiontype Parameter Resmethrin Malathion PBO Pyrethrins Units Aerialconcentrations Gamma(truncated) Location 1.31 10.45 2.24 1.47 (cid:1)g/m3 Scale 1.76 14.02 0.22 1.98 Shape 1.81 1.81 2 1.81 Spraydeposition Weibull(truncated) Location 0.0003 0.002 2.24 0.0003 g/m2 Scale 0.001 0.008 0.22 0.001 Shape 0.91 0.91 2 0.91 PBO,piperonylbutoxide. active ingredients and PBO within 6 h after truck- Schleieretal.(2008)andPetersonetal.(2006),which mounted ULV application. In BEEST, we created a arebrießyreviewedhere. camplayoutwith19tentssetback-to-backinsixrows Acuteinhalationexposurewasestimatedby tosimulatethetentsetupatTallilAirBase.Theas- PE (cid:2)(EEC(cid:3)RR(cid:3)D)/BW, [1] sumptions included: (1) each chemical had a 24-h inhalation half-lifeintheair;(2)theinsecticideswereappliedat where PE is potential exposure from inhala- themaximumapplicationrateasstatedoneachlabel; tion(mg/kinghaBlaWtio)n,EECistheestimatedenvironmen- (3)alloftheinsecticidesweresusceptibletothesame talairconcentrationsasestimatedbyAERMOD((cid:1)g/ weatherconditionsusingstandardizedweatherdata m3;Table1),RRisrespiratoryrateforeachgroupthat fromAlbuquerque,NM,fromJuly1993toJune1994; isindicativeoflightactivitydominatedbymoderate (4)allsprayeventsoccurredat2100hours;(5)each movement or periods of rest (m3/h; Table 2), D is spray release was at 1.5 m; and (6) receptors were durationofexposure(h),andBWisbodyweightsfor positioned radially from the center of the camp, to eachgrouprepresentingthegeneralU.S.population (cid:1)230minalldirectionsandplacedat(cid:1)14-mintervals (kg;Table2). throughoutthecampbothalongthetruckrouteand Acutedermalexposurefromspraydepositiononto inbetweentents.WechoseweatherdatafromAlbu- thegroupwasestimatedby querque because the area is a desert environment that has standardized weather data for use with the PE (cid:2)(ADE(cid:3)CF(cid:3)AR(cid:3)AB)/BW, dermal AERMOD downloader. The maximum application [2] ratesfortruck-mountedULVresmethrin,malathion, PBO,andpyrethrinsare7.85,71.62,43.94,and10.09g wherePE ispotentialexposurefromdermalcon- dermal (AI)/ha,respectively(Table1). tact(mg/kgBW),ADEisadjusteddermalexposure (mg/lb[AI]),andCFisthedermalconversionfactor thatistheincreaseinexposurefromtheßaggersce- AcuteExposure nario.Thereislimitedpubliclyavailableinformation Truck-Mounted ULV Applications. We assumed on dermal deposition immediately after truck- thatmultirouteexposuresimmediatelyafterasingle- mountedULVsprays,soweusedtheU.S.EPAPes- sprayeventwerelimitedto24h.Routesofinsecticide ticideHandlerExposureDatabase(PHED)asacon- exposuretoeachgroupwereinhalationanddermal. servative surrogate (U.S. EPA 1998b). The PHED Assumptionsofbodyweight,respirationrate,andper- contains pesticide-handler scenarios derived from centareaoftwohandsarepresentedinTable2.We Þeldstudiesandexposureestimatesbasedonphysical assumedthateachgroupwouldbeoutsidewhenthe factorssuchasapplicationrate,hectarestreatedper spraytruckpassed,andthedurationoftheexposure day, type of clothing worn, methods of application, was6h.Theexposuremodelingassumptionsfollowed andformulationtype.WeusedthePHEDscenarioin Table2. Assumptionsforbodyweight,respirationrate,andpercentsurfaceareaoftwohandsforadultmalesandfemales Inputvariables Group Parameter Values Units Distribution Source Bodyweight Adultmales Mean 78.65 kg Log-normal(truncated) Portieretal.