Document DG8R6pDE07DjVz8XbeJ1mZq8N

N o v e m b e r I4., 1 9 3 8 Mr. Roger S* Hubbard The Bu ffa lo Gen er al Ho s p it a l Bu ffa lo , lieu York ; My dear Mr. Hubbard: . Please a ccep t my thanks fo r your le t t e r givin g in for m ation on your an alyses o f u r in e samples from Vim. Gu en ger ich , and d is cu s s in g the s ign ifica n ce o f the r e s u lt s . I should lik e to give you our r e s u lt s , t o comment on t h e ir s ig n ifica n ce and then to d iscu ss the ge n e r a l problem of methods of a n a lys is and methods o f ob tain in g sam ples, . On Ju ly 28th we r e ce ive d from Dr . Hillen b r an d a sample o f blood and a sample of appr oxim ately 100 c c . o f u r in e , both having been co lle ct e d in our con tain er s and accor ding to our in s t r u ct io n s , copies o f which ar e e n clo s e d . The r e s u lt on the blood (0,035 mg, per 100 grama o f whole blood) was q u it e w ith in the nonnal lim it s , but t h a t on the u r in e (O.Oif/ ? mg, in a sample of 100 c c . e q u iva le n t t o O,!}.? tag* per lit e r ) was not on ly a t va r ia n ce w ith the blood fin d in g but a ls o was so high as s ca r ce ly to be bona fid e . Desp ite the pre scr ib e d p r e ca u t io n s , samples ar e sometimes contam inated, and when co lle ct e d in in d u s t r ia l p la n t s they are not uncommonly s o . I t is our custom, t h e r e fo r e , in a ll cases in which the i n i t i a l r e s u lt s ar e q u it e h ig h , and e s p e cia lly when the blood and u r in e d iffe r m a t e r ia lly in t h e ir s ig n i fic a n c e , to check them by o b t a in in g a d d it io n a l sam ples, e s p e cia lly a sample of u r in e o f la r ge volume. In t h is in stan ce t h is procedure r e su lt e d in the follow in g data? a sample of u r in e o f 3^4-80 c c . con tain ed le a d to the e xt e n t o f 0*02 mg, p er l i t e r , w hile a sample of fe ce s contained 0,08 mg. o f lead or 0.06 mg. per gram o f ash . These r e s u lt s Ju s t ifie d the con clu sion t h a t the h igh r e s u lt on the p r evious sm all sample o f u r in e was due to contam ination o f the sam ple, and we so r ep or ted our con clu sion t o .Dr. Hille n b r a n d . Subsequently when fu r t h e r q u estion was r a is e d we obtained a d d it io n a l samples o f b lo o d , u r in e apd fe c e s , those giv in g r e s u lt s as fo llo w s : 0,025 and per lit e r 0,03 rag, of urine per in 100 grams a sample o f o3f 1w80hoclec b ,,a lo o nd d0,0,0,085mmg.g, in a sample o f fe c e s , e q u iva le n t to 0,09 mg, per gram o f fe c a l a s h . The combined r e s u lt s in my opin ion remov a ll doubt as to t h e 'ge n e r a l le v e l of lead e xcr e t io n of t h is man, p u t t in g i t w ith in n o r a a llim it s . The magnitude o f the lead exposur e, as in d ica t e d by these r e s u lt s , is in keen in s w ith - N6043 2 the fa c t s os to the occu p a tion a l h is t o r y o f t h is man and con sid er in g the a t y p ica l ch ar acter o f h is c lin ic a l p iet or e w ith r e s p e ct to lead I holier le a d can be excluded as an e t io lo g ic a l fa ct o r * As t o methods o f a n a lys is employed by us* I am sen d in g you s e p a r a t e ly the papers o f Cholalc and Hubbard from t h is la b o r a t o r y* For a con sid e r a b le p er iod o f t im e , and u n t il we cou ld s a t is fy ou r selves as to the s e n s it iv it y and a ccu r a cy o f the spectr ograph! method developed by Choiok and the d it h is o n e method as adapted by Hubbard* we r e lio d upon a chem ical method developed by Edgar* Thamann and Cholak o f t h is la b o r a t o r y and d escr ib ed in the Jo u r n a l o f In d u s t r ia l Hygiene fo r September 1953 i t con t ain s s e ve r a l m o d ifica t io n s of Fa ir b a ll*3 method which ser ved t o . make i t more a ccu r a t e and unifor m in i t s a p p lica t io n as w e ll a s s p e c ific w ith r e fe r e n ce to lead# F a ir h a ll c r it ic is e d our modifies.fcior.s