Document EvRD9JDeM4Bkj5V4ZBqbLo00V

THE SPRAY RESIDUE SITUATION^ By 1 . A. Ra t h Un ive r sity o f Illin o is Ur b an a, I l l i n o i s Ho rtic u ltu ris ts and o the rs in te re s te d in the fr u i t indus try are a l l acquain te d in a ge n e ral way w ith the a ttitu d e o f the o f f i c i a l s o f the Unite d Sta te s Pood and Drug Ad m in is tratio n toward spray re s id u e s , and w ith t h e i r a c t i v i t i e s and po w e rs. It seems, n e v e rth e le s s , th a t we should take t h i s o ccas io n to s ta te the re s idue problem from t h e i r s tan d p o in t, as th e y have s ta te d i t . We should a ls o con s id e r the a ttitu d e o f s ta te and c i t y h e a lth o f f i c i a l s toward s pray re s id u e s . Fin a lly we sho uld co ns ide r the pre s e nt and probable fu tu re a ttitu d e o f the consuming p u b lic , which i s , in the fi n a l co nside ratio n, fi r s t in importance. The a t t i t u d e , a c t i v i t i e s , and powers o f ,the fe d e ra l government have been d e s crib e d re ce n tly in an a r t i c l e by W. B . Wh ite ,2/ Unite d Sta te s Pood and Drug; Ad m in is t r a t io n . The a r t i c l e i s p a rt o f a symposium on in s e c t i c i d e s he ld by the D iv i s io n o f Ag ric u ltu ra l and Pood Che m istry a t the Me e ting o f the American Chemical So c i e t y . The t i t l e o f the a r t i c l e i s "Poiso no us Spray Re s idue s on Ve g e ta b le s ," but the a r t i c l e i t s e l f i s not co n fin e d to v e g e ta b le s . The p r in c ip le s apply to a l l h o rti c u lt u r a l crops and to fo o ds in g e n e ra l. I s h a ll quote somewhat a t le n gth , b u t, be cause most o f you are fr u i t growers, I s h a ll quote nothing that i s not s t r i c t l y re le v a n t to the f r u i t grow ing in d u s try and to the s u b je ct w ith which th is pape r de als "Coming from th is la b o ra to ry ," says Dr. White , "i t i s n atu ral that the whole problem o f po isonous spray re s idue s on ve ge ta b le s should be dis cus s e d from the s tandpo int o f the Pood and Drug Ad m in is tra tio n . The Pood and Drug Act was drawn to p ro te c t American consumers a ga in s t harm ful, r e v o lt i n g , de base d, and m isre pre se nte d fo o d s . We are conce rne d here w ith the harmful a s p e c t. Ve ge table s ca rry in g amounts o f po is o no us spray re s id ue s which may render the fo o d in ju rio u s to the h e a lth o f any c i t i z e n are w ithin the ban o f the s ta tu te . It i s thus our c le a r duty in the in te re s t o f p u b lic h e a lth to impound a l l in t e r s t a t e shipments o f spraye d o r duste d ve ge table s which are capable o f caus in g the s li g h t e s t measurable derangement in the h e a lth of any consumer. Economic d is tu rban ce s r e s u lt in g from such re gu la to ry a ctio n must be s ubo rdinate d to th is aim . The s pray re sidue problem i s no new one, having grown in the l a s t fo urte e n ye ars u n t i l i t i s now abs o rbing about o n e -th ird o f the t o t a l ap p ro p ria tio n o f th is bureau* "There i s a p r e v a ilin g misappre he nsio n, e s p e c ia lly in the minds o f those v/ hose in te r e s t s are in vo lve d , th a t be cause th e y the mse lve s have never been s e rio u s ly in ju re d by co n tact w ith spray m a te ria ls o r by e a tin g sprayed ve ge ta b le s , th at there i s no dange r to human h e a lth in v o lv e d . What c h i e fl y conce rns re gu la to ry o f f i c i a l s i s not immediate acute e ffe c t s e a s i ly diagnosed and re s u ltin g in s e rio us , i l l n e s s or d e ath , but rathe r tho s e more remote and in s id io u s chro nic e ffe c t s which fo llo w the fre que nt adm in is tratio n o f sm all amounts o f po iso n over a pe rio d o f s e ve ral ye ars . Many rumors o f de ath or s e rio u s i l l n e s s from spray re s idue s have been run down, but i t i s o nly in rare ins tan ce s that the cause has been trace d to th is source . 