Document YDw744GQRDdzx9x8KNp2KgwxK

ADDRESS THE SURGEON GENERAL U. S. PUBLIC HEALTH SERVICE Industrial Hygiene Division FEDERAL SECURITY AGENCY U. S. PUBLIC HEALTH SERVICE WASHINGTON 25, D. C. (Bethesda Station) September l6, 1946 Dr* Robert A* Kehoe Kettering Laboratory of Applied Physiology University of Cincinnati Cincinnati 19, Ohio Dear Dr. Kehoe; As you are acting as summarizer and principal discusser of the papers presented at the Conference on Lead Poisoning in Boston on September 30* 19^. Ur* Carl Peterson has requested that copies of the papers to be presented be forwarded to you* I am, accordirgly sending you a copy of the short dis cussion of analytical methods which I am presenting* Sincerely yours. LZPimrk Enel. Lawrence T* Pairhall Senior Scientist (R) Chief, Chemical Section N22124 AftAT.'mgAl, BKgHQflfl x h MAflaOSIS x* s. fMun Xa&iatrial fyglfio* &Uiiaa Uitd st*w* Public Health Service N22124.01 X* 1o net ay pupooo at this aootiag to proooat ony anr aotood of load analysis of any nov preoadurs for too dstsmlaatioa and AotoeUoa of load la biological oubstaaosa, tut rathor to dlooooo eortala pfcaaoo of too analytical preblom toiob aro proooatad Inevitably by too typo of aatorlal being aaaSyood for load* la too courso of too laot ^aortor of a cantor/, to alnoat andlssa tarlaty f mtoodo for load dotoOa*tion with rofarones to too gsasral problm of load poisoning baa too* dotrolcpod sad tola rosy boaltoy atato of affaira baa dona mob to clarify may of too obaoora problem of load poisoning, Xt to portwpo totoer unfortunate toat ta amoral too toadoncy boo bom to osyhast so oaoo of axooatloa ratbor too* aoaar*uay of emoutioa, otto rsforoaoe to toooo aotooda and, to ajr Bind, tola baa boon a detrlmat ratoor toan * holy, too mist dl fttooltart of oeurao, la too analysis of load la body fluid* and tissues bat bom too groat disparity botwoaa too htif miasial analysed and too manta aaonat of subataaoa anutis* toon it lo realised toat too dotoaat&atloa frequently molrpi around a mttor of ailUoatoa of a graa la 1,000 or 2,000 gram of fluid or oubstaaoe Soroato Anneal Ooaforoaoo on Industrial Health boston ~ Saptaaber 30, 1?M> -Kt'os! 2 &d that %h* total w&sxt of othsr Io o t s &r Io coastUuaaU *eooB&aorlftff load la such aaterlal any aaont to 50 or 100 gruas* it in obriotn thtt tha segMoratlea and tjoaotttatlT# soalaatloa of thsso sxtrsmsly aiaaie aoiiai* f load 1 ssosadii^&jr diffloolt* Hsvorsr, tha protlaa la fttjrthar eosplieatad ty the fast that la addition to mr* balk of iMwa^tfogrtac Mittkaou. load la also aMcnM&ioi hr aaall aiwata of athar Mtnli sfaish art potsatially difficult to sopcjrat* Trxm load. It 1 iodead fortos&ti that iha itttitidMi fttiAwwi ti>< *winw>iy k&MA aa dltblsaoit waa brought la light sovsral /oars ago and that th# stagola? prapartiaa of this sutattaaos with raspsot to oaagr natal* m s o tterou^bly iomttgatod by fisbor* Kith tha aid of thia sobataaos, it is pasaibls to Mparato load <|uaUtAtlT02/9 ovsa theu^t it Is prassot la nxtramly aaall awutf fJros a yasgr largo aaouat of Material* It t* ima that a waftor of other atitiMM ere itadlafly separated, tat tho operation of thaso ffen load is sat too difficult a protlon* It is uafortunet*,, hoverer, that so much attoatioa has boas derated to tha further or final evaluation of load by maos of this reagent rather than to tho effeoUvsass* with 4<^ o^43 3 vklea lead l Mjvofetod from etfear wrtula m dtaortbad above* Ada la w&rataadablft baeaaflo ea extroaoly m&ll aaouat of load, glvaa a pro* aooaoad aai very dp ooior under certain eaa&ltiQiu vitb thie reagent and tbe facility vlte vMch ocdexiaetrl* fletoiedaattotte art carried out la gewwral *$ ouab a procedure estraoely iaviUi^. 