SUMMARY--OF TOXICOLOGICAL DATA 0y THE HERBICIDES William McBride, I CONFIDENTEAL SUBJECT . $024720 ff 739,907 pounds SUBJECT :?To PROTECTIVE cc: ~gr0Wth?hormohes (AshtOn,lF.M., Craft; A.S, VModq of 5(mitosis) and cell enlargmc acid}. '0Rbgister?d0ih'194814. I x? afe growth regulatofs,j The ?hc probcnt10300f0a?naturallYI rcg?latpr, indpleatetic acid.' iTh? military in?estigatibn by fbh??bxy.herbicidc uSed as a VCHUtatiOn Weapon-i? 1944f1945' I I I .Phenoxy herbicid?s Presently in Usuthday in Lhc'u'sf I 2i?435'T, Silva-xi, dichlorprop_? ?e?opbOp, 2,4-Dep 1975 the U.S.A. used 59 million po?nds of million pouhds Of and th milli?h pounds of silycx040: Ecpnomics huhd?odk?SL?nford n0R?s?ar?h Instit??e Menlo Park, Califorhia 1976, I 01m 1969; 115626,000 pounds of acid esters 'andfsalt? were produced in In 1070 the .~quahtity rose ?o 12,335,000'pOUhds. and 1074 WCre importtd avdruging .a tbtal of 148,000 pounds per year 5,Herbicide0rep0rt,? _,bocument EPA, Wash;ngton a The phenoxy herbicide @ahd??ncontrolled'?ay. It_iht?rferes with the regulation of growth: gprd?eSSCS normally governed bythe p1ants_own naturally dgcurring ?lCLj1)n (1F: 'Hurbici d?s Wiley Intersticn?e publishers; N.YQ 1973!; The phehoxy herbicides interfere with cell divisidn nt, food utilizatjoh and various Other cesses ne i 7 pic. . cessary to 111e, CONFIDENTML ._to'animals; Plant growth regUlating . SUBJECT PROTECTIVE ORDER .1,th phcnuxy an: Far more 'Stablefat_its melting point. this herbicide is with acetone; ?application generally contains 90 to 92% -3dutuilcd Scientists.do not know_?he pr?cisc mode or actinn. I?Of?cithicn natural plant_ gr?OWth regulator's. They toxic to gvucn pluan than? compounds act on plant cull' -compounds such as Cellulose and 1ignoccllulOse which are nut present in animals. 424,591? 2,4,5-TrichlorophcnOXy acetic acid has a Chemical formula, C8H C1301. ?Thc form oCCurs as and 5 iits weight-is 253,49 grams per mole. melts at.tempcrature$ of ilt is has solubility in wuL?n . million (-ppm) at 250C. Further solubilily octurs of 278 parts per .ethcr; and ethanol.1 Technical grade manuf?cturcd for agri?ultural: of the herbicide and 7 :3:10% impurities. I I compOSitinn 0? the herbicidn giVen by one 01.0 l. 0% 2,4, Tirichlurmihu-nnxyucobi-c ?(Sid-i. LU. U. 1% . 2,4, S-Tvrichlot-unnjisu?lk: I I 2.0 i acid; 9.0 0.3 0;1% bfiS- 2,4 S?Tr'icI?nr'ophcnoxyac?atic aci A n. .3 2 cv acid? I 0.2: 0-1% 504 I H. . II. smljum ?11,4 is); 1L 0.7% H,,o I luv +h+h iu1., u? i an _'rish?r, th. lp?tv .?ln pins; 515, 1f'ypupl hann?cn?IH-rlt with gliwlli-hi?cidte?l, .Ild'fgpill?l?mcn?t nl 'H?nxi 1977-, -E r?tizpul?Ith the gl? (Jiuxjn 1n 11?s. .pruducltjon 2,14,- 5;l'l' impala-rs Jaibuut- (1.11} I'I?hi? Wits ?5tIIipOI'i437d1b5? I 161-. Ragnar-fol: Cu-mwrf Vol 15 I (-L :11 Human Hivrth VPubliC? ll-(rulth; of llc?ellth, New Zealgmd?, 1977-. I Thermal starb'n' - isstuliln at ijts'vm?c'll'irhig; [mi n1, (156?-1 81' oc?lumnicn?l' degradatij Q-n' 2,4,5a?T Slnw'l'y in soil containing; organic under warmimoist, conditions. Half 11' the 'lumbicidu under {hose 'optimul (:undj Lions; (lppl'l?uihvh r? weeks, Metabolic degradation is causud by two concurrent 1 pfoc?sscs. Binding of th? hurhicid?>molhc?lc to Compounds, maihly glucose to Form u?d actual dggradation.gf "the molcCule. I ?Thrce is uS the timc s?an for the herbicide td diS?ppunrComplutuly fl?l-omv?tLhu soil. Disenppuar?unce rate is independent. 01' L110 ul" hur'bicii?dn present. liven ain?tlm presence. of :iunlight m-muins msanth vuly Rnsi duos A an. accumulation :1 product. for .1 jubrriml following; initial, upintHItJ'un. Rusitlu. occur qu-n Lln- in'ihil Th0 ul' m-Hidm- tun FIDE CT PROTE CAN px4oduICt is not, tubully Cause usv .l ?.uxiu lc-uw-s l'l?S?idllItHH Ill active form, Hu- ?mm-ml uml ?(Iur-utiun ul Lhu'l' Luxit'iLy must; . V., .. 69??20 recognised {nulv alppr'0pr-531m Full nwi-(l. (If the particul H'uil Sciontjj'jf? plu-nuxy f?d'H i (luvs ht-v'tk down in Soils -- Andus{ 1..J. Ih'vululnwn ul' ?orbicidC-S in soils. 1? and Lln- Snil li.Kf Wondl'mwl, 10.Sugar (eds), Blackwel] Sc] I'luh. OxInld [,nlgland. and 24-1) form carbon (linxidv, inorganic Chlol?idu and water as final .(lugru'ldatj on . glut. [y i'st out I'r-mn tn six wvuks for? a rumy purcum.? disuppuuruncv f?qu. studies by Stork M. Soil _i 'iun Himh-agr-ni inn (Human Microbial. and [1.15421in mtuhm?lcnl study UH: U.S. Lngistjp? -cmm_nund Lt??t- rungu Hill Utah l-?uncl nu?purtz, ?l?ucum pr?n?iucl. a No Duuwily pr'uvi gr'uund - Duquy Utah 1,975, "Arnoch ct 'l'lif'vu ynar's hi" studjilus on the .sui l, persistence and an-?umpnt nl' (mil TCDD - ,wt-v'c} Scienc? Soc: Am. Moot. [97$ dc:rnn??Lx?dLr:d appliuufh'ms of 2,4,5-1? and 2,4?1) at nmsSiVH not. only-did Hl-Q'l'j Itim- the Sui] but indvud HLOUHHIHLIUU U16 cal" micrul'lnt-n, .I-Ild that this HL.i.n1uluL.i.un m'ny lultwi- Ln ?Llw ul All?- herbicide. I in Llug Pacific Wu:ng SCivnc?Q, 251 5) 4l7, l?nl iiug'u, i?nr?t-?t. livhmr" and [Sui] I'nfr' 2,4, lusi'uns, sumnuu-isml in um .lnuv-nul mywm-(I Hnivmh- wvr'v Hm! within six months hvr'h'icidv t-?vsidUuH ilh?d {m within one ym'u' Ins?; Him/n pvrcan nli Lhu Inn-hicjdc Tho-y found h-oching ul' I'r'mn Llu- rum-st Hum" Lo and no I'numl than 15cm CONFIDENTIAL it . .11, "Chlox?Odioxins pt-Hl. i ?j mm, Vuhd ?Halo, 3? 171;]78, 19735 Vuund LhuL relatively in $011.15.: However; that nLOchvu?nvl. (lam-mum's- .?lt I(:unl vn-t. jncruusv?s. 2,4,5-1? il'll?ldt'lv'utvly muhilv in clay Hoilrivimd (mly m'ul'rh. l't'H i acids and esters are soluble in wutur. In uddltion rapidly dissipates in streams'hy dilutinn and photmlugr'adntion ?in wuLur 501-. Cr?oSby of in watcrl'J. Agr. Fund chgm., 21(6) 1052?:054, 1970. Research r?upur'ts involving" stream cuutumj nuMun H-mn land spraying in Or?ugdn donmner-utvd that peak nl '_phvnoxy herbicidcs's?ldtm HXCvud ppm, residuus vdrqu last for more than.a few hours in almost all'thh streams, . . see (Norris, L.A. et "The of in a Pacifib Forest: Srinnuu, 25(5) 417?, 1977), The report OF thu Advismr?y Conlm?ittcv on 2,4,5?1' Lu 1- the Administration 61" tho Stated that all data indicated that a/Small amount of,? is present-lth (luvs I ORDER pchiSt long because'clay or the bibta?abSorb Lhu herbicide 3 Lu within a matter of" days (F..P.A. Herbicidtf Ducumhnt I EPA Washington D.C., 1974). - 024.20 a? 7Animnl I'l'SidlU?H: A 2 An.i mu] r?usiduus . mm 1d accumu st? luwnum- ul lwr-hj (ii (In build?up elsewhere. Animals- rapidly eliminntc- About. (3 ?3777 4 I I I 5? 'rn Llu- m-c- (Hahn-r'hul'l PT ill - "Flu-I" I iv. pl'nl'jlv nl' .I'ul lnwinp; 197' int-ravenous administratjnu in Nuts." _Tox. App. Il?luu?m? 36: 401?501, (gt-1.1L. of 9 S-T n' RuLs I, Pilnw I I J. . ?baith Aspect/S anlm?idw? 2725 1073.?. Filly?!" notuq .Hs'igni ficant .i Lil?: 11'. I-runmin'j up; 5 lih.?hc dog as compared to the umounL Sh?q in.thu Lutf This .Mdelay?d LimL for ?5 Lu? d?g_js. 5 poSLulatcd as for grcu?er.toxi?iiy of herbicide to dogS {Jun} to patg,v JIUORIQH4 nl. "1Wurrcna1?lyandljuu in the Pd Co?s Tex; 314:: 197,6) Light; .bijw?ndili'xga pl" tho I - ?herbicide tuihthuvjifyil?ll's ?Ipt?uLIcin: ImpurTi-Hw's as" Lluf much-gin} Hm delay-(ed, ur'ii?u: Li'h (ling; I I A study by Gtgh?r'j nu. . "The. I :l'nticl 2 ,4 ?3 1'0116wihg? I st Ln 'l?nx?li; lih?rm. 1.973, 7 suggests that. human uI'LinQ ulmu?a?ld- {morn (2 para I 'Ivd- H'th? rate of in i 2 Years {Toxicity stud)" land bricognuriq study- nl.? -1g 'l?nx; .1979 set. .1135; work; "Residues do I . .?Tht! LP. 1055' l'r?nm "Hm" I?lunvi'ron'mcnt can" clu-micu 17? H5 huul Uh, -- "in various media'in. and Llu(:hunucals phyS'lca1.. 