Document b520m71w7bmYDg7LzzZQp4Q13

Ja n u a r y 12, I960 M EM O RAN D UM : TO: FRO M : SU BJE C T : D r . Rob ert A. Keh oe Biom etrics M o d ificat io n o f D e sign o f Le a d Stu d y 1. T h e e x p e r im e n t a l d e sig n p r o p o se d in th e m e m o of A u g u st '25, 195 7 (D e sign o f L e a d Stu d y ) h a s b e e n m o d ifie d a s fo llo w s: a . Th e p r e se n t e x p e r im e n t w ill n ot v a r y t h e l e v e l o f l e a d in a ir con -: cu r r e n t ly w ith th e len gth of tim e p e r io d s th e su b je ct r e m ain s in th e , ch am b er . D ose d iffe r e n ce s w ill be defin ed so le ly by d iffer en ces in th e len gth of exp erim en tal e xp o su r e s. The con cen tration of le ad w ill be .150 m g / m ^ . b . Th e su b je ct w ill spen d t h r ee d iffe r e n t tim e p e r io d s in the ch am b er in stead of the eigh t d ifferen t tim e p er iod s p rop osed p reviou sly . : E x p e r im e n t s w ill c o n si st o f 4 , 8, an d 10 h o u r s e s s i o n s . F o u r h o u r se ssio n s w ill st a r t in the m orn in g o r in th e aftern oon in m ixed o r d e r . Ten h ou r se ssio n s w ill oceixr on ce ev er y fou r w e e k s. (Th e tim e p e r io d s o f 4 , 8, an d 10 a r e on ly a p p r o x im a t e . Th e a c t u a l d u r a t io n s w ill b e ch osen on the b a sis of p r ac t ical con sid eration s of p rep ar in g the ch am ber, th e food, by th e t o ilet n eed s of th e su b je ct , e t c. ) A copy of th e d aily t im e p e r io d s fo r th e f i r s t 72 w eek s of th e e xp e r im e n t i s ap p en d ed . 2. The ch an ges w ere gen erated predom in an tly by the im p r essio n s gain ed from p ast exp erim en ts by D r. Keh oe an d M r. Sch afer th at d ifferen ces in in cr e m en ts of e xcr e te d le ad , follow in g sm all d iffe r e n ce s in d o se s, w er e too t r iv ia l to b e d et ected o v e r r e la t iv e ly sh o r t t im e sp a n s. If th is sh ou ld be tr u e it w ould be extr em ely d ifficu lt to red u ce th e n e c e ssa r y n u m ber of even tu al exp erim en tal su b jects by reco v er in g in dividu al d o se - r e sp o n se cu rves. H ow ever, it w as d em on strated th at cu m u lative effects of su cce ssiv e e xp o su r e s, alth ough extrem ely sm all, can be iso late d by the elim in ation 2- - of ran dom v ar iatio n s. It w as p r o p o se s, as a reason ab le statem en t, th at not all th e le ad en terin g th rough th e lu n gs w ould be elim in ated over a 24 h our p er io d . Th e excr etio n of le ad sh ou ld th en in c r e a se con stan tly over the w eekly exp erim en tal days (i. e. fr o m M onday to F r id ay ) an d con stan tly d e c r e a se d u r in g th e w eek en d (i;.e . o v e r Sat u r d ay an d Su n d ay. ) By e lim i n atin g som e of the ran d om v ar iatio n abou t th e d ay s of th e w eek it w as in deed d em on str atab le th at u r in ar y excr etion of le ad in c r e a se s con stan tly fr o m M on day to F r id a y an d th en d r o p s a g a in d u r in g Sa t u r d a y an d Su n d ay . (Th e o b se r v e d tr en d w as b ase d on 80 e xp e r im e n t al w eek s an d th e st a t is tical sign ifican ce of the d ifferen ces w as tested by A n alysis of V ar ian ce.) Ran dom v ar iatio n s w ere elim in ated in a v er y cru de fash ion an d one can h ope w ith good r e a so n th at m o r e p ow erfu l n u m e r ical an aly se s w ill be efficien t in r ecover in g even sm a lle r in cr em en ts fo r few er ob servation s. _ 3. The fin al action of the experim en t ap p ear s to be: a. The experim en t w ill be a pilot attem pt to reco v er a d ose-resp o n se cu rve fr o m a sin gle su b ject an d to m ak e cru d e prediction ^ of the effects of u n ob ser v ed d o se le v e ls. (D ose is h e r e defin ed sim p ly a s var iatio n in tim e fo r fixed lev els of lead in a i r . ) * b. W hether or not tim e of exp osu re, r e st betw een exp o su r es, and level of le ad in a ir (an d p e r h ap s even p a r t ic le s i z e ) w ill be v ar ie d con com rn .it ~ an tly in fu tu re sin gle su b ject exp er im en ts w ill depen d on the su c c e ss w ith w h ich th e p r o p o se d an a ly se s can iso la t e d iffe r e n ce s in e xc r e t io n an d st o r age betw een 4 an d 8 h our d o se s an d th e u tility of su ch in cr em en ts in p r e d ic t io n e ffe c t s o f th e.'lO h o u r d o se l e v e l . ' c . Th e an aly se s of th e data w ill p r eced e a s outlin ed p r ev io u sly , takin g con gn izan ce of ch an ges in trodu ced in the exp erim en tal d esign . A s su ggested th en , on ly p ar t of th e accu m u lated in form ation w ill be u sed to d er ive th e d e sir e d e st im at e s an d p red iction equ ation s, the r em ain d er w ill se r v e a s ch eck fo r r eliab ility of the p ro ced u res. d. M r. Sch afer is w orkin g out tech n iqu es th at w ill m e asu r e d irectly the am oun t of le ad rem ain in g in th e lun g of th e su b ject aft e r a stated p eriod of exp osu re. I e . M r. Ch olak h as agr e e d to r ep o r t blood an d u r in ar y lead le v e ls to th ree d ecim als. f. A d etailed sch edu le of exp erim en tal con dition s w ill be given to M r. 0004420 3- - C r e e ch , who w ill su p e r v ise th e co m p lian ce of th e su b je ct w ith exp erim en tal con d ition s. A d etailed calen d er of even ts w ill be given to th e su b ject, to M r, C r eech , an d to w h oever w ill m on itor all p h ase s of th e exp erim en t a s soon a s the st ar t in g date of the e xp e r i m en t is determ in ed. Th is calen d er w ill co n sist of the daily regim en an d in clu de th e follow in g in for m ation : i. Th e h our at w h ich th e su b je ct is to en ter th e ch am b er