United States
Environmental Protection
Agency
Air
Office of Mobile Source Air Pollution Control
Emission Control Technology Division
2565 Plymouth Road
Ann Arbor, Ml 48105
EPA-460/3-81-025
&ER&
Sulfuric Acid Health Effects
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SULFURIC ACID HEALTH EFFECTS
with Contributions by
Bonnie L. Carson Eileen Horn
Betty L. Herndon Joy L. McCann
Harry V. Ellis III Cecily M. Beall
Larry H-. Baker Carol Hopkins
Task 1 Report
September 11, 1981
Contract No. 68-03-2928 Task Specification
No. 1
"Health Effects Support for the Emission Control Technology Division"
MRI Project No. 4997-T(l)
For
Emission Control Technology Division
Office of Mobile Source Air Pollution Control
U.S. Environmental Protection Agency
2565 Plymouth Road
Ann Arbor, Michigan 48105
Attn: Robert J. Garbe
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PREFACE
This report on health effects of sulfuric acid, was prepared by Mid-
west Research Institute (MRI) as Task No. 1 under Contract No. 68-03-2928,
"Health Effects Support for the Emission Control Technology Division" for
the U.S. Environmental Protection Agency.
Health effects literature primarily related to inhalation exposures to
sulfuric acid has been collected, evaluated, tabulated, and summarized so
that this report can be used to derive a range of concern for human exposure
to vehicular atmospheric emissions of sulfuric acid.
Task activities were coordinated by the project leader, Mrs. Bonnie L.
Carson, Senior Chemist. Documents were rated and summarized by senior phar-
macologists Drs. Betty L. Herndon and Harry V. Ellis III, of MRI, and epide-
miologist Larry H. Baker, M.D., MRI consultant, who is an Associate Professor
of the Department of Community Health at the University of Kansas Medical
Center. Data were tabulated by Ms. Joy L. McCann, Assistant Scientist;
Ms. Eileen M. Horn, Junior Chemist; and Ms. Carol Hopkins, Literature Aide.
The aforementioned and Ms. Cecily M. Beall contributed to the annotated
bibliography. This study was performed under the general supervision of
Dr. Edward W. Lawless, Head, Chemical Impact Assessment Section.
Mr. Robert J. Garbe was the project leader for the Emission Control
Technology Division, U.S. Environmental Protection Agency, and Ms. Colleen
DeMeyer served as Branch Technical Representative.
Approved for:
MIDWEST RESEARCH INSTITUTE
Bruce W. Macy, Director
Center for Technqeconomic
Analysis
September 11, 1981
111
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CONTENTS
Page
Preface iii
Figures . vi
Tables ...... vii
Summary . 1
Animal studies 2
Human studies 2
Studies in progress 5
Discussion. 5
Conclusion 11
1. Introduction 13
II. Bioassay 17
III. Experimental Animal Inhalation Exposures 19
IV. Experimental Human Inhalation Exposures . . 103
V. Epidemiology 123
Occupational exposures 123
Exposures of the general public '....'.. 123
VI. Human and Animal Studies in Progress. 133
Annotated Bibliography ... 137
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FIGURES
Number Page
1-1 Form for report rating 15
VI
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TABLES
Number Page
S-l Animal Exposures Near a No-Observable-Effect Level (or
Lowest Levels Tested) 3
S-2 Human Experimental Exposure Data 6
II-l In Vitro Exposure and Maintenance of Hamster Tracheal
Explants in Sulfuric Acid' Medium With and Without
Carbon Particles 18
III-l Mice—Acute Experimental Exposure to H2S04 20
III-2 Mice—Repeated Dose Experimental Exposure to H2S04 .... 28
III-3 Mice--Chronic Experimental Exposure to H2S04 33
III-4 Hamsters—Acute Experimental Exposure to H2S04 34
III-5 Rats—Acute Experimental Exposure to H2S04 39
III-6 Rats—Repeated Dose Experimental Exposure to H2S04 .... 44
III-7 Rats—Chronic Experimental Inhalation Exposure to H2S04. . 48
III-8 Guinea Pigs—Acute Experimental Exposure to H2S04. .... 49
III-9 Guinea Pigs—Repeated Dose Experimental Exposure to
H2S04 68
111-10 Guinea Pigs—Chronic Experimental Exposure to H2S04. ... 77
III-11 Rabbits—Acute Experimental Exposure to H2S04. ....... 79
111-12 Rabbits—Repeated Dose Experimental Exposure to H2S04. . . 81
111-13 Cat—Acute Experimental Exposure to H2S04 . . . . 82
111-14 Monkeys—Acute and Repeated Dose Experimental Exposure
to H2S04 . 83
111-15 Monkeys—Chronic Experimental Exposure to H2S04. ..... 84
