Document rxB3xdXm2gZbrrYgEyXwvXmxv

N y' Lead Ab s o r p t io n , Lead E xcr e t io n and Lead P o iso n in g by R o b e r t A. K e h o e , J a c o b C h o l a k , D o n a l d M. H u b b a r d and R o b e r t R. McHary Prom th e K e 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 g y, U n iv e r s it y of Cin cin n a t i, Cin cin n a t i, Ohio. The p r e s e n t p r o b le m s i n t h e d i f f e r e n t i a l / ') d ia gn o s is of lea d p o is o n in g, in so fa r as th ey d i ff e r from those o f any p reviou s p er io d , a r is e la r g e ly in the e va lu a t io n o f the s ig n ific a n c e of the lea d exp osu r e o f a p a t ie n t , and the in t e r p r e t a t io n of the m eaning of such lea d d e t er m in a t io n s as n a j h a ve b e e n c a r r i e d o u t on t h e f a c e s , u r i n e , b l o o d , s p i n a l flu id , t e e t h , slFin ,cr other t is s u e s , in sea r ch cf s p e c ific evid en ce of le a d a b so r p t io n . These p roblem s, e xp r e ssed somevihat d i f f e r e n t l y , and c o n s id e r e d fr om s l i g h t l y d i f f e r e n t vie w p o i n t s , a r e among t h e mo3t im p o r t a n t p r a c t i c a l q u e s t io n s in r e la t io n to plum bism , both in ge n e r a l m ed ica l p r a c t ic e and in in d u str ia l h ygien e. To t h e" m e d i c a l p r a c t i t i o n e r , t h e f a c t s I n t h e m a t t e r o f le a d exp o su r e a r e o ft e n o b s cu r e . In the ca se of an in fa n t or a c h ild t h e r e may be no r ea so n to s u s p e ct le a d exp osu r e /nnez VT a 3 f a c t or in i l l n e s s u n t i l a ch an ce x - r a y p la t e shews s u g g e s t ive or co n clu s ive evid en ce c f abnorm al le a d d e p o s it s in the s k e le t o n . In the a d u lt , in d u s t r ia l le a d exp osu r e may or may n ot be su ggest ed b y t h e o c c u p a t i o n a l h i s t o r y . The a b s e n ce or t h e o ccu r r e n ce of su ch s u g g e s t i o n m ay b e e q u a l l y m i s l e a d i n g , s i n c e , on t h e one h a n d , l e a l e x p o s u r e m a y e x i s t i n u n s u s p e c t e d o c c u p a t i o n s , w h i l e on t h e o t h e r , r e co gn ize d le a d t r a d e s may be so w e ll r e g u la t e d as to give r is e to l i t t l e or no exp osu r e. In deed t e ch n ica l and o p er a tin g chan ges are c a r r ie d out in modern p la n t s with such d is co n ce r t in g speed and fr eq u en cy, th a t p la n t p h ysicia n s th em selves are n ot always con sciou s cf t h e ir h ygie n ic im p or t. O b viou sly, the d o c t o r who h a s nb d i r e c t and d e t a i l e d k n o w le d g e o f p l a n t a c t i v i t i e s a n d c o n d i t i o n s , c a n n o t b e e x p e c t e d t o p l a c e a p r o p e r v a l u e on the h is t o r y of o ccu p a t io n a l le a d exp osu r e. In many in s t a n ce s , t h e r e fo r e , judgm ent r e q u ir e s t h a t he base h is op in ion as to the s e v e r i t y o f t h e o xp o s u r e on s p e c i f i c e v i d e n c e s o f l e a d a b s o r p t i o n , r a t h e r t h a n on n o n - s p e c i f i c c l i n i c a l e v i d e n c e s o f i n j u r y . In th e ca se c f le in d u s t r i a l p h ys ic ia n , the s i g n i f i c a r : c e v.*'-i. t h e l e a d ex; k n o w n , i n t i m e > t h r o u gh X?JW- p o p u l a t i o n , b u t i t c a n n o t bi j u r e in a p l a n t ca n b e co m e p a r t i a], l y l i n i c a l e f fe c t s upon the p la n t a n t icip a t e d or p r op er ly a p p r ecia ted w i t h o u t r e cou r s e t o s on e p r Lse m ea n s f o r m e a s u r i n g e i t h e r t h e m a g n i t u d e o f t h e p o t e n t i c<-i1a. , : o s u r e , os', p r e f e r a b l y , t h e p h y s i o l o g i c a l X*3s p e n s e t o e: a s u r e i n t e r m s c f t b e l e a d a b s o r p t i o n and le a d e x c r e t io n of the workmen. Sven w ith the n ecessa r y fa c t s a va ila b le as to the n a t u r e : and m a gn itu d e c f th e le a d e xp o s u r e , an in t e r p r e t a t io n o f t h e ir c l i n i c a l s ig n ific a n c e may s t i l l be d i f f i c u l t , p a r t ic u la r ly I f t h e e x p o s u r e i s kn own t o be s l i g h t . The r e p u t a t i o n c f le a d a3 an i n s i d i o u s p o is o n th e m in u t e s t q u a n t i t i e s o f w h ich , i f a b sor b ed r e p e a t e d ly over a p r olon ged p e r io d , m igh t accu m u late In the body v;ith d is a s t r o u s r e s u l t s , has lon g been e s t a b lis h e d b oth in the m ed ical and the la y m ind. G r a d u a lly p h ysicia n s with exp er ien ce .In t h e l e a d t r a d e s , who