Document NGr0ZGNv27OObqGoJEEDDG31y

An A p p r a i s a l o f t h e L e a d h a z a r d s A s s o c i a t e d w i t h t h e D i s t r i b u t i o n ' and Use of Gasoline Containing T etraeth y l Lead. Parti By R o b e r t A. K ehoe, F r e d e r i c k Thamann an d J a c o b C h o la k From K e tte rin g L aborato ry of Applied Physiology, U n iv e rs ity of C incinnati, C incinnati, Ohio. ' In tro d u c tio n and Acknowledgments. The developm ent of a motor f u e l c o n t a i n i n g t e t r a e t h y l l e a d ra ise d c e r ta in q u estions in i n d u s tr ia l and p u b lic h e a lth which have claim ed an unusual amount o f a t t e n t i o n . S ince 1S24 members of the s t a f f of t h i s la b o r a to r y nave c a r r ie d on a s e r i e s of s tu d ie s of the hazards a s s o c ia te d with t i e manufacture, d i s t r i b u t i o n , and use of th is type of g a s o l i n e . From time to time (1925, 1327, and 1328) r e p o r t s of t h e s e s t u d i e s have been made to t a e E t h y l G a s o l i n e C o r p o r a t i o n and United States Public Health Service, but tae accumulated information aas not been p ublished p a r t l y because of tae unw ieldly volume of data, and p a r t l y because tae r e s u l t s of su cc e ssiv e i n v e s t i g a t i o n s were e s s e n t i a l l y s im ila r to those d e sc rib e d by o th e r 'workers/ Thus our conclusions have not d iffe re d m aterially from those reached through animal experim entation by Sayers and h is a s s o c ia te s ( l ) , o r from those a r r i v e d a t by Leake and o th e r workers of the U nited S t a t e s P u b lic H e a lth S e rv ic e (2) through the use of methods g e n e r a l l y s im ila r to o urs. Our data (to 1328) and those of Sayers and Leake were c r i t i c a l l y reviewed by the m in istry of H ealth of Great B r ita in a s i n d i c a t e d in th e F i n a l R e p o r t o f th e D e p a rtm e n ta l Committee on Etnyl Petrol (3), issued in 1530. R ecently, i t has become e v id e n t t h a t more d e f i n i t e con c lu sio n s are j u s t i f i e d with regard to the lead exposure derived from h i e u s e o f l e a d e d g a s o l i n e . A c c o r d i n g l y , i n t n e f o l l o w i n g p a g e s vve snail re state tne problems, and describe b rie fly the experimental N2279 2 o b s e r v a t i o n s , made i n 1929, which c o n t i n u e o u r e a r l i e r i n v e s t i g a t i o n s . I n a s e c o n d a r t i c l e we s n a i l p r e s e n t t h e r e s u l t s o f a l a t e r a n d mo r e p re c is e method of measuring the lead exposure s p e c i f i c a l l y due to le a d in g aso lin e in tne various occup||ations which are concerned. V.e w i s h h e r e t o a c k n o w l e d g e a n i n d e b t e d n e s s t o o u r a s s o c i a t e s f o r a s s i s t a n c e i n v a r i o u s i t e m s o f t h e w o r k ; t o V.'. F . M a c h l e , L . W. S a n d e r s , L . J . S c n r a d i n a n d VY. E. B r o w n f o r t h e i r h e l p i n m a k i n g t h e p h y s i c a l e x a m i n a t i o n s ; . , t o L . YV.. S a n d e r s f o r t h e s t u d y o f b l o o d f i l m s ; , and to I. J . L eElanc f o r the s t a t i s t i c a l a n a l y s i s of t h e d a t a . The e x p en se of t h i s work was borne by tn e E th y l G a s o lin e C o r p o r a t i o n in accordance with an agreement between the Board of D ire c to rs of the U niversity and o f f ic ia ls of the Ethyl Gasoline C orporation. The N a tu re of t h e Lead H a z a r d s . a t an early stage in the use of gasoline containing t e t r a - . ethyl le a d i t became ap p aren t th a t the m anufacture of t e t r a e t h y l le ad and th e b le n d in g of th e c o n c e n t r a t e d f l u i d f o r u s e in g a s o l i n e was a hazardous occupation with unique o p p ortunities fo r the rapid develop ment o f l e a d i n t o x i c a t i o n . The s e r i o u s d a n g ers of t h e s e m a n u f a c tu r in g p r o c e s s e s h a v e no r e l a t i o n t o t h e p r o b l e m w i t h w h i c h we a r e c o n c e r n e d in tne p r e s e n t d i s c u s s i o n . However,, th e i n i t i a l c o n fu s io n of the a c t u a l hazards of manufacture with the problem atical dangers a ris in g from the use of tne finished fuel, has persisted Therefore the d is tin c tio n b e t w e e n them must be made c l e a r . Hazards A ssociated with the manufacture of T e tra e th y l Lead and Leaded Gasoline. Pure t e t r a e t h y l le ad is a heavy, c o lo r le s s , o ily l i a u i d which is retained with d if f ic u lty within jo in te d receptables and pipe lin e s . I t is insoluble in hot or cold water, but readily soluble in alcohol a n d a c e t o n e a n a m i s c i b l e i n a l l p r o p o r t i o n s w i t h f a t s a n d o i l s . As 0021822 3 I n d e e d s k i n a b s o r p t i o n a l o n e may r e s u l t i n t h e r a p i d p r o d u c t i o n of a c u te i l l n e s s and d e a th in ex p erim en tal anim als (4,.5). From a p h y s ic a l p o in t of view, the v o l a t i l i t y of t e t r a e t h y l le a d is low, but in to x i cological terms i t is dangerously high, since a t ordinary temperatures a i r s a t u r a t e d w i t h i t s v a p o r c o n t a i n s a p p r o x i m a t e l y 5 mg. o f l e a d p e r l i t e r . This co n ce n tra tio n is l e t h a l fo r ra b b its in a few hours (4), a f a c t which dem onstrates the ease with which t e t r a e t h y l le a d p e n e tra te s the pulmonary epithelium . Under c e r ta in co n d itio n s, notably in the p r e s e n c e of s u n l i g h t , t e t r a e t h y l l e a d i s u n s t a b l e , b r e a k i n g down to y ie ld w ater-so lu b le, c r y s ta ll in e t r i e t h y l lead compounds. S lig h t a g i t a t i o n s e r v e s to suspend t h e s e f i n e c r y s t a l s i n th e a i r , when i n . a dry s ta te , thereby producing a dust hazard which has the q u a lity u n i q u e among l e a d h a z a r d s - of p r o v i d i n g w a r n i n g of i t s p r e s e n c e , i n th a t a very low c o n c e n tra tio n of these substances induces i r r i t a t i o n of tne nracuus membranes w ith weeping an d s n e e z in g . The dangers a s s o c i a t e d w ith the p r e p a r a t io n and h a n d lin g of te tr a e t h y x le a d are f a i r l y o b v io u s , when th e s e p r o p e r t i e s a r e re c o g n ize d . U n f o r t u n a t e l y , t h i s i n f o r m a t i o n was n o t a v a i l a b l e when th e m a n u fa c tu r e of tiie p r o d u c t was f i r s t c o n te m p la te d . I t i s n o t s t r a n g e , t h e r e f o r e , t h a t wnen th e p r o d u c t i o n of t e t a e t h y l l e a d emerged from a l a b o r a t o r y scale into an in c ip ie n t commercial stage, cases of lead poisioning odcurred, c h a r a c t e r i z e d by the sudden o n set of c e r e b r a l symptoms and a high m ortality. U ith o u t e n te r in g in to a d e s c r i p t i o n of the vairious s te p s by which leaded g asoline i s prepared fo r the market, s u ffic e i t to say . t h a t the h a z a rd s of m anufacture are due m ainly to t e t r a e t h y l le a d . Ui ^ The h y g ie n ic problem a t every p o in t c o n s i s t s in th e p r e v e n tio n of skin c o n ta c t viith t e t r a e t h y l lead, and in the maintenance of co n d itio n s under which i t s vapor is not inhaled. Because of the snarp lo c a iiz a - 0021823 4 o n l y by c o n t i n u a l v i g i l a n c e . The e x t e n t t o w hich l e a d a b s o r p t i o n h a s been c o n tr o lle d in the m anufacture of t e t r a e t h y l le a d th ro u g h the. .use of sp e c ia l equipment and through the in a u g u r a tio n and o p e ra tio n of. s u i t a b l e s a f e t y m e a s u r e s h a s b e e n s a own e l s e w h e r e ( 6 ) . . Hazards A ssociated with tae D is trib u tio n and Use of Gasoline Containing T etraethyl Lead. - The n a z a r d s a