Document V3kaMQKQbjvvKv8077rbBKjkZ

-r ' N; * 00 * 0919 07 09 0049 I34*12$9 11 1550 U5&-2490 1493 * 14 15 1539 Tratst ir A:*?4i Fer M w tiai # / th* ?C 7^4 F istiata falau tos, 0 * t May 13*3 Cpcaiaz tfiiarks Dr* Cirdatr Arar C b je stim tsd ?U as Xtrr C tjcstlT F issi C'9% tj C T VSTf S?<5f7 Air Porto Cbjrctire al P lisa Air Fers* SraaVer 9tfU it0 iccrka J k T c*olrrr / *- * i * a Trra JUtiers? Cea Sfilzare Dr l ^ u s i n Or M in a rli r*a2: OS Frieras at Plma Issicela * Offesso r sl Orari11 C3 Frrr? Mri p i* XtcI s * Cr/cxjc EKi K t'ru c 07 tlArfsri;ht Or s i lvsjp OtfcsalT* Prggrsj *U*Jk CDC Textes 6 '? Dr K esiswigM fa. .Pt Or. Silrer T fc-;.v>*itie-. / la s l - iii 22 s i O m / V ^ ~ Zxtra T ir e ite r ifil Testa A / T---V--^- ^ / Or SllvcT sr ' - Cwl Saur ' / / : 1 Ccd ?A11* C lots *"*?r Cea y d s T c a t ?'2r 12-CtS, So^a 33- I VS,, ' B rie fin g to P r e s id e n t's S c ie n tif ic A dvisory Ccmmlttee 3 Kay 1963 by C5R Agency P e rs o n n e l a n ... POSSIBLE HSALTH HAZARD 0? PHEaXTACSTATSS AS RELATED TO DEFOLIATIOW'OggSATIOSS ..... i a Vietnam T h is r e p o r t t u s a a r l s e s t h e b r i e f i n s g iv e n 9 Kay 19 S3 by members o f t h e CBR Agency t o t h e P r e s i d e n t 's S c i e n t i f i c A d v iso ry C om m ittee. 4 Form ulae - F ig u re 1 shows th e fo rm u la s f o r 2 ,4 * 3 d lch lo ro p h cn o x y * acetic a c id and 2 , 4 , 5*T tr ic h lo r o p b e n o x y a c s tic a c id T hese s u b s ta n c e s a r e u se d a s th e a c id s , s a l ts , e a te rs , and o th er c h m ic a l fo re s . The m ix tu re, "P u rp le", c o n sists o f f i f t y p er cen t n*butyl 2,4*3, t h i r t y p e r c en t n -b u ty l 2 ,4 ,5*T, and tw enty p er cen t iso b u ty l 2,4,5-1 E stim ated P o ssib le Poaa o f "P urple" - Zable 1 illu s tr a te s an attem pt to e sti* a a t a t h a d o se o f " P u rp le " w hich n i g h t h a v e re a c h e d n e a who w ere ex p o sed to th e s p r a y . The m a x im a q u a n t i t y o f " P u r p le 1* d e l i v e r e d i n a n y a r e a was tw e n ty * fo u r pounds p e r a c re . T h is q u a n tity was d e liv e r e d in two p la c e s on two s e p a ra te days. T w enty*four pounds p e r a c r e i s e q u a l t o 250 mg p e r s q u a ra f o o t . The s i s e o f th e se d ro p le ts would m inim ize in h a la tio n and fav o r body su rfa c e contam ination In fo rm atio n o f o th e r chem ical a g e n ts shows th a t th e amount o f ag en t f a llin g on a %man p e r u n i t o f a r e a l a a b o u t s e v e n ty * f iv e p e r c e n t o f t h a t f a l l i n g o n an e q u a l a re a o f th a ground. A o n e -h u n d re d * ten pound man would have a b o u t 1 6 .2 sq u are f e e t o f body su rfa c e . Only h a lf o f t h i s , 8 .1 sq u are f e e t , would be exposed to th e s p ra y . T h is , th e maxim is q u a n t i t y o f sp ra y w hich c o u ld r e a c h t h a man would b e 30 m g/kg, IF t h e man w ere i n a n a r e a o f maximum c o n ta m in a tio n on two days o f sp ra y in g . '" The T o x ic ity o f P h e n o x v a c a ta te s - T a b le 2 shows LD50 d o se s f o r phenoxyace* t a t e s In v a rio u s sp e c ie s o f an im als by v a rio u s ro u te s o f a d m in is tra tio n . Most o f th e p u b lish ed d ata r e f e r to th e p a re n t a d d s o r s a l t s . However, t h is inform atlor j e r ^ n e n t s i n e t h e t o x i c i t y o f t h e v a r io u s f o s s a can ba i n t e r r e l a t e d [NOTS: ** i a th e v a lu e s g iv e s in th e column under "P u rp le " e r e d i f f e r e n t from th o s e 'an in th e s e a t i n g o f 26 A p ril 1963, b ecau se o f f u r th e r v o rk a t C3$U , Work dose : a r t h e m e e tin g o f 9 May 1963 i s g iv e s i s a l a t e r r e p o r t ] l a to x ic doses e l l fo sse o f th a compounds roduct m uscle a t i f fn e s s , a ta x ia , p a ra ly s is , coma, and death These a ff e c ts a re , in ila r i s a l l anim al species i s very high dosage acu te v c s tr ic u le r f ib r illa tio n r tay occur* Bote th a t a l l forms o f 2,4-D and 2*4,5-r 4* have roughly sim ila r t o x ic i ti s s , i s a l l anim al sp e c ie s, and by a l l ro u te s o f ad m in istra tio n , o th er than th e percutaneous route "Purple" i s such le a s to x ic per cutaneous ly than by th e o th er ro u te s o f adm inistration* C lothing g iv es a d d itio n a l ^ faction and i t h a s'n o t been p o ssib le to k i l l clothed r a ts v ith a p p lic a tio n s o f 12.5 mg/kg# Dogs s a y ba c o re s e n s i t i v e th a n o th e r s p e c ie s t o t h a p a re n t compounds* * * T a b le 3 shove l e t h a l d o s e s i n mg/k g a s c a l c u la te d from p u b lis h e d d a ta by th e B lis s method* Where c o r e th a n one a u th o r i s sh o w combined d a ta -v e re used* Three columns p r e d ic t th e d o ses v h ic h m ight k i l l - 1/100, 1/1000, o r 1/10000 - i f a l l o f th e cospound e n te re d th e body by th e in tr a - p e rito n e a l o r th e o ra l route* The p re d ic te d v alu es v e re o b ta in e d by ex ten d in g th a d o s e - r e s p o n s e r e g r e s s io n l i n e to t h e LD 0*1 and LD 0*01 v a l u e s o n l o g - p r o b l t g ra p h *s paper Note, c h at a l l o f th e s e v a lu e s a re h ig h er th an th e 30 m g/kg, v h ich i s th e g r e a t e s t d o se v h ic h c o u ld h av e re a c h e d th e man