Document oedErOYoGDG5GwVJ7MN2z362R

O ct o b e r 9, 1961 M m o to; D r. Robert A . Keh oe From : D r. Th eodor D. Sterlin g Su b ject: For th com in g Ch am b er Exp e r im e n ts Th e follow in g e xp e r im e n tal su gge st io n s a r e b ase d on th e a n aly sis of e xist in g d ata, ou r own d evelop m en ts of a p h y sio lo gical m od el, an d on a se r ie s of d isc u ssio n s w ith you, D r . H orton , an d o t h e r s. A . P r e - e x p er im en tal In gestion T r ia ls :Th e d e t e r m in a t io n o f h ow m u ch o f in g e st e d le a d i s im m e d ia t e ly excr eted h as p roved to be dif fic u lt b ecau se su b je ct s ar e in a state of eq u ilib r iu m durin g th e ir con trol p e r io d s. Th e am oun t of le a d excr e te d du rin g su ch an e q u ilib r iu m e q u als (ap p r o xim at e ly ) to th e am oun t of le ad in gested . E st im a t e s of the p roportion of in take th at p a sse s th rough the gut h ad to be_b ased on v ar iat io n s in in take an d su bsequ en t v ar iatio n s in fecal excretion . T h ese estim ates h ave n ever been satisfacto r y . Yet the kn ow ledge of t h is p roportion is e xt r e m e ly im p o r tan t sin c e the n orm al body b u rd en of le a d c o n sist s la r ge ly of th at in ge st e d m a t e r ia l w hich is not elim in ated im m ed iately . In ad d it i on th e d at a ofjt ie in h alat io n e x p e r im e n t s h a / ' sh ow n t h at a p ar t of th e in h aled le a d m ay be sw allow ed an d so ac t s a s if it w ere in ge st e d . A gain e st im a t e s of the p r o p o r tio n th at p a sse s th rough w ith out bein g ab so r b e d in to the body ar e u se fu l. . Each in divi du al su b ject m ay d iffer , to som e exten t, in the p r o p e r tion so elim in at ed . It w ould be u se fu l t h e r e fo r e t o obtain su ch an e st im a t e fo r each su b ject b efore a con stan t in crem en t of lead is added to h is en viron m en t. Th e e x p e r im e n t a l p a r a d ig m fo r th e C h am b e r Stu d y o r th e l e a d in gestion exp erim en t sh ou ld be m od ified a s fo llo w s: P er io d I, Con trol 1 : M easu rem en t of av er age in take an d of le ad a r e ob tain ed . T h is p e r io d n eed n ot exce e d 30 w eeks in d u ration . * ! ! ? 2 ' . ' " ' i - - - - - - - - - *. t . P eriod II, Con trol 2: E stim ate s of proportion of in gested lead th at a * 7"~f , . . - . I .i - i n * ...i i.....-- -- .. ; . .......... .v O c4*Jbik~.*- bXi.j.- ;j e^e-reted-are obtain ed. Th e su b ject is given orally 'b etw een 1 m g ^ ' t o 3 m g o f le a d e v e r y 7 t o 10 d a y s. A m in im u m o f\ z su ch o b se r ~ < Z 4 ' ^ 0 v at ion s sh ou ld be m ad e . ) , .' P e r io d III, E xp o su r e : (As in p r eviou s e xp e r im e n t s.) P e r io d IV, P o st Exp er im en tal Con trol; (A s in p r ev io u s e xp er im en t s. ) B. Exp erim en ts on V ar iable Intake of Lead One im p o r t an t e xp e r im e n t al q u est ion co n ce r n s it se lf w ith th e e ffe ct of on goin g 24 h ou r lon g in tak es fr o m th e atm o sp h e r e . To evalu ate th e se lon g d u ration e x p o su r e s to le a d in th e at m o sp h e r e it is n e c e ssa r y to stu dy t h e e ffe c t s o f v a r ia b le le n gt h o f st a y in t h e c h a m b e r . Su ch an e x p e r im e n t h as been p e r fo r m e d la st y e a r an d sh ou ld be r e p e at e d at le a st on ce m o r e . Th e d e sig n of l a s t y e a r ' s e x p e r im e n t can b e u ;sed w ith th e on ly ch an ge 1 in trodu ced by the p r e- exp er im en tal in gestion t r ia ls d escr ib ed b efo r e. . A seco n d exp er im en t of t h is type sh ou ld be p e r fo r m e d on in ge st e d lead . Th e le ad m odel d raw s a n u m ber of con clu sion s fo r the c ase w h ere v ar iab le am ou n ts of le ad ar e in gested . Th ese could be v e r ifie d d irectly . W h ile so m e d ata r e le v an t to v a r ia b le in tak e w ould be ob tain ed fr o m th e su gge st e d p r e - e xp e r im e n t al in gestion t r ia ls, an exp erim en t on lon g t e r m v ar iab le in gestion w ould be a valu ab le con tribu tion . __ C . A n im al Stu d ies A cco r d in g to ou r d isc u ssio n on t e st in g t h e o r e t ical d evelop m en ts on an im als I w ould recom m en d th e p a r a lle l u n dertakin g of an im al w ork. I h ave d isc u sse d th e fe a sib ilit y of su ch w ork w ith D r . H orton an d fin d th at h e i s in agr e e m e n t w ith m e both to th e a d v isa b ilit y an d fe a sib ilit y of su ch st u d ie s. Th e e x ist e n c e o f su it ab le le a d iso t o p e , P b 2^0, w ould m ak e su ch a st u d y h igh ly p r a c t ic a b le . I w ould su g ge st t h at we m e e t w ith D r . H or ton an d d iscu ss th is fu rth er. . . -, &K cc; Dr. Horton Dr. P h air HE