n ot ed , t h e r e s u l t s o f v a r i o u s t y p e s a n d d e g r e e s o f le a d e x p o s u r e , came t o b e l i e v e t h a t le a d a b s o r p t io n d id not cause In ju r iou s e ffe c t s i f it d id not exceed ce r t a in l i m i t s . The o r i g i n a l d i s t i n c t i o n b et ween d a n ger ou s and e s s e n t i a l l y h a r m le s s o c c u p a t i o n a l l e a d e xp o s u r e was b a s e d cn o b s e r v a t i o n s o f w o r k e r s rand p l a n t s , w i t h o u t b e n e f i t o f q u a n t i t a t i v e m e t h o d s o f stu d y, k ith the r ecogn ition of the gr e a te r s ign ifica n ce of in h a led le a d as com pared w it h in ge st ed le a d and with th e d e velopm en t o f s a t is fa c t o r y m ethods fo r th e est im a t io n o f p a r t ic u la t e le a d in t h e a i r b r e a t h e d b y workmen,, t h e e x i s t e n c e o f a t h r e s h o ld valu e fo r t o xic lead absorp tion has ap p ar en tly been e s t a b lis h e d , .( However, many p h ys ic ia n s , p h y s io lo g is t s and p h a r m a co lo gist s have e it h e r d is r e ga r d e d th e o b s e r va t io n s made in t h is f i e l d or h ave co n s id e r e d them w it h s u s p icio n and s k e p t icis m * Only r e c e n t ly h a s e vid e n ce been o b t a in e d fr om t h e s t u d y c f human le a d a b s o r p t io n and e x c r e t io n u n d er a v a r i e t y o f c o n d it io n s , 'which s u b s t a n t i a t e s the p osition taken by the in d u st r ia l h ygie n is t , because the m ean in g o f t h is evid en ce has n ot been f u l l y a p p r e cia t e d , I t seems w e ll t c o u t lin e i t h e r e , n ot on ly in r e la t io n to le a d a b s o r p t io n on t h e p a r t o f t h e g e n e r a l p o p u la t i o n and t o t h e d i a g n o s i s c f le a d p oison in g in the hands of the a ver a ge c lin ic ia n , bu t a ls o as a b a s is , in p r in c ip le , fo r I n d u s t r ia l p r a ct ice . _X The p r e s e n ce o f le a d In t h e t i s s u e s and in th e e x c r e t a o f n orm al in d iv id u a ls , q u it e a p a r t from any o ccu p a t io n a l e x p o s u r e t o l e a d c o m p o u n d s , i s now e s t a b l i s h e d . I n 1933# v,e r e p o r t e d In d e t a i l th e d a t a of cu r s t u d ie s up to t h a t time and r evie w ed th e o b s e r va t io n s of o t h e r workers ( 1, 2, 3 ) . Sin ce the p u b lica t io n of t h e se r e p o r t s , many a d d it io n a l co n t r ib u t io n s have d em on strated the occu r r en ce of le a d in the s k e le t o n ( in c l u d i n g t h e t e e t h ) (14., & 7 , 8 , 9 , 10 , 1 1 ) , t h e s o f t t i s s u e s w , 5 0 1, 1 2 , 13 , lip , 15 ) ( i n c l u d i n g t b e b r a i n ( 9 ) a n d t h e c e r e b r o - s p i n a l f l u i d ( 16 , 1 7 ) , t h e b l o o d ( 18 , 19 , 2 0 , 2 1 9Z& * * ') u r i n e ( 9 ,' 18 , 2 0 , 2 2 ^ 52 5 , 2ip, 25 2 c , 2 7 , 28 ) and f e c e s ( 2 0 , 2 c) o f n o r m a l p e r s o n s o f a l l a g e 3 a n d o c c u p a t i o n s . An e x a m i n a t i o n o f th e r e s u lt s o b t a in ed b y d i ffe r e n t a n a lys t s in va r io u s p a r t s of the wor ld shows them to be In r em a r ka b ly clo s e a gr eem en t, wit h due allowan ce fo r va r ia t io n s in the s e n s it iv it y and a ccu r a cy o f th e a n a l y t i c a l m eth od s em p loyed . The g e n e r a l p a t t e r n o f n o r m a l l e a d m e t a b o l i s m w h i c h we h a ve d e s c r i b e d i n r e l a t i o n t o th e Am er ica n p o p u la t io n seem s to h a ve b een co n fir m e d , n o t o n ly in the .m arican en vir on m en t b u t in th e s e v e r a l co u n t r ie s in wh ich s im ila r o b s e r va t io n s h ave been m ade. Of p a r t ic u la r in t e r e s t to us ir th is con n ection a s s o cia t e s / ... > l^/ on the n o r m a l p a r s on 3^J d r e a t re th e r e s u l t s o b t a in e d by Lyn ch and h is ead co n t e n t o f t h e 'b o n e s of pre3um ably r i t a i n ) , a n d t h o s e o f Tom.psecfc a n d An d e r s o n ( 9 ) , a n d T o m p s e t t ( I d ) _n t h e "le a d c o n t e n t , c f t h e s k e l e t o n a n d s o ft t is s u e s cf human fe t u s e s and human b e in gs of w id e ly va r ie d a ges (Gr ea t B r i t a i n ) . Th ese d a t a wou ld seem to show t h a t th e lea d co n t en t of the t is s u e s o f a norm al c h ild and o f a norm al a d u lt as r e p o r t e d b y us (2),. was o f an o r d e r o f m a gn it u d e f a i r l y c h a r a c t e r i s t i c o f n orm al human b e in gs in g e n e r a l. he are ju s t ifie d ,; t h e r e fo r e , In m aking a