Document EvJZwdrz2ZZnrbeXLGde96yZV

- -V <^v:**$ ?gvtf : >44^-f 1^14 ssW/'^'^dj wd' \ ^|'-SJ rr.A'.' ? M. v #%4S3 KOMMISSION DER e u r o p Ais c h e n GEMEINSCHAFTEN COMMISSION OF THE EUROPEAN COMMUNITIES COMMISSION DES COMMUNAUT6S EUROP6ENNES UNITED STATES ENVIRONMENTAL PROTECTION AOENCV .Vk> v* i. i". Uvifflf -'* -`*- v V'brVr%t.*it?&SEs&3 ?mA ':*& ' > '1/'^'<-. * ' **'$ V. VsV -: i;4?s4 ,. -S-Jls. /" ---'I :4| .?.?' V.v'l#1j >14? * 4|;4rJ? SYMPOSIUM DIE GESUNDHEITLICHEN ASPEKTE "'ELTVERSCHP "' `TM DURCH BLEI 1.4 f .'/:*i r;% `': C'c^ils .--* ' ' ry-vr-'v3"'% j s r l&'i r^, .. -t_ ENVIRONMENTAL HEALTH ASPECTS OF LEAD \/ LES PROBLEMES SANITAIRES POSES PAR LE PLOMB PRESENT DANS L'ENVIRONNEWIENT pI*'<'>-v.-:.; j:. wf/il 4'~ ;-v.r : ~* ~- *+* ;"4/4'y4 .: *' * ?447f'- Amsterdam (Nederland), October 2-6,1972 LEAD ABSORPTION AND PUBLIC HEALTH: AN APPRAISAL OF HAZARDS : ZIELHUIS, R L. Coronet Laboratory, Faculty of Medicine* University ofAmsterdam* Amsterdam* Netherhincb ZUSAMMENFASSUNG Dgr Bleigehalt im Blut (PbB) 1st gin indirektes Mafl fiir die biologisch wirksame Kdrperlast. In den moisten Fallen ist der PbB-Wert < 40 jig Pb/100 ml. Bis zu dieser Crenze Sind treder eine nennefiswerte Erhdliung der ALA-Exkret'ton im Harn noch akuie oder chronische Wirkungen des Bids festzusieflen. Es gibt bier einen hoften Sicherheitsfaktor, vergtichen mit der zumutbaren Berufsbclastung. Die ALA-Dehy dratase (ALAD) in den Erythrozyten nimmt bis auf > 1/3 abj zusammen mit dem PbB stellt sie einen empfindiichen tmd spezifischcn indirekten Jndikatarfur die biologisch wirksame Korperlast dar. Die Normen sollten sic/t auf die Gesamtiagesbelastimg und nicht auf die Atc-mbelastung altein beziehen. Die zidassige Gesamttagesbeiastung entspricht den annehmbaren biologischen Parametcrn fur PbB, ALAU und ALAD; fur Personengruppen und Einzelpersonen warden Ricblwerte vorgeschlagen. Wurde dem in Benzin enthaltenen Blei zu riel A ufmerksamkeit geschenkt, so konnten Geldmittel und Arbeitskrafte anderen, weit wiehtigeren Aufgahen entzogen warden, die mit der Beemtrachtigung der Volksgesundbeil dureh den Verkehr zusammenhdngen. Viel mebr Geuiicht sollte auf die dkologischen Wirkungen ties Bleis gelegt werden. SUMMARY Pb in blood (PbB) indirectly measures biologically active body burden. Usually PbB <40 jig Pb/100 ml. This.levelprevents evident increase ofALA in urine andacute or chronic effects of lead. There is a large safety factor if compared to acceptable occupational load. ALA-dehydratase in erythrocytes decreases to >1/3; together with PbB it provides a sensitive and specific indirect indicator of biologically active body burden. Standards should apply to total daily load, and not to respiratory load. Acceptable total daily had corresponds to acceptable biological parameters for PbB. ALAU and ALAD; guidelines are suggestedfor groups and individuals. Undue attention to Pb in petrol misdirects allocation offunds and manpower from other much more important effects from traffic on public health. More attention should be paid to ecological effects of Pb. RESUME La deierminafion du plomb sanguin (PbB) permet Indirectentent de mesurerla charge, du corps biologiquement active. Eli general, le PbB est inferieur ou egal d 40 ng Pb/100 ml. Jusqu'd ce niveau, on ne constate pas d'augmentation de l'ALA urinaire ft Ie plomb n'exerce aucun ejfet aigu ou chronique, On dispose encore d'un facteur de securite important par rapport a la charge professionnelle admissible. La deshydratase ALA erytkrocytaire decroit jusqu'd > 1/3: avcc le PbB, elle constitue un indice indirect sensible et specifique de la charge du corps biologiquement active. U convieiufrait de definir des normes applicables non pas aux doses inhalables, mais bien aux doses journali&res fatales. La dose journaliere totale admissible correspond a certains parametres biologiques admissibles pour le PbB, /'ALAU et fALAD; on donne des principes directeurs pour certains groupes ou individus. En mettant indument Vaccent sar le Pb contenu dans 1'essence, on delourne les moyensfinanciers et lesforces de travail dont on dispose d'autres effets plus importants qu'exerce la circulation routiere stir la sante publique. II y aurait lieu d'accorder plus d'attention aux effets ecologiques du Pb. ! 632 TEH 0470305 DUP050083123 1 -- INTRODUCTION The question to be discussed is: Does exposure to lead by non-occupationally exposed human subjects under normal living conditions produce any biological responses, and if so, do these responses present any risk to health and wellbeing? Specific conditions of slum areas, of living near Pb emitting plants, or of pica do not present "normal living conditions", and are not relevant for the main topic of discussion. Due to limitations in space, this paper may sometimes appear to be apodictical; many literature sources could not be discussed as such. 2 -- PARAMETERS OF ABSORPTION One should like to measure the internal chemical load to those receptor sites which react with a specific and sensitive response, at the same tinre being relevant for health. A direct parameter is not available in epidemiology. In practice one has to rely on an indirect approach: determination of lead in blood (PbB), although valid objections exist against this parameter: 1. It is an indirect parameter of Pb burden in receptor sites; 2. Various internal and external factors may influence Pb distribution through the body; 3. The body burden may be divided into: rapid exchange pool (blood, internal organs), intermediate exchange pool (muscles, skin), slow exchange pool (bone) (Pitrowsky 1970) [42]; PbB therefore does not indicate the total body burden. EDTA-induccd Pb excretion (Tcisingcr et al. 1966) [57] might yield a more valid parameter for the rapid exchange pool than PbB. Conclusion: in individuals PbB has its limitations; in groups variability will average out ; up to the present distribution of PbB levels (x a) offers the best practical tool to estimate the biologically active lead burden in groups of population. Table 1 and Figure I present a survey of PbB levels in various population groups from geographically widely distributed areas, published after I960. We may draw the following conclusions from this table and from literature: > 1, The normal range of PbB is 10-40 pg Pb/100 ml, with mean levels <30pg Pb/100 ml ; 2. In the majority ofcases the upper limit does not exceed 40 jig Pb/100 ml, if high risk groups (a.o. slum areas) arc excluded; 3. In last decades PbB has not evidently increased (Stopps 1966) [54]; 4. Urban PbB may be slightly higher than rural PbB, Qit TEH 0 4 7 0 3 0 7 4W,- ' -i " fcj*'1 1 `lh$&5 '<-$&? rk r" li 11 ** W1' "fe J 1j/;'.sfA*'VrmW/ rV, ' - 'n 3$ 'f -T5, V* >t'V *-A?i - \ ! ' ; J v>#^ * v ,,* ; vy 1 <--h / ,'^ir`t .Kv.', J.r* i I 0E5 so\ a %c a *>, I I-HH .5 1 1 5 " 2 e 8 a sfiu* tfi 3 e| fXfli 2 3 04 I II I 41i 3 * I I I 3 4OO= E .C C<S t3s 3O e> , | | O. M % Ss I2 2'E $v 4 eso ;* e ov> V % f--* or- r 0>6\ (N .wr** C?