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EXPERIMENTAL STUDIES ON LEAD ABSORPTION AND EXCRETION AND
THEIR ^ELATION TO 1'HE PREVENTION', I)IAGF(5SIB"'TNi'TOATWvr
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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
Collection of samples and analyses - 3 parallel methods
Medical observations
Microscopic observations on blood
General Purpose of Experiments
(1) To determine the safe limits of oral lead intake in food
hnd 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
A, lead exposure (and absorption).
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(g) The effect of various factors on the rate of excretion
of lead after discontinuance of lead exposure (and absorption).
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-.`1'Summary of Results
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Physiology of Lead Absorption and Excretion
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On 2 mg . daily - urinary cone .increases in 23 months
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from
----- - 0.032 to 0.107 mg. per liter
(l) Daily absorption i
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effective, no doubt,ims! Urinary output increases from constant, throughout, ( O.O37, to O.136 mg. daily
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therefore, also (2) Excretion of re
tained lead is a fac tor
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Blood concentration increases from 0.029 to O.O72 mg. per 100 g.
2 - is
j jr Jjy. (3) Further shown by the continued high ex
cretion and blood con
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Slide 2 Slide 3 Slide 4
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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 34month
--..... -.......
0.106 to 0.045 mg. per liter
(l) Reduced daily absorption)
/Urinary output drops off from
(2) Slight progres- 0.136 to 0.056 mg. daily
sive reduction
of retained leadl
(3) Relative redis- /Blood concentration drops off from
tribution of re-fO.072 to 0.036 mg. per 100 g.
tained lead.
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Rapid loss from \
soft tissue, slow;
from skeleton, furine still to drop to normal levels
Possible but not^---x
probable because of/
time factor (16 /Blood still to drop to normal levels
months), with still)
Jelevated blood and j
urine levels
P* 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 O.34 mg. to 1.94 mg. dally
When 2 mg. discontinued^ - 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.
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$
110
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5-
slide 6 subjects mg.
t1 mg.
0.22 mg.
9-
.10
11.
Slide 7
12.
Slide 8
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Slide' 9
It. 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. -fo
lbp?
with at least half the amount excreted by way %
of the kidneys.
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Any fecal excretion is questionable
_ __ _ _____as shown by facts pn Subject'JM .R_. __t,
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When 1 mg. daily, dTs continued, the quantity^retained de
creased in 10 months from 118 tO 111 mg .
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with somewhat more than this entire amount ex-'^.
creted by the kidneys.
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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 Cholak^s 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 mg y 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 calculation* airaroximated 1/10 of that ingested, i.e. about 0.13 daily 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.
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4.
Q&vtoJ+fiy Lead Absorption - How influenced?
no slide 18.
By speed of alimentary emptying time.
Lead Retention - How influenced?
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Slide 10 19*
Following factors without influence at dosage of 1 mg. daily with absorption of about 0.1J mg. Pb per day.
1) Milk
2) Apple powder (pectin)
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Slide 11 Slide 12
2) Vitamin C 4) Low Ca and P 5) Low Ca - high P 6) High Ca - Low P
7) High Ca - High P (Ca - Am - P in PM)
20. Same factors without influence on urinary output of lead except to extent of changes in urinary volume
21. S3
Same factors without influence on fecal output of lead ex cept to extent of changes in alimentary emptying time
Lead Loss from Body - How influenced?
Sepeat Slide 1 Slide 2
22. By redtiction 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) phanges 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-.
Practical Applications The apparent increase In output, with changes in concentration occurred also at same time
1. In relation to industinriasl ulbejaedct eExp.Bo.suares s'<h**o&w&.*n in Slides 1 and 2 (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 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.
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5(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 3. In relation to treatment
(1) Discontinue exposure (2) Keep bowels open (J) Give adequate fluids (4) Usefulness if "deleading" questionable
Apparently of little or no avail, at least within limits of retention thus far studied by these methods.
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