1/ Fr om a p a p e r p r e s e n t e d b e fo r e t h e Am e r ica n P o m o lo g ica l S o c ie t y an d th e Co n n e ct icu t P o m o lo g ica l So c ie t y j m e e t in g t o g e t h e r a t H a r t fo r d , Co n n e c t ic u t , Decem ber 1 2 , 1935* 2/ W. B . W h it e . P o is o n o u s Sp r a y Re s id u e s on Ve g e t a b le s . In d . an d En g. Chem. 2 5 , 621, 1933- ' ' 528 N9745 2- - ''From th e a b s t r a c t p u b lic h e a lt h s t a n d p o in t , t h e r e ca n be no q u a r r e l w it h th e view t h a t th e s a fe s t cou r se i s th e com p lete abandonment o f p oison ou s s p r a y s . How e ver , s in ce we a r e n ot o p e r a t in g u n d e r t h e Na p o le o n ic c.od e, t h e n a t u r e o f Am er ican c r im in a l law i s su ch a s to r e n d e r i t d i f f i c u l t t o p r ove th e p o t e n t ia l d a n ge r t o human h e a lt h o f t r a ce s o f c e r t a in su b st a n ce s w e ll known to be p oison o u s when p r e s e n t in r e l a t i v e l y la r g e a m o u n t s . The l i b e r a l Supreme Co u r t o p in io n in t h e c e le b r a t e d b le a c h e d flo u r ca s e goes f a r , i n t h a t i t i s r e q u ir e d t o p r ove o n ly t h a t t h e h a r m fu l in gr e d ie n t must be p r ese n t in such amounts as to have the p o s s ib ilit y or p r o b a b ilit y o f a ffe c t in g the h e a lt h , not o n ly o f those in th e v igo r o f you th , but the young, the aged, and the s ick . . "The p r e s e n t s o - c a lle d w or ld t o le r a n c e fo r a r s e n ic , o f 0.01 g r a in s o f a r s e n io u s oxid e p e r pound o f fo o d , d a t e s b a ck t o 1300, when in En gla n d and Wales more th a n s ix th ou san d p er son s were made i l l , an d se ve n ty o f them k i l l e d by th e con s u m p t io n o f b e e r c o n t a in in g t r a c e s o f a r s e n ic --------------- Whether t h e r e ce n t w or k o f Mye r s , Thone and t h e i r co -w o r k e r s may s e t a n e ve n more d r a s t i c l i m i t r e m a in s t o be s e e n . We have p r e p a r e d t h e fo llo w in g b r i e f summary o f a p a p e r b y W r igh t , Sa p p in gt o n and Ran tou l based on the fin d in gs o f the In d u s t r ia l Clin ic o f the Massach u setts Ge n e r a l H o s p it a l. " '-About 11 p e r ce n t o f a l l t h e c a s e s o f. le a d p o is o n in g i n t h e In d u s t r ia l C l i n i c o f th e Ma s s a ch u s e t t s Ge n e r a l H o s p it a l, o ve r the p e r io d o f 1911-1933 were non i n d u s t r i a l in o r i g i n . One h u n d r ed an d two c a s e s w er e fr om fa m i li e s co n s u n in g d r in k in g v/ ater flo w in g t h r o u gh le a d p ip e s . Of a l l p e r s o n s e xp o s e d , a b ou t 25 p e r ce n t showed g r o s s symptoms o f le a d p o is o n in g -- n am ely, a b lu e lin e a b ou t th e gums, s t ip n le d b lo o d c e lls , and in many in s t a n ce s , p a llo r , w eakn ess, and d ig e s t iv e d is t u r b a n ce s . F o u r t e e n p e r s o n s in g e s t in g a s l i t t l e a s 0 .1 m illig r a m s (a b o u t .0 0 1 5 g r a in s ) d a ily o f le a d o ve r an a ve r a ge p e r io d o f g)r y e a r s , e x h ib it e d t h e s e sym p tom s. I t i s p e r t in e n t t o o b s e r ve t h a t one m o d e r a t e ly sp r aye d a p p le m igh t r e a d ily c o n t a in more t h a n 0.1 m illig r a m s o f le a d u n le s s s u b je ct e d to a p p r o p r ia t e c le a n s in g t r e a t m e n t .' " ( Th is i s a c o n s e r v a t iv e s t a t e m e n t . Washed a p p le s c a r r y in g t h e p r e s e n t t o le r a t e d amount o f le a d , i f e a ch a p p le w eigh ed o n e -t h ir d o f a p ou n d , w ould c a r r y .0027 m illig r a m s o f le a d .) To co n t in u e my q u o t a t io n : "Be ca u s e o f t h e p r e s e n ce i n su ch am oun ts o f a cu m u la t ive p o iso n lik e a r s e n ic in fo o d s a g a in s t w hich r e g u la t o r y o f f i c i a l s a r e power le s s to p r oceed ( i .e ., fo o d s n a t u r a lly co n t a in in g a r s e n ic , w h ich has c e r t a in ly not b e e n a d d e d , su ch a s c o d fis h , w h ich c o n t a in s .O lU t o .03S g r a in s p e r pound) t h e s e o f f i c i a l s must be d ou b ly v ig ila n t a ga in s t th ose fo o d s , such a s spr ayed v e g e t a b le s , w here t h e a r s e n ic i s u n q u e s t io n a b ly an added s u b s t a n c e ." (The same a t t it u d e a p p lie s , o f co u r s e , to le a d .) Dr . White con clu d e s h is a r t i c le by d e s cr ib in g fe d e r a l a u t h o r it y and p r o c e d u r e . T h is i s t h e f i n a l s t a t e m e n t , ''Food s c a r r y in g s p r a y r e s id u e s o f a r s e n i c , le a d or flu o r in e ca n n ot be impounded u n