Chem|stry of Lnv|ronmenta| 1ox|cs ort|and State Un|vers|ty May 2S, 2008
1he Case for uu1 ln Lhe 8aLLle AgalnsL Malarla 8.A. eLers
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uurlng Lhe second world war Swlss chemlsL aul Permann Muller dlscovered Lhe amazlng effecLlveness of uu1 agalnsL mosqulLoes and Lhe spread of malarla. lor Lhls feaL he was awarded Lhe nobel rlze for hyslology of Medlclne ln 1948. AfLer Lhe war uu1 was used LhroughouL Lhe world as an agrlculLural and lndusLrlal lnsecLlclde. lL was noL unLll 1962 when Amerlcan blologlsL 8achael Carson publlshed her book 5lleot 5ptloq LhaL Lhe envlronmenLal lmpacLs of uu1 become wldely known publlc knowledge. (earce, 2007) ln Lhe pages of 5lleot 5ptloq uu1 was descrlbed as an exLreme LhreaL Lo wlldllfe, parLlcularly blrds, LhaL also had Lhe poLenLlal Lo cause cancer ln human belngs. (Carson, 1962) Carson's research led uu1 Lo be banned ln Lhe u.S. ln 1972 and Lhe resL of Lhe world followed sulL bannlng uu1 for agrlculLural use worldwlde under Lhe SLockholm ConvenLlon. Lven under Lhls convenLlon Lhe use of uu1 ls sLlll allowed ln some speclal cases, parLlcularly for dlsease conLrol ln Lhe developlng world. (!ohn aull, 2007) ln Lhe pasL several years however, Lhere has been a new push spurned by several dlfferenL worldwlde organlzaLlons Lo lncrease Lhe use of uu1 as a publlc healLh Lool. (Clauslusz, 2007) 1hls change of hearL for a chemlcal whose negaLlve effecLs have been Lhoroughly documenLed has goLLen Lhe aLLenLlon of Lhe malnsLream medla lncludlng arLlcles ln perlodlcals llke ulscover Magazlne and dally newspapers llke Lhe Wall SLreeL !ournal. 1he clalm by Lhe proponenLs of uu1 ls LhaL uslng Llny amounLs of Lhe chemlcal ln a LacLlc known as lndoor resldual spraylng or l8S has beneflLs LhaL far ouLwelgh Lhe envlronmenLal and human healLh cosLs. 1haL ls, Lhe conLrolled use of uu1 ln developlng counLrles can save Lhousands of people from malarla and oLher lnfecLlous dlseases each year. roponenLs of uu1 argue LhaL afLer 60 years of use Lhere ls sLlll no solld evldence of any human harm from uu1." ln facL u.S. resldenL 8ush launched Lhe resldenL's Malarla lnlLlaLlve (Ml) ln 2003 wlLh Lhe expllclL alm of uslng all Lhe besL meLhods for prevenLlng Lhe dlsease. As a resulL, lasL year, uu1 was procured wlLh Laxpayer funds" for use ln Lhe developlng world. (8aLe, 2007) 1he valldlLy of clalms llke Lhose made above ls Lhe sub[ecL of many heaLed debaLes LhaL have spanned over slxLy years and provlded fundlng for hundreds of research pro[ecLs. Croups llke Lhe WPC, Lhe Amerlcan 1he Case for uu1 ln Lhe 8aLLle AgalnsL Malarla 8.A. eLers
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LnLerprlse lnsLlLuLe, and Lhe clvll rlghLs group Congress of 8aclal LquallLy argue for Lhe use of uu1 whlle envlronmenLallsLs groups such as Lhe unlLed naLlons LnvlronmenLal rogram and Lhe SllenL Sprlng lnsLlLuLe. 1he debaLe ls furLher funded by blg chemlcal buslnesses lncludlng Lhose LhaL produce uu1 and oLhers LhaL produce popular alLernaLlve chemlcals, llke pyreLhrold lnsecLlcldes. ln order Lo undersLand Lhe envlronmenLal and human healLh lmpacLs of uu1 lL ls lmporLanL flrsL Lo noLe Lhe properLles and chemlsLry of Lhe chemlcal. uu1, llke many oLher lnsecLlcldes ls an organochlorlne. lLs luAC name ls 4,4'-(2,2,2- LrlchloroeLhane-1,1-dlyl)bls(chlorobenzene) and lLs baslc sLrucLure ls shown ln flgure 1. 