111-16 Dogs—Acute Experimental Exposure to H2S04 ........ 89
111-17 Dogs--Repeated Dose Experimental Exposure to H2S04 .... 91
111-18 Dogs--Chronic Experimental Exposure to H2S04 93
111-19 Sheep—Repeated Dose Experimental Exposure to H2S04. .. . . 96
111-20 Donkeys--Repeated Dose Experimental Exposure to H2S04. . . 97
111-21 Donkeys—Chronic Experimental Exposure to H2S04 98
111-22 Clearance Studies in Rats and Dogs After Instillation. . . 99
IV-1 Humans—Acute Experimental Inhalation Exposure to H2S04. . 104
IV-2 Humans--Repeated Dose Experimental Inhalation Exposure
to H2S04 117
V-l Studies of Occupational Exposure to Sulfuric Acid 124
V-2 Epidemiological Studies Relevant to Sulfuric Acid
Exposure (Exposure of the General Public). . 127
VI-1 Summary of Pertinent Research in Progress on H2S04
Inhalation 134
Vll
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SUMMARY
The goal of this task is to compile and evaluate data from the litera-
ture on the health effects of inhalation exposure to H2S04. The results
will assist the Emissions Control Technology Division (ECTD) of the U.S. En-
vironmental Protection Agency in establishing a range of concern for H2S04
in exhausts from vehicles equipped with emission control devices (e.g. cata-
lytic converters) and in providing guidance to automobile manufacturers.
The exposures of particular concern are those that may occur in traffic
jams, in public parking garages, in home and repair shop garages, in tun-
nels, and in other situations where little dilution of the exhaust is ex-
pected before inhalation. Most of the report (as directed by ECTD) is in
the form of tables based on the literature reviewed. Since the primary in-
terest is on levels where minimal effects are occurring, the summary concen-
trates on exposures around 0.1-1 mg/m3 rather than those at very high levels.
The effects of exposure to H2S04 are not discussed in depth, since this
is being done in a report in preparation by the Environmental Criteria and
Assessments Office (EPA, 1980). The focus of the ECAO report, however, is
to develop criteria for exposure to sulfates and 862 in ambient air, in gen-
eral as a prerequisite for the examination of the NAAQS, and not for local-
ized exposures to H2S04 itself.
Documents on inhalation,effects of H2S04 identified from manual and
computerized literature searches were rated in a two-step process by the
project pharmacologists and epidemiologist. First, the document received
an A, B, C, D rating according to its applicability for deriving a range of
concern for H2S04 in automobile emissions. Second, if the paper was not a
low-rated foreign-language document*, a theoretical paper, a review, or a
non-toxicology experimental paper, it received a numerical score based on
itemized features that should be present in an ideal report.
The original intention was to tabulate only documents rated A, B, or C;
but since some documents were tabulated before they were rated, there are
data from some D-rated documents in the tables.
Most foreign-language articles rated C and D were usually not translated.
Each foreign-language abstract tentatively rated A or B from an English-
language abstract or brief examination of the paper was translated in suf-
ficient degree to judge the experimental design and details. These
papers were numerically scored from the translation.
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ANIMAL STUDIES
No-observable-effect levels (NOELs) were seldom reported in the animal
tests reviewed. In acute exposures, monkeys showed no effect on respiratory
resistance at 2.5 mg H2S04/m3 in air. The chronic monkey studies are con-
founded at low levels by exposures to fly ash and/or S02; but in some com-
binations, ~ 0.1 mg/m3 appeared to be a NOEL.
Rats do not appear to be very sensitive to H2S04 exposure, but it is
much more difficult to measure respiratory function in rats than in humans.
Minor physiological changes are reported in acute rat exposures at levels as
low as 0.1 mg/m3, but serious effects are not observed until levels are
> 100 mg/m3. Body weight changes were seen in a repeated-dose rat study at
0.61 mg S042 /m3 plus S02 in auto exhaust, but 2.37 mg H2S04/m3 alone was a
NOEL in a chronic rat study.
Hamsters showed reversible reductions in ciliary activity when acutely
exposed to ~ 0.9 mg/m3. The presence of ozone worsened the effect.
