Document YjgYdZY3YgaXe8x29nMOVgaQk

I ' df+ :I t oi-$ edl^Q l M -1 jjU * P cx<$Ltiio,-<~, o A ' EXPERIMENTAL STUDIES ON LEAD ABSORPTION AND EXCRETION AND ' f f ,, their Relation t `M e prevention, Diagnosis,aND treatment h m -- ---------------- FTE33TTSG----------------- ..... \ Introduction /. General Procedure of Experiments / 1 year 4 years 2 years / (l) Dosage of lead - normal diet - diet + 1 mg. PbN03 - diet + / 2 mg. PbN03 S2) Collection of samples and analyses - 3 parallel methods 3 ) Medical observations 4 ; Microscopic observations on blood -General Purpose of Experiments (l ) To determine the safe limits of oral lead intake in food and beverages - General public health problem (2 ) To determine the physiological background of lead absorp tion, retention, and excretion, under conditions of maintained prolonged lead exposure, on a quantitative basis, and to answer cer ; tain immediate practical problems. y4 ; (a) The relationship between urinary lead excretion and the stream of continuing lead absorption, j . ( b ) The relationship between urinary lead absorption and j the quantity of lead in the body. | (c ) The relationship between urinary lead excretion and \ alimentary lead excretion. ' (d) The importance of lead absorption from the alimentary \ tract under the most favorable conditions of absorption. = (e) Th fate of retained lead after discontinuance of ; lead exposure (and absorption). - (f ) The effect of various factors on the rate of lead absorption and retention of lead, under conditions of prolonged lead exposure (and absorption) 1 (g) The effect of various factors on the rate of excretion ' of lead after discontinuance of lead exposure (and absorption). P M , / M l ) t ' / t] V ! 3, 'a ul M *. (fj-i'w*-'7i' " ft ft vlSummary of Results -V- 4 *ft U >u ivi W ---- o ' s .t, , d "5'3r^ri.----*1-- " "3rr**" On 2 mg . daily - urinary cone .increases in 23 months > LxeJ *.0* * * *h from -- 0.032 to 0.107 mg. per liter 7 Causes (l) Daily absorption 1 , effective, no d o u b t U r i n a r y output increases from constant, throughout, ( 0.037, to 0.136 mg. daily therefore, also ( (2) Excretion of re- 'l ft 'Atdjfy tained lead is a fac tor Blood concentration increases from 0.029 to O.O72 mg. per 100 g. 2-- ^Qcv) (3) Further shown by the continued high ex cretion and blood con i~2- centration after N9797 Slide 2 Slide 3 Slide 4 Approaching potentially dangerous levels without illness - without lead line without change in stippling 2 . "When 2 mg. daily discontinued^ Causes . Urinary cone, drops off in l i month ....... 0.106 to 0.045 ms- t>er liter (1 ) Reduced daily absorption.) /Urinary output drops off from (2 ) Slight progres- O.I36 to 0.056 mg. daily . sive reduction of retained lead \ (3) Relative redis- /Blood concentration drops off from tribution of re-lo.072 to O.G36 mg. per 100 g. tained lead. \ Rapid loss from \ soft tissue, slow> ' from skeleton. fUrine still to drop to normal levels Possible but not^--^ probable because of/ time factor (16 /Blood still to drop to normal levels months), with still) . elevated blood and I urine levels______ J Output and concentration vary with season 4 . On 2 mg. daily Urinary output increases in 23 months from 1.00 mg. to 3.60 mg. per 28 day period 5 Varies with urinary volume (season) 6 . On 2 mg. daily Fecal lead output jumps in few days from 0.34 mg. to 1.94 mg. daily ' 7 - When 2 mg. discontinue^- Fecal lead output drops in few ` days to O.32 mg. daily There is no apparent lead excretion via the alimentary-tract at any time but only . passage of unabsorbed lead. ^ 3 3 I Z , These facts shown graphically __ Quantities of lead involved during administration Quantity ingested - in water in food . . administered Quantity eliminated - in feces in urine Quantity retained - about 8% 11 ^ ? z 3E.*u*.j ^ 3- Slide 6 subjects 2? mg. 1 mg. O.23 mg* 910. 11. Slide 7 12. Slide 8 1 **j Slide' 9 14. 15- 16. 