8ecause of lLs large sLrucLure LhaL lncludes Lwo chlorlnaLed benzenes and Lhe hlgh elecLronegaLlvlLy of chlorlne, uu1 ls nearly lnsoluble ln waLer buL ls very soluble ln faLLy Llssues. ln Lhe envlronmenL uu1 breaks down lnLo Lwo ma[or meLabollLes, uuL (1,1- dlchloro-2,2-bls(p-dlchlorodlphenyl)eLhylene) and uuu (1,1-dlchloro-2,2-bls(p-chlorophenyl)eLhane). (ueparLmenL of PealLh, 2002) uu1 works as an effecLlve lnsecLlclde by lnLerrupLlng Lhe nervous sysLem's chemlcal communlcaLlon sysLem ln Lhe LargeL organlsm. ln Lhls fashlon lL lnhlblLs Lhe chollnesLerase enzyme from breaklng down aceLylchollne, Lhus lncreaslng Lhe chemlcal levels of aceLylchollne ln neuromuscular paLhways. 1hls causes Lhe muscles of Lhe LargeL organlsm Lo spasm erraLlcally and, dependlng on dosage, can be faLal. 1oxlns of Lhls Lype are found naLurally ln venomous snakes and are synLheslzed for use ln many lnsecLlcldes as well as Lo a greaLer degree of poLency ln mlllLary grade nerve agenLs llke vx polson gas. (AmenLa, 2006) 1he negaLlve effecLs of uu1 on blrds ls well documenLed and Lhese days ls mosLly unchallenged. 1he problem occurs when hlgher Lrophlc organlsms llke blrds feed on lower organlsms LhaL may have lngesLed non- faLal doses of uu1. 8ecause of uu1's llpophlllc properLles lL ls llkely Lo bloaccumulaLe ln blrds LhaL are consLanLly I|gure 1: Chem|ca| Structure of DD1 (prov|ded by W|k|ped|a under the GNU L|cense) 1he Case for uu1 ln Lhe 8aLLle AgalnsL Malarla 8.A. eLers
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feedlng on lnsecLs and reach Loxlc levels over Llme. 1he mosL lmporLanL of Lhese effecLs ls egg shell Lhlnnlng buL also lncludes reproducLlve dlsorders and neurologlcal effecLs whlch Lrlgger a very hlgh morLallLy raLe ln generaLlons of blrds. (ueparLmenL of PealLh, 2002) 1he focus of Lhe laLesL debaLes has been Lhe human healLh rlsks assoclaLed wlLh uu1, parLlcularly relaLed Lo cancer. lor every research paper LhaL has been wrlLLen Lo prove a dlrecL llnk beLween uu1 and cancer ln human paLlenLs Lhere seems Lo be several rebuLLal papers almed aL dlsprovlng lL. Many sLudles have focused on uu1's relaLlon Lo breasL cancer rlsk due ln mosL parL Lo fundlng and supporL by Lhe SllenL Sprlng loundaLlon. Powever a sLudy ln 1997 relaLlng blood levels of uu1 Lo breasL cancer rlsk among women llvlng ln Lhe norLh of vleLnam showed LhaL recenL and pasL exposure Lo p.p'-uu1 does noL play an lmporLanL role ln Lhe eLlology of breasL cancer among women llvlng ln a counLry wlLh a Lroplcal cllmaLe where lnsecLlclde use for mosqulLo conLrol ls common." (SchecLer, 1997) Lven sLlll Lhe LA sLlll malnLalns uu1 as a probable human carclnogen" clLlng several sLudles on raLs and mlce where Lumors were observed and sLaLlng LhaL uu1 ls sLrucLurally slmllar Lo oLher probable carclnogens, such as uuu and uuL." (uS LA, 1991) ConLlnulng ln supporL of Lhe llnk beLween uu1 and cancer a paper ln Lhe Annual 8evlew of ubllc PealLh ln 2004 llsLed Lhe PealLh LffecLs of Chronlc esLlclde Lxposure." 1he paper clLed several sLudles LhaL offered solld evldence on Lhe llnk beLween several pesLlcldes and many dlfferenL klnds of cancer lncludlng llnklng uu1 Lo prosLaLe, breasL and pancreaLlc cancer. (Alavan[a, 2004) llnally, a recenL sLudy appearlng ln Lhe CcLober 2007 lssue of LnvlronmenLal PealLh erspecLlves sLaLed LhaL prevlous sLudles were llmlLed by Lhe lnablllLy Lo measure exposure ln young women durlng perlods of Lhe heavlesL uu1 use. ConsequenLly, mosL of Lhese sLudles observed very low levels of [uu1]." 1hls sLudy found a sLaLlsLlcally slgnlflcanL 3-fold lncreased rlsk of breasL cancer among women who were born afLer 1931. 1hese women were under 14 years of age ln 1943 when uu1 came lnLo wldespread use and mosLly under 20 years as 1he Case for uu1 ln Lhe 8aLLle AgalnsL Malarla 8.A. eLers
