Document 71mBbpGMgDB8rpDOmvKm53pY6

CONFERENCE ON INORGANIC LEAD AMSTERDAM, NOVEMBER 1968 7fi fcl i To Y1<Y/ m ocl t f (c iff(ortS of Ttus /ria>\cscr( ^ f~~ `1> iZVithq i K W i Di )?{cWf 4y l\.heif~ f- Vu-I>| 1x50-0 a.h \Uel ~f (u& C o >| fpft Udf, a.. >\ A Oi fL c fr *.J,f f/njs kof Wn <N>*|>/f/V j o Uk ; 7X.S 77i< yfi'nj /-t .7tff 7 7 frUotfJ I K 0008092 SESSION I - BIOCHEMISTRY: Chairman: Professor Tiesinger De Bruin presented his paper and also mentioned some new findings. Discussion: it was suggested that the presence of reticulocytes ,, '-'zryTHr^cy was as good a measure of lead exposure as stipple4`^e4ie since f&e btte/ +a ron the increase in siip.jple4r~aells and lead exposure^wes parallel but-- reticulocytes increased first. This was countered by the ftc ? J i lUWnfrv? suggestion that reticulocytes were less specifi^Z-fer^lead^expasTTre- A z.XHtirocvTfi than punctate basophil! '-eeii-e. Several speakers said that because of the high variability both in response and in the method of measurement, reticulocyte counts were not an adequate ^ SudL PX'POS1 trj* & Turning to the correlation between various"^ enzyme ^haag^i*/4-t"was pointed out that the absence of a good correlation between the various tests,although expected^should not lead to the rejection of new findings. It was generally accepted that vitro/'experiments with erythrocytes) cannot beCdirectlyTcompared" J _------- - -- /V 4 t with (in vivo [findings^ (* dhtx^e/iLr Gajdos said that fur 24-hour} urine/'sampies, an increase In^/-aminolaevulinic acid greater than 20 mg/1, >f^r/coproporphyrin !l/ 400 ug/1, ef uroporphyrin slight increase or e/) -and-- /te>` : // jDl? y ft* !Hi testiOiO- cf ^ increase^protoporphyrin in'^erythrocytes^were specific --finrylead absorption. There was no general dissent from this statement, l \i\J Clo Couft'O,^ There was no K 0008-993 on whether all these tests were A  c ?fr0/ y 2 O'- Tlve ci ^f (esJ Il3Z/i necessary in'3'plant .a hr.cfdeB was left for later discussion. Because the use of chelating agents either prophylactically or as f>- \ a provocative diagnostic test altered the levels of coproporphyrins and other biological measurements, no reliance should be placed on them/**iU' <~ctiAi-2S.3'^~hA tC'TL yse j/f , .. ^ e.f tb'fw. ,?w ` Persistence of}raised-lprotoporphyrin in the erythrocytes t/i&covetmt, al(t_c t' t _ esthtSu x? Tijeiui/^ up to eight years after o>;poGU*epares(T.mp'ortant from a medico-legal an/ V ' r' ; ooint of view. Discussion then returned to what measures i Mt&Vt it" ) <* * ` ;;i flu css? of ft* /ivnuav? A*d(e3/,cu f Vvsk,tf^c.cuy>< , ,*s T%> *<!hSr -1t&- a'd_r*i3k. -It rw--a-s- s--u--g--g--e--s-tjedj -Uthq +a' t+>t,,h emnmsot.st1 mimnnpro't'r.taannt,tfa>nfa-tc-4nu>*rT-'OWecrs . , '' /,, ,, >f f 1 - - fr -- ..... __ ......... tr Tkttukh [ Or' - _ ' s.-fv .'hrt eyas 1 " --;-- -- -- - .......---1--- ' j ;s -.the attack on the red-eel^- This suggestion received support but was qualified by stating that the measurement would vary with the 1-tl tp, r-tvifv/?/ method used to determine survival time of rpri. -aells. Because of jj.j'yhi.Vo'" v the removal by the spleen of abnormal .red--eellg, the life cycle of these cells in the peripheral circulation was very short compared with normal cells. It was concluded that^in the absence of gross anaemia,the bone marrow was producing very large numbers of stippled cells and reticulocytes during increased'lead intake. Morphological changes,including mitochondrial swelling and vacuole formation in erythrocytes when seen under the electron microscope^were -nctbeU-^* L. 'v*- vUts ccHwachivo. It was alsp> mentioned that lead was found in high \*f 'fit- p concentration in thej^iver] mitochondria' a#t-e*=shpxdh3SpS3Hre lp 1 tl*'' (jStP&> tf S^ffruJa , rabbiti^ In answer to a question on the relationship between ' hJWsjJuJd-. J 0J the microsome and the mitochondria^it was said that lead wTas K known to affect mitochondria in the bone marrow, liver, and the 0008a94 -3 renal tubules. In the bone marrow, the effect of lead on i fc Ui'ki cU, f (if mitochondria was a primary one;assi-mitochondria were frequently ; <>r~ damaged. They do not take part in the formation of stippled Jtvwr/tT*<f C..f !j but^ribosomes do jtf in their formation. Lead is found in high concentrations in the ir-s^e-r khtio mitochondria of rabbits after a short expoettre-r ''The changes in '27 Vf the renal tubular mitochondria