Document KJO6ywzjw8vK2NaOO0xYNjOO0

KETTERING LABORATORY EDEN AND EETHESDA AVENUES CINCINNATI, OHIO 45219 COLLEGE OF MEDICINE DEPARTMENT OF ENVIRONMENTAL HEALTH July 13, 1967 Dr. Robert J.M. Horton Health Effects Research Program Public Health Service 5008 Federal Office Bldg. Cincinnati, Ohio 45202. Dear Dr. Horton: Me have discussed your letter of June 20, and agree that there is much to recommend a survey of the "tri-city" .type. To clarify think ing on this point, however,' we should indicate that we are dealing here with several questions which are related and yet deserving of pre cise and specific answers. It is useful to comment briefly on these 1) . To what extent is atmospheric lead responsible for body burdens of lead in persons living in certain environments? 2) How accurate is the determination of blood lead in estimat ing soft tissue lead or whole body lead? 3) What is the progressive year-to-year pattern of lead levels in urban populations and atmospheres? 4) What is the minimum body burden of lead which constitutes a hazard to health? * -' # Question number 4 is outside the scope of this discussion be cause it would best tbe conducted on certain industrial grouos known to be exposed to- air concentrations of lead which are "considerably above ambient urban levels. Question number 2 reflects the uncertainty that blood lead levels accurately reflect the body burden (or soft tissue burden) of lead. We have already discussed with pathologists the feasibility of obtaining fresh body tissues from persons dying accidently but who had previously been in good health. Appropriate bone and soft tissue lead assays relating lead concentrations to those in the peripheral blood have been proposed. There is a possibility that this cadaver study might be funded from a different source; however, discussions have been only tentative. There remain, than, two principal questions: one concerned with trends of blood and air lead concentrations and the other which examines the relationship between air concentration of lead and tissue lend Dr. Robert J.M. Horton Page - 2 Of these, the first represents a re-survey of ambient air levels and-populations previously examined. The validity of such work would be increased by maintaining insofar as possible the exact conditions observed in 19b2. Ideally, persons surveyed in 1962 would be located and re-tested providing their location of residence or occupation had not changed during the interim. With respect to correlations between ambient air lead con centrations apd.blood lead levels, we propose that a somewhat more detailed study be: conducted in specific areas. Air sampling should be truly' representat ive of thpsq,'persons being studied. This, is accomplished \by the use of neighborhood sampling ('blood and air) as opposed to more geperal regional investigation. Primary consideration 'Jri.ll be given to women in the study because occupational factors are less important and because relatively more time is spent by women in a single neighborhood. Commuters and people in industrial settings'' ape'less suitable if we are attempting to establish a correlation between lead body burdens and ambient urban lead.concentrations. The question of adding additional cities to those previously included in the study has been raised. We believe that a detailed study should be carried out only in Cincinnati and Los Angeles. Spot evaluations might also be made, however, in Philadelphia, Chicago and New York to confirm the general applicability of the detailed work and to determine the present status of lead-in-air and lead-in-blood concentrations in these large urban areas. We also believe that information derived from the National Air Sampling Network may be useful' in identifying several communities in which consistently low lead-in-air values provide a low end of the curve for correlation studies. While the measured levels are not comparable on an absolute basis with those which may be determined by_the Laboratory, we at least know that levels approximating 0.1 microgram/m are con sistently recorded in Cedar Rapids, Iowa; Massena, New York; St. Peters burg, Florida; Cheyene, Wyoming; and Helena, Montana. These levels are lov/er than the anticipated rural mean. Accordingly, there is much to recommend a. small study in one or more of these areas, providing that the low lead-in-air levels are confirmed and determined continuously by a standard method. We have determined blood lead levels in truly rural areas west of Cincinnati near the Indiana line. On the basis of our findings, it would be appropriate to study air ana excretory lead levels in this community as a part of trie Cincinnati survey. The feasibility of studying the inhabitants of rural religious communities has also been examined.' There is no reason why this cannot be done, but it is probably best not to in cor;. ? :o ur.ic work in the initial "a - RE 0019530 Dr. Robert J.M. Hortbh Page - 3 A natter deserving special consideration is an evaluation of the