Document 9eqnj4V6x76DVDaX6eOxZzD5

Ju ly 5, 1955 D r . T h o m a s L-. Sh ip m an H ealth D ivision H ead er Lo s A lam os Scien tific Lab o r ato r y P . O, Box 1663 Lo s A lam o s, New M exico ; Re: K D ear Tom : . . .: Th an k s fo r you r le t t e r of th e 24th an d fo r the fu r t h e r in form ation on t h e t y p e o f r e n a l d a m a g e t h a t i s a s s o c i a t e d w it h v?e a d m in ist r a t io n o f s u i t able qu an tities of RDTA over su fficien t p eriod s of tim e. The ce llu lar ch an ges d e scr ib e d w ould se e m to m e to be qu ite cap ab le of in duction by th e r em o v al of m in ute, am ou n ts of m in e r a l su b st an c e s fr o m th e c e lls, an d I a ssu m e t h at so m e such , t h in g d o e s o c c u r to so m e d e g r e e . W h at e v e r t h e p r o c e ss m ay b a,th e o b servation is an in ter estin g on e. In tn c m at t e r of th e reten tion o f le ad u n d er a v a r ie t y of con d ition s, an d the t o t a l q u a n t it ie s w.hic h a r e a s s o c i a t e d w it h si g n s an d sy m p t o m s o f in t o xh a uioi, w e k n ow a f a i r a m o u n t fr o m b ot h d i r e c t an d in d ir e c t e v id e n c e o o m g o f chxs i s in t u e l i t e r a t u r e an d so m e {m u ch in fa c t ) i s n o t . W e h a v e q u it e a n u m b e r of fa ir ly com p reh en sive d ata on n ecr op sy m at e r ial, e sp e cially on th e t issu e s o f ch ild r en fat ally poison ed by in organ ic le ad com pou n d s; we h ave a ll th at w ould be d e sir e d in fa t a l c a se s of t e t r a e t iy l lead p oison in g in ad u lt s, an d so m e (but on ly a sc a t t e r in g ) on c a se s of in o r gan ic le a d p o iso n in g in ad u lt s. Th e in d ir ect in form ation ob tain ed in m etab o lic exp er im en ts is ext e n siv e . F r o m t h ese c o m b in e d s o u r c e s , e s t i m a t e s c o u ld b e m a d e fchat a r e i a i r l v r e a list ic . T h er e a r e , h ow ever, two jo k e r s in tee situ atio n , an d one of t h e se can n ot be so lved by th e u se of r ad io activ e t r a c e r s. Th e on e lie s in the in i t ia l o r n o r m a l o r , if y o u w is ., in c id e n t a l, le a d c o n t e n t o f t h e t i s s u e s (p rin cip ally the sk eleton ) of th e ch ild o r th e adu lt at th e tim e on e begin s to m ake ob serv atio n s. The e r r o r of th e estim ation h ere is of the sam e ord er of m agn itu d e (p r o p o r t io n ally ) a s t h at o f e st im a t in g th e con ten t of. th e in d ivid u al who h as b een su b je c t e d to u n u su al e xp o su r e an d is ill. T ie o t h e r jo k e r is th e fac t o r of t im e . Th e am ou n t r e t ain ed w ith out sy m p to m s o r d an ger of sy m p t o m s v a r ie s w ith th e r a t e a t w h ich th e ab so r p t io n an d reten tion o c c u r s. One can in trodu ce a r e lativ e ly sn w U quan tity qu ick ly an d in duce illn e ss, but m uch la r g e r qu an tities can be in trodu ced slow ly, and r elativ e ly lar ge q u an tities r etain ed , w ith out illn e ss. Th e exp lan ation s fo r t u e se d iffe r e n ce s lie in at le a st tw o m ajo r ph en om en a, w h atever m ay be th eir m e ch an ism s: K ? 0 0 0 dSO i N9759 D r . T h o m as L . Sh ip m an - (2) ~ Ju ly 5 , 1955 (1) .Lead i s r e m o v e d fr o m th e p la sm a o f th e b lo o d a lm o st q u an t it at iv e ly b y the eryth rocyte, th ereb y low erin g th e con cen tration (p resu m ab ly the e ffe c t iv e co n cen t r at io n ) in o t h e r so ft t i s s u e s , a t le a st t e m p o r a r ily ; (2) Le ad is rem oved from the so ft t issu e s o f th e body gen er ally by th e sk eleton , th is bcin:.-, a so r t o f s e c o n d - st a g e an d slo w e r o p e r a t io n t h an t h a t o f t h e e r y t h r o c y t e s. Th e le ad taken in to th e sk elet o n m o v es slow ly in so m e m aim er fr o m a p a r t of th e sk eleton fr o m w h ich it is r e ad ily lo st to a p a r t fr o m w h ich it s e scap e is r e t ar d e d (n ever st op p ed ), o r p e r h ap s th is is a m at t e r of it s bein g ch an ged slow ly in to a le ss lab ile fo r m of com poun d o r st r u c t u r e . In an y c a se , th e m atter of poten tial toxicity is a m atter of the type of d istrib u tion in the body (in clu din '; th e sk eleton ) o r e co m p o sitio n w ith in th e body (in clu din g th e sk eleto n ), a s w e ll a:> o f q u a n t it y o r , a s y o u o p sa k o f it , o b o d y b u r d e n . T h e sk e le t o n i s s c l a r *e , arid t o r e l a t i v e l y in a c t iv e (in t '<e m e t a b o lic se n se ) t h at th e t o t a l qu an tity of le ad h eld in it in r e la t iv e ly in act iv e fo r m m