le s s i t can b e e s t a b lis h e d in co u r t t h a t fo o d car r y in g t h e amounts a c t u a lly fou n d may b e , beyond a r e a s o n a b le d o u b t , d a n ger ou s to human h e a lt h ." My s t a t e m e n t s above a r e q u o t e d fr om a symposium h e ld b y c h e m is t s . I w ish t o q u o t e now fr o m a symposium h e ld b y p u b lic h e a lt h o f f i c i a l s . Th is symposium t o ok up on e s e s s io n o f t h r e e s e c t io n s o f t h e Am e r ica n F Ub lic H e a lt h As s o c ia t io n a t i t s a n n u a l co n v e n t io n t h i s y e a r a t Milw a u k e e . My q u o t a t io n s a r e fr o m a summary o f my own n o t e s , t a k e n a t t h e m e e t in g . P o in t s n ot a lr e a d y co ve r e d w h ich d e s c r ib e t h e K f 0008529 a t t it u d e o f th e F e d e r a l Food and Dr u g Ad m in is t r a t io n were p r e s e n t e d in a p a p e r by W. S . F r i s b i e , Ch ie f, D iv is io n o f St a t e Co o p e r a t io n , Food an d Dr u g Ad m in is t r a t io n , They a r e as fo llo w s : . "Me d ica l e x p e r t t e s t im o n y h a s b e e n n e c e s s a r y . Co u r t v e r d ic t s h ave b ee n fa v o r a b le t o t h e Food an d Dr u g Ad m in is t r a t io n . A la r g e number o f p h a r m a co lo g ica l e xp e r t s have been co n s u lt e d , w h ich h as a s s u r e d th e o f f i c i a l s t h a t t h e ir co u r se was n ot a r b it r a r y . Act in g as a com m ittee, th ese e xp e r ts assu r ed th e o ffic ia ls t h a t le a d was more u n d e s ir a b le th an a r s e n ic , A le a d t o le r a n ce was n ot a p p lie d u n t i l 1933* when th e d evelop m en t o f a r a p id m ethod o f le a d a n a ly s is made e n fo r ce m e n t p o s s ib le . "Fed er al to le r a n ce s ar e n ot e n t ir e ly e ffe c t iv e w ith ou t s ta te t o le r a n ce s and the Fe d e r a l government is not a t a l l happy abou t the r e lu ct a n ce o f s t a t e s to ap p ly in t r a s t a t e t o le r a n c e s . There i s no ge n e r a l d is p o s it io n in t h is d ir e c t io n in th e E a s t . T o x ic o lo g is t s r e co gn ize the d a n ger o f m inute amounts o f le a d , bu t the in d u s t r y has not y e t r e co gn ize d th e s e r io u s n e s s o f t h e d a n ge r . Ju s t r e c e n t ly two s t a t e s , one in the Ea s t a n d one in t h e Mid d le w e s t , h ave t a k e n s t e p s t o make a n a ly s e s fo r a p p le s i n in t e r s t a t e shipm ent and have b r o a d ca s t a w ar n in g t h a t s t a t e t o le r a n ce s a r e co n t e m p la t e d . The F e d e r a l gover n m en t w i l l co n t in u e t o e x e r c is e v ig ila n c e a g a in s t a l l t o x ic m a t e r i a ls ." I b e lie ve th at the a t t i t u d e o f Fe de ral o f f i c i a l s has been ade quate ly de s c rib e d . At the same symposium s e ve ra l s ta te and c i t y o f f i c i a l s pre se nte d pape rs . Ty p ic a l state me nts were th e s e , made in a pape r, e n t it le d "Spray Re sidue s from the Vie w po int o f the Cit y He alth O f f i c e r ,"b y Dr. George H. Be cke r, o f San Fra n cis co . "Acute po is o n in g seldom o ccu rs , but chro n ic d is e a s e s are sometimes produced a ft e r a s e rie s o f y e a rs . The demand fo r e vide nce o f to x ic e ffe c t s i s due to igno r ance o f chro nic e ffe c t s . Enforceme nt must be more rigo ro u s . To le rance s in themse lves are not n e ce s s arily s u ffic ie n t p ro te ctio n ." Other t y p i c a l s tate m e n ts , by Dr. William s , Commissioner o f Pu b lic He alth, Ba ltim o re , were th at "o ffi c i a l s around Baltim o re have s tudie d the l i t e r a t u r e , they co nclude th at the s lo gan that an apple a day ke e ps the do cto r away i s m is le ad in g, and the y fa v o r a slo gan to the e ffe c t th a t an apple a day le ads the do cto r a s t r a y ." During the d is cu s s io n w hich fo llo w e d the pape rs, the que s tio n o f "sub ch ro n ic e ffe c t s " was ra is e d . Unle s s the to le ran ce can he met, none o f th is i s good news fo r the apple grow e r. It w i l l be obse rve d th a t the a ttitu d e o f o f f i c i a l s in ge n e ral i s c o n s is t e n t . We know that fe d e ra l o f f i c i a l s are s u cc e s s fu l in e nfo rce m e nt. Als o , ju d gin g by the above state m e nts and by p as t e ve n ts , the y have