Document jgK5b0eDGXp4j8LR1xbgO9EVk

Lead Absorption Serene Lead Poloaning by T'obert A, dehoe, H, l# Tron she scattering Laboratory of Anrlimt dhysiolopy in the Rollera of 'oaiclne of the Univr;iity of Cincinnati. Oospite the availability of ao.ind and `ell cot relished methods for recall ting and preventing danctrous oocupfttlonal load exposure, the**# lo a till an unnecessarily vir*h .incident*# of lead poisoning industrial verb**. Moreover, despite the aalatonee of generally reliable J0 ' diagnostic oritrin* a aurpriainr? defrrea of confusion and / uncertainty often enter* into the consicrnniton of n nuopeetea oaae of plufibiaa whether the mtaetion t loaue la the proper oo.ro of a aids sms* the hyglaslo atetos of a plant, the rrrnt- lag of o rr.^neat ion, or the outcome of litigation* "or the ns i rm.iona one nay. be Justified in restating certain f'-ete \-r!.ch aeea to r'-'i'itre^enphaeit, .no a boo'igro--nd for a p**rxtleal (ilMttiaioo of certain methods of ^roce&ura nnd their significance In industrial hygiene, -'.be Char-ot^r rnd iifyilfloanee of *?or~ni VI V:-_.. It v'ouid seas* olaont & platitude now to state, ns mb Mom criticism! for doing in X'jn-*, tlmt *the presence, of lead in human excreta and harms tissues, ns well - a in living organism in general*. la nn inevitable consequence ->f life on n lead--bearing planet*, without citing the extensive evidence In support of this otatoeirnt* therefore* let ust -avlcv the facte in ao far ?.= they concern the averare normal healthy Anerlosn adult* lln Incest* with his daily food and drink Quantities of leod varying front 0.0*3 ngra.* rarely* to somewhat nor*, than J?*3t f$3* occasionally* t!** aeon quantity over ti period of nonths being Approximately 0.33 regss* Ho takes Into hla body by Inhalation with the air he breathe* a assail and relatively Inaifplficant quantity* vhleh probably rarely orceeda 0.10 sws* per 24- hours* and of which only a portion- doubtless a variable but otherwise un predictable portion --* la retained by the respiratory jseabrtme* and eventually absorbed Into the tissues* the reminder being either exhaled or trapped. In the tipper respiratory tract an^ / eubmr-wmtly swallowed. (`The quantity absorbed 1st m snail as not to be apparent In prolonged studies in which the total l<r*d output la balanced against lead intake by ingestion only. Con sidering the prorrttnees and the eagnitud* of essoretory response under oondltt--c. of oooupatlonal lead absorption fron lnhftlntlo one coy conclude that under averrro noron.1 conditions this type of lead absorption la indeed minute.) Little inreated lead is. actually absorbed into the body. A vary large pro artIon of it traverses the aklstentary tr-'Ct unabsorbed find, arrowr* in the feces. Cone portion Is absorbed and carried to the liver* is partly excrete*! with the bl.le bsclc into the alltwntnry tract* and 13 soon lost fron the body with the f^eu. The result of * I-* (3ltie 1 ) *3 1' db J Slid# 7 * '/3 ' 3 these And perhaps other avenues of, secretion into the t< 71 alimentary treat is to nake' the daily feoal lead output almost equivalent to the total, Intake by Location. '' "Joss# eaaii quantity escapee rcrsov&l by the liver sad Xe carried in the bled fron which It la loot bath to the'tissue* and to the excretion*. scent observet lone would. ieH to oho*# thnt the blood l in . equlXlbrioHi with the ttsaufe* 'of the body- an a with rsspeot to Its load content. In any ones lend is constantly found In the blood and in the urine in cucntitiee subject to but ainor vnriet Ion*' ^hua the whole blood of normal healthy awric&n adults usually coots ins froei -<!f*bl '<* to 0.05 sa per loo %mum9 with a .-seen value of ap^rcxinas^y 0.03 nf per ino r?rmi. (Cnneentrntions as high oa 0.0? n?*s per 100 fprcms are occasionally found). V*ry little .of this is In the plasm* 25 per cent or wore being? found In the cello, noisily* /preq^?sably0 in the erythrocytes, head 1.