co n fid en t r esta t e m e n t of the fa c t s with r e ga r d to norm al human le a d m etab olism in t h e ir s im p le s t t e r r a , The ad-alt Am er ica n i n g e s t s le a d in h is fo o d and d r in k to th e e xt e n t of a p p r o xim a t ely 0 .25 m illigr a m s per aver age day (20) (Ho p r o b a b l y i n h a l e s a s m a l l q u a n t i t y o f l e a d fr o m t h e a i r h e b r e a t h e s (29 3 0 , 3 1, 3 2 , 3 3 * 3b* 35) > a l t h o u g h t h e a m ou n t i n h a l e d and t h e p r o p o r t io n a b s o r b e d fr om t h a t wh ich is in h a le d a r e con je c t u r a l.) Most of the in gested lea d t r a ve r se s the alim en ta r y t r a c t u n a b s o r b e d , b u t some q u a n t i t y is a b s o r b e d as i3 shown b y th e c o n s t a n t p r e s e n c e o f le a d in t h e t i s s u e s , this b lo o d , and t h e u r i n e . The mean d a i l y f e c a l o u t p u t o f l e a d i 3 a p p r o x i m a t e l y O.2 5 m i l l i grams ; 2 C) , w h ile t h e d a i l y u r i n a r y o u t p u t v a r i e s fr om 0 .0 2 m i l l i grams t o 0 .10 m illig r a m s (2 0 , 2 o ) , th e v a r i a t i o n b e in g c h i e f l y r e la t e d to weath er co n d it io n s w it h t h e ir a t t e n d a n t in flu e n ce upon u r in a r y volu m e (26) . The le a d o f t h e t i s s u e s i s d i s t r i b u t e d in accordan ce with a d e fin it e p a t t e r n , w it h .t h e m ajor p ortion in the sk ele t o n (and a p p a r e n t ly with a h igh er co n ce n t r a t io n in such lon g b c r . e s a s t h e f e m u r ( 5 , 1C ) , b u t w i t h m e a s u r a b l e a n d a p p a r e n t l y ff a i r l y con st a n t q u a n t it ie s in the 3 0 ft t is s u e s , e s p e c i a lly in such l i v e r , k i d n e y , s p l e e n a n d b r a i n ( 2 , 9)* The a v e r a g e g r o s s q u a n - p r e s e n t i n t h e a d u l t b o d y i s s o m e w h a t i n d o u b t , b e c a u s e or th e p a u cit y of d a t a ,o u *b p r o b a b ly no' ban i. n o r m o r e t h a n ""ZOO m g. w i t h d u e r e g a r d t o v a r i a t i o n : bod;: w e igh t ( 2 ,5 ,9 > 10 j5 6 ) Barth (56} su p p lie d d ata which in h is opin ion poin ted to a p r ogr essive eleva tio n of the lea d con cen tration of the s k e le t o n w it h p r o g r e s s in g a ge . However th e d i ffe r e n c e s between yo u t h and o ld age were too s l i g h t and too i r r e g u la r to be con v i n c i n g . T o m p s e t t ( 1C) f o u n d s i m i l a r an d e v e n l a r g e r v a r i a t i o n s in d i ffe r e n t bon es of th e same s k e le t o n and In th e s k e le t o n s o f d i f f e r e n t :p e r s on 3 w i t h i n t h e s a m e a g e g r o u p . Tire c o m b i n e d f a c t s fu r n ish e d b y the stu d y of the t is s u e s and e xcr e t a in d ica t e t h a t is m a in ta in ed in which p r o gr e s s ive le a d accu m u lation in the t is s u e s d oes n o t o c c u r , i n t a k e an d o u t p u t h a v i n g come i n t o b a l a n c e a f t e r a cer ta in le v e l of absorp tion has been reached. Sign ifica n t v a r i a t i o n s in a b s o r p t i o n an d e s c r e t i . n o c c u r from, d ay t o d a y, b u t the n o r m a l.m e t a b o lis m of le a d , as com pared w it h t h a t of th e more common m e t a l l i c c o n s t i t u e n t s o f l i v i n g m a t e r i a l , i s r e m a r k a b l y s t a b i l e , '.whether o r 1n o t le a . i i s u s e f u l in p h y s i o l o g i c a l m ech a n ism s is an open q u e s t io n a t p r e s e n t , b u t r e g a r d le s s of th e e ve n t u a l, ans'.ver t o t h i s q u e s t i o n , t h e c o n c e p t of l e a d a s an a c c u m u la t i v e p o i s o n , w i t h o u t r e g a l 'd t o q u a n t i t y , h a s r e c e i v e d i t s d e a t h b l e w . !t e d t h e f o r e g o i n g f a c t s ad p c i s o n i n g ( 37, 38) . ;o g i v e f u r t h e r d e t a i l e d co n - con t o n t o f t h e t l : s r . u e s o: . h e m e r e 17 w i s h t o s t r e s s . s o f t h e ,11m * *- o f n o r m a l f) 1 o f d a t a on t h e 1 ead . ' ? a t i e n t o . r n v i ew o f ( presen t knowledge of the b y a b n o r dX 3T9Ci ' re 4"r> and of lev 1s t indu ced l e a d a u a l y 3S ---K1 * v a r i o u s t y p e s ta.