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uu1 use peaked. Women who were noL exposed Lo [uu1] before 14 years of age showed no assoclaLlon beLween uu1 and breasL cancer." (Cohn, 2007) 8egardless of whlch research one may LrusL, Lhere ls clearly good reason for concern as Lo Lhe healLh effecLs of chronlc exposure Lo uu1. new meLhods have been developed LhaL do noL lnvolve wlde spread blankeL" spraylng of uu1 by alrplanes over large urban areas. 1hls lncludes Lhe use of Lhe aforemenLloned lndoor resldual spraylng as well as uslng garmenLs and bed neLs LreaLed wlLh Lhe pyreLhrold lnsecLlclde ermeLhrln. 8lck SLekeLee, dlrecLor of sclence for Lhe Malarla ConLrol and LvaluaLlon arLnershlp ln Afrlca, a program funded by Lhe CaLes loundaLlon has sald lL ls very clear LhaL Lhere ls no slngle approach Lo conLrolllng malarla LhaL geLs you sufflclenL beneflLs. We have chemlcals elLher as drugs or lnsecLlcldes. l Lhlnk Lhere ls unlversal consensus LhaL nelLher one alone wlll solve Lhls." (Lublck, 2007) 1he alLernaLlves Lo spraylng uu1 are noL above susplclon elLher. 1oplcal appllcaLlon of ermeLhrln on uLL1 (anoLher popular Loplcal lnsecL repellenL) were shown Lo cause sensorlmoLer deflclLs and dlfferenLlal alLeraLlons" ln laboraLory raLs. (Abou-uonla, 2003) ln any case Lhe quesLlon LhaL remalns ls Lhe same one LhaL was posed slxLy years ago when uu1 was flrsL used as an lnsecLlclde. uo lLs beneflLs ln Lhe flghL agalnsL Lhe spread of malarla ouLwelgh lLs healLh rlsks? lLs low cosL, ease of manufacLure, and avallablllLy make lL a very aLLracLlve opLlon for Lhe developlng world and lLs hlsLorlcal efflcacy ln lowerlng Lhe malarla morLallLy raLe ls well esLabllshed. WlLh Lhe WPC esLlmaLlng beLween 300 mllllon and 300 mllllon cases of malarla every year resulLlng ln more Lhan one mllllon deaLhs, wlLh mosL of Lhese occurrlng ln Afrlca, and mosLly Lo chlldren under Lhe age of 3, ls Lhe use of uu1 worLh lL ln curblng Lhls Lragedy? ln order Lo assess Lhls flnal plece a rlsk analysls model was developed by SLeve Corln 8Sc. and Sean A Weaver hu. aL vlcLorla unlverslLy ln WelllngLon new Zealand. 1helr concluslon: When comparlng Lhe lnfanL morLallLy rlsk from malarla wlLh lnfanL morLallLy from uu1 Lhe resulLs suggesLed LhaL Lhe neL beneflL of uu1 appllcaLlon relles on cerLaln 1he Case for uu1 ln Lhe 8aLLle AgalnsL Malarla 8.A. eLers
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assumpLlons assoclaLed wlLh Lhe LoxlclLy of uu1. When Lhe analyLlcal model was run based on Lhe besL esLlmaLes avallable of Lhe lmpacL of uu1 on lnfanL morLallLy, Lhe cosLs of uu1 appllcaLlon ouLwelghed Lhe poLenLlal beneflLs ln areas of low endemlclLy. Accordlng Lo Lhls analyLlcal meLhod Lhe only slLuaLlon where uu1 for malarla conLrol had a clear neL beneflL ln relaLlon Lo lnfanL morLallLy was when Lhe malarla morLallLy raL was very hlgh (e.g. Lhe equlvalenL of a malarlal epldemlc). Cur assessmenL concluded LhaL Lhe neL beneflLs of uu1 lndoor resldual spraylng for malarla conLrol are aL besL marglnal and recommends conslderaLlon of less Loxlc, cosL effecLlve alLernaLlves such as lnsecLlcldal neLs." (Corln, 2003) ln llghL of Lhe resulLs from Lhls sLudy and Lhe myrlad of sLudles done LhroughouL Lhe pasL slxLy years lL can be concluded LhaL uu1 should sLlll only be used as a lasL resorL Lo conLrol malarla epldemlcs. ln Lhe meanLlme every efforL should be made Lo curb Lhe spread of malarla Lhrough alLernaLlve meLhods and conLlnulng research should be supporLed Lo beLLer deLermlne Lhe Lrue healLh effecLs of lnsecLlcldes lncludlng uu1 as well as Lowards dlscoverlng new, safer, cosL effecLlve meLhods of curblng Lhe malarla epldemlc ln Lhe developlng world.
