Document 5b4BGZkxwLwBjXNaXR7ZoYga8

/' t. .' On The Potential Hazard Associated/With The Introduction Of Tetramethyllead As An Antiknock Agent Into Commercial Motor Gasoline, With Respect To The Absorption Of head By The Hndlern Of Such Gasoline. - An Interm Report Made' After Nine Months of Distribution - ; by / . Robert A. Kehoe, M.D., and J. Cholak Ch.E. From The Kettering Laboratory in the Department of Preventive Medicine and Industrial Health, College of Medicine, University of Cincinnati. Introductory Certain questions arose initially concerning the potential hazard of lead absorption in connection with the distribution and use of gasoline containing the antiknock agent, tetramethyllead. The primary factor which might give rise to hazard through the substitution of this compound for. tetraethyl lead in equivalent concentration in gasoline (equivalent in terms of the proportional representation of lead in the molecule, whereby, at the maximum,. 2.03 ml. of TEL are equivalent to 3.00 ml. of TEL), was that of the appreciably greater volatility of tetramethyl lead./ The practical question revolved around the extent to which this higher volatility might operate with significant affect to contaminate the air with '" >' . : ... :. . . ; . ' . tetramethyl lead, or whether this factor would be offset sufficiently by the high dilution of the tetramethyllead in the? gasoline, and, additionally and more pointedly, by the movement of currents of air in diluting any such volatilized lead to insignificant levels of concentration in the air breathed by those who would handle the gasoline under the ordinary, as well as the possibly extraordinary ..ri / . . : . . . . ' .. (from time to time), conditions of the commercial handling of the gasoline. I .' '.' - .' 5 This question, An so far as a comparatively short period of time and . I ?- ' :. . fa specific set of conditions (regarded as uncommonly severe) of use were concerned, |had been answered in the negative (See Report of The Kettering Laboratory of November 1 10, 1959).' It was believed, however, that the matter was of sufficient importance 7 ;l *`7 t y T T . <nt * * * i * K * & 0l ^ rn * c 2- - R. The essential principle of the experimental approach was that of feeding a suspension of the plastic material in a soup to a human veieH*er who had been under continuous observation for some months for the purpose of determining the pattern of his metabolism of lead, in preparation for a more bs /*f *J ''Clj r( * 'l 'Tt*x-3 c-f;,\gAUtUt& bfp.'if.J' elaborate experiment . This subject carried on tf&v essputially-fiegmalr-atoa-tin v nf '%* HM &iJAif *j & ' ( & <0 AftUudL * * . - . g^E^sr, and. was not exposed to any unusual source of lead in his home or working "S' environment. The schedule of this experiment included nine days of on-t-roi (p'A"u^ ") observations, during the first five days of which he adapted his dietary routine to the extent of including the specific kind and quantity of soup in which the plastic material was to be suspended. After the preliminary period of nine d a y s . a/second (control) period of five days followed, during which time his diet included the same soup containing 0.25 grams of a lead-free glazed paper which /' a)''J ' simulated in appearance and texture the veilting1material^ An initial dose of 0.25 htJ grams of the coating material was ingested with the soup^fthe fifteenth day of the experiment, after which from the sixteenth to the twenty-eighth day, the control diet (containing the soup and the lead-free glazed paper) was resumed. During this entire period, the output of lead in the urine and feces were being observed, as indeed, they had been in the entire preceding period during which the subject - 3- had been under investigation. . iUHIft*' /fit From the twenty-ninth ^ the thirty-third day, the plastic coating o^-the was ingested by the subject in the amount of 0.25 gram per day, , Cklc<HL, the subject returned to the control diet from the thirty-fourth the thirty- eighth day. The determinations of the lead in the urine and feces were continued. The analytical results on the food, feces and urine, covering the entire period represented above, and continuing through forty-one days, have been assembled in fnrm_, nf . . . Experimental Results . " i m~ - ' i .