'DjOXins Recognised. in ?1957 as 'an' [impurity in the of herbicide TCDD is one hf. the most, potent small toxins known to man.? Small amoUnts of c?normoUS changes animalpells. Currently technical 2,4,54'1' in: U.S..V t'niminv'l?y h-Vvls utmnr? lwluw H. 1? ppm. 02472537. LIE ORDER. NFIDENTE AL To 9:20:qu gx?st5?as-u Whine 'I?rygiulii?cfsomjd:nuv1ng muleculur_w91ght'of 322 grams mole; Jt'meitg at temperatufvs 3050C. and ducOmpoxus 980 - About 99.5% 9f th d?uxxn' decompogus at thmvoruturus of uriSCH-v aarjng the of LutfachloroanZe the ihdustriaiprecursor of 2,4,S?Trichiorophonoxyu?cv I has a jaw water a hip? fuL sOlU?liity. Dioxih can gecumuLuL? in the en?;r6n?cntlundvt somu iio?n's .- huwuvu?r ls decomposed by: II I ?iighL-Which helps to diminish potenti?l accumulation.of an ?humrrul. I Crosby and wong (1977) - ?Enviro?mentul Degradation or Science, 195: 1337;1338 found that hgphicidu.' foymu]ationS With TCDD contamjnurd 1030 most or all their withih A single day when the leaves. or grass of'thf treated-foliage receiVe natural sunlight. Photochemical .Idechlorinutio? causvs.t?is degradation 9f TCDD. Whil?_thv st?hilify [of'pur? TCDD gs a p?rsistont residuv.in_th? ?nQirnnm?nL is it is not stable of its hefbicgdo-vchiC10; 'Appoafing on the foliage in a thin hfrbiCidQ film, the contaminoht dimi?isheSas it isjexp?S?a to 'Croshy'and Wong?ost?blighed_ :thf??_f?dUirCantS f?r significu?t?diOXin br?ukdoWn {h th dissglution iqia'light tranSmitting film. Th?l prQS?hce of an organic su?h as snlyunL OE pvnticidv\ -qnd (3)Iultruv1olut light.a Th?y propose that all three conditiuns ?azkginorm?tily 1r: Lhug' foe] data 'silguust than, [1 7 Voftcn will be cousidurubly I055 than previn?sly vxp?ctvd.? _c24?2? I a, - 1 SUBJECT TO. PROTECTIVE m. ?esiduo have mo?n?iixmml Hm 'I?Cmi ?lvw?l??v .i lland, ?Vwatcp ?.691: Various '11le Jun-wt play-t, ??siid?e levels comp?gr?c Lg? 'Jtlu; uiymui'ml ul' i-n?i t. i nl' ?i'uppl?icatiun and an: it?l? {unity I Llu- [Xm- cc?nn'hemy ul? Mile-iuulm, 'r??llciased a ?r?npbr?i n-MHi nu; nl'. hyf?pr?mluCL: 3 of' nor-mu], combustion Analyzing Samplt-S I'l'bm numle -Comvbu:st?ion primlutaturle [such as Automobil? exhausts, Firupjucv'snnt, pharpoul?grills{ Cigarette smoke and particulat?e ,(Emiss?tcm Vlf?lv?um q?antitiyely mo-asurud' thf-liunu'mnt, 'ul' "l?CDDii ?rescnt. (Dow chemical cbmp?ny Midluhdg'Michig?n, 1970.) f? I If envitr?wonnumtuj, [?r-Osch! or gdjioxins from Ibo {Ur?thgr cs?a?li?hcd .i?L Iwiil-l LcCOmc V'd'jfvf'iculit if n'g'c- ?lth-possible to link chvir?onmcr?xfatl residues uquiimcally and solely to spruinle Toxicitx: 'I'lu! way 01' ('Xlil'HSHillf; (:lu-mittuls mull.? Luxirity is Lin-nut. "its LDSU defined as the amount of chemical. Suffic Lent to cause ?duuth in 50% of the test. animalsvalue can dun to such variableb db am) ,sqx of test animals, state; i'nI-mulutj on' ul? ?LuxjcunL, Likluu rout-u o-l' adminisLI'a'Li'on? and temput'uturu. "Mudu nl' untrunm: and Chumjca] I'nrm nl' le Suhstumm (Tun-H.115? alternun nhsur'vahln'vi luct; .luvu] .1 :Cndpoint. Chumi?uls administered- (:nlnm:'r10 ilqu?l??u 1.- An 'i mu"! 5 tux ic Vui'l'ccts 21 4 i (It-mgmus ra?ngihg? from 10 mi I igr-mim pur? kilogrampi" body wvighl Any" I SUBJECT TO PROTECTIVE - . lldl?l?hw u! 5,4,9" 'ni? i c'ul Luxi wul'Uly - (I, ?Al Inn tJIXjC-j?tdyl "Vi ?1 ?my. app (:xpucfli-d by (Ii H'm-t wi! hin .n I I qu-ciq-s; - nu'ull?h? Clli?mic-?ll entrain-?- HHU HI. "iutly Jud lungHu-s or time I?m"th duration 01' is I'mulumvntul Lu any lu'xit-ulugiCU] A u'i affect an ?Ilnlii nu Ln-xiCiLy 'I?Cl)l) .?lI-v put-l 1w? .sillfl'y TCDI) Id-i -. In!) .t II?ilu- Inn-zui 1.. HLudy li'uxi? in Van MI I .nul. I Al ?nd V.u. I'lul' Iv( 'in (uumuninaz In vuntujnjnu luw 1.4.4 l-?nml (fusm. IS: dun-jun? Thu-S lmusf'tl- .ululL mu-h \u'k?i'l?llzu': ii! an qrnvi'rmmu-ul Hu-il' ?Mural lmhit'u'l (lm-H?n: muting Hu?l?ull, For six mouths!"invuhljgulmwt gram-u" ,lluilltil i'hd Ivnluhs (:unlr?ul I'm' the study. LIN: uml nl? this tinu~ Huey (lividvd ith twu ui'nunm nl' right. animals w?mh. Om: group was 'wa DIN "'l'llt: group :110 an? (Ind without. .?r'uod intake: was (?run-Huitinted} I?ol' (-zuth gltnup un-r [)vII-ihcl? hf imv. Al'Lut' six Un- ulul ?livlt ,2 Hus. l'umnlurs wur-v mul?ad Lh' ?(?llkv rum l'ul gum?. nvillw monLHs Um expur'inneutal animals Hm (livt .?gnd- ?imzt-Shad ,il Cuntt'ul (lit-t .m '..u dit ?mul- I Inn-v hay. .Rum-au-clun's ushi muted tuLal- I lit-51Hun-?- ll. I l7.? 2.01m ?ul Inwnm ntnu Hu- ?luv: . ?7 EAL, SUBJECT TO PROTECTIVE ORDER. .u 1 ?Lllt?h?n (?anges 0? '?x?gguruLcd iu':ix Qf the ?chu munkuys months an the dicL, mummy: Artur Lure? ?Opiulmj't?uj cucum, [0:55 of luCLuJ. Mum and gullu,? ?canmuutud and dry scaly ski-u". After six munth thc? (right Juimuls, cpncul??ud. Al? ?(ilu ?ix ?ninth, munlu-ys {Ilsa ?lnumuuglulnn .md ?lidcmatocrit? (?ill Ln I'cd culls). ,lhusc I-bcCumu especially- the nine mouths- uu uxpux'iuuenL (11' . Animals in the 'uxpcr'imcutul ghoul, ?at. weight. ?duapitg' nvo '.chungg: scvm?cly dual,? virtually. no platc1?L5 luxv-EI whim: blond (2011.5. in UN: following four- moule similar Clinical, changes and :01. unjijvn'uls .Lhut'sur'ViVUd Um [1:511an all. displayed. 'liuixt 1055 and [ml-ior-bjLu?J. ch-um. During the .uiinl l'uml uumLh the study, Um nmukc?y duwdeud a reduction inilmlh plululuLS unth wllet- blond culls. Autopby findings I'uvuulud Scum-.41 ur'cus- 01" damage .l"ucu-l . umjub; ul? llumuorr'hugu Appealicd in the lung and 5?Lmuucll,? adrenals, skeletal and burn.- nuu'l?ow. ?l"illgg:rngjils dlld_LQU nazils- grew .il'l'?agulquy; ul?Lcn accumpuniml lby'gimgruoub uucx'usja death olf Cull? surruuigdud by living 'Vu'lso sull'fgr'cd from .151:.iL1::. (an abnormal fluid in Ulc peritoneal 82%??33 Lin.- pm?i Loneum) Cuyjyy, II is age? J?-cuaus of ughcinumq,l Lujwr-c?ulusis .?ma i'nl'lqnunutiou: 01' dilatim?x?mL?Ium, and hydro-{Sic inn nl' ivnwulJ. unimuls. Thvi? IuI-?y- hurl uhqu-d markgd dilation $155091 utc?d ?ju?uudicc .. 4. - glands; Um in .lmnc marrow ur'nd hypt-N?lv?l lull.?- Ivl'uml "mi-(ling on many luvqls .nHl-yq-Iiul ly in the 'l'uucoLls if?nr." (?ch IN). lining 53/31;an nth?tru?sj?timuilxn I uf' of the ("Hm n?l' t-l?m eyelids). 'l'lmy Hm. Hm I'm- nm?x?lluimgnl primut (Mnnluq?! is I In: (blond .fpr'oanji?g A5 i?vo1?jllg the rm! liclm .{fol?m?tikm of Mpiltu hJ?io-Od Cullh? "and ?Imrw mun-row for (tn-.115 inn, in Ly. z-n?tlditimml ILIIa?vnulls, Hum-H (1150-7 ovccur?. .AHun .?Imd asse'r?t't Inn flu-Hr (i-I'i I'I'cl'vmzt-s Jive-vshuv?y tn ?mama ?i-nlnx?it?nl inn. "l'lu; tfungv (It-nth; In SUf'i. iqi an m-ulv Spin-?i: >uv?l. tfj'v?w, in Tum-11' ?110.30 01'; vairg M: hiu-ly'IinL-zhl, wily-'1- yji-Jdl illu- smult- wlu?n udhiinnguI-?Fcl (hi-r u, nine-month [Sid-rind.- Alilun . And Van Mi .115?. 1' . I hut MIL-?putlmlugicu] ('Tllulluqss' (n'utkvd' by 'tll? Cw? >(lum? lbw? I I'c-nm i 2(le i 4- mi Lil". 1, Vt l'uV-Iy'ln? Lln-?j 1' that luw i (ms 01?. Cill-l [)I'Ostcc w1' (lusprbud . ibus kn? hu? R"le "f .a 2 yen" chrome. LUXJCJ .jnul ?M'f'y I Ln rats. - . CONFIDENTEAL 4 c.2473: DDn?-h-r-n iv? A - Hun-m. 371L303, 107R, Wuru- I .. . pldcud rut?; nut-(I LO Sivvt'n iwml?kg' wirv huLtnm (Flak-<8. - Thin-(l .?lml wutv'l' uv1'11uM'v to ?this animals Ud l'j-bjillm- ?r (. 5f)" m'a?l??s 50 ['Inmn?l vs) in. diet? that Ln? two Year?s". ITIVIU. i of Mir (fun! '[erl'tilip? (?96 "1.1.10.9, 9.6 'l'unuili?s?) 172 ?1':th wily- Hu- ?no Tin?" "was by Dow chomirnl chnpu?ny I by Cnp?urc?: gas chromatogrfzillijl1y. I guild. l'?b?dqunmuanan (Li-Id 13H form-rips 'ilt lin' (?ju?h ?mOnU1s .st'udyhand al "ranting i?u-lx-ryuls Elli-hf- Puts picP-St?x m'npp urns-lulled sample's nil. tw-l'vv .?m?lil- [kunii .H?u-vnv' Sin?p] gs ,erux'OJhft?tml 54-wth 1. rats parlisg?x pol; group at. Silmfc I?L'iluui. ldwu?lsih. s-pcci t'i'c. p1?, sugulr? bi Jj.r-ubiu, it?! not (flu '1 f. 1. 00d . ,At terminal necropsy, investigator-.5 collected scrum. ?sumplc-H 'l?r-om? all survivors or - maximwh ol'. per Sex Lfr?nup In!" (l'utuf'mi nut. ion, - All rats dying or killed 'oi' Llu?y :51,me underwent?gross pathologic- and putrLinns ol' nm?jOr? organs and any lesion suggestjw- of sign-i [patholo?iic' o'r? tumour fumuatiun war-i: prim-rived, ?i n' .107. . CONFIDENTIAL SUBJECT co co CONFIDENTIAL 413::- Terminal (Examination Look p'lilCL? ht th. Mulh yhuys weighLS- ol? th? Igid?nn-Iy, height, Spleen, and wvr'u for; a ?maximumiofhlo r?u-tispojlrf' sr??x- pul? group. . l?spnu marrow sunk-ups.