Document pekZ74XDonZ0Y8dMQZe9wV7Rw

LsClt-Ccl ,'7,.. /3 -/7 EXPERIMENTAL-STSDES-N-EBB-ABSORPTION-AND'EXCRETION-AND -m-i y-m-iK-n-g-r-w i 'rHirir-^m^nrTtaimm-- ta........ ...... Slide 1 Introduction General Procedure of Experiments , "........... 1.........1 yajr " 4"'ye ars . . 2 years (1) Dosage of lead - normal diet - diet + 1 mg* PbNOs - diet + 2 mg* PbNO# 2) Collection of samples and analyses - 3 parallel methods 3) Medical observations 4} Microscopic observations on blood General Purpose of Experiments (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 under conditions of maintained prolonged lead exposure on a quantitative basis and to answer cer tain Immediate practical problems (a) The relationship between urinary lead excretion and the stream of continuing lead absorption* (b} The relationship between urinary lead absorption and 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) The 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)* (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 1 ,effective no doubt butUrlnary output Increases from constant throughout , 0*037 * 0*136 mg* dally therefore also 1 (2) Excretion of re- \ tained lead is a fac- ,Blood concentration increases from tor \ 0*029 to 0*072 mg- por loo g. (3) Further shown by the continued high ex- , . cretioa and blood eoncentratioa after dis- 0 008700 N 9799 /\ 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 fra 1.0 0 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 unabsorbed 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$ iide 6 3 subjects 2 mg. 1 mg. 0 .23 g* 9 10. Slide 7 .11. 12 Slide 8 15. I Slide 9 14. 15* 16. .1 7 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 adalnif tration when 2 mg. daily, discontinued, the quantity re tained decreased in 16 months from 110 to 70 Eg. with at least half the amount excreted by way of the kidneys # -- --- - Any fecal excretion is questionable as shown by facts on Subject M.'Su 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 beuio doubt that ~the~most -important meahs' oA lead' excretion Ts " W way of 'Ihe.kidney Toxicity of Lead In Quantities Here Involved Threshold of toxicity in terms of urinary lead ccncentratlo Industrial lead exposure As shown by Cholak*s data, concentration dees 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 dally, by indirect calculatioi approximated 1/ 10 of that Ingested, i.e. about 0 .13 daily for Subject M.E. and about 0.24 dally for Subject E.E. Both rates of absorption are probably dangerous if sufficle*: time is allowed. t Lead Absorption - How influenced? no slide 18* By speed of alimentary emptying time* Slide 10 19 * Slide 11 Lead Retention Hoff influenced? Polloing factors without influence at dosage of 1 mg. dail with absorption of about 0 .15 mg* Fb per day. (1) Milk (2) Apple powder (pectin) ij>) Vitamin C *f) Low Ca and P 5) Low Ca - high P 6 ) High Ca - Low P 7) High Ca - High P (Ca - Am - P in PM) Slide 12 20. Same factors without influence on urinary output of lead except to extent of changes in urinary volume 21. 22. . Repeat Slide 1 Slide 2 Same factLoerasd wLiotshsouftroimnBfoludeync-eHown fiencfalluenocuetdp?ut of lead ex cept to extent of changes in alimentary emptying time By reduction In rate of daily absorption By increasing or decreasing urinary lead excretion (1 j By changing urinary volume Ko 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 EEUC1 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 dos&g 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 exposure has come to an end. 0008733 (2) These reveal only the magnitude of exposure and absorp tion, but not illness . (3) 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 bowels open \Z>) Give adequate fluids I-t ) Usefulness if "deleadingquestionable Apparently of little or no avail, at least within limits of retention thus far studied by these methods. . .