Document emYodnG0N6NdEBbr4nV3v1y8y

SAL.TIMQRS Cit y Ho s p it a l s ,s J .,' '. o. nii*e o *mc x o h ' * /- 4040 e.Ksrr.nN-AV.NU5i . . . .OALTIMORS. MARYLAND Z44 ;; v\ * . ; v'. \ * July 26, )m :;v V`:' ^ * .. *.,v . :.vv v ,V;v-v> i -.;' ;.-* > ;-..> ; * . ** ' * ?' Vaon A,, Nev/ill, M. D, . \ ` Assistant for Health Effects r > .> ** ' * V , Office of Research and Monitoring, . . 'United States Snv.ironmantaI-Prote-c.Kon Agency ** * Washington, D. C. 20460 , ' .* . -. , . .`M * '**1 * in r^i'wy iuff* T. v*Decr.D% NJewI 11: *. t . *; * ? .... This Is* In response to your letter of May 31, 1972* I beg your indulgence for c:.y delay In answering; I shall comment on those of the many questions you posed upon which ! can , best comment* * * - '. . . , # With respect to question number (1) (Goldsmith-Baxter equation), ! wiii make or.;- . a general comment* When dealing with vary low levels of exposure* from.a variety of source^ seems almost Impossible to sort out the relative contribution of each individual source through a , human epidemiologic approach, l presume that you have had response from competent biostens- ticians on the actual equation, ` i Question (2)* It would appear to me that whole blood lead concentration* do nor * . provide an adequate index of total body lead burden. On .the one hand, the Tri-City Study indlco.*- ' in living persons, no increase in v/hole blood lead concentration with age/ On the other hemd, autopsy studies do indiccte an increase In bone lead concentration, but not int/fe con cen tre r, o ~.s y in ike soft tissues. To my knowledge,* serial blood lead and bone biopsy studies {un contaminate: with bone morrow) have not been done. 1 be! ieve that the NAS document adequately summeri the in formation on relationship between blood fead concentration and the "mobile" and "peony diffusible or non-mobile** fractions of the total body lead burden, it would be helpful in one's thhrking to divide the bona lead pool into Vincorpordted'1 and ,,cd$orbsdu fractions. Whether **.r stored In bone Is totally physically "inert11 would probably depend upon the presence of conc/'c* . which affect the rote or dissolution of bone. It seems likely thot only disorders associated v/irh rapid dissolution of bone might be associated with significantly rapid mobilization of lead Into ; . tissues. Whether such things occur in human populations would have to be studied io cbrorr.l: * *' whether the? rate of mobilization of load from bone v/ould bs sufficiently rapid to be harmfu;. Appropriate sub}acts for study might include those with "renal rickets, " hyparparothyroidfem, v./;* / .'/**' `v v ,*, * Vi..../ - * , 4 % -. , * * * * ; . * .' * .* * . >*., * >.'* , , _ . * *.A* . . *** * * ', M40748 DUP050058502 ;V/ V::un A. Nuwili >Iy26, 1972 0 2 pilot's disease of bon>, high-close: long lorn/ .cor ti cost c.riod ih.trupy <uv\ powilly orl* r group* of dJwojivis. Willi resjvrcf to young children, the -issue might ha mom uppropnnpdy in wcurtliiwj oniirvdu It r /ay opinion that the* following statornunr in your Ic j IN-i* i: incorrect; 11 Wo know I lint chulatioo therapy 6f children \vi th elevated blood I acids con result in acuta cjln'i-r.: . symptom* of lead poisoning as a result of mobilizing. Jjcid from bone," In my opinion, If;a backgrc/ for fiiis Statement has found its \voy info the medical literature largely on I ho basis of experience prior fo the use of chelating agents and that today, such apparent occurrences ore more oftan due to inadoqueto and/or inappropriate use of chelating agents In children with.very severe iiIncsses and blood lead concentrations that ordinarily are wall above the 100 pg Pb/i'GQ g whoi* blood level. My thinking on this point is given In the attached reprint. I know of no evidonco thcr lead incorporated into bone i.s removed by chelating agents. Unfortunately, .most of the animal data on this point have been obtained.in acute experiments, which are not suitable to answer fids question.' . ' . t i .