v°/EPA
United States
Environmental Protection
Agency
Health Effects Research
Laboratory
Research Triangle Park NC 27711
Research and Development
EPA-600/S1-80-035 May 1981
Project Summary
Effects of Sulfur Oxide
Pollutants on Respiratory
Function, Particle Deposition
and Bronchial Clearance
Morton Lippman, Richard B. Schlesinger, Roy E. Albert, Marc Holpern,
George Leikouf, Donoven B. Yates, and Kim Wales
The effects of sulfur oxide pollu-
tants on respiratory function, particle
deposition, and bronchial clearance
were explored in a series of three
studies, two on donkeys and one on
humans. In the first study, the effects
of one-hour inhalation exposures to
0.3 - 0.6 jum H2SO4 and (NH4)2SO4
aerosols in the donkey were studied in
terms of alterations in pulmonary flow
resistance and dynamic compliance,
and changes in the regional deposition
and tracheobronchial mucociliary
clearance of an inert test aerosol. In
the second study, the effect of chronic
inhalation exposures to sulfuric acid
mist upon mucociliary clearance from
the lungs was studied, using the
donkey as an analogue for man. Four
animals were exposed one hour per
day, five days per week, for six months;
two to a concentration of 102 u.g/m3,
the others to 106 jjg/m3. In the final
study, the mucociliary particle clear-
ance and respiratory mechanics of
twelve healthy nonsmokers exposed
to 1/2 jam H2SO4 at 0 (control), 100,
300, and 1,000 ng/m3 for one hour
per day for four days were examined.
Introduction
This report summarizes the work per-
formed under Contract 68-02-1726
through its termination at the end of
January 1979. It includes descriptions
of experimental studies on animals
which ended on April 15, 1978 and also
studies on human volunteers which
ended at the end of January 1979
Discussion
The work under this contract was
divided into three studies: (1) effects of
short-term exposures to sulfuric acid
and ammonium sulfate aerosols upon
bronchial airway function in the donkey;
(2) effect of chronic inhalation of
sulfuric acid mist upon mucociliary
clearance from the lungs of donkeys;
and (3) effects of sulfuric acid aerosols
upon mucociliary particle clearance and
respiratory mechanics in healthy non-
smoking humans. Each of these studies
is described in the following pages
Short-Term Exposures in
Donkeys
A series of tests were conducted to
study the physiological response of the
lungs of four donkeys to H2SC>4 and
(NH4)2SO4. The response was charac-
terized in terms of changes in
pulmonary flow resistance (RL>,
pulmonary compliance (CL), regional
deposition, and mucociliary tracheo-
bronchial clearance. The sulfate
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aerosols were in the 0.3-0.6 /urn size
range.
Measurements of Ri_and CL were per-
formed, using the esophageal ballon
technique, following one-hour
exposures to (NH4)2SO4 at mass concen-
trations up to 3.0 mg/m3. No significant
change in RL or CL was observed; how-
ever, normal intra-animal variability
was found to be quite large and,
depending upon the specific donkey, a
25-40% change in RL and 10-20%for CL
would have to occur before any change
could be considered significant.
Mondisperse, insoluble ferric oxide
aerosols tagged with a x-emitting iso-
tope, were used to monitor any changes
in regional deposition and clearance
induced by exposure to the sulfur
oxides.
The relative tracheobronchial tree vs.
alveolar distribution of ferric oxide was
not altered by prior, one-hour
inhalations of up to 3.1 mg/m3
(NH4)2SO4 or up to 1.4 mg/m3 H2SC>4.
The lack of measurable effect upon
deposition supports the lack of measur-
able effect upon RL, since both indices
would be affected by alterations in
bronchial calibre.
Mucociliary clearance of ferric oxide
was not affected by one-hour exposures
to (NH4)2S04 at concentrations up to 1.6
mg/m3. However, significant effects
were observed following one-hour
exposures to H2SC>4. The responses
differed in the different donkeys. Two of
the four animalsexhibiteda progressive
change in the control rate of clearance
during the course of the year-long
series of —12 one-hour exposures to
HzSCU exposures.
The other two animals exhibited a
definite, short-term slowing of clear-
ance following single exposures to sub-
micron H2SO4, but had no changes in
clearance in control tests There was
however, considerable inter-individual
variability in response at comparable
exposure levels, with one donkey
responding at concentrations >~700
/yg/m3 and the other responding as low
as 194 fjg/m3. The short-term effect of
H2S04 upon clearance does not become
apparent until —30 minutes following
initiation of acid exposure.
Chronic Inhalation in Donkeys
The chronic exposure study involved
the inhalation exposure of four donkeys
via nasal catheters to 100/ug/m3 of sub-
micrometer H2SC>4 for one-hour per day,
five days per week for six months.
The animals were studied in pairs,
with the initial series of chronic expo-
sure tests being done on Donkeys Ethel
and Gus. They had both exhibited
transient, but no persistent effects
following single one-hour exposures.