- also pf?ubill?cd; >"I?hcy {11,50 (mu/v. ul? fat, lchr? and?kiidnuy From a maximum of fj Vt: r?ats m'uup fox; pus-sibl?u- analysis..- . All Vr?u?ts from the Control and, thc? high dusc luv?ul? .?lngUP-dl?cssi of; whuthnb Idi?iud (l?ur'ihg? th courmf ?If. study- Vwere? Hits hjstu?logic i-(m ?l?ji?s'tol; tissues lintumlgd .Lu include .1 muj'nrui 14y It-h?osi?e ulmvc uml ?Lhum-r at. the Linus nl' 411 rats doSc luvois wcrur to histologi?ul ciun?n?ution of those selected tilssuus tl'ib-d Has .pd-S-sible? {liar-goth h'rl?va organs ini- addition to" grassla- S?gu'csti?: ?f'nr'nmt'inn. I I. I'l. I, - They L?puhd ?at the ?If-?lm study (1.) - {flutes-Minn. 0" (1101.3 Cunt-{linian 220? pup-1, I I (?nlglug/kgi/duy?) Itwo? ?ye?t'vsi? Cuungd- m-ulltzi pic. taxi? (including: body weight.- pp'nebsj'ou ui" Curtain hacmatollogical parameter-s,? increased urinary. ER (?XC?l-?Ot?ion 01? ms um: A-amj no luvulj nic acid. ?Incrr-nm-d 0RD Serum ilctivj GCT, and SCPT u'nd primarily of th l'issm- 01' the. hmly. 7 This; high (-1050. lawn]. seemed to I'udlu?n Hm im'idc-mm of 'Chl'nn?ic renal" disease .in aged mul?v rains. I l-?c-nmlc- I .nr7_ .C24.3o rats givml this high (lusts vl'm? two years had l?chnt in ]:ivi-r. 'l?his'compar?cs wj th 34,600 pm. [nu-sch! in Um Jivm- ul' I'vmulv 'l?ilL-S? grim-.11 this dose for LhirLI-vn wm?kh, Ihus' SUBJECT TO PROTECTIVE eating uLtui nun-m, ?of steady state in Ll?, purl-y (?ppt'nximhutrlY ill? pm. in (Hth .n [(?hglf?lf llh'Lfl't?fL? Luxicityi . l?lu- in! mum-{l i ul' - rowdy ihcfunscd ur?i?nul?y i m. nl' us (liumulmis ?1-1 iv?n. toxicity,- J'nplud i In}: an I?i-ncj (10mm 301"} ?l?mputncioiilulur' ?nkluluS 01' [but] .?llvcol url? in LIB: l?ungs'. 'l?m'minnli livhl' .?uul I?nl} Iul' 5100 and i7mL pp!" y; 'l'hi.sl cuihpurus with 371)? in?. [ire-{sent In Llu- li?vm" this dose leynl l. i i'uti?mv' at. a of 22 approx. ppt. in L-lw die-1.) (:ausud considered Ln be significant-v. ?l'lu- liwer Umd rut, uuch contujnml' lmxi?city ul' Uu-l can be cuns?idur'ml nsLM- ?l-Ql'm ul' 540 of TCDD at thu'ond gr [ifutimv ingusLion a; this u" a dorm AL Llu- th-e? nu Lnxi?: rcsponsu uttributul?u L6 inclusion of in dilj ly (lint. aims?. to rats a Lw0,yv;n- CONFIDENTIAL SUBJECT TO PROTECTIVE ORDER.- or Lime. ?l?nx i (?in 1} Summary: curitmninutcs 2,4, (LT, no ?CUIIHidnl?dluiull n?l' Lox] c. [Ly ul' Lhu lumbj cidc.? ?wiLhouL Drone:- attontj on (in Um Tuxip and mum?: mm with?: Ll) For t?angu from si'uuglh u'liqfurjn' HH- (Inf; to $00 if] rut (.?u?itl Fu' ()Is 9; 024?34 7 i' CONFIDENMAL TODD (hv inl' Lhu gli'ltuwi l5 ?JimThis nlipumsiul? dog?s ,Ih? Mining/kg. . high as Ilium; Lu. lnil i-u?i luxit'. rusponsu Lu appear?; git (inn?uLh?H .nf' InllIg/ku? in l-iu,? ?(Ing and (fo?iilLOb? tn .in the momma Wright. mum-ii- wi-nluu-ss'nml Mtvumpun-ying tissue Changes r-upijvm-ul L-hi? mqu ('unmmn ul' 2,4,5?1' l?hxicilty. In .1 _lwn yinu' >4.me (Intni in]; nil' le?umiv?lhiwli-y ruins, iul. (1070) usci-l-mlimgd laws] (Ring/kg) whum: tlu- uriinul'l-s tilnxic el'l'uci? I'rmn (:h?imnic hvithiridv [hm-d in this. prin?iui?. was. ('uiltuin?inf; ppl) (?Tumunil'irihi munpit-h'nl' lihv I'Hlli im-l)? 'l'lu- .l rit'SHIi'I' (lv?l'uv, Lht: thlH? ?nd home inurruw including: '(IyScruhius dnr?j Vud l?i'nm dam-ago there) urn thi- which ?:xhihit u' Luxig: r'usnunm? in Two. ?Micu are least senSitiv'u Ln toxic (-i'l'ucts, Quint-.1 pig?s Hind ChiCkH Sui'l'ur? thu gl-vuhrsl. Initial i-nxit? .?ippi-JII?H Hinultx nl? .hig/ku,? in Hm guinea: yum! up oi' Lin-Hit: i?ilL.? . Exposure of Rhesus numkuy 1.0 ppt. 'F(Il)l) in Liu' dim by Allen :lild Vail Mj.l]nr? (1077i. 'i'ih' author's (it-tai inx'it?. to death in I'i vu tho {right- munli?vys sLudii-tl, ni'ilc-r- What Lht-y- to he (iin [y doses of 2?3 lig/kg-WTLIH) I'ul' :1 chmmi'c lui-I'inil ni' Aih-n and Van Milim- .Hiumu-slvil thl. Iht- ('i'l't-iris "mind" in_ Liluil': ?'sxpur?iillL?JIL'pu'i'hl Hu- I ?eval?ivnu-d administration am .?u?ult-i LC dum- -i 024735 SUBJECT .TO PROTECTIVE ORDER. - -Kmri m (197?) (w ymu- (hr'fllit'. . uh Hpriig?v?JMWl;ny rut-:5. glq'mv? Vtuxiy (lint ul (lug-:03 \ul' .Imd (Lin-(H. dussuv signs, wilfi-VIXV 'lnwh??. (lush (?lming/kg) (:u-usml nu n?f'l'ccts n" Hit-U113Hrguuw?. My: (Mu Ial'ul'l?uut hum" in UN. l'frqn? I?ll}; The i Sc i 1m" Oil'- [l?u-mVL (jutvgru'ihs; causing; and A 'I'is 1an (External clement. ul-l?} RU cit-jug agent). These agents specific ways. culilsr I I - Mudmniwns; 1'11: ll alt",- HM: many, mid (-uvirul'nnu-ul gull UP in Du)? .in ?I'I'luil?uns "r?ojbructory ?pmaiod'f. I?Vr-ur-nvduy d-uy tlu- VerylsuchpL-iplu (liutsivdc Al: Ll?rixlsi sLdg?v' stigma (31' tisSu-?l?e 'sz'l Lulu: ipl?u?v? (l'n?jm' (li Show?: ?ll, inn-.614; (?Mingle-Lit?: .in days L?ffu) in {nun ?d Mn. .1 l.ll_ R'l?scivs .pyl?i?ut'LoI? "ms-1; I'l'a'11gilc-Ilvni nut si'du inlilucm-ug?. - hU-pnll- im-I gvnt?l?uta?c an zulvvl-zm?: ?Until-go,- but, ?Mm! lliyv'i? UH: form growth .l'n'nvl imurl ullum'ut inllH'. 7 CONFIDENTIAL . ,0 SUBJECT TO PROTECTIVE ORDER. Cog lwa 1mm, LC, mi mm mire-m.- nun? .4, I'I'vsh?, NUW Yut'k .nul [07-31, ?Wilson. U515 (L ,nt' on LIN: germ?type: .?lmI 1i which ?t?h with adverse I'I-uthn-H: I wit-J1 (IUVCJ eminent.? at, Iluf I imv vx-mmum-?Iu: .m .?HIv?fl'sv 3. ?gt-Ills m-l in spuri?t ways (nu-q-huuisms) (m (luweanjnu And I In initiuh? m-qumuxus ,uvl? ulnmr'nml, (It-v1:Inpnluntu41h:- {whims pl? LIIU (Mr-Jun.? I. A I.nl-l' (-IthU I upnihnI (Il?.lI Im'n I and [In?ll fIt?I?jt'lI . (3. I'thL-glL-th-S abnormal. glgquleypiuunl; umI I'I'nm Llu-I (Intul lly Ioth'u ICVQI any Hu?Iml mun-I p?I$$imxv5 In .I pan-m i-n?L qu'IH I'mu-Hs .mmqu .x m; sum cilnl .u l'ul-I I u'I' IA ln'Imd gl'I-V ('nm?lmuiu?lS I'ul? myriadul' binlnmivnl .mu'l (:Ilumjrulf vl'l'c-g-Ls. 1 I CONFIDENTIAL . SUBJECT TO PROTECTIVE 19- some types of Drugs and ?thr ?humicals that have been shnwu Lu-hu l)r\lg 1.vlwn I I salicylutcs I usprin, All of wintergfcun curtain alkaloids I C?lwbinu,niC0LinC: tranquilizers. nmLu, chlor?pr?onulz-j nu, r?uscr'p?inu u?tihistuminus IHH'li/jnu, mcclizinc, cycLizLUu iu?LiILiULdic,i I tx?Lruuyt1 = hy?oglycemics I curhutumjdn, Lolhgtamidc, steEoid hormones tfiumcjnulnnu, cortisbnu, alkylating agen?s busulfun, antimalarials? ?chluruquiuu; guin?crinc, pyrimuthuminc anesthetics I I hulothunc, urvthunu, nitrous nxidv,_puntnhufbit folic acid, purine, and pyrimidine analbgs solvents II I bcn7cnc; propylene glycol;- puStibidno . curhary], captan, folput industrial effelucnt some compounds of Hg, Pb, As, Li, Cd. 'miSCelinnco?s -trypah blue, tryp?ranul, dium?x 'T?ratngg?ic effects Wuru usually seen dnly at doSvs well above therapeutic levels fof the cxposur? luvcis far chiro?muntal chemicals. Source .VWilson, J.C. ul7 Gvnuru] pr?inciplvs and Vutiulnliv, Clarke (eds) Plenum va York and London, N77. CONFIDENTE AL SUBCIECT TO PROTECTIVE ORDER. . .C . 30 CONFIDENTIAL SUBJECT PROTECTIVE ORDER.- . 'W115()n in his book my! lyirllu hc-I'm-t (N722) 'nlm?j't? 1i); 5? th? necessary criteria for r'uCOLuLi i HQ7 mm; 1 urnl?uavnh . agent in man. 10? 