s s o c i a t e d w ith th e h a n d l i n g and u s e of th e . f in i sued gasoline d i f f e r both in q u a lity and q u an tity from those which occur in i t s p re p a ra tio n . Nothing could dem onstrate the d ifferen c e in the magnitude of the p o te n tia l lead exposure of the two s e t s o f c o n d i t i o n s in a more p r a g m a t i c manner t h a n th e f a i l u r e on tne p a rt of such gasoline to produce a su b sta n tia te d case of lead in to s - i c a t i o n up to tne p r e s e n t (November, 1933) a f t e r more than 10 y e a r s of continuous use in c ertain p a rts of the United S tates and almost 8 years . throughout the en tire United S ta te s. (This basis of d iff e r e n tia tio n is tn e more s i g n i f i c a n t when one c o n s i d e r s t h a t th e h y p o t h e t i c a l o p p o r t u n i t i e s fo r tne ab so rp tio n of lead, as a r e s u l t of the d i s t r i b u t i o n of leaded g a so lin e, are so v a rie d and so widespread as to defy re g u la tio n .) But ta e re are o th e r p o in ts of d iffe re n c e which did n o t re q u ire the t e s t of experience for th e ir recognition. T etraethyl lead is introduced in to g a so lin e in amounts so small th a t the so lu tio n la ck s the e s s e n tia l to x ic a lo g ica l p ro p e rtie s of te tra e th y l le a d . Thus, whereas te tra e th y l lead alone, or in high concentration in gasoline, is rapidly absorbed t h r o u g h txie s k i n , i t s a b s o r p t i o n i s r e t a r d e d g r j e a t l y by d i l u t i o n i n g a s o l i n e . I n d e e d we h a v e b e e n u n a b l e t o o b t a i n e v i d e n c e o f l e a d absorption through the skin of experimental animals a f te r th e ir , prolonged exposure to concentrations of 1 p a rt of te tra e th y l lead p e r 1GCG p a r t s o f g a s o l i n e b y v o l u m e ( 5 ) . T h e d i l u t i o n o f t e t r a e t h y l . 5 Ina d ifferen ce between the v o l a t i l i t y of te tra e th y l lead and the various g a s o lin e bases w ith which i t i s mixed, i s so g r e a t t h a t a p p ro x im a te ly h a l f t h e g a s o l i n e may b e e v a p o r a t e d b e f o r e l e a d c a n b e f o u n d i n t h e vapor I t follow s, from tn i s fa c t, th a t the vapors r is in g from tanks co n tain in g leaded gaso lin e do not co n tain a p p re cia b le amounts of lead. .;O'y?0V9r j biti.i s G.O0S no \j in3tin t n o t e t r a e t h y l l e a d may b e e v a p o r a t e d . u n d e r any of tne p r a c t i c a l c o n d itio n s of Handling and u se o s p i l l a g e ' of lead-containing gasoline. A lth o u g h y e a r s of e x p e r i e n c e have n o t shown th e e x i s t e n c e of danger to tne community in the use of g a so lin e c o n tain in g te tr a e t h y l lead, and although tae q u a litie s of the fu e l, as described above, ex p lain ta is re s u lt in a larg e measure the p o ssib le lead exposure asso c i a t e d w i t h t h e g e n e r a l d i s s e m i n a t i o n o f s u c h a p r o d u c t may n o t be dismissed i i ^ n t i y . A f u l l a p p re c ia tio n of the o p p o rtu n itie s f o r ex posure is req u ired fo r an u n d erstan d in g of the problem which they provide for investigation. Leaded gasoline is handled at re fin e rie s, bulk storage plan ts, s ta tio n s , and in public and p riv a te garages. I t is tra n sp o rte d from one to another of th ese s i t e s in tank -ships, tank c a rs , tank tru c k s , b a rre ls , and tin s . In the United S ta te s and in Canada an overwhelming 0021825 p r o p o r tio n of t h i s motor fu e l i s d isp e n se d tirrough f i l l i n g s t a t i o n purnps. In England a larg e amount of gasoline is d is tr ib u te d in tw o-gallon cans '-..e have found t h a t no a c c u m u la tio n o f l e a d o c c u r s in r a b b i t s a s tn e r e s u l t of iioiUas of exposure f o r s e v e ra l hours d a ily to such vapors, in experiments in which the gasoline vapors were s u f f ic ie n tly co n centrated to maintain the animals in a sta te of mild in to x icatio n . lu waicri a re f i l l e d by a u to m a tic equipment a t r e f i n e r i e s and a t s to r a g e p o i n t s , ~ a r g e numbers o f p e r s o n s come i n c o n t a c t w i t h tn e g a s o l i n e througn. sp illa g e , as an unavoidable r e s u lt of the various methods of o s u r f a c e s on wnich th e g a s o l i n e i s s p i l l e d . At r e f i n e r y l o a d i n g ra c k s, a t f i l l i n g s ta tio n s and a t o th e r p o in ts where g aso lin e is handled r e g u l a r l y , t h e r e p e a t e d s p i l l a g e o f g a s o l i n e c o n t a i n i n g l e a d may b r i n g about toe accumulation of higher b o ilin g petroleum fra c tio n s , and small amounts of t e t r a e t h y l le a d , by re a so n of t h e i r a b s o r p t i o n in to wooden platforms r o t.e r surface m aterials such as concrete,, asphalt, gravel, . c i n d e r s o r e a r t h . Under t h e s e c o n d i t i o n s some p o r t i o n of the t i t r a e . t h y l lead is evaporated slowly, and the remainder undergoes decomposition. In e i t h e r c a s e , o p p o r t u n i t y f o r i n n a l a t i o n of l e a d on th e p a r t of p e r s o n s i n t h e v i c i n i t y may be p r o v i d e d , t h o u g h , no d o u b t , m o s t o f t h e accum ulations a re d i s s i p a t e d by fre q u e n t ho sin g , o r by r a i n f a l l . Under p re v a ilin g marketing conditions, the decomposition of tne tetraethyl lead in gasoline is almost inappreciable, but over a p e r i o d o f y e a r s , v a r i a b l e a m o u n t s o f l e a d d e p o s i t s may b e f o u n d i n t h e s c a le on the s id e s and a t th e botiom of s t o r a g e t a n k s , . ta n k c a r s , and other containers. Attempts to clean these containers in a dry state may c a u s e t h e i n h a l a t i o n o f f i n e l y d i v i d e d d u s t c o n t a i n i n g t r i e t h y l ' lead s a lts . In general, the p fg cau tio n s which are required to prevent t n e i n h a l a t i o n ox d a n g e r o u s a m o u n t s o f g a s o l i n e a r e a d e q u a t e s a f e g u a r d s a g a i n s t t,ne a b s o r p t i o n o f t h e l e a d d e p o s i t s , b u t t h i s p o t e n t i a l s o u r c e ,i o f l e a d a b s o r p t i o n nay n o t be i g n o r e d . The s a l e of th e g a s o l i n e to the consumer ta k e s i t i n t o th e p r o v i n c e - of th e g e n e r a l p u b l i c where some d e g r e e of e x p o s u r e to s k i n c o n t a c t a n d t o v a p o r s may o c c u r . Of more i m p o r t a n c e , h o w e v e r , i s t h e a p p ea ra n ce of a new s e t of c o n d i t i o n s b a se d upon th e com bustion of the fuel. le tra etay i lead is converted, thereby, into finely divided in o rg a n ic le a d compounds ( c h i e f l y le a d brom ide), which a re d e p o site d , in p a rt, along the exhaust system, but which otherw ise, are discharged 7 i n t o one a t no s p i i e r e w i t h t i l s e x h a u s t g a s e s o f t n e m o t o r . T h e . e x t e n t o f t a e a c c u m u l a t i o n of e x h a u s t g a s e s from many a u t o m o b i l e s i n busy c i t y s t r e e t s , and e s p e c ia lly in poorly v e n tila te d a re a s where cars operate in considerable numbers, becomes a question of im portance. This aspect of the m atter concerns tne en tire urban population, but i t develops a sp ecial sig n ific a n ce in tne case of garage mechanics. Garages, in g e n e r a l , a re p o o r l y v e n t i l a t e d . Few of them, in d e e d , a r e e q u ip p ed to m a in ta in an adequate d i l u t i o n of e x h a u st g a se s u n d e r th e most f a v o r a b le c o n d itio n s , ana m e n doors and windows a re closed in cold weather, v e n tila tio n is often n eg lig ib le. For th is reason, througn the winter m o n t h s , many m e c h a n i c s d e v e l o p l a t e a f t e r n