(2007) SD 13.23 Adultfemales Mean 65.47 kg SD 13.77 Respirationrate Adultmales Mean 15.14 liters/min Log-normal(truncated) Allanetal.(2008) SD 5.3 Adultfemales Mean 13.26 liters/min SD 4.64 Percentsurfacearea Adultmales Mean 5.2 % Normal(truncated) U.S.EPA(1997) oftwohands SD 0.5 Adultfemales Mean 5.1 % SD 0.3 696 JOURNALOFMEDICALENTOMOLOGY Vol.46,no.3 whichaßagger(personmarkingthelocationforpes- PE (cid:2)(AR(cid:3)SA(cid:3)DAR(cid:3)TC)/BW, surfaceresidual ticideapplicationwhiletheapplicationisoccurring) [7] wasexposedtoaliquidapplication.Weusedauniform distributionandassumedapersonwouldbeexposed wherePE isthepotentialexposurefrom 10Ð100timesmorethanintheßaggerscenario(Schleier surfaceresidual contactwithsurfaceresidualsprays(mg/kgBW),AR etal.2008).ARisapplicationrate(kg[AI]/ha),ABis isthemaximumapplicationrate(mg/m2),SAisthe dermalabsorptionrateforeachchemical,Disdu- body surface area (equation 3) in contact with the rationofexposure(h),andBWisbodyweight(kg; sprayedsurface(m2),whereweassumedthat50%of Table2).Surfaceareaforallgroupswasestimated thebodywouldcontactthesprayedarea,DARisthe using dermalabsorptionrate,TCisthetransferablesurface SA(cid:2)(4(cid:3)BW(cid:4)7)/(BW(cid:4)90), [3] residueofinsecticides,whichweassumedtobe20% (Williamsetal.2003),andBWisbodyweight(kg). whereSAissurfaceareaandBWisbodyweight(kg; The maximum application rates for lambda-cyhalo- Table2)ofthegroupbeingassessed(U.S.EPA1997). thrin,cyßuthrin,bifenthrin,chlorpyrifos,andcyper- Toadjusttheßaggerexposureforadultwomen,we methrin are 120.56, 21.53, 26.12, 112.08, and 125.88 used mg/m2,respectively.Thedermalabsorptionratesfor lambda-cyhalothrin,cyßuthrin,bifenthrin,chlorpyri- ADE(cid:2)FE(cid:3)(SA /SA ), [4] female male fos, and cypermethrin are 25, 5, 25, 3, and 2.5%, re- whereADEistheadjusteddermalexposure(mg/lb spectively(U.S.EPA1998a,2002,2004a,b,2005a). [AI]),FEistheßaggerexposure,SA isthesur- female faceareaofanadultwomanasestimatedbyequation SubchronicExposure 3, and SA is the surface area of an adult man as male estimated by equation 3. We assumed a triangular We assumed multiroute exposures per day after distribution,withthemaximumexposurebeingaßag- multisprayeventsoverthe165dinwhichtheLCPwas gerwithnoclothing(0.053mg/lb[AI]),aminimum implemented. Routes of insecticide exposure were exposure being a single layer of clothing with no from inhalation and dermal. The same assumptions gloves(0.011mg/lb[AI]),andthemostlikelyexpo- aboutbodyweight,inhalationrate,andsurfacearea sure being a person with his or her face, arms, legs, wereusedasstatedaboveforacuteexposure. hands, and feet exposed (0.0327 mg/lb [AI]) (U.S. Subchronicexposuresfortruck-mountedULVwere EPA 1997, 1998b). The dermal absorption rates for estimatedby resmethrin,malathion,PBO,andpyrethrinsare2,10, 