9a that and, long and ulsborete procedure* have bean adapted la ardor to alslaimi tfce effaota of Interfering aabateaooe vltiwait too greatly affecting the precise evaluation of leed lteolf* 3&ia bring* vp a point which I fceul& sov XUca to dlaous* nor* in detail* the oudytteal ohie&et is confronted la 11a liberate*? voile vlth Aiwxifii af ooiittticfiB iMUirLie tha ^rftAtiiit Doit a&j I of ncalsNi* l&tlon* i^secUflatl? this rMulni & m&t deal of tine >& * muiui. earaettng attention to datall tfalafo la olaoot uai<2u*, Xn tilde toaiw, eeah MuOyeU ffpjraaoata a teobalaal Mtol*rmm% of fcii ardar and the latent* goat ***lyt usually aeeka neea* to shorten the ar&wea labor Uorolrod la tfc# vorloua etepa of owdyaia by ahorl^'^lroidUag anefe etepa la mob a wgr tfc&t neodlaa* labor Is avoided* It la tfcla foot largely that 1 renpo&elble 4 for the development of "new* methods of naelyeia. JU the Med for by passing needles* work has grown, particularly in the indastrlol field, tofcalogiot& advances have kept pace with the chemist end instruments have teen developed which greatly simplify hit work and perhaps prodsc# a great increase in output* M the same tine, many of these instruments have permitted him to evaluate quantities of mbstanoes so small as to ho undreamed of at an earlier day* Vie, for Instance, have the quarts rtcro-balaMMi, the spectrograph and the Oeiger counter whloh respond to the presence of very small amounts of saterial indeed* Ouch instruments are of the greatest utility and have tended not only to extend the field of activity of the analyst hut, in many oases, to extend accuracy of observation* Xt ilk u * fortunate, however, that with the acquired facility of operation end the widening horisan of application, cu well as the extreme sensitivity of each instruments, there is a tendency on the part of many to shortcircuit operations without too dose an attest to find whether each shart-outs ere validt to substitute, la other words, for the Ko S64B 5 kaowa dellooqy of tbs lnstruswat working under the beat of oandltloaet the application of the iantraaent to procedures of uncertain Mwanwy* It is sistple to do thlo end to shift the responsibility frws the catalyst to the instrument, hut ho knows procedure can he carried very far without the analyst'* ummiag responsibility* She feet that an laatrrment of exeat delicacy and carter proper circoast&aoes of aoearmcy it aaed, does act la itaslf effect the true eolation of aa analytical problem* the analyst met etill accept refpoaeiW.iltjr and the degree to abide thie refpoasibility 1* iapwrtaat rents* of coarse, upon the nature of hie prutolaa* &a an instance of thie* X oaa cite the appliestic* of the apeotrograph and the pelaragraph to the determination of lead ia biological sobataaces* 4hout SO year* ago refineamts began to appear JLa the quart* spectre* graph which greatly facilitated ita uee aad exteaded it* image ia the field of analytical obeaUtry, and quantitative applications of the spectrograph mere rapidly developed* Shi* has been facilitated by several mean** perhaps the simplest of which ie the aaqperlaoa of the densities of a siraa lino at various concentrations with refereaoe to the deadly <lD?4b of a oonparison oubstanos In Vaaowa concentration* sen? modifications of fVKuh procedure lw Ik w b l&tvoduMd| 4ip&diBg on tha uttot of ths notarial for analysis* While at firstspproaoh this soon* to Vo a nethod of solution of sway analytical problens and indeed is of ths greatest i*w portanee to nosy analytical problems, ther# are phases of this prooaduro whioh have natural Xinltattoos* are spectrun, for instones, is In general aost suitable and aost sensitive for neny application* of ths spectrcujraph hut thors are factors, which, whan oloaaly investigated, indioata that frequently there ar difficulties in securing tree ene* lytieal values* She are itsolf is not ths sisals thing that it first appears to ho* Xber# ar gradations of tesperatux* varying fron ths positive to tho negative eleotrode and as a natal holla off, thsrs art variations with tins in ths aawvnt of natal at various points between ths electrodes* it ths tesperatur* of ths arc, iddcfe is around ft700eC, all tha substances In ths are are parti/ ionised and, duo to tha electrical field, theos ions wander la ths gas ooltam* She nstal tons sdgrnto to ths cathode and axe neutralised there, diffusing away ns vapor* She result J* is & aunaentratiGu of nautral siatel p-torw* end ions oanoontrated In & thin lsyer Juat above the cathode, Sldo cathode layer effect is ne*t notable uhen &aiHl mounta of subatanoos arc Yaporisod in the area 2l*o types of Haas uaitted ^ their Intensities ore also affected ty the proumae of auuU easily locisable