i n m axim al s p r a y c o n ta m in a tio n * Remember a l s o t h a t t o x i c d o se s by th e p e rc u ta n e o u s r o u t e v o u ld b e t h r e e t o te n tim es h ig h er than those shovn here fo r bare sk in and perhaps t h i r t y tim es g re a te r fo r c lo th e d skin* S a fe ty Record o f Ph& r.oxyacctates - The o u tsta n d in g s a fe ty re c o rd e s ta b lis h e d / f^n-ie su b sta n c e s d u rin g -n o r a th an f i f t e e n y e a rs o f e x te n siv ei o p e ra tio n a l us I s , germ ane Co t h i s d is c u s s io n * ' r - .' r ' S ine 1947 s o r e Chan th re e -h u n d re d s ill lio n pounds h a v e b e e n p ro d u c e d an d u s s d Co c o n t r o l v e g e t a t i o n on a c r e Chan fo u r-h u n d re d m illio n a c r e s o f la n d i n Che U n ited S ta te s * H ates o f a p p l i c a t i o n ra n g from one- s ix te e n th to o n e -h u n d re d -six ty pounds pax sere* The annual p ro d u c tio n i s e stim ate d to sxcssd f i f t y a i l l i o n pounds and f i f t y a illio n acres a rs tre a te d annually* * ** T hese h e r b i c id e s a r e r e g i s t e r e d b y t b s US D epartm ent o f A g ric u ltu re which means th ey a re co n sid ered to be (l)'n o n p o is o n o u s , (2 ) n o n co rro siv e, (3) noninflansaable, (4) a v a ila b le in q u a n tity , (5 ) econom ical, % and (6 ) e ffe c tiv e . The D epartaent o f A g ricu ltu re m aintains co n stan t c o n tro l in a re a s v h a rs h e r b ic id e s a re ap p lied * {Hiring f i f t e e n y e a rs o f e x te n s iv e 'u s e th e c> a rta e n t o f A g r i c u l t u r e h a s n o t r e c e iv e d a s i n g l e c o m p la in t o f I n j u r y t o hum ans, liv e s to c k , w i l d li f e , o r s o i l from th e phenoxy h erbicides* K ajo r m an ufacturers have c e r t i f i e d t h a t none o f th e workmen in t h e i r f a c t o r i e s have shown any i l l e f - facts* Commercial spray o p e ra to rs re p o rt no adverse e ff e c ts except fo r a very fe v a lle r g ic s k in re a c tio n s* These companies re p o rt v ery fev claim s fo r damage to A liv e s to c k and none o f th e s e have been proven* Only f iv e s u s p e c te d human in to x ic a - *i Cions have appeared in the .literature in all of the years that these herbicides have been used* m The use o f th ese h e rb ic id e s i s not re s tr ic te d to th e U nited S tates* The R ussian s c ie n tif ic p u b lic a tio n , "P ro te c tio n o f P la n ts from P e sts and D iseases, pp 55-57, 1961", re p o rts th a t in th e re c e n t years' f iv e a i l l i o n h e c ta re s o f g ra in , crop in th e S o v iet Union have been tr e a te d annu a l l y v i t h 2 , 4 - D. T u r th a r , s y s te m a tic tr e a tm e n t f o r t h r e e o r fo u r g e n e r a tio n s has not affected th e q u ality of the grain. A n o th e r p u b l i c a t i o n , " P ro b l in Zcocook* s , Moscow, No 1 1 , pp 8 6 -9 0 , 1961", s t a t e s t h a t i t l a p la n n e d t o u s e t h i r t y - n i n e thousand seven- hundr ad f i f t y to n s o f p h en o x y acetates on t h i r t y a i l lio n h e c ta re s i s an' e f f o r t to- in c re a s e food production A th ir d p u b lic a tio n rob lea s in K u tri- t i o n " , by t h e M e d ic a l S t a t e P u b lis h in g B o u se , Moscow, Bo 4 , 1961, s t a t e s t h e torn- i d t y and c a rc in o g e n ic ity o f a g ric u ltu ra l chem icals vas in v e stig a te d by th e In te r- d e p a r t a c n t a l Ce om m ittee f o r th e S tudy and R e g u la tio n o f T o n ic C hem icals a t t h e S t a t e S a n i ta r y I n s p e c t i o n O f f i c e , USSR. The p h e n o s y a c e ta te s v e r s among e ig h te e n approved f o r a p p lic a tio n I t v&s s t a t e d Chat cro p s t r e a t e d a e p r e s c r ib e d w ith 2,4-D p re s e n t no. danger when consumed ee food F rid a y , 26 A p ril 1963, a com m ittee o f m e ric a a e x p e r ts on h e rb ic id e s n e t a t Edgewood A rs e n a l, M aryland, t o c o n s id e r th e 'u s e o f p h en o x y aeetaces in Vietnam* They concluded th a t no h a z a rd to h e a lth v as In cu rre d a s a r e s u l t o f th e q u a n tity o r th e method o f u se in th a t o p e ra tio n . C aco d y llc A cid (F ig 2) - In tome o f th e o p e ra tio n s in Vietnam c a c o d y lic a c id v a s used The maximum d o sa g e a p p li e d v a s f o u r pounds p e r se re * D etailed d a ta on caco d y lic a c id a re more sp arse th a n t h a t f o r th e 2 ,4 -D and 2 ,4 ,5 -T What i s a v a i la b l e (T a b le 4} i n d i c a t e s Chat th e a rs e n ic a l Is only o n e -th ird as to x ic as th e phenoxyacetates M oreover, th e p amount o f eaco'dylic a c id p e r a cre vas only o n e -s ix th th a t fo r th e phenoxyacetates. 2,4-B 5- TABLE 1 POSSIBLE DOSS OF PU?.?LSM BY DELIVERY METHOD Ground Dosage 24 lb s (10.9 k g )/a c re (43550 sq f t ) 250 a g /s q f t \ ft Ground/Xan Dogate R atio 1 og/#q f t on ground O *75.og/sq f t on oan A v a ila b le Body A rsa on P rona Xan (n ak e d ) 0.75 sq a c ta r s (o l sq f t ) (250 ag /sq f t ) x (0*75 ) * ( 3 .1 *q f t ) (ground dosage) x (nan/ground r a tio ) x (a v a ila b le bo d / area) 1519 a o /a a n 50 kg (body v alg h e) " 1519 eg 1519 ag TABUS 2 TOXICITY OP PHKW0SYACETATE8 ( S p e c ie s Hat R ab b it Route ip is It pc pcc lv ip 1(5 it A cid 3750) 2 .4 -0 S alt V ----5(2(2)-589(2) 66G (2)-805(1) 400(2) 000(2) Li)50 tnp./kfi____ :___________ ____________________ _____ 2 . 