due to lead cuere similar to those seen in the bone marrow. A question on the effect of lead on mature red cells was not resolved. i if ziiMfcl .Vs- __ The practical significance of ALA dehydrase was^Limited, because it was easily inhibited by lead and there was very little jltJl .ft r KU difference between ^ mild and severe exposure -and dehydrase ^ ^L, ^ would not, therefore, have diagnostic value. L Y ci`- It v;as queried whether^a so-called normal levelbwas--ajrrgady all).ei^ttsy--normal asiblent--3read~legsjrgy It was stated that h ^ Vce^' p-hyaroxyindolacetic acid was rai'sed 60* in^vhole blood of exposed subjects^ compared with controls 'When exposed to 0.3 - 0.4 mg./fT Pb,. (lit values rose from 10 ug/1 to 16 ug/1 in whole blood. Kernberg, commenting on his paper, was not able to explain the relationship between ATPase and potassium ion efflux from red cells, but he norfulened that different storage conditions in tracer experiments gave different results on the rate of potassium influx and efflux. If potassium loss is high in vivo. / the cell will die and be removed from the circulation. The importance of SH groups in relation to the effects 0008995 4 of lead on enzyme systems was mentioned .but it was said that not only SH dependant enzymes were affected by lead. It was noted fyi* L cf hj, V iivvyj 'K SDTA^in w^-vird experiments^would prevent the effect of lead on SH grouos. W/W ' t=*saa=heirrcueried=w,hat concentration of lead hasr- / ilu y iUv&j ic -{ *f SvclpnjzePfvj -fo bean-added: in these experiments and wars - t-hi s~lev-el__relevai--tp -*-kst j?? "X'i fvj&ulfr the level's Tff~numan blood in industrial exposure, In rfeply, it -1 7 ^7^ was stated that 10 raoles/gram of lead had been used.and this I Of $6 wuret-o ^ P't-'y'' ? cc` was about IpO times the concentration reppesentedaJay-a--blVed-~t&ad of--SOuJ?! y ^ s cj 41 q -U Jp /vc cl t It v;as noted that Westerman had found similar P/ .eu#v3it, -H* hind cr\i Hind M? :oncentrations in the rmarrovjA^SroTaod-lead levels nf^JP.Du^. f 7\ I** <-< * Albahary, presenting his paper, said that there was little departure from the normal types of haemoglobin in saturnism and that this fact was imoortant in Mediterranean countries because Ita- :he differential diagnosis from t'halassaemia .when^foetal type . o c c v j v <? c .V hi iU^w. CcwSiH Tvvttcc was-high. Lead ctees causes some variation in foetal type -/ haemoglobin/but only In children up to six years' of age. In adults, an increase in 4.foetal type4 haemoglobin -wildr tih cay'~occuc?jin severe cases of lead poisoning. In lead poisoning, HbA^ varies linearly with haemoglobin^ and although the mechanism Was not well understood in plumbism, there is a reduction inyg chain and an increase in o( chain. K- 0008996 - 5- SESSION II - CONCEPTS OP LEAD INTOXICATION Chairman: Professor R.Lane Lehnert introduced his naper and suggested that: fk r, ft CT 1. Lead poisoning is not necessarily directly related to/afesorption or dose, ZfltboCfL A&sz vw.ds/' aje&jv'f? ' VaCi 3 f~t o>i s rfso/ts . j, There are wide di sorepanei-as. irylaboratory tests \ zA(A 3 hw, 0\i\cxTOii^/r y/ u (Ae di s c.re j^vuc-tes, v y v fk v(softs refnTed. Ay f&k&i-gYbriesr j. On first exposure, men may exhibit mild symptoms which then resolve , A. There is an increase^^sensitivity to lead after a,ipeteagaae't epi sode .<f k i i v,t > Asked for experimental evidence to support the cybernetic approach, the speaker replied that it was largely hypothetical but that the^ facts may be understood by such an approach. It is eXc^lf ar T!i? Inoiniit'iti TtreshfU ef r?sj>t*e, difficult to fix TLVs because the organism is capable of accepting certain doses without clinical manifestations. Feed-back mechanisms, when the body reserves are depleted, will lead to functional loss increasing with absorption. lo/v cei f d rht / Kehoe objected to thej^pparentTabsence of any_dose/response 7^< e<sri<3bi/i'lf <? relationship. Lehnert replied that this was due touthe sensitivity ukwici o'y/r <?