o o n n e a d a c n e s fro m t h e a b sorption of carbon monoxide. Their exposure to lead in tne exhaust gas of automobiles burning leaded gasoline is g reater, therefore, than th a t of any otner group of persons in the community. F u rth er, the hand l i n g and tn e s p i l l a g e of g a s o li n e , th e a d ju s tm e n t of c a r b u r e t o r s , and tne r e p a ir of o th e r p a rts of the c a r o fte n involve shin c o n ta c t with tae g a s o l i n e a n d w i t h l u b r i c a t i n g o i l w h i c h may c o n t a i n m i n u t e a m o u n t s of t e t r a e t h y l l e a d . Tne s p i l l a g e a n d e v a p o r a t i o n o f g a s o l i n e may l e a v e behind tae le ss v o la tile te tra e tn y i lead to be slowly v o la tiliz e d a t a l a t e r time, o r to decompose, and by so doing to add to tn e le a d d ust in tne garage. In tne dism antling- of motors -the combustion p ro d u cts of t e t r a e t h y l l e a d may b e e n c o u n t e r e d b y t h e m e c h a n i c , a n d a l t h o u g h t h e s e c a n n o t b e a b s o r b e d t h r o u g h t h e s k i n , t h e y may be a me ans o f c o n t a m i n a t i n g n i s h a n d s , h i s c l o t h i n g , a n d h i s s u r r o u n d i n g s . \7e m u s t r e g a r d t h e s e fa c to rs , as well as tne deposited lead of the exnaust gases, as c o n tr i b u to rs to the accum ulations of iead dust w ith in tne garage although tne amounts of i e a d in v o lv e d are p ro b a b ly n o t so g r e a t as th o s e which o r ig in a te from tne r e p a i r of e l e c t r i c a l sto ra g e b a t t e r i e s and tne use of p ain ts and solder in the re p a ir of autom obiles. - One f u r t h e r p o i n t must be c o n s i d e r e d i n a c o m p le te a n a l y s i s - 8- o f t n e p o s s i b i l i t i e s f o r g e n e r a l l e a d e x p o s u r e i n t.xe u s e o f g a s o l i n e c o n t a i n i n g l e a d . The d e p o s i t i o n of l e a d compounds upon th e Highways, c i t y s t r e e t s , - i n s n o r t , upo n t h e s u r f a c e o f t h e e a r t h - may c o n c e i v a b l y i n f l u e n c e trie amount of l e a d b r e a t a e d by a n i m a l s a n d men, a s w e ll as tne q u a n tity in co rp o rated in and dep o sited upon v e g e ta tio n employed as food. Tn e D i s t r i b u t i o n a n d S a l e o f `L e a d e d G a s o l i n e i n t h e U n i t e d S t a t e s . Tne c h a r a c t e r of ta e le a d h a z a rd s developed through the use of lead ed g a s o lin e i s b ts e d upon tne methods of i t s d i s t r i b u t i o n and use. Tneir general magnitude is dependent upon the extent of 'f.,e d i s t r i b u t i o n of suca g a s o li n e , tne volume of consum ption in a given area, and the period of time over which d i s t r i b u t i o n and use have ex t e n d e d , t i . e ; e f a c t o r s b e i n g m o d i f i e d t o some e x t e n t by t n e v a r i a t i o n s in t..e lead c o n c e n tra tio n in g a s o lin e , which nave occurred in various sections of tne country. G a s o l i n e c o n t a i n i n g t e t r a e t h y l l e a d was d i s t r i b u t e d f i r s t i n t n e e a r l y months of 1923 in D ayton, O h io . A few months l a t e r i t was on s a l e in C i n c i n n a t i and in th e d i s t r i c t ab o u t t h e s e two c i t i e s . Thence i t s u s e was e x te n d e d to m iddle w e s t e r n and s o u t h e r n U n i t e d S t a t e s , i n t o areas represented most s a t i s f a c t o r i l y by tne c i t i e s of Chicago, D e tro it, 3 t. L ouis, J a c k s o n v ille , A tla n ta , and Savannah. The q u a n tity of t n i s g a s o l i n e s o l d up t o 192o c a n n o t be e s t i m a t e d a c c u r a t e l y , b u t i t was l i m i t e d to t h i s g e n e r a l a r e a , and t h e r e was a s t e a d y i n c r e a s e in th e volume of d i s t r i b u t i o n during th i s time except f o r a p e rio d of almost a y e a r b e g i n n i n g i n Lay, 19 2 5 . (At t h a t tim e l e a d e d g a s o l i n e ?/as w i t h ' Kk 0021828 drawn from tne market pending an i n v e s t ig a ti o n of the U nited S ta te s P u b lic H e a lth S e rv ic e , though f o r v a r io u s re a so n s i t s use was not i n t e r r u p t ui in c e r t a i n a r e a s . ) The ex p an sio n c o n tin u e d u n t i l t h i s autom obile fu e l had become a v a i l a b l e in a l l p a r t s of the U nited S ta te s , - a b l e x. s n o w s t h e d a t e s a t w h i c h s a l e b e g a n i n v a r i o u s c i t i e s o f t h e _Q_ is a lso recorded up to tae time of ta e o b serv atio n s wnich are to be . d e s c r i b e d . Tiie a p p r o x i m a t e q u a n t i t i e s s o l d d u r i n g t h e y e a r s f o r w h i c h f i g u r e s a r e a v a i l a b l e a r e snown i n T a b le 2. I t sh o u ld be n o t e d t n a t t a e g e n e r a l a r e a s i n t o which th e g a s o l i n e was f i r s t i n t r o d u c e d m ain ta in e d the la r g e s t p ro p o rtio n a l and gross consumption. In.. Ohio, where the g r e a t e r p a r t of ta e e a r l y i n v e s t i g a t i o n s were c a r rie d out, the c o n c e n tra tio n of t e tr a e t h y l le a d in g aso lin e up to 1S2S was m a i n t a i n e d a t See. p e r g a l l o n - a p p r o x i m a t e l y 1 p a r t of t e t r a e t h y l l e a d in 2bO pa r t s of g a s o l i n e , by volume. In c e r t a i n o t h e r a r e a s , d u r i n g t h i s p e r i o d , a s l i t t l e as 2 c c , was u s e d . S i n c e t h a t time, the lead concentration has varied in accordance with the quantity required to b rin g the a v a ila b le g a so lin e base up to a d e f in ite stan d ard of performance in a t e s t engine, exeept th a t th e amount in troduced has ' n o t exceeded 3 cc. of t e t r a e t h y l l e a d p e r g a l l o n of g a s o l i n e . The average lead c o n ce n tra tio n by y ears f o r d i f f e r e n t regions of tne country may b e s e e n i n T a b l e 3 . a b rie f study of the contents of these tables is s u ffic ie n t to give a c l e a r in d ic a tio n of the a re a s in which the g r e a t e s t o p p o rtu n i t i e s fo r lead exposure have been provided. They also y ie ld a graphic c o n c e p t o f t h e p r o p o r t i o n s o f t h e p r o b l e m w i t h w n i c h we a r e d e a l i n g . In the l i g h t of the in fo rm a tio n f u r n is h e d by p re v io u s in v e s tig a tio n , th e re can be l i t t l e doubt th a t c e r ta in of the h y p o th e tic a l h a z a r d s d e s c r i b e d a b o v e , do n o t e x i s t . h o w e v e r , we s n a i l d i s r e g a r d t h e s e d e t a i l s and d eal, p rim a rily , with one q u e stio n , namely, - is the magnitude of lead exposure a r is in g from the combined hazards of tne use of leaded gasoline such as to bring about appreciable lead a b s o r p tio n on the . a r t of any group of in d i v i d u a l s in the community? Kf 0021829 10 3. Experimental In v e stig atio n . Tiie S e l e c t i o n of E x p e r i m e n t a l S u b j e c t s . Groups of s u b je c ts were s e le c te d fo r d e ta ile d study of tne e ffe c ts of tiieir occupation upon th e ir Heal t h , and upon such physiolo g ic a l p ro cesses as are s p e c i f i c a l l y in flu en c ed by an in c re a se in le ad absorption. Table 4 shows tne numbers and types of s u b je c ts , to g e th e r w ith tne l o c a l i t y in which they were employed. The three groups of w o r k ma n who h a d e x p e r i e n c e d a l l t n e t y p e s o f l e a d e x p o s u r e a s s o c i a t e d w i t h t h e u s e o f l e a d e d g a s o l i n e a r e r e p r e s e n t e d by 56 f i l l i n g s t a t i o n a t t e n d a n t s , 5C t a n k - t r u c k h a n d l e r s o f s u c h g a s o l i n e , a n d 201 g a r a g e mechanics. The f i l l i n g s t a t i o n a t t e n d a n t s were chosen w ith a t t e n t i o n to s e v e r a l m a t t e r s : men who h a d