Document Rj9wK04qz7GYXvJb4561rE3vV

KINETICS OF RESPIRATOR V LEAD UPTAKE J\ HUMANS KNELSON, J.H. ami JOHNSON, R.J. Clinical Enrironmental Research iMboratories, ICnvfroimientiil Protection Agency Unicersity ofNorth Carolina. Chapel Hill, North Carolina, U.S.A. and COULSTON, F.. GOLIJERG. L. and GRIFFIN, T. Institute of Experimental Pathology and Toxicology Albany Medical College of Union University, Albany, Netc Pork, U.S.A. ZUSAMMENFASSUNG Am Uiitersitelmngeii iiher die hMogischcn Wirkungen ciner klugere Zeil dtmernden Beltts- ttmg ties Menxchen (lurch hleiiudtige Loft warden die Oaten hescfmJTt, die :ttr Ausarbeiltmg einesinatlienitithcheti Motkllsfi'tr die Kiuetik der Btekuifnaliinc milder AtemUtfthei Mensclteii benbtigi warden. MTmidiehe erwaehsene Yersnehsperstmen witren zircitntd fiir 18 IToc/ien mittkren B/eiexpositionett eon eimntd IG.93,1 ng/mJ ttttd zttm uttderen 3,2 0,6 ns/m3 ctttx- gesetzt. * file lUeikanzcttutitioncu in tier Lttfi tntrdctt m'mdestens ztreitmil ttigUch titifgezeielmet. Oie Hlcihonzcnirotiton-tt int Bhit mtrden irdchentlich oder ally zwei IVociieu hestimmt. Die Yeriin- dertmgeu tin Blntbleispiegcl Wcdwend der Exposition warden mit dent thireliscftiiitfliclwii Blttl- bieigcludt for der Exposition rergliehen: dartins trunk file die Prtdtamkn die dtir.cbschniltliclia /.tmtthttte ties BlaibleigeJuilts tr.Shrettdjetlcr der heithn Yersiiehsabselmiiic errechnet. Die 'paten- tielle '/.nhnahme der llieilttsf ties Harpers win! tit Abidingigkfit volt Expositkinsgeod. Ex/msi- thmsdimer, Liingenmitiltition amiprozeiittmler Retention dcs eingeutineten Illeis gesehatzt. lYt'r fattden, dad die Zttmthmett in .der Gesamtmengc des Bftttbleis, trie sie hei betden Expositions- niveous beohuehtet warden, eng mit dent Logaritbimts des potentieilen Kdrperbelasiinig zttsatn- menbiingeti. Aidttmd dieser Fcstsfeilnngcii trunk eitt ttmihemoliselies Modell entwiekell, das es ermoglicht, die icaheschcinliciic Yeribitkrnng in der Blathkikonzentration trie attch das Yer- hdUms Zwisehen dent gesamten Bluthlei and der potentieilen Ztmahme der Korpcrbelasltmg cut- spreehenddenjetceiligen Expositionshedingungen zu bercehitcn. Aits dtesein Yerhiihnis Uiftt sick die Yerteihtttg zwisehen den beidett titeoretisehen Bereichen mit raschem and laitgsanten Unisatz abkiten. Die ciriki/cbtendsten Hypothesen in hezttg attf Ventilation und Retention loafen darattf liintms, dttJS ettro 90 % tier potentieilen Gestimtkorperhelmiiaig attfdett Itmgstmien Bereich etU- fidkn. ll'escurlielie Erlmiumgen des Blutbkis werden sclion fiie soiclte inlui/krlctt Bleimengen torunsgesagt, die erhebfich miter denen liegen, tele sie gewdhn/ich in der Aufenluft oorgefttnden werden. SUMMARY ., Studies of the biological ejfrrts of long-term human exposure to airborne lead produced the data usedto prepare a maiheinatieal model ofKinetics ofrespiratory leaduptake. Adult mule subjects were subjectedto tiro I8 week exposures of leadmean concentrations afWt.9 3.1 pg/m' and of3.2 0.6 pg/m J. Air lend levels in the room were recorded at least tnice daily. Illood lead lerefs tcerc defertieiml erery irecK or crcry tiro trrcKs: ('hangex in blood lend during exposure trere compared to . .the mean blood lead before exposure 'to calculate mean increase in blood leadfor the subjects through hath studies. Potential increase in body burden is computed as a function of exposure leech duration ofexposure, pulmonary rentilatiau, and percent retention ofinhaled lead. Wood lead concentrations tiiitlliplicd by total blood rolitme allow one to estimate the fraction of potential body harden appearing in blood. We found that increases in total blood lead observed at the two levels ofexposure were closely related to the logarithm of potential node harden. A .mathematical model was developedwhich enables one to compute the relationship between total blood lead and potential increase in body burden. From this relationship, distribution between two theoretical compartments with rapid and stow fnrnorer (an he inferred. The most reasonable assumptions concerning ventilation and retention