-ze t n e o r p l a c e a s i n v a l u a b l e - .gn o 3 * ' O 3. *' :-i - s u r e f u l c l i n i c a l and m e d ico - le ga l e vid e n ce . H owever, ;ueh p r oced u r es lead in g u n less th ey are ca r r ied o u t w i t h p r e c i s i o n an d i n t e r p r e t e d wii tth d u oc r e .nt a r d f o r t h e a v a i l a b l e kn owledge as to the b eh a vior of le a d . Iloreover, a n a ly t ic a l d ata cannot be s u b s t it u t e d fo r sound c li n i c a l o b ser va tion s in any of the f i e l d s in w h ich t h e y h a ve come t o b e u s e f u l a d j u n c t s . The u lt im a t e s o u r ce s o f t h e le a d wr.lch is fou n d in human food : m e r it s fu r t h e r co n s id e r a t io n and fu r t h e r d e t a i le d st u d y. As we h a v e p o i n t e d o u t p r e v i o u s l y ( 39) t h e i n c r e m e n t o f l e a d c o n t e n t a b o ve t h a t wh ich i s a n or m a l c o n s t i t u e n t o f cun fo o d s u b s t a n ce s , is due t o co n t a m in a t io n from a g r e a t v a r i e t y of s o u r c e s , some o f wjhlch a r e c f r e c e n t and some o f e a r l ' e r o r i g i n . A number of th e e a r l i e r so u r ces of con tam in ation of food and d r in k h a ve d i s a p p e a r e d , some b y a c c i d e n t an d o t h e r s b y i n t e n t . Cu r d a t a on t h e f e c a l l e a d o u t p u t o f n or m a l p e r s o n s in v a r i o u s p a r t s c f th e U n it e d S t a t e s and Can ada, as c o l l e c t e d o ver a p e r io d o f more than a decade, do not give evid en ce of a tendency toward a pro gr e s s ive in cr ea se in d ie t a r y le a d . This is not to im ply th at our sam plin g of t h e p op u lation has been such as to yie ld adequate in fo r m a t io n on t h e e n t e n t or t h e ca u s e s o f v a r i a t i o n in t h e s e r e s p e c t s . N e ve r t h e le s s re have been s t r u ck by the e s s e n t ia l u n i f o r m i t y o f t h e d a t a o b t a i n e d f r o m y e a r t o y e a r , a n d we d o u b t the o ccu r r en ce of any r e ce n t p r o g r e s s ive in cr e a s e in th e le a d I n t a k e o f t h e A j e r i e an p o p u l a t i o n . *.Ve d o n o t s u g g e s t , h o w e v e r , any over-.ee/ nfid0 (51 r e la x a t i o n of t h e e f f o r t s b e in g m a le by t h e s e / en gaged In the s u p e r v is io n , h a n d lin g , and p r o ce s s in g c f cu r food m a t e r ia ls , to prevent' con ta m in ation with le a d . An u l t i m a t a b a s i s f o r d e t e r m i n i n g t h e _ l i m i t s o f s a fe t y, in th e m a t t er s f le a d a b s r p t i ' n , In doth th e g e n e r a l and t h e 1n d u s t r i u l a t i on, can be fou n d o n ly In fu r r i e r exp er im en t a l s t u d i e s o f t h e f a t e o f l e a d when i n t r o d u c e d i n t o t h e hum an b o d y through va r io u s avenues of e n t r a n ce , do have i l l u s t r a t e d c e r t a in a b n o r m a lit ie s in the lo a d co n t e n t of th e t is s u e s snd e xcr e t a of persons exposed to abnormal q u a n t it ie s of lead both of occu p ation al and n o n - o c e u p a t io n a l o r i g i n (I4.0). In o b s e r v a t i o n s made c h i e f l y in v a r i o u s l e a d t r a d e s , we fo u n d , a c o r r e l a t i o n b e t w e e n t h e r a t e o f lea d e x c r e t io n and th e s e v e r i t y of le a d e xp o su r e . The a v a i la b le d a t a a p p ear ed t o in d ic a t e t h a t -within c e r t a in lim it s o f in c r e a s in g e x p o s u r e a n d p r e su m ac l e a b o o r p t i on , . t h e r e wa s a p r o p o r t i o n a l in cr e a s e in th e u r in a r y e xcr e t io n ; with fu r t h e r in cr e a s e s in exp ose t h e r e was a p r o g r e s s i v e l y d i m in is h in g in c r e m e n t o f i n c r e a s e in th e e x c r e t o r y r e s p o n s e . Th er e was a ls o an in co m p le t e ly d e fin e d r e l a t i o n s h i p betwieen th e m a gn it u d e of t h e le a d e xp o s u r e , as p o r t r a ye d by r a t e of le a d e x c r e t io n , and the o ccu r r en ce of lea d in t o x i c a t i o n among t h e wor km en , h e came t o t h e c o n c l u s i o n , wh ich S h i e ls (4I) h a s s in c e r e a ch e d from h i s o b s e r v a t io n s , t h a t le a d p oison in g may be exp ected to occu r under o ccu p a tion a l con d ition s in wh ich l e a d i s e x c r e t e d b y r e p r e s e n t a t i v e workmen a t a mean r a t e a b o v e 0.21 m g. p e r l i t e r i n t h e u r i n e . I n s u b s e q u e n t p l a n t s t u d i e s we h a v e k e p t i n m in d t h e n e e d f o r d e f i n i n g m o r e p r e c i s e l y in berms of lea d e x c r e t io n , th e h igh e s t l e v e l o f len d exp osu r e co m p a t ib le w it h com p lete fr eed om from c li n i c a l- le a d in t o x ic a c i n . As e v i d e n c e o f s om e p r o g r e s s t o w a r d t h i s g o a l , t h e f o l l o w i n g ?'3c e n t o b s e r v a t i o n s a r e r e p o r t e d . * Groups of men, s e le c t e d