Document 6BNvx77J3NEEVXM25rG76bL59
PROPOSAL TO INTERNATIONAL LEAD ZINC ORGANIZATION FOR THE CONTINUATION, THROUGH THE YEAR 1971, OF THE FINANCIAL SUPPORT OF A PROGRAM OF RESEARCH, IN THE KETTERING LABORATORY, IN THE DEPARTMENT OF ENVIRONMENTAL HEALTH OF THE COLLEGE OF MEDICINE OF THE UNIVERSITY OF CINCINNATI, ON THE GENERAL SUBJECT OF "HUMAN EXPOSURE TO PARTICULATE LEAD COMPOUNDS IN THE AIR, UNDER EXPERIMENTAL CONDITIONS"
Subtitle Project LH 160 (Present Phase of Experimentation) Effect of Particle Size In Air on the Absorption of Lead by Man
The background of this investigation of the metabolism of lead in man, under a variety of conditions, over a period of years, will have been presented in prior proposals, and, thus, a repetition of their substance would be redundant. An experiment has been initiated recently, involving one aspect of the matter, namely, the examination of the relative rate and manner in which lead sesquioxide, dispersed in particles of comparatively large size (mean diameter of 0.5 micron) may be absorbed into the body, as compared to the same compound in much finer dispersion (mean diameter, 0.05 micron). In other experiments, the size of particles to which
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human subjects have been exposed have ranged from 0.75 to 1.2 microns (mean diameter).
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Funds were made available, through the Lead Zinc Organization, for the conduct of this experiment, to begin promptly in 1970, but difficulties were encountered in securing a suitable subject for the experiment, Only in May was a subject, believed to be suitable for the purpose, found and employed (a young woman. Subject P.B.). The preliminary observations (for the purpose of establishing the pattern of the Subject's normal metabolism), initiated on May 10, 1970, have been under way since, and are to be continued as long as may be necessary to reveal this pattern (through two seasons, at least, so as to range through warm-hot and cool-cold environmental climatic conditions. No female has been employed previously as a subject for this type of experimentation, so that it is necessary to carry out the preliminary observations with unusual care, and to subject the early data to unusually critical examination, before initiating the exposure to the designated aerosol. (Not only was it difficult, at this time, to obtain the services of a
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suitable male subject, but also, after confronting this situation, it became
increasingly obvious that some portion, at least, of this general physiologic
investigation should concern itself with a thorough-going examination of the
metabolism of lead in the female human being. After the enforced fact, this
opportunity is welcomed, especially at the present time, when the exposure to lead
in the general environment has come to be a question of importance in the field of
public health, as well as in the area of occupational health.)
As indicated previously, the duration of the exposure to lead is to be
limited to eight (8) hours per day, on five (5) days per week, at the level of
one hundred-fifty (150) micrograms of lead (Pb) per cubic meter of air, in simulation
of the more or less standard industrial time schedule, but at the same level of
concentration at which other observations have been made (which, in fact, was the
accepted standard for reasonably safe occupational conditions at the time these
experiments began). This part of the experiment will not -*be attempted before (or,
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at most, not much before) the endj'of 19^70. It will extend into 1971, therefore, far
a length of time which cannot now be determined precisely, but which will not be
shorter than six (6) months and may well be longer.
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The cost of carrying out the work now being done has been examined with
some care and has been set down in one of the sheets (budget 1970) attached to this
proposal. On another sheet is the estimated budget for 1971. No doubt some portion
of the funds requested for 1970 will be available for .use in 1971, and the actual sums
of money provided for in the continuance of the project in 1971 can be regulated
according to the desires of the sponsors. It is recommended, however, that provision
be made for continued work throughout 1971, since a program can be submitted for
another experiment in the series, which might well extend into 1972, conditional upon
the advice and consent of the sponsors. With respect to the suggestions made above, it is not presumed, at this
time, that the work on the metabolism of lead will be continued indefinitely under
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the present sponsorship, or that the present principal investigator will, necessarily, be the instigator of such continuation. This principal investigator, nevertheless, is of the firm belief that the facilities and capabilities within the Kettering Laboratory, as provided by considerable effort and investment, and seasoned by long experience, can be and should be further cultivated to the end that these investigations may be further advanced in the years to come. lead is an extremely useful element in the technology, economy and comfort of mankind, and it should be as thoroughly understood,in its relation to human physiology, as the reasonable scope of scientific investigations can make it. The extent to which the present and future Staff of the Kettering Laboratory can penetrate further into the scientific and practical aspects of industrial and public health will depend largely upon the quality of the cultivation of the resources of the Laboratory. This proposal is conditional upon the desirability and practical importance of that end.