\ O 6 6 6 -x 8X I sI ux Seo P /\ P v 2 > |2 .^ s^r as a B 62 I4 I M I S * 2 A ,1 t4j < n fb. 00 00 ^*HI >-- ^--s oj -H v---s: .c*~** NN g o |5S O_h/ *>m04 v ro <N t vH> -Hn M* O**ro i .= r-H> S 8 s Ov r; OO 00 t n n in * &*Hl X-H -oHs v-H% rl 4f o X r-. 3 i?I tj ^-Sa Hh2S Txo*3 4 is - 2 fEw? zgo 4<sc= HI O xx *--* qps> %^ i j> * 2 |Ol Sft 3 0^-0 e 45 "S -tj 0 O r a a J? " 8 i 2 *s :s aaw J?S e 7*2 2S <h s t> 42s 28 i? |; ll Sa 2C S cC CQ Bmi o5 05 i o QV^> QWQVa/ (3 >>>,?% g s' 3 Q -Soo -o 64 . ov S M _ >> S .2 <3la n 16 . g gW g<U C</1 *co c < wj ^.5 ?g * OOQ D ^ u. w TS 8x w? ^3 C : .5 pM. cC C (J A IP <A < > I SXX lla* * u C C U05D I< mS 532 634 country i0. ...1i0 20` n Grrmany 176 S3 i (00 (( to USA 3637 26 Finland Sweden Switzerland 16 too 76 Italy 116 japan 63 U.K.' $. Amer.,$. kit., Auslr. 6 204 WHO 601 4t e 30 40 50 60 70 Q i>9 Pb/100 ml adults V Germany U.K. Sweden USA. 196 80 30 27 IS 746 children Fig. 1 -- PbB levels; 3e2<r (--|--) or range {----) in various countries, published after 1960, The question to be discussed may now be rephrased as follows: Does an internal chemical load as indicated by PbB levels up to 40 pg Pb/100 ml present any risk to public health? 3 ~ PARAMETERS o f r e s p o n s e The internal chemical load induces biological responses (effects), A no-effect level of PbB only indicates absence of specified effects to be determined with specified methods (analytical, statistical), and does not indicate absence of any effects. .4** 3.1 -- Effects on porphyrin synthesis If effects on porphyrin synthesis do not exceed specified limits, acute intoxication or chronic sequelae will not occur. Hb does not decrease below PbB <50 pg Pb/100 ml. The workshop on inorganic lead Perm. Cee Int, Ass. Occ. Health agreed upon follow ing limits for aduit occupationally exposed workers: PbB 70 pg Pb/100 ml, PbU130pg/l, ALAU 10 mg/I, CPU 300 pg/l (Zielhuis 1969) [64]. ALAU (amino- 'vi, < . i 4 -V S. * i ' ' - ,-; v - -' h A . . Ti'.-tiv . .V.S.A'*- *. -i V * - .. - 7-Ai. ."fife/-'* *K ^ ^ '-> ' ; *: \ t /S } y-i' -nyss%fjJ-'` , -. ,.. ^ i r,i -l ."'^v.-. :. 3&.i ' ; .> . : fv* \>*.-..*?5*r5; . /" ,, >vr*^<" <<sO >* V>* <*' -,) vS: * ; 4M- ~* ** , .vV; .,. * * - ` Jf */; <*' J*-*; '"t .J*VV'.** * 7 "- _. /sf e>`7 *' *5>Vo,, " * '*'$. `* - '*iA'f Al h - , ' "^S* ' $5f -u - `4>i^V*W,s ' -'; '"UllUi $?## * ', .^V* Ji 1 - v vn. :>r- A> AAA v:; A AAiJ P'- "v>4';'*': ^ a ,^ a a s Ii ^ -*t '-X ''syu^j >y; 'f-'-Vy>i ^i'M^ 4-:^ ; - - ,. a\ * *'*, ^*TK. *?* ` <>\* -<'?/*&-* ' a ? ' '* ^^f< v,*-`^-Vvav!^>>, , ' t^s 'A'-;V ' ' .C-<. j<: ; i *. ^ .-.,> p j ". ' ' * t '., 1 ^* vS V! * 1 < ^!S.si^ .. '?-. 4y*'v-.,*.i. X1. s'.. V^.-'..`v'A..Al_;^Wiiai J b ^ ^, x * -,**,->;* * B<;*?^ Vj-A.sj'' -* "rPr'i-t S *5 '''SckSSB laevulinie acid excretion in urin) i$ more specific and more sensitive than CPU (coproporphyrin in urin), so for public health ALAU is more relevant. Table 2 and Figure 2 present the relationship between PbB and ALAU. The following conclusions may be drawn: 1. The no-effect level of PbB is abaut 40 pg Pb/100 ml; increase in Figure 2 below 40 pg Pb/100 ml derives from mathematical calculation and is hardly evident in practice; 2. ALAU does not present a sensitive parameter for biologic monitoring in public health. According to some authors (a.o. Chisolm 1971) [12] ALAU does not appear to be sensitive in children. More sensitive and more specific is the decrease in activity of 5-ALA-dehydratase TABLE 2 Relationship between PbB {x) and ALA-U tv) Aulhor(s) Year of publica- lion Number of subjects Relationship Remarks Hacgcr- 1971a [19] 110 log y - 0.01294*-0.8605 PbB 10-120 pg/100 ml Aronscn y in mg/100 ml r " 0.61 Lchncrt el at. 1970 [66] 158 no increase of y PbB<55 pg/lOOml Lehnerl et al. 1969 [67] 127 y = 0.9 *+6.1 PbB 47.3 24.8 pg/100 ml r = 0.36 138 no Increase PbB 26.0 12.4 pg/100 ml Hernberg et al. 1970 [23] 141 *<50pg/l00n>i no increase of y; *>50pg/100 mi PbB 10- I30pg/100 ml ` increase of y Hacgcr- 1971b [20] 260 *<50 pg/100 ml PbB 10-90 pg/100 ml Aronscn et al. no increase of y; *>50 pg/100 ml increase ofj< Sclandcr et al. 1970 [50] 150 log y 0.0157 *-1.0985 y in mg/100 ml in erythrocytes (ALAD); it appears to be too sensitive for use in monitoring of workers. Table 3 and Figure 3 present the relationship with PbB. From these and other literature data the following conclusions may be drawn: 1. ALAD is highly specific for early responses to lead; 2. In patients with neurological and haematologicai disorders no decrease of ALAD has been noted; 636 TEH 0470309 DUP050083127 mg II 0 20 40 60 80 PbB pg Pb/lOOml Fig. 2 -- Increase of ALAU in relationship to PbB. Harnberg at at >970 Hi 11r at at 1970 b .H|t9r-Ardnrt a I at 197.1 -*-* PbB in jig Pb/IOO ml Fig. 3 -- Pcrccntual decrease in A LAD in relationship to PbB. ; * s^/.1/f.-_v*. , tV'<y*'^ r>;vJS-;1?^-i ,,'*f,** 'v * Jl TABLE 3 Relationship between ALKV-actirity (y) in erythrocytes and PbB ;(.v) AuthorCs) Year of Number publica of tion subjects Relationship Remarks Wcissberg 1971[61] 234 linear in total blood; children and et at. adults; PbB<80 pg/100 ml Schallcr et ai. 1971 [45] 196 no relationship PbB 11,5 4.9 pg/100 ml 30 significant, r - --0.41 PbB 16-30 pg/100 ml 15 significant, r = --0.63 PbB 20-30 pg/100 m) 70 significant, r - --0.25 adults, average PbB 14.9 pg/100 ml Hernbcrg 1970123] 158 log y = 2.274 - 0.0! 8a: PbB 5-95 pg/100 ml et pi. r = -0.90 Haeger- 1971b [20] 260 logy .= 2.29i --0.020a: PbB 10-90 M8/100 ml Aronsen et ai. r - -0.83 children and adults ,M illar et ai. 1970(40] 57 logy = 6.7685-0.0436a: children. PbB 10-20 pg/100 ml r - -0.80 Sccchi et ai. 1971 [49] 102 r = -0.41 PbB probably <50 pg/100 ml not occupationally exposed Basecqz et at. 1971 [7] 47 curvilinear PbB 20-75 pg/100 ml r - -0.82 (expressed as pg/100 ml ery) 7. 100 80 60 40 20 public health occupational health ALAU 20 io 60 80 100 -*-* PbB In jig Pb/lOOinl Fig. 4 -- FcrccnUial change in ALAD cii ALAU in relationship to PbB. 638 TEH 0470311 DUP050083129 3. Haemsynthcsis is probably not affected if ALAD > 1/3 normal level; 4. In rats there exists a linear relationship between ALAD in blood and in brain; 5. Relationship PbBx ALAD is the same in adults and in children; 6. There do exist indications that the no-clfeet lcvcl ofPbB is about 5-15 pg Pb/100 ml (Schaller el al. 1971) [45], The difference in sensitivity in regard to PbB between ALAU and ALAD is presented schematically in Figure 4: ALAD has little significance for occupational health, ALAU has little significance for public health. As far as known decrease of ALAD as such has no or little significance for health, if the activity remains > 1/3 normal level; the body appears to possess a high reserve capacity, ALAD is a highly sensitive and specific parameter for early response, and indirectly for biologically active internal load, but as such is not relevant for health. Protoporphyrin in erythrocytes (PP) increases from about PbB=40 pg Pb/100 ml (Haeger-Aronscn 1971 a) [19]; it is less sensitive than ALAU (Albahary 1968) [2]; and therefore not relevant for public health. 