as r e p r e s e n t a t iv e of th e va r io n s o ccu p t 1on3 in t h r e e d i f f e r e n t i n d u s t r i e s , wero exam in ed b y me oh o a s w h i c h we h a v e d e t a i l e d p r e v i o u s l y {Ip2 } . V a r i o u s s a m p le s o f b l o o d , u r i n e .and f e c e s , as i n d i c a t e d in t h e d a t a , wo r e o b t a in e d w it h "OT?t a b le c r s c a u t ; one :en 4- ! y. r *I o n . work o f ea ch group in vo lve d exp osu r e on ly to p a r t ic u la t e in o r ga n ic l e a d c o m p o u n d s . Th e men i n Gr o u p A. a l l e n g a g e d i n t h e sa m e g e n e r a l type of work, h a n d led a fin is h e d m a t e r ia l which co n t a in e d load ' n an e s s e n t i a l l y i n s o l u b l e f o r m i n a s i l i c e o u s b a s e . 'The c o n d i t i o n s o f The f u l l d a t a o f t h e s e s t u d i e s w i l l b e p i ve n e l s e w h e r e . B r e v i t y n e c e s s it a t e s use of on ly th ose item s of in for m a tion and d ata which illu s t r a t e the poin ts under d iscu ssion h er e. exposure ::srs n ot th ough t to he such as to perm it ab sorp tion o f lo a d t o m or e t h a n a t h e o r e t i c a l e x t e n t * The men in Gr ou p B were em ployed in va r io u s typ es o f s o ld e r in g a c t i v i t i e s , but a l l had the same t yp e , and a p p a r e n t ly abou t the same d egr ee o f exp osu r e t o h ::.33 o f m o l t e n l e a d a n d t o f i n e l y d i v i d e d m e t a l l i c l e a d a n d l e a d o x i f e . The m en i n Gr o u p C m e r e l i k e w i s e e x p o s e d o n l y t o fu m e 3 a n d to p a r t ic u la t e le a d r e s u lt in g from va r ie d t yp es of o p e r a t io n s w it h m olt en lea d and le a d c a s t i n g s . However th e o p e r a t io n s in t h is p la n t , as r e p r e s e n t e d b y t h is s m a ll grou p of workmen, in vo lve d somewhat v a r i a b l e d e gr e e s of le a d e xp o s u r e of a g e n e r a l l y g r e a t e r s e ve r it y than th at of the oth er p lan ts. fh e c l i n i c a l d a t a on gr ou p s A and 3 were e n t ir e ly d evoid of evid en ces of lea d ab sor p tion or lea d in t o x icati:n, I:n the case of Group C, however, certain indi' seen tc ha-c ; a0sorbed lead in sufficient quantity to p o^1Xwi-l*i- %U,<X*'j- definite gingival blue lines, eharaci teristi in t h e b?.o.od p i c t u r e , a n d s l i g h t b u t u n m i s t a k a b l e e v i d e n c e s o f n eu ro-m u scu lar dam age. In a d d it io n to th ese o b je ct ive fin d in gs th ere were s ca t t e r e d bu t s u g g e s t ive evid en ces cf m iner t o xic e f f e c t s i n t h e f o r m o f v a g u e g a s t r o - i n t e s t i n a l c o m p l a i n t s ' . One t y p i c a l h isfco r jf a f a r e c e n t e p is o d e c f s a t u r n in e c o l i c was o b t a in e d . Ho h i s t o r y o f f a t a l o r p e r m a n e n t l y d i s a b l i n g p lu m b is m c o u l d h e', e l i c i t e d from m anagem ent, p la n t p h ys icia n , or em p loyees over the p e r io d o f t h e i r d i r e c t kn owled ge and e x p e r i e n c e . Im p r ovem en ts in v e n t i l a t i o n h ad b e e n made some two ye a r s p r e v i o u s l y , s i n c e wh ich time ca s e s or s u s p e ct e d ca ses of in c ip ie n t in t o x ic a t io n had been ca r e d fo r e i t h e r b y t em p or a r y c e s s a t io n o f em ploym ent or more fr e q u e n t ly b y t r a n s fe r to work in vo lvin g lo s s exp osu r e. 01562 'The a g e d i s t r i b u t i o n o f t h e -r.en s e l e c t e d to r e p r e s e n t th e va r io u s occu p ation s in each in d u s t r y, as given in Table 1, is of i n t e r e s t on ly b ecau se i t d em on str ates th e r e p r e s e n t a t i o n o f vvid e ly d i v e r g e n t a ge g r o u p s . The d u r a t i o n o f con t i n u o u s e x p o s u r e , s h own i n T a b l e 2, i s c o r r e s p o n d i n g l y r e p r e s e n t a t i v o f b o t h s h o r t a n d l o n g p e r i o d s , e x c e p t I n t h e c a s e o f Gr o u p A i n whi th e lo n g e s t p er io d o f em ploym ent co in cid e d w it h th e l i f e span of t h e i n d u s t r y up t o t h e t im e o f o u r o b s e r v a t i o n s . The d a t a in T a b l e s 3 a n d Lf on t h e f e c a l o u t p u t o f l e a d , ( r e s u l t s w e r e n o t a v a i l a b l e f o r Group A) , s h o u ld be i n t e r p r e t e d in r e l a t i o n t o our p r e vio u s demon s t r a t i o n o f th e r o l e o f a lim e n t a r y le a d as an a p p r o xim a t e m ea su r e of t h e m agn itu d e of exp osu r e In d u s t y le a d t r a d e s . The d iffe r e n c e b e