'an ?u'bru'ptinclr?cqsc in the? incidence of gulp?artirullur (luljioil' Or ?ssdcidtion 2. this increase ?with u. La. usu?ol' a. ricw dr'ugli 3. Lk?nibwn Lhu in y1?1ding Icharacteristica11y (lcf'cct'ive infaan absence of other factors _c,_0mmon to all pregnancies the (:Hux'qcturjistjc defect. Since chemical res-pony: varic's'withxdosagc ?adminj Htr?atjun' and particular agent, Wilscm (1977) opcit, has ?established cri categories for classifying to .tJ-loir? (rnlliary'otox.ic (causing; (a damage in early "pregnancy? ant?IM?JuI (i?ISHuming ??xposum- 1-0 therapeutic or higher ls'tT . established pl'utlucvs' .1 higher fnl' . m- death nl' ?expum-(l wununy" [than slrimiilnr Ilwiumt-u. Hut": hm ugh appariunt. i-ncrt'um- a!)an background [cw-J nl' .?nl defects 01' (It-.5411) among, .i'nl'unl 5 ul? husud nn lill'g'u t-xpum3d mum-n, ul,? accumulated (in 'Hl?ll'Vt?yh imlivui ilu'lwulsc- rul? (lt?ld?CLS vur? (195th of (exposed lunt bins" :ilL', ul' i?n?j?udllt?v? sul'h'ys .imlic-uim significant ilm I'C?a?lhl? -Mutagenicitz genetic effeots DNA) activity. Numerous t?auLjus hQVu been conduotud,dutujlxnu th ?Lppq?ggcnio-embryotuxic and {htotoxic hy_ and 1ts contaminant thsc.nc ora [1 .with a Variety of Species and have demonstrated both no and lethnl levels in many cases. .The prime target areas for: ?teratogonic respthe from and dioxin afc'cleft paluLp' and kidn?y anomalieSQ Thc'ubility induce kH143ruLiuns, Because of the similarities of basic-molecular mochanisms by which chemical mutagongyand'most chemical.cartinogens appear to induce I poStulate that mutagcnic effects can be predictive of carcinogcncity - Scientists b?1y on.short torm tests to indioutc Ithe mutagcnic_potcntia], a chemical-passosscs.a Thuso_tests-includu: 1. 'tests for mutation in bacteria and cukaryotic microorganisms for_mutations in somatic mammalian cullsr 3? tests on chromosomal cffects'in higher cukuryotcs inclujdnu'meHJJH, DNA repair All of tho ity 'cither negative or results in tests covering primary DNA-damage, gene mutations and chromosome effects; The soivntiric? 'dispute resolution conference on 1979 AugUSt, ,St?c'ilt??d . h_ . i I ruasunably adequate eXperimental data has been generated regarding and that these data are not-suggestive of . CONFIDENTIAL I SUBJECT TO PROTECTIVE ORDER. 0247415 'Fhla sxxicnxti.fi(t ?n1 also {Juft bcsults n??nu?)hLI HLNdiph: ,hav? determined that TCDD incpcases the frequency 0! gene muLutinuh.h Microbial duLa suggests that DNA repair processus urv nn'lhh "mechanism ol" action since-no mumgnnir LVN-NI HI studius using rcpui?r dcl-?uctfgi?Vo. 'l'hu Inu?l?a-IViu (lulu Huggusts that TCDD acts as a direct initiator.of malignunL 'Lransformation since most of thu'iniliulur class. Few promoters or cocarcinogens Show activity. -2Carcinogcnicity Animal-mndc] Studies havv Inng been used fur hcarcincgenichpog?ntial in man.. specius'of-animnls Used in thsu studies bu as carefully cunsidurud us thv.duLn'rcsu1Ling from Rodents meet certain specifications that muku them ?highly desirable for carcinOgcnicity 'Thcir lichpan is lshort whiCh alloWs?the fullest expressinn'of pcsitivc "carcinogenic response. Rodents are small, relatively inuxpcusiyc,T ?casily bred,'ull of which encourage largo study samples and .cOnfirmation of Lust results by other inVUHtigaLn?s. Y?nt ru?ull? obtujnud using cuts ur mim- (:(lgllilul. bu Locmun ol' Curtain hiulng?irul di ,Sucond rat. and sever-u] ?(died x? 11 (xl' 11?: llri(*(l . . 1n 50 (rm-(e must. In: Lulacn 1.0 ln-twc-un. tumors and (,lm'sv- causch .by carcinnm-nh: "IucliunzimnH. ALSO 6' carcinogun'ic x'cspunsv can hucomc apparent lohg'ul'Lur qu m'iuinnl rel i n uul Llri l1. ri i (yunrs ipl' (51"l It: - 1;l1<: 'a1 i .. ix DOAWJI ultvrutions can tdku years to develbp? u? Xv?: SUBJECT TO-PROTECTWE ORDE N) L. I not. wj-L-h Um 'Cu-r?c i nug?un i 3A1: these be considcyud when un?Lyz{ugl Chc?icdl?fof it? possible Carcinog?nic anpertius. Research_cbndu?th oh a?imal models Cur-Tinog?un-ic (Irl?licc?ts 2,4,54!? 'hghve 1.30, Yield I?Ob?j t-ihgvt? [?esufl-ilis. The ,Ca?-ci?Och nip-orb. in. Fcbr'?an'y abknowlc?gcd theS? con?lusions; ."On the basis or LHQ I?ic? and rat studiuS'thur? is no sighificdht eVidcn?c_hf 'Thcy add?d that had not, Eco-n] (T i 1y: in nii 'cci?. I 1~ TCDD is an inducer of huhutit aryl ??tiViLy in the rut ?(scc Poland GLder a potent'inducur 0. with 'Pll'a'r'mguiolg, "349-359, 1974.); This'c'n'zymu' System is proposed as the. promoter of carcinugun'ir l-?urftJu-r, in Hu- 01' known Carcinoma} is weak tumor TirniLiuLUI? 'in stage system of mouSu skin R. InvestigAtignsloF the carcinogenic.putentiai"or H?Ihzlnivn p'r?odu?cd n?isul?ts. At lilymg t-gebm (Insus, a diet "has bot-n found Itnktuuslcg iv'?c't'uus?cd- I inhidunc? of liygy-?nd lph?LUmOF as "plal'a-t? t'u'm-ors rat. Species; I ?wat?i . avni?mu] ?st?dins?l-am? ?ig?Mpm?L?nl. 'iTu nl' (:an'ci nugtr?ryr?ivs [ml anti?! o'l' l. v-u? two year K'ociba at Hall. I97RQ ITO Tux. ,gHIdJpr'l. 6, 279-303, I 2. - inn/qu igupilm'l Van Millm' ?at ill-V ll - .1 . Incrcusvd 1n. rats .uxpusml Lu l-nw luv?rlf ONFIDENTEAL . (x 1" A DER.- SUBJECT T0 PROTECTIVE OR .>thv experiment only invaVnd both wul?c- Hu- dusagn- ~Ultfirl? (?pul?jmunLR slim-i Inn I highly Lnij'c I?l?cVulh" nl' 220? um]. gun pm: W?ly? Hi;- incril'us?Vin j-nCJdI'lH-w- ul? .l-ivt?l' .?uul L?U'I?Iimf?s runs; AL LIN: [um-r (lum- rlmw-Ib Lliui l? LH (Ii Vft'l't'd. Kucibas group ?Llw 310mm dose ranch nvg?ulJVu I'm- carcinogenic": effect. citing; Mu.- uppuur?uncu of, huimLic d. modules. flrom a?mtxiiwn dose ?151le. only change Van Miller r'opo?l'vllud Signi l'l?i?cant putt-n1. i (-117 at. doses Well below the 500 ple dose. Tumors, {u Clajmpd, ?mun-Wm, with TCDD. lchl-Sf of .1000 pp_L,_ 500 ppt, 50 'und 5' ppt? Only (11 a. did Van? Miller" uCknan-cdng'nn cthnivnl effects. There have been svvur?nl cr?i Liicisms or fVan Mil l'ur'H' jnvx-HLignL'iun. 'I?hu cur?cix'ummn mm?; nudih?d Hn' study and found that had major shortcomings in dysign and conduct, that 1imi?cd the reliability 0f_duta dose than 100 EPA, 1977.)." '1?h'cfel'oru its carcinogenic" ?effects could only be" verified at the twO hig?liu?-St dose levels. In addition the "in?cstigators in um sLudy r?u'por'tud no in Lhu animals .1. highly. unl'i knly rats" ?Thi le?ui nl' Puts .j partic?ulnr? I suscc-pL ivh.l ?to tumbr induction and lack of tumors in controls is highLy suspect. ~Also the aneas of tumor induction at lower ranges of TCDD did not enrrulate With the epxeceed target Organs dct?rmincd from thC'highvr doses lung and liver; .Also. 10 animals per- test. group; "I?Lhis small number is. bulb-w, Um minimum _numh(:r? rccomnuindcd .hy .Llu: Nut imml C5hcer-InstitU?c. Th? H?Uuly has urlHn hcon vl found hyperblastjb ?Tnunnh. ?in (hv livcr' at. Vthf- .ZIU mu,? (lqu- and ??15 4" "im'liu?- 4n audit" avcl?h?W?i-ict. oI' [givutlivhni 10f hyperpluSt?iC?nah-??75 ?(5041-1110 C?ddunt?. I?u?(evaJl?IuLud. :1 the StUdy and ?Cory?cll?i?lh'i'd- ?lilt- UIP (:nml?ned 1an dent-(2 of hhdulquand (hr: statistically Sign?ill'jy?cnnt, for both and, zlStudies by ?Ll'ut?il and 1979? Pei??hlstA-ncu 7017 Liver NnduloS inn nl NCI. [979 Thins, ihv?ustjgutcgl I the hum! of rat Mid 'f?epx?lusan a dit'f?c?rmil, typo 45m Itll?nln, possibly" .1 hvhign- m?up-J usm. '1?wa nodulebj mic not m??lczuj?snrs of. (:urcttinnum. .1th Imuhy. Iii'rn If;ch Ihu in that I autonomous 'I'hvif 01'- nndulp isf ?n lwniun i?thn?t'v is ni' Crohnt?i 1mg:th . hut. is nui. m' nimlilnuy Only acquire- .ln slinky, llu. Ll-ilnsi Lion 01' Lu carcinomas. AL intervals after cessatinn of uxl'pnsur'u, ,nndu I vs (Ii .splu'yud plunges w- nl' phonoi-ypv ?nr' (Inge-nut?atjon that. wvr?o nut. proscnt. in carCiliomas .v I - - - Thom: support the kooLhu this ONFIDENTHAL ul? ass-non?pruul' of cum-innm-njuiLy; TO ORDERLam/x I'UI?Ulurf bulwort. l-m huch rut Lunalu .11 us ill the Jack 0! (nu-c I unucm-?t - - . an' nodules Lo tumors I'wj thin tho. LWU yuan Lust} pi-IriMl ul' Km-ihu 51,HY, ONFIDENTEAL PROTECTIVE ORDER. 'wm-k-v?rs Mm ?(h'vululn'd 5.3""53? mus nl" (:hlur'ncm- .1 The Scienti Advisory hm?) VR?vivw Atit'iml and Silw-x, s. H. -l 131 lru btK?Lion -. ?Alqo ms?gownuons :15 (.0 whether hyperplastic nml'ulus c. - . precursors, pp? 5.: hi" lu'lmtum-llulm? carcinoma. HUMAN and 1; 'Duw chu?ital plant workers. study examines.th nlol?Lu] iLy ql' 204 par-Suns during?- it? mamH?mrturu from! 1950 to 1971 at thu anvclu-m'icul. plant.