-3 found norrs.nlly in the urine in quantities varying fro 0.01 nqn / to 0*011 njys per liter vith a assn value slightly in excess of 0*03 nsn per liter. The ese&a urinary lend aancerr&rr.tlnn a? bo s area to npp rends*te one tenth of that' in the blood* lord la the tissue# IhtHUlatrlbuted in canoe^n with a definite partem* with the stator portion in the skeleton and'with a 'Higher concen tration In such lonq bene* ns the fcuur* ut with aensurtAble and fairly constant quantities in the other tissues awmq which the liver* kidney* spleen and brain are specially noteworthy. The average grosa quantity Of lead present in the body of the nnrml hamn adult is sonwhat In doubt* because of the scarcity of data* but it is probably not loan than 100 sir. nor wore than three to four time# this quantity* with due ref^ard to variation# 01 678 ~4- la body weight. Barth believed hi# data on the skeletal lead content pointed to a progressive increase in the consent; rati one with age, but the difference# In youth and old age were too alight and too irregular to be convincing* Calvary has drawn the unwarranted conclusion that Tonpaett*8 results on the lead concentration in various parte of the human skeleton (Bootland) demonstrate a progressive accumulation throu^out human life* There ia admittedly a statistically atgolfleant degree of positive correlation between the ages and the lead concentrat ions in the femur and the tibia of Tompsett** cases* hvt there are almost as large variations within narrow age groups as can be found in relation to extremes of age* Moreover* Calvary* 11 assumption that the tissues of persons with significant occupational or incidental lead exposure shortly before death has not been in- * eluded in these analyses Is Justified neither by To;ipsotta statements nor his data. One may properly suspect* therefore* that variable environmental factors (dietary and otherwise)* with variable individual lend intake* serve better to explain differences between normal individuals with respect to the lead 's content of their bodies* than can the variability in the duration of an essentially common and constant lead intake* The indirect evidence against the indefinitely progressive accumulation of lead in the tissues of parsons exposed to fairly constant en vironmental conditions ia much too great to be ignored. ifes n 1 h79 It lias been demonstrated clearly that the urinary lead excretion of individual* and of groups of persona varies with the magnitude of their current lead absorption, and that an abrupt change in the level of lead Intake results in a (31'do 10) fairly prompt excretory response, decent observations show { " 11) that this response to a known and constant magnitude of increased lead intake is not immediately anxiawl, but that it gradually builds up to a level which is dependent primarily upon the quantity of lead which has been absorbed and retained in the body. Within the Units which have been studied it does not continue indefinitely to inorcaae but reaches a level which is maintained so long m the lead intake remains at a constant level. These facta are In complete harmony with the information (dilde 12 ) obtained on groups of workmen with prolonged exposure to fairly constant nnd srr'&rently safe occupational conditions. The urinary lead excretion of representative workmen clearly defines the magnitude of the lead exposure not only of ah Industry as a whole, but of characteristic and well isolated occupational groups within the industry. Moreover, the group levels of urinary load (Jlide 13) excretion deMk increase progressively but remain substantial)7 " lh) constant over long periods of"tine (years) during which little or no change occurs in plant conditions. Such observations combined with the facts obtained in the ntudy of nim?le Individuals can hardly be explained 0x0ept on the basis that the rate of urinary lead excretion la determined chiefly by the gross lead content of the body as an organic whole, and that the maintenance of a constant or nearly constant rateof urinary lead excretion la evidence of tm /AA essential''.;/ constant quantity of lor, i. in the body, There la *d*euat# factual baofcprround, therefore, for the concept that V within certain limits of load intake, a atat dynamic equilibrium la mlnt&ined within the h-^aisn body hereby lend Intake and output are balanced over loni? periods of S1 : , and proj-preseive aecuem- Intion in the tissues doea not occur. The i&potanee of the consideration* outlined in ao* detail in the fors-fttinej paragraphs cannot be overemphasised in their relation to the problems of nubile and industrial hygiene that arise from the use of lead ooenoonds, ^ince lead is an inevitable constituent of hoeurn tissues and excretion** iyia quite obvious that there