t w e e n t h e r e s u l t s on c o i n e d i n t h e t wo g r o u p s i s n o t s i g n i f l e a n t J s t a t i s t i c a l l y , on t h e o a s i s ' o f c o m p a r i s o n o f t h e mean v a l u e s f o r l e a d f o u n d in a s i n g l e f e c a l e v a c u a c i n . H o w e v e r , t h e t o o g r o u p s m v> -y i g n i f l e a n t l y d i f f o r e h t w i t h r e s s e c t t o a l i-.is n t a r y 75h e n c o m p a r e d a s t o t h e i r m e a n l e a d o u t p u t p e r gr a m o f r1ws.1*13_ i n d i c a t e s t h a t t h e e x p o s u r e o f Gr o u p G t o p a r - t i c u l .n t h e a c m o s p h o r e wa s .gr o o t e r t h a n t h a t c -vi -r\ me an v a l u e s a r e a b oye mean n o r m a l ^ d e l s . The r e s u l t s ' o n t h e u r in e ( Ta b le ) a r e muon more s i g n i f i c a n t t h a n t h o s e on t h e f e c e s , b o t h In t h e i r g e n e r a l p h y s i o l o g i c a l m e a n i n g an d I n t h e c l a r i t y w i t h i 0^1 t h 3y p o r t r a y d iffe r e n c e s in the le-.d a b s o r p t io n of the thre gr ou p s o f workmen. Th e m ea n r a t e o f u r i n a r y e x c r e t i o n f o r Gr o u p A i,ss w i t h i n n o r m a l l i m i t s , aS:Va3 e x p e c t e d ; t h a t f o r G r o u p B i s h i g;hheerr , a n d t h- ;t f o r Gr o u p C i s s t i l l h i g h e r , b o t h d i f f e r e n c e s b e i n g o f s t aaftciiss ttiicc?a l l y s i g n i f i c a n t p r o p o r t i o n s . Th u s t h e a n a l y t i c a l r e ss u li t s on t h e v e r ify the e xist e n ce of th ree d iffe r e n t le v e ls of lead exposure and a b s o r p t io n . * I t is a n a t t e r of both s c i e n t i f i c and p r a c t ic a l im p o r t a n ce t h a t t h e r e s u l t s o b t a in e d on s a m p le s o f b lo o d ( T a b le b) fr om workm en in Gr ou p s A and 3 do n ot d i f f e r e n t i a t e t h e s e two gr ou p s with r e s p e ct to t h e ir a b sor p tion of le a d . I t is probable th a t a d i ffe r e n t ia t io n would have been e ffe c t e d i f a la r g e r number of b lo o d sa m p les from Group 3 had b een a n a lyze d , fu r t h e r m o r e t h r e e a n a l y s e s on b l o o d fr o m i n d i v i d u a l s i n Gr o u p C, y i e l d i n g 0.09 r ag** 0 . 2J m g . , a n d 0 . 2+9 mg p e r IDO gr a m s o f b l o o d , l e a v e l i t t l e d o u b t a s t o t h e s t a t u s o f t h e gr o u p in. t lii.s r e s p e c t , n e v e r t h e l e s s , t h e fa c t rem ain s t h a t w it h due r e ga r d to the numbers of sam ples a va l' ' . a b le f o r a n a l y s i s , t h e r e s u l t s on t h e b lo o d do n o t y i e l d a3 d e f i n i t e e v id e n c e as t h o s e on th e u r i n e , w it h r e s p e c t t o t h e c o n d i t i o n s u n d e r s t u d y , ( T h e m ea n v a l u e o f 0.078 + 0.007 To r the u r in a r y r e s u lt s which correspon d to the fou r teen an alyses on t h e b lo o d in Group 3 i s s i g n i f i c a n t l y g r e a t e r t h a n t he mean f o r Cr o u p A. ) Th e r e a s o n f o r t h i s c a n b e f o u n d , v;e b e l i e v e , i n phy 3 i ol cgi-ea l c o n s id e r a t io n s * U r in a r y le a d e x c r e t io n v a r ie s from p e r s o n t o p e r s o n a n d i n t h e s a n e p e r s o n s wi t h a v a r 1 e t y o f i n Gi v i Gu a * D e t e r m i n a t i o n s o f t h e p a r t i c u d a t e 13 ad 1n t h e a t m os p h e r e o f P l a n t 3 , a s c a r r i e d ou t wi t h s t a n d a r d - V A'*?w* "-grr o t h e r e b s 0 r v e r s Cl a som ewh a t e a r l i e r d a t e , p r o v i d e u s e f u l c o r r e l a t i v e d a t a . The o b s e r ve l e a d c o n c e n t r a t i o n s r a n g e d fr o m 0 .0 3 3 m g. Pb up t o 0. 6p mg. ?b p e r c u b i c m e t e r o f a i r , w i t h a m ea n v a l u e o f 0,21 + 0,02 m g . Pb p e r cu b i / m et er in t h ir t y - o n e a i r sam p les t a ken from va r io u s p a r t s o f th e p la n and e n vir o n m e n t a l fa c t o r s . H owever, the co n ce n t r a t io n of lea d in a sam ple of u r in e c o lle c t e d over a p er io d of t w e n t y-fo u r to s e ve n t y- t w o h o u r s , in a cco r d a n ce w it h our p r a c t i c e , shows some degree of respon se to a ll the p h ysio lo gica l fa cto r s a ct ive du rin g t h a t p e r io d , in clu d in g va r ia t io n s in lead a b so r p tio n . k s in g le b lo o d s a m p le , on t h e c o n t r a r y , i l l u s t r a t e s o n ly a m om en t a r y p h y s i o l o g i c a l 3 t a t e , .hich, u n d e r e s s e n t i a l l y c o n s t a n t c o n d i t i o n s of lea d exp osu r e, may co n ce iva b ly r e p r e s e n t the ge n