6 ,5 -T . Mixed B utyl A cid Mixed B utyl "Purple*' ( 6 ) E nters C aters 436 620(1) 527(1) 481(1) 448 . * 543 3309 >12500 6 2 6 (1 ) 2 1 2 (1 ) 573 638 501 pc 1351 pcc m- Dog ip is it 1 0 0 (3 ) 100(3) - 353 305 Mouse Guinea f i g C hicks --PC -- ip i<: ip in ij5 -_ 368(1) 6_r.9 m 369(2)-426<2) 3 7 5 0 ) ____ 576(2)-600(2) 5 5 l(l)-1 0 a 0 (2 ) 713(1) 8 4 3 (1 ) 2(U )(1) - 3)9(1) m ax 310(1) 9 6 0 (1 ) 250(1) . >1250 * ( 1 ) Roi.o & Hyman, Am J Vet lie d , Vol XV, Co 57s p 622, 1956 ' ( 2 ) (1111 & C b r l l s l a , J In d llyts & T ox, 2 9 :8 5 , 1967 ' ( 3 ) D r i l l h l l l r a t i k a , Arcli In d ilyg 6 Occup Mod, 7 :6 1 , 1953 ( 6 ) CllDL -7 TA3LS 3 LETHAL COSES FOR PISSromCSEATES S p e c ie s R oute Uo o f AaL-sals L. 250 - , ag/kg * Rat Guinea Fig Mouse Rat Guinea F ig Mouse - P 72 ip * 43 io 200 ig is is is ft 90 166 13 20 it is Guinea F ig is Mouse _ _ _ i z __ 40 2 27 512 590 3C-? 637 630 481 357 527 330 373 ------ "" LDl ' LD0.1 LD0*01 S/kg og/kS tag/kg ....................-? H efarenee ,| m 2,4-D * 223 170 296 235 nhVp.wn 165 240 130 231 170 . 390 375 237 205 IA>.5-T 235 230 252 220 156 113 133 H i l l , 1947 195 H i l l , 1947 U O H ill. FitElweh. 133 u n i , ( u & *.dA) , 130 H i l l, Rove, F itsa u ^ h , (Na) I 340 Rove, 1934 i 135 Rove. 1954 : i 195 Rove, 1954 195 Rove, 1954 93 Rove. 19 54 1 6- TTGCaS- (c a 3) oa 9 TABLE 4 LETHAL SISSSIg DOSES OF CACOPYLIC ACID IN RATS H jaber o f R ati R o u te LD50 LD1 LD0 . 1 LD0 . 0 1/* . T ine to Death - Ad - In trag aatric - 1350 0 3 /kg 700 ng/kg 565 ng/kg 480 ng/kg - <24 hours -10- P IA SLq 4*0 "tC *, i ^M*0 / J L j^ ^ r s ^ t y X .r^ -7 fv ^t 4*~t> L C r^t "k * J h s h 0'l*>~cfiLA*+Cm~ ' % o j b * * ^^^n? TV. --& /& & **% , ( lL ^ L ^__ ^ a U ^ jL IW ^ ^m- V ^ U o /La- - * ^ < .b x 'U rvx ^ xjc.- C*3 S isu ^ > 0 ^- -^ -- x ^ j , - v _ - y s J .S x J ' j J ^ 4 I t) 2 ^ r u ^ 5 fe *^ ^Vw-^O'W wA? y*. lr+~~~ J$,4?^~**C*m ' 7/ V w ' l^C -"w < * * '* - < - * ' y~ . 3^' V?- . 'S jL/Ui ^ i^X i. ` !?*" * J i w%(^ - ^ y | /. y i c*+ *~~dr ^jj^A<.^3*c ,, `^ *r k> w /\.^<- t " ^vv^v ? e ^ < # r - cJ^. ^- -- \ j4 c - ^ q r ir*- Z--O X""*0 -o * j^-J / 4 , fu v '-A jj r v n - i ^ UDL I, ft ' /v t^ o -C 0-O " ,, I Z --q ^ < C ^ < , ^L c"V < ^-- /.' -6-( - w U D \ ffUr)^o O c d c 'ts 's - C it^ ts z } <n c ? v ' , ^T L c*^-- 7^- J^A*& *s-C *~. -- /r A & 9 -& ^ > Uv^pW ^^rJM W * i / ' rM ' W O U -- /{ U - U D f c to X Jb '*r$* .X *0 ^ *(/-- {>**-<? . aJU**+Q+m /^*o 1 K C /<-- 5-< ^__ ,cr*^Su^-ce a M/C^ ? i ^ aL^i ti /C k *A ***~ L V A -/ C / T ^ ^ j i ^ C '**'*C TU , K iM ^ } --D Y"? /X ^ 7 ^"Vv. t L . sf ^ ij^ j^ *X - --C>/ . JU-A^ * / / / / t o Z--D / y r - w -^ ' n> *;A/ *.--i I^3^U ^ r= 4^*-^- b )& / '-ft -fcC~* " C U -*- i . ' * - ACDTE ORAL TOXICITISS 2.4 P es Form * A nim als P u r i f i e d Na P u r i f i e d Na P u r i f i e d Na C rude Na * Combined a l l S a le s 24 18 12 18 90 e nea Pigs icks gs Na A cid Na Na A cid A cid A cid A cid 44 60 : 20 166 29 18 30 12 LD50 mg/kg 670 612 697 677 637 665 375 '*89 630 357 4SI 401 100 1 LD1 mg/kg 311 ! 158 324 167 240 . 379 . 187 | 193 ` 231 } 237 * 390. : 135 ! : 59 LD1 ' Tower 9 57. 162 44 155 45 164 271 129 90 174 ; 164 i 273 ! 53 11570 R eference H ill - T ab le 2 , 19*7 H ill - T ab le 3, 1947 H ill - T ab le 4 , 1947 H i l l - T a b le 3 . 19'*7 H i l l - T o ta l d a t a , com b in e d Na + KH^ Rowe * 1954 Hove - 1954 F itz h u g h H i11-R ova-Fitshush Rowe * 1954 Rowe - 1954 Rowe - 1954 D r i l l - 1953 i ; x ^ k ^ T & -U ' b y c g !Q t~ * t' * T - i - 0 ( v r ^ x - i T w ti ^ _ tr V J 2 s * ^ X X ^ V'O -- < * V-- J Li~ ^ S ^ ' f~ fn V&~ a . TU. SJr*- &;'- & **& lc*$ ' Ef' SfQ***- ^ $ - 3 ^ * t t L 4 w > 0V- .j 1r J t - !Le~L4''mts* * l^s\S O ^ C ^ C jL ^M , \ -- JU ^ /V^* \ - W r'V 'A - -Ti C ^ r v ^ |> M .f J .- f - W ~ - N , L o ^ / u ^ W K . t u . -^Z C /" ''^ lt'- A. Ca * , *T-C- * ^^ fc-*\ 7 ^ ^ - & -'-- (>- tr > ^ ^ * j^ ^ e J L <J 'T 3-j ~ 0 \ J - C ^-''< -_*jx H : G -***& -- V W r i . -- f c ^ r * JL - A st* L ` " . '^ 'L 't '* ~ l& a C C u L t^ L < J L b 'sJ jU J L ^ p * U f 'h ^ J ) 2 -/^ , r r <_ 4ft o f ^ U - * C ~ ^ ~ * -K .. J > 1 i^'3S--,'* A- ^ s ? fc-. `T O - v 6 -v t, - * /* l^ c x * _ C - , ORAL TOXICrriES 0 ? 2 .4 .5 T j Species ii | R ats Guinea P ig s M ice C h ick s Form No o f A nim als A cid . Add ; Acid ; Add 40 20 27 33 - LD50 mg/kg ` 527 389 373 ! 312 l LD1 mg/kg . 285 252 156 144 j LD1 : Lower 957. R eferen ce : 2S0 i 171 69 83 , Rove Rove ! Rove Rove ~TcrV-c*J*^ /? *** Vi M ^ % ^ 4 ^ 'V * -'^ - lA rC fc L * . "D6 - 0 r iAi J~M /'C- <^- .i^*C-v^-- V<-.' '- C # l - , /*) --4 * <r T U - - ^ S - - t ^ A i c T3C-? y / V c O i L ^ * \ L r & S - V ^ V l^ T'-~_,iV`"- ' *'*''' ' ' W l*3 'J-q _ &-+~C-. -^^y~uv^v% _ V *. A '-'b -lx 't 'S- 'fe fc rr* fc * f* <tJ. / , ..> :U -i-psAl C-C o s t> ^ o ^ L - W^V1 ^ A . . <5 f - U f.JL L / 4 -0 /J t 'w-^-a4^C 2-- /? f f A jC * - Z - i< ___ ! r` ^ i t-/. -o ACUTE TOXICITY O? PURPLE nrmnm ACUTE TOXICITY OF PURPLE Rouee & Doses a g /k g O ral LD50 LD1 LD1 (9 5 ) is LOSO LOI LDI (95) 1C LOSO LOI LDI (95) LOSO LDI LDI (95) I -R aC s 1 566 213 124 ! { 586 : 121 i 64 569 244 . 107 ! 