*! in 7 (it. < /kd,i/- goals' I'lideY -vari-atlons,, but went on to say that what he meant to stress was that\M-gh absorption^'dld not equal poisoning. Attention was drawn to the differences between acute and chronic poisoning. Many animal experiments were of an acute nature,and there was a tendency to draw general conclusions from these. The speaker.agreedwas easier to predict the effects h !9jl il L-foloU'yid of an ae-wt-e^ dosage than long-term low dosageybecause at low 00089a? -o t> L 11* !k ib dosage rates there is no ^increase in^iccd" concentration^,'du--to--a n ioaxance-mtchaasi-sja. brief: ,, H Vr-s P Comment was made on the different effects of .high^-acute- fybltM?d exposure such as shipbreaking, and the slow, chronic effects in battery workers. if ifYiof Some found Lehnert's paper difficult to ' I rT rKechi /3 </'<//_ anderstand/but it was thought that thepapproach w;as jf useful and general -one- to all types of poisoning. Cramer had plans to study <S-arainolaevulinic acid in urine to answer the question whether this index was of greater sq s-?/ey value for- ae-wte exposure and whether urinary ALA values increased more rapidly in such circumstances than did blood lead levels. Williams and Zielhuis then presented theirr-paper. In * r ryc-isf/t/ ; comment, 'Williams said that we cannot measure lead absorotion ./and < we should use this 'word more carefully. What is an unacceptable response? What matters in regard to fixing this level is the i it * effect on the motor system or sense data, not biochemical effects. V_i{ocorcLy^ fc EftM itO\fS' ; The word ' poisoning^should be reserved for its major clinical g i f&fh'CY ~t(<3k . the>s% uiluck p no merf -rt^. b> ` In response to Williams' statement that lead absorption could not be measured directly, Cramer stated that he found this paper confusing and of little help. He considered that absorption can be measured indirectly with blood lead. The real issue was the definition of poisoning, and he would agree with the authors vo'a.su <( e\ if they would add^"unlimited spare-time activity" to their 6 __ jin! 0008998 bps ?_ /Stns'ery .V'vw/>.\ vi. ' ' A . W /< // / Vp ( -7 6-kj ~fkdto, tLk cj,ifiot'fd definition .as well as preventf'gainful employment". -He also* hit ffef 'imfatr iiiegf of ic.xcTioii, 0/ (csz, f aftU^L TAeyf irrp , accepted~thatw thers~were~-soei-^-^conQmiju-pj^bTeffls. 7 ' -5-r 10-i?c a <5 iu<e c> (> tews tesceofoJ ta.f/v Scfa'iktk & <^V f 1 u 17/ ^/( The conference accepted the definition. / It was stressed that we must consider the v/hole man^, jrj h the ^3^ . ~to ~f~L$ -moy? cfn'ioCi jit/o'noiiS.' w~f{pets -first biochemical change^ -and-then-^f-urther-ef-fe-c-^s.. Epidemiology may be an aid in this problem. Williams himself had shown that "/jfc1 -e fffc/iff personal samplers gave a good indication of-absorp>tion. /Kf* I* f 1/ Another speaker mentioned that "poisoning", particularly for medico-legal work, must be a matter of clinical judgment. However, prevention was more important. The real problem for che conference was "what constitutes permissible exposure?" The next speaker supported this idea but stated that he could not accept socio-economic factors in the determination of accepted levels. The conference should separate medical and social acceptability;and keep to the former. Anything that impaired health was regarded as medically unacceptable. Some workers who do not complain of poisoning feel better following 0c V"A' iMih/ino i'C ~kc !kiJt their removal from/lad__&ork. <The1 speaker regarded this type of fij t change as''unac ceeppttaab1lee/w'aanndd ssuuggggeested that this was, in fact, early poisoni.ng^hWav. if" ,1 fa f$tf ly jofatk -fo be (,J. , Complex social factors ma^ it difficult to decide whether to allow men to continue at work at or above accepted maximum safe levels of blood lead or other criteria. Doctors Sbecifas should attempt to stick to medical criteria/but there were bCQ(i{' ci countries where,'dthJ--to malnutrition, the whole population had a low haemoglobin and-in some circumstances, probably with a HE 000899/) 8- - ft <A'iy W f! >o; expectation of life, a job along v:ith a low haemoglobin was han no job and might increase life expectation. helhuis thouglit that too much emphasis was being oaacea on poisoning ana not enough on wnat wv,raas an unacccceeppttaaobllee / / xe `*-'(7? \f&d > ~(t ' 3.(Zhi i Y. response. Threshold limit values were not!medical"'"decisions &)tc<cU. ,,, * \'Wi/ & i4 A 'tftjia_ ,?nd-wnn~d ~cagy/^rom~^nrSntry to country. Acceptable* did'not fmean ' desirable. f Acceptability of blood lead levels was then discussed. Zielhuis said that if the blood lead level stayed below 80ug Pb/lOOirJ s> peak exposure was unimportant. V.'hen pressed to say if this figure was safe, he stated that he thought errors in the estimation "" >& Jvs would reduce the safe level to 70ug Pb/lOOrals to give an adequate // margin for safety and experimental error. 