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The Potential Hazard Associated With The Introduction f Tetramethyllead a Antiknock Agent Into Commercial Motor Gasoline, With Respect To The
sorption 6f Lead By The Handlers f Such Gasoline.
- An Interm Report Made After Nine Months of j&S
by Robert A. Kehoe, M.D., and J. Cholak Ch..
From The Kettering Laboratory in the Department of Preventive Medicine and Industrial Health, College of Medicine, University of Cincinnati.
Int roduct ory Certain questions arose initially concerning the potential hazard of
lead absorption in connection with the distribution hnd use of gasoline containing
the antiknock agent, tetramethyllead. The primary factor which might give rise to
hazard through the substitution of this compound for tetraethyl lead in equivalent
concentration in gasoline (equivalent in terms of the proportional representation
of lead in the molecule, whereby.
] of TML a^equivalent to
3.00 ml. of TEL), was that of the appreciably greater volatility of tetramethyl
lead. The practical question revolved around the extent to which this higher volatilit
might operate with significant affect to contaminate the air with tetramethyl lead,
or whether this factor would be offset sufficiently by the high dilution of the
tetramethyllead in the gasoline, and, additionally and more pointedly, by the
movement of currents of air in diluting any such volatilized lead to insignificant
levels of concentration in the air breathed by those who would handle the gasoline
under the ordinary, as well as the possibly extraordinary (from time to time), condition
of the commercial handling of the gasoline.
N9578
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This question, in so far as a comparatively short period of time and a specific set of conditions (regarded as uncommonly severe) of use were concerned, had been answered in the negative (See Report of The Kettering Laboratory of November 10, 1959). It was believed, however, that the matter was of sufficient importance to justify further investigation of the conditions associated with the gamut of commercial operations over a period of time sufficient to reveal any even slight increase in the occupational exposurejof the handlers of such gasoline. (It has been shown that persons subjected to varying degrees of exposure to lead, in the course of occupations that follow approximately the normal schedule of 40 hours per week of employment in the U.S.A., reach a practical equilibrium with their environment. with respect to their absorption and excretion of lead^as demonstrated by the concentration of lead in the blood, and by the rate of the urinary excretion of lead, in from five to eight months, after which no further increase will occur so long as the conditions of exposure remain essentially constant.) Accordingly, a program of investigation, to be carried out over the period of one year, was designed along two general lines - one concerned with the periodic measurement of the lead in the air in the areas in which men were cariying on various relevant occupations, and the other involving the determination of the approximate rate of theij urinary excretion of lead from time to time. (Determinations of the lead content
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of the blood of the workmen were to be made at the beginning and at the end of the
investigation,/as not to ignore any evidence of the absorption of lead in any form. However, the absorption of tetramethyl lead cannot be detected by determinations of lead in the blood, but, rather, is revealed by the measurement of the lead in the urine. The latter, therefore, was to be followed at intervals of
three months throughout the year, so as to assess in quantitative terms any degree
of occupational exposure to tetramethyllead that might be incurred by individuals and groups.
Investigative Methods.
Inasmuch as a final report to this investigation is to be made in full detail on its completion, it may suffice for present purposes to deal briefly. with the experimental design and the methods of procedure. A preliminary survey of the principal area^'in which gasoline containing tetramethyllead was to be
distributed, resulted in the election of the sites at which air analyses would
be carried out systematically, and in the selection of various groups of employees,
whose exposure to the potential hazard was regarded as representative of the iftpafe-
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environmental survey will be
described brief ly,y in the following Part J of this report, while the general
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the employees is outlined in the following paragraphs. A
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Men engaged at Jg&. various occupational sites were selected for
periodic investigation, according to the numbers of such persons available, or
in such numbers as would be representative oi their occupation. When the total
'i \i^ number^ of available persons was ample, every effort was made to select tfeseSte employees
whose service could be expected to continue uninterruptedly^ ^ ' -rm-ni'.i--.