1 5562 3178 I 2034 R abbits Dogs 1994 363 178 12034 493 40 i 1 *250 j > 850 1 500 >250 I >1250 : j i ! i 1 1 ! ! , ! j 1 j j 1 srWK 2* a 230 .7 / v*4'O u - tt* . Y cf -vi A V V 'W 1 r s S j u ^ y ^ y J sj c ^ 4 -< r y ^ - U ^ L ^ - C - mX l ^ S s l^ iX 'ti fi b ; - a _ - o c * -<-<*. cf~ ~ JZ J^ i ^ a -e _ L***^ Y rtf * / r ^ J *-4 fOtft fj$.t.c+ TZ-~P~ }?C_ LJDl - L . U P ' -^ I C?'5') * <* 4 - 0 T C u t t - ^ -w--v p < ^ - r " -* .~ C C L , ( ^ - >-- 3 W -a 4-*-v*^C-- - yp .( 2 - 5 ^ o 7"? > \ ~ 6 ^ 4 / '^ + t'+ ' ^ S V & ^ C f I j3 , V*^ > ,C - J* f9-<iL , I ri.'~c*A J A jty ^ O ~ t *>P. -- *-- x - o a *> j i o yp _ *4 .P i ^ B f t? ^ 2J o W-C>'1>c 44- ^ l A s j ^ u jj. - < * r) L - / J6- p l f I rv i <>t '*r* ' *5 /^ C & jL ~ ^' jL - r- & - & -- T O i-W 6 T h- ^ k l^ c c ^ / c ^ f * . mP+ L * * * i 7 * r^ <j` l IT" So - - w/ t ^r-*-. i , *S*^ / Hr u K -* O ir \ fc o , 6 f J \ s ^ ! .( `t - - f ) ta i) /w ftr s -iF i 0 .'"v O jp u f t , ' ' \ , S 7 ( 2 1 - v i s . - * * * } . '& . , v * b ;^ LDS? i'O) ^ 2 J ( ~ r - ~ 'Z 'd is ir ( ? /- Z-t/O V*x mn { s s s - f/) to I / 4* ( T2-,- : U>0 i^o i > /^,>0 0 > /^ > fg k`Vt U>s> *r; - /v "O to / s W / i t * - g***0 i <, ts r " r ?n TO'0 i r i ' - ^ '- - -#w) 3 * 3 - * * V' /^ 3 k > i - b -ya) 2 = - * 3 i.r ) T il}' / ^ar ^ cL ~ /s * 7 ) > /ifD > /w o I } I-- f* J * H/v UjS'J U) H & f ' f 1i 7-2- 5"/1 _ i 1 -.r #t l * * i* ' Q t J\ y f tL c ; y . i I2*fe . i . . ; i 6. i 4-* j 5 i # -s-o o ii i */*'T . .Z jL t, ko \^ , , t -*<>". 6 ! 570 j 1i / 7 2 - ij 1 3-0 0 j / f o I i iij 1 1 11 ; : .37 ; Z 3 i1 1 ; l t >o Z3 i ; /7 V t U r* * fc 't e . y jJ L -r lfw * .- h r r - p. ' \\ li*rc7 l u! < ^ i1 ` 11Cju \ ( & X ;j<24 * \ r1 ii 15 H - f l 30 1 t e n 1 * /ic? Qt / !/ s C i o/ *;>y*. !!.; i &0 m'* O 527 * O 11 . 2 .37 i \ i .7 *3 IL * \ -s r ! ^ -2 . n/ i2tfvt-c f fb 't tL & i.5 iii i i1 /./? ! 1/^ 1* i 1 y "9 f/. 373 i $"3 /-^ 7 0 /7 ; i /3 7 : /7 ; 7 77 J" D -'j \ ! / JL-.. iV l vUt? \j /' . ' * i i /V- (9 :-> ? ro * 4 -i" /V >I . /s r i ?; W\UiJ iti *^i* M -w . V7_ ^ rc.,3 /-?/ i 70. - i i LETHAL DOSES OF 2 . <t D TH ANIMALS [Given In s a lin e ) S p e c ie s Route Rat * Sodium S a lt Sodium P u rifie d . tp Guinea Pig Sodium P u rifie d ip Guinea P ig ' Sodium Crude ip LD50 mg/kg 589 576 * 600 Rat Rat , House \ Rat Sodium P u rifie d oral Sodium Crude oral Sodium S a lt oral P ure Ammonium S a l t ip Crude Nil S a l t 4P _ ip _ o ra l 612 677 697 396 426 670 LDl LDl R a tio s Lower 95 LD50/LD1 LD50/LDK957.) mg/kg R eference 257 127 413 309 160 15 * 158 .A4 1 167 45 324 1 155 y .^ 263 191 178 99 311 162 2,3 1.4 3.7 3.9 4 .0 2 .2 1.5 2.4 2 .2 4 .6 1.86 40 14 15 4 .5 2.1 4 .3 4 .2 H ill t. C a rlis le - Table 3 JIIM.T 29. p 8 8 . 19A7 11111 i C a r l i s l e - T ab le 3 JI1I&T 29. n 8 8 . 1947 H ill f. C a r l i s l e - T ab le 3 J1IIJ.T 29, p 8 8 , 19A7 Low LDl because r e s i s t a n t a n imal fla tte n e d slo p e. Itili h C a ritsle - Table 3 J III&T 2 9 , p 8 8 , 1947 H ill & C arlisle J1HAT 29. p 89. UHI & C arlisle JIII&T 29, p 8 9 , UHI & C arlisle JIII&T 29. p 89. H ill h C arlisle JUI&T 29. p 8 8 . - Table 1947 - Table 19A7 - Table 1947 - Table 1947 4 5 5 2 nt acote israAmrroHZAL TOZiciTTes n Specie* Fora Ho. A nim als Rat * Guinea P is - * H ice * P u r i f i e d Na Ha + KH4 C rude Ha 4 P u r i f i e d Ha Ka + NH4 P u re Hd4 C rude NH4 Ha + NH4 24 .72 24 24 36 40 40 200 uso ng/kg .539 512 600 576 590 396 426 369 lda -01 ng/kg 257 223 . 160 413 296 263 178 200 LD1 Lover 95Z 127 156 15 309 172 191 99 190 . R eference B ill - T abi. 3 H ill - Combined d a ta H ill - Table 3 H ill - Table 3 H i l l - Combined d a ta H ill - T able S H ill - Table 5 H ill & Fitzhugh* * ; - * ' ACUTS ORAL TOKICITISS 2 .4 D S S p e c ie s Fora Ani-ials KiC* P u r i f i e d Na P u r i f i e d Na P u r i f i e d Na Crude Na * Coabined All Sales 24 13 12 18 90 1*050 a g /k g 670 612 697 677 637 R ats * Hice Guinea P ig s Na A cid Na Na A cid A cid A cid A eld 44 665 60 375 20 489 166 630 29 357 13 431 30 401 12 100 LSI mg/lcg 311 158 324 157 240 379 137 193 231 237 390 135 59 101 _ Lotrer 957." R eference 162 44 155 45 164 271 129 90 174 164 273 53 11570 'H i l l - T able 2 , 1947 H ill - T ab le 3 , 1947 B ill - T able 4 , 1947 Hill - Table 3. 1947 Hill - Total data, cca- blned Ka Rowe - 1534 Rowe 1 9 5 4 Flt?hugh Hlll-3.ovw?itz hu Rove 1 5 5 4 Rowe - 1954 Rowe - 1954 Drill- 1953 il ill- ACUTE ORAL TOXICTTIES v . r . Rove & T.A. Hysas Am J V et Med, V oi XV, lo 57; p 622 , 1954 Species * A cid R ats 375 L350 - 2,4 D 2 4 5 T 50:50 Brush H ille r fU S a le H i* =d B u ty l A cld E sters Mixed E u ty l 277. - 2 ,4 0 E s t e r s 277. - 2 .4 .5 T 805 666 (2 ) 620 500 431 1070 H ice 363 Guinea Pigs 469 375 (2 ) 551 1000 (2 ) 713 389 848 381 940 800 750 1160 R ab b les Dogs C h ick s 800 ( 2 ) 100 (4 ) ' 541 424 2000 ICO ( 4 ) 310 712 1420 4000 (2 ) K i l l L C a r l i s l e - J Xnd Hys & Tox; 2 3 :3 5 , 1947 (3 ) B jorn & H o rc h e n * S c ie n c e ; 103:479, 1943 (4 ) D r i l l & H ira tz k a - A rch Ind Hys & Occup Med, 7 :6 1 , 1953 ORAL TOXICITI5S OF 2 . A .5 T S p e c ie s F o ra . Anisia fI s R ats Guinea P igs M ice C h ick s Acid Acid A cid Add 40 20 27 33 LD50 ng/kg 527 389 373 312 LDl ag/kg 235 252 156 144 LSI Lover 951 280 171 9 83 R eference Rove Rove Rove Rove TOSICITY or 2.