Document wqkpQG0okpJxxm91bV0b1YjYD

P R O G R ESS R E P O R T - P R O JE C T NO . LH -75 IN V ESTIG A T IO N O F H UM AN E XP O SU R E TO P A R T IC U LA T E LE A D CO M P O U N D S IN TH E AIR UNDER EXP ER IM EN T A L CO NDITIO NS : Th e w ork ou tlin ed in p r e v io u s r e p o r t s of p r o g r e ss, th e la st of w h ich w as dated Sep tem b er 10, 1964, h as been d ir e cte d p r im ar ily tow ard the d eterm in ation of th e m axim u m con cen tr atio n of id e ally r e sp ir a b le (th at i s , p a r t ic le s of le ad too sm a ll to b e d e p o sit e d in th e u p p e r r e sp ir a t o r y t r a c t ) in o r ga n ic le a d in th e a t m o s p h e r e , th at can b e in h aled con tin u ou sly th rou gh ou t a life tim e by n o r m al, h ealth y p e r so n s, w ith out d e m o n st r ab ly p r o g r e ssiv e accu m u latio n of le ad in th eir b od ily tis su e s. Th e ap p roach to th is p rob lem isp atte rn e d on th e r e su lt s of b alan ce e x p e r im e n t s (in tak e of le a d in fo o d an d b e v e r a g e s, an d ou tpu t in th e fe c e s an d u r in e ) c a r r ie d ou t p r e v io u sly w ith h u m an su b je c t s u n d er v a r io u s co n d itio n s. In th e p r e se n t e xp e r im e n t , su ch su b je c t s, a ft e r p r e lim in a r y o b se r v at io n of t h e ir le ad m e t ab o lism u n d er n o r m al con d ition s, a r e su b je ct ed to th e in h alation of a ir con tain in g lead in a know n con cen tration o v e r p e r io d s of tim e su fficien t to d em on st r a t e th e o c c u r r e n c e o f n o n - o cc u r r e n c e of a p h y sio lo gical r e sp o n se in th e fo r m of an in c r e a se in th e u r in ar y output of le ad . (T h is r e sp o n se can be d etected b e fo r e an y oth er in th e in tact h um an o r gan ism . ) It is p ostu lated , on good gr o u n d s, th at th e r e sp o n se of h um an b ein gs to con tin u ou s exp o su re of th is type can be d eterm in ed w ith ap p r o xim at e a c c u r a c y by e x t r ap o lat io n fr o m th e r e su lt s of r e g u la r in cr e m e n t al in c r e a se s in th e d u ration of in term itten t exp osu re - th at is, x h ou rs of exp o su re p e r day fo r a su itab le tim e , follow ed by 2x, 3x an d 4x h ou r s of exp o su r e , fo r co m p a r a b le p e r io d s of tim e , w ill y ield a se r ie s of p oin ts on a cu r v e w h ich can be exten ded tp 24 h ou rs p e r d ay, e v e r y day. In a con tin u ation of p r ev io u s e x p e r im e n t s, Su b je cts an d ' m e sse n t ia lly p a r a lle l e x p e r im e n t s, h ave b een su b je ct e d to e x p o su r e to lead se sq u i- oxid e d isp e r se d in th e a ir of th e tw o r e sp ir a t o r y c h am b e r s in p a r t ic le s ran gin g fr o m 0. 01 t o 0 . 18 m ic r o n in d ia m e t e r (m e an siz e 0. 05 m ic r o n ) in th e c o n c e n t r a tion o f a p p r o x im a t e ly 10 m ic r o g r a m s of le ad p e r cu b ic m e t e r . (A fter p r e lim in a r y con trol o b se r v at io n s, o v e r a p erio d of m on th s p r io r to the y ear 1965), th ese su b je c t s w er e in trod u ced in to th e c h am b e r s fo r 3 h o u r s on e v er y o th er d ay (10.5 h o u r s p e r w e e k ) o v e r t h e p e r io d o f 12 w e e k s. Su b se q u e n t ly t h e d u r a t io n o f t h e exp o su r e p er day w as doubled, tr e b le d , an d fu r th e r m u ltip lied u n til, at p r e se n t, A u gu st 18, 1965, on e of th e su b je c t s (^pf^k) is sp en d in g 6 3 .0 h o u r s p e r w eek , in t h e c h a m b e r , w h ile t h e o t h e r ({^pF. , w h o s t a r t e d a b i t l a t e r ) i s sp e n d in g 5 2 .5 h o u r s p e r w eek , both h avin g p a sse d th r ou gh p e r io d s of ap p r o x im at e ly 16 w eek s of e x p o su r e fo r 10. 