3.2 -- Effects on erythrocytes Lead affects erythrocytes: decreased: Na+-K+-ATPase activity in membranes, life span, increased: K* efflux, glucose consumption, osmotic resistance, pyruvate levels after glucose dosage, prevalence of Heinz bodies. These responses however are less specific and less sensitive than ALAU; they probably do not appear below PbB = 40 pg Pb/100 ml (Hcrnberg 1970 [22], Qazi 1971 [43], Moncrieff el al, 1964 [41], Ghelberg 1966a [;6]). 33 -- Other biochemical effects Numerous effects have been reviewed by De Bruin (1971) [10]: decreased: immunobiological reactivity, alkaline phosphatase, cholinesterase, carbon anhydrase, amino acid levels, increased: serum aldolase and catalase, modifications in serum protein pattern, etcetera. Most or all of these effects have only been observed in workers with symptoms of poisoning or with relatively high exposure. They do not appear to be relevant for PbB <40 pg Pb/100 ml: One animal experiment (Bingham 1969) [65] may appear to be relevant: decrease in alveolar macrophags in young male rats, if exposed to Pb in air (PbA} = 10 pg Pb/m3; this reversible effect still has to be studied in human subjects in order to evaluate its relevance for health. Ghelberg etal. (1966b) [17] found increased urinary excretion of 5-hydroxyindolaceiic acid in 11 year old children living in the vicinity of a lead emitting industry (PbA about 31 pg Pb/m3); this parameter is less sensitive than ALAU (Urbanowicz al. 1969) [59], 3.4 -- Effects on clinical health and life span Possible effects on kidney function, tension, cerebrovascular incidents are only seen in subjects with longterm high exposure (PbA > 1 SO pg Pb/rn3) or with acute intoxications in their medical history (Malcolm 1970 [38], 1971 [39] ; Cramer et at. 1966 [13], Stopps 1966 [53]). Hickey et at. (1967) [25] studied specific mortality rates in the general population in relationship to air pollution with metals (PbA: x -- 1.1396 pg Pb/m3); there was no relationship with disease classification, in contrast to possible relationship with Cd and V. Szadkowsky et at. (1969) [55, 56] did not observe any pathogenetic relationship between PbB and various internal diseases. In a soft water area with relative high Pb intake the increased cardiovascular mortality did not appear to be related to Pb intake (Crawford et at. 1969) [14], Effects on chromosomes have been reported, however only in subjects with high PbB (Schwanitz et at. 3970)[48]; in drosophila there was no effect of inorganic lead (Ahtberg et at. 1972) [!]. The animal experiments of Schroeder et at. (a.O. 1968) [47] have drawn much attention: in mice and rats long term oral intake of 5 ppm Pb in drinking water gave rise to Pb levels in soft tissues in the same order of magnitude as in American adults; moreover there was a decreased life span. However, these data cannot be extrapolated to human beings, because apparently the kinetics of lead in rats and mice differ _ considerably from those in man; the daily oral intake of these animals was 400-500 pg/kg body weight, about 80-100 times that in human beings; moreover the rats received a Cr-deficient diet. Schroeder et at. (1968) [47] found increased Pb content of ribs in American adults up to the 5th decade; the lack of increase in older age groups might--according to Schroeder et at.--be caused by shortened life span due to increasing Pb body burden. These data have been severily eritisised by Kehoe (1969) [29] and cpuld not be confirmed by Barry et at. 1970) [6]. Conclusion : A lead body burden, represented by PbB <40 pg Pb/100 ml probably is consistent with absence ofeffects on A LA U, PP, many other biochemical parameters, clinical health and life span. Conclusive evidence of such effects have not been established, and data with suggestive evidence hardly exist. 4 -- RELATIONSHIP DAILY Pb UPTAKE AND PbB There does not exist adequate information on the relationship between longterm daily exposure and PbB. The Nat. Research Council---NAS (EPA 1972) [15] suggested a curvilinear relationship between total daily uptake (PbA in pg) and PbB: PbB * -- 69.2052 + 54.7605 log PbA. This aequation apparently is very approximate, more or less a "guestimate". The following assumptions have been made: 1. 24 hr continuous exposure -> overcstimation of daily exposure; 640 TEH 0470313 DUP050083131 '--S' - '' 2- Daily respiratory volume 23 m3 -* overestimated; 15-20 m3 appear to be more reasonable; 3. 30% retention and 100% resorption; one may assume maximal 100% resorption after maximal 50% retention (Schlipkdlcr 1972) [46]; 4. Daily oral intake 300 pg Pb, which appears to be questionable. The aequation probably gives maximal PbB in regard to current PbA levels and overestimates the realistic relationship. Some data from other-sources (Kehoc 1961, 1966[28]; Williams 19.68) [62] (respiratory and/or oral intake) have been recalculated, and added to the NASaequation (Table 4); multiplication of PbA with 5 corresponds to multiplication of PbB with about 2. The maxima! allowable PbB for adult workers is 70 pg Pb/100 ml according to Working group on inorganic lead Perm. Cee int. Ass. Occ. Hlth (Ziclbuis 1969) [64]; this corresponds to a safety factor of 10-20 for continuous 24 hr exposure to Pb for the adult general population. This safety factor is large if compared to safely factors as applied in food additives (from animal - man; 10; from man -* man; 10). TABLE 4 Relationship between lead in air (PbA in pg Pb/m3) and lead in blood (PbB in pg Pb/100 ml) NAS PbA Kchoc Williams NAS PbB Kchoe Williams r 2.o Sx 4.0 5.0 Lio.0 20,0 5x -- -- .50,0 100.0 --w 5.0 -- 15.0 -- 25.0 -- -- 150 [2.1.3 . -- 7x 27.3 -- -- 30.3 30 to.o L40.0 P-n *T-- 55 -- 53.8 -- 2x 70 40 -- -- 50 71.6 .-- TM 87.2 -- ---- r--.. 