extent to which lead in food and drink may account for bod;/ lead or differences in body lead of dissimilar populations. The tri-citv scudy made no attempt to examine this variable which must be considered if we are to attempt a blood-air lead, correlation. It is essential to identify 'the'^xtpnt t: 'which lead.ih"ingested food and'drink, is re sponsible for any variations in blood lead which may be encountered. Recognizing the difficulties associated with collections of duplicate samples of food and beverages, we feel that it is important to incorporate a'fecal and urinary ja^say program in the study.. Until this (or food assays} are done, we shall remain unable to present conclusive evidence that the cause of biological variations in lead levels is a specific reflection of lead in the atmosphere. There are obvious difficulties in the collection of excretory samples from neighborhood populations, but with iLt.ble instruction and orientation this .hopefully can be. accomplished with good accuracy. We feel very strongly that a tight experimental design is fundamental to the appropriate conduct of this work. Discussions have been held with Dr. John Varady of the University Computer Center, whose group is prepared to provide statistical consultation and com prehensive data management and analysis service. To develop a feeling for the, magnitude of this project, vie summarize below an estimate of the sampling patterns and the volume of analytical work: Stations Cincinnati Los Angeles 10, including rural - 6-8 Philadelphia 2 Chicago 1 or 2 New York - 1 or 2 NASN low-lead sites - 2 Air Sampling 24 stations x ^6 weeks x 3 filters/ week = 4,032 air samples. (It is possible that a 2 x/week filter change would be adequate. It is also possible that pooling of aerometric analyses would represent certain economies of effort without significant loss of data. On the other hand, taped sequential samples should be used selectively and limited studies of particle size are warranted.) HE 0019531 Dr* Robert J.M. Horten Rage - 4 Blood Sampling 20 geographic groups of 50 people each - 1000 samples 10 occupational groups of 50 people eacn = 500 samples Metabolic Sampling 6 groups of 10 persons x 10 days x 2 excretory samples/personday = 1200 samples Cadaver Study 2k cadavers x 25 samples/cadaver = 600 samples (4 cadavers in each of 6 decades of life) We should like to comment briefly on the points raised in the minutes enclosed with your letter. Revised Hjnutes - 14 March 19o7 1. We agree that the three city pattern is useful and propose that it be repeated in a modified version. 2. The study should be initiated as soon as possible after detaile planning has been concluded. This is particularly important inasmuch as sequential sampling and analysis are contemplated. Subsequent studies v/i depend upon the initial findings, but to a great extent the nature of the possible subsequent studies must be established before any data are collected. 3- We propose that for 1907-68, Cincinnati (including at least one rural station) and Los Angeles be studied. Two low-lead sites identified by the WASH are proposed to establish correlations at the low end of the scale. While it will become necessary to confirm that general inferences can be made from specific areas, the immediate need is for reliable and specific local information. This is better achieved by meticulous, and repeated observations in related controlled situations than by more general surveys. Stations in Philadelphia, Chicago, and New York are recommended to detect trends and validate basic correlations k. Ten survey sites in southwestern Ohio and 6 to o in Los Angele are proposed. This will provide ample contrast and specific local infor mation. Two additional low-level sites identified by NASI! are recommend-; to extend the low ranve. KIT 0018532 Dr. Robert J.M. Horton Page - 5 3. Pooling of results from a given station -is' permissible since integrated lead exposures are desired. The extent Of; the.pooling remains open to discussion-. Insited. tap sampling and particle:, sizing is warranted, but certainly hot on a continuous basis. 6. We agree that no change in analytical methods is advisable and that urine leads should be omitted. It may be worthwhile considering an investigation of gas chromatographic assays of lead as a chelate in order to establish the accuracy and precision of this highly sensitive technique. 7 and 8. While the use of selected population groups is recommended we are not fully enthusiastic about police officers. The problem is that they move about a great deal and live and work in varying places. We believe that population groups living in stabile neighborhoods represent a more, suitable source of study groups. Ideally air sampling should be conducted in the immediate neighborhood of persons sampled. We have approached neighborhood groups in both urban and rural communities and have.obtained good cooperation. We have also conducted preliminary talks with members of religious conimunities and find no administrative bar to sampling air and blood, representative of such communities. The importance of fecal surveys is again emphasized. While it is not necessary that all participants be on a collection regimen, it is im portant that we eventually document tha_t alimentary lead Is not responsible for any variability noted. 