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June 24, 1970
Values Reflecting Pb Intoxication in Humans
Proposed Levels-URINE
Criterion
Normal
Pathologic
ALA Texposed 10 to 15 days)
5 to 10 times normal
2.5 mg/24 hr.
19.07 mg/24 hr.
<1 yr. post exp. 1 to 3 yrs. " 3 to 9 yrs. "
1.3 to 2.8 mg/24 hr.
29 mg/24 hr.
15 " " 4.6 "
Based on creatinine excretion
2k hr. output
0,85 to 2.4 mg/g creat.
Up to 4 mg
>2.4 mg/g creat.
Up to 110 mg.
2.8 mg/24 hr.
1.5 mg/100 ml
PROTO
4.53 mg/1
21.2,^^100 ml TEL
30 rg/l
. ^ 3.0 r.--/?4 hr.
312 >V.-yiO-0 ml ib
COPRO
150 mg/1 <100^-/24 hr.
up to A50 rng/l
P3G
1.5 mg/2k hr
1.94 ng/PA hr.
' CriMorion
ALA
<1 yr. Fost exr:. 1 to 3 yrs. " 3 to 9 yrs. "
Plasma ALA
Plasma PBG
Proposed Levels-PL PL
dermal
tnoio i e
0.02b mg/100 ml(max)
0.026 ng/100 ml
0,065 ir.f/100 ml 0.043 "
0.032 "
0.046 mg/100 ml 0.030 mg/100 ml
126.7 mg/] 00 mi O.O29 mg/100 ml
Kettering Abstract Ref, T 41
1-66 1-75
ir f ft
1-259
1-960
11-116 ' T -- ** ?.
r-261 I s5
;r-11/
3
p* ** : -T 9
!l ft
t
11-116 1-66
It
L - 28
0
4A
4A
O i~
i
Criterion
RBC
Proto IX ALA Dehydrase PROTO IX <1 yr. Post exp. 1 to 3 yrs, 11 3 to 9 yrs. "
volume survival time
it 11
BLOOD Pb
adults children
adults
PBC vol. Kgb Hct. MOV MC Hgh cone. Reticulocytes Stippled cells-R3C Icteric Index
Stippled cells-PBC M rr 11
Sp. G. (bleed)
Proposed Levels-BLOOD
Normal
Pathologic
Kettering Abstract
Ref.
0.035 to 0.055 mg/100 ml 1.03^ Vhr/ml.
45 to 55 days
1.08^ M/hr/ml
0.232 mg/100 ml.
0.225
"
0.159
"
reduced reduced 37 to 69/ 21 to 4l days
1-75 1-66
1-75
II If
1-39 ft
I 4o8
0.08 mg/100 o' 0.04 " C
0.025 mg/100 S' (0.005 to 0.<&0) 5X106/mm5 14.5 g /
45/ 80 tO 94 33 to 38 g/100 ml 0.5 to 1.5/
3 to 5
.1.057 (I.05' to I.O63)
o.o4 to 0.08 mentally deficient
1-290 ft
1-387
3.5 to 5.4XX06/mm3
8 to 12.8 g % 28.8"to 43/ (35/ ave.) >^70 tf 92 (79 ave.) 27 to 36 g/100 ml (31 ave.) 1.5 to 11.6/ (4.4 ave.) 0.1 to 7.5/ (1.8/ ave.) 4 to 10 (6.5 ave.) 1
1-263 r.
fi
ft ft ft it ft
>200/106 cells >'>.5/
<1.054
1-271 1 387 ' 'i
1 387
L - 29
Criterion Urinary Aminoacetone Urinary Pb adults non-precip. precipitable "
Total Pb-urine " Urinary Pb children Tissue Pb adults
soft skeleton Pb inhalation
Spinal fluid
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Proposed Level^-Miscellaneous
Normal
. Pathologic
Kettering Abstract Ref.
0.59 to 1.05 mg/g 0.002 mg/l
vdthin normal limits
0.027 mg/l
I 259 11-117
0.047 mg/l
^absorption 0.100 mg/l Pb intox. 0.204 "
0.049 mg/l
/fabsorp. 0.127 mg/l Pb intox. 0.300 "
0.04 to 0.28 mg/100 <y
0.67 to 3.59 "
0
0.06 to 0.182 mg/l
10 to 20 X more absorption, than by ingestion
.__, 18^ g/100 ml
25 to 50yd s/100 ml
fatal case- :
100 "
'
(
11-117
II It II
1-88 1-56
1-256
1-856
L - 30
pi A .4
p