145 -- --p. 35 -r-r- 65 73 --. The relationship between PbA and PbB is based upon calculations used in occupational health for uptake of particles with aerodynamic properties, and about 1 pin diameter. Recently Lawther el at. (1972) [33] seriously critisized this procedure, because in sampling air near a heavy traffic road in London Pb proved to be present in aggregates and particles of much smaller diameter, c.g. 0.01 p; according to Lawther one may presume a maximal retention x absorption of 10-12%, much lower DUP050083133 than assumed retention X absorption of 30-50%. This appeared particularly true for Pb emitted by motorcars. Therefore the safety factor in regard to respiratory Pb uptake from traffic exhaust may increase with a factor 2-4, and become 20-40. In Table 4 a daily oral uptake of 300 pg Pb has been assumed (review by Karhausen 1972) [27]. This intake may differ considerably: 100-500 pg Pb/day. In Europe Lehnert et al. (1969) [36] calculated a daily intake of 518pg Pb for Germany (DBR), in U.K. Thompson (1971) [58] measured average 274 pg Pb (70-750), Kloke et al. (1968) [30] estimated for Germany (DBR) an intake up to 1400 pg Pb/day, Vigliani et al. (1969)[60] estimated 400-500 pg Pb/day for Milan, Italy; Horiuchi (1970) [26] measured 230-320 pg Pb/day forJapan. The Comm. Europ. Communities undertook a comparison of total diets, excluding alcoholics, of adolescents in various countries within the Common Market (Smeets et al, 1970) .[51]. If we apply the data of Lehnert et al. (1969) [36] to the average diet, we arrive at a relative difference in oral daily Pb intake with a factor 2 (Table 5). If between groups the long term oral Pb uptake differs 200 pg Pb/day, then daily gastrointestinal absorption will differ about 20 pg Pb. This corresponds to a difference in 12 hr respiratory exposure of about 5 pg Pb/m3. Such a large difference in daily respiratory exposure appears to be more unrealistic than a corresponding difference in oral exposure, at least for Europe. These considerations emphasize an important point: the total Pb uptake mainly stems from oral uptake; it is therefore unrealistic to propose MIC values, one should determine an acceptable total daily load. However, it is very difficult to measure this. This may emphasize the feasibility of biological sampl ing, either through parameters of absorption (PbB) or parameters of response (ALAD), both indirectly measuring the biologically active body burden, and at least in groups of the population with a reasonable degree of reliability. In adults the biologically active body burden appears to a large extent to be independent from age (Barry et al. 1970) [6], in contrast to the slow or hardly exchangeable body burden in teeth and bones. Children, especially in younger age groups, should be regarded as a special group, distinct from adults. They probably differ in: 1. Increased hazard of oral uptake, particularly in toddlers; 2. Increased gastrointestinal resorption: in young rats up to 80% if milk with a low Ca/P ratio is being administered (Kostial et al. 1971 a [31], 1971 b) [32]; 3. The daily oral uptake if taken per kg body weight far exceeds that in adults (Chisolm et al. 1956 [M], Baltrop et al. 1967 [3.]: average 120-130 jig Pb, 95% <183 pg); 4. The relative proportion of the body burden present in the slow exchange pool is smaller (Barry et al. 1970) [6], 5 -- ASSESSMENT OF RISKS FOR ADULTS IN THE GENERAL POPULATION The data regarding adult population groups so far discussed may be summarized as follows: 1. PbB normally does not exceed 40 pg Pb/100 ml; 2. The no effect level in regard to increased ALAU is about 40 pg Pb/100 ml and very probably higher for most signs and symptoms relevant for health: 3. ALAD in erythrocytes decreases from PbB = about 10 pg Pb/100 ml to 1/3 of its activity at PbB -- 40 pg Pb/100 ml; up to now there is no evidence that this decrease as such has any significance in regard to health or wellbeing, either at short or at long term: 4. There exists a safety factor of at least 10-20 in respiratory 24 hr uptake for the adult general population if referred to acceptable respiratory uptake of workers., based upon the relationship between PbA and PbB: 5. Between population groups ora! uptake probably differs to a larger extent than respiratory uptake; total daily uptake mainly stems from oral uptake; one should determine total acceptable daily Pb uptake; 6. Biological monitoring (PbB or ALAD) provides an easier, more realistic and more valid indirect yardstick of total daily uptake in population groups than a multitude of individual direct measurements of Pb in food, beverages and air. There are gaps in knowledge; even When research is going on, gaps in knowledge will always remain. Nevertheless, at this moment there are sufficient data available in order to conic to a justified policy for establishing acceptable total daily loads for adult population groups. However, we should bear in mind the gaps in knowledge as mentioned by for instance Hardy (1969) [21] and Smith (1969) [52]: 1. Not enough data exist regarding the extent of variability in total daily exposure; 2. High risk groups (PbB 30-50 pg Pb/100 ml) especially should be studied more fully; 3. There exists the possibility of increased susceptibility due to genetic defects, e.g. sickle cell trait, or due to pregnancy. 6 -- ASSESSMENT OF RISKS FOR CHILDREN For children we must add some extra points for discussion, summarizing the data mentioned so far: !. The total daily load per kg body weight is appreciably higher; 2. The possibilities for oral uptake, particularly in toddlers, are higher, whereas intestinal resorption may appreciably go beyond the 10% as assumed for adults; 644 TEH 0470317 DUP050083135 3. The oxygen consumption in the brain is relatively high; there are indications that a body burden corresponding to PbB > 40 pg Pb/100 ml may aggravate an already existing mental retardation; 4. The rapidly exchangeable body burden is relatively higher; 5. The acceptable limit of PbB == 70 pg Pb/100 ml as proposed for healthy adults, probably docs not apply for children; the margin of safety is probably smaller. Future research should especially be directed at gathering data from young children; measurement of daily total uptake, body burden (also with EDTA provo cation tests), biological responses; particularly long term follow upstudies are needed, taking fully into account data on mental development. 7 -- a c c e p t a b l e b io l o g ic a l l imit s Environmental standards have to take into account total daily uptake; this can be measured indirectly by biological monitori ng of PbB, A LA D and A LA U. Particularly for more or less homogeneous groups one may conclude to acceptable biological limits, characterised by group average and upper limit: for individuals one may present upper limits. These limits should not be regarded as fine tines discriminating innocent from nocuous environments; however, if these limits are exceeded the possibility of undue acute effects and/or chronic sequelae increases. The data as established In population groups should always be interpreted by experts, and not by the lay public as such. Single values moderately exceeding upper limits in individuals should cause awareness and caution: the measurement should be repeated. Group data have a stronger significance than individual data. The following acceptable limits are suggested as guidelines; For adults PbB ALAU ALAD individual limit : 40 <6 20 group average < 25 <3 2* 30 unit |ig Pb/100 ml mg/I urin procenlua! decrease from 100% (at PbB = 10 ng Pb/100 ml) For children PbB ALAU ALAD individual limit < 35 <5 > 30 group average 20 <3 5s 40 as above as above as above 8 -- Pb IN TRAFFIC EXHAUST Within the Common Market recently much attention has been paid to the public health aspects of exposure to traffic exhaust. A few comments should be made: 1. There are insufficient data regarding the effect of Pb in petrol on total daily intake; as yet there are no indications that oral intake of Pb in adults has increased due to traffic exhaust. PbB levels in USA have not evidently increased in last decades (Slopps 1966) (53). 