9. On the basis of the Three City Study, a detailed biostshistical framework should be prepared for the projected study. 10. Continuous quality control is central to the entire study. May 31, 1967 1. A 13 - 14 month period is suitable; however, the decision to discard certain data should be made before those data are collected. 2. We propose that limited serial sampling be performed on members of the study groups. While previous studies show no seasonal variation, serial samples would confirm- this observation. They would, also tend to establish more precisely the true level of blood, lead in a given population 3- We agree that blood levels of 50 u/100 g deserve prompt re- check and investigation as warranted. ' k. Children should be excluded. '' K* 0019533 Dr; Eo'oert J.M, Horton ^age - 6 5. We suggest that SAIA not be investigated in the survey. This may possibly be a valid measure of one biological effect of lead, but we are not looking for biological effects of lead in this survey. If We, webe, v;e would recbmmehet 'startirig by inyestlgating. persons known to be exposed to relative high levels of environmental lead. 6. We agree that newcomers should be excluded. We are looking for persons who reflect the environment which is tteing measured and to 'which they are' exposed. In pijlqt ^.studies."We>''haw arbitrarily; used 5 years local residence as a reqjuii'ement for Inclusion. In stabile neighborhoods this is not difficult. 7. The repeated reference to quality control is warranted. Quality control specimens should not be identifiable by persons per forming the essay. We agree that 20 ml of blood is desirable; however it Is not always convenient. For this reason we have suggested preliminary studies of gas chromatographic techniques. The proposed study is not the place to Introduce new analytical methods as a primary tool.. However, the usefulness of this technique as a check and an eventual method should be considered, and this Is an appropriate time to do so. In response to the request for a description of a quality con trol plan, the following outline may be useful: a) 30 - 40 tubes of blood, each containing 12 - 15 ml, are filled in rapid succession by means of a doubled-needled plastic tube, one end of which is in the ante-cubital vein of a paid donor. The usual blood donor represents a blood level close to the anticipated mean. From a known high-lead patient representing a level of approximately 50 - 60 yUg/100 g a similar series of tubes is obtained. We have not found that significant hemodilution occurs during the few minutes that 30 - 40 samples are drawn from a single subject. The samples are stored by freezing. b) At suitable intervals a control specimen is withdrawn from storage, given a label which cannot be distinguished from the study group, labels, and introduced into the general sample load being presented to the analytical group. Specifically: the control is not marked as such, its presence in a batch of tubes ip not known to the technicians or laboratory supervisor, and it arrives at the laboratory in the conventional manner, i.e., it is not handed/to someone while all other tubes come air parcel post. c) Tubes are available to other laboratories for cross-checking. d.) A single individual of the department is responsible for the entire control tube puo-rr-;':. a prime responsibility ill be - > hsenre ---at the ''secret17 nature 01 the program'Is maintained. 0018534 Dr. Hobert J.M. Horton Page " ? 9- Cross-checking to determine comparability between original and new,studies is appropriate. 10. We have not discussed in any great detail the advantages of cooperation with either Dr. Vigliani of Milan or Dr. Petrovic of Belgrade. Both are established investigators; and have staffs adequate for the conduct of air and blood sampling programs. They, in addition have access to populations with relatively high blood lead levels, although the source of the absorbed lead is not entirely clear. The source of the high atmospheric lead in these communities is presumably motor fuel, although gasoline consumption and lead con tent are. relatively low. After consultation with our epidemiological aivisers, we will consider the way in which we might invite Dr. Vigliani or Dr. Petrovic to submit a proposal to us so that an efficient integrated survey can be accomplished. The sponsors of this entire project will oiuriously be kept informed of extensions in this direction. We believe that a study can be developed which will provide specific answers to questions pertaining to lead in the atmosphere. We look forward to our discussions with you next week with respect to efforts in this direction. LBT/lh