are certain norsinl and physiological mechanisms into which this el**ent enter whether incidentally * or usefully* there orm be no doubt lead can be introduced into the h nan >-<kty/without prejudice to the normal health and dv*-lo ent of the orgsm a, and that a toxic effect on the part of this element as well aa of raany-other* la a matter of c,on-- centratius* The dcfsree of control of ; ublic And industrial lead osinsure vhlob is necessary ":o ovoid. b non hagard, thr'^rfr^"* not to be d*4UHaaained on th bneia -.if the praqmila avoidance of the warst effects of th* absorption of mt Intrinsically ntnoocuc element, but on precise information ns to the li/.Sta of load ex posure and absorjition vMeh are unattended by any toxic manifes tation*, or, which, in other verds* ore physiological, The dyidefiflce of itocunatlonal head Absorption. , The evleteno* of occupational lend exposure can usually be recognised by a surrey of the miter id* and activities in an industrial plant, '`.'lie rrener?^! order of magnitude ni po1 U I OO i of tho axraj sure erm ho octirsrtert by ih defnrssinntiori of the lead content of the ntjaoophere of work in." spree** by t!\e ue of net hods which liare beers on well described and are no entlsfafitwry for their purpose that they need -not bo rlrr*n .oo^e than pans ins: mention here, out raaet esaphasise the fact that throurh their adequate and consistent isc, it la yo9 -ibis to det-rmine the' decree of the occupational !ta.s*rd and the extent of the need for preventive ami precautionary neaouma. Indeed if the lend content of the atmepfccre of verkroon* in the lead trade generally *? maintained within. the Halta now "eoo?~ni& ns eo?* in practice* ooctroi t ioncl saturnine* fro any othrr than Occident *.n Innt operation* would coarse to occur, However* so lomr ao the hsasar a of raany plants are 'not under ouch control, end no lonf? a* opportunities for coetdsntnl and. Lnadvortcnt lend Trcap.src oxlnt in industry* It vill be neoestmr* to provide redical rm-'prvln ion . hich will he on the alert for the rnrlloat rjlpms ofotentlol ;/ damper- ua Xc j h I nbaorpti :>nm/ fh phy-nio topical /i-cncoo .`f lead und^rnto > -*x>w this normal level eftou".d P *~i 41 m 5 va irscopniffcd.. f not *yn la* cuiat auoh evidence do not necessarily nifraify exist Inrr nr '^pondlrwt lead intoxication, !end absorption i.i not rsynohoomto wl load ciooninr, fhe absorption and excretion of puan title* of considerably In excess of the usual and nornal levels la wholly compatible with nonanl end hoaithy human life and Activity* anti if oertnln limits are not exceeded* no intoxication In to he antlei* . cited. ^ .'-j I 0 D6 ; i > The earliest sign of elevated lead absorption* end one vhich fortunately# 5.3 specific for lead alone# is found in an increased rate of urinary load exorot ion. The deeionatra? ion of a small irarMas requires careful procedures for the collect ion ' of omapleo and saaft detailed knowledge of the phyaiolarlcal factors concerned with the urinary erorction of lead* Various published statements fcav* ap: eared to the offset thatjjbs urinary le&d fail* frequently to reveal the extent of lesad absorption, that the moult* obtained on urine sample* are too variable and that the blood# rare constant ea to its lead content# should bo used for ah twining analytical information* These mmVmXom here sprang fro.a Inexperience or frota the use of inadequate methods for the collection and gfinlysis of sample*# 3te 1* true that urinary sample* of small volun* obtained at random arc subject to onnni.lemble varl-'vticm in their lead content* In individual eas4# the latter varies chiefly with the voter output of the period of t&oir collection# i*o* if the urin Is concentrated the lead cored*.