2,and0.22%,respectively(U.S.EPA2000a,2005b,c, PE (cid:2)(PE (cid:3)SE)/D, [8] subchronicULV acuteULV 2006d). where PE is the potential subchronic Acute dermal hand contact with sprayed surfaces subchronic ULV exposurefromtruck-mountedULV(mg/kgBW/d), wasestimatedby PE istheacutepotentialexposureforinha- acuteULV PE (cid:2) lation,dermal,andhandcontactwithsprayedsurfaces handcontact asestimatedbyequation6(mg/kgBW/d),SEisthe (SA(cid:3)PSA(cid:3)EEC(cid:3)AB(cid:3)TC(cid:3)HC)/BW, [5] numberofsprayevents,andDisthe165-ddurationof the exposure. The number of spray events for res- wherePE ispotentialexposurefromhand handcontact methrin,malathion,PBO,andpyrethrinsare59,26,68, contact with sprayed surfaces (mg/kg BW), SA is surface area of the group (m2), PSA is the percent and 9, respectively (Coleman et al. 2006). Because PBO is present in both resmethrin and pyrethrins surfaceareaofthehands(Table2),EECistheesti- formulations,weaddedthenumberofsprayeventsfor mated environmental concentration for spray depo- sitionasestimatedbyAERMOD(mg/m2;Table1),AB bothchemicalstoobtainthenumberofsprayevents forPBO. isdermalabsorptionrateforeachchemical,TCisthe Subchronicexposuresfromsurfaceresidualspray- transferablesurfaceresidueofinsecticides,whichwe ingwereestimatedby assumedtobe20%(Williamsetal.2003),HCisthe number of times one half of one hand contacted a PE (cid:2)(PE (cid:3)SE)/D, surfacewithinsecticidepresent,whichweassumeda subchronicsurfaceresidual totalacute uniform distribution of 1Ð10 times, and BW is body [9] weight(kg;Table2). wherePE isthepotentialsub- Total acute exposure to active ingredients after subchronicsurfaceresidual chronicexposurefromsurfaceresidualsprays(mg/kg truck-mountedULVapplicationsforeachgroupwas BW/d), PE is the acute potential expo- estimatedby surface residual surefromsurfaceresidualspraysasestimatedbyequa- PE (cid:2)PE (cid:4)PE (cid:4)PE tion 7 (mg/kg BW/d), SE is the number of spray acuteULV inhalation dermal hand-contact events,andDisthe165-ddurationoftheexposure. [6] Thenumberofsprayeventsforlambda-cyhalothrin, SurfaceResidualSpraying.Dermalexposurefrom cyßuthrin,bifenthrin,chlorpyrifos,andcypermethrin contactwithsurfacesafterresidualsprayeventswere are 65, 24, 9, 7, and 3, respectively (Coleman et al. estimatedby 2006). May2009 SCHLEIERETAL.:TALLILAIRBASELCP 697 Table3. Adultmaleacuteandsubchronicprobabilistictotalpotentialexposure(PE )a(mg/kgBW/d)andriskquotients(RQs)b total atthe50th,90th,and95thpercentiles Acuteexposure Subchronicexposure Percentile 50th 90th 95th 50th 90th 95th Resmethrin PE 0.0003 0.0007 0.0009 0.0001 0.0002 0.0003 total RQ 0.003 0.007 0.009 0.001 0.002 0.003 Malathion PE 0.003 0.006 0.007 0.0004 0.0008 0.001 total RQ 0.02 0.042 0.051 0.005 0.011 0.014 PBO PE 0.0002 0.0004 0.0004 0.00009 0.0001 0.0002 total RQ 0.00004 0.00006 0.00007 0.0006 0.0009 0.001 Pyrethrins PE 0.0004 0.0008 0.002 0.00003 0.00006 0.00008 total RQ 0.005 0.011 0.014 0.0006 0.001 0.002 Lambda-cyhalothrin PE 0.074 0.081 0.083 0.028 0.032 0.033 total RQ 29.42 32.45 33.32 28.97 31.97 32.83 Cyßuthrin PE 0.0026 0.0028 0.003 