2. Regional variability in oral uptake probably exceeds variability in uptake due to traffic exhaust. 3. Traffic exhaust appears to yield a smSffi contribution to Pb uptake in children if compared to many other sources of lead (Baltrop 1972) (5). 4. Up to the present moment there are no indications that under conditions prevailing in the Common Market health and wellbeing of adults and children has been negatively affected by lead in traffic exhaust. 5. The overwhelming attention in the Common Market to Pb in traffic exhaust yields a greatly distorted picture of-thc total range of negatieve effects of traffic on public health': accidents, noise, traffic congestion, traffic axhaust. The most promising and rewarding approach to tackle the problem of traffic and public health is to decrease the distance between traffic and human subjects (living quarters, working quarters, playing grounds, etc.). If available money and man; power are solely or mainly directed to restriction of Pb in petrol, we may have a somewhat cleaner environment in respect to Pb, but the much greater other risks to health and wellbeing continue to exist and to increase. 6. Much attention is being paid to direct effects of Pb on human health. However, Pb ultimately pollutes the environment, particularly the oceans. If this affects primary production, indirect effects on human health and wellbeing may occur. This field of study deserves a higher priority in allocation of funds and manpower than research on direct effects on public health. 9 -- GENERAL CONCLUSION Pb is a non-essential element; therefore presence in the human biological system should be minimised as far as possible. In this respect restriction or elimination of Pb in petrol should be promoted. However, within the total significance of traffic for public healih, other measures should receive a higher priority. If these measures-- politically much more difficult to achieve--arc taken, the potential risks of Pb in petrol to public healih will indirectly decrease ai t the same time. 646 j TEH 0470319 DUP050083137 REFERENCES 1. Ah l b er o , J,, Ra me l , C,, and Wa c h t me is t er , C.A., Organolcad compounds shown to be genetically active. Ambio, I (1972) 29. 2. Al b Ailah Y, C., Views on actual occupational lead poisoning. Report H'ork Conf. inorg, lead, Amsterdam 1968. - 3. Bar l t r o p, D. and Kiu .a l a, N.J. P., Faecal excretion of lead by children. Lancet, ll (1967) 1017. 4. Bar l t r o p, D., Environmental lead and its paediatric significance. Postgrad, med J., 45 (1969) 129. 5. Ba r l t r o p, D., Children and environmental lead. Conf. Lead in the enrironment, London 1972. 6. Ba r r y , P.S.1. and Md s s man , P. B., Lead concentrations in human tissues. Brit. J. industr. Med., 27 (1970) 339. 7. Bas ec q z, J.M., La u w er y s , R., et Bu c h et , J. P., Etude comparative de divers tests biologiqucs d'exposition au plomb. Arch. Mai. prof., 32 (1971) 453. 8. Bl a n k s ma, C. A., Sa c h s , H. K., Mu r r a y , E. F-, and O'Co n n el l , M.J., Incidence of high blood levels in Chicago children. Pediatrics, 44 (1969a) 661, 9. Bl a n k s ma , A., Sa c h s , H.K., Mu r r a y , E.E., and O'Co n n e l l , M.J., Failure of ALA lest to delect pediatric lead poisoning. Amer. J. din. Path., 52 (1969b) 96. 10. Br u in , A. pe, Certain biological effects of lead upon the animal organism. Arch, emironm. Jflth., 23(1971) 249, 11. Ch is o l m, J.J. and Har r is o n , H.E., The exposure or children to lead. Pediatrics, 18 (1956) 943. 12. Ch is o l m, J.J,, Screening techniques for undue lead exposure in children. J. Pediat., 79 (1971) 719. 13. Cr amer , K. and Da h l iie r g , L. Incidence of hypertension among lead workers. Bril. J. industr. Med., 23 (1966) 101. 14., Cr a w f o r d , M.D. and Cr a w f o r d , T., Lead content of bones in a soft and hard water area. Lancet, 1 (1969) 699. 0 EPA report; Nat. Research Council, Nat. Acad, of Sciences: Airborne lead in perspective. NAS rcpori 1971, ref. EPA publication 1972. 16. Gh el ber g , N. W. et a!.. Investigation on the appearance of Heinz bodies under the inllucnecs of small lead concentrations in the atmosphere. Igiena, 15 (1966a) 209, 17. Gh el ber g , N.W., Go r g a n , l,, and Ch ec in , !,, 5-Hydrpxy-mdolacetic acid excretion in a population chronically exposed to slight atmospheric lead. Igiena, 15 (1966b) 87. 18.Go l d w at e r , L.J. and Ho o v er , A.W., An international study of "normal "levels of lead in blood and urine. Arch, environtn. HUh, 15 (1967) 60. 19.Haeg ek -Ar o n s en , B., An assessment of the laboratory tests used to monitor the exposure of lead workers. Brit. J, industr. Med., 28 (1971a) 32. 20. Haeg er -Ar o n s en , B., Ah d u l l a, M., and Fr is t e d t , B.J., Effect of lead on <5-aniinolevulinic acid dchydrasc activity in red blood cells. Arch, emironm. Wilt, 23 (197lb) 440. 21. Ha r d y , H.L., Discussion in J. Air Point. Control Ass., 19 (1969) 701. 22,Hek n ber q , S., Effect of lead on some erythrocyte functions. Congr. Chemical pollution and human ecology, Prague, 1970. 23.He r n b er c , S., Nik k a n en , J., Me l l in , G., and Lil iu s , H., <5-Aniinolcvulinic acid dchydrase as a mesure of lead exposure. Arch, emironm. tilth, 2! (1970) 140. 24.Her n ber g , S, and Nik k a n en , J., Effect of lead on d-ALAD. Prac. Lekartsui, 24 (1972) 77, 25.Hic k ey , R. J., Sc iio f f , E.P., and Cl e l l a n d , R.C., Relationship between air pollution and certain chronic disease death rates. Arch, emironm. HUh, 15 (1967) 728. 26.Ho r iu c h i, K., Lead in the environment and its effect on man in Japan, Osaka City Med. J., 16(1970) 1. 27.Ka r h aUSKN, L. R., Intestinal absorption of lead, F.EG doc. no. 1146/72 d, 1972. 28. Keh o e, R.A., Criteria for human safety from the contamination of the ambient atmosphere with lead. 1,5thint. Congr. accup. kith, Vienna, 1966; Vol. Ill, p. S3. 29. Keiio e, R.A., Toxicological appraisal of lead in relation to the tolerable concentration in ambient air. J. Air, Pollitt. Control Ass., 19 (1969) 690. 