* tration Is relatively hiqh # if dilute from hi^h water iota be or <Huresia the lead ooncentrrtlon in relatively low* This fno tor can he cent railed.. in the ones of assail volumes# by p"o-^r aaiaatio? of the time of sampling so oa 'to avoid extreme of uwter into ate . end output | it can be eliminated altogether by oollretinri several lit are of urine# rsahin** aure that no unusual quantities of liquid are taiten to speed up the collection of the ssusple* 'Equally iryortant is the avoidance of contamination of urinary aa-r'les# and the motUer t!se sample the frrenter must be the cafe in this raapeot, Heine sables collected in the-usual types of vashreoae or medical quarter* in manuffteturinr? plants# or obtained by oustooary capital procedure# or# in -fast* aocured by any other than by precis jo ioo controlled by the X^ier# ,a.r not only valueless taut grossly nlalCAditi# to their lead content* Lead In ubiquitous# on& It ia difficult under the Most favorable cir cumstance to avoid all source of oont&M nation, llumerous case report in current journals include analytical data oa the urine which by faero Inspection can bo discarded a erroneous, la eoas instances the quantities found bear no relation to the ooruiltion* -jf exeura tnwm or believed to have existed# and in other they are entirely beyond the imj&ml llraita of urinary lead escretion. In this connoetlon it should bo pointed out that a urinary lead concentration .in xceoa of 0*5 ***>>* per liter 1 a vary great rarity# that oonssatrati-ans Mghsr than 0.3 sga per liter are associated arsly with gronnly dangerous condition of lead exposure and absorption# wi4le Values esoesdlnf* 0*00 e per lit or cannot oorur without a definite and fil^nlfleant a^oaaro to lm& such a is a.iooiatftd with the admittedly hazardous lead trade. Prolons^el oxcretorj/ rot in t-ie tir rna is not always feasible, l?or*ov*r# per day. Tor comparative purposes# therefore# analytical result should alv&ya be o.rpres.-usd in **ni8 o* concents?;Ion, and* If possible* 3ii a tl:" basis as veV, The greater atsbuny of the bio a* with respect to its load concentretIon* from hour to hour* as ooip#r*d to the urine* is unquestioned* On the other hand the ehmirs in the blood concentration a* a rsaponas to lead absorption Is proportionately leas than that of the urine* the result being that the effects of exposure are more eeatly dectonstrusted by the urinary Xmd concentration than by that of the blood* The ehisf advantage of the analysis of the blood* for di&gnoctlo purposes* lies in the foot that it requires no nanlpnlation on the part of the person exasained. If proper precautiona nr c token .by the examiner* therefore* no factor of contamination need be on* aldered* Blood staple** however* must be s*sfcen vith the utmost precaution in a d*i*it-re raoa* by men# of specially fabricated needles* into specially cleaned containers* The ainotset detail# of haadl ing ere of the same Importance* though of different type* as those used In the maintenance of aseptic technique in surgery, hand* lihe minute living orgi^nioas* enter# into anaplse through the air and by r.cana of oantn.ot with any nave the -ant mticulously * ***> purified water* recreate, fjlassware and otb^r aouluajnt, *he significance of the feoal load content in relation to lead espocure- and. absorption lias been ably presented elaewhrre and need .not be dlaeuaned hare* other signs of load absorption above normal .level# are CD changr# in the -quantity and distribution of baoophUle material yrithin the erythrocyte*# and (2) the appearance of punctate deposits of load sulphide In certain mucus rsenbr- nos* especially in the uargin of the gua tissue, Neither of then# airna* contrary IX to opinion* and vrrltton sentenant* of aany, la indicative of lead Intoxication* Both occur In: entirely healthy persons, except that the lead 11 .' does not appear without bacterial iwraeio* of the gingival tissues, 1** done decree of gingivitis Is nee*soar; for its develercwnt* Punctata basophilic, or "stippling* of the erythrocytic, within certain 11 "ita* la of normal occurrence in the hussar* h o-ud* In exaninlnu the blood of soae thousands of apiJorently norsal healthy adults free of oceopettonal lead exposure, vie hAV*> found *naoh srythrosyte* la fiunbers ranging froo one or two up to as high an air thousand per million erythrocytes* hope 6 per cent >f the group showed one thousand or vors per million crythreoytes, while the neon figure for persona m 3T2.1S 2*72 Pr still ion erythrocytes* She masher of such stir-pled erythrocytic In tube blood shone little or no change with qftii ) irerersonts of increased lead inta&s, hut at higher levels of 7 exposure and absorption their liussber In the circulating blood tends to Increase* Considerable variation In the degree of - individual response is observed, and fairly wide variations occur frx-i day to day, but- with inorepeingly severe oondltlone of lead exposure there is a definite trend toward inorecsing n'aabere of stippled erythrocytes in the blood of exceed worteaen, if cor;*. narioone ore b -aed on growpe rather than individual reactions* These facte are responsible both for the ueefulneee of regular sioroscovio extinctions of the blood of worteBon as a ncane of set luting the eignl? loanee of their occupational lead oX!