& D IS FTS3 R eferen ce G erk in s. 1943 Hanson, 1952 H a rris o n & R eas, 194 6 King & Pen found, 1946 > Dosage 100 on 1 lb/acre 2000 o=3 100 ppm 65 oca 675-850 c m 630 ppm 100 lb s /a c rd in 3 -f t pond E ffects i'o d criice t o i n v e r t e b r a t e s ?'o c s n a tc t o v i l d l i f e in c a r s has L050 f c r c a t f i s h , a in n j vs Some d e a th s in bream s and b a a s * Sore deaths in cam 2 i-h s i2 r, LD50 f o r c ln n o v s Ko d e a th s i n b l a e g i l l s o r ninnofca i n 29 days " i u c t . J li|>L O ) EFFECTS OP REPEATED DOSES OP FMEN0XYACETATE3 . Compound 2,4 D 2,4 D ron Brush K ille r 2,4 0 Animal R ats R ats Route O ral D iet S teers Oral R abbits In jected Dosage E ffects Reference 10 m g/kg, 3 tim e 3/w eek, 4 weeks No e f f e c t s Rowe & llymas 30 mg/kg, 3 timofl/veelc, 4 weeks No e f f e c t s Am J V et Med, 19: 100 mg/kg, 3 tim es/w eek, 4 weeks D ecreased growth cloudy ' sw elling of liv e r 300 iuk/Icr. 3 t lines/w cck. 4 weeks D eath s 100 i4 100 ppai - 113 days 300 ppm - 113 days 1000 ppm ^ 113 days No e f f e c t s No e f f e c t s Toxic e ffe c ts & deaths Ibid 3000 ppm - 12 days Toxic e ffe c ts s a c rific e d %% 100 mg/kg - i s days Some p a th o lo g y o f Ib id liv e r , kidney, & Cl 500 mg/kg - 3 days tract No e f f e c t 500 mg/kg - 2 days Decreased a p p e tite 1000 tng/kg - 3 days Du-ith 50 mg/kg - 4-13 dooes N othing re m a rk a b le some H i l l & C a rU l k id n ey d e g e n e ra tio n J - 1 Hyg & T ox, 19 hyperpliaals o f bone marrow, decreased hgb 100 mg/kg - 3 - 7 doses D ecreased h&b, d eg en cra- Clon o f kidney, hyper- phasis of spleen, 2,4 D 2,4 D 2.3.5 T * Dogs Dogs lv iv 25 m g/kg/day - 6 days Bleeding guua, leg Ib id u lc e rs 50 rag/Ur/d a y - 23 days 2/2 deaths 10 m g/kg, 5 tim c s/w cc k -9 0 days No e f f e c t D rill & lU rstcks 20 mg/kg 5 tlm es/ueck-O O days D eaths Arch 1 Rye Occ Med. CONCLUSIONS! In summitry anil a T i e r c a r e f u l r e v i e w o f lu x i en I o g i c a l lulir r r l u i c i l lu 2,4-1) anil 2 , 4 , 5 - T u l n a llie k n owl e dg e us to llie manner t h e s e m a t e r i a l s have liccu used f o r d c f o i l u l i o n i n m i l i l u r y s i l u u l i o u s i n S o u t h e a s t . A s i a , no l i c n l il l i a n i r d I s o r was i n v o l v e d l o man o r d o m e s t i c a n i m u l s f r om the amounts o r manne r th es e m a t e r i a l s were used in the aforementioned exercise. i fr* \ ACUTE TOXICITY 07 PCaTLS * R oute & D oses Bg/kg O ral LOSO LD1 LDl ( 95) l LOSO LDl . LDl ( 95) it LD50 LDl LDl ( 3 5 ) LD50 LDl LDl ( 95) . R ata R abbits Dogs . 566 213 124 L/ / 586 64 569 244 107 -- - 1? 1994 - 3 6 3 --------178 "0 ' 5 0 0 - <? * -- 5 5 0 _Bu ' 5562 3178# - 2034 12034 493 40 1250 Ilu*: ny>i uj Compound 2,4 D Ha 2,4 D li.ilta 2,4 0 Ha 2,4 D N:i 2,4 D all:: idatalne 2,4 D 2 ,4 *> a a l t .8 o p rca;y le n te r 2,4 D .a o p ro p y le s te r - 2.3.5 T _ 2.4,5 t EFFECTS OP REPEATED OOSE3 OP PlIEHOXYACBTATES Animal Mice llata Route sc Feed Dosage 1/3 LD50 (90 m g /k g /d ay ) fo r 3 months About 6 mg/kg/day-24 days R u ts Feed i 95 mg/kg/dny-lOO weeks Doga Feed 12.5 m g/kg/day-100 weeks Chicks Sheep Cows Horaea C attle Sheep Sulne Chicks O ral 200 rcg/kg, 3 tiiacs/w cck, 4 weeks ( a c u te o r a l I.D50 " 300*745 m.`*/kft) P a sc u re About 2 .7 7 l b s / a c r e f o r 12 days P a stu re 4 lbd/acre) 3 .3 l b s / a c r e ) *p r ^ 3.3 lb s/acre^ 8 Steers Oral 16, 17, 52, 55, 114, & 161 mg/Ug/day-78 days 2 S teers Oral 50, 58 oiR /k/day*l54 days E ffects Ho e f f e c t s Ho e f f e c t s Ho e f f e c t s Ho e f f e c t s Ho e f f e c t s Ho e f f e c t s Ho e f f e c t s Ho e f f e c t s % Ho e f f e c t s Reference " Bucheri Proc Soc Exn B io l & Med. 19/ U lll & C a r lis le , It F ltz h u g h F ttz h u h Bjorn & Horthcn S c ie n c e , '1940 H ltchell, et e l. J AuIkmI S c l . 194 Grigsby & FarueU M ic h A g r Cap S ts Qt B u ll, 1950 Anderson, A rndt, Codbey, Jones JAVMA, 1949 # ** ACITS TOXICITY OF PITIPLS O ral & -*?/kg ?.at 3 io i t oc 12.5 4/4 7 .5 6.25 5 .0 . 3.75 3.13 ft 6 /6 2.50 6/6 1.83 7/7 1.25 10/10 0.94 7/10 0.75 8/10 0.63 6/10 6/10 0.50 4/10 0.47 0/10 0.33 0/10 0.31 1/10 0.25 1/10 0.16 2/10 0.125 0/10 0.03 2/6 1/6 0/6 0/6 5/6 6/8 2/6 0/8 0/6 0/6 D eaths T* b e l t s it PC c CO23 ip i t 3/6 8/10 2/6 3/8 2/8 0/6 0/6 1/6 0/6 1/5 0/6 *5/4 2/4 0 /6 0/6 0/6 0/6 0/4 0/4 0/6 0/4 0/4 0/6 ce 0/4 0/4 0/4 ~ Icr{j-C*cLrO i- h{&A*,`ui "" J I.S ' %** f} CLo ^ 4 c- l - i> L D S O -Tu / u L . LD l Ni O 'f .. ^ A ,{'*w I X fe-- \J iL n ^ .r~ \j^ f l ut'i-a `j &. P C - LD I , 0 ^ k * *f S\ ilP ^ $ A **r~ ^CC- WI.UO /^ V h ^ 0 ^ V l- t. E- *v i-*t 'V^. /1 v/ l O v 4 ^ 1 /> W a w X /u X 'f' ^W\ I cv ^ >v- / ^ iO Lu*<w * < - S i*V ** . vA f : "* ltv rv c -L '-^ ,* 5 T? / J A , ' '1 3 e to c ? y s v a J-V /(> % /* & -^ - /> , f f / 'a ? / / / r , fV ^ ^ , , !Q O TZ _ -J _ .~ j H * * ./ j a J f - /* , "8?, ses J -* ~?L- H *t j.* * -a * v u -* 7 t^ - /j* " * " s /D ? *? f - ( j h r C'< t T* ' - 9 7. ,y JT ri .4^' ; ^ .tfC in r l ' J *J / / J // D r J 'S s - y / . ,-v 'A 2 .T & jK ` - Q X . 7 5 " &j / / 7f -- -j v a Q 'n e f,. * / J *2? ^ u ** ** / i4' /. J IP O L irt* J j^ O J& . / .Jt** K ' ~ *2*: *T y -**.--*7 , ~ <Jy //< / y / iT/K A< y } f*ifV*A*JGJZ~ J LcjJ l# ^ Jgu ^ a t pUAj^ ^ M 0 -- , **< IL*f iC^~JL r - -a-M u ; / s ^ u . 