- Midla?clOMichigun. The health status of workers exposed for a pur?j 0d of Over" one year; Investigators concentrated on'th crew directly involvpd in the manuchturc process; In general; at (exposure of (cu?uLuini-m; loss than 1 TCDD) uxpvridncud by the workmen in ?hc study, nu - effects haw: ?Iurnn ubsul?Vud uLLrihuLuh'lq- ?mph. cnvi?pnfucnt. Mortalityicnmpur?cd well'with that 01' all. whih- main?. ?And also compares well with the background Hi), expmwiimimv in gvogmiphical area See of, al. Mortality analysis'o-l' engaged manufacture Acid? J. Mud. "l'lHi Siriglv drill?II us run: ll ul' igngun-y xlihruvul-ml in 01d N'Lil'm." boon tn I'ur- uiLith. yG?Hl'h?. Th0??mploy?b ?15? a past history of smoking up Lu th Ducks uf per (lay; 2' accidq-nl NiLr-o, Wusl. Virujuj .1 A Sh'dy Chronic huuth" nl' (.0 024745 i'Ln Virginia! [049. (3: x? ?v 4/ . SUBJECT TO PROTECTIVE ORDER.- _;1n(l to cold; g:0n(? your after th [-inumillimunt indicated by hupuLmnugwly (l'iVUi' nxnmim-d. 21 general regression of Cllt-?l?llH-?lS and non cutaneous ?1 Skid-disc'usu h?y cyh-LH, an?! Iuilm'ccs?3usi. Hui?. may In: 'lu-lml ir (Alvym'uncligm ul?" functibn uI' th is (hr. Muriel} disgl?dm'S' If.? nu-th?lism fam?l .1. Cln'unjr Hkin lySim: ?-mlili'iun (ul-qudr by in motqhu?min. (fluimutuly- i3", to. TODD. Mara] 194?), (hp plum, TCDI) in! (3 funl inlm'im' ul' lumi- Idiu- 'in tlu- pit-gm.le invmde'J'IttJI' ?ynmhuu> --. im' ludiing my.? um!" I inwl.? ?irt-italliiwn, hieuclu'cljc, dizzim-Ss and [l-ullh?uil and Svym?v il'l?Ivi'ldlU- rvqut-Jivnln ul? exposed ski?. 'Al-?tvr? Lin-~51: subsidy?ud ('h'lgh-acnv glpp??rcd; A four-?1?Vye-rul' fol low I. :tcn?u I'r?m 10810115, 2, [nuns Hurst-Inn ul'nppur and luwur shOUlduvs .nml mu vxq-rt-iun H'nd irritability (lucm-nm- hl' libido S. (II. vertigo 01? Llu- six Worker-s examined had livm- (.enlurm-mpnt. ?Also {mind wu?r-c livm? On] ur'gunwnL )5 right upln-r quadrant. and (-pigustil'ium and (It: I 1' nm . 01' tho Six origirml ?wor'knr-s Were . . I I I ugui I All Workers exhibitud a murkvd jmpl'uvmm-m. -i'n Hwir' skin lesions.? I ENTHAL SUBJECT TO PROTECTIVE ORDER, CGNFID .111? Journal Ucciupul?.loud] inv I-bpuI-t In? January ,a 1980" curried but, 29 yqu' liulluw?up ul l'l ("Ll?liginal Study? .. Inmulmrs wm-cf liv i um], ?wm'v ?an?i?l'i Cd chcusod. by (Itiil'Lll ?urLi I"i ?Mm?ullrlur'disud nmrtu] jL/y ratio. dunHu?e ms HAN (h .12 (It-.1111.? observed cxpuCLu?d. 'l?hv report, by RIM Aun-ricnu Council on sciuncc "and L'lw uuly' significant \Ilalvuc- dutcrfujjzi?ud. nilu- in?ul it?ljnl? 0.04 5 Nu (I?m-TillillS I I 7 >liv?r? camccp'. Cancer deaths occurred IVCl-?fius 'O?ne- skin?cancm?. fibrous. histidcytomu) pr?chd [fend-11; (Expected in?cidcn?c of its appearance is 0.15. Thr'me? dvuths from ?ymphatic-und hcmutupoetic neoplasms resulted with 0.88 expuuLvd. 'l?hurm? wurru >17 "du?u?ths l'r?um dj senses of" the: circu ?Lur?y sVs? mu wi Ll.- 25;01 expected. B'cciuub'u thugs-study rthr?L qu small (ml 32 (humps. "Wan observed thu_rusu1Ls From this study cannoL be conclusj v0, this is the bust lung; Lunm study. 01', Lu?dntv?. y?lhc oi mortallty on pvr'snunv]: at. this [mint indjcum- nu 'uppar-unt cheSscs oi" mun-Lu! ity or of dm?kth- (luv Lu malignant. neoplasms, Idim-umm; .7. Arkansas pulutv .Ht.Udy. study 1.0 (luLnr'minu what, 11" .uny, human ?vl'l 1 ,wux'o uncut! (va' ?xx-posur?u" to 2, A rut. i w: study palate in areas o'n ,Lhu incidcl?l?Cn nl? In H. R-Lzsuarc?lugr?rs?r unu'lyxud I'm: i ul Cleft rates and concur-Ment- nl? 2,4, I'ISlel?lilLud Hw was as hj?gl-I, medium nl' luw vxl-mwn-u my; mum: basis or dc? ?Crow-'50 during 6 -7 year intervals lwuinnin'g NFIDENTIAL SUBJECT To PROTECTIVE ORDER-.1 .4 .t-hut. facial-Cleft" by shx, 921 7 Nelson (st a] ".th study or the re] uLj ii, butw?g-n? ugrfi-cu1tllur?a] luscs' 0" mid Cleft Palate 10(3): 377-3U3, 19793.7 Nulsm?l'uuml? period and (-xpus?l?c group gunme ly rust? thrl? Link. .Nu? significant-1HI'lk'nivncus wart: any uI-uuping The .?mHmr's that ?to increase .in invzidnmru bf this anomalijS (luv 91,0,hottul" gage. r?tlmr Utah lactuuil in?feasn. 'l'Ilmyf that "The stud-y (ices not. any cguSu?l I ILlury "?l'llt. is} 2 S-T use and Wu: i-gxl . to ?recOgnisc tlmt.."such am ?Affect; i_l' it were tn ?exist,- would .thC hubn (Iutucbu'd, 1 {slur i'ht'ruust? in fan: in?l (- ?ails was. -I (:55 'than two f0 1d. tun fold in?cruum- in any anomaly wnu (I Iw y- large. ?Wc hull'cvv [mwur-lul ?midi-min!uui-cnl Studios. ul' 1? 54'? nuududl' 1-H yh'f;1;4- (rum: i I it"s (ch'v-cl' op?m'unt?li uhdmj' Cum? Lions (3 utml ?9.50 . 4 . ."Count?y The I ?Cai?li i 1 rurri ml. um :in- dumj (I) Li?m?i ca on 'gqu-ss .t,luUN: ()r-luan? CuT'i Emu} all-nix; Whirl: inch-mus pli?cnoxy? spray - Tim" nu'l?hudb? '01?7. i I1Vc?tjvguti . i null . I 1. vaj-vvwl inl'v 'hulml'm v.1 Ln] 1 record? ?l'nr "i Human-mat i_ (HI H. Iii-Y0. Di lis- .a?uu. (In-(l .i "falli-t dual-?S ,1 ?nd (Lung-?? i d] "mill. .i n-l'unto? burn in. mm mean-by rqx-(Sill? 'duljjv'ng UH: yuayS 1974:1979 ?r 1 0f Spraying phcnux-y hut-hiridvs 'wi'tshin? _024?43 R) kuvinw Hnn'pn MvdiCil C1 inic- room-(ls f'nr' iva- rhi liradius of (hr'luilnbf RU lnttEI'Viuwg. in I?ml' (luhrs and [h prul?vnT'S. Wi (.hin .StUd)? Perl-0d, R7 {?xtunnug?ivw I flu-ms, night, 9% und'ud in SpuntallCUUS (.1 in 11.14.11 'pt-uvj any) and UN: 79 in l'iw- Impuls- n? . Rug-run, (,?uliibrnia 01' [HuaJLh Sul'v'igttm l-?anhuP 'ivvnvust.igutiui'rs .?inLu reports of ul' ln-ng?nuncjuh 'births, six {7.7p) lip andeaiqte, Hinfant death CONFIDENTIAL and trinity cuuhTth, April Ol' the tim- wur'u born with birth (lul?uchs (twu hyposlmdia?, two with :inlciiunml'ut'hc hip Socket/Tr mn- Unit?: suddnn at. age: sun?an I Phcnoxy herbicidu Spraying has hmen carried out in the fall of thej?c?r sing-g: with {.thhex-Caption 01' 1062, '1972,? and Spraying Cunym-(l: jn NTanxbx-n- 19-76.; Thul'ci?ut't: spraying consistency cannot be ?estuhl in this When-the 16' abhor-mu] prugnuncicb wm'c; Ln Lhu pregnancy outcome for that r-L-aipn, thu ?pii?cllil?u (?umv inin ?l?l'hl' SINHHLIHHEUUS "abortion Put ul? ih 'lnsh 5 rate (H. .h Mujnrf (zung?unj ?mnll'ur'm?uhi (ms (urcur? jut.- (Q?hv' lg'nt ?a 7325' wlulc inclusion ul? mignuh (lcl'ucLF; lnjings 15%. NH: VOrlunus r-atc' oi occur-runne- - su Hm f'ignr'us Wivm- within the expected 3) Um? ?till (hfgl?l and um} sudden infant .a'n puttgn?n's l'ur thu HIJILM. SUBJECT To PROTECTIVE ORDER. - CONFIDENTHAL SUBJECT TO PROTECTIVE ORDER. ?gastrbintestinal ?fCharaCterissd by .yiclded negative icontrol dust . concluded appears unlikely Lulu-?11 them.- him been dn unusually high rate of pregnancy wastage in Orleans". StanuiI-s Missouri, Horse il-l?LHIil. ?nale .31, 1977, Lang?tih-m ?el?l?eets-?oi' dioxin exposure. to editor, 748. August. 1972?, the Missouri: Division Center-fat." Disease Control reported an investigation of ahm?Su arena in 'Eas?t?rh' Missouri where 94 of 57 llor'ses exl?wosv?ed to the ur?unu :had, died' of lain illness charaCter'iSed by skin lesions, sown-g weight loss, and" hepato?tox?icityg Birds, dogs, cats,? insects and rodent.?- uere dead in and-arbund the arena. A.si? year 0[d girl who ffequented.the a?ena as a.?layground; dchlop epis?uxjs, eo?plaiut and Sevehehhcmurfhegjc cys?itis? - hc?aturia.? Bacteriai and viral urine cultu?es results?"Three o?her persons suffered_frpm: milder illnesses with headaches and nausea. They all so I Qisited the. arena though for Shorten periods than, young: git-1.. sub-sequent. soil analysis- showed that both e, . (tri'chlorophe'nol) and TCDD were the probable toxic substantive? causing the adverse health el't'eetsv. lt?was found that the mien; sujll 31.8 to 33ug/ngpm) of 5011;. The contamination was traced .back'tu waste? oil used in the urea to (32-4750 0n reexumituition 01'. this young girl after .?Li'im- 'yeul' _1r1terva1v51nce exposure-l the. patlenL had grewn normally, Beth height and weight exceeded the 75th percentile. Detailed physical, neurological and chemical cacaminutiens revealed iLies. The same studies were, gond'uc-ted un' sister Land mother expusud" 51m?1t3?00u51?th0ugh less extensi'VGly to V'l?CDDg'und the ?m I SUBJECT. "To. PROTECTIVE ORDER. 