Document 6wY93bMJNEnjRXjXXbzbB5JkR

American Petroleum Institute (THE METABOLISM OF LEAD) March 15 Robert E. Eckardt, M.D. c/o American Petroleum Institute 1291 Avenue of the Americas New York, New York 10020 Dear Doctor Eckardt: I am sending herewith a revised copy of the propo to the International Lead Zinc Organization for as may be taken in connection with this project b American Petroleum Institute. Pages 1 and 2 are (so as to keep this portion of the record as it w August 1965), while pages 3 and 4 have been alter bring matters up to date. I trust that this will be satisfactory for your p Sincerel RAK: wp enclosure Robert A HE 00123: LABORATORY, IN THE DEPARTMENT OF ENVIRONMENTAL H OF THE COLLEGE OF MEDICINE OF THE UNIVERSITY OF ON THE PROJECT "HUMAN EXPOSURE TO PARTICULATE LE COMPOUNDS IN THE AIR UNDER EXPERIMENTAL CONDITIO On October 3, 1362, the general experimental procedure o together with the details of a specific experiment to be were described in detail. Further proposals, relating t of the work, were made on September 4, 1963 and on Septe work has gone on in essential accordance with the purpos described in these proposals, and is to be continued in similar lines indicated herein. The immediate goal of the experimental work in 1965 was through human experience, the maximum concentration of i and absorbable (i.e., pulmonary absorption, exclusively) the ambient atmosphere to which normal, healthy, human s subjected, continuously and for indefinitely prolonged p incurring the potential risk of a demonstrable degree of in their bodily tissues. The experimental principle involved the exposure of two parallel respiratory chambers, to air containing lead (a of Pb, as lead sesquioxide, per cubic meter) dispersed i (ranging in diameter from less than 0.01 to 0.18 microns of 0.05 microns), on an intermittent schedule of increas per day every other day for approximately IQ weeks, i.e. 6 hours per day every other day for approximately 16 wee week; and so on to 31.5, 42.0 hours, etc.) until the eff became evident through a slight (statistically demonstra output or concentration of lead in the urine, presumably experiments) without demonstrable increase in the concen blood, of the subjects. During 1965, these observations have continued as schedu adaptation of the periods of exposure to the tolerance o disruptions of their daily lives. That is, when the sch of requiring the subjects to spend more than 12 hours pe (on alternate days) it became necessary to shift to dail Obviously, also, the continuation of the family life of at least, one day per week of freedom from exposure. Th schedule, involving the proper number of hours of exposu into equivalent periods on six of the seven days of each (August 1965), one of the subjects (N.K.) is spending 63 is not anticipated at present that it can go fa 6 days per week, with due regard for the comfor subjects. If then no response shall have been of lead in the chamber will be increased by a s incremental increases in the duration of exposu beginning at a level of intensity (time x conce duplicate that of previous steps. It will be n a response, and such response must be graduated intensity through at least three levels in exce to provide data for extrapolation to the effect (24 hours per day on 7 days per week). Accordi expected to continue through the entire year 19 It is conceivable that the experimental regimen shorten the time required to obtain definitive doing are under consideration at present, and t be explored critically at the end of this calen risk, however, in any radical alteration of the experiment, in that too sharp an increase in th excessive response, and threaten, thereby, the subjects. It was for this reason that the init of lead in the chamber was set at 10 micrograms which could be counted on (from indirect but sa yield negative results at first, with the possi a positive response as the time factor progress With the present facts and anticipations in min program in 1966 is expected to be similar to th may be affected, since it seems unnecessary, in analyze duplicate samples of the food of the su between the lead in the food, day by day, with is so satisfactory as to enable the former item apparently without introducing an error that is error. Further statistical work will be necess in this regard with certainty, and this feature critically at the end of the current year (1965 H S 003t* First, with reference to the experimental results now said that one of the subjects (N.K.) completed the des 16 weeks, to air containing 10 micrograms of lead (und described in detail previously) on February 20, 1966. reasons explained previously, will not reach this poin being no significant evidence of a response to this ex (approximately half of each 24-hour period), it is evi of lead in the chamber will have to be increased, and have to go on for somewhat more than a full year from in order to provide the points on a curve from which a made to the effects (on the urinary excretion of lead of the blood) of exposure for 24 hours per day every d experimental regimen can be inaugurated is somewhat un because of the uncertainty of the willingness of the t continue for an additional period of eighteen or more matter is being worked out. (It will be considerably proceed with the same subjects, than to go through the on two new subjects, with their period of indoctrinati There is hope that this can be avoided.) Second, it is now somewhat uncertain, for several reas of funds, whether the renewal of the application to th be approved and activated. The expectation is that th the expenditure of funds is being scrutinized so as to the experimental program if this should not come about the expectation that a share of the expenditures (as I assumed by the American Petroleum Institute, a new bud submitted at this time, together with a statement of t funds. Curtailment or some degree of accelleration of affected in accordance with the outcome of the financi way. (In this connection, the economy that may be rea eliminating the analyses of food and beverages, has be Recent consideration of the direct usefulness of the i the food of the country, have convinced us that these abandoned unless it becomes necessary to do so, for th The following budget is recommended for 1966, on the b made in 1964 and 1935, and of those now visualized; For personnel and services (direct and indirect costs) For special reagents, supplies, allowances for food, e Overhead (proportional share of cost of operating the Laboratory) Total HE 00.1 '4 International Lead Zinc Research Organization American Petroleum Institute U.S. Public Health Service Total Should the public Health Service grant be discontinued, be made to stay within the limits of $100,000. Date: March 11, I960 Kettering laborat 0H X f. 3