'i- Professor Kehoe agreed with Professors Lane and Zielhuis b/>M' iiKt'T in accepting YOug Pb/lOOmls blood as the^Tfff: ' ..U < :r //c^<hcr icf rttKa t/crvijrfrc;,' ) Referring to definitions of absorption and poisoning. D- VJilliams said these should be dictionary definitions and not decided separately by individual doctors. He raised the question <? V> as to whether faLA dehydrase a=3=i should be compensaM^ Kehoe tMi not. ix rh -ft? ft ,k / * >. 7^ i Yi(#t,c,alai? sUo/dk( * rfus <5- ?s 'icfttcifiTf caucf '.vill/iams accepted the W.H.O. definition of health, but ;aid that acceptability depended both on time and country//-? fa 0--c;twl f ;-nie'cf>'i?Tvhc,i ) Malcolm suggested the use of an international ouestionnaire addressed to various experts in an attempt 00 relate biochemical to other findings. He thought "chat there should be an agreed medical standard Jout recognised that nations k 0003000 - 9- might not he able to adopt these at a particular period of time. 7it j x 'iiicdUCi' of The definition of alisjOf^ti-onrivbuid be clarified by the experimental A use of personal samplers to relate environmental to biochemical and clinical findings. There was also a need to define toxicological parameters parallel to the clinical statement published in the British Medical Journal. , i( 7l\f * lend z k strphot/ \ ^ fa c ove-s' f ^^cf ef The vf&rd-ilab&orntiPn,'/should.Aonl.y..be used -where-ao -expcSGW ft Uad u ^u.u.L denarture from normal well-being .^i^^Soalifardfele^^SLikely to 4ny ' dciZJ* -cLe k* ,Tnil icAce, mv ^ s use? ^should ndM Be`il't^wed----t-o----hidexde- leterious effect?/ f Sbjv)' fit'li'Jb7 ' A? cf lead. Lead poisoning is a clinical term buvthe current concept _Stu 'fZsfaecfS^' t i . is likely to changer!n the "future as it has over the last ten years. Uhu^'H \v Acceptability should depend on the absence of any effects on the well-being of the individual. On Professor Zielhuis1 recommendation, the conference accepted this definition. irf ____ It was agreed that the presence of symptoms;*e^uated with poisoning. Zielhuis stated that the conference should not determine Lw meiKtHj b~t iIIms s f h(iScf>k< !&//. phi4asnoh^e-l3-jout_pnovide-dat,a. / h* ti'ay *~f' // W/-a>i -">*3 d~sia/ KZ 0003001 \ 10 SESSION III - DOSS/RESPONSE RELATIONSHIP Chairman: Professor R.Xehoe Williams introduced, his paper. The first speaker in the discussion thought that this was one of the few papers that covered all the variables but questioned the use of the Donath scale for urinary coproporphyrin. Williams said that although this was a semi-cuantixative method, the mathematical correlation gave an acceptable method of indicating lead absorption. It was suggested that the relationship should be curved and not linear, but Williams said that the regressions were tested within limits for linearity Another speaker thought the statistics did not prove linearity. It was observed that Williams' use of the personal sampler gives better regressions than static samplers, and it was suggested that personal samplers should be used to fix MACs and TLVs 'I fay Cramer suggested that on Williams' evidence, 15 mg urinary '-p ifcbeJtr fa f ^-aminolaevulinic acid should be used as the-dj&g and asked whether there was a possibility of diurnal variation or day to day variation in the levels of r35EfcA. Mfa - <*-<> i uAiiiW Williams replied that all his samples were taken at the same time of the day and that a further paper on diurnal variability v-zas in preparation. It was suggested that the paper should have contained confidence limits. The speaker said this had been done in another paper and all the relationships except haemoglobin were significant. It was accepted that the data were useful in setting MACs. HE 0009002 \ - li - Professor Kehoe then showed slides illustrating the +- EjMJJ i'll ' ^i I O 6A-fz c-f ku n.l(l I! 5 v jof QC~/? toy' uniformity' of th'e/'airborne r. A - - Vi sit-eviii Kq -jdoing_m|ldejra $s--work!/ by ZcM.eevifa'yi'icHi trf 3ss=^t^=9=^sa-HKiv/ (T hj4"PT' >p{z~&&(>( feW ' fifr/ bhc^. <1 > a V, < wr. Ait-fJi7tWvl o>, It was stated that the--activity-4ma normal--af--an--air , tVcouzl *?s h-rxfcry jat^ty sVvjofVf^ T6e 3* consumption of about 5 M per eight-hour day. It v?as suggested >' A;[_./ '"/y/j ' r chat 10 M"' oer eight-hour day would be more appropriate tojIndustrial work. Another speaker suggested that it was important to define <k Lc7rT C"f ~t(.f sh?