2 _-thut-pcoplc cXposvd ';-uppahcnt scquolu from the Lox1n. I ?c'xposUr?c to dioxin in product taken from Lhurcuctor "head or 3 . 35 UFCDD. '32? 'I?Bulzg'ic?lui :11 cono'l-udcd "Our'oxpor'iom-o I. to djox-in?. can recover. Completely with no I It. bun tl?xcsu chi 31:51:11.: joy ohm-urinal pregnancies or affect. their vamo,? H41 lJy: The lamest; (Industrie Chimichc Modo?ociotu Am-mjnm) chemical plum. did not pr?oduco but inudu bacterial agent.- "Thc. herbicide and g?hoxac1110r'opshlone - share a Common donomj natolr?, 2 Setr?ic?ll ol?oplumnl 'ih?thcih manufacturing prOccss. . The; Icmosa", factory explosion occur-red in a reactor" 1 "that produced 21,4", S-triichloropl'mnnl by combining sodium hydroxide in an solvent. "l'ln: .pr'oplulled ?irth a"vtroxic white cloud Which-'when Cooled, duscundgul? ~"510le over the surrounding: arch. . Among?th?l?lchemicals that. cootraminat?d during cooldown was the 'chcmioal: dioxin I '?aSod: on. ?doter?minatiions made by "p-irfodu'ctj an 41,00!) 5,000 kg-Iof reaction product-owns lost into LIN: Estimatc? of tho rah-god Vii'rbm 650 grams to 1,700 grams K'ourncy,. ail. in lithe onv?ir?onn?icht, I sourcos fate aod? Ilinv-i Perspective, .5, 273-277, 1973). of Hit: uscupilrdi For analysis ranluud 024751 . . . . I A . Ragga-Lulu ?l'hc ostlmution Suvcso Pupor- prom-nu Llu- 2111.11 V-?Congross liuropuun Society of Toxicology, Harlin WJ?u'n?vl 2572.9, 197?. .- Rtiggiur?' reported t?fhat bird's, I-th?iLS (UNI. Ur poliss'b?ning wuhd of?i' Tug-?1 hm. - the {'91 lowj nL: ?Vlhuavlcsil'L-om p1uan..uul tun-5 turn?d brawn and. xii-'1] .i-n un .?u?lluu mun?igll??il?l?; . 1 ,Wm 3,00?: luvl ~l?wm: um?ll 1m) ??H-iLcr??L-i ?(Itentutf?tsd uni-(mind L-ln- . M?gausgI?n?un?u?t? 'ulf 'reSiduc bn ?cgc?atio? in this urpu from 1 to?65 ppm,. "with ?ne r?cddi ng as high as 50 p-pm, I I '-_9Chi1drcn 35d adults expuscd t6 thu dust and clcvulupgtl??l?lj lesions .hy redneSs and swelling. .S?mv uxpcrianvd-t bur?s and blis??ps to ca?s?i? material. I ngfutt','j nj -- poisoning at?. '26: 2852-9. ftpor?tmgd .thu hjgl?fst Contc?r?it'wgi'n? d'ctveirm?imul in ?the? herbi?gbous animal's . Pilunplc 'oi' nervous ":s'ymp'tnms, ?mo?od- Changes ?11111 Serious ruSh?Vlihke skih?lcsinn liinh-r '.dia?noscd as chlorucn?. The Imiug; (l-i'vvidvd l-wn mums - Gj 6vunnr'di nut, i pl'ug??S { lb??uh 1' 1nd!? Gd Y. ('lluipliijkiLrlu .8 4'"th pvrih??bdi mg?u'LAI ity- z'kuin flu-(i eructlut'ally (2.1-. '1 This that ml; 3.1 I thin. pm? n. (lat-Ia dill-'1} .?wni hub] Thu consi All tlm' malformations Marc in the tin: l, ions SUBJECT TO PROTECTIVE ORDER. "l :u?tl.d Inn Hu- 'Zu'mv. 'l'l?ufvh't? increases might. 'h'd'Vt" [Him gunu?ra?llyl, I'mt? ituulidx unit. this [)gnr?tfi?ula? area pri (in; typespgil: mu lil'm'r'nu-Lfi mm.- with those whiCIL-WOuld'bu dioxin Wur?c huluk dutiwta'bhe Inn? u Hu- I?l?f?vl' mu in [4:79, ml .zllul't lull Kerk: l-fr-umnuntud dun?: ml i'm- \I'ali?mt 'i an any th?.?c?z ill thu' ,inCi-dunct'? ul?_ uhut'! mm. inn-u 'Shuu- u'll it'llt' ahmktim-is? flu-Vt? Lu Mu: 5'1 (agar; at: wmw; um I incidunczu mm. ?ithiu, lght-e range In: to us? I .wgutgn \ful?t? t. ah?mfsl . - and, .R'Ii'filn?nrs; _wlmf?e - 1 imi L25 '024754 gross I'm I't'lm?rla! mm (mm I) ?my-no cy?)g?nbtic 'I'ln; Iimm' nt- Hu- i'mbuilaition not} CVCH: ?t in." am [0190" Wu? I .th'l?tuvi'nc?d. . dismilJ: ?30ft; Vil'lt?ruz?h' (ill in add HY. lx?ul?ivr pl?CS?thcd Vdal?.? Vf?o?ll?owi?g'?l?ua vxp'uaugnz- 1} ?Ili?ent-y?eight in}; I were tpf'bdu'ctls of ?cuncuptsjon 3h?! dun-rm.- c??rfet?vta'ge and I'ul" LHa-l icig 7N0 'mu] formations wcu- nated in (my .11" Hunks? in; Al?slight increase .in {Hilm' jncid'nmnf nl" .1!va um}. ?was determined in ?w ?Iil IZiile. "l?l?uEsv incr?udScS might. fun-?1. due r'egj {sown ah-?-tidns. ?11m. hay;- I'bl'gmnj. he: (35:2; ul? nipunl '7 algal-fun; ?nd Ipwr'inatul mm?lnl i {ant-m my-d Wurll'u Foirmlud (2.1-. . 'I'lli i lu'jdunc'u mills LII i Ch}: range that mull!" "zfv li'mvl (.?QLl?ldi Hut. Lu alv?uawp'r'iroi? uLcidg?n? as? ?n (Lit-u an; luv}. i-l?lji?tu. Th?! 011' ?mul l'iu-nlujtimm qu-c- I Cons-1: stunt. iWi?lH ?I'l-hosc} whi?h . Woufld bu. uxpccium?l ?All ?in?w?sd r?nal Mu'c' in pine and RT int-ms I: emu'ullLI'at-ions 01'. dioxin were below 'dui.:wi.ab1ulimj Ls.- TO PROTECTIVE, ORDER. 024.755 SUBJECT TO PROTECTIVE ORDER. ?Alseu,11. The? Study duals with-u limited number 01' residing in the Alsca Basin Oregon.? A living in] this treated wrest area which they said'were correlated with the spraying season. Initially .16) miscarriages were reported by eight?- women; Subsequently 13 were II'ort-ed from? nine women. 'l'wtdve' of the 1.3?m.isearr1 awn-5? rep Toccurred within the first 20 wuvks of gestation. When this data was compared to the live birth rate in Alseu_(86 in the six-year period studied) a miSCurriage rate 'of 12-13 lies well withln the limits of an expected.one miseurriagc for every seven.live'births. The report noted a seasonal variation in miscarriage ,jncidenCe when the Alseu values were compared with them: from nearby Corvellis,0regon. HoweVer, insufficient evidence'preeluded any establishment of proof or noneproof for a.relation between miscarriages and Mantel, (An evaluation of the statiStical methods?used in EPAS report of assessment of-a field investigation-of six years 'spontaneous abertion rates in three Oregon areas in relation to forest spray practices.? (Alsea 11 report) George 'University, March 26, I979) - commented that "the.possibility thus arises that at least some Of these miscarriages were eXpericnced by miscarriageeproncvhomen. He also felt the "publicity about and spont3neous abortion could huve caused more previoux spontaneUUS abortion to he recalled and reported"( '024?55. sea I A continuetion of the Alsea study, this epidemiologicf investigetion further anilyz?d the possible reluthn between Spraying~ 0f events. 'The'rcsults of this I study provided the hasjs?ior the EPA suSpension order in February 29, rt atutihcludcd Lhu' inland towns of Corvallis and 'h05pit?l 3nd indludhd coded diagnoses, spontaneous abb?tion data, geStution period and zip Code ;in a six year IliVeabirfLs for the respective_ureas. .by the EPA Study are summariSud Thu culluctud dALu Prnm.thrvu which includvd an aruu?nL-c I."approximately miles 'of? Dragon (tuithl .?nul nmuntuin rung?. The "urban" whivch ljlus hind) and the rural'?contbol" arna_which is in sparsely populated-oustuyn Oregon On {.110 Light; 'bor'du'r', The inl'ohnution gathered in the study cunu? agency [NIL-lil?l-lt, (n 1? put; i (Ants. investigators limited themselves to SpunLunvuus abortibh? of legs than 20 ho$p@ta1$ I Wok-c than rum-plut?ud tun: CO?clusionS revealed 43 f?libws.j 1) the Spantaneousuabortions_inde* (hoSpiLuliScd >'1000 for the Alqu study Jru? u?pd than the index for the urban And afeas,.where there was no knoWn of I ZIVTherc was a dramatic increaSC in the spontanCOUSraborLIOH iudvx "forth" urea l?clutiVe- to the urban and control uni.ij in month of Jq and July. This increaSe followed by appruxjmutuly ?t'wO months": a. period in MilI'Cll' and. April Mm ?sun to. control. vegetation in study. area. ?Rirlu-Lj V6 to Hm and control'arcus in This . the month of JUnc-und July. ?hyi mun'tihs a pur?iud in March Jud- Alnn'il ?when Usu?d 1.0 cuntr?ol vegetation?in the study Hui-ha. . . ?f:gwp? SUBJECT TO PROTECTIVE ORDER, ?3 CONFIDENTIAL Statis?i?alha?ulysis of these data that there was a umUUHts of usod'jn. th'chstudy drca'dqring spraying 50.2150? and ?i'uplmusi: in_the Spontaneous abobtion indox in th?.study arch. I >"The Agc?ayis systematic survey of tho ocoupAUCu of SpontaneOUS abortions in an area of indjvulng that there was an unuSUully high number of spontaneous-abortions in.thc area, and that the incidenCe