ay be qu ite v a r ia b le fr o m in d ivid u al to in d ivid u al, w ith in ce r t ain lim it s. Th is is n ot t r u e to an y t h in lik e t > ext-* 'it t a t it w ar: b e lie v e d to b e by Au b an d h is a s s o c i a t e s , sin c e L :e r o h ; n o su e 1: - i a s r e a l l y in e r t st o r e d l e a d . T.;.er e i s a lw a y s a r av e o f e x c r e t io n w i<; - 1; d e t e r m in e d in t h e fin al, se n se b y t e e b od y b a r d e n , b a t t ^ e t im e fa c t o r in v o lv e d in. th e st o r e , r e n e c e ss i t a t e s t h e in t r o d u c t io n a m o v in g v ar ia b le in to toe equ ation by w h ich one w ould calcu lat e t e bu rd en fr o m m e r a t e of e xcr e t io n . I fe e l su r e th at a car e fu l stu d y of toe av ailab le d at a w ould p r o v id e u s with, a su it a b le e q u at io n , b u t t h is h a s n ot b een d on e an y e t . I sop e t o ;.ave a. ch an c e t o do it , with, t h e h elp o f a m a t h e m a t ic ia n , in th e n ot to-.-, d ist a n t fu t u r e . To giv e you no m e idea, of th e e xt e n t of t.-e v a r ia b ilit y I r n i,.at m en tion a few fi- u r e s fr o m m e m o r y . A ch ild e xp o se d to le ad fr o m on ly n o r m al so u r c e s w ill h ave th e co n ce n t r at io n of ab ou t 1 m illig r a m p er 100 g r a m s C t r e e '- b o n e . A h e alt h y ch ild m a y n av e a c o n c e n t r a t io n o f fr o m ) to 5 o r -1 m i l l i g r a m s o f le a d p e r 100 "r ar e r - o f f r e s h b o n a, t h is b e in g fr o m 7 J to oG p o r ce n t o f t - e le a d in t h e b o d y . A fa t a l l y p o iso n e d c h im m a y ave ir o n . 10 to 40 m illig r a m s p e r 100 gr a m s of fr e sh bon e, th is again con stitu tin g 75 p e r cen t o r m o r e o f too le a d in th e b od y ; o r a ch ild fa t a lly .p oison ed by th e in ge st io n o f lead, o v e r t %e p e r io d o f a few d a y s m a y ;a.v<y s o r 4. m i l l i g r a m s o f le a d p e r 100 "r a m s o f fr e sh b o n a , an d 50 p e r c e n t o r l e s s o t.:-e le a d in t u s b o d y in t h e sk e le t o n . A ll of t h is co n ce r n s it se lf w ith in o r gan ic le an . D esp ite t n e se v a r i a b le s, h ow ev er , giver? a fa ir ly co n st an t se t of con d it ion s in an in d u st r ia l e n v ir o n m e n t , r. d e fin it e p e r io d o f e x o o su r e , t h e d a t a on- t h e b lo o d ar .d u r in e of th e in d ivid u al fr o m tim e to t im e o v er th e p er io d or an ap p r e ciab le p ar t of it, an d t -e w e igh t an d h e igh t o f t h e in d iv id u a l, t-:-e q u a n t it y o le a d in th e bod y c a n be e st im a t e d w ith r e a so n a b le a c c u r a c y , on th e b ack grou n d o ou r in d u st r ial an d m e t a b o lic (e xp e r im e n t al) e x p e r ie n c e . It is qu ite c e r t a in th at tr,e m e t a b o lism o f le ad in th e h um an o r r an is m is c h a r a c t e r iz e d by a r e m ar k ab le d egr ee D r . T h o m as L . Sh ip m an - { -) - Ju ly 5 , 1955 of st ab ilit y . Th e m ech an ism s .t h e r e fo r e , a r e su b ject to but lit t le in terru ption an d v a r ia t io n , an d if an d w h en w e Suave a b it m o r e in fo r m a t io n on t h e se n isC 'iKu sm s, the problem of determ in in g the burden, w ill be very sim p le. Tr-.e e n t ir e r&n-'.e o f a c t u a l q u a n t it ie s o f w h ich I'v e b e e n sp e a k in g a b o v e (in t e c e n t ir e h u m an body of th e ad u lt) exten d s fr o m 139 m illig r a m s o r so , in tn e n o r m al p e r so n , to 300 m illig r a m s in th e e n t ir e ly h ealth y p e r so n who h as t ak e n in som ew n &t m o r e th an th e u su a l (u n avoid ab le) q u an tity o f le a d in b is food an d d r in k , up to 2500 o r p e r h ap s a s much, a s 3000 m illig r a m s in so m e of t:*ie m o r e ''h e a v ily l e a d e d " p e r s o n s . F a t a l p o iso n in '- m a y r e s u l t w h en t n e r e a r e q u a n t it ie s o f 1003 m i l l i g r a m s o r l e s s in t u s b o d y , bn.: c o n sid e r a b ly ? r e a t e r q u a n lt ie 3 (two o r t h r e e t im e s) m ay b e fou n d w h en th e b u ild -u p is sn c io n t ly g r a d u a l, I d ou b t if it e v e r g o e s m u ch a b o v e V: e c u t sid e fig u r e cs 3001- m i l l i gr am - ':, b u t on e mi;-, d d e v ise c o n d it io n s, p e r n a p s, in W ish it w o u ld . T'II .cave to lo o k o v e r th e d a t a to se e if I am c o r r e c t in t h in , b u t I a r . n ot fa r t o m u c h fo r t h is b u s i n e s s , v<h ic; I did r t in t en d to p u r su e w h en I st a r t e d i n i s. Cin e a r e ! v rcv.v iiA:'.. e i C . C . : M r . ivianired. Bo w ait c R o b e r t A . I t s ' :o e D