Document zdrj2jenOLL7j2ozEoGG2K090

F e b r u a r y 22, 1962 M em o to: Dr. Robert A. Keh oe From : T. Sterlin g Su b je c t : ' A n a ly sis o f C a lifo r n ia T M L Stu d y Th e ch an ges o b ser v ed in th e excr etion of le ad an d in th e blood p ictu r e A w o r k e r s (who sw it ch e d fr o m h an d lin g T E L con tain in g p r o d u c t s t o th ose con tain in g T M L) a r e of su ch co n sist e n cy an d m agn itu d e a s to p r eclu d e an y ch an ce fa c t o r s. Th e p atter n of r e su lt s w ould o r d in ar ily fo r ce on ly one con clu sion on th e in v e st igat o r ; n am ely, th at u n derlyin g ch an ges in p h y siology o r body ch e m ist r y h ad tak en p lace du rin g th e p e r io d su b je cts h an dled TM L. It is tr u e th at th e data w ere co llected in a som ew h at h ap h azar d an d c a v a lie r fash ion . H ow ever, th e m o st im p ortan t fin d in gs a r e b ase d on lab o r ato r y an aly se s of u rin e an d blood sam p les an d m ay be above reproach . 2i i s a g r e a t m isfo r t u n e t h a t t h e m e d ic a l fo llo w - u p d a t a t u r n e d ou t t o be u s e l e s s . T h e r e s u l t s a v a il a b l e n ow w o u ld m a k e it a p p e a r d e si r a b l e to com p lete th e collection of a ll th e d ata an d do it in th e fo r m o r igin ally plan n ed a s w ell a s to.exten d the follow -u p on th e lab o r ato r y an aly se s fo r an ad dition al y ear . Le ad Le v e ls in U rin e an d Blood 1. D a t a on l e a d in b lo o d a n d u r in e v / e r e a l m o st c o m p le t e . F iv e u r in e sam p le s: w ere ob tain ed du rin g th e y e a r o f stu dy w h ile tw o blood _sa m p le s w ere tak en , on e in th e begin n in g th e o th er a t th e en d of th e stu d y. T h ese d ata a r e p r e se n t e d in a se r ie s of t ab le s a t the en d o f th is' m em o . .Con secu tive exam in atio n s a r e id en tified a s "R o u n d s" one to fiv e . Th e n u m b er o f sa m p le s a r e given in th e secon d colum n of each tab le. St a t ist ic a l evalu ation of d iffer en ces o b se r v e d betw een con secu tive rou n d s a r e b a se d on A n aly ses of V arian ce. The st a t ist ic a l an aly sisri s m ade extrem ely com plex by th e fact th at, w h ile m o st m e a su r e % /ere m ad e rep eated ly on th e sam e su b je cts, not the sam e n u m b er of su b je ct s w as t e ste d each rou n d . Th e a n a ly se s a r e n ot r e p r o d u ce d h e r e . W hen th e p r o b ab ilit y of fin din g, by ch an ce, a v ar iatio n am on g m ean s a s la r ge a s th e one 0 uUOb'i '0 N9600 observed was sm aller than . 05, a s t e r i s k s w e r e p la c e d o n t h e table. ( F o r exam ple, t h e m ean s on T a b l e s 1, 2, 3, an d 4 d iffe r w ith acceptable st a t ist ic a l r e lia b ilit y . T h is i s in d ic a t e d b y p lacin g ast e r isk s on e a c h sid e o f * T a b le 1* , * T a b le & , e t c . ) Le ve ls of le ad in u rin e an d blood a s w ell a s u rin e volu m e an d sp e cific gravity a r e given in T ab les 1 to 5 fo r a ll w or k er s com bin ed, in T a b le s 6 t o 10 f o r v / o r k e r s in Sa n F r a n c i s c o , a n d in T a b l e s 11 to 15 fo r w o r k e r s in JLos A n g e le s. T h e r e i s a n o b v io u s, c o n sist e n t and st at ist ic ally sign ifican t declin e in th e le ad con ten t of blood an d u rin e. T h is con clu sion is r ein fo r ced by th e p r o g r e ssiv e d eclin e in u rin e lead , o v e r th e p e r io d of th e stu dy, tow ar d a n ew st ab le st at e . Su ch a p r o g r e ssio n w ou ld b e e x p e c t e d , on b a s i s o f th e le a d c h a m b e r stu d ies, w h en ever the burden of en viron m en tal lead d e cr e ase s. (Statist ical sign ifican ce am on g u rin e volu m es fo r "A ll D ata" is n ot accom pan ied by any sy stem atic in cr e ase or d e cr e ase an d m ay be d iscar d e d a s sp u riou s.) T h r ee occu p ation al su b gr ou p in gs w ere sin gle d out, who w ould h ave r elativ e ly u n iform exp o su r e. T h ese w ere se r v ic e station atten dan ts in Sa n F r a n c i s c o ( T a b le s 16 t o 2 0 ), s e r v i c e st a t io n a t t e n d a n t s in L o s A n g e le s ( T a b l e s 21 t o 25) a n d B l e n d e r s ( T a b le s 25 t o 30 - a l l Ble n d e r s a r e lo c at e d in San F r a n c