indicate that about 90% of the total potential body burden goes into a slow compartment. Substantial increases in blood tepd are predicted even for respiratory doses well below those commonly encountered m ambient air, RgSUNffi Des etudes des effets biologkpies exerces sur Vhamate par tine exposition de longue Hur/c an p/ontb atntospMrhpte out pernu's d'obtenir les domtees ntilisees pour efabprer tot inodcle mathcniathpte de la cinei'nine de Fabsorption respiratoire deplomb. Des adultes de sexe mascnlin oni itd sounds it deux expositions de 18 sentaines choctaw d des concentrations moyennes en pbmh de 10,9 3,1 pg/m3 dans Ie premier cas et de 3,2 6 pg/m3 dans ic second. Les nireaux de plomb atmospherupw present dans la piice out He enregistres an mom? dettxfois parjour. Les niveaux de plomb sanguin ont He determinis routes les semaines on deux. Pour chacune des itudes on a Habli tuie eomparaison enfre les changements inierremts dans k plomb sanguin an coitrs de Vexperience et !e tanx moyett de plomb sanguin arant!'experience, pour chacun des sujets. On a ea/cnle Vangmentation potentiellc de la charge da corps comnu fonction da niveau de I'exposition, de sa dnree, de la ventilation pufmonairc et de la retention de plomb exprjmie en ponreentage du plomb inhale. On a troure ipte les auginentations de plomb total dans le sang enregistrees aux deux niveaux d'exposition correspondent prathpiement an agarithme de la charge potentiellc du corps. On a elabore tut madele muthcnwlhpie tpd permet " de calcnler la relation existant enfre le plomh total contain dans ic sang et 1'a.ccro.issement potenthj de la charge du corps. Sur la base de eettc relation, il cst possible dc caJcalcr la distri bution entre ileux rompartiuienls tbeoriipies it totalisation ntpide et lente des resultant. Fn gadnil, les resulfdts obtains it partie da modele correspondent remanpniNrmeal Men aux risnltats abteuus jntr ifmitres rherehenrs ii partir de donnees Iris dijfirentes. Fit ee ttnieoncerne la rendlatitut et la riteation, les hypothises les pins roismmohies indiipienf 'ipw 90% enrirmt de la charge potentiellc tolalc da carps entreat dans tin fompartintent lent. On pease que mime des doses respirataires uettement iufericures ii cedes ipw Von rencontre gcitcrulement dans rah anihiant pcuccnt praroqner un tieeroissemenf considerable du taux de plomb sanguin. m TEH 0470729 DUP050083547 1 -- in t r o d u c t io n ** Toxic properties of lead have beep recognized since antiquity. Modern industrial use of lead and compounds containing lead has. however, made human exposure to amounts of lead exceeding the normal "background level" almost universal. In particular, since introduction of tetraethyl lead as a motor fuel additive about fifty . years ago. there has been a widespread dissemination of lead particles of respirable size into the atmosphere. Goldsmith and I lexlcr have argued that absorption oflcad from respiratory exposure may be similar in magnitude to that from gastrointestinal absorption [I]. . Apart from the pioneering work of Kchoc and Cholak, there is a paucity of data relating the body burden of lead to gastrointestinal or respiratory exposure levels. A large amount of information has become available relating human blood levels to ambient air lead levels in urban and rural areas, but some controversy exists concern* ing the interpretation of these data. Most recently, prolonged exposures of men to carefully controlled levels of lead in the air have been performed. Although a great deal of information concerning biological effects resulted from these studies, only the data related to kinetics of lead uptake from respiratory exposure are considered in this report . 