Document a1EnokNj1aVpMLNp7ZgVQ47ve

// Ju n e 30, 1953 D r . S. I. Gleason D irector of R esearch & Developm ent Wynn O il Com pan y 1151 V/est Fift h St r e e t A zu sa, Californ ia D ear D r. Gleason : ' I h ave b e fo r e m e you r le t t e r o f Jun e. 19 a d d r e sse d to th e New Yor k o ffice of Eth yl Corporation and th at of correspon d in g date ad d r e sse d to m e . In asm uch a s I am th e M ed ical D ir e ct o r of Eth yl Cor p or at ion (by a st r an ge com bin ation of cir cu m stan ces th at date back to 1925} and the D ir ector of th is Departm en t in th is M edical College, of which Th e Ketterin g Lab o r at o r y is a p ar t , I w ear two h a t s, an d you r le t t e r to New York w as bound to com e to m e . . With r e sp e c t to the cir cu m stan ces r e fe r r e d to above, I w as an a ssist a n t p r o fe sso r of ph ysiology in th is m ed ical sch ool in 1924, when som e of th e p r ob lem s con cern ed with tetraeth yl lead w ere brough t to m e for in vestigation by C. F . Ketterin g and Th om as M idgiey, Jr . The p u r su it of th ese prob lem s within the lab o r at o r ie s of the m ed ical sch ool an d within the In du stry put m e in the w ay of bein g ju st about the only sou rce of scien tific an d p r actical in form ation ou h ygien ic m atter s r elatin g to tetraeth yl lead , end so , without relin quish in g m y u n iver sity r esp on sib ilit ie s, I becam e the M edical D ir ect o r to Eth yl Corporation and h ave so con tin ued. The m ain problem s of the in du stry in volved r e se ar ch and sin ce th is w as m y field of act ivity , I could c a r r y on both jo b s without con flict. Sin ce I can an sw er both le t t e r s at on ce an d with the sam e b ack gr ou n d of in fo r m ation , it is ju st a s w ell that i w as delayed in my reply to the one that cam e d ir e ct ly , In ciden tally, the fact s u sed by D r . Ran kin in hi3 t alk s h ave com e fr om th is Lab o r at o r y . I h ave no r esp o n sib ilit y fo r h is in terpretation of th em , alth ough fr o m m y acqu ain t an ce with D r ..R an k in I sh ould exp ect th em to be fa ir ly soun d, fo r durin g the y e ar s up to 1945, when E. I. du Pont de N em ou rs and Com pan y w as en gaged in th e m an u factu re of tetraeth yl lead u n der con tr act with Eth yl Corporation .I was th eir ch ief m edical ad visor on the h ygien ic asp ects of th is p r o c e ss. I sh all speak to th e poin t of you r qu estion s quite without r efer en ce to an y apparen tly o r p ossib ly con tradictory opin ion s exp r e ssed by D r . Rankin, e sp e cially sin ce th is is a m at t e r on which m isu n d er stan d in gs can e a sily o ccu r . F ir st , let m e say th at the gr eat bulk of the experim en tal work on tetraeth yl lead, an d on th e h ygien ic p r ob lem s a sso c iat e d with th is com poun d and it s u se in gasolin e w as dr ne in the late tw en ties and e ar ly t h ir t ie s. The experim en tal w ork on the m etab olism of le ad com poun ds* ge n e r ally , with em p h asis on th e in organ ic com pounds of lead h a s.continued sin ce then to the p resen t tim e. Reprin ts of m ost of the e ar ly publication s ar e no lon ger availab le and 1 can 0005057 D r . S. I. G leason - (2) - Ju n e 30, 1958 sen d you on ly a few th at give r e fe r e n c e s to th e o t h e r s. Th e la t e r in v e st igat io n s, so m e o f w h ich a r e st ill in p r o g r e ss .h ave b een p u b lish ed only in p a r t , bu t t h ose available ar e being forw arded to you. 1 th in k Xsh ould w arn you th at it i s som ew h at d an ger ou s fo r you to u n dertak e th