Document o9MNgjX79KYDwjoawqVRKLjD

June 21, 1973 Mr. R. J. Sherwood Environmental Health Advisor Esso Research Centre Abingdon., Berkshire 0X13 6AE England Dear Mr. Sherwood: Your letter of June 15 to Mr. J. Cnolak of this Laboratory, was referred to me for a re ly, after talking the matter over with me. First, let me answer your request of Mr. Cholak, in relation to methods of analysis of the urine, especially in relatiLon to tiie form in which lead may appear in the urine. This is strictly in CRolak's province, since I, a physician, am no chemist, in the sense of dealing with or mpioying analytical methods. He provides me with two reprints to send you in wihich the methods of analysis of urine for lead are described. You will note at once that no effort is made to identify the compound or compounds of lead which rna appear in tile urine. Rather, the effort made is that of destroying any chemi cal linkages which would, or might, mask the quantity of lead (Pb) in the spec .mens. The matter of the diagnosis of the type of lead which induced the poisonin $ is left to the physician to determine, essentially, on the basis of the clinical type of the illness. This may not always be feasible, but it is generally, and is pdeferable in our view to measures of analysis that do not measure all of ' the lead being excreted. We have not carried out investigations which would enable u to differentiate the compounds which may have been absorbed in the first in:stance, nor oo we believe that this would toe feasible under ordinary clinical situations. Wuen such compounds as the alkyl lead compounds have been absorbed, some degree of decomposition of the compound may occur in the body. Tetraethyllead decomposes to trietjiylleau - anu probably on through diethyl and monoeiny.l compounds, as it does in yitro, unucr appropriate conditions. The alteration then, as you know, doubtless, proceeds to the inorganic form of lean (Pb'5"*'), slowly. To what extent all of this occurs in the body, we do not know, nor do we know the extent to which .time- is required for the processes (if it occurs). When, ito./ever, the alkyl lead compounds are absorbed (i.e., tetraethyl- and tetraoet!^lyl-lead) in sufficient quantities to cause illness, the clinical syndrome from, the onset, differs from that of the absorption of inorganic lead, chiefly because, as it seems, the fat soluble lead is absorbed promptly into fatty tissues, i n d u din ; the brain, with the result of inducing mental symptoms as the outstanding pattern of the illness. Moreover, the lead does not mount in the blood (erythrp cytcs), as at does in poisoning by inorganic lead, because, no uoubt, the lead off ared to the blood stream is not in such form as to diffuse/readily into N 6298 Mr. II. J. Sherwood Page 2| June 21, 1973 the bipod or to be absorbed into the erythrocytes if it does penetrate the capillary wall. There is here, nuch that is unknown, of course, but the fact is thai the lead content of the blood in tetraethyllead poisoning is low (rarely exceeding 0,05 mg/100 grains) despite the high concentration of lead in thejurine (which may be as much as a large fraction of 1 mg. per liter, or yen more). We have never seen tetraethyllead poisoning as the result of a long piriod of absorption at a low level of exposure, and so the problem of (dhronic cumulative) tetraethyllead poisoning has never appeared. I hope this discussion will be of assistance to you, but if you have further questions, I shall be glad to attempt to answer them. Cordially yours, RAK:wb enclosures as stated Robert A. Kehoe, M.D. Professor Emeritus of Occupational Medicine 0002412 ESSO EU R O P E I NO. 50. STRATTON STREET, LONDON , W1X 6AU ENGLAND O FFICE OF EN VIRON M EN TAL A FFA IRS ' R. J. SH ERW OOD --Environmental Health Advisoi OFFICE LOCATION AND M AILING A D D RESS: ESSO RESEARCH CEN TRE. ABIN GDON . BERKSH IRE 0X13 6AE T EL: ABIN GDON 1600 EX T . 3 0 8 Dr. J, Cholak, Kettering Laboratory, . University of Cincinnati, College of Medicine, Eden & Bethesda Avenues, Cincinnati, Ohio, ^5219 15th June 1973 > ' :. ; -u. ; J . ' -) 'i Dear Dr. Cholak, ' 'f . . I am writing to seek your advice on the analysis of lead ill urine with particular reference to the chemical form of the lead. In a recent situation we had a serious need to distinguish between inorganic and organic lead poisoning, as diagnosis had been made of chronic lead poisoning from alkyl lead exposure. I think we can expect to find some of the lead present in urine after alkyl lead inhalation in the trialkyl form 'as shown by Bolanoviska in rats, and should be able to distinguish chemically from inorganic lead. ! I should be most grateful for your advice on whether this has been studied, and-if so, where is it published ? If not, I would be grateful for your advice on possible analytical procedures, and on the likely form that inorganic lead appears in urine - can it ber conjugated as glucuronide, or is there some other mechanism involved in elimination ? Finally, I would be glad to know the technique you currently use for routine analysis for lead in urine. My apologies fpr troubling you with these questions; I shall certainly appreciate your comments. ' Yours sincerely, RJSif V* H v: : \