2 -- EXPEKIM ENTA L DESIGN These studies were conducted under the direction of Drs. Frederick Coulston, Leon Golhcrg. and Travis Griffin in cooperation with the Slate of New York Department of Correctional Services at the Clinton Correction Facility, Dannemora, New York. The subjects were carefully selected to exclude anyone with an acute or chronic disease. Baseline blood lead values were determined for several days before the controlled exposure began. Th(\fc>4Lrtl:cn men finally selected for the study inhabited the exposure room nearly 23 hours a day. seven days a week for a" total exposure duration as long as 18 weeks for ^npiiy^jaTthe men. Although the subjects were encouraged to participate in the study for the entire period, no coercion was exercised ' and some elected to leave before the exposure ended. In order to create as large a data base as possible with the space limitations of the exposure room, other men were entered into the study already in progress. Lead oxide aerosol was generated by bubbling propane through a solution of tetraethyl lead in dodccanc and burning the resultant vapor in a highly oxidizing flame. The combustion products, almost entirely lead oxides, were introduced into the separate air conditioning system for the exposure room. Temperature and humidity control, for comfort was maintained and an electrostatic precipitator removed all particulate matter .from incoming outside air. ,* 393 "* Lead in i! room air was monitored through sampling ports located at various sites in flic room and analyses performed four limes daily,. The samples were split for immediate analysis by a colorimetric method and subsequent analysis by. atomic absorption spa iropholomclry. Particle si/c was estimated using a modified Andersen cascade sanvplci as well as by electron microscopy. Well over 80% of the particles had a mass median diameter of 0.18 micron or Jess, Most of the particles seen oil the electron microscope grid were between 0.05 and Q. 10 micron in diameter. Electron diffraction analysis indicated a major fraction of the particulate material was com posed ofstPbOj with traces of Pb,C207, Pb(OH)CI, and PbCI2 also present. Two exposure studies were conducted. The first resulted in a mean air lead concentration of 10.9 (3.1) pg/m\ measured as elemental.lead. The. second resulted in a mean exposure of 3.2 (0.67) pg/ni3. Blood samples were drawn in lead-free Vacutainers and blood lead concentration determined by atomic absorption spcctrophotomclrv according to the method of Bessel [2]. 3 -- MATHEMATICAL METHODS Mathematical procedures used in this initial data analysis were selected Tor thrii relative simplicity and because they could be programmed on a small computer Preliminary results of much more detailed and complex mathematical modeling nov in progress support the general conclusions of the simpler model presented here Potential daily intake of lead by inhalation is calculated by multiplying the mem air lead concentration each day hv pulmonary ventilation. Potential daily increase in body burden is calculated by multiplying potential daily intake by lhe(fractioi^ o inhaled Ica^TsstimocOto be retained. Total blood lead content is calculated by multi plying blood lead concentration by total blood volume. Cumulative potential increav in body burden was calculated Tor each interval for which blood lead determination were available. Mean increases in total blood lead content were plotted agains't uvea' potential increases in body burden for the same exposure interval. These plots rclat total blood lead content to potential increase in body burden at a given daily rate o respiratory intake of lead. When increase in blood lead content is clotted against the logarithm o potential increase in body burden a good linear relationship result?. Therefore increase in blood lead concentration or content can be reasonably well predicted for an respiratory exposure at a given level of pulmonary ventilation and percentage retenlior 4 -- RESULTS AND CONCLUSIONS The following abbreviations will lie used: IBL (pg/100 ml) =* Predicted increase In blood lead concentration; BB (nig) = Potential increase in total body burden; 9 394 DUP050083549 ,* H ;i > /. (gg'nr1) Air lead concentration; * V (m'/day) = Pulmonary vcnlilaliou; R >, A (days) a= Fraction of inhaled lead ihat is retailed; == Duration of exposure. Potential increase in total body burden: BB=* L'V'R-D' 10" Arbitrarily setting K=t 15, R -- 0.37, for the 10.9 pg/m3 exposure: JBLft ?