( rfic7t/0^ \ V^y?'l'g ft o.\. the particle size and distribution in rel at left-1 o ...--it. wag. ti tLx. 5tii(vd <?T st?? t`4?p <i *^C|Vv3 (oAify< cj trf> agreed that the relationship between particle size and absorption h caa naf notr-eoaretefre-ly known. <-> uaK ! i Tqtrtpiy. *i tfE" 0009003 12 - SESSION IV - THE CHRONIC EFFECTS OF LEAD ABSORPTION Chairman: Professor Beritic Urbanowicj introduced the paper by Kosmider and emphasized the following points: 1. No conclusion can be drawn about the effects of lead absorption;or the subsea.uent biochemical changes,on the vascular system. 2. The influence of lead on the blood vessels walkthrough the autonomic nervous system rather than by a direct effect of lead on the vascular wall. 3,. ApazMtaclx_wi o*p//i.t-->w* a-i s./<iRoxt 1 aalzwiZ-aaoy-1^s-.a'3i.r"ectly rel.ate, d, t,o h.uman experience. 4. Variations in the electro-cardiogram due to the effects of lead were shown on slides. The first speaker v,!as surprised that systolic murmurs had been heard. He had neither found nor suspected these in cases of lead poisoning. It was suggested that the ECG changes would only be convincing if the controls were properly chosen. This was not clear from the paper. It was then suggested that the effects of poisoning were not relevant to the discussion on TLVs. Urbanowicj promised to refer these queries back to the author. As Professor Albahary had had to leave the conference, his paper .was open for discussion. 0009004 1? - In general the conference felt that ^'clinical cases were Yi; Jzisi w,j, ttf/ot Staid*-fis /<?>" ffa />>'js> ? p-f?\'?uf<< not relevant to sette^t^TV^,^ andTdiscussion` v.-as^cTirtailea. ----------.......- - p 'u N> / Malcolm then introduced his paper. He stated that it li CJ'f if ^ <s"t was important that TW^s-and--MAs should not only prevent departures from normal well-being in the short term but should also prevent any long-term sequelae. Lane reported that his original work on causes of death in three battery factories had shown an increase in cerebrovascular deaths and that these were related to lead levels of about 0.5$p;/M^ LL w 1 for many years of exposure, Jaut he emphasized the difference d-s *f- / between organic and inorganic lead. The next speaker agreed with Lane that kidney damage arose from heavy dosage. He showed slides suggesting an increase in incidence of hypertension and albuminuria 15 years after episodes of colic. It vvas suggested,regarding Malcolm's data on the lack of any effect of degree or time of lead exposure oh blood pressure, -fit cfiirjtttin ~y.{>cs <>*% "to K&4 e/'f> that -expoeure-djifne-warS'''related to age, whichXcbuId obscure the effect 1 7 /A of lead. Group comparison, age for age, was necessary. Malcolm stated that over 1,000 measurements of blood Uaj ZfSSCCtifTfOit pressure had been made and that these gave no ranking orderywith l_gad'>exposure), and that the average age of the group was 45 years. One speaker suggested that because of the effect of age on blood YtncAv pressure, the findings saiild imply that lead lowers the blood pressure. There was some pharmacological support for this idea. It was generally agreed that long-term sequelae were 00090-05 \ - 14 - prevented in groups which were adequately controlled to avoid any departure from normal health, but that long-term sequelae occurring ic -fix C c- H Wl? V #ft Ct/ subsequent to episodes of poisoning were not relevant te-osteblisluisg ^ C^ i & il i C- A~c7}\dC'h. Professor Beritic referred to the endemic nephritis in t Yugoslavia. He had seen many cases of lead colic but only transient kidney lesions. He said that cancer was reported to be rare at *fl Trepca where rfne inhabitants were -segl La ry* t'Mv. (i(i sh> A-high-dose of leadfSa'rats exposed to lead. 7~o gave rise to renal cancer. Williams referred to the work of Lillis et al,-published in the British Journal of Industrial Medicine ;showing long-term renal lesions following repeated episodes of colic and observed over a long period. t v? -LLzf- Workers removed from lead at the Trepca lead works 15 years ago had no renal lesions, but EDTA had been used in their treatment. Cramer stated that he had found a low incidence of hypertension with no long-term effects in battery workers ir\ 20 years' follow up despite bad conditions, and another speaker supported these findings. Malcolm accepted that no renal lesions occurred after e<ts>> of a single attack of poisoning, but considered tBatbchronic inter'ty~f<oil tui tL __ stitial nephritis would occur a-t-r ^-speated attacks of poisoning ticlVJ and continued/exposure to lead over many years. A It was suggested that the long-term effects following <3~f c i'HiXtn J i__/ repeated episodes of poisoning were not reie-vant to-the /conference. /' Another speaker stressed the long time 'which was required for lead levels to reach normal after being increased. 