0.0003 0.0004 0.0004 total RQ 0.13 0.14 0.015 0.016 0.018 0.018 Bifenthrin PE 0.016 0.017 0.018 0.0008 0.0009 0.001 total RQ 1.59 1.76 1.81 0.058 0.064 0.066 Chlorpyrifos PE 0.008 0.009 0.0092 0.0003 0.0004 0.0004 total RQ 1.64 1.81 1.86 1.16 1.28 1.32 Cypermethrin PE 0.0076 0.0085 0.0087 0.0027 0.003 0.0031 total RQ 0.077 0.085 0.l 0.0001 0.0002 0.0002 aPE isestimatedbyequations6Ð9. total bRQ(cid:2)PE /referencedose. total BW,bodyweight;PBO,piperonylbutoxide. Risk Characterization. We used the risk quotient spraydeposition,dermalconversionfactor,andder- (RQ)methodforourriskassessment,whichiscalcu- malexposure)todeterminepercentcontributionof latedbydividingthetotalpotentialexposureasesti- theinputvariabletotheoutputvarianceofthemodel matedbyequations6Ð9foreachgroup,chemical,and for each group and chemical for the truck-mounted durationofexposurebyitsrespectiveingestiontoxic ULV.Sensitivityanalysisisdesignedtoidentifyinputs endpointvalue(RfD).Themultirouteexposureinour thatarehavingasigniÞcantimpactonthevarianceof assessmentwascomparedwiththeingestionRfDbe- themodeloutput(CullenandFrey1999).Wechose cause it provided a conservative endpoint, which is only uncertain and not variable parameters to help basedonthemostsensitiveNOAEL.EstimatedRQs direct future research examining the fate of the in- are compared with a RQ level of concern (LOC), secticidesindesertenvironments.Sensitivityanalysis which is set by the U.S. EPA or another regulatory wasnotperformedonsurfaceresidualspraysbecause agency to determine whether regulatory action is ofthelackofuncertainparameters. needed.TheRQLOCusedinourassessmentwas1.0. AnRQ(cid:5)1.0meanstheestimatedexposureisgreater thantherelevantRfD. Results ProbabilisticAnalysis.Probabilisticriskassessments differfromdeterministicriskassessmentsbysampling AcuteRisk valuesfromthedistributionsofexposuresandbiolog- icalparameters.Toperformtheprobabilisticriskas- Truck-MountedULV.Riskquotientsdidnotexceed sessment, we used Monte Carlo simulation (Crystal theRQLOCatthe50th,90th,and95thpercentilesof Ball7.3;Decisioneering,Denver,CO)togeneratethe exposureforanygroupandchemical(Tables3and4). exposuresandRQs.ProbabilitiesofoccurrenceofRQ Adultmaleandfemaleexposuresatthe95thpercen- values were determined by incorporating sampling tilerangedfrom0.0004to0.007mg/kgBW/d(Tables fromthestatisticaldistributionofeachinputvariable 3and4).MalathionhadthehighestandPBOhadthe usedtocalculatetheRQs.Eachoftheinputvariables lowestRQsofthechemicalsassessed(Tables3and4). wassampledsothatitsdistributionshapewasrepro- SurfaceResidualSpray.Adultmaleandfemaleex- duced.Thevariabilityforeachinputwaspropagated posuretolambda-cyhalothrin,bifenthrin,andchlor- intotheoutputofthemodelsothatthemodeloutput pyrifosexceededtheRQLOCatthe50th,90th,and reßected the probability of values that could occur. 