2 -^ n\' - u. 7 tr2 > >r^T ' ->*7 *5 ( /9* "l^* # f . ( * ,7 T x o-ro ^[t. y ^ rvo/zo ^ %& -- 1. /? / - H * t - J e - _ - - ------- -------- 1 ^ ic, X * ^ ' ^ i/^Cm " /Of** ^ " " --~L' *-^^- * * it ^jc"i>--* ^ gVfa<7 ^ *} ** V v*- <s\ ^.U-cva-^ --*~r i C*t*jj fZ*"" pli * * TM* p * C * *" A'- 3 - f O (y ' 5> ? l 'u*--^ -- l cl<C p v ^ E tfi.'v -- --" ^ 3 o * ^^ ^ r1-' Yuvt^ /k4A^ m^'4'cfc- t . j^A+M***~ ^***' 'SCC^Jl**~----z>- try^ `3c*_ ^ *" **-`'**" ^|>-ot-o c/^ 9 I) - n -t-Co k^ . --* * J ^ - S i . V. Q if.y P w W i9 ^ JLiXZW 0*0 -- ** *. pci L jL ^ JLS*- - 7 / ) U*9 * ^ AuJwx, * ^rU-ot**- / f -- ri -- Jci tu t* e*-*~i*p * tt** tr r fiy -Lj , \ . ^ . .-V. I *^ r^JC A C yStXi+t* Z\*~** "^O * " ****--^ "= ^ f-DO w i c**"sJ s~La*&t~> u- .if* * -- ^ *2-- & uyz~~- ft'Cm u*'-*-**&{ X*C " J --/O L~ wyh- ^ZwC>X, y^LCl***" ^ ** - -- ^ """ ^ ^ ~^C - ^1----" ^ \ . c X Z ^ f * ^ S LIZ^ r u ^ r \ i,* w ~ n (JP v.. C. !< ? /? / J" *^ 3 - -: *** --- ^ Ui*S T j? R C 5^ ; T W e ^ C3> ,, > l u *> *-*'. {) yy*y<7^J\**r>~-. > iT / U U t. - *~*i-Ji z 7 ; * --*/ i ( ^ 2v-t ^ .^r'W'^V, .**-**<-- *&?** ^-r^ `>WLpv,^-= +2*s+ tife* -* ^^*v*a^-x-^ <--s ^ t S f'^, *^- /rrr *Sy>^A 7 y * V e t /V4-*-- cr~ * p + + ~ f- 4-x? sy * * * ~ ^. r u - U tA .. 6 *yK/^y*t ^ . `efa'ysKj th^*-tr-& ^ut< - / j U r " <*^~~-? A \. /? / + %my*`i' t / -- V-tf-5t-^. ..r r < i,/ -h . 'At-*-* <*r . /+m-`^ JT .ii.i'JJfrifF / . y '-j "T-^>-fc--#!<t-fc*!ur G) f h <t> il' i.tV gai,>. pwcjXujit^i- C^Jhw " }}U*9^ & U?Uu*_ <S> *i *''* ^2y-^ --**< A * x , * "rfww*W -- r-w-^-WW^ *xL e ( ^!cC? ^ */[vtaoo ----- *| C** `^"*7 ' /** 1*^ * >W ~ *r i ^ p & t wx^v^a 1 &>--- W '-~",Aj^/l^ -- >>*, t < . y t, 4*-i < i( wv-*-e-- C*r* f'JL& .&t* -- *2. UM-%kv*^ > ,*f OE> f*vuv*MC^ n*~a Lny f t -fi- X*t* 0 tMte X^-oa-C y*lu ru r~ * l/t*+*** (^v[j *." - ---- dX>~+~ Xt.*-ji "" xrZiLi-cf . u~ "^C _ ^ /t 0 * /V. 4^fc.*w^w1 / J" L---3 i^o (J ? S - . g c f ^ / 7 - >*3 ^ O =: >y*pi Ln^ii^Vy* <*-<s 0 k< 1 >*' i 1 jj h \ j ? ^ i i^* i% t*L/ ^ "* ut-S. j^? y*^*7r**<*I^^V'W ) i o /w4^VU y* ~ >^w/ *7^\-L-p r~ jj** / . ^ .i-zn-f. VdLwi- *f*C0 4>t5t~f<-* '*-* ^ `*-''v>`^s--- /rTziz L ! ' P* C-SVfc/K l%4^U^U0%c. **'***>m^ *i.m*m9 r>****r{ -***+ *--*-" ^ >^>^*< . P x$Vf* M t *-*- Cr~*p+% ~f- J-o i'u J'-iA - . ***/-^ f -* 6 - ^ /v * y *jksut& b* .*j+4Z*r *2^ A ^ * -- *<r*- j f s- '*'*'t^-w; ''W ^ ' ^yK/tyy* y, V^j- Z ^ 1/ / / ^ >^U *1r***^*t- /? -y,/ /V 7* * / / / ^ *s</-. S lid e 25 ..r > 63 OSAI. T o s t i c m s s OF 2 .A .5 T S p e c ie s F o r a . A*nitra fI s R at* Guinea P ig s H ice C h ick s A cid A cid A cid A cid 40 20 27 33 LD50 a g /k g 527 389 373 312 LD1 =S/*S 235 252 156 144 LSI L<r:sr 951 280 171 69 83 R eference Rove Rove Rove Rove TOXICITY 0? 2 A D IS FISH R eference Gerkitv*. 1943 Hanson, 1952 H a rriso n & R ees, 1946 King & Fenfound, 1946 # Dosage 100 non 1 Ib/aere 2000 non 100 ppa 65 owa 675-350 n :n 630 ppa 100 1b s /a e r d in 3 -f t cond E ffects i'o d a r^ c e to i n v e r t e b r a t e s J'a c a n a te to v i l d l i f e in c a r s h n s 1050 fo r c a tf is h , ainnovs done deaths in breaas and bass Scr?e d e a th s in c a m 2 4 -h o u r, LD50 f o r minnows Ko d e a th s i n b l u e g l l l s o r in n o 5t3 In 29 days EFFECTS OP REPEATED W lC S OP PIIEN0XYACETATE3 Compound 2,4 0 2,4 D ron finish K ille r 2,4 D 2,4 0 2,4 D 2.3.5 T AnIras1 Rata a R ats S te e rs R abbits Dogs Dogs Route O ral D iet O ral In je c te d Iv Iv Dosage E ffects R eference 10 m g/kg, 3 tim es/w eek , 4 weeks No e f f e c t a Rowe & Hyniss 30 mg/kg, 3 tlfiLOs/veek, 4 weeks No e f f e c t s a Am J V et Hed, 1934 100 mg/kg, 3 tim es/w eek, 4 weeks Decreased g routh cloudy ' availing of liv e r 300 mR/h'!. 3 tlines/ucp.k. 4 weeks D eaths 100 ii 100 ppm - 113 days 300 ppm 1 1 3 days 1000 ppm 113 days No e f f e c t s No e f f e c t s Toxic e ffe c ts 6 deaths Ib id 3000 ppm - 12 days Toxic e ffe c ts - s a c rific e d 100 rag/kg * 15 days Some p a th o lo g y o f Ib id liv e r , kidney, & Cl tract 500 mg/kg - 3 days 500 mg/kg * 2 days No e f f e c t Decreased a p p e tite i 1000 mi*./kR - 3 days D uith 50 mg/kg 4*13 doses N othing re m a rk a b le some U l l l & C a r l i s l e k id n ey d c g c n c ru tla n J - 1 llyg & Tox, 191 hyperpliaols o f bone m arron, decreased hgb 100 mg/kg * 3 - 7 doses 1D ecreased h g b , d e g e n e ra tio n o f kidney, hyper* phasls of spleen, lym phoid. A*bond marrow 25 m g/kg/day - 6 days B leeding gums, leg Ib id u lc e rs 50 rag/kg/day - 2.3 days 2/2 deaths 10 m g/kg, 5 tim c s/w cc k -9 0 days No e f f e c t * ID r i l l & U lra tc k a 20 tng/l:g 5 tim es/w eek -90 days D eath s Arch 1 llyg Occ Med. b i l a n -> Itpi. U J Compound 2,4 D Na 2,4 D M it 8 2,4 D Na 2,4 D N:i 2,4 D all;:* idatalne 2,4 D 2 ,4 ') a a l t .so p riv y le n te r 2,4 D .a o p ro jy le s te r 2,3.5 T 2,4,5 T EFFECTS OF REPEATED DOSES OF FIIEHOXYACETATES Animal H lce llata Route sc Feed Dosage 1 /3 LD50 (9 0 m g /k g /d ay ) Cor 3 Months About 6 mg/kg/day-24 days R ata Feed 1 95 m g /k g /d a y -100 weeks . Doga Feed 12.5 m g/kg/day-100 weeks Chicks Sheep Coua Horace Cate la Sheep Sulna Chicks O ral 200 mg/kg, 3 tlraes/w celc, 4 weeks ( a c u te o r a l f*D50 -- 3M0-765 n**,/kn) P a s tu r e About 2 .7 7 l b s / a c r e f o r 12 days P a stu re 4 Ibd/ucre) 3_ .3_ ) lb s/a c re ) for 12 d a 1y s 3.3 lb s/acre^ 8 Steers O ral 16, 17, 52, 55, 114, & 161 m g/kg/day-78 days 2 Steers O ral 50. 