= m,,+6,,log,q BB: IBL,, =s 6.80318+ 10.8101 log,n BB\ ir = 0.97). . Similarly for the 3.2 pg/nv* exposure: //?/.,== log,,, BB: //)/.,- -4.283 + 3.774 log,,, BB; ' (r as 0.92). .' In order to calculate increases in blood lead concentrations resulting from air lead levels lying between those used in this study, the following relationships are used: Am f=W|_; Ab = = lO.Vitg/nr'; Lu = 3.2 pg/nr*; I * . A. " Aj -- L-L, "ft* >-----: &ni + nt\ A6 + K iog,0 BB, A,, Simplifying and substituting: JBL = 0.327X+3.236+(0.914L+0,85) loglo BB. Figure 1 shows a semi-log plot of increase in total blood lead content and potential increase in body burden. Again, pulmonary ventilation is arbitrarily set at 15 ni'Vday, retention at 37% and blood volume at 4.9 liters. For the exposure to a mean level of 10.9gg/nVs of lead aerosol: r = 0.33+ 0.53 log,0.v. For exposure to i a mean level of 3.^(1g/nv1 of lead aerosol: r = 0.21 +0.18 IogI0 x. Figure 2 shows the ume plots without transformation as well as two curves predicting the results of Ik intermediate exposures. Those plots indicate that toward the end of the actual expo sures, approximately 10% of the potential increase in body burden could he accounted for by increased total blood lead content. This figure agrees in general with the observations of Sehroeder and Tipton that as equilibrium is approached, about 90% y of the total body hurden of lead is in the skeleton [3J. If one assumes that circulating ! ?'fi Mov'd volume represents a compartment with a turnover rate considerably greater than that for bone, it is seen that this fast compartment reflects small increases in i : : bod) burden at the beginning of exposure, hut as exposure is prolonged a continuously I I i *tii*! n ii1? r !-::{r LEAD UPTAKE FROM RESPIRATORY EXPOSURE 37*. RETENTION IS N? VENTILATION 4.9 L BLOOD VOL. UC/M> 09* MO/0AT t > -* ,,* ^^ P J UC/M3 0ITA*O/0*Y 14i ..>i.a*#*>i I1 POMNTIAL IMCRfAH IN BOOT BtVOIN (*> 4 T' 4 / I Fig. I IEAD UPTAKE FROM RESPIRATORY EXPOSURE 97% untmtoN is M* ViNTILAllOH > i BLOOD ypt. '* Nl*J M*OM'' III MS*VAT POTENTIAL INCRIASi IN BOOT IUVMN t" Pig. Z 396 MO DUP050083551 Air lead (ns/m3) TABU- I Predicted increase in Idund tend (ug/lOO ml) for representative exposures* Days pfexposure 25 SO 75 too 4 .3.4 4.7 5.5 6.1 6 4.7 0.6 7.7 8.5 8 6.2 *.7 10.1 U.l to 7.V 10.9 j. 12.7 13.9 ^ * pulmonary ventilation = 15 mJ/day j-t Retention 37% ' ir increasing Traction of increased body burden can be accomodated in the slow com- partment. Thus continued exposure to even low levels of atmospheric lead may result !> in significant increases in total body burden without proportionate increases in blood lead levels. This concept supports the observations of those investigators who have v a found age-related increases in bone lead concentrations [3.4] and the conclusions of C. tracer studies in animals {5-8]. Similar age-related increases in blood lead have not | ; been found [9, 10]. .. 5 -- DISCUSSION |s ' Interpretation of data in a way that allows one to predict the outcome of future experiments is a pastime that is often amusing, at times helpful, but always hazardous, * Assumptions inherent in development of the argument may go unrecognized or be vV- misinterpreted. The temptation to extrapolate'beyond the data always exists. Yet, when experiments as time consuming and costly as these are performed, one feels1 compelled lo extract as much information as possible from the results. When the iff subsequent experiments cannot be done, a model makes possible best judgment deci`Mr sions based on available information. When they can be done, the model should fe, assist in improving their design efficiency. We hope, therefore, that any predictions Xs based on the calculations developed here, will be interpreted with great caution. & Extrapolation beyond the exposure levels or duration of exposure used in this study f\ may not be valid, * Retention rales for lead particulate of respirable size lias been estimated by t8s% irtcral authors [I!