substances as codica chloride* It is apparent, therefore, that the direct current aro is far ora complex than it is customarily believed to he a&d that exacting quantitative work requires consider&tlon of these factors* However* in spite of the fc&own difficulties of explication of the epoctrctruph to tko doterixu*tioa of lead end perUap* In total disregard uf I have Heard of deUrainetiane mM of urinary lead vith a circle drop of urine* While this my he inpre&siY* to eons, it is to myoft* fsailiar with the field. Merely ridiculeue* la spite of the eeny difficulties attached to the application of the spectrograph to doter* juianfcions of this diameter, it is in the hands of the oonsoleations aanlyat, tin instrueeut of the very greatest utility, -An interesting nothod for the dsterulnation of lead is that of the dropping mrtsay electrode \hioh, v*ua first proposed for this purpose by Shik&ta, a JopeneBa student of Beyrovsky'a, about 1^J. She poXarogrsph utilising the dropping aercury electrode has been applied to tbs detersdnatica of paall eouat of a variety of substances In addition to lead for a nunber of years* Us application depends span tbs interpretation of ourreaWolUge carves obtains* daring electrolysis and it esploys a dropping oercuiy electrons in order to provide a fresh cathodic surface continuously* %y applying a snail and steadily inoreaeijg voltage, a point is reached corresponding to the deposition potential of the ion sought* M this point there is a sudden currant sorgo owing to Mm discharge of the ions at the o&thodn and dissolution of Mercury at tbs anode* She voltage at the onset of the current surge represents a Opposition potential characteristic of the ion* This current sorgo reaches a Halting value depending upon tbs ion oemneatratiaa, sad. tbs \ proportionality hetvssn the total rise and the oanoeatmtian of the desesltins ion is dstmdisd by ealihratlon ajsslnst kana standerda* Tha application of the polaroeraph to load analysis of body fluids It toritingly single end if ptm is content to acaept iastruBantal readings without farther checks, the analytical threoglfr'put of the instrunent 1 Iarea. With extrooe acre one otm, however, Obtain analytical values, say for lead In urine, cooparsble with those obtained V other neons* In order to attain the desired accuracy, however* great earn nuet be used In the purification of nerctuy and reagents, the calibration of the tnetxuBent* and the interpretation of results, m veil aa to the constancy of salt content and acidity of the solutions analysed* Organic aatarial met be absent* loctracrdioaxy precaution met be tahen to re neve oxygen front the nitrogen gee need no * bubbler to sweep oxygen fro* the cell preceding electrolysis, X motion this Uttar since the iapreeeien ajpeara to be scnewhat prevalent that eoamrcinl nitrogen 1* suffiolently pure far this purpose* In fact the accurate deterolnatian of urinary lead with this instrunent is nor* or leas of a reseerch 4ob end is es tlro-eGnsnaisg that it presents no advantage* to the routine analyst whose interest Ilea beyond a quick value of any sort* He odcrlnetrlc detentlsatlcn of lead by n^irm of dlthlsom hoe 10 partep* rooalvad sort sttanUc* la raoaat year* than alsost uqr otter sotted, It 1m tea tea advanta^a of rapidity fcfid Whara tte aacuata of lead, guffidantly larga, and la tte absanoa of intarfarlsg eubstanoaa. It la vary usaful for this purpose, tea principle difficulties teat u encounter* for tte detaaainatioa of slant# asouat* of land ora first of oil tea prsaanoa of certain otter natal# end tte tendency of dithison# to aal&lae and give a eltghtly adored eolation with certain oxidative eubetsaoee, tel* beocsa* particularly pertinent la tea dstersdnatte of blood load tear# on estinetion la usually recorded la terse of 3 or U sleregrsBe of load la a 10 gras aaapla of Hood* tell# lead la unquaaticxmbly present In tte blood atreaa la axtxaaoly adnata naouats* It 1# doubtful If It la present to tte extant teat a nusber of individuals hav# postulated as a raault of aeasttraasnts of thla typo* Bo far a# X as swart, outside of oar laboratory, no oaa baa takas tea troubl* to oospare tte analytical values for tea usual 10 grass of