Guinea pigs, which appear to be the most sensitive species, showed lung
function changes when repeatedly exposed to 1.3 mg H2S04/m3. Increased pul-
monary resistance was observed in acute exposures to as little as 0.1 mg/m3.
In chronic tests, lowered growth rates were observed in females (but not
males) at 0.08 mg/m3.
Dogs showed a NOEL in acute exposure to 1.4 mg H2S04/m3 when the parti-
cles were 0.3 |Jm in size, but detrimental effects on tracheal mucus clear-
ance were noted for 0.87-|Jm particles at 0.49 mg/m3. In repeated-dose tests
in which particle size3was not mentioned, 3.5 mg/m3 increased pulmonary re-
sistance, but 1.0 mg/m was a NOEL. When tested with auto exhausts contain-
ing levels of H2S04 as low as 0.09 mg/m3, dogs exhibited emphysematous
changes even after a ~ 3-year recovery period beyond a 68-month exposure.
Donkeys showed erratic responses in repeated dose tests; but at 0.071
to 1.364 mg H2S04/m3, bronchial mucociliary clearance was generally slowed.
Two of four donkeys, exposed at 0.102 or 0.106 mg/m3, for 6 months showed
impairment with erratic improvement over the next 3 months.
These studies are summarized in Table S.-l.*
\
HUMAN STUDIES
No conclusions useful for the present objectives can be drawn from the
literature on occupational exposures to H2S04 because the exposure levels
were relatively high, and inadequately measured. Almost no epidemiological
The time abbreviations used throughout this report are those recommended
by the American Society for Testing and Materials Standards for Metric
Practice. For those unfamiliar with these abbreviations, they are:
d for day, h for hour, rain for minute, and s for second. No recommen-
dations were made for year, month, and week, for which we used y, mo,
and wk, respectively.
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TABLE S-l
ANIMAL EXPOSURES NEAR A NO-OBSERVABLE-EFFECT LEVEL
(OR LOWEST LEVELS TESTED)
H2S04 Type of
Level, mg/m3 Exposure Species
2.5
2.37
acute
1.4, 0.3 |Jtn acute
1.3
1.0
-0.9
0.61 S042-
(presumably
most H2S04)
in auto
exhaust
acute
repeated
dose
monkey
chronic rat
dog
repeated guinea
dose pig
repeated dog
dose
hamster
rat
Details and
References
in Table
111-14
III-7
111-16
III-9
111-17
III-4
III-6
Effects
No effect on respiratory
resistance.
NOEL (lung function, blood
chemistry, behavior).
NOEL
All-or-none effects due
to H2S04 are seen in guin-
ea pigs. Lung function
changes.
NOEL. (At 3.5 mg/m3, in-
creased pulmonary resis-
tance.)
Reduced ciliary activity.
Reversible. Ozone wors-
ened the effect.
Lower body weight.
0.49, 0.87 pm acute
0.49, 0.3 |Jm acute
0.102 or
0.106
dog
dog
chronic donkey
(6 mo)
111-16 Slight, nonsignificant in-
crease in trachea! mucus
velocities for Si d. Clear-
ance .significantly de-
creased 1 wk after expo-
sure.
111-16 NOEL.
111-21 Sustained impairment in
bronchial mucociliary
clearance in two of four
donkeys. Some improve-
ment within 3-mo recovery
period.
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TABLE S-l (concluded)
H2S04 Type of
Level, mg/m3 Exposure
-0.1
plus fly ash
and/or S02
chronic
0.1-1.0 acute
alone or with
0.4-0.5 ppm
03
0.08
Species
monkey
rat
0.1
-0.09
in auto
exhausts
acute
chronic
(68 mo)
guinea
Pig
dog
chronic guinea
pig
0.071-1.364 repeated donkey
dose
Details and
References
in Table
111-15
III-5
III-8
111-18
111-10
111-20
Effects
NOEL for some combinations
of pollutants.
Increased activities of
lysosomal hydrolases, etc.,
in lung homogenate.
Tracheal explants showed
increased rates of mucus
glycoprotein secretion.
Increased pulmonary resist-
ance.
Emphysematous and other
microscopic lung changes
3 y after 68-mo exposure.
Lowered growth rates in
females. NOEL in other
studies.
Bronchial mucociliary
clearance slowed.