--13J. These rates may range from about 30% to 50%, but 37% is frequently used as itn arbitrary intermediate figure. Pulmonary ventilation depends on level of metabolic activity and can range from 10.8 irr'/day for a sedentary man to 22.8 nv'/day for one engaged in light activity [14], The men in this study were not entirely sedentary, hut space restrictions prevented normal activity. We chose to use an intermediate value of 15 nr'/day. Blood volume was not measured in the subjects participating in this study. The value of 4.9 liters was used for the calculations presented here. In this report we have emphasized increases in blood lead content because we wished to study its relationship to potential increase in total body burden. We could not measure baseline total body burden in these subjects, so only potential changes could he used in the modeling. We did measure baseline blood lead '.concentration before exposure liegan (I'J.b t.4,X jig/HKt nil). This is a level somewhere between that reported for rural and city dwellers [10].. l-or this reason we believe predictions based on this model will he relevant to a large fraction of the general population. It is very diflicull to compare the results of these analyses with those done by others. The kinds of assumptions and manner of presenting data arc so varied that we have elected not to attempt comparison. Validation of the model will depend oa future experiments, in the meantime, however, internal consistency of the model has been demonstrated by different methods of analyzing the same data which results in substantially the same predictions. Details and results of these analyses will be the subject of future reports. REFERENCES t. Go l d s mit h . J. R.t ami Hl mt k , A.C., Respiratory exposure to lead: Epidemiological experi mental dose - response relationships. Science, I5H: 132-134, 6 October. 1967. 2. III.ssi I , I).\V,, A simple and rapid quantitative determination of lead in blood- At, Absorption Norsk"., 7: 55, MX. 3. .Somoi oi K, II. A. and Til*io n , I. It., The human body burden of lead. Arch. Enriron. Health, 17: 965-978, 1968. 4. tfouiucTii, K,, tlOHUiVKlii. S.. and Su i.k a n t , M.. Studies on the industrial lead poisoning. I. Absorption, transportation, deposition and excretion of lead, 6. The lead contents in organ- tissues of the normal Japanese. Osaka City Mol.. J. 5: 41-70, 1959, 5. Bf.Li., R.F. and Gil l il a n d , J.C., Urinary lead-210 as index of urine radon exposure, pp. 411-423. In Radiological Health ant! Safely in Mining antI Milling of Nuclear Materials, Vot. 2. Vienna .International Atotnie Energy Agency. 6. IIo i.a n o w s k a , \V,, I'niiitmvski. J., and Tk c u a n o w s k a. B., Tlie kinetics of distribution and excretion of lead (l'b-210) in rats. pp. 420-422. lit 14//i International. Congress .on Occupational Health. Proceedings, Madrid, 16-21 Sept. 1963, Inter. Congr: Scr. No. 62. Amsterdam: Exerpta Medica Foundation, 1964. , , 7. Lik as , II. F. Jr. mid .Sia n iiik u , J.l:., Excretion of tead-210 in rals. pp. 105-110. ANL-7360. Argonne National Laboratory. U.S. Atomic Energy Commission, July 1966. 8. Tc is in c ik , J.. PnrvovsKA, F,, Sujtvix, V., Fii:k , J., and Rout, Z., Attempt on determination of biologically active lead in organism in experimental poisoning, hit. Arch. Geteerbepath. Garerbehyg., 25: 240-255. 1969. ' 398 DUP050083553 . 9. Ihwitviu. K. ami Ta k a im, I.. Studies on tin; industrial lead poisoning. 1. Absorption, trans portation. deposition, ami excretion of lead. I. Normal limits of lead in the blood, urine, anil amcntf healths Japanese urban habitants. Osaka Cily Mrd. J., I: 117-12 s. (954, (0. U-S. Department of Health, Education, and Welfare. Public Health Service, Division of Air Pollution. Survey of lead in the atmosphere of three urban communities. PHS pub, 999-AP-I2. _ Cincinnati; PJIS. 1965, p,'94. 11. Ktuoi, K.A., The metabolism of lead in man in health and disease. The Harhen Lectures,' I960. J. Kay. Iml. I'nhlic llnillh Hyy.. 24: 1-81, 101-120. 129-142., 177-2(11, 1961. . 