Document 5bdz3aEoGpRd8qK6dM081o5zJ

/3 -/ 7, / EXPERBffiHTAb -STUDIES -63? ~EEAD -ABS0RPT20R -AMD -EX0HETI0K -AMD - `SP1SA35 POIWOT------------------------------ Slid 1 Introduction General Procedure of Experiment ~........ 1........ I year,rn!r"u '"4"' years -.. . 2 years (1) Dosage of lead - normal diet - diet + 1 mg. PbNOs - diet + 2 mg. PbHO* 8(2 Collection of sauries and analyses * 3 parallel methods Medical observations Microscopic observations on blood General Purpose of Experimentb (1) 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, wider conditions of maintained prolonged lead exposure, on a quantitative basis, and to ansver cer tain Immediate practical problems. (a) The relationship between urinary lead excretion and the stream of continuing lead absorption* (b) The relationship betveen urinary lead absorption and the quantity of lead in the body. ( (c) The relationship betveen 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) .The fate of retained lead after discontinuance of lead exposure (end 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). (g) The effect of various factors on the rate of excretion of lead after discontinuance of lead exposure (and absorption). Summary of Results Physiology of Lead Absorption and Excretion 1. On 2 mg. daily - urinary cone .Increases in 23 months from ( 0.032 to 0.107 rag# per liter Causes (1) Dally absorption effective, no doubt, bi tUrinary output Increases from constant, throughout, 0.037 to 0,136 mg* daily therefore, also { (2) Excretion of re- t tained lead is a fao- Blood concentration increases from tor 0.02$ to 0.072 mg- por 100 g. (3) Further shorn by the continued high ex cretion and blood con / \ Slide 2 Slide 5 Slide 4 continuance of administration Approaching potentially dangerous levels vithout illness without lead line vithout change in stippling 2. Wien 2 mg. daily discontinued. Urinary cone, drops off in 1 month 0.106 to 0.045 mg. per liter Causes (l) Reduced daily absorption Urinary output drops off from (2) Slight progres- 0.156 to G.056 mg. daily sive reduction of retained lead {5) Relative redis- Blood concentration drops off from tribution of re- 0.072 to 0,056 mg. per 100 g. tained lead. Rapid loss from soft tissue, slow from skeleton. Urine 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 urine levels 5. Output and concentration vary with season 4. On 2 mg, daily Urinary output increases in 25 months free 1.00 mg. to 5.60 mg. per 28 day period 5. ' Varies with urinary volume (season) 6. On 2 mg. dally Fecal lead output jumps in few days from 0.54 mg, to 1*94 mg. dally 7. Wien 2 mg. discontinued * Fecal lead output drops in few days to O.-52 mg. daily - - - - There is no apparent-lead excretion via tfae alimentary tract at ~any time hut only passage' of unabsorhed^lead . "' " These facts shown graphically 8. Quantities of lead involved during administration Quantity ingested - in water in food administered Quantity eliminated - in feces in urine Quantity retained * about 8$ Kr 0008731 ^iifie 6 9* 5 subjects 2 mg. 1 mg. 0.25 Jag. 10* Slide 7 .11 .12 Slide 8 13- Slide 9 14. 15- Id . 17- Bate 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 0.25 Mg. daily. Calculated maximum dosage without accumulation between 0.5 and 0.6 mg. Quantities of lead involved after discontinuance of admlnls tration when 2 mg. daily, discontinued, the quantity re tained decreased in 16 months from 110 to 70 mg. with at least half the amount excreted by way of the kidneys- -- Any fecal excretion is questionable as shown by facts on Subject' M'.'Rl "When 1 mg. daily, discontinued, the quantity retained de creased in 10 months from 118 to 111 mg. with somewhat more than this entire amount ex creted by the kidneys. There can be~no doubt that ~the -most -important means of leaff excretion is by way o'f 'Ihe IcTdiiey Toxicity of Lead in Quantities Here Involved Threshold of toxicity In terms of urinary lead ccncentratlo Industrial lead exposure Ab shown by Cholak*s data, concentration does not continue rise indefinitely but comes to a maximum characteristic of the industry and its exposure. Subject E.B. on 2 mg. on 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 clusion 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 calculatioi approximated 1/10 of that ingested, i.e. about 0 .13 daily for Subject M.B. and about 0.24 dally for Subject E.E. Both rates of absorption are probably dangerous if Hufficier time is allowed. ^ 0008732 iwaaft-l.tfMtf<m3WiMif ut t & i i & b^ l wnwi^ 4 Lead Absorption - How influenced? no slide 18* By speed of alimentary emptying time* Lead Retention * Ho t ? influenced? Slide 10 19* Following factors without influence at dosage of 1 mg. dail a}with absorption of about 0.15 mg* Pb per day. Milk Apple powder (pectin) 5, Vitamin C [4, Low Ca and P 5, Low Ca - high P High Ca - Low P High Ca - High P (Ca - Am - P in PM) Slide 11 20 Same factors without influence on urinary output of lead except to extent of changes in urinary volume Slide 12 a. Same factors without influence on fecal output of lead ex cept to extent of changes in alimentary emptying time .22 Repeat Slide 1 Slide 2 Lead Loss from Body - How influenced? reduction in rate of daily absorption By incx-easing or decreasing urinary lead excretion (1 j By changing urinary volume Ho other influence experimentally tested was of any avail. ( 2> Changes in acid-base equilibrium and gross increase In Ca and P output had no influence KH*C1 was effective only to the extent of it diuretic action and not by virtue of acid shift. The apparent increase in output, with change 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 (1) 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 dosag of lead, by month or by inhalation (4) Importance of adequate water intake and renal output .2 In relation to diagnosis of lead poisoning {1} 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. 0008733 r>- .C' (2) These reveal only the magnitude of exposure and absorp tion* hut not Illness - (3) Fecal lead of no diagnostic significance except in re lation to an existing source o*. exposure 3. In relation to treatment (1) Discontinue exposure (2 ] Keep hovels open \%)) UGsiveefualndeesqsuaitfe f"ldueidlesading u ^fin^^l.e. ast within limitsof retention thus far studied by these methods. . 0008734