0009006 Professor Beritic then summed uo. - 15 - SESSION Y - INTER-RELATIONSHIP OF PARAMETERS Chairman: Professor Vigliani Zielhuis introduced his paper. Williams then presented his paper and emphasized the low correlation of haemoglobin with all other indicators and reported that analysis of a further 250 samples still indicated no correlation between haemoglobin and blood lead. King then presented his paper and indicated that he would accept curve relationships between some of the parameters but had plotted linear because of the scatter and the width of confidence limits. Malcolm produced data for workers at two battery factories, also revealing no correlation between haemoglobin and blood lead. Th$s%iata included all individuals with blood lead concentrations in excess of 80ug$ at the first factory. He stressed that both his and Williams' data 'were derived from factories^where increases above the acceptable limits^led yfycWRr/^ to prompt action. Stoops then presented data supporting Malcolm and Williams, showing no correlation between blood lead and haemoglobin. Data plotted from the literature N = 155 mean PbB of 89.9 and mean haemoglobin of 12.6 ug;5. A five-year study at Du Pont of 202 employees and also in a storage battery manufacturers of 109 employees failed to indicate any correlation. The first speakers agreed that it was most important that blood lead measurements should be taken concurrently with K 0009007 - 16 - ''exposure if misleading results were to be avoided. Rainsford's results were quoted in support of Zielhuis' findings of a correlation between increase in blood lead and a fall in haemo globin. It was pointed out that in Rainsford's two studies, the first had referred only to factories reporting low haemoglobins. These were poorly run factories and high blood lead levels were found. In a later study of good factories, Rainsford had found normal haemoglobin levels. Zielhuis maintained that there was no bias between good and bad factories and he considered Rainsford's data to be valid. It vms pointed out that the difficulty of comparing results from different investigations due to the different time intervals between exposure and measurement. In addition, where employees started with a low haemoglobin, it was more likely that there would be a further decrease. The next speaker referred to the effect of iron deficiency, for example, that reported by Goldberg in the Glasgow area, v/here 80$ of the oooulation were affected-rbomoared with /i ` London where there was no iron deficiency. An objection was made to the use of group data for statistical analysis unless ^-reliability of the groups-were k&cl pct*)l established by rigorous testing of individual points. ruf could be done, it was pointless to plot group data. When this King pointed out, however, that his data wa<r plotted on the basis of individual results for non-selected labour force 0009008 - 17 - not subjected, to lead control. The regression lines for groups and individuals were very similar, and this supported Zielhuis' use of group data. It was suggested that better correlations might be i n f? o-.t h ~f~lt W i*C'*17 ^ ^ obtained if blood lead values were expressed as a weight, of erythrocytes rather thanjwhole blood. A Stopps reported his study of haematocrit and blood lead levels in 433 workers. Haematocrit levels varied between 21 and 54. blood lead levels varying between 2 and l47ug^, but there was no correlation. A reduction in haemoglobin was not really a direct response to the "dose" of lead in the blood but a failure of the haemopoietic system. A fall in haemoglobin is a serious response. Since there were various mechanisms to restore blood; it v;as probably better to correlate blood lead with reticulocytes. In