>oeure* and for the inadequacies of such neaearce for diagnostie purposes in indivldTjal cases* -Hxffioe -imi nu a! Ds ots)- 12 It* in this necessarily limited discussion, to point out, that hazardous exposure to lead oosipdunds is associated with the appearance of definitely abnormal numbers of basophilic erythrocytes in the blood of a considerable proportion of exposed workmen, while the absence of suoh erythrocytes in a suspected or alleged case of lead poisoning, during the period of active intoxication, is very nearly conclusive evidence that the toxemia is due to some factor other than lead. A "lead line" may appear in gum margins which are somewhat inflammed by bacterial invasion whenever the lead content of the involved tissues la sufficiently elevated. We have observed the appearance of a faint blue line in an infeoted gum pocket in one person whose blood contained lead to the extent of 0.05 mga per 100 grams. Thre is little doubt s that easily identified lead lines signify somewhat hitler levels of lead absorption, nevertheless obvious deposits of lead sulphide are seen in the gums of persons withnodemonstrable symptoms or signs of intoxication. They must be differentiated from similar deposits resulting from the precipitation ofs other metalllo sulphides, notably of bismuth, and they must not be confused with the normal pigment of negroes and correspondingly dark-skinned peoples. The former differentiation la sometimes provided by the medical history of the person inquestion, but may require analyses of the blood or urine or both; the latter oan usually be made by careful study of the locus and appearance of the pigment. The natural pigment is rarely, if ever, found in the gum tissue on the lingual side, while, despite the scant attention given the fact by clinicians in general, a favored site for the first appearance of lead line is in the extreme lingual edge of the - 13 - Sun opposite the bicuspids and lower molars. The bluishpurple line of gingival congestion may be taken for lead line by the inexperienced, and especially if no examination is made after expression of the blood by means of a transparent applica tor (such as a glass slide). More commonly, the stained or discolored surface of a tooth Just visible beneath a thin layer of gum tissue is called a lead line. The differentiation is not always easy and resort must sometimes be had to the use Of a hand lens, or even to biopsy followed by aloroohemical or better by spectrographic analysis. The Recognition of Dangerous Lead Bypoaure Time does not permit a useful or adequate description of the symptoms and clinical signs of toxic lead absorption, nor is it ay-purpose to do more than to stress the necessity for basing the recognition of such absorption on the actual occurrence of illness which is compatible with the known clinical pioture of saturnism, or upon sequellae which can at least be attributed plausibly to the effects of such absorption. It will be objected thatrthis point of view leaves the matter to the judgment of the clinician and takes it out of the realm of conclusions which can be reached by methods and instruments of scientific preoiaion. One can only answer this objection by reminding the properly enthusiastic proponents of laboratory methods in industrial hygiene, that their most significant function is to chart the conditions under which illness ia likely to develop and to point the way for the identification of such conditions. The demonstration of signs of lead absorption above the normal level constitutes a useful exercise of this function. The actual 01688 - 14 - recognition and identification of illness is a function largely and logically reserved to the physician* One may confidently anticipate that the further correlation of the signs of load absorption with detailed clinical data on the types of toxic response and their frequencies of occurrence, will delineate dangerous lead exposure in quantitative terras oo explicit as to compel Its recognition and elimination. /