e r a l le v e l of t h e le a d m eta b olism more a d e q u a t e ly than a sam ple o f u r in e , but which under con d ition s of va r ia b le or in t e r m it t e n t exposure cou ld s c a r c e l y be e xp e ct e d t o do s o . -h o c l i n i c a l and a n a l y t i c a l d a t a ao a wh o le do n ot j u s t i f y sweep in g c o n c lu s io n s . F u r t h e r s t u d y of t h e s e i n d u s t r i e s a n d o f o t h e r s w i t h d i f f e r e n t b a s i c l e v e l s o> l e a d exp osu re w ill be r e q u ir e d to d efin e-, in terms of le a d m etab olism , th e u p p er l e v e l o f le a d exp o su r e wh ich is co m p a t ib le w it h human s a f e t y . However t h e s e o b s e r va t io n s r e p r e s e n t a n o t h e r s t e p toward that goal. 13 1. Kehoe, R. A., Thamann, F, and Cholak, J. : On the normal absorption and excretion of lead, I. Lead absorption and excretion In primitive life, J. Indust. Hyg., 1^, 257, (19 33). 2. .......... On the normal absorption and excretion of lead, II. Lead absorption and lead excretion in modern American life, Ibid, 275, (1933). 3. .......... On the normal absorption and excretion of lead, IV. Lead absorption and excretion in infants and children, Ibid, 11, 301, (1933). 4. Kehoe, R. A.: Unpublished data. 5. Lynch, 0. Roche, Slater, R. H. and Osler, T. G. : Determination of traces of lead In biological materials, with special referen to bone, The Analyst, 59 78 7* (1934). 6. Maulbetsch, A. and Rutishauser, E.: La teneur des dents en plomb, Arch, internat, de phamacodyn, et de therap., 53, 55, ( 19 3 6 ) . 7. Pernice, H.s Die Leber bei Blei- und Kombinationsvergiftungen, Arch, f, Gewerbepath. u. Gewerbehyg., 538, (1936). 8 . Pfrieme, F.: Ueber den normalen und pathologischen Blelgehalt der Z&hne von Menschen und Tieren, Arch. f. Hyg., 111. 232, (19: 9* Tompsett, 13. L. and Anderson, A. B. The lead content of human " tissues and excreta, Blochern. J., 2^, I85I, (1935) 1/ ) 10. Tompsett, S.L.: The distribution of lead in human bones, Ibid, 30, 345/ ( 1936) . 11. Weyrauch, P. and Mller, H.: Das sogenannte normale Biel lm menschlichen KBrper, Ztschr. f. Hyg. u. Infektlonskr., 115. 216, (1933) 12. Boyd, T. C'. and De, N. K. : Some applications of the spectroscope In medical research, Indian J. Med. Research, 20. 78 9, (1933) 13* Esser, A.: Klinischanatomische und spektrographlsche Untersuch ungen ds Zentralnervensystems bei akuten MetallVergiftungen unter besonderer Bercksichtigung ihrer Bedeutung fur gerichtlic Medizin und Gewerbepathologie, II., Dtsch. Z. gerlchtl. Med., 26, 430, (1936) l4. Okajima, S. Spectral analysis of metals, especially heavy metals, in every part of the organs of the Japanese, Acta Schol. Med. Univ. Imp. Kioto, 15 4l7, (193D 15 . Sheldon, J.H. and Ramage, H . A spectrographic analysis of human tissues, Blochern. J., 2^, I0O8 , (1951) - 11+ - 16 . Rabinowitch, I . M . , Dingwall, A. and Lack ay, R.H.: Studies on cerebrospinal fluid, I I . The occurrence of lead in cerebrospinal fluid, J. Biol. Chem., 105, 725, (1933) 17. Schmitt, P. and Basse, : Bleiuntersuchungen im Liquor cerebrospinalis Normaler und Bleikranker, Klin. Ws ehr., l6 , 6 5, .(1937) 18 . Bass, E.: Die Beziehungen des klinischen Bildes der Bleivergiftungen zum Bleigehalt in Blut und Urin, Deutsche med. v7sehr., 59, 16 6 5 , (19 3 3 ) 19. .20 Dutoit, P. and Zbinden, C.: Analyse spectrographique des cendres de sang et d 'organes, Compt. rend. Acad. d. sc., 188 . 16 2 8 , (19 2 9 ) Kehoe, R . A . , 'Thamann, P. and Cholak, J . j Normal absorption and excretion of lead, Jr. Am. Med. Assoc., lOk, 90* (1935)* 2 1 . Te.isinger, J.j Eine rasche mikropolarographische Methode zur quantitativen Bestimmung des Bleies im Blut, Ztschr. f. d. ges, exper. Med., 8 * 520, (193^)^;", ./XcM f<^ji.awj w-****A , Vw.*&*** r**/ sdc* . T 24^ 6 * . . /?3 22 f ' Berg, R.: Das Vorkommen seltener Blemente in'den liahrungsmit te] und menschlichen Ausscheidungen, Biochem. Ztschr., 165, I4-6I, (1925) 23. Boyd, T.C.: Lead in the urine, Indian J, Med. Research, 20, 75j (1932) ^ k2 k . 