95th percentiles (Tables 3 and 4). Cyßuthrin and Weperformedthisbyusing20,000iterationswiththe cypermethrin were below the RQ LOC for both assumptionsoutlinedinTables1and2.Wetruncated groups(Tables3and4).Adultmaleexposureatthe respiratoryrate,bodyweight,percentsurfaceareaof 95th percentile ranged from 0.003 to 0.083 mg/kg twohands,airconcentrations,andspraydepositionat BW/d(Table3).Adultfemaleexposureatthe95th zerobecauseitisnotpossibleforthesequantitiesto percentile ranged from 0.003 to 0.09 mg/kg BW/d havenegativevalues. (Table 4). Lambda-cyhalothrin had the highest and Sensitivityanalysiswasperformedusing20,000it- cypermethrin had the lowest RQs of the chemicals erationsonuncertainparameters(airconcentrations, assessed(Tables3and4). 698 JOURNALOFMEDICALENTOMOLOGY Vol.46,no.3 Table4. Adultfemaleacuteandsubchronicprobabilistictotalpotentialexposure(PE )a(mg/kgBW/d)andriskquotients(RQ)b total atthe50th,90th,and95thpercentiles Acuteexposure Subchronicexposure Percentile 50th 90th 95th 50th 90th 95th Resmethrin PE 0.0003 0.0006 0.0008 0.0001 0.0002 0.0003 total RQ 0.003 0.006 0.008 0.001 0.002 0.003 Malathion PE 0.002 0.005 0.007 0.0004 0.0008 0.001 total RQ 0.017 0.038 0.048 0.005 0.012 0.015 PBO PE 0.0002 0.0004 0.0004 0.00009 0.0001 0.0002 total RQ 0.00004 0.00006 0.00007 0.0006 0.001 0.0011 Pyrethrins PE 0.0003 0.0007 0.0009 0.00002 0.00004 0.00005 total RQ 0.0045 0.01 0.013 0.0004 0.0009 0.0011 Lambda-cyhalothrin PE 0.08 0.009 0.09 0.031 0.035 0.036 total RQ 32.17 35.91 36.93 31.62 35.36 36.39 Cyßuthrin PE 0.0029 0.0032 0.0033 0.00042 0.00047 0.00048 total RQ 0.14 0.16 0.017 0.017 0.019 0.02 Bifenthrin PE 0.017 0.019 0.02 0.0009 0.001 0.0011 total RQ 1.74 1.94 1.99 0.063 0.071 0.073 Chlorpyrifos PE 0.009 0.01 0.011 0.0003 0.00041 0.00043 total RQ 1.79 2 2.06 1.27 1.42 1.46 Cypermethrin PE 0.008 0.009 0.01 0.0001 0.00017 0.00018 total RQ 0.084 0.094 0.l 0.003 0.0034 0.0035 aPE isestimatedbyequations6Ð9. total bRQ(cid:2)PE /referencedose. total BW,bodyweight;PBO,piperonylbutoxide. SubchronicRisk theydidnotexceedtheNOAELs.Forexample,acute adultfemaleexposureatthe95thpercentileforlambda- Truck-MountedULV.Riskquotientsdidnotexceed cyhalothrin,bifenthrin,andchlorpyrifoswas37,2,and theRQLOCatthe50th,90th,and95thpercentilesfor 2% of the NOAEL, respectively. Subchronic adult anygroupandchemical(Tables3and4).Totaladult female exposure at the 95th percentile for male exposure at the 95th percentile ranged from lambda-cyhalothrin,bifenthrin,andchlorpyrifoswas 0.00008to0.001mg/kgBW/d(Table3).Totaladult 36,1.9,and1.5%oftheNOAEL.Withourconservative female exposure at the 95th percentile ranged from 0.00005 to 0.001 mg/kg BW/d (Table 4). Malathion had the highest, whereas pyrethrins had the lowest, Table5. Sensitivityanalysis(percentcontributionoftheinput RQsofthechemicalsassessed(Tables3and4). variabletotheoutputvariance)ofuncertainfactors(airconcen- Surface Residual Sprays. Adult male and female trations,spraydeposition,dermalconversionfactor,anddermal exposuretolambda-cyhalothrinandchlorpyrifosex- exposure)usedinthetruck-mountedultra-low-volumeacuteand ceededtheRQLOCatthe50th,90th,and95thper- subchronicexposuresforresmethrin,malathion,PBO,andpyre- thrins centiles(Tables3and4).Cyßuthrin,bifenthrin,and cypermethrin were below the RQ LOC for both Subchronic