12. Miiia m.S., Lead retention by the lungs of lead-exposed workers. Ann. Ocettp. lfyg.,9: 165-171, 1966. I.L Nu /a k i. K.., Method for studies on inhaled particles in human respiratory system and retention oflcad fume. Itnl. IfeaMi (Japan), 4; 118-128, 1966, 14. Airborne Lead in Perspective. National Academy of Sciences. Washington, D.C., 1972, p. 31. DISCUSSION WILLIAMS (L'.K.) " The speaker refers to one paper which says Hurt symptoms and signs occur at blood leads of 40-50 pg/ 100,0. This is a rather freak paper. I would draw his attention toa paper in the U.M.j. signed by about I* cvperts who said that symptoms and signs do not occur at blood leads of less than 80pg. 100 G. Also, could his results differ from those found vv ith antiknock lead because of differences in the aerosol 7 KNKI.SON (LLS.A.) I appreciate your concern with arbitrarily defming a narrow''range of blood lead concentration at which symptoms may begin to occur in some intliv iduals and recognize this point is still a subject of controversy, tin the other hand, in the N^S monograph attention was drawn to the fact that clinical signs and symptoms a re not always reliably related to blood lend concentrations. Many occupationally exposed workers appear to he symptom-free at levels- above 80 pg/|00 Gwhcrcas overt toxicity occurs in other individuals at substantially lower levels. With respect to composition of the aerosol generated .in this study compared to that occurring as a result of automotive emissions. 1 would like to make these observations: Dr. La w iiii k just showed us many pictures demonstrating the great variability of lead-containing particles occurring '`.naturally", I'lectron micrographs made of the artificially generated particles sho.w .many of the same eharucteristicsof aggregation. There is not. of course, any Organic matrix in the chamber aerosol. Neither is there an appreciable amount of lead halide compounds. A1 the eoncentrafions of lead aerosol in this study, and those occurring naturally, however, it seems likely that any particles will either go very quickly into solution or be ingested and digested by pulmonary alveolar macrophages. CRAMfiR (Sweden) I would like to say to Dr. Wil l ia ms that I am sorry that I can no longer support the view that no lead poisoning occurs below SOpg 100 ml. It occurs.'aceordinglo my opinion, although it may be rare. The data of Dr. Km i.s o m once more make me doubtful about the conclusions from the Seven City Study, presented bv Dr. Co l *, yesterday on behalf r ILZRO. If you omit the point at the extreme right efhis figure 5, there must exist a positive correlation between lead in air and lead in blood. Ilovv valid the data from Pasadena, i-e. your point with Ihc highest lead exposure? COLE (U.S.A.) Referring 10 Dr. Cr ami'k 's .suggestion that elimination of the upper right hand value in (lie air-lead vs.blood-lead curve of the Seven City Study would give a significant regression. I feel that it is not justified to eliminate a set of approximately 200 of 2000 data points without scientific justification. The particle size and form of the lead particles and (lie lack of extraneous particulate material in the inhalation chamhcf was quite different from (bat quoted by La w tut a in his sumplvs of atmospheric lead panicles. Would this hoi all'ecl the absorption of le.nl from die lung- KENNEDY (H.s.A.) What was ihc general health of the volunteers prior lo and following exposure Upload in .lire chambers? (Excluding the elicits such as increased lead levels, ALAI? activity?? KNEI.SON (II.S. Vi Their health was imi mal as determined by routine medical history, physical examination and clinical chemistries. None of these parameters deviated fronj.normal limits throughout either exposure period . for any subject. KENNEDY (VI.S.A.) Could you comment on the period of exposure required to reach blood lead equilibrium ? It would ap pear front the data (10,9 Me/m1) that this point was reached between 120-170 days of exposure. KNKI.SON (U.S.A.) I don't know when equilibrium occurs. Casual Inspection of the data suggest