enough e xpe rt backing and co u rt sup po rt to go s t i l l fu r t h e r . Fi n a l l y , what i s the a ttitu d e o f the layman? By layman I mean the man who i s n e ith e r a h o r t i c u l t u r i s t nor a h e a lth o f f i c i a l . I f he has read "1 0 0 ,0 0 0 ,0 0 0 Guine a P igs " by Ka lle t and Sch lin k , o f Consumers* Re se arch, and the re i s a good chance th at he has , h is a ttitu d e toward consuming ap p le s , e i t h e r p e rs o n a lly o r by members o f h is fa m ily or by h is fr ie n d s , i s pro bably not fa v o r a b le . In th a t w ide ly re ad, fre q u e n tly quote d, and a t t r a c t i v e l y w ritte n book, a rs e n ic and le ad on apple s i s mentioned re p e ate d ly and d is cu s s e d a t le n g th . Pu blic h e a lth o f f i c i a l s are s e ve re ly take n to tas k fo r t h e i r le n ie n cy . On the se cond page where i t can s ca rce ly be missed KE 0008530 -H- we fi n d t M s a t t e n t io n -c o m p e llin g q u e s t io n : "Th a t M g , ju i c y a p p le yo u h ave a t lu n ch -- do yo u know t h a t in d i ffe r e n t Gover nm ent o f f i c i a l s l e t i t come t o yo u r t a b le co a t e d w it h a r s e n ic , one o f t h e d e a d lie s t o f p o is o n s ?" I t w ould he a w aste o f tim e to sp ecu la t e on th e e ffe c t o f t h is hook and s im ila r p u b lic a t io n s upon a p p le consum ption e xce p t , p e r h a p s , t o s a y t h a t i t m ust b e c o n s id e r a b le . One ca n a ssu m e , a l s o , t h a t i t w i l l have an e ffe c t upon le g i s la t i o n . Be ca u se o f the fo r c e w it h w h ich i t s a u t h o r s make t h e ir s t a t e m e n t s , th e book i s l i k e ly t o be a cce p t e d i n i t s e n t ir e t y . I t i s n o t t o o much to sa y t h a t t h is book w ould be l i k e l y to sway m e d ica l o p in io n , e ve n w it h o u t s u ch fo r c e fu l s t a t e m e n t s in th e m e d ica l lit e r a t u r e a s th e fo llo w in g , w h ich i s q u oted fr om a cu r r e n t is s u e o f th e Jo u r n a l o f t h e Am e r ica n Me d ica l As s o c ia t io n :.!/ "Lead p o is o n in g may w e ll b e t h o u gh t o f a s a co u n t e r p a r t o f s y p h i l i s , n o t o n ly in th e v a r ie t y o f i t s e ffe c t s on th e human syste m , b u t in t h e manner in which i t may be dormant and u n su sp e cte d in th e t is s u e s fo r y e a r s , a p p a r e n t ly in n o cu o u s, u n t il some a lt e r a t i o n in t h e m e t a b o lic p r o ce s s e s lib e r a t e s i t w it h u n im p a ir e d ven om . Like s y p h ilis , i t i s a co n t r ib u t in g cau se o f many a d e a t h fo r w hich i t does not r e ce ive i t s r i g h t fu l sh a r e o f b la m e ." I do n ot need to d is cu s s a t le n gt h the ge n e r a l n e c e s s it y fo r r e s id u e r e moval to meet the p r ese n t t o le r a n ce s , o r the extrem e d iffic u lt y in m eetin g th e p r esen t t o le r a n ce s in c e r t a in p a r t s o f th e co u n t r y . In o n ly one s t a t e t h a t h as p u b lis h e d r e s id u e s t u d ie s t h a t I have seen h as i t been, fou n d u n n e ce ssa r y to wash to remove r e s i d u e . Th is s t a t e i s Co n n e ct icu t , where o f n in e t e e n sam ples o f sp r ayed a p p le s ta ke n in 1932 fr om s o r t in g t a b le s a n d s h ip p in g c o n t a in e r s in d i ffe r e n t p a r t s o f t h e s t a t e , o n ly one sam p le co n t a in e d a s much a s o n e -h a lf th e t o le r a n c e . It is a ls o unnecessary to d escr ib e in t h is paper the sear ch fo r eth e r sp rays, w h ich may, o f co u r s e , so lve th e p r ob lem . P r e d ict io n s o f fa ilu r e or su cce ss in t h is s e a r c h a r e f u t i l e . We ca n o n ly a c c e p t t h e s i t u a t i o n a s i t i s , w it h le a d a r s e n a t e t h e o n ly in s e c t ic id e g e n e r a lly recommended fo r com m e r cia l c o d lin g m oth c o n t r o l. The q u e s t io n w h ich , I h o p e , n a t u r a lly a r i s e s a t t h i s p o in t i s : What i s th e a c t u a l e vid e n ce o f d a n ger to th e con sum er fr om e a t in g a p p le s c a r r y in g t h e am oun ts o f le a d and a r s e n ic now t o le r a t e d ? Is t h e g e n e r a l a t t it u d e o f p u b lic h e a lt h o f f i c i a l s , p h y s io lo g is t s , t o x ic o lo g is t s , and p h ys icia n s ju s