groups(Tables3and4).Adultmaleexposureatthe Acuteexposure exposure 95th percentile ranged from 0.0004 to 0.03 mg/kg Adult Adult Adult Adult BW/d(Tables3and4).Adultfemaleexposureatthe males females males females 95th percentile ranged from 0.0001 to 0.036 mg/kg Resmethrin BW/d(Tables3and4).Lambda-cyhalothrinhadthe Airconcentrations 90.7a 99.9 96.8 100.0 highestandcypermethrinhadthelowestRQsofany Spraydeposition 9.2 0.1 3.2 0 chemicalassessed(Tables3and4). Dermalconversionfactor 0 0 0 0 Dermalexposure 0 0 0 0 Malathion SensitivityAnalysis Airconcentrations 88.6 98.9 99.3 99.2 Spraydeposition 10.9 0.8 0.5 0.6 Sensitivity analysis of acute and subchronic expo- Dermalconversionfactor 0.4 0.2 0.2 0.2 Dermalexposure 0.1 0 0 0 sures from truck-mounted ULV chemicals showed PBO thatairconcentrationscontributedthelargestamount Airconcentrations 56.8 49.8 47.6 47.7 ofvariancetotheoutput,followedbyspraydeposi- Spraydeposition 33.0 36.2 43.2 35.5 tion,dermalconversionfactor,anddermalexposure Dermalconversionfactor 7.8 11.1 6.5 12.6 Dermalexposure 2.4 2.9 2.7 4.2 foradultmenandwomen(Table5). Pyrethrins Airconcentrations 89.8 100.0 71.3 99.7 Spraydeposition 10.2 0 28.6 0.3 Discussion Dermalconversionfactor 0 0 0 0 Dermalexposure 0 0 0 0 AlthoughtheLCPÕsuseofresidualspraysresulted in exposures to lambda-cyhalothrin, bifenthrin, and aPercentcontributionoftheinputvariabletotheoutputvariance. chlorpyrifos that may have exceeded the RQ LOC, PBO,piperonylbutoxide. May2009 SCHLEIERETAL.:TALLILAIRBASELCP 699 assumptions, exposures at the 95th percentile most Inthisanalysisofrisks,wedidnotprobabilistically likelywouldnotresultinadverseeffectstoadultmen assessPPMssuchaspermethrin-impregnatedBDUs, andwomen.Despitethefrequentapplicationsinthe bednets,andrepellentsbecauseofthelackofdocu- LCP,ourresultssupportpreviousriskassessmentre- mentedvariabilitydatafortheseexposurescenarios. sultsthatexposuretotruck-mountedULVinsecticides Macedo et al. (2007) showed that the use of per- are most likely negligible (Peterson et al. 2006, methrin-impregnated BDUs and bednets presented Macedoetal.2007,Schleieretal.2008). negligible risk to military personnel for acute, sub- To predict deposition and air concentrations, we chronic((cid:6)180d),andchronicexposures((cid:5)180d). usedAERMOD,whichisanindustrialplumemodel An exposure assessment of permethrin-impregnated thatisnotdesignedforULVapplications.However, BDUs in the German military showed that the con- AERMOD was the most appropriate model for air servativeriskestimatesofMacedoetal.(2007)sufÞ- concentrationsanddepositionontosurfacesbecause ciently protected human health (i.e., they overesti- thereisasubstantialdatagapinairconcentrationsand mated exposures by (cid:1)16-fold) (Appel et al. 2008). fateofinsecticidesindesertenvironments.Previous Antwietal.