The second series was done on Donkeys
Kevin and Leon, who had not previously
been exposed to any inhaled irritants.
Each individual animal had a character-
istic clearance rate which was quite
reproducible on repeated test runs in
the pre-exposure control series.
In all four animals, clearance times
became erratic within the first week of
exposure to the sulf uric acid mist, with
the rate becoming significantly different
from control on many test days. How-
ever, the degree and the direction of
change in rate differed to some extent in
the different animals.
Among the four animals, the most
dramatic response was shown by
Donkeys Leon and Kevin; of these two,
Donkey Leon demonstrated the most
severe effect from the acid exposure.
Donkey Leon exhibited transient
slowing and speeding of clearance
during the first two months of acid
exposure. However, these transient
slowdowns became more severe, and
beginning in the fifth month and
continuing until the end of the exposure
series, a sustained impairment of clear-
ance occurred, and clearance remained
abnormal throughout four months of
follow-up measurements.
Donkey Kevin initially showed some
transient slowing, but appeared to have
returned to within normal limits during
the first month of exposure. However,
beginning within the fourth month,
clearance became erratic and exhibited
a progressive sustained slowing until
the end of the exposure series, with
abnormal clearance persisting through-
out the four month follow-up after the
termination of exposure.
Donkey Gus exhibited transient
clearance slowdowns during the first
three months of acid exposure, but
returned generally to within normal
limits after this period. The magnitude
of clearance slowdowns in the last three
months was much less than during the
initial three months. Occasional excur-
sions were observed during the follow-
up period, with most tests tending
towards the lower limit of normal clear-
ance time.
Donkey Ethel also exhibited some
transient slowdowns; however, the
general trend was towards an acceler-
ated rate of clearance beginning at 4
about the third month of acid exposure."
Subsequently, she exhibited clearance
which was faster than that of her pre-
exposure average in all but one test
performance during the follow-up
period
The sustained, progressive slowing of
clearance observed in Donkeys Kevin
and Leon, two initially healthy and
previously unexposed animals, is a very
significant observation, since any per-
sistent alteration of normal mucociliary
clearance can have important patho-
logical implications.
Aerosol Effects in Humans
Twelve healthy nonsmokers inhaled
Vi/um (o-a = 1.9) H2SO4 at 0 (control),
100, 300 and 1,000/ug/nY'for one hour
via nasal mask in random sequence on
four separate days. Respiratory me-
chanical function was assessed by body
plethysmography, partial forced expira-
tory maneuver and nitrogen washout
before and V4, 2 and 4 hours after the
HaSCU exposure. A59mTc tagged Fe2C>3
aerosol (7.5 /urn AMAD, crg = 1.1) was
inhaled —10 min. before each HaS04
exposure, with flow rate = 1.0 Ips, tidal
volume = 1 liter and breathing rate — A
15/min. Lung retention of the deposited "
radioactivity was monitored by two
12.5 x 5 cm D.Nal scintillation detectors
located within cylindrical collimators
and placed externally over the right mid-
lung field. A tracheal probe containing
six rectangular (1 x 4 x 2.75 cm) colli-
mated scintillation detectors was used
to determine the tracheal mucus trans-
port rates (TMTR's) of boli of activity
No consistent changes in respiratory
mechanics were observed following
H2SO4 exposure at any level, but muco-
ciliary clearance was markedly altered.
In individuals whose control run tra-
cheobronchial clearance half-times
(TBi/2) were greater than the mean,
there was an increased rate of bronchial
clearance (ATBi/2 = -56 min., p*= 0.01)
following exposure to 100 /jg/m3.
Following exposure to 1,000 /ug/m3,
clearance was slowed (ATBi,a = +60
mm., p=£ 0.05). At 300/yg/m3 there was
a wide range of response with increases
in some and decreases in others. The
TMTR's for this group increased signifi-
cantly (p=s0.09) with increasing concen-
tration. On the other hand, for the
individuals with faster than average
control run clearance rates, their TBi/2's
were unchanged following exposure at*j
all three concentrations, while their^j
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TMTR's decreased with increasing
concentration (p=£0.10). Thus, brief
exposures to submicron sulfuric acid at
concentrations that may be encoun-
tered in both the ambient and occupa-
tional environments can affect
mucociliary clearance, an important
pulmonary defense mechanism.
Morton Lippman, RichardB. Schlesinger, Roy E. Albert, Marc Helper n, George
Leikouf. Donoven B. Yates, and Kim Wales are with the New York University
Medical Center, Institute of Environmental Medicine, New York, NY 10016
John O'Neill is the EPA Project Officer (see below).
The complete report, entitled "Effects of Sulfur Oxide Pollutants on Respiratory
Function, Particle Deposition and Bronchial Clearance," (Order No.
PB 81-168 288; Cost: $8.00, subject to 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
1 US GOVERNMENT PRINTING OFFICE 1981-757-012/7076
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