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study ever mentioned H2S04 levels, but H2S04 is considered a sizable frac-
tion of the measured sulfate values. The primary problems in attempting to
use data from epidemiological studies reviewed herein are the co-variance of
sulfate with other pollutants (particulates, 63, NO , S02, HC1, etc.) and
the confounding of these general exposures with localized phenomena (such
as occupational exposures), smoking (active and passive), genetic factors,
etc. These factors are seldom addressed. When they are considered, it is
difficult to be convinced that they have been considered exhaustively. In
addition, the analysis of time trends is difficult. Some results show con-
vincingly that smoking and other pollutants are bad, but the effects of all
the ingredients in polluted atmospheres are inseparable.
The more pertinent human experimental data are summarized in Table S-2.
Large particles are more objectionable at comparable concentrations. At
~ 0.1 mg H2S04/m3, a few lung function changes and bronchial mucociliary
clearance increases are sometimes reported. Some pulmonary function effects
were seen down to 0.066 mg H2S04/m3 (Gardner et al., 1978). We might ques-
tion whether these statistically significant effects are toxicologically im-
portant or are within normal biological variation. No lung function changes
were seen in a 2-day experiment by Klein and Hackney (1978) and Avol et al.
(1979) at 0.075 mg/m3. The exposures in these tests were very short (usu-
ally ^ 2 h), and the repetitions in the repeated dose tests were apparently
few. Some well-designed tests [Chancy et al. (1979) (2 d at rest) and
(1980) (1 d with exercise)] have so far yielded negative results on blood
parameters after exposures to 0.1 mg H2S04/m3. The lung function data have
not yet been published, but preliminary data suggest that they will not show
toxicity at 0.1 mg H2S04/m3, either.
STUDIES IN PROGRESS
MRI contacted, by letter, nearly every principal investigator who had
pertinent research in progress. Data from every written report received
from those queries were incorporated in the tables of the appropriate chap-
ters. However, a few studies that were rated only from brief research pro-
ject notices are summarized in Table VI-1 in Chapter VI.
DISCUSSION
Acute exposure to aerosols of sulfuric acid at levels above ~1.8 mg/m3
is irritating to the lining membranes of the human respiratory tract. The
irritant effect causes reflex bronchoconstriction, slowing of mucus flow,
and depression of clearance of inert particles from the lung; and when the
concentration is above a level of about .06 mg/m3 or in especially sensitive
individuals, sulfuric acid also produces narrowing of airways as quantitated
by measurable change in pulmonary function tests. Similar levels produce
visual effects as quantitated by change in sensitivity to light.
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TABLE S-2
HUMAN EXPERIMENTAL EXPOSURE DATA
H2S04
Level, mg/m3
1.1-1.4
Type of
Exposure
acute
acute
acute
Data and
References
in Table
IV-1
IV-1
IV-1
(several
studies)
1.0
repeated
dose
IV-2
Effects
Clearly irritant; respiratory rate
increase;.
Increase in airway resistance,
changes in light sensitivity,
throat irritation.
Still clearly irritant to some.
Threshold of detection for some;
but others do not detect by odor,
taste, or irritation below this
level. Some show respiratory
clearance increase with exercise.
Even asthmatics did not show
changes in lung function or gas
transport.
Bronchial mucociliary clearance
decreased, but no pulmonary func-
tion changes after nasal exposure
for 1 h/d for 4 d. Particles of
2-5 |Jtn were too irritant for deep
breathing at 0.75-1.0 |jg H2S04/m3.
0.107-0.983
0.6-0.85
^0.750,
1-2 |Jm
acute
acute
repeated
dose
~0.500-0.750, repeated
2-5 fJm dose
IV-1 Little effect on ventilatory
mechanics, but mucociliary clear-
ance was markedly altered.
IV-1 Throat irritation.
IV-2 Slightly irritant but no consistent
lung function changes.
IV-2 Very irritating, producing severe
coughing upon deep breathing with
erratic effects on lung functions.
Large particles impact on upper
respiratory tract, where they are
still relatively strongly acid.
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TABLE S-2 (continued)
H2S04
Level, mg/m3
-0.4-0.75
plus similar
S02 concen-
trations
Type of
Exposure
acute
Data and
References
in Table
IV-1
Effects
Some combinations caused an in-
crease in light sensitivity.
0.3-0.5 acute
alone "or with
S02 and/or 03
0.3-0.5 repeated
dose
^0.250,
2-5 M">
0.195
repeated
dose
acute
exptl.
IV-1 Rapidly reversible increase in
respiration rate. Effects of 03
not changed much, if any, by pre-
sence of H2S04. No change in light
sensitivity with 0.3 rag H2S04/m3
and 0.65 mg S02/m3.