t ifie d ? I f i t i s , i t sh ou ld a ls o be our a t t it u d e . I f i t i s , the use o f le a d a r s e n a te sh ou ld be a b o lis h e d , and th e le a s t t h a t t h e s t a t e s co u ld do a t p r e s e n t w ould b e to p a r a lle l th e p r e s e n t F e d e r a l t o le r a n ce s . Is th er e an y evid e n ce t h a t le a d can be in ge s t e d in m inute amounts w ith ou t a ccu m u la t io n and w ith o u t h a r m fu l e ffe c t s , e it h e r a cu t e , c h r o n ic , or "s u b -ch r o n ic"? In th a t ca s e , to le r a n ce s are ju s t ifie d . I w ill answ er th e se q u e s t io n s in o r d e r . F ir s t , th e r e i s no d ir e c t evid en ce t h a t a p p le s c a r r y in g t h e am ounts o f le a d a r s e n a t e now t o le r a t e d a r e h a r m fu l t o t h e co n s u m e r . The ca s e a g a in s t le a d a r s e n a t e r e s t s up on in d ir e c t e v id e n ce , vh .ich lia s many s o u r ce s . I t i s b u ilt upon th e e ffe c t s o f le a d in d r in k in g w ater , in d r in k s fe r m e n t e d in u t e n s ils gla z e d w it h a le a d compound, in flo u r , in s n u ff, in house p a in t , i n fa c e p ow d e r s, an d u p on t h e e f f e c t s o f le a d i n c e r t a in le a d - u s in g i n d u s t r i e s . The t o x ic it y o f le a d a r s e n a t e to humans i s a b io lo g ic a l p r ob lem . Because i t i s b io lo g ic a l, in fe r e n c e s , no m a t t e r how p la u s i b le , a r e n o t e v id e n c e . In t h e for m o f b io lo g y w it h w h ich I am a cq u a in t e d , i t i s n o t uncommon t o fi n d h yp o t h e s e s b u i l t upon in fe r e n c e up s e t by d ir e c t exp er im en t; m oreover, th e exp er im en t must be a s d ir e c t a s p o s s ib le . I f the t o x ic it y to humans o f le a d a r se n a te on a p p le s were to be t e s t e d , the w eathered le a d a r s e n a t e t h a t r em ain s on sp r a ye d a p p le s w ould be u se d in s t e a d o f u n w eath er ed le a d 17 Ep id e m io lo gy o f Lead P o is o n in g , A . J . La n za , M. D ., A s s is t a n t Me d ica l D ir e c t o r , M e t r o p o lit a n L i fe In s u r a n ce C o ., Jo u r . Am er . Med. A s s o c ., 10U, 5, 1935 -5' a r s e n a t e o r le a d a r s e n a t e made in the la b o r a t o r y ; th e e xp e r im e n t a l s u b je c t s w ould he human b e in g s , n ot a n im a ls , and t h e a p p le s would be fe d , a s w e ll a s th e le a d a r s e n a t e . The s l i g h t e s t n eed fo r in fe r e n c e w ou ld be r u le d o u t , b e ca u s e in fe r e n c e s in v a r i a b ly in v o lv e u n c e r t a i n t i e s . Be ca u s e o f t h i s la c k o f d ir e c t e v id e n ce , t h e common a t t it u d e toward le a d a r s e n a t e can n ot be s a id to be ju s t ifie d . Moreover, not a l l p h y s io lo g is t s b e lie v e t h a t m in ute q u a n t it ie s o f t o xic m a t e r ia ls ar e t o x ic . The fo llo w in g p a r a gr a p h s a r e q u ot e d fr o m an a r t i c l e i n "Scie n c e " f o r Ja n u a r y 2 6 , 193^ , b y D r . Jo h n J . Ab e l, Em e r it u s P r o fe s s o r o f Ph a r m a co lo gy an d D ir e c t o r , La b o r a t o r y fo r En d o cr in e Re s e a r ch , t h e Jo h n s Hop kin s U n iv e r s it y . "Le t me s a y to b e g in w it h t h a t no one Ir as e ve r b e e n a b le t o g iv e a co n cis e an d a ccu r a t e d e fin it io n o f a p o is o n t h a t w ould a p p ly to e v e r y one o f th e many th ou san d s o f known p o is o n s . A l l a t t e m p t s to do t h is have sim p ly ended in o ffe r in g d e fi n i t i o n s t h a t do n ot d e fi n e . The m e d ica l ju r is p r u d e n ce o f t h i s co u n t r y an d o f En gla n d h as n ever a tte m p te d t o d e fin e th e word p o is o n . *** "Hature has not a ffix e d a p oison la b e l to any p a r t ic u la r su bstan ce or c la s s o f s u b s t a n c e s . The p h a r m a cis t d o e s t h a t . I h ave met i n t e l l i g e n t p e o p le who a c t u a lly b e lie v e t h a t once a p o iso n alw ays a p o is o n , and t h a t i t co n t in u e s to e xe r t i t s n oxiou s pow er in some d e gr e e t o t h e l a s t m o le c u le . I f t e n m illig r a m s o f n i t r a t e o f s t r y ch n in e be d isso lve d in fiv e hundred cu b ic cen tim eter s o f s t e r ilis e d p h y s io lo gica l sa lin e s o lu t io n , e