30. Ki.o k e, A., urn) Ltat, H.O.. Vexuntreinigung von Kulturpnanzcn mil BIci ays Kraftfahrzeugab- gasen. Proc. First Ettrop. Congr. influence ofairpollution on plants ancl animals. Wageningen, 1968. 31. Ko s t iai., K., Simo n o v ic , i, and Pis o n ic , M,, Reduction of lead absorption from the intestine in newborn rats. Environm, Res., 4 (1971 a) 360. 32. Ko s t ia i., K., Simo n o v ic . I., and Pis o n ic , M., Lead absorption from the intestine in newborn rats, nature, 233 (1971b) 564. 33. La w t h e r , P.J., Co mmin s , B.T., El l is o n , J.Mc K.., and Bil es , B., Airborne lead and its uptake by inhalation. Conf. Lead in the environment, London, 1972. 34. La w t h er , P,J., Communication. EEG seminar on lead metabolism, 1972. 35. Leh n ek t , G., Der Blutbleispicgel und seine Bedeytung fur die Pathogenesc und Prevention deT bcruflichbedingtc Bleivergiftung. Stuttgart, Centner, 1968. c..36. LEiin e r t , G., St a d e l man n , So u l ie r , K.H., und Sz a d k o w s k i, D., Usucllc Blcibelastung durch Nahrungsmittel und Gctriinke. Arch. Hyg. IBcrl.), 153 (1969) 403. 37. Lo b, M. ct Des bau mes , P., Etude dc plomWmie ct de la plomburie Chez deux groupes dc detenus, les uns internes a la campagne, les autres it proximite immediate d'une autoroute. Schweiz, med. Wschr., 101 (1971) 357. 38. Ma l c o l m, 0., The effects of lcud on the kidney. Trans, Soc. otettp. Med., 20 (1970) 50. 39. Ma l c o l m, D., Prevention of long-term sequelae following the absorption of lead. Arch, emironm. Hith, 23(1971) 292. 40. Mil l a r , J.A., Ba t t is t in e, V., Cu mmin g , R.L.C., Ca r s w e l l , R, and Go l d be r g , A., Lead and ALAD levels in mentally retarded children and in lead poisoned suckling rats. Lancet., 11 (1970) 695. 41. MoNCRiiar. A.A., Ko u mj ij es , O.P., Cl a y t o n , B.E., Pa t r ic k , A.D., Ren w ic j c , A.G.C.'and Ro ber t 's , G.E., Lead poisoning in children. Arch. Dis, Chihih., 39 (1964) I. 42. PioiRowsKt, J. K,, Kinetic behaviour of lead. Congr. Chemical pollution and human ecology, Prague, 1970. 43. Qa z i, H., A simple rapid test for lead poisoning. J. Pediat., 79 (1971) 805. 44. Re ic h e l , G,, Wo b it h , F. und Ul mer , W.T., Akule und chronische Wirkung von Straszeoluft an verkchrsreichcr Kreuzung. Ini. Arch, Arbeitsmed., 26 (1970) 84. 45. St iiAU.iiR, K.H., Ma c t ii , K,, 1!aas ,T., Ma c h .e, W,, und Va l e n t in , H., Methoden zur Bcsvim- riiung dcr Dcltu-Aminolilvulinsaurc dehydratasc-Aktivitat in der Erythrozylcn und ihre Bedcu- tung fur die bcruflichc und usucllc Blcibelastung. Eur. Gemeinschaft Dgk. 3107/71 d, 46. Sc h l ipk o t e r , H.W., Die Deposition und Resorption von inhaliertcm Blei in dcr Lunge. EEG doc. no. 1056/72 d. 1972. 47. Sc u r o ed er , H.A., Br a t t l e iio k o , V., and Tip t o n , I.H., The human body burden of lead. Arch, environm. Hith, 17 (1968) 965. 48. Sc h w a n it z, G., Le h n e r t , G., und Ger h ar t ., E., Chromosomenschaden bei beruflicher Bleibe- lastung. Disch. med. Wschr., 95 (1970) 1635. 49. Se c c h i, G.C. and At.Essto, L.. Studies on ALA-dehydratase of erythrocytes in subjects not occupationally exposed to lead, living in industrial and rural areas. Personal communication 1971. 50. Se l a n d Er , $. and Cr amer , K,, Interrelationships between lead in blood, lead in urine,and ALA in Urine during lead work. Brit. J. indtistr. Med., 27 (1970) 28. 51. .Sw eet s , J, and v.o. St r ic u t , E., Comparison of (he radioactive contamination of the total diet ;k . of adolescents in the community. Eur 3945, 1970. s52A Smit h , R.G., Air quality standards for lead. Air quality monograph, no. 69-11. New York, Amcr. Petroleum Inst., 1969, 648 TEH 0470321 t DUP050083139 53. St o pps , G.J., Ma x f u i.d M. E., Mc La u o iii.in , M,, and Sp f l i,, S.. Lead research: current medical developments. Trans,. 31 stann. meeting Induslr. hyg. Found., no. 40 (1966) 72. 54. St o pps , G.J., Discussion J. Air Pollut. Control Ass., 19 (1969) 719. 55. Sz a d k o w s k i, D., Sc h a l i.f r . K.H., und Ra d u n s k i, K., Das Vcrh.atlen dcr Blathlcipsicgcls bci einigen internen Krankheiten. Arbeitsmed. Sosiulmed, Arbeitsing., 4 (1969) 54. 56. Sz a d k o w s k i, D., Wiimf r s iia l s , E.. Lin d n e r , K.. SniAU.iR, K.ll., und LtHNFRr, G., Eiivflusz von Aidostcron auf Einflux und Efflux Mincralicn. bit. Z. angeie. Physiol., 27 (1969) 99. 57. Te is in g e r , Pr er o v s k a, I., und Se d iv l c ., V,, Vcrsuch uni die Bestimmung vom Blei-Pcpot Im Ktirpor bci cxpcrimcntcller BlcivcrgifUmg. 15t/iint, Coiigr. oentp. ifltli, Vienna, 1966; Veil. Ill, P. 79, 58. Th o mps o n , 5, A., Balance between intake and output of lead in normal individuals. Brit, J. indnstr. Med., 28 (1971) 189. 59. Ur b an o w is c z, H., Cr a b e c k i. J,, and Ko z ik l s k a, J., The urinary excretion of 5 HIAA in indus trial lead exposure. Med. d, Laroro, 60 (1969) 582. 60. Vic i.ia n i, E.C. and Zu r l d , M-, Lead in .blood and lead in urine values of adults not exposed to lead, living in Milan. Report Work Con/, inorg. lend, Amsterdam 1968. 61. Weis s bf .k G, J.B., Lip s c h u t z, F., and Osxi, F.A., ALAI) activity in circulating blood cells. New Engl. J. Med., 284 (197!) 565. 62. Wil l ia ms , M,K,, Relationship between dose estimated by personal sampler and some biochemi cal tests in workers in a battery factory. Report Work Conf. inorg. lead, Amsterdam 1968. 63. Wil s o n , A.T., Effects of abnormal lead content in water supplies on maternity patients. Scott', mcd. J., I I (1966) 73. 64. ZiELMUts, R.L., Permissible limits tor inorganic lead in industry. Proc. 16//i ini. Ctmgr. occttp. . Hlth, Tokyo, 1969, p. 510, 65. Bin o h a m, E., Trace amounts of lead in the lung. In: Trace substances in cue. health. 111, p. 83, University of Missouri (1969). 66. Le h n er t , G., Ma s t a l l , H., Sz a pk o v v s k i, D., und Sc h al l e r , K.H., Berufliebe Bleibclasyung durch Autoabgase in Grossstadtstrassen. Dtsebe. Med. Woch., 95 (1970) 1097. 67. Le h n er t , G., K a d e, Ch., Sz a d k o w s k i, D., und Sc u m.h r , K. 11., Praklikabilitat, Zuvcrlussigkeit und Dignilul dcr HSmvorlaiiferbcstimmung bci der (Jberwachung Blciexponiericr. hit. Arch. Cewerbepath. Cexrerbchyg, 25 (1969) 267. DISCUSSION ABBR1TTI (Italy) Are the acceptable biological jimits you propose in your paper also valid for workers occupationally exposed to lead ? In a statement published in the British Medical Journal (1968) the acceptable level of 8-ALA in urine of workers exposed to lead was fixed at 20 mg/day. As the increased excretion of 8-ALA and coproporphyrin means that haem synthesis is affected (whereas the decrease in ALA-D docs not necessar ily and always mean an impairment of haem synthesis, this enzyme being " non limiting" in the haem biosynthetic pathway), don't you believe that this limit is too high and unacceptable also for occupa tionally exposed people, and that also in view of the importance of haem in many fundamental functions of ceils and considering the presence of other pollutants in the environment that can inter fere with haem synthesis? ZIELHIJIS (Netherlands) No. In november 1968 a working group under the auspices of the Suhooni. on MAC, Perm. LComm. Int. Ass. Dec. Hlth., convened in Amsterdam and promised the following acceptable limits; 649 'V#JS ' -- Ys*.1rr-?