* i j With regard to question (3), 1 know of no additional evidence besides that cited in the N'AS report relative to the amount of air breathed per.day. Suffice it to say that one would anticipate some variation in respiratory exchange in relation to body size, metabolic rata ana .physical activity# ** .r ** * ,,_ With regard to question (4), it is my opinion that it Is not entirely appropriate to > extrapo!ate industrial threshold limit values to the general population inasmuch as the Industrie! . population is likely to be selected and is unlikely to include individuals who may show increased susceptibility to certain occupational levels of exposure to lead. In particular, tfvK* with iron deficiency states due either to deficient intake or chronic increased .blood loss chi*3/ from the G* i. tract may be more susceptlble,as was pointed out In NAS document. Jn this regard, the recent report or Six end Gayer on experiments in iron-deficient weanling rats is appropriate. . (J. lab. and Clin. Med. 79:128-136, 1972, The influence of iron deficiency on tissue content and toxicity of Ingested lead in the rat}. The data in this study indicate that absorption or lead ; fronf'The gastrointestinal tract may be greater in the iron deficient experimental subjects. With regard to the occurrence of clinical symptoms attributable to plumbism in humans, one should -cm that where such episodes have occurred in individuals with blood lead concentrations in the 50-60 p Pb range, such individuals are generally found to have moderately severe anemia - usually of the iron deficiency type. ' . .' ' ... ^ * 'With regard to question^(5)., i recently forwarded to Dr. Bridbord some comments on the occurrence of Increased lead absorption in children in the Smeltertown area of El Peso, Texas, With regard to the lead content of dust and soil in urben areas, there is no data known ;o me which identifies the relative contributions of automotive exhausts on the one hand, and Iccc from point derived from the weathering and demolition of old buildings to which lead-based paints iCve been applied, particularly on the exterior. Relatively speaking, the direct ingestion of loedcN joint flakes by young children provides a far greater dose of lead than does exposure to dust.* If s certainly true that intake of lead from all sources is additive with respect to the total dose lSsimiiGted. However, the dose provided by the repetitive ingestion of small flakes of paint appear ar greater then all other sources combined, if one cxciudes'such things as moonshine whiskey end DUP050058503 .j'V.rvyv:*.V| A, Nvtwi.il ; My 26} 19/2 '' ' ` 3 improperly lec:J~;ku:ec! corc.nviewarc and other unusual sources. CPAs proposed (eduction o: ioaci onviisioos may help to radu-co the incidence of minimally .elevated blood lead conear,trr:,`Ior.. In young children^ but it is unlikely tlie;! It will ha vs ct measurable effect on the occurrrvvcc* or iky sort of cl ini eel disease associated with definite residual deficits, as seen today in children* At issue is the question of whether blood lead concentrations in the ^0-60 pg range sustained over a period of Iwo to three years or longer In early childhood is associated with adverse effects on function, development and growth In young children. At the present time, it can be stated on'y that -measurable adverse metabolic effects in the form of increased ALA excretion in unm-s and increased levels of protoporphyrin in bleed may be found in a significant proportion of such chil dren. Whether these metabolic observations are associated with significant cicveiopmenrai end functional defects is not known and is difficult to determine because the affected children ere also subject to many other sorts'of environmental deprivation which, in turn, may cdv^rvoly cZhzt fham. 1 co,nngt agree entirely with those who say that all lead npjson!no in young children h no: 'dua to Five inaestion -or loaded painLchjj^ red ornon areas 1 :?r /nrj Vv:TtjV. thorough seqrch-f^J!r?:^.;v-?.jpri.rt, Wr.Mo it is certainly desirable to reduce the lead content of dus/*and dirt, the hazard of lecci and o!d paint, is certalnly-a far more concentrated and hazardous source of exposure. Appropriate studies . with respect to housing area and source of exposure,and particularly to the Cl Paso group of chi-ers*, *-might provide more definitive answers to your questions. * ' `* In view of the likelihood that we mcyVnever obtain epidemiologic data in humans v/t.i . can provide clearly defined limits,, if would appear appropriate to limit exposures from various v * * `-so that total assimilation in 'the general population Is such that blood lead concentrations are rr.c at 40 -jig Pb/IOG g whole blood or less-. 'This probably would provide due*allowance-for suscepfio factors known and unknown. . ` ***** ^ * .' v- /:vf- Yows sincerely/_ . ' .*. , s>/? "*. * . J JCiOV Enc;*. cc: Dr. Paul F. Wekrle, Chrnn., * *vV1 *?*?: }1vJ jf\.y* .. . Co.T.r.1. yn Enviroiimenrai Hazards, AAP V: W-' " ' ' * * j , * *.v* '-/' '*% '.i.* *'y.?* **>.,. .*. ,*v' ... .'* i* *,/*'. * '* .* /* . - *-. . : : : .... .i ...*** ' ` u:'11 **. .svX**7r . > ... , . V v^' /'*.*v>*-' ..*.*,* ... . *I ^.. -'^-v^* ;Tv ^v ,V.-.: .. <. S'&Y.-K'-"- -v DUP050058504