blood with a luffldeatly largo tjwntity of tea bo s s blood to fix lnoonteatibly tte value for norsal load* Instead, repeated *detrslnatlana" of load soda upon 10 gras u Masqat of blood have been uaed as the basis for fixing value* for blood load# it twy ba> aaid that theoe rsluo* hors been aubatun-Uatad V apaetro- graph!a, polarogrephle and elaotrelyiio Methods end that they all art ecnsiataot. It i only vhea ana attempts to asks a serious study of lead la these ooaoaatrationa of 3 or 4 aiarugrmg par staple of blood and ia coafroatodt with the tedanlquee of imrasUgstlon, which art sufficiently * siaple, but with tha vagaries of the notarial sought, end readings attri butable to other footers, that ha Is like3y to revise his opinion. X regard aoet reported blood load values with oonsldaroble reserve and suggest that none tsrostlgntion be node of bleed with rafaraaoa to its lntrinaie land oantent. Certainly, it should not be difficult to test this V separating laad quantitatively firm one hundred tinea the usual mount used for analysis, if analyses eaa ba aada of 10 gran samples with aim Mpsat MAturaeor nlnlund fop this flash sMlrui >1# mmi. with pooled lots of huasn blood, ns we hears done, or anlnal blood can be ueed, ocapsrlson being nod# between 10 gran and 1 or 2 kHograx aaouate of the eawi blood. 12 X bring up this point because there hot been & certain tendency to have a blood lead doterolnRtlon n&de in suspected oases of lead poisoning and to rest the diagnosis on the analytical report as reoelved* In oases of this type, a child with an apparent high blood lead Is in the uaforttwete position of possible treatment for lead poisoning when diagnosis of disease of an infectious nature is difficult or obscure* , Xf blood load values are to be important in tho diagnosis of lead poisoning, further in vestigation should be node of thin subject in the Interest of scientific accuracy* X have referred to the {Enaction of blood lead soaewhat at length because the disparity noted vlth reference to the actual sacuat present under ordinary condition* introduces an uneoafortable sleneat In regard to data representing the anoints present in actual oases of lead poisoning* (hie further point X should refer to in connection vi.th chealoal data* fe the entcisnUfio sdad* powtive results frequently cany sore weight than lev or negative results, and the greater the values reported, the acre drtuaatio the effect* Perhaps it night be as veil If ve look behind &3S63 the comet sore ami itBdjr the source of teohatocl amrii It mb Id he unfortunate If ia the field of blodumietry we here e eltoatloa analogous to that referred to by 2* S* Snith la certain phases of ooaneree ia %&ioh profoatioaal aaeljrete tre alaoelfied m 'high* anelyetf rad "lev* analysts, the oellora favoring one claaa and the buyer* the ether* A yy erect deal of reepoasibillty ie attached to the deteniaatlea of lead a* a diagnostic aid in lead poisoning* Xastruneatsl readings ef the greatest oecnamoy are obtainable froa the aodem agjparettta available to the present day chaolst, hat the iastrtmat lteelf cannot eupply the tatelUgeaoo asooeeary for accurate analysis* She coadaet ef in analytical Operation should aateh ia acre the accuracy of the reading; to whioh the iastruaeat ie nuoeptible. Za other words* Urn ehmlgt hae a groat responsi bility ia aaslytiool work of this type* fbr eo very Much dipea&a *>< the ootooae of hie analysis* It Ie aot eoffioleat to follow a reotiae pro* oedure and to aeeuoe that* because he hae followed the Aireettaae word by word, that hie waalyUcel results mot he correct* A poor ohee&et nay obteia poor roenlts with a good preoedurei a oonpeteot oheadet oaa ebtala Ik fairly aoourato reaulta with an indifferent aathod, Shoao abeerrniiono *re offered, not in a critical apirit, but In order to focus attention on certain points that frequently arise with reference to analytical nathoda used aa diagnostic aids in oases of suapceted lead poisoning, A. largo aunher of lorestimator* have been and arc ssplorlag notch of this field, end froa their porssrrcranec and Toaourcofolnaoa it la to ho hoped that aany of the obacura chapters in load poisoning will hacoao nore corapletely clarified.