b e e n e m p l o y e d a s s u b j e c t s p r e v i o u s l y , who h a d b e e n h a n d l i n g l e a d e d g a s o l i n e f o r t n e l o n g e s t p e r i o d o f t i m e , who nad handled gasoline containing the h ig h est concentrations of t e t r a e t h y l l e a d , a n d wno h a d h a n d l e d t h e l a r g e s t a m o u n t s o f l e a d e d g a s o l i n e d a i l y , -were e s p e c i a l l y d e s i r a b l e . U n t i l h a y I S 25 a s m a l l m e t e r i n g d e v ice c o n ta in in g a l i t e r can of E thyl F l u i d was u s e d on f i l l i n g s t a t i o n hose lin e s to tr e a t gasoline with the lead mixture as required. This method of d i s t r i b u t i o n b r o u g h t a b o u t some d e g re e of e x p o s u r e t o con c e n t r a t e d t e t r a e t h y l l e a d on the p a r t of f i l l i n g s t a t i o n employees. T h e r e f o r e , t h o s e s u b j e c t s whos.e e m p l o y m e n t d a t e s b a c k t o t h i s p e r i o d have had o p p o rtu n itie s fo r the ab so rp tio n of leLd from th i s source. They were p a r t i c u l a r l y fa v o ra b le s u b je c ts f o r the d e te rm in a tio n of the maximal lead exposure a s s o c ia te d with t h e i r occupation. I t has been pointed out p rev io u sly th a t in the c i t i e s of Dayton, C in cin n ati, Savannah, J a c k s o n v i l l e and A t l a n t a t h e r e had been no i n t e r r u p t i o n i n K g' 0021830 11 tils employment turnover of f i l l i n g s ta t io n a tte n d a n ts had been such t h a t i t v;&s n o t d i f f i c u l t t o f i n d a s a t i s f a c t o r y g r o u p o f men who h a d d is p e n s e d le a d e d g a s o l i n e s in c e i t was f i r s t m a rk e ted from t h e i r s t a t i o n s , due consumption of le a d e d g a s o li n e has been g r e a t e s t i n c e r t a i n c e n t r a l s ta t e s re p re se n te d by tne c i t i e s o f ' Dayton, C in c in n a ti, D e tro it, Chicago and St. Louis. In these c i t i e s individual a tte n d an ts a t c e r ta in well l o c a t e d f i l l i n g s t a t i o n s h a d h a n d l e d m o r e l e a d e d g a s o l i n e t h a n h a d men s i m i l a r l y employed in any o th e r p a r t of tne c o untry. Tne tank wagon h a n d l e r s were s e l e c t e d on tn e b a s i s o f the s e v e r ity and le n g th of t h e i r exposure to leaded g a so lin e . Twenty-four o f them h a d s e r v e d a s s u b j e c t s f o r s t u d y i n 1987* Thus a d i r e c t com p a r i s o n of t n e r e s u l t s o b t a i n e d on t h e two o c c a s i o n s was made p o s s i b l e . Tae g a r a g e m e c h a n i c g r o u p was made u p o f 1C9 p e r s o n s wao h a d been worhing on c a r s which used only le a d e d g a s o l i n e , and an a d d i t i o n a l 9 3 who h a d b e e n r e p a i r i n g c a r s o f w h i c h a h i g h p e r c e n t a g e u s e d s u c h ' g a s o l i n e . 3 f f o r t was made t o f i n d a i l t h e m e c h a n ic s i n t h e U n i t e d S t a t e s who h a d e x p e r i e n c e d p r o l o n g e d e x p o s u r e i n g a r a g e s i n w h i c h a l l the cars had used le ad e d g a so lin e e x c lu s iv e ly over a p e rio d of se v e ra l . y e a r s . Ten members of the group had been employed in a p u b lic s e r v ic e garage in Dayton, Ohio, in which only leaded gasoline, had been used from 1983 to the time of the p r e s e n t i n v e s t i g a t i o n . T h ir ty - n in e s u b je c ts had had from 3 to 6 y e a rs of d a ily r e p a i r work on c a r s in which lead ed g a s o l i n e was th e e x c l u s i v e f u e l . The e n t i r e group was composed of s u b j e c t s who h a d b e e n e m p l o y e d i n - c o n t i n u a l r e p a i r w o r k o n f l e e t s o f cars. From every p o i n t of view the s u b j e c t s s e l e c t e d f o r e x am in atio n had the maximal o p p o rtu n ity fo r exposure to lead a r is in g from t a e i r r e s p e c t i v e o c c u p a tio n a l r e l a t i o n s h i p s to le a d e d g a s o l i n e . The garage Kh 0021831 p o s e d o f men whose o c c u p a t i o n c o m b i n e s a l l t i i e p o t e n t i a l l e a d e x p o s u r e d eriv ed front tne g a s o lin e in an i n t e n s i f i e d form, to g e th e r with c e r t a i n o t h e r l e a d e x p o s u r e s '.vnich a r e n o t r e l a t e d t o g a s o l i n e . F o r t h i s r e a s o n i t was e x p a n d e d t o a l a r g e number a t t h e e x p e n s e o f l e s s e x p o s e d g r o u p s . Tiie b a r r e l - f i l l e r s r e f e r r e d t o i n T a b l e 4 a r e i n c l u d e d among th e s u b j e c t s f o r a s p e c i f i c re a so n which w i l l a p p e a r l a t e r . The d ata are av ailab le t..rough a fortunate combination of circum stances. Several y e n s of o b serv atio n of persons noose occupation involved c o n sid e ra b le exposure to gasoline had aroused our in te r e s t in the influence of pro ion.; ed g a s o l i n e a b s o r p t i o n . A c c o r d i n g l y , a s e a r c h . w a s made f o r a g ro u p Ox 3<XOj cC v3 hiOSc 3Xp 0 S'. V3 tsQ g a s o l i n e was s e v e r e a n d u n c o m p l i c a t e d b y 0 L i l 8 V O G G-. `J . t i o n a i f a c t o r s . I n t n e s u mme r Gi- I S 28 s u c h a g r o u p w a s f o u n d i n a r e f i n e r y i n wh i c h l a r g e q u a n t i t i e s o f g u s c i i n e w e r e p u t i n t o f i f t y g a l l o n b a r r e l s f o r t r a n s p o r t a t i o n . Tne b a r r e l s were f i l l e d in a sp ed a i l y c o n s t r u c t e d room p ro v id e d w ith f o r c e d v e n t i l a t i o n . D e s p ite t n e ma g n i t u d e o f v e n t i l a t i o n t h e c o n c e n t r a t i o n o f g a s o l i n e v a p o r was i i X e n o u g h t o b e i .media t e l y d i s t u r b i n g t o o n e who was n o t a c c u s t o m e d to sucn vapor. In au dition, the skin, clothing' and shoes of tne workmen were f r e q u e n t l y and a lm o st c o n t i n u o u s l y wet w ith g a s o l i n e . Tne b a r r e l s were l i n e d up in a double row along c o rre sp o n d in g rows of p ip e l i n e s each of which was p r o v i d e d w ith an elbow, a f l e x i b l e h o se and a f l o a t v a l v e . Each hose l i n e w ith i t s v a lv e was i n s e r t e d i n t o a d r u m, .-.nd t n e v a l v e was o p e n e d . G a s o l i n e f l o w e d i n a t c o n s i d e r a b l e p r e s s u r e u n t i l tne l e v e l of l i q u i d in the drum r e l e a s e d tne v a lv e, thus c lo s in g i t , O c c a s io n a lly the v a lv e re fu s e d to work p r o p e r ly , a t which time a stre a m of g a s o l i n e ro se from th e Arum and th o ro u g h ly Irene..ed any workmen in i t s immediate v i c i n i t y . 13 n e n u i b e r o f men e n g a g e d i n f i l l i n g a n d h a n d l i n g t h e d r u m s of g a s o l i n e was small b u t trie s e v e r i t y of e xposure was such a s to g ive e x c e l l e n t o p g o rtu n i ty f o r trie d e t e c t i o n of any e f f e c t s which might r e s u l t f r o m g a s o l i n e a b s o r p t i o n . T h e s e men w e r e c a r e f u l l y e x a m i n e d i n a m a n n e r will oil w i l l be d e s c r i b e d l a t e r , a n d s e v e r a l t y p e s , o f l a b o r a to ry d ata were o b ta in e d , in c lu d in g the le a d consent of the u r in e and f e c e s . (The l a t t e r d a t a 'were o b t a i n e d b e c a u s e of o u r i n t e r e s t i n t h e l e a d e x c r e t i o n of g ro u p s of workmen w ith no o c c u p a t i o n a l e x p o s u r e to lead compounds.) Shortly a f t e r these examinations had been completed the re fin e ry in q u estion undertook the d i s t r i b u t i o n of leaded g a so lin e . Ine l a t t e r was h a n d l e d i n t h e manner d e s c r i b e d above f o r o r d i n a r y g a so lin e. Inasmuch as experim ental evidence in d ic a te d th a t the hazards of ead a b s o r p tio n from skin c o n