IV-2 Bronchial mucociliary clearance
affected but not lung functions
(at least not consistently).
IV-2 Irritant but breathable. No
consistent lung function effects.
IV-1 No significant changes in pulmonary
function, respiratory rate, or
tidal volume.
0.1
0.1
(several
studies)
repeated
dose
acute
exptl.
IV-2 Bronchial mucociliary clearance
increased but lung functions not
affected after 1 h/d for 4 d. No
effects seen in blood parameters.
IV-i Neither normals or asthmatics showed
pulmonary function changes in a study
with 0.1-|Jm particles nor did normals
in a study with 0.5-|Jm particles. No
effects on blood parameters whether
subjects were at rest (repeated dose
study) or exercising during exposure.
At 0.055 |Jm, 2 of 18 lung function
parameters were significantly altered.
With 1.8-|Jm particles, a slight in-
crease was seen in airway resistance.
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TABLE S-2 (concluded)
Data and
H2S04 Type of References
Level, mg/m3 Exposure in Table Effects
0.066-0.098 acute IV-1 No significant differences seen in
lung function parameters except in
3 of 18 in the study at 0.066 mg/m3.
In the other two studies, no dif-
ferences were seen between smokers
and nonsmokers or between asthmatics
' and normals.
0.01 acute IV-1 No changes in lung function or gas
transport.
SO.001 plus acute IV-1 Pulmonary changes were seen in the
0.37 ppm 03 test where there was a period of
and S02 plus exposure to S02 alone. Otherwise,
hydrocarbons no effects were seen in sensitives
(2 tests) or normals.
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Synergism between sulfuric acid and the pollutants normally found in
auto exhaust has been shown in animals, which confounds isolation of a H2S04
effect. Adequate demonstration has not been made of the total effects of
S02, ozone, and metallic aerosols with sulfuric acid in man. Studies in
which humans have been exposed to combinations of sulfates and sodium chlo-
ride aerosols have not consistently shown the synergistic effect seen in
sensitive species. The variability between experimental animal NOEL, the
all-or-none response seen in some species, and the anatomical differences
that naturally exist in man and experimental animals make the establishment
of human exposure levels very difficult to base on animal data. The number
of studies that exist, and the variety of species exposed under many condi-
tions, however, allow an overall generalization to be made where effects are
tabulated not by species but by exposure level (See Table S-l). In spite of
the variability of human studies and the high levels reported in industrial
exposures to H2S04 aerosols, human exposure work furnishes our best data.
The physiological responses found under controlled conditions, in human
experimental exposure, allow establishment of H2S04 effect levels, but can-
not address potential synergisms that might be found in contaminated urban
air. Exposures of populations to mixed aerosols which approximate urban air
may produce a realistic and controlled effect, but the data derived from
such exposure will be difficult to use for determining a range of concern
for only one component of the mixture. If this premise is accepted, it is
realized that closer analysis of existing work may be more valuable than
collecting new epidemiology data in determining a realistic air range of
concern for sulfuric acid.
One of the more interesting findings in the toxicity of H2S04 is the
nature of the irritant effects in the primate, characterized by decreasing
sensitivity with both repeated exposure and continuous exposure. The nature
and timing of many human epidemiologic studies obscure these effects, so it
is not possible to state positively that they occur in humans. Hackney
(1978) showed that primates, given H2S04 aerosols of 0.4 |Jm diameter at 40%
relative humidity, had an increase in airway resistance that occurred at
60 min exposure and then tended to decline. Bushtueva (1957) noted a de-
creasing effect in the human eye with successive exposure to a low level of
H2S04 mist: 0.6 mg/m3 produced a very slight increase in light sensitivity
on the first exposure, but no effect on the second exposure. Sensitivity
returned to normal in about an hour. This decrease in toxic effect as a
function of time of exposure, if this response is generalizable, could help
interpret many inconsistencies in some human exposure studies. If, in fact,
the H2S04 response is a transient one, group-averaged data taken without
consideration of individual differences and of changes over time, will flat-
ten the dose-response curve and underestimate the response. Many of the ex-
perimental studies that utilized H2S04 aerosols without other particulates
found that the spray was acutely low in irritation. There was also an indi-
cation that ammonia in breath and upper respiratory passages neutralized
the H2S04 spray to a large extent. The other particulates in the aerosol
are of high importance to H2S04 effects. Carbon particles, in particular,
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furnish a site for H2S04 adsorption. The carbon-acid particle is hygro-
scopic, attracts moisture, and enlarges in size. It then becomes poten-
tially damaging to the lung, unless mucociliary clearance occurs. This
clearance rate is variable depending on individual lung health and smoking
status. This example demonstrates the two prime variables in establishing
the single "toxic" limit of H2S04 to man: the differences in exposure con-
ditions reported and the physiologic differences in the human population ex-
posed.