time, it might be better to measure the activity of other early Indications. The discussion centred on the merit of using haemoglobin itself/compared with the use of a haemoglobin/blood lead correlation, to justify (a) a reduction in 'working levels and (b) these or other biochemical Indicators. It was suggested that a fall in haemoglobin due to lead absorption was not acceptable and there fore should not be used as a primary means of csfnu&fni^ c/ \<wMV "\i-f fU loot s I It was suggested that measurement of the haemoglobin level was less satisfactory than the measurement.of change in haemoglobin on an individual basis. This might yield different HE 0009009 - 18 - regressions. Beritic then introduced his paper dealing with changes ^ jij' .i'n.L-'in-t \ & f 111 Q' y ---- ' liculocyte andV\stlnoled" cell countg4^and myelocyte/erythrocyte ratios in the bone marrow. :,?7W A decrease in haemoglobin 1-eve-l^with a decrease in < Y{tkrif''r{-S`^ reticulocytes-3rvei;and an increase in stippled e-eil-s should be h befie\led > __ added^. to Gajdos' observation about the specificity of increases in ALA* coproporphyrin., and -recUoell^rotoporphyrin in lead poisoning. / The chairman considered* however, .that blood lead gave the best correlation with lead exposure. Zielhuis queried the level of 80ug$ for blood lead as a biological TLV with respect to a significant fall in haemoglobin. It -was pointed out that while the fall in haemoglobin at this level may be statistically significant* it -was not necessarily meaningful if small. More crCt-v>i It was then suggested that haemoglobin surveys should be extended so that changes in individual levels were examined. The -fij. ef {- [oe'T /oo .s ` f' b/oj<X^ speaker accepted 8dugff^as~n;^biological(yperrni3sible limit^utr In H?ri(,hO{ considered it might be a little high for populations not under continuous medical control, U s'vfu) c (- ~i(^ Z>tvlyflrt/ <yWiff/W< Xehoe stated that 80ug could not be used as an absolute figure without regard to the accuracy and reproducability of the analysis, even in the best laboratories, and referred to the recent American surveys. He questioned the accuracy of.Jauli=i of the reported data for blood lead because of varying methods. He had, however, observed cases of lead poisoning in individuals at a reported level of 80ugfi, but he insisted that it included a KET 0009010 - 19 possible laboratory error of 10$. Zielhuis, applying Kehoe's 10$ error, suggested that to safeguard workers' health the blood lead limit should be 70ug$ which could be ^ <>X j In ^secijff^ \oifk lea<! In urine of not^> 130ug/l, ALA level of. not 9> 10ug/l, CP level of not 300ug/l, taking into account confidence limits. It was then proposed that an analytical comparison exercise should be carried out to check the consistency and uniformity of data from different laboratories. The speaker referred to the variation of up to 20$ in the results of samples he had exchanged with other laboratories. He suggested that the analysis of lead in urine might prompt a greater degree of comnarability. Ik ^ Professor Xehoe said that lead^in^urine w4-^t~&g--at&feafajje 1 ItfltU/Oiq 9Q>ie*\t'J o~f Th fk .j5 o'x!, -f~2 . if \f T*ifiw ,i^or_-a^roupul>ut-G-ouM-^e%--be-nsedA^atirS-ga-o:top-i-ly--f-or-t-he--control .T fw g/tbay ?ur to cb-^h^nh -faf *' vtT'i'iir>7c ,4//'^ ' -orfur-i-nvdaivfe-i-do-ufal sA-ft* ' *+r- , MI - *I ~'"P * *- 4-"~ ` r ' If >x(4 ('(,, < 5'fe c \ ? fr 'Tl 1 ` yi^fl TL<i y-z-aC'>r&f ((v?t Ycfff > The idea of analytical comparisons was supported vV and t-/r.. ' reference was made to previous symposia in Paris and Prague. It was also urged that all laboratories reporting blood lead and other data should be asked to indicate the sensitivity and accuracy of their methods. Professor Xehoe revealed that in a forthcoming U.S. survey on ambient lead levels in the air, it had been decided to carry out all of the analytical work in one laboratory to avoid \ie 0009-011 20 errors and variations found from laboratory to laboratory. He * h i* also mentioned that the dithiazor.e method of blood lead analysis as Ca<r?~>rf'L zuifrtyad s'- < was - the-bestr established. i of- Tie niTUtfi firhts 'aTtne^ , t`5 /#tr>T~ Beritio presented his paper on blood lead and lead colic. The first two speakers revealed experiences of blood lead levels below 80ug^ in the presence of colic,, but it'was not "Ho?