* ti:V>* :/MviSP A*'C - yf:: "7' TSPi' i1 ' - ' At.' % yfj&m t A1, t Vs 'E'gSW i 'Zs/fr ^ MS"' A r, 'X "Vs. ' w-': ' 1 r : ;v.r,. l tV, (, ' ' ` 5 4 :;5 - felb'yki&ZZA si-.-:- ; iCtvvie.'-. - ,i7'i "* * **4^v' . ' :Jt Sw v *4.' '.Li *> -.ff ,*y i ; : mt ' >- 'r ' - " i I? * ' '" ^ 'i0M * ; '. 'urjf.e' x v' *. TEH 0470322 DUP050083140 Pb in air 1 JO tig/m3 in blood 70 jig/100 ml in urine 130 jig/I ALA in urine 10 mg/I Coproporphyrin in urine 300 pg/l Sec: Arch, em ironm. tilth, October 1971 and R.L. Zie l h u is , Proceedings 16th Int. Congress Occ, tilth., Tokyo, pp. 510-512, Tokyo, 1971. CRAMfiR (Sweden) I whole-heartedly agree with the guidelines given in your paper, although I know that it will be diffi cult to live up to those standards. I would only like to make the remark that your average values must represent the median values and not the mean values, as these distributions (end to be truncated to the left. ZIELHUIS (Netherlands) Most data in literature are presented as x 2cr, although distributions probably are skewed. For the provisional tentative guidelines I proposed average levels and maximal levels, but I agree with Or Cr x mf .r , that in the final proposal acceptable percentile levels should be given: recommendations for < 50%. as 95%, ?S99% of population groups; the size of the monitor groups should also be given. SCHUPKOt ER (Federal Republic of Germany) With the present-day air lead burden of large cities, man is already taking up as much lead with respi ratory air as with foodstuffs. ZIELHUIS (Netherlands) If we assume: -- oral intake 300pg Pb/day, 10% absorption; -- average Pb in ambient air 5 pg/m3; -- 1:2 hr exposure every day to ambient air outdoors; -- 12 hr exposure indoors to I pg Pb/m3; -- retention 50%, absorption 100%, 10 m'/l2 hr outdoors, 5 m3/l2 hr indoors; then uptakc/day: -- gastrointestinal = 30 pg -- respiratory 10.5.0,5. " 25 pg 5.1.0,5. = 2.5 pg total 57.5 pg Pb According to "Air lead concentrations in the Europ. Comm. April 1971 - March 1972" the assumed air lead concentration of 5 pg Pb/m3 for 12 hr/day appears to be too high for everyday exposure of the "normal" public. Also, taking into account the work of La w t h e r , the respiratory retentionabsorption of 50% may be too high. Therefore, the above presented calculation--apart.frOm being a "calculated guess "--probably presents an unrealistic picture of the tong term daily intake of the "normal" public; presumably the respiratory daily absorption generally is below 50% of total daily absorption. SCHLIPKOTER (Federal Republic of Germany) As long as we are uncertain whether the reduction of ALA-D activity is of importance to health, we must take into consideration this enzyme change when assessing the effect of lead. ZIELHUIS (Netherlands) Clinical physicians in their treatment of patients very often have to make statements, although they always have to hear in mind the possible uncertainties. However, they have to carry this burden .themselves, and not burden the patient with scientific doubts. Also public health physicians have to bear a responsibility in giving statements to governments, and should not stay away from it because they still have theoretical questions. 650 TEH 0470323 DUP050083141 Certainty can be given in three levels: (a) general scientific consensus or dose-cfTccts relationships, (b) reasonable doubt: scientists discuss together potential risks, albeit there is not yet a certainty, (c) theoretical risks', asking questions without reasonable basis in scientific hypotheses; science-- being science--will never stop asking questions, neither now, nor in the future. Acceptability should be based upon a and b; reasonable doubt is covered by a safety factor. Level c cannot be covered. Progress of research may lead to change in levels a and h, and therefore also of c. Some environmentalists say: " It does not hurt to be too safe". However, this may be a false statement, because all preventive measures use resources, and this policy may use up limited resources for the wrong cause. SCHUPKOt ER (Federal Republic of Germany) Your mean blood lead values can be accepted. A blood lead level of 40 pg% for individuals is too high, since such values are harmful to the health of pregnant women and sick persons. ZIELHUIS (Netherlands) Average group levels and maximal individual levels should be dealt with in combination. My pro posal has to be discussed. Some changes may have to be made. Up to the present I do not think that levels 40 pg% (and not higher) have been proven to be harmful for pregnant women and sick persons. LOB (Switzerland) With progress in occupational medicine and medicine in general, Pb sources tend lo decrease. There is only one source which is continually increasing, i.c. pollution by exhaust gases. We arc obviously, without any criteria for assessing the health hazards, although wc have one parameter, the decrease in ALA-D activity of which wc do not understand the real significance, but which is apparently a factor in cerebral activity. A reduction of the part played by exhaust gases would appear to me to be a moot question. On the other hand blood lead docs not represent the total lead in the organism. Lead is stored in the bones and may be mobilised under the influence of various stresses, e.g. malaise, ZIELHUIS (Netherlands) There are at least two methods to reduce traffic exhaust Pb: reduce Pb in petrol, or reduce number of cars/number of people. The second method also results in a reduction of other risks to public health: accidents, noise, other exhaust gases, etc; however this reduction also has some negative ef fects: decrease of degrees of freedom (easy transport, holidays, etc.). There is a benefit-risk balance. Paying undue emphasis to Pb alone disregards other public health risks.From the medical point of view there is nothing against a decrease of Pb in petrol (if this docs not induce increase of other exhaust gases!), but at the same time from tlic medical point of flew there is little to propose this measure as a very important contribution to puhlic health. The relationship traffic-public health should be considered in its total benefit-risk balance and not in the context of one (and not the most important) factor. Lead is stored in the bones. There is inadequate basis for the statement that thisdeposit-- ifas a result of long term low level exposure--contributes to ill health under the influence of various stresses. What is "malaise"? PALUES (U.S.A.) For years in Philadelphia 1 have watched the growing interest in tend absorption in children. We once had a death or two a year attributed to lead, but not in recent years. 