To analyze animal H2S04 exposure data and extrapolate some value to man
and potential human exposure limits, it has become important to choose a
target measure that will best reflect human toxicity. As a target tissue
the respiratory system may be more difficult to quantitate than the eye's
light sensitivity, but more data have been gathered on the lung. Human
bronchial clearance increased with exposure to 1 mg/m3 (Newhouse et al.,
1978). Donkey bronchial clearance decreased with 0.200 mg/m3. Sheep tra-
cheal clearance did not change with 4 to 14 mg/m3 H2S04 (Sackner et al.,
1978b). Mouse lung clearance decreased with 15 mg/m3 (Fairchild et al.,
1975a). Studies in equines (which are anatomically good models for human
lung work) found severe decreases in bronchial clearance with no change in
tracheal clearance, indicating that the more sensitive measure of H2S04 cil-
iary damage appeared to be the bronchial clearance rate (Schlesinger et al.,
1978; 1979).
From the experimental studies it is possible, therefore, to look at or-
gans of importance and extrapolate the exposure studies based on the impor-
tance of these organs to human toxicity. As an example, the trachea is
known to be high in endogenous sulfates (Dahl et al., 1979). When radio-
labeled H2S04 was experimentally instilled onto the trachea, no lung deposi-
tion occurred. The indication is, therefore, that the body has areas of
high acid and also has natural mechanisms such as respiratory NH3 for its
neutralization.
Most data indicate the importance to H2S04 toxicity of the synergism of
H2S04 and other particulates in the air. For example, without other particu-
lates on which to deposit and grow more hygroscopic, an inhaled H2S04 mist
is rapidly neutralized (Lawther, 1980), probably by NH3 in the expired air
(Barrow and Steinhagen, 1980). The particles may also deposit in the tra-
chea, which already has high levels of sulfates, or even higher in the
respiratory tract. Human experimental data have demonstrated that an in-
creased respiratory rate occurs with exposures as low as 0.350 mg/m3, but
that these respiratory increases are related to the central nervous system
(presumably respiratory control function stimulation) rather than to lung
changes (Bushtueva, 1957). At these low levels of exposure, overall changes
that are reported are often physiological repair mechanisms in progress,
and the final result reported is that of minimally detectable change from
control group effect. Chronic studies that evaluate kinetics of several
systems in exposed groups have been carefully evaluated, therefore, since
they may furnish important clues to the long-term effects of H2S04 exposure.
10
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CONCLUSION
The toxicity of inhaled H2S04 to humans appears to depend very heavily
on the individualized response (health, length of exposure) and on the pres-
ence of other particulates in the air. H2S04 is hygroscopic and tends to
take up moisture from the breath to form larger droplets that impact high in
the upper respiratory tract where they cause less damage. The H2S04 may
also be partially neutralized by ammonia in the breath and its effects thus
reduced. When other particulates are also present, the acid may adsorb on
them and be carried more deeply into the respiratory passages. Such deposi-
tion carries a greater potential for irritant effect.
It is of interest in this regard that asthmatic humans, who are consid-
ered more responsive to bronchial irritants than the population in general,
suffered no greater effect than normal humans to H2S04 aerosols, even when
exposed at levels approximating "worst case" situations (Sackner et al.,
1978b; Avol, 1979).
A lower exposure level that appears to be safe for man is in the rangev
of 0.066-0.098 mg/ra3,* but this level is suggested with several caveats. In
particular, several temporal and synergistic factors must be considered.
The frequency and duration of exposure appears to influence significantly
the effects of H2S04. The individual's exposure to other particulates (e.g.
cigarette smoke) appears to influence the chronic effects of H2S04 more than
certain general health conditions (e.g. asthma). Thus temporal and syner-
gistic considerations in exposure conditions must be considered in deriving
a range of concern for sulfuric acid in automobile emissions.
In the USSR, the value of 0.1 mg H2S04/m3 is the average maximum allow-
able concentration for the ambient air of populated places; however,
a peak value of 0.3 mg/m3 is permissible (USSR, 1972).