(2008)showedthatadultmenandwomen studies of truck-mounted ULV applications in tem- exposed to DEET concentrations (cid:3)40% exceed the perate and subtropical climates have observed LOC for subchronic ((cid:6)180 d) exposures, but expo- 1Ð22.3%oftheinsecticidesprayedduringapplication sures did not exceed the LOC for the acute and settledontotheground,withconcentrationsdecreas- chronic((cid:5)180d)scenarios. Inadditiontoriskfromtheinsecticides,thereare ingsubstantiallyover36h(Tuckeretal.1987,Moore alsorisksofcontractingleishmaniasis.Theminimum et al. 1993, Tietze et al. 1994, Knepper et al. 1996). Þeldinfectionrateoffemalesandßieswas1.5%in2003 Concentrations found in previous Þeld studies are (cid:1)0.6Ð12.5%ofwhatwasmodeledusingAERMOD. and2%in2004,with(cid:1)15%ofthosefemalesandßy pools ((cid:1)12 sand ßies per pool) testing positive for Inadditiontodepositionontosurfaces,weuseda leishmaniasis parasites that cause human disease ßagger exposure scenario to model deposition onto (Colemanetal.2006).Thisindicatestheprobability skin,whichwasdesignedforagriculturalapplications. thatabitecouldresultinleishmaniasisinfectionwas The default ßagger scenario in the U.S. EPA PHED overestimatesexposureby(cid:1)40%,supportingthecon- (cid:1)0.3%.Witheachadditionalbite,theirriskincreased, andsomesoldiersatthebasereceived(cid:5)1,000bitesper servatismofthemodel(Driveretal.2007). night(Colemanetal.2006). Fortheresidualsprays,weassumedthattherewas The risks are not limited to the insecticides and nodegradationduringthe165-dperiod.Previousstud- infectionbyleishmaniasis;therearealsorisksfromthe iesexaminingd-phenothrin,d-tetramethrin,andres- curativemedicaltreatments.Currentlytherearethree methrinshowedthatthehalf-lifeoftheinsecticides approvedmedicationsthathaveshowneffectiveness was(cid:1)31Ð75donßoorsandwalls(Matobaetal.1998a, intreatingleishmaniasis:antimonials,miltefosine,and b).However,thesestudieswerecarriedoutinhouses amphotericinBdeoxycholate.Antimonialsareusedas andnottents;therefore,moredataareneededonthe the Þrst line of treatment in leishmaniasis, whereas persistenceofresidualspraysontentsurfaces. miltefosineisusedwhenpatientsdonotrespondto Inadditiontouncertaintiesindeposition,aircon- antimonialsorrelapse(Aronsonetal.1998).Thecost centrations,andbreakdownofinsecticides,thereare effectiveness (U.S. $/death averted) of treatment is alsotoxicologicaluncertaintieswithrespecttoPBO. highestformiltefosineandantimonialsbecauseofthe PBO has been shown to increase the toxicity of py- relativelylowcost;however,themosteffectivetreat- rethroids and pyrethrins to aquatic organisms, but mentforleishmaniasishasbeenshowntobeampho- thereisnoindicationthatPBOactsasasynergistin tericinBdeoxycholate,whichcosts$30to$40more mammals(Knowles1991,Pauletal.2005,Amweget per patient than antimonials (Vanlerberghe et al. al. 2006, U.S. EPA 2006a). If a 10-fold uncertainty 2007). factor was applied to the RfDs based on the toxico- AntimonialsmustbeadministeredbytheU.S.mil- logical uncertainties of PBO synergizing with res- itary under an experimental protocol at approved methrinorpyrethrins,neitherwouldexceedtheRQ medicaltreatmentfacilitiesbecausetheyarenotreg- LOC, which is comparable to past risk assessments isteredforuseintheU.S.