11 is difficult today lo demonstrate clinical illness referable to lead. Yet wc are devoting hundreds of thousands of dollars every year to the removal of lead from the environment of children who are living in wretched surroundings where they arc severely malnourished, nibbled on by rats, breathe carbon monoxide in large quantities and arc exposed to other hazards of known deleterious cll'cct. if we succeed after the expenditure of vast efforts in removing this suspected hazard causing unknown but suspected harm wc will leave these children in a totally wretched environment but a lead-free one. There is, as Prof. Zieuiuis has said, a need for examining our priorities and devoting our efforts to helping these children rather than running scientific investigations of academic interest. WOIITF.RS (O.F..S.C.) Concerning standard* lo be observed fur workers employed in /Inc and/or lead ore processing plains, which, in your opinion, arc ihe standards regulating a) temporary withdrawal front work, b) permanent withdrawal from wprk'! Zl KM I td.S tNetherlands) In 1968 a Working Group on inorganic lead, Perm, fee Ini. Ass. Ooc. Hlth., proposed the following guidelines for occupational exposure Pb in air 150 pg Pb/mJ Pb jn Wood 70 pg Pb/100 ml Pb in urine 130 pg Pb/I ALA in urine JO mg/I Coprop, in urine 300 pg/I These guidelines should be regarded as "warning signs"; the industrial physicians should rcchcck le vels, examine working conditions; the levels should not be regarded as sharp tines, demanding withdrawal from work. The industrial physician (adequately educated in lead toxicology!) should pay particularly attention to the health of these workers. Temporary or permanent withdrawal from work demands an experienced judgment of workers and work situation, and cannot be laid down in "standards"! ELLISON (U.K.) I should like to draw attention to the fact that Dr. Ziu.tiuis is mistaken in staling that Law t iif .r n a/, (1972) suggest thul one may presume a maximal retention x absorption of 10-12%. Law t h er et ah quote the data of Dav ies and his co-workers (references below) as indicating that for tidal breathing and for insoluble monodispersc spherical particles of diameter 0.5 pm the pulmonary deposition was in this range, and further say that the experiments on which this conclusion was based were ofsuch quality that they must be taken as indicating that for these particles the I.C.R.P. curves were too high, La w t iie r et ot. also accept the inference that the I.C.R.P. curves were too high over that part of the size-range on either side of this, and since a large proportion of the particles observed in their electron micrographs of particles from vehicles arc aggregates of about this size they conclude that deposition is considerably lower than the figures often quoted. They do not venture to pul forward a figure in the paper referred to. Aerosols front industrial sources cannot be assumed to have the same particle size distribution and may therefore have very different pulmonary deposition. References: Mu ir , D.C'.F. & Dav ies , C.N., Annuls ofOccupational Health, v. 10, 161-174,1967. Dav ies , C. N,, Hk y pe r , J., & Su b iia Ra mu , M.C., Journal ofApplied Physiology, v. 32,591-600^1972," and Dav ies , C.N., same journal, 601-611. He y d e k , J. & Dav ies C.N., Aerosol Science, v. 2, 437-452, 1972. BRIDBOKD (U.S.A.) My own calculations indicate that the differences (safety factor) between industrial lead exposure and general population lead exposure are considerably less than the 10-20 time factor that you quoted in your presentation. Any calculation of the difference between occupational and general population lead exposures must consider the difference in total lead exposures that exist between the groups. For example a worker in occupational exposures is commonly exposed to air leads of ISOpg/m3 for a 40 hour week. This is equivalent lo breathing air Containing approximately 150 * 40 + 2 x 128 _ 6000 + 256 168 6256168 ' 37jig/m3 This assumes breathing air at 2 pg/m3 when not on the job. Linder the additional assumption that approximately 30% of airborne lead is retained in the lungs; that nearly 100% of this retained lead is absorbed; that an adult male breathes 20 nv1 per day and has a dietary lead intake of approximately 300 pg per day of which 10% is absorbed the following table cun be constructed: 652 ' " . .. i ' ' \ '' ^ . * * , -* , ... "f - 7. . -.V*>-, . V-+" f* . DUP050083143 Daily lead absorption Absorption from air Absorption from food Total Occupational Exposure Community Exposure 37 x 20 x o.J = 222 2x20x0.3= 12 300x0.1 =30 300x0.1 =30 >51 Relation factor or safety factor - 6 252 42 Can you please comment. Z.IELHUIS (Netherlands) Wil l ia ms found PbB = 75 pg Pb/100 ml in workers exposed ip 200 pg Pb/m3 (personal .sampling), 40 lir/wk. This increases (as far as assumptions prove to be correct) the safety factor calculated by Dr Br id bo r d with f ; it becomes 8. According to my table 4 PbB = 65-75 pg Pb/100 ntj corresponds to PbA = 40 pg Pb/m3.24 hr; a safety factor - 2 in PbB corresponds to a safety factor = 8-IQ in PbA = 5pgPb/m3 and 20 in PbA - 2 pg Pb,m3. I agree with Dr. Br iu b o k u . that his method of calculation is more correct, taking into account the total (air + nutrition) exposure. Another calculation is also possible: porker, 150 pg Pb/m3, 8 hr, 40/wk: ^espiratory absorption 5 workdays: 150 pg/m3 x 10 m3 2 pg/m3 x 10 m3 resp. absorption weekend 2 pg/m3 x 15 nv3 nutrition, 7 days x 0.4 x 5 d( 8 hr) = 3000 pg x 0,4 x 5 d( 16 hr) = 40pg x 0.4 x 2 d(24 hr) = 24 pg 210 pg week total 3274 pg Pb general population, light activity, 24 hr exp. 2 pg,'m3; .15 m3: respiratory absorption 7 dajs: 2x15x0.4x7= 84 pg nutrition '2l0pg week total 294 pg So safety factor (between acceptable exposure in adult worker and general populalion):3300 300 "n' Both safety factors, taking into account various assumptions, are of the same order of magnitude: 10. In food toxicology a safely factor of 10, covering variability in sensitivity between human subjects, generally is regarded as adequate. Moreover 150 pg/m3 is--in Western countries -regarded as an ucccptublc exposure already itself containing a margin of safety. Jf the criticism of La w t h e r proves to be valid, then respiratory absorption of exhaust Pb is lower, say 15%, this increases the safety factor in regard to Pb from vehicle exhaust.