la r g e ly because he was offen ded by our comments ou h is method, bu t the fa c t is t h a t he had never d escr ib ed h is own Improvements of tho o r ig in a l method In such d e t a il as to per m it p r e cis e r epr oduction o f h la pr ocedur es, and th er efor e he had l i t t l e ju s t ific a t io n fo r h is ir r it a t io n a t u s* That Ir r it a t io n has s in ce been d is p e lle d * I b e lie ve * now t h a t he and h is a s s o cia t e s In the Pu b lic Health Se r vice ar e u sin g both a d lt h ls o n e method and a spectr ogr aph! method s im ila r to Cholak*s* and ar e fin d in g them q u ito s a t is fa ct o r y and fa r su p er ior to the chromate method* V7 r ecogn ised year s ago t h a t the chromate method was n ot adequate fo r h an d lin g blood and sm all samples o f u r in e * and i t was p r im a r ily fo r t h a t r eason t h a t we were compelled t o develop more s e n s it iv e methods fo r ca r r yin g on ce r t a in phases o f our exp er im en tal work* You ar e q u it e r ig h t in your fe e lin g t h a t the ch ie f c r it ic is m le ve le d a t the chromate method r e fe r r e d t o It s lo s s o f le n d and i t s consequent low r e m i t s , n e ve r t h e le ss we found I t Im possible to avoid o cca s io n a l h igh r e s u lt s In u r in e samples* and fr e q u e n t h igh r e s u lt s on fe ce s due t o the pr esence o f oth er m e t a la , w ithout the in cor p or a t io n o f a su lp h a t e s t e p based on th e work of the Au s t r a lia n s , Avery* Hemmlngway t a ll* m w e ll as a s p e cia l procedure when bismuth occur r ed* Hot on ly ar e s ig n ific a n t e r r o r s a s s o cia t e d w ith the us o f th chromate method as d e scr ib ed by F a ir h a ll* under the most fa vo r a b le cir cum stan ces* but gr oss e r r or s can b in tr od uced * and in our exp er ien ce ar e in tr od uced * by the s lig h t v a r ia t io n s In techn ique which a r is e fr o m In fr eq u en t and ir r e gu la r performance of a n a lys e s , and by va r ia t io n s in the a n a ly t ic a l environment and in r eagen ts employed. The la s t two fa ct o r s may r e s u lt in gr oss e r r o r s * A plumber r e p a ir s a pip lin e and the samples handled in the la b o r a t or y fo r t h a t day or fo r s e ve r a l days y ie ld h igh r e s u lt s * A dust la r a is e d in cle a n in g or in moving o b je ct s In the la b o r a t o r y and the a n a ly t ic a l r e s u lt s go wrong* The glassw ar e is handled w ith le s s than the u su a l p r e cis io n and e r r or s a r is e * By 3- reason o f sad exp er ien ce we have found i t n e ce ssar y to e lim in a t e one fa c t o r a ft e r another * and now we change n othin g in our a n a ly t ica l la b o r a t o r ie s w ithout stop p in g the work and cle a n in g thor oughly t h e r e a ft e r * We have had t o exclude ou tsid e soot by filt e r in g the a ir supply o f our la b o r a t o r ie s , and we haw had to d iscon t in u e smoking in such la b o r a t o r ie s . Dust is avoided w ith the utm ost ca r e . Glassw ar e is washed in accor dance w ith a s p e cia lly pre scr ib e d te ch n iq u e , and C. P. bichromate Is used in the cle a n in g s o lu t io n in st e a d of the customary t e ch n ica l gr ad e. Reagents ar e a lso s p e cia lly p u r ifie d to a known p u r it y as determined by sp ectr ogr ap h ic a n a lys is *'4 The dangers o f e r r or a s s o cia t e d w ith a n a ly t ica l pr ocedur es in the hands o f even a ca r e fu l and exper ienced man are ver y g r e a t , but they ar e as n ot h in g compared w ith the op p or tu n itie s fo r er r or in the co lle ct io n o f samples, I am sure you would be u t t e r ly aston ish ed a t the oppor t u n it ie s fo r contam ination which we have d iscover ed in some fift e e n year s o f work with thousands of sam ples, b u t I s h a ll not bore you w ith these d e t a ils * Su ffic e i t to say t h a t the a n a ly s is t is w astin g h is time