isc o ). A gain le a d in u r in e an d blood d e c r e a se s fo r a ll occu pation s. It is in ter estin g to n ote th at the d ecr e ase ap p ears to be m ost pron oun ced fo r Blen d ers. Blood A n aly ses A. s e r i e s o f la b o r a t o r y t e s t s on r e d a n d w h it e b lo o d c e l l c o u n t s w e r e m ad e. Not a ll coun ts w ere rep eated so th at com p ar ison data a r e lackin g fo r : H em atocrit - P e r Cent Reticu locytes - P er Cent M. V .C . . M .C .H . M .C .H . C. P oly s - M etam yelocytes M orph ology P latelets C om p arison s of the coun ts list e d above could n ot be m ad e. 0(\uo Un un J'i i 3 Th e data w ere com p lete fo r co m p ar iso n s on the follow in g blood c e ll cou n ts; Red Blood Count H em oglobin - gr am s Color* In dex W hite Blo o d Cou n t P olys-N eu tral Total p e r Cent P oly s-Filam en ted P er Cent P olys-N on filam en ted P e r Cen t Rym phocyte s M onocytes Easin op h iles Basoph iles (Tab le 31) (Tab le 32) (T ab le 33) (T ab le 34) (Tab le 35) (Tab le 36) (Tab le 37) (Tab le 33) (Tab le 39) (Table 40) (Table 41) T h e b lo o d c e l l co u n t i n c r e a s e s c o n sist e n t ly (e x c e p t fo r .Ly m p h o cy t es]}. Not all in cr e ase s ar e statistically sign i fican t; h ow ever, sin ce a ll in c r e a se s a r e in th e sam e d irection , th ere can be no doubt a s to th e o v e r - a ll ch an ge in th e b lood coun t. One very in terestin g fact e m er ges fr o m the in spection of cell coun ts In each c a se th e ch an ge is fr o m a low n or m al to t h e m ean of th e d istr ib u t io n w h ich d efin es n o r m al b lood ce ll cou n t. In th e c a se of Ly m p h ocy tes th e ch an ge is fr o m a h igh n or m al to the m ean . Th e blood data ar e too fr agm en tar y to p erm it fu rth er breakdow n by city or occupation . Som e C o n clu sio n s Th e co n sist e n t ch an ges d e m o n st r at e d by th e d ata le ad , w ith out d isp u te, to th e con clu sion th at th ey r e fle ct fu n dam en tal ch an ges of p h ysiology or body ch e m ist r y en gen d ered by th e ch an ge in lead ed gaso lin e . Th e total p atter n of r e su lt s is su ch th at even if n one of th e ch an ges w ould h ave reach ed an ap p r e ciab le m agn itu de of st a t ist ic a l sign ificitn ce the fo r m e r con clu sion w ould h ave to be r each ed . T h er e is no qu estion , th er efo r e* o f s t a t i s t i c a l m a g ic o r m an ip u lat io n on w h ich c o n c lu sio n s ir e b a se d . Two b asic ally d ivergen t in ter p r etatio n s of th ese fin d in gs ap p ear to be p o ssib le . (Th e a lt e r n a t iv e s w e r e d e r iv e d th rou gh d isc u ssio n s w ith H orton , Ch olak an d Gru pp. ) \ A. T M L p r o v id e s le ad w h ich i * d e p o sit e d in so ft t issu e in e x c a s s f # \ ddse&atioa. T h e r i s e in b lo o d c e l l co u n t m a y b e a c o m p e n sa t o r y KfT 0 0 G o >KSrtWWi! u- r e act io n 's for/example, to interference ~^th blood oxygenation acr oss the lung tissu e as a reaction to organic lead deposited th ere. B. Because of the in cr'e'ased vo' Ila't'i.,l.ity of th ^gasoUn e, lead is either inhaled in sm aller/or exhaled in lar ger amdtmts.i'TiHe body burden ^ P of lead being decreased the amount foundin urine and blood declines *' to a new stable state and the in crease in blood cell count represen ts the reaction of the bone m arrow to the decreasing amount of lead in surrounding tissu e and blood supply and a return to a more normal (if such an expression baa be .used) state bf ihe blood cells. A Sin ce hypothesis A would indicate heightened toxicity to relatively sm all occupational exposure,one would expect that this in crease in toxicity . would have been spotted during the manufacture of TML-, where v/orkers are exposed to much higher concentrations of lead in the atmosphere than are the occupations presen t in th is study. However th is was not .the case in the plants of the Ethyl Corporation. Hypothesis B appears more reasonable and there is then substance to the conclusion that TML pre sen ts le ss of a lead h azard than does TEB under normal procedures of handling. ~ t c i jo-**tA^-4t.A TT h it . ' l l '> rf- J cJL A'' S ' ,, * 1 .1 c . i--* I: am*.'tri iU4. 1--.vvf t J t i ^ 1 jtA* <* w " & ' 'A.C C-l-Kt3 JS i s K i '