e in terpretation of m edical proced u res and p r actices b ased upon the experim en tal d ata. Th is is a com plex se r ie s of problem s, and even after th irty y e ar s of in ten sive study of th em , it is n e c e ssa r y fo r m e to b e cau tiou s in th e m at t e r of con clu sion s b ased on an alo gie s. Xsu gge st th at you exam in e th e lit e r at u r e which I sh all sen d you, bein g car efu l n ot to m ake in fer en ces beyon d the d ir ect eviden ce, an d them su bm it to m e any qu estion s con cern in g the p r act ical occupation al situ ation with which you a r e con cern ed. Now with r efer e n ce to th e ab sor p tion of lead th rough th e sk in ; th ere is abundant eviden ce con cern in g the ab sor p tion of tetraeth yl lead th rough th e sk in , and on th e exten t to which th e dilu tion of tet r aeth y l lead with gasolin e slow s up th e r at e of ab so r p t io n . . Th e fa c t s h e r e a r e known in so m e d e t ail. With r e sp e c t to th e ab sor p tion of lead soap s th rough the skin th ere is m uch le ss in form ation , and the eviden ce on which cu r r en t opin ion s a r e b ase d is both scan ty an d p oor . Our exp erien ce in in du stry le ad s u s to b elieve th at th is is a m atter of litt le im portan ce We h ave in vest igat ed but on e of th e so ap s in t h is r e ga r d an d h ave foun d th at it s absorption is too sligh t to be of p r actical im portan ce. Th is one w as lead octoate. So fa r a s I know an d can e st a b lish on a r e aso n ab le b a sis of in fe r e n ce (not pr oof) t h e r e is no eviden ce th at an y one of th e le ad so ap s (oleat e, n aph th en ate, styph n ate) is ab sor b ed in an y m ore th an th eor etical am oun ts th rough the sk in . On the oth er h an d, if I w ere to h ave th e r e sp o n sib ilit y fo r a gr ou p of m en w h ose w ork calle d fo r fr eq u en t .or prolon ged con tact of th eir sk in with one of t h ese com pou n ds, I would e st ab lish the fa c t s with eviden ce an d n ot in fer en ce. Th is can b e don e. It h as n ever been a problem to u s in this Lab o r at o r y . We h ave fun ds to in vest igate on ly th ose p r ob lem s which in d u stry b r in gs to u s and pays fo r , an d on ly one com pan y h as ever ask ed u s th is question out of a w illin gn ess to fin an ce it s in vestigation . Th ere ar e sat isfact o r y m eth ods fo r su ch an in vestigation both in th e La b o r a t o r y anc^in th e fie ld of o p e r a t io n s.. One oth er poin t of p r act ical im portan ce in th is connection is th at a ll in dividuals a r e ab sorb in g lead a t a ll t im e s in not in con sequ en tial am ou n ts.: Th e av er age ad u lt Nor th A m e r ican t a k e s in abou t 0 .4 m g. of P b++ d aily an d e lim in at e s ap p r oxim at ely th at am oun t d aily. Th e so u r ce s a r e food an d b e v e r age s, in cludin g w afer , an d the a ir , which is con tam in ated with a sm all quan tity of lead from m an y so u r c e s. You se e , t h e r e fo r e , th at u n le ss th e am ou n t a b so r b e d th rou gh th e skin u n der un u sual o r occu pation al con dition s is ap p r eciab le, it w ill be lo st in th is n orm al in take and output of lead . F o r exam ple, p er son s who handle co m m e r cial lead ed , gaso lin e do n ot a b so r b en ough le ad out o f th e gaso lin e (the con cen tration of tetraeth yl lead is alw ays low an d n ever in e xce ss of 3 m l. p er gallon in autom obile gasolin e o r of 4 .5 m l . p e r gallon in aviation gasolin e) to D r . S. I. G le aso n - (3) - Ju n e 30, 1958 m ak e an y m easu r ab le ch an ge in th eir n