5, 21, 3 1 .5 an d 42 h o u r s p e r w eek, r e sp e c t iv e ly , w h ile Su b ject N . K. w a s su b je c t t o , a d d it io n a lly 5 2 .5 h o u r s p e r w e e k fo r 16 w e e k s, b e fo r e u n d e r goin g th e p r e se n t p h ase of th e exp erim en t. Th ere h as been no d em on strab le excr eto r y r e sp o n se on the p ar t of eith er su b je ct to th e e xp e r im e n t al r e gim e n . T h at is to sa y th at th e qu an tity of lead ab so r b e d d aily in th e lu n gs of t h e se su b je c t s h as n ot b een su fficie n t u n d er th e se con dition s to b e d em o n str ate d in th e face of the v a r iab ilit y of the u r in ar y excr etio n of lead fro m day to day in duced by th e ab sor p tio n fr o m the alim en tary t r act . O r to be still m o re sp ecific, the qu an tities of lead ab sorb ed from the alim en tary tr act fr o m day to d ay a r e so m u ch la r g e r (th ey can b e exp ected to b e m u ch m o r e v a r ia b le , a lso ) th an th e q u an tities ab so r b e d d aily fr o m th e lun g th at th e lat t e r can n ot be detected. It is n e c e ssa r y to obtain a r e sp o n se , an d in fact to obtain a se r ie s of in c r e a sin g e x c r e t o r y r e sp o n se s, in o r d e r to ob tain th e d ata fo r extr ap o latio n fr o m in ter m itten t to con tin u ou s e xp o su r e . T h e r e fo r e the exp erim en t m u st b e con tin ued in in c r e a sin g in cr e m e n ts of se v e r it y (co n cen tration of le ad in a ir an d d u ration o f e xp o su r e ) u n til su ch d ata h ave been ob tain ed . One w ould w ish to exp ed ite th e e x p e r im e n t al p r o ce d u r e so a s to obtain d efin itive r e su lt s m o r e p ro m p tly an d at le sse r co st . H ow ever, in view of th e * to tal lack of exp erim en tal p reced en t, and b e cau se of the r isk of oversh ootin g th e m ar k (in t e r m s of co n ce n t r at io n of le ad in a ir ) an d th u s r e n d e r in g th e su b je c t s u n fit fo r fu r th e r o b se r v a t io n s, it se e m s w ise , at th is tim e, to follow th e o r igin al exp erim en tal d esign du rin g th e com in g y e ar . If th is is don e, and if it is n e c e ssa r y , a s se e m s lik e ly , to go beyon d th e le v e l of 10 m ic r o g r a m s of le a d p e r cu b ic m e t e r of a ir in o r d e r to ob tain an e x c r e t o r y r e sp o n se , th e p roced u re w ill be th at of begin n in g th e new le v e l of e x p o su r e at a p oin t, in t e r m s of con cen tr ation an d t im e , w h ich is ju d ged to be eq u ivalen t to th e n ext se r ia l in cr em en t of in c r e a se in in ten sity . O n ce a r e sp o n se h as th en been obtain ed an d st ab iliz e d (oth er d ata in d icate th at a p la t e a u o f r e sp o n se w ill h av e b e en r e a c h e d in 16 w e e k s, a t m o st ), th e c o u r se is se t fo r th e ad d ition of fu r t h e r p oin ts in a cu r v e w h ich w ill y ield th e ap p r o x im at e valu e fo r con tin u ou s exp o su r e . Th ere d oes not ap p e ar , at th is tim e, to be a sh ort cu t to th is r e su lt , an d in view of th e in vestm en t of tim e and m on ey in th is e x p e r i m en t an d in th e m e tab o lic evid en ce on w h ich th e e xp e r im e n t is fou n d ed , it w ould se e m u n w ise, now , to a lt e r th e d e sign . H ow ever, at th e end of th is y e ar (1965), th e exp erim en tal d ata w ill be review ed c r it ic a lly , a s a m ean s of ch eckin g th e e xp e r im e n tal d e sign an d of affe ctin g su ch r e d u ctio n of t im e , effo r t an d m o n et ar y e x p e n d it u r e .a s m a y b e fe a sib le . Su ch m o d ific a t io n o f p r o c e d u r e a s m ay se e m fe asib le an d w ise w ill b e com m u n icated to th e sp o n so r s for com m en t and c r it ic ism , so a s to ach ieve th e m axim u m b en efit fr o m th e c o lle ct iv e cr it iq u e . Con sid erin g th e p r e se n t sit u a t io n of th e p r in c ip a l in v e st ig a t o r (on le a v e in th e se r v ic e of P an A m e r ic an H ealth O r gan izatio n fo r th e n ext th r e e m on th s) as w ell a s th e p r esen t st a ge o f th e e xp e r im e n t , it is b e lie v e d th at no u se fu l p u r p o se w ould be se r v e d at t h is tim e by a sse m b lin g th e d ata th at w ould m e r e ly illu st r a t e th e n egativ e r e su lt s of th e e xp e r im e n t a s con d u cted up to t h is p o in t. It sh ou ld be e m p h asiz e d , p er h ap th at th e v e r y n egativ ity of th e r e su lt s, in relation to th e poin t of sign ifican ce th at r e m a in s to be e st ab lish e d is an e xtr e m e ly im p o r tan t fin d in g. , P rin cip al In vestigator D at e : A u gu st 18, 1965