a ch c u b ic c e n t im e t e r w a ll c o n t a in 0 .0 2 mg o f th e s t r y c h n in e s a l t , b u t no one in th e w or ld co u ld d em on str ate e it h e r a h a r m fu l o r a b e n e fic ia l a ct io n a ft e r the . in je c t io n o f a h a lf or one cu b ic ce n tim e te r o f t h is s o lu t io n un d er n eath a p e r s o n 's s k in o r when so sm a ll a q u a n t it y a s t h is is ta ke n by mouth. "The e xp e r ie n ce o f p h y s ic ia n s t h r o u gh o u t t h e a ge s h a s co n v in ce d them t h a t e ve n th e most d e a d ly o f p o is o n s a r e e n t ir e ly in n ocu ou s when give n in c e r t a in m inim al q u a n t i t i e s . S c i e n t i s t s haVe a r r iv e d a t t h e same c o n c lu s io n on t h e b a s is o f t h e ir e x p e r im e n t a l w or k. To be q u it e a c c u r a t e , h ow eve r , we ca n o n ly s a y t h a t n e it h e r a h a r m fu l n or a b e n e fic ia l in flu e n ce can be d e t e ct e d a ft e r such m inim al d oses by any m ethods known to us a t e r e s e n t . "Ther e i s , how ever , a n o t h e r fa c t o f fu n d am en tal im p or tan ce fo r e v e r yt h in g t h a t i s endowed w it h l i f e , w hether i t be a p la n t or a n a n im al or som ethin g t h a t li e s somewhere b etw een t h e t w o. Th is fa c t may he e xp r e s s e d a s fo llo w s : The h a r m fu l e ffe c t s o f a la r ge dose o f a d r u g or a p o iso n do n ot f a l l o ff p a r i p a s su w it h the d im in u t io n in d o s e . The law o f co n co m it a n t v a r i a t io n in r e s p e c t t o t h e two v a r ia b le s d o e s n o t h o ld fo r t h e l i v i n g c e l l . On t h e c o n t r a r y , w it h t h e d im in is h in g d ose t h e r e may o ccu r a tu r n ab ou t in th e a ct io n o f the dr ug w ith the appearance o f a h ig h ly b e n e fic ia l a ct io n , one in deed t h a t is in d is p e n s a b le fo r the con tin u an ce and m ain ten a n ce o f h e a lt h , a s i s t h e ca s e when we p a s s fr o m t h e t o x ic d ose o f a hormone t o i t s t h e r a p e u t ic d o s e . Exam ples o f t h is b e n e fic ia l a c t io n ar e seen d a ily in m e d ica l p r a c t i c e . Many p o w e r fu lly a c t i n g d r u g s , t o w h ich t h e p o p u la r d e s ig n a t io n o f p o is o n i s e n t ir e ly a p p lic a b le , such a s s t r ych n in e , q u in in e , the d i g it a lis g lu co s id e s , ce r t a in a r s e n ic a ls , in s u lin , p a r a th yr o id e x t r a c t s , the vita m in s , and a lon g l i s t o f oth er d r u gs illu s t r a t e t h is p r in c ip le when t h e ir dosage is r e s t r ic t e d to a c e r t a in amount. Th is fa c t h o ld s a ls o fo r o t h e r a ge n t s o f our en vir on m en t t h a t may be h a r m fu l in t h e ir a c t i o n when t h e y come in c o n t a c t w it h o u r t i s s u e s in t o o h ig h a c o n c e n t r a t io n . Sun l i g h t an d o t h e r for m s o f r a d ia t io n a r e in s t a n c e s in p o in t . In o r d in a r y co n ce n t r a t io n s 6 - s u n lig h t i s b e n e fic ia l, b u t i t i s d e a d ly in i t s e ffe c t on many or gan ism s when th ey ar e exposed to i t fo r too lo n g a t im e . It s sco r ch in g a ct io n on th e skin o f a d u lts a t h ig h a lt it u d e s an d in th e t r o p ic s i s w e ll known, and i t i s a ls o w e ll known t h a t ve r y youn g c h ild r e n have d ie d a s a r e s u lt o f exp osu r e fo r too lo n g a tim e to the b u r n in g rays o f the noonday sun w ith ou t h avin g been p r e vio u s ly in u r ed to i t s a ct io n . P o is o n s in Our Bo d ie s "An e x c e lle n t i l l u s t r a t i o n o f o u r p r in c ip le t h a t t o x i c s u b s t a n ce s may be h ig h ly b e n e fic ia l and even in d is p e n s a b le to l i f e is fu r n ish e d by ce r t a in p oison s t h a t a r e p r od u ce d i n o u r own b o d ie s and c i r c u la t e i n o u r b lo o d , a t a c o n c e n t r a t io n b e lo w t h e t o x ic l e v e l . Many w i l l be s u r p r is e d t o le a r n t h a t we o u r s e lv e s a r e w a lk in g d r u g sh o p s, an d t h a t an e xp e r ie n ce d ch e m ist o r p h a r m a co lo gis t would h ave no d i f f i c u l t y in p r e p a r in g a r r ow p o is o n s fr om some o f ou r own o r ga n s t h a t w ou ld have d e lig h t e d th e h e a r t o f p r im it iv e m a n ." There