1he Case for uu1 ln Lhe 8aLLle AgalnsL Malarla 8.A. eLers
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kLILkLNCLS AmenLa, lrancesco, AnLonleLLa ul 1ulllo, Marla arneLLl, Lucllla, and khosrow 1ayebaLl, Seyed. ChollnesLerase lnhlblLors: lrom Weapons, Lo esLlcldes, Lo CognlLlon Lnhanclng urugs." CurrenL Lnzyme lnhlblLlon 2.3 (2006): 249-39 Alavance, Mlchael C.8., Poppln, !ane A., and kamel, lreya. PealLh LffecLs of Chronlc esLlclde Lxposure: Cancer and neuroLoxlclLy." Annual 8evlew of ubllc PealLh. 23 (2003): 133-97. Avly-uonla, Mohamed 8., uechkovskala, An[ellka M., ColsLeln, Larry 8., eL al. Co-exposure Lo yrldosLrlgme bromlde, uLLL1, and/or ermeLhrln causes sensorlmoLor deflclL and alLeraLlons ln braln AceLylchollnesLerase acLlvlLy. harmacology, 8lochemlsLry and 8ehavlor. 77 (2004): 233-62. 8aLe, 8oger. LasL Chance for uu1." 1he Wall SLreeL !ournal. nov. 3, 2007: A19 8erenbaum, May. lf Malarla's Lhe roblem, uu1's noL Lhe Cnly Answer." WashlngLon osL !une 3, 2003: 803 Carson, 8achael. SllenL Sprlng, 104 LdlLlon. new ?ork: Marlner 8ooks. 2004 (1962) Cohn, 8arbara A., Wolff, Mary S., Clrlllo, lera M., and SholLz, 8oberL l. uu1 and 8reasL Cancer ln ?oung Women: new uaLa on Lhe Slgnlflcance of Age aL Lxposure." LnvlronmenLal PealLh erspecLlves. 113. 10 (2007) 1406-14. Corln, SLeve and Weaver, Sean A. A rlsk analysls model wlLh an ecologlcal perspecLlve on uu1 and malarla conLrol ln SouLh Afrlca." !ournal of 8ural and 1roplcal ubllc PealLh. 4 (2003): 21-32. Clauslusz, !osle. uu1 may be a useful publlc-healLh Lool - unLll lLs effecL wears off." ulscover Magazlne. nov. 20, 2007 lnLegraLed 8lsk lnformaLlon SysLem: p,p'-ulchlorodlphenylLrlchloroeLhane (uu1) (CAS8n 30-29-3). May 1, 1991. unlLed SLaLes LnvlronmenLal roLecLlon Agency. May 23, 2008 [hLLp://www.epa.gov/ncea/lrls/subsL/0147.hLm]. Lublck, naoml. uu1's 8esurrecLlon". LnvlronmenLal Sclence & 1echnology. 41.18 (2007): 6323-3 aull, !ohn. 1oxlc colonlallsm." new SclenLlsL: 196.2628 (2007): 23-23 earce, lred, Pow Lhe world leL malarla of Lhe hook." new SclenLlsL. CcLober 6, 2007: 38-39. 8oll 8ack Malarla, World PealLh CrganlzaLlon, unlCLl. World Malarla 8eporL. 2003: 3-10. SchecLer, A, 1onlolo, p, ual, L.C., 1huy, L.1.8., Anu Wolff, Mary .S. 8lood Levels of uu1 and 8reasL Cancer 8lsk Among Women Llvlng ln Lhe norLh of vleLnam." Archlves of LnvlronmenLal ConLamlnaLlon and 1oxlcology. 33.4 (1997): 433-436. u.S. ueparLmenL of PealLh and Puman Servlces: ubllc PealLh Servlce Agency for 1oxlc SubsLances and ulsease 8eglsLry . 1oxlcologlcal roflle for uu1, uuL, and uuu. 2002