ta c t and i n h a l a t i o n of vapor from g a s o li n e c o n ta in in g t e t r a e t h y l le a d were p r a c t i c a l l y n e g l i g i b l e , no f e a r s were en t e r t a i n e d as to the consequences of the a d d itio n a l f a c t o r of a low con centration of te tra eth y l lead. nevertheless, tn is co n stitu ted a unique s e v e r i t y of e x p o s u r e . T h e r e f o r e i t was c o n s i d e r e d a d v i s a b l e to o b t a i n ' i n f o r m a t i o n w h ic h would show w h e t h e r o r n o t t h e men 'were a b s o r b i n g lead. accordingly, a t the end of a p e rio d of 5 months, during which leaded gasoline had been handled d aily in the p reviously described manner, the workmen so employed were examined, and samples o f t h e i r e x c r e t a w e r e o b t a i n e d f o r a n a l y s i s . I n t h i s s e c o n d g r o u p , made u p o.f 22 men, t i e r e w e r e t e n who h a d b e e n i n c l u d e d i n t h e f i r s t s e t o f e x aminations. Except in the case of the b a r r e l - f i l l e r s , comparable groups of s u b je c ts unexposed to t..e p o t e n t i a l dangers of le a d e d g a s o lin e , were k Jr 0021833 of tue U n ite d S t a t e s in which the s e l e c t i o n of e n t i r e l y unexposed s u b j e c t s could be made, sin c e the use of le a d e d g a s o li n e had in c r e a s e d so as to in v o lv e a i l p a r t s of th e c o u n tr y . T h e re fo re i t was n e c e s s a ry to r e l y on in fo r m a tio n o b ta in e d p r i o r to the g e n e ra l d i s t r i b u t i o n o f l e a d e d g a s o l i n e , f o r c o m p a r a tiv e d a t a on s i m i l a r groups o f s u b j e c t s i n d e p e n d e n t o f t h i s f a c t o r . On t h e o t h e r n a n d , s i n c e r e p e a t e d o b s e r v a t i o n s h a d b e e n made on th e same i n d i v i d u a l s u n d e r c o n d i tions of continuous exposure, tne successive findings furnished a means f o r tne discover;,' of p r o g r e s s i v e e f f e c t s of any ty p e. Experimental Methods. E x p e r i m e n t a l s t u d i e s on a n i m a l s a n d men h a v e e s t a b l i s h e d t n e existence of a relatio n sh ip between the magnitude of the lead exposure and absorption: and the r a t e of l e a d e x c r e t i o n , in t h a t f e c a l e x c r e t i o n i s a measure of in g e s t i o n on the day p re c e d in g the c o l l e c t i o n of the s a capa e , . v a l e t n e u r i n a r y e x c r e t i o n i n d i c a t e s t h e m a g n i t u d e o f l e a d a b s o r p t i o n ( q , 7, G ) . N e v e r t h e l e s s , we w i s h e d t o l e a v e n o s t o n e u n t u r n e d w h i c h m i g h t y i e l d a d d i t i o n a l i n f o r m a t i o n . A c c o r d i n g l y , we s e a r c h e d f o r c l i n i c a l 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 w i t h t n e s amd c a r s t h a t we a p p lie d to tne c o l l e c t i o n of a c c u r a t e a n a l y t i c a l d a ta . Care was ta k e n to o b t a i n a l l the in f o r m a t i o n p o s s i b l e from a ac n s u b j e c t , and to r e c o r d such i n f o r m a t i o n in an u n i f o r m manner. F or t-iis reason cards f o r recording data were provided as reproduced in F i g u r e s 1 to 5 i n c l u s i v e , and th e work was d i v i d e d among f o u r p h y s i c i a n s e a c h o f whoM* c a r r i e d o u t t i i e s ame t y p e o f o b s e r v a t i o n s o n e a c h s u b j e c t . ^ do f a r as p o s s i b l e q u a n t i t a t i v e i n f o r m a t i o n vas o b ta in e d in the p h y s ic a l exam ination, but w ita o u t th e s u b o rd in a tio n of c l i n i c a l judgm ent. Thus w h ile i t was r e c o g n iz e d t h a t a s t a t i s t i c a l s tu d y of a l l t h e d a t a was 0021834 were regarded as of g re a te r importance in determ ining whether or not ). any e v i d e n c e o f l e a d i n t o x i c a t i o n h a d a p p e a r e d among t n e s u b j e c t s . a s an example o f Uii s o o i n t of view, e acn s u b j e c t was t e s t e d f o r e v i d e n c e s o f a .j r o o n y o r m u s c u l a r w e a k n e s s b y p a l p a t i o n a n d oy o p p o s i n g vie exc; mi n e r ' s strength, to tu a t of one c o rre sp o n d in g muscle group of tne s u b j e c t , o u t f o r t.. p u r p o s e s o f s t a t i s t i c a l c o m p a r is o n of a s i n g l e n e u r o r m u s c u l a r f a c t o r , one g r i p was t e s t e d by a h a n d d y n a m o m e te r . (The same i n s t r u m e n t was employed tu ro u g k o u t th e t e s t s . } m easu re m e n ts of the b l o o d p r e s s u r e o f e a c . i s u b j e c t ( s e a t e d ) 'were nade w i t h a s t a n d a r d imanme t r i e a p p a r a t u s . A f r e s a s p e d men o f u r i n e was o b t a i n e d f r o m e a c n s u b j e c t a n d e x a m i n e d , a t o n c e f o r i t s r e a c t i o n , te p r e s e n c e o f a l b u m i n , a nd s u g a r . M i c r o scopic examination of the u rin e and a t e s t fo r acetone were c a r r ie d wu t* Oj' j i l \ - j i C i c '5 uj/ bhur mi Cal >TlOr'UlfclX1 1/1 S V by Sd S S Xi1V0 c lin ic a l fin d in g s. T rythrocyte, leucocyte and d if f e r e n tia l leucocyte c o u n o s were .ladeas, r o u t i n e p r o c e d u r e o n l y o n t h e b a r r e l - f i l l e r g ro u p of s u b je c ts . O therw ise, such p ro c e d u res were fo llo w e d only \cen i n d i c a t e d f o r d i a g n o s t i c p u r p o s e s . H e m o g lo b in d e t e r m i n a t i o n s were made on eacn s u b j e c t by means of trie Dare hemogiobinorneter. A s in g le i n s t r u m e n t was employed f o r a i l o b s e r v a t i o n s , a n d a l l r e a d i n g s were made by tn e same o b s e r v e r . Blood sm ears were made on a l l s u b j e c t s , and were examined f o r s t i p p l i n g of trie e r y t h r o c y t e s by a s ta n d a r d iz e d me t r i a d w h i c h w i x i b e d e s c r i b e d e l s e w h e r e b y L . W. S a n d e r s . Samles of u rin e and fe c es were o b tain ed from the sub- j e c t s f o r ?,he d e t e r m i n a t i o n o f t h e i r . - l e a d c o n t e n t . Tne c o l l e c t i o n o f tiiese and t..e a n a ly s e s were c a r r i e d o u t according to methods waicii we . l a v e d e s c r i b e d p r e v i o u s l y ( 9 ) . I n a f e w i n s t a n c e s n o s a m p l e s w e r e o o t o i n a O x e . ... f u r t a e r s m a x l n u m b e r o f s a m p l e s w e r e l o s t i n t r a n s i t and in p ro c e ss of a n a ly s is . D'ith these few ex ce p tio n s, the a n a ly t ic a l 15 4. Experimental Findings. F o C..SS o f l e a d i n t o x i c a t i o n wa s f o u n d a mo n g t h e s u b j e c t s , n f a c t , no c o m b in a tio n of symptoms and p h y s i c a l f i n d i n g s was s u g g e s t i v e o f l e a d i n t o x i c a t i o n . Sue a 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 a s a r e common among l e a d w a r d e r s were c c n s p i c o u s l y a b s e n t . Of s p e c i a l n e g a t i v e c l i n i - ' cal im portance were tne complete absence of le a d l i n e , the la c k of s i g n i f i c a n t microscopic- blood changes \ s t i p p l i n g ) , and the in freq u en cy of v j 0ue symptoms of i l l h e a l t h . Under t h e s e c i r c u m s t a n c e s any e v id e n c e s of s ig n ific a n t lead absorption as a consequence of exposure to leaded gasoj-ii;;- ,m s t be so u g h t in th e d a ta on the e x c r e t i o n of l e a d . P e rta in of the c l i n i c a l fin d in g s and a ll of the a n a ly tic a l data fo r the groups are p re se n te d in a s e r ie s of ta b le s which re p re se n t t..e exact manner of tne s t a t i s t i c a l study except as otherw i se n o te d , onerous o th e r c l i n i c a l items which were su b jec te d to s t a t i s t i c a l a n a ly s is , nave been o m itted because of t h e i r n e g a tiv e s ig n if ic a n c e , and f o r the sake of brevi tv. fa b le 5 shows tne c l a s s i f i c a t i o n of the s u b je c ts acco rd in g to the duration of ta e i r exposure to leaded g aso lin e. One-half of tne f i l l i n g s ta tio n a tte n d an ts and a l i t t l e le s s than h a lf of the t a n k wagon h a n d l e r s ha d b e e n e x p o s e d f o r 5 y e a r s o r more, w h i l e 69 p er cent of the garage mechanics had re p a ire d c .rs which Used leaded gasoline over a p eriod of 3 years or more. V/netrier o r n o t i t has any b e a r in g on jthe problem a t is s u e , t n e o c c u r r e n c e of p r e v i o u s i n d u s t r i a l l e a d e x p o s u r e among tne s u b j e c t s may .n o t b e i g n o r e d . I n f o r m a t i o n on t h i s p o i n t . o b t a i n e d f r o m t h e o c c u p a t i o n a l H i s t o r i e s i s shown i n T a b l e 6 . H e r e i t may be s e e n t h a t a la rg e p ro p o rtio n of the su b je c ts had been employed in tra d e s which in v o lv e d some o p p o r t u n i t y f o r le a d a b s o r p t i o n , p r i o r to t h e i r e x p o su re 0021836 i r o ui uJi 6 f a c t o r o f l e a d e d ga s o l i n e . H o w e v e r X5'.