i s , m or eo ver , d i r e c t e vid e n ce t h a t le a d i t s e l f ca n be in g e s t e d in m in u t e amounts w it h o u t a ccu m u la t io n ; in g e s t e d i n m in u t e q u a n t it ie s i t i s n o t a cumu l a t i v e p o is o n . T h is e vid e n ce r e s u lt e d fr om v e r y e x t e n s iv e w or k a t th e Ke t t e r in g La b o r a t o r y o f Ap p lie d P h ys io lo gy, w hich was e s t a b lis h e d a t th e Un iv e r s it y o f Cin cin n a t i w it h the im m ediate o b je ct o f s t u d yin g th e p r oblem o f le a d a ccu m u la t io n . Ta n gib le r e s u l t s , p e r t in e n t t o t h i s p o in t , a r e sum m ar ized b y D r . Ke h o e, t h e D ir e c t o r o f t h e Lab o r a to r y, and h is a sso cia te s-l/ a s fo llo w s : "A r e ce n t s e r ie s o f a r t i c l e s in a n o t h e r jo u r n a l h a s d e t a ile d t h e m ethod and th e m ajor r e s u lt s o f our s t u d ie s o f le a d a b s o r p tio n and le a d p o iso n in g d u r in g the p ast t e n y e a r s . So f a r a s the:/ a r e co n ce r n e d w it h n or m al le a d a b s o r p t io n an d e x c r e t io n , t h e r e s u l t s may be sum m ar ized b r i e f l y a s fo llo w s : 1 . Two gr o u p s o f n a t iv e Me xica n In d ia n s , whose mode o f l i f e an d e n vir on m e n t were d e v o id o f o p p o r t u n it ie s fo r c o n t a ct w it h th e le a d -co n t a in in g p r od u cts o f h ig h ly o r ga n ize d and in d u s t r ia l p o p u la t io n s , were fou n d to have le a d in t h e ir b lo o d and to e xcr e t e le a d in t h e ir fe ce s and u r in e , as a co n se q u e n ce o f le a d in th e s o i l an d h en ce in v e g e t a t io n and a n im a l p r o d u ct s em ployed w it h fo o d . 2 . Va r io u s gr ou p s o f h e a lt h y c h ild r e n and a d u lt s in the Un it e d St a t e s , w it h no o ccu p a t io n a l e xp o su r e , were shown to have le a d in t h e ir t is s u e s and in t h e ir e x c r e t a , c h i e f l y b e ca u s e o f t h e r e g u la r in g e s t io n o f le a d w it h t h e ir fo o d s . 3 L'he r a t e o f le a d e x c r e t io n among Am e r ica n s i s h ig h e r t h a n t h a t o b s e r ve d in p e o p le l i v i n g under sim p le r and more n a t u r a l co n d it io n s ( n a t ive Mexican s) in cor r espondence w ith the h ig h e r le a d co n t e n t o f c e r t a in Am e r ica n fo o d s t u ffs . 4 . Ev id e n ce was o b t a in e d t h a t th e in g e s t io n o f t h e s e "n or m al" amounts o f le a d d id n ot r e s u lt in s t e a d y a ccu m u la t io n o f le a d in the b od y. Ap p a r e n t ly an e q u ilib r iu m i s r each ed a ft e r a t im e , so t h a t a s u b s t a n t ia lly co n s t a n t co n ce n t r a t io n o f le a d r em ains in the t is s u e s , and le a d outp ut becom es e q u iva le n t to le a d in t a k e ." I t i s in t e r e s t in g t h a t th e mean norm al d a ily le a d in t a k e was a p p r o xim a t e ly O.25 m illig r a m s ( .OOU g r a i n s ) . The a u t h o r s a ls o co n clu d e t h a t the b u lk o f n or m al le a d in g e s t e d w it h th e fo o d i s p a s se d th r ou gh th e a lim e n t a r y tr a ct unabsorbed. E a r ly l a s t summer P r o fe s s o r P i c k e t t , a s P r e s id e n t o f t h e Am e r ica n Por n ologi c a l So c ie t y , a p p o in te d a com m ittee to fo r m u la te le a d a r s e n a t e r e s e a r ch . Ce r t a in members o f the com m ittee and c e r t a in o t h e r in t e r e s t e d in d iv id u a ls v is it e d th e l/ ~ Ke h o e , H. A ., P r e d e r ic k Thamann, and Ja co b Ch o la k , Jo u r . Amer Med. As s o c . 10U, 90- 92, 1 9 3 5 . Kg 000853 3 W -"" ; : , , 7- - Ke tte r in g Labo rato ry e a rly in Se pte mbe r. Those who made the t r i p were Pro fe s s o r Talb e rt o f.t h e Mis s o uri Experiment Sta tio n , Pro fe s s o rs Greene and Kra y b ill o f Purdue, Pro fe s s o r Howiett o f the Ohio St a t i o n , and m y s e lf. Our purpose was to v i s i t the la b o ra to ry , to make the acquaintance o f the s t a f f , and, i f i t was p o s s ib le and de s ir a b le , to o u tlin e a p lan fo r re s e arch a t th a t i n s t i t u t i o n . The la b o ra to ry , we fo und, i s remarkably w e ll-e quippe d and s t a ffe d . Ph y s io lo gica l le ad re se arch w ith human s u b je cts has be e n, fo r a lo n g tim e , i t s p r in c