17. Rate of accumulation constant on given regular dosage Regularity of absorption, quantity of absorption, and duration of absorption therefore, of primary importance. Accumulation does not occur if dosage is sufficiently small. See curve on Subject I.F. on intake of 0.23 Mg. daily. Calculated maximum dosage without accumulation between 0.5 and 0.6 mg. __* ________ _. , __ ,, Quantities of lead involved after discontinuance of adminis tration when 2 mg. daily, discontinued, the quantity re tained decreased in 16 months from _ 110 to 70 mg. lb p7 with at least half the amount excreted by way % of the kidneys. Any fecal excretion is questionable % ,, ^ as shown by facts _on Subject.' -- ---- * When 1 mg. daily, dTs continued, the quantity retained de- - creased in 10 months from . 118 to 111 mg. /* **7 ^ Ao. with somewhat more than this entire amount ex-'^ creted by the kidneys. ^ There can be no doubt that the most important means of lead excretion-is by way of the kidneys. Toxicity of Lead in Quantities Here Involved Threshold of toxicity in terms of urinary lead concentration Industrial lead exposure - As shown by Cholak1^ data, concentration does not continue to rise indefinitely but comes to a maximum characteristic of the industry and its exposure. Subject E .B. on 2 m g y o n contrary, was still increasing at 0.11 mg. per liter when discontinued. This level of lead absorption was greater, or else it was more regular than that in a safe industrial occupation. In any case It was safe for 2 years, but potentially unsafe if carried on further, and was,therefore, discontinued. There was, however, no clinical sign of lead absorption, or of incipient intoxication, such as would justify transfer of a workman from a dangerous job. The correctness of the con- elusion of Sanders, with reference to the failure of stip pling to reveal significant lead absorption is clear. - The actual absorption of lead daily, by indirect calculation^ approximated 1/10 of that ingested, i.e. about 0.13 da'ily for Subject M.R. and about 0.24 daily for Subject E.B. Both rates of absorption are probably dangerous if sufficient time is allowed. Lead Absorption - How influenced? no slide 1 8 . By speed of alimentary emptying time. Lead Retention - Hov influenced? Slide 1C 19* Slide 11 20. Slide 12 21. Folloving factors without influence at dosage of 1 mg. daily with absorption of about O.13 mg. Pb per day. 1 ) Milk 12 ) Apple powder (pectin) 3) Vitamin C Same factorsV ) witLhoowutCaiannfdluePnce on urinary output of lead except to ex5t)entLowofCacha-nhgiesghinP urinary volume ' 6) High Ca - Low P Same factors7 )wiHtihgouhtCainf-lHuiegnchePon(Cfaec-alAmou-tPputinofPM)lead ex . cept to extent of changes in alimentary emptying time Lead Loss from Body - How influenced? Xvic S3 22. Sepeat Slide 1 Slide 2 By reduction in rate of daily absorption By increasing or decreasing urinary lead excretion (l ) By changing urinary volume No other influence experimentally tested was of any avail. (2) hanges in acid-base equilibrium and gross increase in Ca and P output had no influence. NH4CI was effective only to the extent of its diuretic action and not by virtue of acid shift-. The apparent increase in output, with changes in concentration occurred also at same time in subject E.B. as shown in Slides 1 and 2 Practical Applications 1 . In relation to industrial lead exposure (l ) Threshold of Intoxication Urinary Standard " (2) Dosage x time factor in exposure ' Intermittent exposure and non-exposure Intermittent accumulation and loss (3) Importance of normal alimentation in relation to dosage of lead, by mouth or by inhalation (4 ) Importance of adequate water intake and renal output 2 In relation to diagnosis of lead poisoning _ (l) Lead exposure and absorption and clearly demonstrated ` by the levels of lead in the urine and blood, even for - considerable periods after exposurehas come to an end. * 1 '*-**- (2 ) These reveal only the magnitude of exposure and absorp tion, but not illness. (5 ) Fecal lead of no diagnostic significance except'in re lation to an existing source of exposure In relation to treatment ' (1 ) Discontinue exposure (2 ) Keep bovels open (3) Give adequate fluids . (4 ) Usefulness if "deleading" questionable Apparently of little or no avail, at least vithin limits of retention thus far studied by these methods. KT 00087,