* -3&Tetri e mechu. n i e s h a v e mo r e t h a n a s l i g h t of t h e i r normal d a v ' s work, s i n c e s .all j o b s and -as occasional repair of a storage b a tte ry have not produced a n o t i c e a b l e o c c u rre n c e of i e a " i n t o x i c a t i o n among g arag e m echanics . Gne t a n k wagon d r i v e r a n d 8 g a r a g e m e c h a n i c s h a d b e e n em ploye d a t some p r e v i o u s ti>..e i n h a z a r d o u s l e a d t r a d e d i n w n i c h t h e i r e x p o s u r e h a d n o t been aevere either in quality or duration. The d i s t r i b u t i o n of th e s u b j e c t s a c c o rd in g to age, seen in 7. g n u l e a n t o m y m t h a t i t d e m o n s t r a t e s t h e i n c l u s i o n o f wide*y v a r y i n g age gro u p s among th e s u b j e c t s u n d e r i n v e s t i g a t i o n . .aDj.es o and 9, the fin d in g s as resaro s aaemoclobin of t u e c l o o c , a n d s t i p p l i n g o f t h e e r y t h r o c y t e s a r e r e c o r d e d . Mo me a n v a lu e s were computed f o r tne o c cu rren c e of s t i p p l i n g by re a so n of the n i g . i p r o p o r t i o n of n e g a t i v e r e s u l t s . I t may b e s e e n f r o m t h e t a b l e s tn~ t no s i g n i f i c a n c e may b e a t t a c h e d t o v a r i a t i o n i n t h e s e m u t t e r s i n r e l a t i o n to le a d e d g a s o lin e exposure, s in c e p r a c t i c a l l y a l l -the fin d in g s a r t w ituin normal l i m i t s . However th e re is a high frequency of low h e m o g l o b i n r e a d i n g s and o f a b n o r m a l num bers .of s t i p p l e d e r y t h r o c y t e s among th e b a r r e l - f i l l e r s e xposed to o r d i n a r y g a s o l i n e . These men w e r e e x a m i n e d i n t h e summer wnen i n h a l a t i o n o f g a s o l i n e v a p o r was a t i t s l . e i g h t . A p p a r e n t l y , e x p o s u r e t o g a s o l i n e v a p o r s may p r o d u c e blood changes, in c lu d in g the appearance of s tip p lin g . Tne f a c t s o b ta in e d from th e a n a l y s i s o f the e x c r e t a of tne s u b je c ts arc p re s e n te d in Tables 18, 11, and 12. A survey of the tab u l a t e d r e s u l t s shows t h a t a few high r e s u l t s are s c a t t e r e d i r r e g u l a r l y t h r o u g h t h e d a t a . Wher e t h e s e o c c u r i n f e c a l s m a p l e s i t may b e a s s u m e d K 0021837 t..e in g a s tio n of unusual amounts of lead with food m a te ria l, and tn a t cnay nave no n e c e s s a r y or p r o b a b le r e l a t i o n s h i p to o c c u p a t i o n a l l e a d e x p o s u r e . The i n c l u s i o n of s u ch f i n d i n g s in t h e 'c o m p u t a t i o n o f mean v a lu e s i n c r e a s e s a p p r e c i a b l y one p ro b a b le e r r o r of the mean, and m i l i ta te s a g ain st s a tis fa c to ry com parison.of the groups of su b jec ts, n ever t h e l e s s , sucn r e s u l t s nave been recorded, and have been in c lu d e d in the calcu latio n s unless otherwise sp e c ific a lly noted in the ta b le s. M ere a r e s u l t has been excluded i t has been f o r the purpose of e lim in a tin g a f i n d i n g v/aicn h a s no p r o b a b l e -r e l a t i o n t o t h e p r o b l em a t i s s u e . I n tae esse of tne u rin e samples, a b e rra n t r e s u lts are of rare occurrence, a s w o u l d be e x p e c t e d . On t n e o t h e r n a n d , c o n t a m i n a t i o n o f a n o c c a s i o n a l sampie luring tne process of c o lle c tio n is ap p aren tly unavoidable, des p ite tne .lost carefu l in s tr u c tio n of the su b je c ts. This is not remarkable ..nil t u e u b i q u i t y o f l e a d c o m p o u n d s i s a p p r e c i a t e d , a n d when t n e l a c k o f understanding of caemical c le a n lin e ss on the p a rt of the su b jects is tj.xen in to account. Tixe a n a l y t i c a l r e s u l t s s e r v e t o c l a s s i f y t n e v a r i o u s groups of subjects as d is tin c tly outside the hazardous lead trades. XC o m p a r e wi t i l d a t a f r o m c e r t a i n l e a d t r a d e s ( 6 ) ) * A t f i r s t g l a n c e , t.;e mean v a l u e s f o r t n e l e a d c o n t e n t o f t h e f e c e s o f f i l l i n g s t a t i o n employees, tank wagon h a n d le r s and garage mechanics seem n ig h , as compared to t h o s e f o r normal p e r s o n s w ith no o c c u p a t i o n a l l e a d ex p o s u r e . On t h e o t h e r n a n d , t h e s m a l l g r o u p o f b a r r e l f i l l e r s who w e r e n o t e x p o s e d t o l e a d e d g a s o l i n e , a n d who h a d no o t h e r o c c u p a t i o n a l le a d ex p osure a t th e time of th e e x a m in a tio n , show s i m i l a r l y h ig h f i n d i n g s . F u r t h e r m o r e , when Che f e c a l l e a d i s e x p r e s s e d i n q u a n t i t a t i v e l y comparable term s, (in m illigram s per gram of ash), the a p p aren tly high KE" 0021838 -19r e s u l t s l o s e t h e i r s i g n i f i c a n c e . F i n a l l y , f o r r e a s o n s w h i c n we n a v e p o in te d out elsewhere (6) i t is im possible to draw exact conclusions as to t-e magnitude of lead a b s o r p tio n , from tiie r e s u l t s o b tain ed on samples of feces, and i t i s n ecessary to r e s o r t to tiie study of tne u r i n a r y e x c r e t i o n f o r s u c h i n f o r m a t i o n . As j u d g e d b y t h i s s t a n d a r d , tn e groups f a l l in to tiie cate g o ry of p erso n s la c k in g o c cu p a tio n a l exposure to lead compaunds. A special sig n ifican ce is attached to the f a ilu r e of the b a r r e l f i l l e r s to show any in c r e a s e in t h e i r le a d e x c r e t i o n as a con s e q u e n c e of t h e i r e x p o s u r e to l e a d e d g a s o l i n e . Not o n l y do t h e two groups f a i l to d if f e r e n tia te themselves from the p o in t of view of lead e x c r e t i o n , b u t i t i s e q u a ll y t r u e t h a t no s i n g l e i n d i v i d u a l in the g r o u p s c a n be d i f f e r e n t i a t e d . Of t h e 1 0 p e r s o n s who w e r e e x a m i n e d p r i o r to exposure to leaded g a so lin e, and again a f t e r 6 months exposure to le a d e d g a s o l i n e , no p e rso n shows an i n c r e a s e i n h i s r a t e of le a d e x c r e t i o n . T h i s c a n be i n t e r p r e t e d o n ly a s meaning t h a t t h e r e was no s ig n ific a n t lead absorption as a consequence of th is exposure. Thus, i t seems q u ite c le a r , t h a t the. i n a b i l i t y of anim als to absorb measurable amounts of t e t r a e t h y l le a d out of g a so lin e in d ilu te s o lu tio n (5), (1 p a r t p e r 1000 b y v o l u m e o r l e s s ) i s s h a r e d b y man. 5. Comparison of the Findings with. R esu lts Obtained E a r li e r . In view of the importance