of spontaneous abortions muy' related to tho uso of in that grcu. Thu 'data'furthe? indicates that the miscar?iage experiences which the ',eight Alsea women reported to the Agency Wero representativc orU the eXp?fienpes of the large pOpuldtion_Of women living in SUBJECT To PROTECTIVE ORDER. ?T?Numcrous critics of the Alsca II study An evaluation of thc'statistichl methods in, report of AsseSSment of a field investigation of six year VSpontaneous abortion rates-in the three Oregon areas in relation . Vto forest spray pestiCidus (the Alseu II repOrt) George Washington UniverSity,?Mabch Lamm? 1979:. An of tho Alsea 11 hopOPt, Tober?haw Associates, August, 1979, I 3) Witt, 1979f ,A'diScus?ion of tho su?pension and the .EPA Alsoa:115tudy; Orugon state Univcroity, t979._t 4) Wancr, ct al, soi?nLiEic critique of the EPA A1503 11 study hand roport; Environmontul Health Soiencos CenCon; Oregon Siato in 0.247753 UniVersity, Oregon, 1979; revealed statistical and epidemiological I?luws that. Lhu majority of cummUnity has accorded little if any weight to the EPA concluSious .7 A .q CI . huspituliscd approximately 70% of _1 I t.i Igui 55( a: liy?i (II 5 Occur j? um (Juan: nm?nLlim .. Slur.? .citic miiscu?r'r?i'ngu imtidmu-u ul': In. an] fatw must (tulnumnly In the U.S.A. hospitaliz?tion ratc fpr-spOnt?nvnuh ?pprOachus 8% or 92 pcr'fnnu matur?jty admissiong. MuELlun? ufspontun'cuus'IabQI?Lion will depends 0n: 1. Qhutl'lur; Um women, ,f?cCog?ni And Lljl'c cvvc?t as dun, 2. how anxious the woma? is about abortion" and Mini Sncjul System her life style proyid?? hug 3; whether the woman is financially able to secure trcatman, the tr?ating physicianLig a??pc?ialjs? 5 deals ru??iurly with ab?rtip?n Cases . S. the availability bf uh oui?putiunL Clini?. 6; the standand'uf hgulth Cure in the ?ndM?hiLy? 7. Lhc: um: 91? L'luLcuncupLu; .?lu-Id; ,cQ?np-lcumin?; '?He abortiqnl(Lqmm, 1979); ?Alsua ?rip-1y ?(Lipitvil-l ubor'tjm-Ist 'A?LL?c'ndud- Clvi nics; .unsu?yLn?ndiud abulfLiunH, and thQ?e events {hat plac? At'arc? hoSpiLuls nOtkincJudud in thu ?Lhdy,arcu were considered. Study numbers, thus don't atcurateiy;?ef1ect the indid?nCC in either the Con??or of study group. I 'Thc Alsca II.study stdt?d that Obs?ctricians in the urca [hOSpitaliscd only 10 parcunt.of persons abortion, while general practitioners faced with the'samn.prohJcm . . CONFIDENTIAL 024:7: . SUBJECT To . PROTECTIVE ORDER. 3 Tth: was tn the abortion puttlur?n munlner' nl' spontaneous 111.1114: [utter- fin?. Study mums.? "l5 .1 . lvlu? mvdiC'nl ('H'uct. lining." munsumrtl is l_.lu- gunman! Impuldti?un. ?A'll?lvm?iuhlus must 1-1 did Fm" ?ilk? in?) . lc'Vcl .01; medical practice. . age of mother nutritional? state, client, a I'vavl?j Qty mus geneti? ahnormu l. i mud i i m- uml drugs, ?Huc i i g? alius 01.1; consumption-01' ulcnhuJ ur' tobacco, Thusf the of the stress agent, 'nm. In; "adcquat?ly'ases5ed; Also the towns in '1.le st?llig?ly' Alscu (Study) and Corv?llis (control) do not m?aituiril constant populations. Alse'a a coastal resort .Lown has an influx of people during the summer months- Co?I?Vullis i1 Cu'l (expm'iq-Iurcs stumn?gc'r exodus lat. end uifthic yvur?; The lil?Av cited "a increase in miss-carriage; which have I'Citonsisvt?ntiy (mCur'r'e-d: avtfan ?lm-mi rate. uttrihuh: to: the spr'ayi?ng?oi' hcr?hicidc 1 Yet. H?ly .c'xuminutivm; ni' Lil?v (1.1.th irll'luA? (I?I-nmntic ".lulag: Il?uruk-wus in only my- nl'IVH'm sj-x" was nu .s?r lmckur?nund scarring]: .1: In was in yuujl's nl' 1.1m study, ?lg-mull ll'wmr- [wus Hi-unil'irunl; iucr'nusu in llu: amount ul" 13,41,5-1' le'uy'utl in Hut Lust. amen. ()Hun' pmiks and Lrnug'lus nu 4?15"? grill?i?? S?i'vj'Lll' lJvmug'lmuL L'hu your and ?mm nul. Input-.erlhutvgl - ?1 souls-(Snail, QHBJECT PROTECTIVE c-vimlt . 024750- - I win-n 411E w;n~ (?yrlx?cw?ul 14{ u.u l.h(v 14:I;1l Mluyln:x- Ls;wl abortions :uur 'th? values ?re: 7 Qhudy urcp? 4,11,4? urban control;- 14.0%? alrc;y 9.i3%_ 1] study ("Mild only :thc in hbspital'spon?qnuous ub?fjion indgx {of its test area; ?Thu study has bcC? Ln shuh an ugL?uLiLhuL 1L is no Inng?r? uScf'u] study [nu unalys-?j 5-4 0?1? Ute allug'ml J's Um? affects o'l' hurliic?itlu 17,41,? on ?J?'n'pr'odui'ct inn . SUBJECT To; PROTECTIVE ORDER. \i 'cxamincd is the absence of Down's in Lhu list of St: i (EH-ti l'ic Stud i ?2.5 Thu l'ii'bt Pupul'LS linking ?(man-hic- mud?, LO Agent" U'x'unQo murmured in ViuLqum'hv Juno 1909 and Jul); 5, I909 2547"? The public Response to Lh?csc reports prwuptvd' Hu- l't'Ll'n??Hw? .vg- sLudicb? of." ViotnamcSevhospitui records comlucLud'nnduluzmiuut ly by VCutting (1970) and Mcsulson (1.971){ The President's Agivisory ConuniLLuv on 2,4, Invaluutcd'thoso studios and conciudod Ilvlu: following; "Swnmul?izing tho data on hunmn omIH-yol?Monty, it can be said LhuL tho sumpluvui' hirle _w.?ns I'njm?u yea-14 to year a varioblc but. usually Very small of total_nwnboz{: [it was quite uru-opro-bc-nt.uLiVo or Llu: gong-41min and ethnic the uml dl?cilb? mii'o greatly umlor?rupl?osontod,I and _Uu- hirlih ?I'ucm'db? Won: noti trustworthy and, or l-In'u-Lln, undgospeciully 01' congenital muixl'oml?mpiou, doriw-u I'z-om Lhmu ,wm-o equally unrealizablo. For example, the OVurqii conguniLul malformation rate found in South Vietnam, 4.91 1000,iiVobithh, Lb'ubout half of what ?wus roportud in oLhL-r sLudics in Various pul?Lh' of Asia; undvpussiblyv?a qtial?Lcr oi" wlluL might. ?ucLuuily exist. at term. A our-the!? indication LhuL Llu: newborn childl'on won: not. curm'ulJy 1' I mulfonnqtio-ns compiled by the Army (-1- ul?. (W70) - a . I I 'desplte.the tact that, Isomu UrlcuLuJ populations ln?uw: boon LOhuVe an inCidQ?HCt? ol' Uni: condition not uni'iko Lin-1t, in WI-Hlul?ll populations . CONFIDENTEAL SUBJECT TO PROTECTIVE-ORDER 324752 NFIDENTIAL SUBJECT To PROTECTIVE ORDER. .Among the 70.childrEn, numerous?cuSus of deformabiuns (oCulur' .lumps on forehead, valgus [ch (feet that QuLward) and [Finu11y, Lhuru lh, and can hu, NO prleP Hy .fuusonublc_upphuxlmatjun of PXUUSU ?lb? 244,5 (?nd .uipcricnced by pregnant VchHumcS? ammunth -th?l? ing?stcd or. whcul this may hum: during pregnancy; Thus, any att?mpt Lo bIth dulpuLs ur Milling-HIS Ito'h?fbicidc eXposure is.prcdestincd to failure. It can nuly h. contluded,that the birth records that haVu been suVVQyud, andW pr?bably any that will bu in the futubc, f9r.SuuLh ViuLHdm. ?fo? th? period 1900?1970 ?annot answer posjbiyuly.thv qustjuun about_?oasibl? qdversc prendtul effects fplluwlng?humqn EXpUh?rF-lu l214;5;l. bust be mnphusized, that Lug bug; made almost ccftai?ly Would have PCVualcd any mafkud ln t?c'incidc??e of or tJu: sLFikiug*r u?dcfuct such as that produced by Lhalldumidc.? lu or IcopSidcrable effort; #0 such cecufrcuc?s wcru fuuhd". . A furthp?.study on birth defects j?'SnuLh Vlrtuum was l'l'on? That lung, 1:1. .11. (-1971) 'l'lluy I'c-purlud Lhut. out of 903 south chtham? scuki Shelter in Lhu North, ln hQSpitalsand lodgings ip_Hanoi, 19 adult Hoan, including [our muthurs and 70 children between the ages Of'b u?d 14 had ?QXpos?r? to h?hbicide sprays while living in Lhc,5buth. ?01 th .four mothers, two had given birth to children WiLh Downs has i ullb, chromosomal aberrations becamc.cvidcnt.' Tung concluded: (translation.in Young; et'u1;; 1978) "Though still limited in number, our clinical - ob5chatio 5 Confirm the results obtained on animals by Nncricun researchers. Thu masslvu and pr010ngcd utiliZuLion of defopmuuLs busidua Cutting (1.9 ahd (1971). pupulu?tibnb?. I Sitic?ntil'itt Studi?s fir-at. linking liq-.ullh (d-l-(icts Lo uppuul'lzd. ill June 26, 1909 and Juli/,5, [90.9 lc-q- ?uu 2,4 The public response to Llu- T'vlm?ualnut Studies of Victnm?cs? hospital l?u'c?pl'db? cumlucL-ud ly by (IQ7I) The President's AdVism-y CununiilLutf un_ (:V'uluutcd Mic-Sc studies and concluded Uu: I-Ull'ulelfq': "Smnmurizing tho. Vietnam Tlul'u nu hunmn fit can'bc 'Sdid?thut, (Il)_Lhu sample of births. bul'wryt-d was I'I-uui ,y'eahb?to year a variable but usually. l'l'utthu? ul' th'v total nmnbur, it. was ul' Llu: gc-ugruphit'uud- distributions, (3) the hchin Sprayed ?uml ?them-um- exposed drums Wul'c greatly undur?represented, and (4) ifucnl?d? wul't: noL and, ?