/ clear whether the blood lead levels had been measured concurrently with exposure. It was important to deiiaraine=the-`delay between exposure, appearance of symptoms, and the measurement of blood idsilteyf leii' f 2x >'* f> i f lead levels, and also to know whether the A -w^ewbased on -I single or multiple determinations. ** " Beritic said that only single determinations were taken because of the need to treat patients with severe colic. The need to take more than one sample was emphasized 3ry>i -f(C. ?/ (>>( e-f C w T'C \ 7%P hi Srf"*'f'(C.3/ <*>>( e-f ' particularly because of/son m;rs--fbr--smadTr--eamsL&s. U W \ '-| S "a l-, 5 5 v//i (i -hA.;. King had ho experience of colic in conjunction with &( blood lead levels below 80ug in over 50*000 determinations v?hich H< cecsv/vy__._ he had made. Blood lead levels found during colic had no/bedrevance A in the control of lead workers. Another speaker pointed out that colic was a clinical syndrome not dependent on blood lead level alone. Cramer and Selander then presented their paper on ALA, blood lead, and lead-in-urine relationships. The first speaker said that the discovery of an increase in ALA did not necessarily mean that the blood lead levels for purposes of control should be reduced. Kg 0009012 It was not yet oossible \ 21 to interpret the clinical significance of -& -raised1^ ALA. A There was then a discussion ojrthe social implications of removing workers with an increased 6-ALA at low blood lead levels from lead work with reference to the law in various countries. This point was not resolved since social systems and allowances were different in each country. It was suggested that it was possible to have ALA levels in urine even up to 40 mg/1 without any certainty of clinical symptoms developing* but Cramer said that consistent levels of 0-40 mg/1 were often associated with symptoms. Stoops then presented his paper on urinary ALA showing a logarithmic curve against blood lead levels in lead 'workers. This was confirmed by the experience of the first speaker. Teisinger then gave his paper showing ten years experience of diagnostic challenge of EDTA. The first speaker queried the advisability of using EDTA `for diagnostic purposes. The chairman suggested that should not be discussed at this meeting. Vigliani presented his paper showing blood lead and lead in urine distributions in urban populations. The first speaker commented on the high levels and noted little difference between urban and primitive populations in the skewness of the distribution. Commenting on the 2/ who had blood leads of between 70 and 80ug/, he thought cases of poisoning should arise. Kehoe said that such high levels were not found in the ^ 0009013 22 U.3.A. except in abnormal exposure and doubted the analytical methods, -which were admittedly difficultysEgsaay. Schlegel then presented his paper describing monthly screening with urinary ALA and urinary coproporphyrin. Various methods of urinary ALA determination were discussed and it was suggested that the simple methods gave higher levels at lower exposure. The next speaker said that at his institute the simpler methods had been elaborated in order to be used for screening purposes, and it was commented that the screening method ought to give false high rather than false low results. The methodrpufillTsHed in the Archives of Environmental j\ Health was referred to as being quick and good. Nobody had much experience in the use of the present tube method for urinary ALA measurement, but the importance of PEG interference with ALA was stressed. The speaker said he found the orthodox methods were not difficult to apply at 40 estimations per day and warned of the inaccuracy and non-specificity of the simplified methods. Stankovic then presented his paper, followed by Urbanowic j's paper. Comment was made that the ALA and coproporphyrin lines calculated for Urbanowicj's data were lower than those calculated for other work, and Urbanowicj stated that the data came from people exposed for the first time to lead. Vigliani, in summing up, said ALA was one of the most important parameters for indicating biological response to lead 0008014 23 but much further study was needed to assess the damage or risk to health on a basis of ALA or other biochemical indicators. He also added that the methods for analysis of lead in blood and urine should be checked for comparability. ******** HZ' 0009015