of the conclusions of the above paragraphs, in d ic a tin g the negative c h a ra c te r of the fin d in g s, i t is p r o p e r to p r e s e n t o b s e r v a t i o n s of a com parable c h a r a c t e r on groups of su b je c ts s im ila r in every m atter save th a t of exposure to leaded g a s o l i n e . A c co rd in g ly , T a b le s 13 to 13, i n c l u s i v e , show r e s u l t s o b t a i n e d i n 1 9 2 7 , i n a s t u d y o f g r o u p s o f p e r s o n s who h a d n o t b e e n exposed to t^e conditions asso ciated with the use of leaded g aso lin e. Tne m a d i c a l s t u d e n t g ro u p i s composed o f members o f a n e w ly m a t r i c u la te d c la s s . For tae second group, f i l l i n g s ta t io n a tte n d a n ts and 0021839 30 la r g e group f o r s t a t i s t i c a l purposes* U n f o r tu n a te ly ,, no a n a l y t i c a l d a t a a r e a v a i l a b l e i n one Cc.se o f trie b u l k h a n d l e r s of g a s o l i n e , because of th e ir unw illingness to provide us with samples of th e ir e x c r e t a , and t h e r e f o r e v .3 a n a l y t i c a l f i n d i n g s r e l a t e o n l y t o f i l l i n g s t a t i o n a t t e n d a n t s , as i n d i c a t e d in th e t a b l e s . The c o n t r o l garage m e c h a n i c g r o u p i s made u p o f o n l y a s m a l l n u m b e r o f men c a r e f u l l y s e l e c t e d in 1936 as l a c k i n g any e x p o s u r e t o l e a d e d g a s o l i n e . The rig id regcirements in the l a t t e r regard introduced considerable d i f f i c u l t y i n t o t.*e p r o b l e m o f o b t a i n i n g c o o p e r a t i v e s u b j e c t s . ho e x p lan a to ry comments a re re q u ire d , sin c e tne t a b le s p re s e n t the observed f a c ts ad equately. I t should be p o in ted out th a t ti.e o b s e r v a t i o n s r e c o r d e d i n t h e s e t a b l e s w ere made by t h e same p e r s o n s wv.o c o l . e c t :-d. t n e d a t a o n t-..e e x p o s e d s u b j e c t s p r e v i o u s l y d e s c r i b e d , fna c l i n i c s ! methods employed in the two i n s t a n c e s were s u b s t a n t i a l l y tn e same, w hile the a n a l y t i c a l methods were p r a c t i c a l l y i d e n t i c a l . T able 19 summarises th e mean v a lu e s f o r a i l th e groups of exposed and unexposed p e rs o n s, in such m a tte rs as would seem to have special sig n ific a n c e . (Since the frequencies of occurrence of s tip p lin g d o n o t l e n d tine ms e l v e s t o c o m p u t a t i o n o f me a n v a l u e s , c o m p a r i s o n o f t h i s i m p o r t a n t f a c t o r must be made from t h e t a b l e s o f d i s t r i b u t i o n . ) Comparison of the means r e v e a ls a lack of s t a t i s t i c a l d i f f e r e n t i a t i o n of the groups* The m edical s t u d e n t s show a s i g n i f i c a n t d i f f e r e n c e in age, b u t i n no o t h e r f a c t o r . The b a r r e l l f i l l e r s n o t exposed to l e a f e d g a so lin e snow a s i g n i f i c a n t l y low hemoglobin c o n te n t of t h e i r blood, a s p r e v i o u s l y p o i n t e d o u t . Tn e m..-an l e a d c o n t e n t p e r s a m p l e o f f e c e s a l s o s h o w s c e r t a i n s t a t i s t i c .i l y s i g n i f i c a n t v a r i a t i o n s w i t h i n t h e g ro u p s , c u t no a c t u a l im p o r ta n c e can be a t t r i b u t e ' to t h e s e d i f f e r e n c e s K B 0021840 21 ia x ,te r f a c t o r i s c o r r e c t e d by e x p re s s in g the le a d in the f e c e s in r e l a t i o n to tne q u a n tity of ash, the v a r i a b i l i t y of the g'roups is statistic a lly insignificant. Th e i n f l u e n c e o f 1-r e v i e n s O c c u p a t i o n a l L e a d E x p o s u r e . I t h a s b e e n i n t i m a t e d t h a t some s i g n i f i c a n c e may be a t t a c h e d to tne f a c t th a t a co n sid erab le number of the s u b je c ts had been exposed t j lead compounds in previous o ccu p atio n s. Likew ise tne handling of lead compounds o th e r than those a ss o c ia te d with leaded f u e l * ...i r u t c a e x p e c t e d t o n a v e some i n f l u e n c e u p o n t h e l e a d a b s o r p t i o n o f t h e g a r a g e m e c h a n i c . As a means o f a s c e r t a i n i n g t n e i m p o r t ance of t.^ese m a tte r s , the a n a l y t i c a l r e s u l t s d e riv e d from two small groups of p e rs o n s v.nose o c c u p a t i o n a l h i s t o r i e s f a i l e d to g iv e e v id e n c e K F 0021841 CD 0 i* / f v V I J o ^ A. rL rl ,ay' ~q q were subjec ted to studs,'. (Table 6 h a s ri. * . ;u Lu - o i s Lr I ou Li o n U i t : t e s u b j s c t s a s t o p r e v i o u s o e c u p a t i o n a l j- 0 -u J -T O 0 J. T 3 y - cl X 3 .-OU p r e s e n t s t h e -lea n v a l u e s f o r t h e 1 e a d excretion of these subjects as sepa.rate groups and in combination. ITi-e r e s u l t s a r e s e e n t o b e s l i g h t l y l o w e r , b u t n o s i g n i f i c a n t s t a t i s t i c a l d iffe re n c e s nave re s u lte d from the exclusion of the previously exposed su bjects. Lead E xcretion in R elation to Length of Exposure to Leaded G asoline. an exam ination in to tne r e la tio n s h ip between le n g th of s e rv ic e and le a d e x c re tio n , might p ro v id e a means of a s c e r t a i n i n g tne significance of tne lead exposure associated with the occupation of t n e g a r a g e m e c h a n i c s . T h i s was done by s t u d y i n g t h e c o r r e l a t i o n between the magnitude of lead excretion and the period of continuous employment as m e ch an ics, and then by a c o r r e s p o n d i n g s tu d y of tne mugnitude of lead e x c re tio n in r e la tio n to le n g th of exposure in r e p a i r i n g c a r s w h i c h `u s e d l e a d e d g a s o l i n e . Tn e r e s u l t s o f t h e s e a tte m p te d c o r r e l a t i o n s a r e s.-.wn in T a b le 21. There i s a com plete c o n c lu d e e i t i i a r that, t n e l e a d e x p o s u r e a s s o c i a t e d with, th e o c c u p a t i o n is in s ig n if ic a n t, o r th a t i t is nf such ir r e g u l a r occurrence as to .. - v j no i i i e a s u r a b i e t i i e r e l a t i o n s h i p . There remains one o th e r means of examining the a v a i l a b l e d ;ta in search of evidences of lead ab sorption from the handling of l e a d e d g a s o l i n e . among t h e s u b j e c t s s t u d i e d i n 1 9 2 9 , t h e r e w e r e 26 f i l l i n g s t a t i o n a t t e n d a n t s , a n d 24 t a n k wa g o n h a n d l e r s who h a d b e e n employed as su b je c ts in 1927. Presumably, i f t h e i r occupation con t a i n e d a s i g n i f i c a n t l e a d h a z a r d t..ey s n o u i d snow some e v id e n c e of Change i n *ead e x c r e t i o n a f t e r Z y e a r s . The f i n d i n g s f o r th e two y e a r s , as to a ead e x c r e t i o n , a r e snown in T a b le s 22, 23, and 24. Tne a s m v a l u e s a r e s u m m a r i z e d i n T a b l e 2 5 . Mo s t a t i s t i c a l l y v a l i d d i f f e r ent e I ? demonstrable. 