11
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SECTION I
INTRODUCTION
This report was compiled as the first of several tasks under Contract
No. 68-03-2928, "Health Effects Support for the Emission Control Technology
Division (U.S. Environmental Protection Agency, Ann Arbor, Michigan)." The
goal of the project is to evaluate health effects literature on specific
compounds emitted from automobiles equipped with emission-control devices
(particularly, catalytic converters), not for the purpose of creating a cri-
teria document, but to help in the identification of ranges of concern for
each compound to serve as guidance to automobile manufacturers in their de-
velopment of future emission-control devices.
Many people may be exposed directly to sulfuric acid emitted near
ground level from automobiles equipped with catalytic converters. Exposure
can occur repeatedly and for many minutes at a time in confined quarters
(e.g., enclosed home or public garages) or in congested traffic. Under such
conditions the acid may be only slightly diluted before inhalation. This is
a quite different situation from exposure to sulfuric acid produced in the
upper atmosphere from sulfur oxides emitted from tall stacks by fossil-fuel-
burning power plants and sulfide-ore smelters. The latter situation usually
requires unusual atmospheric conditions for the general public to be exposed
to high concentrations of sulfates and sulfuric acid in aerosols near ground
level. The Environmental Criteria and Assessment Office (ECAO) of the EPA
at Research Triangle Park, North Carolina, has been assessing environmental
exposure to sulfur oxides and particulates (the latter includes sulfuric
acid) and has been reviewing the pertinent sulfuric acid literature.* An
ambient air criteria or standard may not, however, apply directly to the
.situations described above where people are in such close proximity to the
source. Hence, the present task addresses this narrower but still possibly
important safety question in a timely manner. Because of the intentional
shortness of time under which this material is prepared, some of the subtle
but nonetheless important issues contained in a complete examination of the
health effects of sulfuric acid may not be investigated. The criteria docu-
ment when completed and published should be considered the definitive source
of comprehensive information on sulfuric acid.
* Much of the sulfuric acid health effects literature evaluated herein was
reviewed in EPA's April 1980 draft document Air Quality Criteria for
Particulate Matter and Sulfur Oxides, Volume IV. Health Effects (EPA,
1980).
13
-------
The work directive for this task, issued May 6, 1980 by the Emissions
Control Technology Division, noted that "No suitable tabulation of sulfuric
acid health effects data is available for use in determining an acceptable
level for sulfuric acid emissions from motor vehicles." The present report,
therefore, was meant to be largely a series of charts or tables of these
data with the tests logically ordered according to exposure levels. The
narrative summary was not meant to describe again each paper in detail.
There are admittedly some disadvantages in not doing so; e.g., some of the
gradations in effect the authors of a particular paper observed may be di-
luted or lost when the details are spread throughout an exceptionally large
table (such as the 19-page compilation of acute exposures of guinea pigs).
Also, we only compile reported results, and do not evaluate parameters not
reported. Papers described in a largely narrative fashion are in fact dif-
ficult to compare. An advantage of our approach, however, is that results
that appear within their source paper to be quite definitive may appear less
so or even anomalous when juxtaposed in tabular format with other results
from similar studies. Hence, the present format was designed to facilitate
comparisons.
Literature related to health effects of inhaled sulfuric acid was col-
lected mainly by computer search of TOXLINE and manual search through the
EPA draft criteria document on SO and particulates (EPA, 1980). Approxi-
mately 270 papers and other documents were obtained, almost half of which
contained original data suitable for tabulation. After consideration of the
length of the tables generated in this task, future task reports will be
pared to a more manageable scale by including only the most pertinent stud-
ies. This would tend to exclude studies limited to such topics of marginal
relevance as lethal effects of high doses and studies that appeared to have
serious deficiences in method or presentation of results. x
Experimental animal and human exposure studies were evaluated and sum-
marized by senior Ph.D. pharmacologists. Studies related to exposures of
the general public (herein tabulated as epidemiological studies) and occupa-
tional exposures were rated by an epidemiologist with an M.D. degree. Fig-
ure 1-1 is the form used for rating documents by the project pharmacologists
and epidemiologist. Each document was rated in a two-part procedure accord-
ing to the applicability of its subject matter and to the quality of the ex-
perimental methodology. The letter assigned in rating the document A, B, C,
or D was derived from the corresponding lower case letters under item 7 in
Figure 1-1. Thus, a study was rated A if it directly applies or assists in
establishing a range of concern for exposure to sulfuric acid. The second
part of the rating is the methodology score. The document reviewer checked
off which score should be given for each of the first six items in Figure
1-1, and the total was written at the top of the page along with the letter
that rated the paper's applicability. In some cases, such as reviews and
theoretical papers, a paper may have received an applicability rating but
none on methodology.
