Document 156o0nzYEed2X6x9B9JLNOzaK

UNIVERSITY OF WISCONSIN - MADISON CENTER FOR ENVIRONMENTAL TOXICOLOGY School of Medicine 101 Agricultural Hall School of Natural Resources College of Agricultural and Life Sciences Madison, Wisconsin, S3706 School of Pharmacy December 12, 1972 Dr. Alex Azar Haskell Laboratory Newark, Delaware 19711 Dear Alex, Thanks for the copy of Pallies remarks on the Angle paper on lead in black school children. I have had a reply to my letter to Dr. Angle and I am enclosing copies for your file. I haven't yet digested her reply, so I'm not sure she answered all my questions. Maybe see you soon. If not. Merry Christinas. Sincerely, J. Wesley Clayton, Jr Director JWC:js Enclosures < e r. ,v v- f N40765 THE UNIVERSITY OF NEBRASKA MEDICAL CENTER 4ZND AND DEWEY AVENUE OMAHA. NEBRASKA 68105 December 7, 1972 J. Wesley Clayton, Jr., Director Center for Environmental Toxicology 101 Agricultural Hall School of Natural Resources College of Agricultural <S Life Sciences Madison, Wisconsin 53706 Dear Doctor Clayton: I wouldn't have been so slow in answering if you hadn't asked such tough questions, . ut,in reply: 1. Regarding standardization to the mean hematocrit of 38%*,was done in an attempt to eliminate any concommittant effect of anemia, and the data outlined in Table 1, with detailed hema tologic data in Table 2 . The question here is what is the effect of the non-significant difference in hematocrit? An even more basic question is the effect of iron deficiency on lead absorption and membrane permeability, i.e., the increased peroxide hemolysis of iron deficiency producing a decrease in reductive capacity just as does G-6-PD deficiency. 2. As noted on the enclosed Table 3 listing the hemoglobin and 3. hct at each school, school 6 is geographically in the middle distance group although NNE. The general health status of the G-6-PD deficient was hot noticably altered (although we subsequently admitted one girl with acute renal failure, enclosure 4). Socioeconomic conditions, housing and general health are worst at schools 7-8 and best at: school 6, and are reflected in the hemoglobin values. Schools 1,2, and 6 are all in relatively good neighborhoods of single dwelling houses in good repair. Housing deteriorates from school 3 to 4 to 7 and 8. THE UNIVERSITY OF NEBRASKA LINCOLN Tur i i m : u cd c i t v nr . N4Q765 THE UNIVERSITY OP NEBRASKA AT OMAHA DUP050058761 Dr. Clayton Page 2 4. Regarding Table I, 57.0 vs 48.8 is not significant, as stated in the paper; the other 3 t_ values were all double checked. Tt would take an afternoon to repeat them - please let us know if you strongly suspect an error. 5. Since we don't even know which type G-6-PD deficiency these children had we can only guess that the severity of the defect associated with the different variants may be the critical factor. Ganzoni and Rhomberg (Acta Haemat 34: 338) reported the case of an Italian worker (presumbably with the Mediterranean variant since he had no increase in enzyme activity with reticulocytosis) with acute hemolysis associated''^* a blood lead of 65 ug%. Shafer & Tague reported 2 blacks, each with moonshine nephropathy and hemolysis at blood leads of 70-100. Additional infor mation might be available by calling Dr. Shafer at the University of Oklahoma (405) 336-1366 or the Oklahoma V.A.: 235--9421. The same phenomenon occurs in thalassemia. The Swiss and French write very indignant reports of Immigrant workers with thalassemia trait who develop obvious hemolysis at blood leads well below 80. 6-10. The garbagemen are young, strong looking blacks of transient residence and undocumented health. The lead workers .particularly those with red cell leads above 130 (which corresponds to a blood lead of 70-80), had frequent complaints of fatigue, insomnia, colic, and "ulcer pain". The only specific studies we did in these were of platelet agglutination (grossly impaired) and electron microscopy of the platelets. After inter viewing these men we were convinced that their complaints were valid and their health less satisfactory than comparable blue collar workers. Workers at Plant A rarely had red cell leads above 100 and were in general good health. Air leads at Plants B & C were investigated by OSHA office and found to exceed 20 mg/M^L resulting in multiple OSHA citations and fines and a definite cooling in our relations with industry. Alice Hamilton lives 1 7. The data on ALA-D as given on Table 6 is insufficient for discrimination of enzyme deficient and non-deficient. Please note, however, that ALA-D correlates