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as well as those whose work appeared to involve the maximum severity
and duration of exposure. Table I, below, indicates the sites, the specific
operations involved, and the types and numbers of personnel projected for
investigation in the San Francisco area:
Sites
Types of work
Refinery 1. Blending plant 2. Tank Truck Loading Rack
3. Wharf
4. Barrel Filling Area
5. Chemical Laboratory
Service Stations~iir .Sh F.
Regular mixing of TML with gasoline
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Loading petroleum poriocto including
gasoline containing TML. Approxi
mately 60 drivers have irregular^
intermittent exposure^but only the
loaders, 12 in number^, are
exposed regularly.
Loading barges, inspecting, sampling and testing contents
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Workmen fill drums with gasoline containing TML ^ 2.
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Testing and distillation of v gasoline, bj /X
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Sites
Types of work
Memb er cJ of workmen wlt h^significant
exposure
Service Stations in S.F. 10 very busy and widely distributed in area
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Regular dispensing of gasoline
to consumers, Sr.tsTtliw&'f/J
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Approximately
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-.a-fc--tha,. r,,eingr-y "in the Los Angeles areafc ^v^ra,,.iwejrgc^ed. The actual numbers of
persons
be shown later in the tabulation of the analytical
data.
Each individual in these groups 4tiMe examined by a physician associated
with the medical department of the oil company concerned. The details of these
out. The examination consisted of a medical and occupational history, a complete
physicial survey, a hematologic examination and certain`other laboratory procedures
according to routine or as required in specific instances. At the initial examination
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v- samples of blood for analysis for lead were obtained, together with a sample of
urine^collected in containers supplied by The Kettering Laboratory and in
accordance with the instructions of the Laboratory. All of such samples were
forwarded to The Kettering Laboratory for analysis.
Additional samples of urine were collected at intervals approximating
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three months and forwarded to The Kettering Laboratory. A terminal series of samples of urine is to be collected in May jgt June of 1961, at which time a second and final series of samples of blood will be obtained.* fin teims1 uf' 1 the fiadings up to the present
.plan of .the.investi'gatTon) .
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In general^ the data as presented in the foregoing tables give a clear answer to the question which led to their collection. With a few exceptions, so few indeed as to be regarded as fortuitous or irrelevant, the concentrations of lead in all of the samples of urine of all of the subjects are so consistently within normal limits as clearly to demonstrate that the groups of persons, regardless of their specific occupations, sustained no appreciable absorption of lead during the period of approximately nine months during which they were subjected to periodic investigation.
When all of the analytical results obtained from the investigation of all of the subjects were assembled and separated only with respect to the three periods of sampling, no valid statistical evidence of any xhsH abnormal absorption of lead on the part of the mifaiwc group could be found in any period of the observations. The data distributed themselves statistically in strict accord with comparable types of data obtained from entirely normal persons devoid of occupational or other unusual exposure. There was some variation in the data of the three periods, but the variations showed no consistent trend with the lapse of time, and they were well within the O O limits of physiological variation, as these have been observed in other data
* involving samples of urine of small volume. A few individual findings
deviated appreciably from the general trend of the results and could be regarded as being outside the statistical universe represented by the data
2
as a whole. For this reason, and also because the combined data
were composed of results from inhomogeneous groups of employees, the
findings were rearranged for more detailed study, according to the
occupations and the geographical distribution of the employees.
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After exploring every relevant combination^ they were reassembled
into the tables represented above (Tables 7,8,9 and 10) in which all
of their characteristics can be seen readily. Only a few comments are
called for.
The few aberrant results, four in all, are in no wise
remarkable. Samples collected with the most minute care are contaminated
from time to time. These
results could be discarded as being
irrelevant on the'basis of their departure from the statistical universe
represented by the other data. However, they have been included in the Ao
fables,and have also been examined individually and in their specific
relationships# The facts concerning them are as follows
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it In Table 8, under Loaders^ of Tank-trucks ? fa result of 0.11 mg. per liter ^which is not entirely beyond the extreme upper normal limit of
the concentration of lead in a ii fit**#**
sample of urine of small volumeA-
ii 14
^probably invalid, because of the
results obtained by the analysis of the first and third samples of this
same person, 0.015 and 0.03 mg. respectively, per liter. (The value of
0.07 mg. per liter which occurs in the same table is not to be take too
seriously, from the aspect of any physiological meaning v/hich it might have otherwise, because of -3N8* small volume, by which the analytical error is magnified. It is not, of course, remarkably high, but it stands out by comparison with the other values in this table.)