(has ul? ETAndyospeciully of cbngun4L malfubmuciun, duride Frum thm-wuru' 'cqually unrealizublc. example; the OVcrull'cunguniLul ?Jrate found in Suuth Vietnam; 4.91 per 1000 livaithh; L: about half 'of what S?Ecportcd in oLhcr_sLudic5 in of Asia, and possibly a'quartgb uf-whut might ucLually:?kisL nL term, IA. surthef?. indication 'Lliut LIIQ newborn Cl'liVl-d'l'cn Men: not, curullully? >cxaminud is th? ubsuhcc of hdejfny Tmulformqtibns compiled by LhcAEmy (1970) despite the fact? (hm. somT: OricuLaJ populations h?uvu ELO have anin'Ci-dencu 91' this culldiLiun not. leL in CONFIDENTIAL . SUBJECT To PROTECTIVE ORDER.- .024754 I I . 44/, . I CONFIDENTIAL . .l SUBJECT . T0 PROTECTIVE ORDER, :cipcrichcd?by Vietnamese Finally, 4'5, and lav, pl'g-r'im- ui' Llu? uxluisulw: Ll) 2,45'; T?1?))gl Iwoumn, including; what. .um'nuun_ -thcy ingested op ub?orbcd and when this mQy-huvu uncurrud during - pregnancy. I Thus, un?yfattompt to relate birth dun-?L5 ul' Isl i Ln?.th to herbicide exposube is predestined to Failure. It can nuly hv' .conbluded that'tho birth rcCordS that haVu boon SHrvaod, Jud' 'prbbably Edy that will be surveyed in the future, for South for the periOd 1900?1970 th about p055iolc quehsc homau vxpu5uyr Lu It most be mnphusiged; ?OWUVcri-that the Suarchc: that thU- been havolrcholcd any morkcd Jnyfuhsp in? the incidence of ?birth defects or the. or a atl:'ik'ilng -dcfuct such as that producod by thalidomide; or? .Kcousidcruble no such occurrcucus woru found"; A further _study on birth dol'ucts in South was ?pcl'for?mcd by Dr?. Ton. That 'l'ung, at al. 1971) They reported that. out of 903HSOuth Vietnamosc seeking Shelter in tho North; in? hospitals and lodgings ih [our mothers '?and'7olchildfen between the ages oflb and dicevL ouxposure to hefbicidesprays whilo living.in tho sooth. two had Igivcn?bi'rth to with Downs lAmong the 70 children, numerous Cases of deformations (oculul' lt'h?lullh, lumps on Io?eh?gd, vulgus feet (foot that cxtcudud ootwufo) and chbomoSomal'?berrhtiohs becumc.cvidcnt1 _Tong?cohclodcd:l (translation in? Young, et' ?ul. 1978) 'fr'hough still limited in iiwinbur, our clini'cu1_? observatiOhs Goofihm the rosultg obtuihod ou_ Animols bmi?cricun resoubchurs;_ Thu ?assch and prolonged utilization of deformunts?busldusI to. gum?sh?ul Soil and L?lufa'u anxo?ng Lhuil' progeny the impuftuncc ul' Mlich {?cl?dills Lu bu In the w? sc?n such an inhuman fut; fay the surviVHPs? except in_the case uf?utomic'yur?" similar 0" DP. 'l'ung' Mus by Rose? and The author's r-cpux-Lud mquSLI?uus bith?s, SponLahULJuH abortions and douLh suugmg man and manual.?- exposure to the defoliunt?._ n'Thu linkage of Dpwn?s and exposure .sugg??ted by Tung has been subportcd by Grumne? in a rpport*- jbyi?onoboff (1973)). after inspectiou'ui'I both North and South Vietnam wcr?: ?"Providgd that it be LhaL Lhi$f?5LimQLu. ?chnnof'b? anything but.a?cuuLious ?ne, it @uy Ebe?ass?med that there ab?-at least HY with h?rcditury dcfuct$ J?vsnuLh'ijf?nm. VThis-docs not include all Lh? unborn Labia; whogu'7 a mother; were sprayed LhuL ?were flansih recent months; .It dug? not includuv - who were S-Li-Illbol?n, or: died bx??l hi 12111",- 6n accognt of their-scriuus chrumusumuLic duh-thg1 'Even after the war, it will probale b9 pugsu?lp to Afrivc at only an approximuLiuuVuf (Mg u?turv ?rqlp "of-this will only :bc? ablu Lu lt-VM?A?mim? I . I 't?e.5ub?ivdr$ the time CONFIDENTIAL SUBJECT TO PROTECTIVE ORDER. 0 2 4 '7 Q, . 'l??ngilv?t; .Inl . ulSU my: unuLlufl.? ht?ult :l?uil I cl.vf.?cit.thc attributde LL, In 197'}, "l'u'up?V "rup?ixggeduvan incr?gus?i?h till-w Algersqn?s- I?liivver? in?lmppor?ion?to. all??guc?r" puLJ admitted to "Hanoi huspi'guls during 1 per'J 9d 9 62-- . He. cut-5gb out. 7,01; with athob?c??dgcumuxitcd yum . -- 11-111,qu Chaos of. ?61,141}. .cang-Vuri'v cram, . I i In. Agent)? 'Rus?iur?h uni ?1 th? Tum.r Btu-d)! Cli'ifti'c 11011 [of 1-1.va i in Jilwhic'h they.pu?nsidem?d: .Lu? (Lyn inu'cl'?q?giw httl?bigidvci lsil?njgy (ou ll ivm. (Anna-p . "fred?chcy.giy I I I thdy??hg? offered uly' Lille: of." um I of ?lm East; Aflutogin decaf: HuLu-ai-ully': ?us a; @?riiLJnuj Hunt.- ?ji; grains I add has.? been. angg?stgd g: LL'hcif ll'i?vulr' Ic?-?ncyv Ivi'vn?cidunc?c?, kurl' .cuu?di (gm ?wuulld:' h?nr._ cxipcci?d'? "?aflqtoxin in din lu'blt-~ [bud nu; I fIn 1:974, tuliu Nutiu?ldl I Sciuzuct? .nii'uquVu-Yg-dh insults, ql' study; of? {luring 1972-19-73,. 'l'hu' NAS ?naught mil- e'viglc-Ikcv' lurruu- I'dgtgi?h Lind i-bfl?l?L-h Iivn limitluus. 1 ~Ain- unul'y?srisl lhquipj Lu} If?In-u-?l-c- Ip?hu?u?c?l .uu Cullsib'LunL unati'qu.li unf butwc?nmniaL?l'drmuLinnm "uhd?Tm?muul, '91? herbicidus I I To, ddt'c'v'chli?ru ugh-km? >l'u4nf' Hei'l??cts (?uhj??ltin?- l?x?mu h?mun. ?:xpOSp-Ih to Ami-Ml.- . Vi ,bf ?l'ung lug-v.1: I gaunt-u] ly Iii-pm un-L I CONFIDE - - i In . in cereal grains and has bucn suggeSLcd a; an thing, (.1, d] . ,v ?150? reported uu? .ulvt-rmj I. ?ch'f'cct Hhc' attributed to dc?l'oliu'nt 197T: 'rcported an incheuSc in the number of personS-dingnusud*wiLh? primary Iii/Her cancers in proportion to all culicur' 4ij UHLH .Hanoill'mSpiLul-S during the per] ml ?Hc COmpaPCd th-c? 790 linl" 7,011 Cdlu'u?i' with 11?: uurligr [xv?spraying yams, 1955-1961. liver-canes out of total cuHCUr incidunCu In a 1977 InternaLionul' Agun?y- for 'Rusuurch o?n (lum?gh (1977.), the Tung study Was c'ri Lvicincd? ?lfui?l' '1 Lb limitations in which they considered l?uaulLud .?uyan ~1nudcquatu assessnumt between lu:rb1c1_dc apl'uyung .md Juvm' (Hutu-I" fr'cqucn?y. . Fb-rd,' at (197-8), ul't?crudr?u fur-t.th wm?Lhy c'o'nl?sumpoiuu ul'latoXiu-CQi-meuim'ntu? I?uml ?u in 13;:tiva the "jEustL occurs 'nuLurully us Lhc? increase in?l'i?vm' cancer incidence. ,Wur- cumljumm ?mmld- In; cx'chted risks . in uVuilublv mod gl?uius. In 1974,? thc'INuLiuual Academy (um results ol'?i?sl?gtudy pf Vianum (Lu-ring 1972-1973; NAS cu?nclmusiv-c?evithc-c ub?suciutiun ?bfL-I'L'h luminan?. An (??lly-Sis of hospital rug-:urds UVI shown] nu [zuLLc1:nn_0l' unsuc I .H .. malformation; and annual amounts ul? hex?bicidu5_ (11' gm" To dam: than: is still gll?ltdt? dchLu ubuut harmful .el'i?ccts result.ng l'x?um uxposuz?c to Agent. In Vit?lld?l. L) gtluurful I CONFIDEN i. Mi. . 024.7 SUBJECT ORDER- ignto . 1, Levinsk?as, GZWF (4-380c 8; 1982 I ,B'erendt, -E2ND . . - - HV.S..Scott, E2ND ax Agent Litigation . I . .LL- To; Bistlin'e-, The' d0cument Summary of?: ToXicologic'al Data Of. the Phenoxy'HerbiCides" by DerWilliam McBride contained 45 pages. Q'Sincethe last page ended in the middle Of a sentence,- I am not-.sure- how-much of that document did not- "see. 7_ Nevertheless; the part that I read Was well written.? It is ?a-good, objective review- of the subject. It is a balanced presentation with 'which I have no quarrel, - - . On page 27, I.- noted a'question mark that you had put alongside the phrase . "four of the six original workers were examined" in 1953'. I do nOt know that {is .?correct or incorrect. While the statement can be checked, it is unlikely that we can get an answer. back .to you before the scheduled. March 19 submission to the Australian Parliament. One difficulty in checking out 4 that statement'is?the' absence of aspecific reference to'it. As I-noted earlier, the document appears to be incomplete Certainly; no bibliography- . was attached; I I suggest that McBride's review-be given to Charlie Love 'who is defending .?Monsanto in the Nitro' litigationJGeoirge J, Levinskas talw CONFIDENTIAL SUBJECT TO PRGTEVCTIVE. ORBER024758L