extremely well with red cell lead - data is in progress to see if the correlation is better than with Pb-B. DUP050058762 Dr. Clayton Page 3 8-9. Detailed studies are now in progress of air, soil, water, milk, house dust, house paint, hair, teeth and dead cats of schools 1 and 9, and 2 control suburban schools (also preschool sibs at school 1). If you know of any way to measure ingested lead without doing balance studies please let us know instantly and save us from all this nonsense. Your questions are all highly pertinent and provecatlv . After looking at our data of the effect of iron deficiency on red cell partition an I b lood lead [ wonder if it wouldn't be worth while to study the effect of lead on glutathione peroxidase and peroxidase hemolysis in the neonate. An other related phenomenon would be the possibility of increased placental transfer of lead from the mother with fewer red colls to bind lead. Our own data shows that 90-95% of lead is found in the red cell fraction in most normal adults, but that the fraction falls off to as low as 50% with anemia, high lead and with caus<>s unknown - See Table 7. Enough of these tables. \.e look forward to hearing of your own studies. As associate editor of CT.INICAL TOXICOLOGY, I am always most interested in clinical studies that you might have in preparation that should reach clinical toxicologists as contrasted to epidemiologists or experimental pharmacologists. If so, please submit to: Richard T. Rappolt, Sr., M.D. Editor, CLINICAL TOXICOLOGY 4141 Geary, Suite 403 San Francisco, California 94118 With best regards, Carol R. Angle, M.D. Professor of Pediatrics CRAimls enclosures DUP050058765 BLOOD AMD RBC I.r.AD AS RLLATLD TO LOCATION AND C-C-PO ACTIVITY Blood Lead (May) G-6-PD 0- 4 4,1-15 > 15 Total t for enzyme (0-4 vs >15) 1 &2 Schools 34.2 +9.5 (20) 34.2 +6.8 (ID 32.8 + 10.8 (13) 34.1 + 9.7 (44) n.s. 3-9 27.2 4 7.1 (53) 25.3 + 4.1 (18) 25*.8 4 7.9 (51) 20.3 4 7.1 (122) n.s. Total 29.1 4 8.4 (7 3) 28.0 4 7.6 (29) 27.3 4 9.0 (04) 28.-1 4 9.0 006) n.s. ^ for Location (),? vs 3-9) 3.2C0 p ^ 0.005 3.572 p <0.005 2.196 p -cO.05 4.808 p < 0.001 38% Blood T.ead ng% x Hmt% G-6-PD 0- 4 4.1-15 >15 Total t_ for enzyme 1 &2 Schools 3-9 38.2 + 12,8 (9) 30.9 (7,1 (23) . 38.3 4 10.4 (77 27.2 +8.3 (Tl) 27.0 + 11.2 (5) 25.4+8.2 (24) 35.6 4 12.6 (27) 27.9 + 8.2 . (Sfi) N.S. p< 0.025 (Mean & S.D.) Rbc Lead pg% G-6-PD 0- 4 4.1-15 >1S Total t for enzyme (.(Mean S.D.) 1&2 Schools 57.0 4 15.5 (10) 52.0 4 16.4 (17) 48.8 4 25.5 (6) 54.1 4 18.5 (29) N.S. 3-9 42.4 + 11.5 (32) 36.1+13.13 (Ts> 33.1 - 11.6 (32) 37.4 + 12.6 (79) p < 0.005 Total 32,9 4 9.7 (32) 31.5 4 10.7 08) 25.7 * 8.8 (29) 29.9 4 10.2 (79') P <. 0.005 J, for Location (1-5 vs 3-9) p< 0. 1 p< 0.05 N.S. p< 0.025 Total 47.3 < 14.7 (48) 33.1 4 11.6 (32) 35,6 4 15.8 (38) 41.9 4 16.2 (10ft) p< 0.001 Jt lor Locdtiun (1-2 vs 3-9 p < 0.001 p ^0.05 P<0.025 p<0.001 DUP050058766 HEMATOLOGIC DATA G-6-PD 0-4 Het % Hb gm% RBC x 106/mm3 MOV m3 MGH y~r Reticulocytes Haptoglobin mg% (all ages) 37.4 + 3.6 (391 12.7 +1.0 (40) 4.38 + 0.37 (40) 84.2 + 5.2 (40) 29.2 + 2.3 (40) 1.2 +0.6 (40) 53.4 + 36.4 (40) / * n.s,, corrected for ago G-6-PD >15 38.1 + 4.C (34) 13.3 + 1.4 (34) 4.52 + 0.64 (34) 83.6 +5.0 (34) 29.8 4-2.3 (34) 1.05 + 0.6 (34) 74.5 -i 40.0 (30) A o _t - test n.c. n.s. n.s. n.s. n.s. p <.05* DUP050058767 4JJ\ vJ' *` X') rJ --) -t-! ri ,*., Cu>v u> lr> m Vi AC*v:O cn '"o**or*-i CO to CM V CM CO fM M4 O cn M4 lO o cn o CD cn CD c cni J(XO. +i +i + 1 + 1! +11 + 11 + l+l1 +1 CD *COr CD DO ro O') r^. 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D> V-i w * CM CO * *3 * 0x3 V) r^J o oO XoX XX o O CO CO 4- 4~ f0 fO +i CQ 1 o *Q K %* Jc DUP050058768  BJH G C PD ACTIVITY ^MOLES/MiN/IOn R5C 80 32 fo ol---- :------------------------------------------------ <0.7 MILE 0.7 _ 4.0MILES DISTANCE FROM EMISSION SOURCE DUP050058769 9 9 DUP050058770 fiW- Vb X Hd % A ;( j ~& / ! 5oWcU PtawYtftf'MA (! ; ..................... ?....... .. IJ .............. 1 ' SKJdcM-j 10/12. . j A 5wc\4erj-' .i 1 ''A i ;_________ _____;_______; .................. .............. jC-y ___: j....... - . h .... I . ...i i : Ct* %, * (3V>c- ( V 4____ 3, 2 i f % rV>t~ * C <>. r* t> I......... . * 4 A 6' & ------ 4-' A \ (lyvlcs t lilifil! .u 30 3o 4o f'b-'B i*-() 0 !c> to loo l X DUP050058771 Legend Figure 1: Correlation of red cell load with red cell ALAD activity in 90 subjects, y =2. 3713 - .01 x r - 0.888 -medical and nursing students, a-urban school children, b> - battery workers, o - lead workers . DUP050058772 JJ MOLES PBG/IOO ML R B C /H R DUP050058773