United States
Environmental Protection
Agency
Health Effects Research
Laboratory
Research Triangle Park NC 27711
Research and Development
EPA-600/S1 -81 -047 July 1 981
Project Summary
Hematologic and
Immunologic Studies of
Humans Exposed to SO2
Mirdza L Peterson, Shirley Harder, Delores Elliott, Ve'fva Milholland,
Geraldine Orlando, Beth Margolis, and Dennis House
Immunologic and hematologic
parameters were used to evaluate the
effects in humans of a single 2 hour
exposure to either clean air or 0.75
ppm SO2. Venous blood samples were
obtained before, immediately after,
and 24, 48, and 72 hours following
the end of exposure. Parameters
studied included complete blood
counts, enumeration of lymphocyte
populations using surface membrane
receptor markers, evaluation of
lymphocyte mitogen stimulated re-
sponse, and concentration of secre-
tory immunoglobulin A (s-lgA)
content of nasal washings.
No statistically significant changes
were seen in s-lgA, blood erythrocytes
or immunologic parameters exam-
ined. A possibly significant decrease
was found in monocyte 48 hours
following SO2 exposure, but this
recovered after 72 hours. A
stimulatory effect (not statistically
significant) was noted at 48 and 72
hours post-SOz in s-lgA and in
lymphocyte numbers bearing
receptors for the Fc portion of IgG,
while a decrease occurred in active T-
lymphocytes with receptors for sheep
red blood cells.
This Project Summary was develop-
ed by EPA's Health Effects Research
Laboratory. Research Triangle Park.
NC, to announce key findings of the
research report*that is fully docu-
mented in a separate report of the
same title (see Project Report ordering
information at back).
Introduction
Twenty-eight healthy, non-smoking,
male volunteers between the ages of 19
and 27 were studied after informed
consent was obtained. They completed
a comprehensive medical questionnaire
and were examined by a physician.
Exposures to 0.75 ppm SOa or clean air
took place in an airtight chamber with a
relative humidity of 60% and tempera-
ture at 22 2°C. Subjects rested during
the 2 hour exposure, except for a single
15 mm. exercise period on a treadmill at
4 mph with a grade of 10% that began
45 mm. into the exposure.
Venous blood samples were taken
prior to, and immediately following each
exposure and again at 24, 48, and 72
hours post-exposure. All samples were
processed immediately following col-
lection.
The hematologic analyses included
red blood cell (RBC) and white blood cell
(WBC) counts, hematocnt (HCT), mean
cell volume (MCV), hemoglobin (Hgb),
and cell differential on stained blood
smears.
The effect of SOa on cellular immunity
was determined by the characteristics
of membrane receptors (rosette forma-
tion) and by the mitogenic in vitro
responsiveness (transformation) of
lymphocytes
The s-lgA content of nasal washings
was quantitated by immuno fluorescent
methods.
There was no significant difference
between the air and the S02 group
means in the RBC counts, cell differ-
> US GOVERNMENT PRINTING OFFICE 1981 -757-012/7195
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ential, or the associated parameters
(MCV, Hct, Hgb) at any of the four post-
exposure sampling times A possibly
significant decrease was found in the
percentage of monocytes in the SO?
group compared to controls at 48 hours
post-exposure (p = 0.005; 4.8 + 0.5%)
This change paralleled a progressively
decreasing mean total WBC count
which was decreased to 5481 ±
367/mm3 at 48 hours from 6025 ±
382/mm3 at 0 hour. Both the leuko-
cyte and the monocyte values had
slightly recovered in samples taken at
72 hours post-SCb exposure. It may also
be noted that at 48 hours the percent-
age of lymphocytes was increased in the
S02 group (34.2 ± 1 4% at 0 hour; 37.1
± 1.5% at 48 hours).
Lymphocyte transformation included
data from only 6 subjects in the air
group and 4 subjects in the 862 group
No significant differences were found
between the SOa and the air group
means in the responsiveness of
lymphocytes to phytohemagglutinin
(PHA) or pokeweed mitogen (PWM).
The results of active T-lymphocyte
numbers bearing membrane receptors
for sheep erythrocytes (TEa rosettes)
showed no significant differences be-
tween the means of the SOs and the air
groups (p — 0.746), however, the TEa
values in the 862 group continued to
decrease after the exposure including
the 72 hour sample (567 ± 75 at 0 hour;
417 ± 63 at 72 hours). In contrast, the
mean TEa cell number for the air group
showed a partial recovery at 72 hours
No significant differences were found
between the air and SOa group means in
the lymphocytes bearing receptors for
the Fc portion of IgG (p = 0.227). How-
ever, there was an increase in Fc cells at
48 and 72 hours in the S02 group (363 ±
42 at 0 hour; 41 1 ± 45 at 48 hours, 420
± 45 at 72 hours) in contrast to a de-
crease in the air group (423 ± 54 at 0
hour; 360 ± 55 at 48 hours; 359 ± 42 at
72 hours)
No significant differences were found
m the s-lgA means between the air and
S02 groups (p = 0.279). The s-lgA
levels, (expressed m mg/dl), in the S02
group, however, remained elevated
throughout the post-exposure sampling
period (0.455 + 0 074 at 0 hour; 0.653
±0.181 at 24 hours, 0.776 ±0.220 at
48 hours, 0 61 9 ± 0 178 at 72 hours)
Conclusions
The data provide some suggestive
evidence that exposure to SC>2 may
transiently affect the circulatory blood
cells and may cause parallel effects on
the upper respiratory airways. The data,
however, give no information on indi-
vidual responses nor on the mechanis,
by which the effect is brought about.
This study was performed using young,
healthy, male subjects and conse-
quently provides no information on the
possible effects of SOa on other seg-
ments of the population which might be
more susceptible to this air pollutant.
It is suggested that future research
should include immunologic assays to
measure pollutant-induced changes in
lymphoid cell numbers and functions
which are considered as early indicators
of cellular injury. Measurements should
be made in populations at risk such as
asthmatics using SOa combinations
with other pollutants to resemble
atmospheric conditions. Finally, the
follow-up sampling should be extended
beyond 72 hours post-exposure period
to allow an immunologic response to
develop.
The EPA authors Mirdza L. Peterson, Shirley Harder. Delores Elliott, Velva
Milholland, Geraldine Orlando, Beth Margolis, and Dennis House are with
the Health Effects Research Laboratory. Research Triangle Park, NC 27711.
Shirley Harder is the EPA Project Officer (see below).
The complete report, entitled "Hematologic and Immunologic Studies of
Humans Exposed to S02,"(Order No. PB 81-213 381; Cost: $5.00, subjectto
change) will be available only from:
National Technical Information Service
5285 Port Royal Road
Springfield. VA 22161
Telephone: 703-487-4650
The EPA Project Officer can be contacted at:
Health Effects Research Laboratory
U.S. Environmental Protection Agency
Research Triangle Park. NC 27711
United States
Environmental Protect/on
Agency
Center for Environmental Research
Information
Cincinnati OH 45268
Postage and
Fees Paid
Environmental
Protection
Agency
EPA 335
Official Business
Penalty for Private Use S300
PS 0000329 cnoN
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