58 m g/kR/day-154 days E ffects No e f f e c t s No e f f e c t s No e f f e c t s No e f f e c t s No e f f e c t s No e f f e c t s No e f f e c t s No e f f e c t s a No e f f e c t s Reference * Bcher, Proc Soc Exd M o l & Med. 1946 l l l l l & C u r l l . l e , 194: Fitzlm gh Fltzhugh Bjrn & Northen S c ien c e. 1948 H ltch ell, et 1. J An lins 1 S e i . 1946 G rlgaby & F a rv e 11 Mich Agr Exp S ts q t B u ll, 1950 Anderson, A rndt, Codbcy, Jones JAVMA, 1949 * CONCLUSIONSi In summary uiiil l i f t e r d i r e f u l r e v i e w o f l u x i r o I U |;i c u t (lu U r r r l u l e i l I n 2 ,4 -1 1 m id 2 , 4 , 5 - T u l u s llic k n u w l e i l g c u s l o llie Mimiici* t h e s e t a u t e r ! i l l s h a v e h e c n u s e d f o r d e f o l i a t i o n lu m i l i t a r y s i t u a t i o n s in S o u t h e a s t A sia , no h e a l t h h u a i i r d i s o r was i n v o l v e d t o man o r d o m e s t i c u n i cauls f r om th e amounts o r mauner t h e s e m a t e r i a l s were .used in th e aforementioned exercise* ACraS TOXICITY OF PIIR7LS Route & Doses q g /ic g O rel LOSO ID I LDI (9 5 ) B LOSO LDL LDL (9 5 ) it 2D50 LDI LDI (9 5 ) 2D50 LDL LDL (9 5 ) . Rats R ab b it* Doge 566 213 124 586 1994 - 363----64 173 569 244 * * 107 - * - Q 500 -- 50 5562 3L7S? 2034 12034 493 40 > 1250 a ,rD ACUTE TOXICITY OF ?-J1PL2 Oral & -fr/kg ?.at3 1*5 it pc 12.5 4/4 7.5 6.25 .5.0 3.75 3.13 6/6 2.50 6/6 1.83 7/7 1.25 10/10 0.94 7/10 0.75 8/10 0.63 6/10 6/10 0.50 4/10 0.47 0/10 0.33 0/10 0.31 1/10 0.25 1/10 0.16 2/10 0.125 0/10 0.03 2/6 1/6 0/6 0/6 5/6 6/8 2/6 0/8 0/6 0/6 0e3ths abbits iP it P Dora ip it _ PC .. 3/6 8/10 2/6 3/8 2/8 0/6 0/6 1/6 0/4 0/4 0/6 1/5 0/6 'iik 2/4' 0/6 * 0/6 0/6 0/6' 0/4 0/4 0/4 0/6 0/4 0/4 0/6 r~ I-- ** I * S T ^ -* j ~ fo v ^ / v ^ . . c*-~ 4e. 2- " ) SO h LD \ ,, l- ijr ts \ X u S \J L y> -. a *(**- J I/2lC ^ V s -c * a? /* 'll'* V A A ^ r v a fx * '^ 4 * 0 PC. - LD I l - d . &f; r~f .r-\J0^ V.f }/* ^- V " XA* V A * l . 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JSu^c - y %&4J\dfcl. i iTM**yL*L*ry U* pP -ti* * * . i - ? / 7 -> T > * o * ^J * * u * . Z u t : ? ^ # -- 1 **<lJ---1-Ii^>*T^r^A*>W-S,rTi'Wi*I% 3> i- lU /i? A-*V%. * 7 "fl /w e /^ rv t. ^*1 <t< L-S. "^ f" C'^"SjjSjfsi'-s. ' ^ . / *fmC+ 4ff5f3j<m ^l- *r +w >m2**--*m9J vyr>t*w-'**-r^r* - 1- ` - V 7 'Y ' i t /VI-*- Cc*~^++~>f- G >-t+ & * r * - v<^c, > % ^ & ~ x * & Z ' ` K /s m * ..-W m /j*V -fr-> 9 U i< l/J <^ 't VP-- 'r* ^1 1 * /* ' /4+*~~* J n . >A .y>*.yV- F?y -- V*^'>-t-y. .,*.Sy/ " .'VhW 7*/ *"' ~r<- y ^ PO SSIBLE HEALTH HAZARO OF PHENOXYACETATES AS RELATED TO DEFOLIATION OPERATIONS IS V IE T NAM 1 Formules* .% ' . ' Figura I shows the formulas for 2,4-Q, dlchlorophenoxy-ecatlc acid i and 2,4,5-TJ trlchloropheneecyacetlc acid* These substaneas ara used as the i acid*, salts, esters, and other chemical forms* The fixture, "Purple,** consists of 50i h-butyl 2,4-0; 30S n-butyl 2,4,5-Tj and 20i Isobutyl 2,4,5-T* 2* Estmated Possible Pose of "PuraIs*" Table* I Illustrates an atto*?t to estlaate the dosa of "Purple" which night have reached men who were exposed to the spray* The moxJeum * quantity of "Purple" delivered In any area was 24 lbs p er acre* Twenty-four pounds pe r acre Is equal to 250 ra/sa ft* The size of these droplets would minimize Inhalation and favor body surface contamination* Information of ethe chemical agents shows tnat the amount of agent falling on a nan per unit of area Is about 75i of that falling cn an equal area of the ground* A H ' M b man would have about 16*2 sq ft of body surface* Only half of this, 5*1 sq ft would be exposed to the soray* Thus, the maximum quantity of spray which could reach the nan would be 30 mg/kg* 3* The T o x ic it y o f S in g le Doses of Phgnoxvacotates*. T a b le 2 shows LD50 doses o f p h en oxyacatates In v a r io u s s o o c le s o f an im als by v a rio u s ro u te s .o f a d m in istra tio n * Most o f tno p u b lish e d data re f e r to th e parent a c id s o r s a lt3 * However, t h is In form ation Is p e rtin e n t s in c e th e t o x ic it y o f th e v a r io u s form s can be I n te r r e la t e d * In t o x ic d o se s, a l l fo re s o f th e compounds produce m uscle s t if f n e s s , a t a x ia , p a r a ly s is , c o re , and death * These e f f e c t s a r e s l n l l a r In a l l anim al s p e c ie s * In v e r y h ig h d o s a g e s , a c u te v e n t r i c u l a r f i b r i l l a t i o n may o c cu r* * K ota th a t a l l forms o f 2,4-D and 2 ,4 ,5 -T havo ro u g h ly s lm U a r t o x ! - e lt t e s , In a l l anim al s p e c ie s and by a l l ro u te s o f a d m in is tr a tio n , o th e r than th e p e rc u ta n e o u s ro u te * " P u r p le " I s much la s s t o x i c p e rc u ta n e o u s Iy th a n by th e o th e r ro u te s o f a d m in is tr a tio n . C lo th in g g iv e s a d d it io n a l p r o t e c t Icn and I t h a s n o t been o o s s lb le t o k i l l c lo t h e d r a t s w ith a s p l l e a t l c n s o f 12*5 gm/kq. Coos nay be more s e n s it iv e then s e e d as t o t h e p a r e n t c cso cu n d s* How e v e r , even f o r doqs th e I n t r a p e r lt c n e a l and th e I n t r a t r a c h e a l LOSOs a re 358 and 305 rng/kg, r e s p e c t iv e ly , Tho 1350 by th e bare p ercu ta n eo u s ro u te Is g r e a t e r th a n 1*25 gm/kg In t h i s s p e c ie s * 4 Tho T o x i c i t y o f ^anented In tra r> a rfto n e a l Doses o f " P u r p le " In Hens* T a b le 3 shews t h a t 5 d a lly doses of 30 mg/kq o f " P u r p le " d id n o t . p ro d u c e an y t o x i c s ig n s o r c a u sa death In any o f 6 dogs* L a m e r d o s e s , ICO eg/kg^ dld cause weakness and w e ig h t lo s s on th e 4 th day o f compound a d m in istre l i o n . D eaths o c c u rre d on th e 5 th - ICth day e f th e t e s t * The LD50 f o r "PurpJ by th e In tra p e rito n e a l ro u te In dogs Is 358 mg/kg. -r \- . i. / *0 CHj c CH c : Cl Cl - t Cl CHj C CH F ia ra i ' * . ,I i i ' i. "- TABLE !