equilibrium was attained within the period of study. Models that are not yet in equilibrium, however, account for as much as 92% o! the variance in the experiment. I think the subjects of this study were nearing equilibrium, were approaching asymptotically a limit, and the distance front such a limit was probably of about the same magnitude as the "noise" in the measurements. .KENNEDY (JU.S.A.) Could you comment oil the time required for blood lead levels to return to pre-test levels following cessation of exposure to the lead in the chambers? KNE1JSON (U.S.A.) We are still analysing the data concerning return to baseline levels. CU1NKE (U.S.A.) According to your calculations a lead air concentration of 10 |tg/nrJ breathed at a rate of IS m1 per day Would yield an exposure or 150 pg per day, one third of which is retained or 50 pg. Why do you think 50 pg which enters by the airborne route is reflected in the blood whereas an increment of 50 pg via the diet would probably not cause an increase in the blood lead level? KNECSON (U.S.A.) ' ' Well, I don't pretend to understand all the details of gastrointestinal vs. respiratory lead uptake. So I can on|y speculate on those relationships. How ever, tile generally accepted figure of 10% retention of Gl-dosc must have a considerable damping cllect on any fluctuations in dietary lead. WILLIAMS (U.K.) How docs Dr. Kn i.l s o n account lor the apparent conflict between his results and those of the .Seven City'Survey: And I might comment that it is more important what happens in cities titan in peniten tiaries. KNELSON (U.S.A.) Interpretation of data from the `'Seven City Study" is still under discussion. As for your remark that what.huppcns in cities is more important than in penitentiaries. I assume it is facetious, One is probably an important function of the other. With respect to our discussion of lead uptake, however, I believe the problems of simulating ambient exposure conditions lor the purpose of carefully controlled clinical studies arc no greater than the problems inherent in the large number of uncontrolled, and uncontrollable confounding covariates in population studies. SANSON! (federal Republic or Germany) According to Ihc writer, artificially manufactured lead-containing aerosols chiefly contain a Pb02. Is this compound also the main source of lead in ualimil lead-containing dust 7 If-not, to vvhul extent can the results obtained be extrapolated') ' ~ 400 -.f. ' rt . r.' - ft'.tjvv-. r -#. - "i-Z'C-. . V.'.-v, ... . .'$ V'*'.' V'-T- ., -' '1 j','-* ' .. ' V :-,c ' " '* VS&ifKia TEH 0470737 DUP050083555 KNKI.SON (I'.S.A.) In addition lo the lead oxides, natural lead containing clusl includcvsomc halides a- Bellas a variety of other materials that may be contained in street air ami included in the particulate xeregatc. Ur. La w tin * discussed these factors w ith much more authority than can I. Because of il*e comparatively very bw concentrations of Ph in the inhaled air. even the relatively insoluble lead oxides must he expected to go quick ly into solution. The more amorphous particles arc probably ingested and digested by ma crophages with resultant ionic Pb rather than any particular Pb compound. CLAYTON tL'.S.A.l Please briefly summarize the health status of your subjects especially in relation to time. Even though jour paper's title does not necessarily require this, it would seem to be needed because of the objectives of the symposium. tNKLSQK <l!,,S.A,) Among the many criteria for inclusion in the study were those concerning the health status of the sub ject*. in brief-- they were required lo have no chronic or acute diseases delectable by ordinary medical . history and physical examination, in addition, they all had normal baseline ECO. chest Him. urinannlyli\,hemogram. SMA-U screen, urinary AI.A. erythrocyte AI.AO. and Wood lead. Although some of \ these values changed during the study, none were outside normal limits. Any changes in " health status indices"were, therefore, subelmical, although in some cases statistically significant changes occurred.