In the same table, under "Barrel Fillers", is a result of 0.12
per liter. This was sufficiently unusual, especially in thjs small group
of men engaged in an occupation that might (under certain unusual circumstances)
give rise to/significant degree of exposure, that a further sample was called for and obtained^ -3S3$d on analysishielded the value of 0.02 mg. per liter.
>0 The prior and subsequent samples may be seen to have been 0.025 and 0.02 > '!.<# ,
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respectively,
per liter. This relatively high finding can be dismissed
ly from further consideration.
In Table 9 is a single result, obtained in the first round of
'V
observations^of 0.15 mg. per liter. This result in a service station
attendant could not^by any stretch of the imagination, be regarded as
evidence of a dangerous occupational condition, and the aberrant character
of this finding could be inferred from its unique relationship to the,fbthers
in the same category. Accordingly it was not checked by obtaining a further
sample within a short time. The results obtained in the second and third
samples from this same subject were 0.025 and 0.045 mg. respectively, per
liter.
Essentially the same situation as that above is repeated in
Table 10,in which a result of 0.20 mg. per liter, obtained on the first
round of sampling, was followed by the finding of 0.015 and 0.02 mg.
respectively, per liter, in the second and third samples from the same y~"'y
man. /One additional comment may serve a useful purpose in relation
to the urinary findings. The idea has been advanced and has gained
Cy s ..c ^x c JL .widen in certain circles, that samples of urine of small volume, such
as those voided w--e
do not convey valid information concerning
the general level of the urinary excretion of lead. This is true only
of;samples that are of quite small volume because of the unavailability of
suitable quantities of water within the body of the person who supplies the
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sample, or of samples of unusually large volume voided at a time whe# the
throughput of water is unusually high. (Assuming, of course, that
the renal function is essentially normal.) In short,
a
KHHKKKXxa highly concentrated sample of urine will contain an unusually
high concentration of lead, while a highly dilute sample will yield the
opporite result. Attempts have been made to correct the analytical
result to a standard specific gravity, or a standard concentration of
some allegedly invariable or less variable constituent of the urine.
Thus far, no such correction factor can be held to be valid, even though
it may move the aberrant result somewhat closer to the mean or medium
value of a related group of results. The correction is especially
questionable in dealing with the extremes of concentration, and it cannot
be counted on to do more than artificially to reduce the variability
of a series of results. This fictitious and often misleading procedure
has not been considered for application to the results presented herein.
Rather, we have relied upon a broad experience with awide variety of
results obtained by methods comparable to those employed in this instance,
which, without artifice, have supplied the background for the differentiation of "normal" from "abnormal" results. Finally it should be said, that the
comparison of a series of samples of urine of small volume, with samples of
large volume from the same individuals, shows the former to be
somewhat more widely variable at both ends of the spectrum, i.e., the
small samples make a wider universe, but there is little difference,
otherwise, in the distribution and the statistical characteristics of the
two sets of results. For the purposes of this investigation the lower
incidence of contamination of small samples collected under supervision
and instruction, greatly outweighs the advantage which might otherwise
be gained from samples of large volume^ {#i-'Ulr'"f
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# 000788X
Summary The principal facts obtained in this investigation, as carried out
thus far, are summarized under the two main headings indicative of the dual
character of the investigative approach.
Lead in the air at the occupational sites. (a) The highest levels cf concentration of tetramethyllead are
being encountered in the areas in which the antiknock compound is
mixed with gasoline, at the domes of tank carsy when
. . r,*, L11 u'pwnod.