and m islead in g h is c lin ic a l colleagu es i f he does n ot provide chem ically cle a n con tain er s and d e t a ile d in s t r u ct io n s fo r the avoidance o f contam ination in the co lle ct io n of sam p les. Hothlng th at we have been ab le to do in h o s p it a l p r a ct ice has enabled us to escape o cca s io n a l gr oss contam ination o f samples of u r in e . Blood samples taken w ith h o s p it a l syr in ges and n e e d le s , clean ed and s t e r iliz e d in the u su a l way w ill always be s e r io u s ly con tam in ated. (We use a s p e cia lly clean ed pyrex tu b e, sup plyin g with i t a s p e cia l a ll-s t a in le s s s t e e l n eed le s t e r ilis e d by b o ilin g in t r ip le - d is t ille d water and encased in a second cor r esp on d in gly cleaned pyrex tube r eady fo r u s e .) Ur in e samples co lle ct e d in h o s p it a l u r in a ls and poured in t o a b o t t le as in the ca se of or dinar y 2lj. hour sam p les, w ill usually be gr o s s ly contam inated. Here our exper ience enables us t o say t h a t r e s u lt s In the u r in e over G.30 mg. per l i t e r are pr obably the r e s u lt s o f contami n a t io n , s in ce in the most s e r io u s cass o f le ad exposure and in t o xica t io n one r a r e ly fin d s r e s u lt s in excess o f t h is le v e l, v/e have found a ve r y few r e s u lt s as h igh as 0*50 mg. per l i t e r , m ostly in ch ild r e n , b u t figu r e s above; t h is r ange do n ot occur excep t as the r e s u lt o f massive doses associated with acute and u s u a lly fa t a l in t o xica t io n . Re s u lt s of t h is order of magnitude or gr e a t e r ar e the e ffe o t o f contam ination o f the sample e it h e r in it s co lle ct io n or a n a ly s is . I have no h e s it a t io n , t h e r e fo r e , In savin g t h a t the r e s u lt s obtained in your la b o r a t o r y on August 29th and September 2lj.th are fa n t a s t ic a lly and im p ossibly h ig h , as was a ls o our r e s u lt o f O.lt f mg. p3r l i t e r in a 100 c c . sample co lle ct e d a t the p la n t . Such co n ce n t r a t ion s sim ply do n ot occur excep t under the most unusual cir cumst a n c s . Even your la t e r sam ples, however, yie ld e d h igh r e s u lt s . Our samples o f blood on October 2 1 st yie ld e d 0.025 and 0.03 mg. of lead per 100 gr ams, k and oar u r in e sample on October 2l|.th. yie ld e d only 0*05 mg* per l i t e r , as co n t r a st e d w ith your r e s u lt o f 0.12 rag* per l i t e r on the same date* Sh is is in s p it e o f the fa c t t h a t our a n a ly t ic a l methods ar e more accu r ate and more s e n s it iv e than yours a t it s b e s t , i*e * ther e 13 l i t t l e or no inherent lo ss a sso cia t e d w it h the a p p lica tion of our methods. There must have been some fa c t o r of contami n ation t h e r e fo r e , or some fa ilu r e on the p a r t o f the a n a ly t ic a l p r oce d u r e s. I have gone to some le n gt h to d iscu ss the d e t a ils o f t h is ca s e , but I should be gla d to con sid er fu r t h e r any other p oin t s which may be r a is e d * By reason o f our exp er im en tal work and i t s im p lie s t lo n s , I have been rauish more in t e r e s t e d in such cases than c lin ic ia n s in ge n e r al would b e , and m oreover , I am gr e a t ly d ist u r b ed by the in cr e a s in g r e lia n ce on ce r t a in la b o r a t o r y d a t a , the s ig n ifica n ce o f which ar e not ad equ ately a p p r eciated by cur c lin ic a l colle a gu e s* , I should a ls o be gla d i f you would send us the a liq u o t o f the sample you have a n a lyse d . We w ill an alyze i t s p e ct r o gr a p h ica ily and by the d ith izon e method* In cid e n t a lly we w ill be gla d t o determine the lead* cop p er , aluminum a n d ' s ilv e r q u a n t it a t iv e ly , and bismuth as w e ll i f i t Is found to be p r esen t under our co n d it io n s o f combustion. Co r d ia lly you r s, RAKji s Rob er t' A* Kehoe, 1 ,D.