ip a l a c t i v i t y . The s t a ff was in te r e s t e d in our proble m, and, to ge th e r, we worked out a plan fo r re s e arch . . This p lan c a l l s fo r work w ith human s u b je cts who would be fe d apple s com m e r c ia lly sprayed w ith le ad a rs e n a te . It would c a l l fo r a ve ry la rge number o f a n a ly s e s . The immediate o b je ct would be to de te rmine the p o in t a t which le ad arse n a te becomes a cum ulative p o is o n . The minimum co s t would approximate $2 0,0 00 a ye ar, and i t would be b e s t to a n tic ip a te thre e ye ars 1 work. The co s t o f the experiment i s s ta gge rin g i f we lo s e s ig h t o f the fa c t that such e xpe rim e ntatio n o ffe r s the o nly p o s s i b i l i t y o f s o lv in g the proble m. The monthly c o s t can be reduced i f le s s work i s done , but le s s work.means slow e r p ro gre s s . So f a r , the committee and those o f us who v i s i t e d the Ke tte rin g Labo rato ry have con ce rne d o urs e lve s almost e n tire ly w ith the fo rm ulatio n o f a plan fo r re s e arch, which was the purpose fo r which the committee was appo in te d. The p o s s i b i l i t y o f carryin g on the experiment depends, o f co u rs e , upon fin a n c i n g . One way to secure money would be to o rganize fo r t h i s experiment a l l o f the in d u s tr ie s , s o c i e t i e s , and in d iv id u a ls who are d i r e c t l y or i n d i r e c t ly in te re s te d , which the American Po m o lo gical So cie ty co uld l o g i c a l l y unde rtake . Re p re s e n tative s and o ffi c i a l s o f m anufacturing companies to whom I have talk e d a l l see the need o f the e xpe rime nt, i t s l o g i c , and i t s p o s s i b ilitie s . , Fi n a l l y , a l l o f us are agre e d, in clu d in g the re p re s e n ta tiv e s o f some o f the most important m anufacturing companie s, th at the purpose o f the experiment i s s o le ly to fi n d fa c t s . Tie b e lie v e th a t i t i s o nly upon fa c t s th at s ta te and fe d e ra l to le r ance s can be i n t e l l i g e n t l y bas e d . We a ls o b e lie v e that i t i s o nly fa c t s th a t w i l l s a t i s fy the fr u i t in d u s try, which c r i t i c i s e s the enforcement o f f i c i a l fo r s e t t i n g the to le ra n c e s too low , and the type o f c r i t i c who says that e nforcement i s too l a x . We are not atte m ptin g to .embarrass the Unite d Sta te s Pood and Drug Ad m in is tra tio n . We f e e l , in fa c t , th a t the y w i l l be as much in te re s te d in the experiment as s ta te o f f i c i a l s and the in d u s tr ie s , and th a t the y sho uld be re pre s e nte d in i t s o rga n iza tio n and p ro gre s s . I am ta k in g the l i b e r t y to quote from a l e t t e r w ritte n by an o f f i c i a l o f one o f the la rg e s t in s e c tic id e companies to one o f the members o f our committe e . I am q u o tin g the l e t t e r be cause i t shows the a ttitu d e th a t in d u s try i s l i k e l y to take , i f the plan i s p ro p e rly pre s e n te d, and be cause i t emphasizes what I haye ju s t s aid about the purpose o f the e xpe rim e nt. "Lou p e rs o n a lly , and in fa c t your whole committee, as w e ll as a l l o f the r ig h t t h i hieing producers o f in s e c tic id e s are f i r s t o f a l l in te re s te d in g e t tin g the t r u t h in regard to the p o s s ib le harmful e ffe c t o f a rs e n ic a l re s id u e s . We are not m e re ly conce rne d w ith pro ving th a t our pro ducts as now manufactured are harm ful to in s e c ts but harmle ss to humans, nor in p o in tin g out in a ccu ra cie s in U. S. Department proce dure or r e g u la r i t i e s , but in suppo rting w ho le he arte dly any program, governmental o r i n s t i t u t i o n a l , th a t w i l l give to the grower a product o f minimum co s t and maximum e ffi c i e n c y and s a fe t y ." KF 0008534 8- - Fi n a l l y , we are fo rtu n a te to have a v a ila b le a t t h i s tim e , fo r t h i s e xp e ri me nt, a s t a ff o f men such as th a t o f the Ke tte rin g la b o ra to ry, which has a back ground. o f s e ve ral ye ars 1 e xpe rie nce in lead, an alys e s and le ad s tu d ie s w ith human s u b je c t s , and a lab o rato ry such as the Ke tte rin g Labo rato ry, w hich was de s igne d and equipped fo r t h is s p e c i fi c work. H10F K" 0008335