> ~ . i.i i, i i i 'I. i n. Of _. A' -* ..C ' Crb<JA,J,:>.-j,f - , . t, , /J f i '' The results referred to abovef^re set forth in Table lT~ It may be seen that the quantities of lead in the food, feces and urine, during the first nine days of this period^were essentially the same as those in the subsequent five days. The initial period of fourteen days may, therefore, be taken together to be the control period. The relationships of the findings, in terms of the degree of balance between the intake and output of lead during this control period, are shown in Table 2. CO : . . . '- to With the first feeding of plastic on the fifteenth day, the ^fanateEES co CO q ingested 30 milligrams of lead in the plastic. The output of lead in the feces, $ AUi on the sixteenth, seventeenth, and eighteenth days, oontsSiraod-a3^w k w b b -of V 29.82 milligrams j f c w that which would have been expected had the 30 milligrams wjfi.Mi - 4- lead not been ingested. The average quantity of lead excreted in the urine, |J|ff .W "Jff ' '' ' ' during the same three-day periodjwas 0.019 milligrams, which was essentially the '' ' " ' 7 1 ' same as, actually slightly lower than, the average quantity excreted daily during the control period. During the second period in which the plastic coating was being fed, the ingested 30 milligrams of lead per day in that manner (in addition . #*/^ .' to that contained in the food itself)rach of five days. The -feces evacuated during the thirty-first through the thirty-fi^thj^contained 155.34 milligram of lead in excess of that which would have been expected had the 150 milligrams of lead in the plastic not been ingested. (The discrepancy here, that is^the apparent excess of output over intake, may be ascribed to small sampling errors (plastic or food or both) which are almost inevitable in an experiment of relatively short duration. The point of importance is that apparently all of the lead ingested an this form is accounted for in the fecal e^Vacuation^ The conclusion might be drawn that no lead was absorbed from the plastic during this period*- This *3 to ov ro O o hi is not necessarily true, but certainly the quantity absorbed was small. Sksxst The data obtained by the analysis of the urine represent the Kxxa crucial evidence, with reference to the absorption of lead. It may be noted that the urinary output of lead during the pertinent period of seven days (thirtieth through thirty-sixth) appeared to be slightly and persistently elevated. The average for T 5 tfris w e i e t e period is, in fact, significantly higher than that of the control period (t = 4.5, d.f. = 18, p ^0.01). The increase was indeed slight, and but / for its consistent trend it would have little, if any significance. It is a matter of importance that it increased progressively from the thirtieth to the thirty -thirdthy, when the peak value of 0.033 milligrams was reached, after which could not be differentiated from the earlier results after the it fell off and fortieth day. The data as to the concentration of lead in the blood of the v O T t w w r before, during and after the experimental regimen,are given in Table 3. The concentration in the blood was unaffected by the feeding of the plastic. <x xarge quantity of lead in the alimentary tract Py,<rV z>.> s-i'*'*' -7a > r- \. This qufisa^^t,.y was so minute, however, that it could be considered to be significant only in statistical terms. The lead excreted in the urine during LO LO C';> co o o: V ''"5-11 the relevant period never exceeded ts quantities that are often found in the urine of ordinary, normal persons, and the slight elevation above the previous (control) level would have had no significance even statistically but-for the fact that it prs persisted o w r several days.and then disappeared just when . t - . x . . ; _ .,, / ,-v j .' . `'.v; v:'V.. f rJq.1 Z k*. JU. -< t ~ u'{-.. .. -l.:f U it should httve--o~physi^lgica.l-rg r o tmds. Thd-e may havea-he^f=:g *']natt'gr,~Ufl-ChdUCiT, - ^ y ' C'`- y / Q j L a.,hlL, 7 .'