- *. I ** B tm * POSSIBLE DOSE OF "POPPLE* ST DELI YEW f^ETHOD Ground Oosaos 24 lb s (1 0 .9 k q /a c re - 43560 sq f t ) . 250 g/sq f t Ground-Man Dosac.e Satlo I mq/sq ft cn ground 0.75 iwj/sq ft on nan A v a i l a b l e Body A rea on P rone Man (Naked) \m * 0 .7 5 sq asetors (S.t so f t ) ,(250 ng/sq ft) x (0.75) x 3. I sq ft) 1519 mg (ground dosage) x (nan/ground ratio) xCavallable body area) 1519 mq 1519 mn/rart 0 kg ( body we1y n tJ 30 irg/kg *f i% 3 TAJLc 2 TOXICITY OF PllENXYACETATES ( < r ' k o u te orf rn sri^ A n T T ^ r Sp^clot .Administration11 Acid Mx.*d d u ty Fstorfl Ibtf "(rWk* iV 2 ,4 ,^ -T field" * iilKud * i i r" Cst^fB Rot Pull* I t Ip lO It PC pcc Iv Ip h It pc pcc 5\2?)-m ?i 375(1 V, 666(?)*>0t)3(11 400 (2) # 00 (2 ) 620(1) * 527(1) 401(1) 424(1) 1 7I2(|) i 436 44U 943 3009 > i2 ,o a o 570 430 501 1351 CuIiisq P ig C h ick s Ip h It. pc Ip lo Ip . lo *0 100 (3) 100 (3) 360(1) 469(1) 541(1) 369(2)*426(2) 375(1) 576(2)^600(2) 551(0-1000(2) 713(1) . 399(1) 1)40(1) 2000(1) 301(1) 3j0(|> 940(|) 759(1) 350 305 >1250 (I) Roua A Hymat, Am J, V#t Mod, Vol XV, No 97; p 662, 1934 (?) H I M A Carl Is lo, J. Ind. Hvn A Tox, 29iH5, 1947 (3) Drill A Hlratzko, Arch Ind ily'j A Cccup *^0, 7lf>l, 1953, (4) CfiDL * In * Iritni'icrfrononl; It ? Intrnr,ns1rlct It Intrntrijchosi pc pnrcutnnoous, boro; * TA3LE 3 TOXICITY OF FIYE DAILY ItfTRAFE'ilTWEAL DOSES OF "PlPPLE" IM DOSS Sally Dose sig/kg 100 NO, Of Dons * 6 Toxic "0~3PV.S r ir f i's fay " :'*arns Weight loss and weakness on 4th day "^ 6/6 5,6,6,7*7,10 +- 30 6 No to x ic signs 0 /6 3m . Safety Record of Phnoxyacetatas The outstanding safety record established by those substances urlng moro than 20 years of extensive operational use Is also germane to >hls discussion _ * From 1947-1963 more than three-hundred million pounds Were produced and'used to control vegetation on more than four-hundred million acres of land In the United States* Pates of application ranged from 1/16 - 160 lbs per acre* The annual production as of 1963 was estimated to exoasd fifty million pounds and fifty million acres were treated* These herbicides are registered by the US Department of Agriculture which means they are cons (dared to bo U.) non-poi sonous, (2) ton-corrosive, (3) non-inflamrnoble, (4) available In quantity, (5) economical, and C6) effective* The Department of Agriculture maintains constant control In areas where herbicidas are applied. During fifteen years of extensive use, the Department of Agriculture had not received a single complaint of Injury to humans, livestock, wildlife, or soil from tho phenoxy herbicidas, ajor manu facturare have cerMflod that none of tho workmen In their factories havo shown any III effects.- Commercial snray operators report no adverse effects except for a very few allergic skin reactions* These companies report ver/ few claims for damage to livestock and none of these have been proven. Only five suspected human Intoxications have appeared In the literature 4n alt of the years that these herbicides have been used Cas of 1963) The use of these herbicides Is not restricted to the United States. The Russian scientific publication, Protection of Plants from Pests and Diseases," 1961, op 55-57, reports that In the recent years, five million hectares of grain crops In the Soviet Union have been treated .annual ly with 2,4-D* Further, systematic treatment for three or four generations has not affected tho quality of the grain* *V Another-'publ 1cat Ion, "Problems In Economics," Hosccw, No* II, pp 86-90, 1961, states that It Is planned to uso 39,750 tons of phonoxyacatates on thirty million hectares In an effort to Increase food production. A third publication, "Problems In Nutrition" by the ffedlcal State Publishing House, Moscow, Mo. 4, i J6l, states the toxicity and carcinogenicityof agricultural chemicals was Investigated by the Interdepartmental Commlttoo for the Study and Peculation of Toxic Chemicals at the State Sanitary lnsnectlor Office, USSR. The phenoxyace+a+es were among 18 approved for applIcntlens. It was stated that crops treated as proscribed with 2,4-D present no danger when consumed as food. Friday, 26 April 1963, a committee of American experts on herbi cides mat at Edqawood Arsenal, Maryland, to consider the use of phenoxvacat'ites In Viet Noa. They concluded that no hazard to health was Incurred as a result of the quantity or the method of use In that operation. ^ / M ^ c . h \ l -cmr A c . r # /z J / Q u i . a J A i. J-a c / U i.. llt . d-u> h M ^ - 0 ^ 7 . l A l > z A l A '-- i^ 4 ? L } r u / J u jf c > i U S r l* ' A l- )j- - JL 11 V ^ U K -*> ^. , i jfr f*./V 5/L1 \^ i "V a U .'a- si^flj& Z lsL J& + - cb u h t '/* ^ A ^ c A alS 7 tsS -O d l vvj^ (J^ t JW OlW-^V9 . 7. -- A -- P .f--f^ , A_ ^ w t ^ > VL^-C~cf jf. V . m i_ . <