2rd3 , I . : Lead poisoning and its determination fh?om chemica] point of view, Samm. v. V ergif tungsf., , 11, (1931+),/ 2 5 . Horton, B.T., Powelson, M.H. and Osterberg, a .E.: Incidence of lead in urine in patients with oeripheral vascular disease, Proc. Staff Meet,, Mayo Clin., Ij., 2 9 6 , (1929) jKehoe, R, A., Thamann, F. and Cholak, J.l) 2 6 . \....... /An appraisal of" the lead hazards associated with the distribution and. use of gasoline containing tetraethyl lead, II The occupational lead exposure of filling station attendants and garaJpechanics, J. Indust. Hyg. and Toxicol., l8 , 1+2, (193S) " 27. Ross, J . R . snd L u c a s , C.C.: A new method for the determination of minute amounts of lead in urine, J. Biol. Chem., Ill, 2 8 5, (1935) 2 8 . Eehrens, B. and Taeger, H . : Quantitative Bestimmung der BleiausScheidung im Harn Gesunder und Bleikranker mit Diphenylthiocarbazon, Ztschr. f. d. ges. exper. Med., 9 282, (1935) 29. Bloomfield, J . J . and Isbell, H.S.j'The presence of lead dust and fumes in the air of streets, automobile repair shops, and industrial establishments of large cities, J . Indust. H y g . , 11, (1933) 30. Dunn,J.T. and Bloxam, H.C.L.: The occurrence of lead, copper, zinc and arsenic compounds In atmospheric dusts, and the _ - 15 - 31. Pinal Report of Departmental Committee on Ethyl Petrol, Minis try of Health, London, 1930, 32. Fuchs, W.: Rare elements in German brown-coal ashes, Ind. Eng, Chem., 2J, 1099, (1935) 33. Goldschmidt, V. M.: Rare elements in coal ashe3, Ind. Eng. Chem., 22, 110 0 , (1935) 3I4.. Hartley, W. N. and Ramage, H.: The mineral constituents of dust and soot from various sources, Proc. Roy. Soc., London 68, 97, (19 0 1) 35. Public Health Bulletin No. 16 3s The use of tetraethyl lead gasoline in its relation to public health, Treasury Department, U. S. Public Health Service, Washington, D, C., 1926. 36. Barth, E.: Untersuchungen ber den Bleigehalt der menschlichen Knochen, Virchows Arch* f. path. Anat., 281, lij.6, (I93D 37 Kehoe, R.A., Thamann, P. and Cholak, J.: Lead absorption and excretion in relation to the diagnosis of lead poisoning, J. Indust. Hyg., 3, 320, (1933). 3 8 . Kehoe, R. A.r The diagnosis of lead poisoning in the li^it of recent infomation, J. Med. (Cincinnati), 16, 5^7* (1935) 39. Kehoe, R. A., Thamann^ P. ^and Cholak, J.: On the normal absorption and excretion of lead, III. The sources of normal lead absorption, J. Indust* Hyg., 15. 290, (1933). I4C. ....................... ............ Lead absorption and excretion in certain lead trades, Ibid, l^, 306, (1933). Ip.. Shiels, D. 0* s The concentration of lead-in the urine of workers at Mount Isa Mines Limited, Queensland, with special reference to its value in the diagnosis of lead poisoning, Med. J. Australia, 1, 559, (1936). i42. Kehoe, R. A., Thamann, P. and Cholak, J.: An appraisal of the lead haxarda associated with the distribution and use of gasoline containing tetraethyl lead, Part 1, J. Indust, Hyg., 16 , 10 0 , (133k)* Distribution of Persons Dmployed in Three Lead Industries Accord in,3 to Age ' Age In Ye a r s 20 - 2 Li . 25 ~ 29 10 - 3I4. 35 - 39 i+o - 1+64-5 - k 9 , ; o - 5h 35 - 59 60 o r more / Total T m Industry A 2 /'1 5 Jj. <L 2 3 27 _ P r eq u en cy m In d u stry B In In d u stry 0 3 ii2 3 63 8 10 k2 "T 3 7 36 22 Table 2 f c r i b u t i o n o f P e r s o n s Employed in Three Lead Indus tries Ac o r d i n g t o D u r a t i o n o f Continuous Exposure in 3a;xe Plant r e r icd of Exposure n ears U n d e r 1 .0 1.0 3.0 ;-.0 7*0 9*o - - 2.9 4.9 6 .9 3.9 nJ.Wr>. /*>) 12.9 -3 ' > -4 * y "! r Lr' r> v. o r e ' Total In indus t r y A frequ en cy In In du stry B "T^ i n d u s t r y C cn . 15 i+ 6 6 k k 7 5 O 5 9 3 5 1 )^ /3 i o r? ^i 3b 22 u ; p M strib u tion of Persone 1 i n Tv.'o Le a d I n i n s t r i e t o Lead in I n gle r e c a i E va cu a t io n ccorirn ;; Lead in Milligrams per Sample frequency _n industry B >*< -i.*2WUti`1'X v-< 0 - O.lIj-9 V* TfT - 0.099 0.3C - 0.8-;9 c.U5 - 0.599 u bO - o .Tl-9 *> ^cr - 0.899 0 .90 - 1.01,9 1.0 5 -4.4^ over Total 8- ( o 4* "T ?9 / >9 . / 93 - ( - 1+ 5 c; 5 1 4 of Cm k 35 , Mean Standard D evia tion 0 . 8-57 z, 0.037 + 0.304- 0 . i ' l e jr 0 # J (- J M 0. 8-55 t: n i distribution of Persons Employed In Two Lead Indus ie: ccording to Lead per Gran of Ash In Feces Lead in Milligrams per dram of Ash. 0 - O.Ol# 0 .0 5 - 0.099 o.io - c.ili9 0.15 - 0.199 ' J C- *" 0 *<- I4.9 0 .2 5 an- over In Industry L 3 lir r~> ( 2 4 3 Local " 33 Frequency In industry C 1 / b Q 7 7 Or 35 ' Lea n rfcndard Lev iatiO'- 0 .12 5 + 0 .0 10 O.OSp '. lbij. Ai D i s t r i b u t i o n o f P e r s o n s Zm p lo ve d i n :nr e c .ood xn Cu n t r i o s Ac c o r : in ~ t o C o n c e n t r a t i o n -2 g o 1 i_ead. i n H i l l i n r a m s pe r L it e r 0 ^^ ~r^ - - 0 .10 o 0 C. _ 0 . 01, 9 0. 099 0 -1 I4.9 "i no 0 . 2 0 - 0 .0 a 0 .25 - 0 .299 - 0. 529 0. 35 and ever - .- T- .r1..*u U Vb*viv*~ .11 17 s 0 frequ en cy I n I n d u s t r y B i n :n "*u-r>"r C 10 15 6 O Os 10 3 3 O '3 / Tou u l _______ 2 2 _______ u 1 a Mo an 31a n u a r a D e via t io n nv*vn J3 r|? ^ Va v *^*'-r 0 0 . 002 0 .0 50 --># --W T H o \ O