.<A r '" ./ . <<V*- ` '.Vx.eSj-J'i,..*.<._ _ > . J-i. " t ' */ . . *WLta? i. >but it is reasonable, at least, to attribute try elevaLion-oiy the rnmm V Tab3-e 2 Summary of The Analytical Data Representative of the Control Period Lead ingested In food (mg) Summation of results obtained during 14 days. 3.23 Daily average of results obtained during 14 days .23 S.D. .150 Lead eliminated In urine (mg) In feces (mg) Total (mg) Balance Intake less output .25 2.65 2.90 +0.33 I .02 19^ 21 +0.02. .038 .20 K ? 000395? TABLE 3 Concentration of Lead in Blood at Various Times Day of Experiment 1 6 13 19 24 32 37 43 Lead in milligrams per 100 grams 0.024 0.023 0.015 0.024 0.019 0.020 0.021 0.015 0003958- COMMENT *J The results obtained ip this experiment correspond tu~ f .p-- expectations, The absorption of the inorganic compounds of lead,:<Seven at * .A best, when soluble compounds in aqueous solution are ingested, xx occurs to only a modest extent. In this instance, it could be expected confidently CZvl) that the basic lead carbonate^jnixed in fete essentially inert plastic material^ .. if)*&a.efihisu__ ---- " "* would not be accessible "to any appaaBoiable,`<fcgTtro,`""f'Ogr','abfaua'p,t'it31r. It was ' y* , C-i;>4.'' r-<*j j ,, i f ' in no sense surprising, therefore, that the alimentary absorption of the ingested lead was negligible, and th&t the lead which had been swallowed was evacuated in the feces without significant diminution in its quantity. . ijU --*ft r. ' |'i-iww '-iX`-Ut^iC v Qv~y pn^tlty. .'' ' ' . the ingested lead was absorbed during the period in which there was a large quantity of lead in the alimentary tract#*0 P~) i y A 't ' V j .-.Of ~>P' O.'iO)J1-: *! - ./ . - . 1 ^ Sir'cf' . ' UiZZi tcJ : i:. .. . / / ' . / This qunw&Lfcy was so minute, however, that it could be considered to be significant only in statistical terms. The lead excreted in the urine during the relevant period never exceeded tttft quantities that are often found in the LO C '5 urine of ordinary^, normal persons, and the slight elevation above the previous K * 0003 (control) level would have had no significance even statistically but for the It, it-UtUt-'"-jI f I fact thiaatt it pxxS 'persisted -4 several days,and then disappeared just when r\ \/ ' _/ .* f 'tCu^UjiJL t <&> uK, (*)'*&***-') it shuul-d- h-ave op-pphkysAelogical grounds . This may have*b*Lin S'limtler~Ulg-'''U-hauC'e', $L*0 -y -J1&0+ ^**if******^ !, d**A**} */'OfAslUdJ- U>t^= i>-|' --t--itWglvui. AM. jX^jT jH shuut it is reasonable, at least, to attribute this temporary d u ratio n o f''the _ /> __ __ Hx? a~i af *ff-***~jiAjld}^ dl^$ CiU HtirinnrjT lead outpifrfe--to tiio-expej.li6ITfc^r^nge1n!ir*'o`f U^ak t plaeM-e . vIn any case.the evidence is adequate to demonstrate the complete , __ ? i> \ .'- i insignificaihce of tho ~preseneo df- ' ln the _al 3, from the aspect of any hazardous degree of absorption of lead. CONCLUSION This experiment has demonstrated conclusively that the accidential or intentional ingestion of the lead-containing plastic employed to coat '" ' ' incadescent lamps (bulbs) would be unattended by* any hazafd ` of the Absorption of lead from the alimentary tract. The coating material is essentially inert within the alimentary tract, and the lead contained within it is absorbed therefrom only to an entirely negligible extent. From The Kettering Laboratory in the Department of Preventive Medicine and Industrial Health, College of Medicine, University of Cincinnati. Observation/by A. Davis, M.D. Lawrence Schaffer Ch.E. J. Cholak, Ch.E. T. Sterling, Ph.D. Report by : A. Davis, M."D. R.A. Kehoe, M.D. Approved Robert A. Kehoe, M.D. Director March 28, 1961