6 . Summary and D is c u s s i o n , T h r e e h u n d r e d a n d o n e men vno h a d i n c u r r e d w e s e v e r e s t a n d lo n g e st exposure to le ad e d g a s o lin e and i t s combustion p ro d u c ts were studied as to t a e i r p h y sical f i t n e s s and t n e i r le ad e x c re tio n , during t n e w i n t e r m o n t h s o f 1 9 2 9 - 3 0 No c l i n i c a l 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 o r o f 19 ad i n t o x i c a t i o n 'were f o u n d i n a n y i n d i v i d u a l , a n d no i n d i c a t i o n of le a d a b s o r p t i o n , as a consequence of t h e . e x p o s u r e , was d e t e c t e d wuen t..e s u b j e c t s were compared as to t h e i r l e a d e x c r e t i o n w ith c o r r e s p o n d i n g g r o u p s o f u n e x p o s e d p e r s o n s who h a d b e e n s t u d i e d p r e v i o u s l y . -a r e a v e r t h e r e was no m e a s u r a b le change i n th e l e a d e x c r e t i o n of a g r o u p o f f i f t y o f t n e s u b j e c t s who h a d b e e n S t u d i e d i n a s i m i l a r manner in I S 27. | The le a d e x c r e t i o n of a number of workmen was d e term in e d before and a f t e r a 6 monta p e rio d of in te n se sk in exposure to leaded g a s o l i n e . .No i n d i v i d u a l i n t n e g r o u p s h o w e d a n i n c r e a s e d l e a d e x c r e - ;o - Li on Li3 p e rio d of exposure. l u e l e v e l o f h u ma n 1 e a d e x c r e t i o n Lias b e e n s h o w n t o b e H i g h l y i v e t o L.;S .a g n i t u d e s i n c e t oxeO -sOuh ob ^g e0c t ss fm. xi iilee ad t o s n o w a n i n c r e a s e i n t h e i r l e a d e x c r e t i o n , i t i s a p p a r e n t t u. x sC-1. tb; l1i tmt l ee e x p o s u r e t o 1 ad e x i s t e d , a n d t ha t no s i g n t u'o s 0r 01i o n o f l e a d i. i ,-v ^ ,-7 > - S i j . i CU X X. . - a - -v 0 Ci O oO t i i e 1ead absorption and excretion of unexposed jt 0 c t o n s e j z! j j j. j ii'i'3 ty 0 0 r e co:g n i z e d t h a t t h e m a g n i t u d e a n d v a r i a b i l i t y 0I i inx iv i t h f o o d i s s u f f i c i e n t t o ask a s l i g h t l e a d a b - s o r a t i o n . . b u --may r e s u l t f rom e x p o s u r e t o +vi -i>e c o n d i t i o n s a r i s i n g f r o m m a use of * a*-ied g a s o l i n e . I f t h i s has o c c u r r e d , th e r e l a t i v e i n s i g n i f i c a n c e of m e c o n t r i b u t i o n made by l e a d e d g a s o l i n e to the t o t a l l e a d a b s o r p t i o n o f t h e e x p e r i m e n t a l s u b j e c t s i s o b v i o u s . On t h e o t h e r h a n d , m e tec..nio employed in m e foregoing o b serv atio n snould be modified so as to c o n t r o l t h e f a c t o r of i n d i v i d u a l l e a d i n g e s t i o n on th e p a r t of 0XOO303 >0r s omn s , i f m e p r e c i s e m a g n i t u d e o f t h e o c c u p a t i o n a l l e a d e x 1O 1 . m i s t o bc e im.ieeaassuurreedd . Y.'e s n a i l p r e s e n t t h e r e s u l t s o b t a i n e d t h r o u g h 0 " 0 ' i 0x t x e l a u u8 r in0 od o f s t u d y i n a s u b s e q u e n t a r t i c l e . view of th e ne Live e v id e n c e o b t a i n e d i n t h i s stud;/ of p e r s o n s './hose e x p o s u r e to l e a d e d g a s o l i n e and i t s c o m b u s t i o n p r o d u c t s was m a g n if ie d to a p o i n t w e ll above t a u t which i s p o s s i b l e i n the v,enerax p o p u l a t i o n , th e r e i s no re a so n to f e a r the e x i s t e n c e of d..nger to m e :ublic n e a itn from the d i s t r i b u t i o n and use of leaded gasoxine. 0021843 -24- 7. R eferences S a y e r s , R. R. e t a l : i x p e r i u e n t a l s t u d i e s o n Rice e f f e c t o f I t i i y l G a s o l i n e e n d i t s combustion p r o d u c t s , U. 3* B u r e a u o f line 5 b l i c - . t i o n 19 .-jb,ntr* , "* i'w' - -* * *i 3 a -.1. .c- a; o o f t s t r a e t n y i l e a d g a s o l i n e i n i t s 1 a t i o n t o t .. 3 yU i e a l t n . U. 3 . P u b l i c H e a i t i l iSU i. J. c: w*x x*l No . 3 , 19 25. n i l R e p o r t o f -,,:i n i s i r ^" o f Ae London. 1930. A e n o a , R o b e r t a . : On t n e t o n i c i t y o f t a t r a e t n y l l e a d a n d i n o r g a n i c lead S i l t s , J r . .ab. and J i i n . Led. 1 2 : 554, 1927. Hence. Robert ; and Tnamann, F r e d e ric k ; ?ue b e n a v io r of l e a d in or.cam s ; t :i T e t r a e t n v i U, m.r \ i i i t r . H y g i e n e , 1 3 ; 473, 1931. Kona, R o b e r t A ., Tharaann, F r e d e r i c k , nd C a o l a k , J a c o b ; Le ad a b s o r p t i o n and e x c r e t i o n in c e r t a i n ad trades., J r . Ind. Hyg. O. j , 19 3 o . no e , Rob e r t > &nd "Hi-.Id .l.i...i a n n , F r e d e r i c k ; f n e be.i i a v i o r o f l e e l i i i i i a i o r g u n i s a . T . Am. J r . P u b . H e a i t n , 10 : 5 5 5 , 1 9 2 3 . n o e , R o b e r t ,A . f u a ; n a n n r F r e d e r i c k , a n d Ciiols i k , . J a c o b : On normal a b so rp tio n and I I uBcilu a b s o r p t i o n a d I n d . *' V-Tr$;~=?> 15 : 273 , 19 3 0 * d Cn o l a k , J a c o b : On oii 3 I. Lead abo o r p t i on and r , 1 iV>/ pUcj'S; 7, 1 9 3 3 . K 0021844 I. e r i od Of D i s t r i b u t i o n of L eaneo. G a s o l i n e i n V a r i o u s A m e r i c a n C i t i e s Uo t o O c t o b e r 1 9 2 9 _ ocai i v- "at- of Fi r s t Di s t r i bu l i o n Interval 0 Discontinu ance Ye a r s o f C o n t i n u o u s Di s t*r i o l ii c n Dayton, Chi o F e b r u a r y 19 23 none Cincinnati, 0. v- "i 1323 none . V a s e l i n e , A. Va. l a i c a t o , Tl i . buii::`i? r .-.u t a un. 19 33 : .o v 1C t 0 su. liic r 19 26 1r\ -otr n n -! 13 d ? t ro 111 .i c.i o'; 0* - i i r -, : '7. IS 34 n U -u J -3 n 1 21 1 :r - r ^ * c j - * Q 0-.~*4 v- D 1 9 2 4 '41 H 13 13 ko r i no 19 34 1> H ! ;i 13 7;71 ' ' -i 3 orin--' 19 24 M 13 11 il 11 H a i t i m o r e , A-f. Sprint 1 >7cj_- M *1 il 13 o a s . i i n p t o n , D. C, Lp r i nTM 19 24 W ' !l rt 13 Han A n t o n i o . T e x a s 3 ) r i n e 19 24 14 11 ;i 11 --- *\7 'rD-- "'1.^ ,-.u t u u n 19 24 none a t l a n ta , Oa. Autumn 1 9 24 31 J a c k s o n v i l i e , F i a . Autumn 19 24 J1 Few 0 r l a n s , L a . 3 o rinr- 19 35 1 o l v s i & n <3, C a i o "Uiniae r 1 9 2 6 41 5a 9i. n i a . i ' a . Uu mme r 19 25 11 5.7 6.5 3.2 3. 2 <----. ;O_j tr, o 3.2 3.2 3.2 3 .2 3.2 3. 2 5. C 5.0 5.0 3. 2 3.3 3.2 ' 'OSl-Of:. i.i2.3 S Denver. Colo. Cummer Summer 19:26 19 26 n n 3. 2 2.2 OcOivCL; C t v:ri Sii . ,Ui Sa, uiii. Summer Summer S a n " r a n c i s c o , G ai. i n t e r 19 35 1925 19 25 ` n w n 2.2 2. 2 2. 2 Approximate Gross and Comparative Consumption of Leaded G asoline in V arious Areas o S t a t e s From 1936 to O c t o b e r of 1S3S T 3 6 1 9 37 1 S 28 Di s t r i b u t i o n Areas of tue United States New E n g l a n d Spates end Le w To rk Li 11 io n s of Gallons of leaded G a s o l i ne 11.9 Percent, Pillions of Leaded of Gallons G a s o l i n e * :> o: l e a d e d I'o ta l Case G a s o l i n e line 0.8 54.8 Percentage of Leaded Gasoline to * ot&i, caso** 1i ne 0.1 Li 11 i. on s of Gallons of loaded G asoline c- f . 7 Percent Pill of ^ead-' of G Gas. t o of l o t a 1 G a s o Ga soline 4 _A q r. Pennsylvania 7.9 1.4 31.7 4.6 73.9 9 .7 83.1 A tlantic Coast States '!. C. 0 0.9 5.8 0. 4 15. 8 1.8 90. Onio Kentucky Georgia Flo r i da L i s s . , and n i a b a it:a 1 6 0.3 ' 17.5 4 . 3 C'. 6 30. 3 3.3 3.5 89.7 36.9 10.4 147. 4.3 49. ~oui si anna Arkansas Tcj'ineso ee C . 3 G.:3 0 .3 0.07 10 v6 2.3 49. Central States i. 6 X 3. ^ K i- Cl Li 0 ill ; Rocky ; k . Skates i 6 c t* ' j 0 Q. 3 1 1 u Ci t r~ S n - *1 *! r i \ j i h L, L7 *) * srrJ 1.6 4. 0 0.0 7S.4 1.3 0. 3 1.4 0.0 0.8 11 3 .5 3.9 11. 5 31.7 388.8 'F C> 0 o 3. 4 3, 3 3.4 163.6 5 .3 1X wr' Po 38. 4 5 27.8 4.1 333. 0.6 16. 4.0 16. 1.7 41. 4.1 821. .-ive r a z e Te t r a - e t n y l L e a d C o n t e n t o f G a s o l i n e i n V a r i o u s Areas of The U n ited S t a t e s from 1926 to 1929 L w i i J s-> - d i; v 2 6 an^ x a n d and dew York JX y 3 5 Av e r a n e T e t r!a e t h v" l L e a d 19 27 Content I ! i n C ubic IS 25 Centimeters per.Ga ! r I 19 29 . . . . . . . . .. . 1.4 > 1.1 - i 1.2 ! 0.9 Rennsyv ni a A tlantic Toast Stave s 1. 3 1 1.7 : l.G : 1.6 : : 1.4 * 1--1 1 . 6 5 ........ i i 1.5 On i o O.S 1.2 1. 1 ! 1 . 5 Kentucky, Georgia, i flo r id a . Liss. and j l.G A l a b a m a ------------------------ ij-- ou i s i an n a , A rkansas n essee Ten t r a e - 1c i t e s 0.9 1* T e x a s a yi ' O'C-L.i10 l Roc ity :.io u n t a i n States 1.4 f 1 1.3 1.7 0.6 1.6 1.7 2.0 . 1.7 ` 0.9 * - ... . . : 2.2 i = ' i : j ; 2.0 ` ..s : 2.4 ' 1.9 ' 1.3 2 . 0 ...... 2.7 2.4 T e s t Co --OO O Ld uc: is 0.7 ' 1.5 1.5 Uni t e d S t a t e s as Tuoi e 1.4-::- Tn e s e f i g u r e s a r e 6St i 1 1 . 6-:>- ^ 1.75 ' 1 . 6 2 ...... ti ri S o n l y - a n d . - m a y - ~be... s o m e w h a t . i n e r r o r . . .... - HE' 0021847