Occasional concentrations up to 35 micrograms per' cubic foot were
found. This situation is fleeting, and it involves no necessary
or likely exposure of the operators at these sites. The average
levels of concentration at these points in the blending areas in
the vicinity of Los Angeles and San Francisco, respectively,
were 5.44 and 1.53 micrograms of lead per cubic foot of air. The
lead in the air at other locations in the blending areas averaged
less than 2 micrograms per cubic foot.
(b)
IThe levels of lead concentration inthe
11 ing
stations averaged 0.132 microgram per cubic foot of air in Los
Angeles, and 0.26 microgram per cubic foot in San Francisco. The
higher level of concentration in San Francisco derives from the
GO relative nearness of the sampling apparatus to the tanks of the
co
cars during their filling. In consonance with this factor, CO CO
approximately 55 per cent of the total lead in the air at filling
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stations in San Francisco was organic lead; in Los Angeles, the
organic lead approximated but 35 per cent of the total lead in the
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air at the filling stations.
(c)
Samples of particulate matter collected in central
commercial sections of the two cities contained average quantities
of lead amounting to 5.3 micrograms per cubic meter of air in
Los Angeles, and 1.9 micrograms per cubic meter in San Francisco.
These levels are somewhat lower than those reported in investigations
carried out in both cities during 1954.
2. The significance of the occupational exposure of the personnel#
(a)
Groups of individuals engaged in the several occupations
involved in the preparation and distribution of gasoline containing
tetramethyllead as an antiknock compound, failed to give any
J
evidence of their absorption of lead in the course of the$f? regular
performance of their duties over a period approximating nine months.
(The response to occupational exposure to lead in even low and
hygienically insignificant levels of severity occurs promptly in
the form of an increase in the concentration and output of lead
in the urine. The failure of such a response is indicative of
a negligible degree of exposure.)
(b)
The numbers of persons engaged in certain of the occupational
groups was too small to provide data for statistical treatment, A&
3
& that comparisons must be made of the^findings
cJiffltvtJiaeils. In no instance was there a progressive increase
beyond the level of strictly normal variability) in the concentration
of lead in the urines/
0
(c)
The statistical comparison of the levels of lead concentration
in the urine of the two groups of service station attendants
-r" *f~ (in San Francisco and Los Angeles) revearied certain rnconsis-e^irtr
iiJt'ferences. These differences, while of statistically significant magnitude in some instances, cannot be regarded as of physiological
significance in relation to the hygienic question under investigation.
because of their erratic occurrence in time. Moreover, all of the
differences noted are within the range of normal or incidental
^i variability^' and, therefore,
must be accepted as being
within the range of.deviations agf/tHe-general methods of investigation.
(e) The statistical comparison of the data obtained at the three
j u stages of the investigation from each of the two groups of filling CO
station attendants also reveals certain differences within the CD CO
*-U individual groups. These differences have the same characteristics
a^chose referred to above, and, therefore, are of no significance
in relation to the^Jj primary problem of this investigation.
The results of the surveillance of the industrial and commercial
activities associated with the handling of an antiknock compound containing tetramethyl lead in a petroleum refinery and with the distribution of
gasoline containing this compound of lead, as carried out over a period *
approximating nine months,
atHttwariaod,.lari ei.fy below. These results
coincide with those of an earlier and less prolonged investigation of this
problem, in demonstrating that the exposure to lead, specifically to
tetramethyl lead, under the conditions which jaaossosHi: prevail in association with these activities, is negligible. The quantities of lead which escape
into the atmosphere during the performance of the relevant operations are
small, and the contamination of the atmosphere therewith is intermittent
and is regarded as of insignificant proportions in terms of occupational hazard. ,the insignificance of the occupational exposure to lead is
fully confirmed by the lack of any evidence of the absorption of lead by the persons who have been engaged in the performance of the various operations. No
zo individual in any of the categories of employment represented in this survey
CO
CO has manifested any physiological response to the environmental conditions of co CD
his work in the form of a demonstrable increase in the rate or magnitude of
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t*ta?s excretion of }.ead in his urine. Inasmuch as such a response can be counted on to appear in the event of the occurrence of a significant degree
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of occupational exposure to lead in any form,the non-occurrence of such exposure in these relationships is clearly evident.
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