orm al r ate of excretion . On the oth er h an d , m en who h an dle t h e t e t r ae t h y l le ad it se l f (with out dilu tion ) sh ow a g r o ss in cr e ase in th eir lead output in th e u rin e on the n ext day aft e r th ey have su ffe r e d accid en t al con tact with even a sm a ll quan tity o r h ave been su b jected to con tact with an ap p r e ciab le (m easu r ed ) quan tity on t h e ir sk in . In an experien ce of n early a life tim e in the lead t r ad e s, Zh ave n ever seen a c a se o f lead poison in g th at w as due to the ab sor p tion o f the in organ ic o r organ ic sa lt s of lead th rough the sk in . I do not believe it o ccu r s, but I r ep eat th at X would su r e ly in vest igat e th e m at t e r car e fu lly if I h ad the r esp on sib ilit y fo r the safe t y of exposed person n el in the sp e cific in stan ce. It is not n e c e ssa r y to d e pen d upon gu e ss w ork in su ch a m at t e r . I sh ould call atten tion to th e sim p le , but n ot alw ays r ecogn ized , fact th at when the skin of m en , e sp e cially of h an ds, com es in con tact with le ad com pou n ds, th ey m ay fa il to o b se r v e , su fficien t ly , th e n e c e ssit ie s of p e r so n al cle an lin e ss, an d so sw allow sign ifican t am ou n ts of lead w ife th eir food and d r in k s, not to sp eak of t h eir tobacco an d oth er ob jects th at th e fin ger s put into th e m outh. I t r u st th at th is m ay ser v e to point up, if not to an sw er som e of your qu estion s. Very tru ly you rs, RAK ef Robert A. Keh oe, M .D. En c. Exp osu re to Lead - Keh oe Exp er im en tal Stu d ies on the In gestion of Le ad Com poun ds - Keh oe, Ch olak, H ubbard, Bam b ach , M cN ary an d Story On the Toxicity of Tetraeth yl Lead and In organ ic Lead Salts - Keh oe KE" 0005059 EVVOOD 4*2908 CABLE ADDRESS: W tEPO DEPARTMENT OF RE SE ARC H 6- D E V E LO P M E N T ? 1151 W E S T F I F T H STREET AZUSA, CA LI FO RN I A Ju n e 19, 1958 Eth yl Corporation 100 Parle Avenue New Yo r k 1 7 , New Yor k At t en t ion : Medical Research D ivision Gen t lem en : We h a v e a c u r r e n t i n t e r e s t i n t h e p o s s i b l e r a t e o f a s s i m i l a t i o n of le ad p o i so n i n g by a b so r p t i o n t h r ou gh t h e s k i n on t h e h a n d s . Our i n t e r e s t l i e s in t h e f a c t t h a t our p r o d u ct w h ich c o n t a i n s an o i l so l u b l e o r ga n i c le ad s a l t in very sm a ll p r o p o r t io n i s som et im es used with or added to con ven t ion al m et al working c o o la n t s, e it h e r so lu b le type or o i l base t ype, Could you a l s o a d v ise us i f the Et h y l Co r p o r at io n h as ever p u b l i s h e d a n y a v a i l a b l e l i t e r a t u r e on t h e s u b j e c t o f l e a d p o i s o n i n g and t h e r a t e o f d e p l e t i o n o f l e a d fr om t h e human s ystem . I n 1 9 5 4 we h ad t h e p l e a s u r e o f a t t e n d i n g a s y m p o si u m on le ad p o i so n i n g a t wh ich time v e r y r e l i a b l e and i n t e r e s t i n g in form ation r egar din g the bioch em ical elim in at ion of lead fr o m t h e human sy st e m was p r e s e n t e d . A l s o v a r i o u s m e t h od s f o r d e t e r m i n in g lead in bot h t h e blood st r e am and t h e u r in e were d iscu sse d . Ou r i n t e r e s t i s p u r e l y t e c h n i c a l an d we w o u l d a p p r e c i a t e h a v in g an an sw er from someone in a u t h o r i t y in your D e p a r t ment at your e a r l i e s t con ven ien ce. Very t r u ly you r s, SI G :g c S. I . G l e a so n , Ph . D. D ir ect or of Research & Development 0005060 N 7224.01