(AFPMB1999,Weinaetal. (Petersonetal.2006,Macedoetal.2007,Schleieret 2004).Duringtreatment,3.2Ð60%ofpatientsexperi- al.2008). enced arthralgias, myalgias, anorexia, herpes zoster, Ourtruck-mountedULVsensitivityanalysisissim- nausea, vomiting, diarrhea, abdominal pain, chest ilartothestudyperformedbySchleieretal.(2008), pain, local pain, headache, rash, itching, and fever showingthatairconcentrationsanddepositionofin- (Aronson et al. 1998, Mohebali et al. 2007). Sodium secticides onto surfaces contributed the largest stibogluconate and meglumine antimoniate have amount of variance to the model output. Acute and shown cure rates of 88.3Ð97% (Aronson et al. 1998, subchronic inhalation exposure, hand contact with Mohebalietal.2007).Thesideeffectsofmiltefosine sprayedsurfaces,anddermalexposurecontributed95, are nausea, vomiting, diarrhea, motion sickness, ab- 4, and 1.5% on average to the overall exposure, re- dominalpain,coughing,headache,itching,andfever spectively, which is comparable to past risk assess- andhavebeenobservedin1Ð41.4%ofpatientsduring ments (Peterson et al. 2006, Macedo et al. 2007, treatment(Sotoetal.2004a,Mohebalietal.2007).The Schleieretal.2008). curerateformiltefosinewas(cid:1)50%(Sotoetal.2001, 700 JOURNALOFMEDICALENTOMOLOGY Vol.46,no.3 2004a, b; Mohebali et al. 2007). Amphotericin B de- Aronson, N. E. 2007a. Leishmaniasis in American soldiers: oxycholatehasbeenapprovedbytheU.S.Foodand parasitesfromthefront.InW.M.ScheldandJ.Hughes DrugAdminstrationforthetreatmentofleishmaniasis (eds.),Emerginginfections7.ASMPress,Washington,DC. (Herwaldt1999).ThesideeffectsofamphotericinB Aronson,N.E. 2007b. Leishmaniasisinrelationtoservicein deoxycholate are back pain, sweating, headache, di- Iraq/Afghanistan, U.S. Armed Forces, 2001Ð2006. Med. SurveillanceMon.Rep.14:2Ð5. arrhea,itching,shivering,respiratorydistress,and/or Aronson,N.E.,G.W.Wortmann,S.C.Johnson,J.E.Jackson, cardiac arrhythmia, which have been observed in R.A.Gasser,A.J.Magill,T.P.Endy,P.E.Coyne,M. (cid:6)40%ofpatients(Bermanetal.1998,Muelleretal. Grogl,P.M.Benson,etal. 1998. SafetyandefÞcacyof 2008).TreatmentwithamphotericinBdeoxycholate intravenous sodium stibogluconate in the treatment of hasacurerateof(cid:1)92%after6mo(Sundaretal.1997, leishmaniasis:recentUSmilitaryexperience.Clin.Infect. Muelleretal.2008). Dis.27:1457Ð1464. Despitefrequentapplicationsandmultipathwayex- Berman,J.D.,R.Badaro,C.P.Thakur,K.M.Wasunna,K. posures, our probabilistic estimates of exposure to Behbehani,R.Davidson,F.Kuzoe,L.Pang,K.Weera- lambda-cyhalothrin, bifenthrin, and chlorpyrifos ex- suriya,andA.D.M.Bryceson. 1998. EfÞcacyandsafety of liposomal amphotericin B (AmBisome) for visceral ceededtheRQLOCbutdidnotexceedtheirrespec- leishmaniasis in endemic developing countries. Bull. tiveNOAELs.Becausetheresidualsprayapplications W.H.O.76:25Ð32. didnotseemtoaffectsandßypopulationsorprotect Coleman,R.E.,D.A.Burkett,J.L.Putnam,V.Sherwood, soldiers, future uses could be discontinued to lower J.B.Caci,B.T.Jennings,L.P.Hochberg,S.L.Spradling, the risks from insecticides. Furthermore, the health E. D. Rowton, K. Blount, et al. 2006. 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