Data, including the MRI-assigned rating, from the A-, B-, and C-rated
(and a few D-rated) papers were tabulated by mid-level and junior-level sci-
entists. Information for each topic heading was looked for; so if blanks
14
-------
Article No. 4997-1-
CHECK WHERE APPROPRIATE:
1. Do they state/limit the problem?
2. Adequacy of sample
3. Replicability
4. Controls /control procedures
5. Completeness and comprehensibility
of results
6. Validity of conclusions, inter-
pretation of data
PAPER
DEFECTIVE
0
PAPER IS
SUB-
STANDARD
1
STANDARD
QUALITY
2
SUPERIOR
PAPER
3
7. Applicability to health effects of sulfuric acid as guidance for estab-
lishing a range of concern in automobile emissions.
(circle one)
,'
_a. Clearly, directly applies/assist in establishing emission criteria.
b_. Research requires major inferences; potentially applicable.
£. Useful hints or suggestions; tentatively applicable.
_d. Not directly applicable (Peripheral useful information).
Figure 1-1. Form for report rating.
15
-------
appear in the table, the reader can generally assume the data were not
given. Sometimes a group published several papers that described the same
tests. To avoid redundancy, all pertinent papers were cited and the test
was described as well as possible from all the papers' descriptions. If the
same test was described in a way that we did not immediately recognize, jux-
taposition in the final tables usually made us aware that condensation was
possible. However, in certain groups of papers, the authors' rounding of
the results in some and using more significant figures in others may have
led us to list the same test more than once. We have cited abstracts as
well as the corresponding published papers because they have helped us to
fill in the gaps. In a few cases, we have not located a full published
paper, but we felt the brief abstracts should not be excluded. They can
often be recognized in the tables by an A or B rating accompanied by a low
numerical score.
The final summary of the tabulated data was also performed by a senior
pharmacologist. This summary attempts to reflect objectively the scientific
community's thought as a whole and does not reflect the tabular material by
weight (since a few particularly prolific groups have published many papers
compared to the overall literature on the subject). The tables reflect the
amount of data generated, and the summary puts the evaluated data in per-
spective with the overall scientific community's opinions.
The references are cited in an annotated bibliography that includes not
only each document's rating but also a brief comment on its pertinence (or
lack thereof) to the study. The annotation is not meant to be an abstract.
The report is organized into the following chapters: II - Bioassay
Tests, III - Experimental Animal Inhalation Exposures, IV - Experimental Hu-
man Inhalation Exposures, V - Epidemiology (exposures of occupational groups
and the general public), and VI - Human and Animal Research in Progress. The
Summary precedes the entire report, and the Annotated Bibliography follows
Chapter VI.
16
-------
SECTION II
BIOASSAY
Few pertinent papers were found relating to the action of sulfuric acid
in bioassays. In an early mutagenesis study by Demerec et al. (1951) (rated
C-12), 3-h treatments with 0.002-0.005% sulfuric acid solutions gave nega-
tive results with 107-108 Escherichia coli (10.9-74 mutants/108 bacteria
compared to 8.3-147 mutants/108 bacteria in the controls).
In a study of peripheral interest, Hoffman and Campbell (1977) (study
rated C-9) exposed chick embryos (in the egg) to airborne sulfuric acid over
a 14-day exposure period. The embryos showed a significant (20%) decrease
in serum lactic dehydrogenase (LDH), which might indicate a delay in normal
development.
The in vitro exposures of hamster tracheal ring explants to a medium
containing H2S04 or H2S04 plus carbon particles are described in Table II-l.
These results should be compared with the results obtained with iji vivo ex-
posure plus in vitro maintenance described by Schiff et al. (1979) that are
in Table III-4. Exposing tracheal explants to a nonsulfuric acid-containing
medium at the same pH (pH 5.0) gave no lasting morphological changes. The
toxicity produced by H2S04 was not due to its acidity.
17
-------
TABLE II-l.
IN VITRO EXPOSURE AND MAINTENANCE OF HAMSTER TRACHEAL EXPLANTS IN SULFURIC ACID MEDIUM
WITH AND WITHOUT CARBON PARTICLES
Medium
H2S04l 2 (Jg
in culture
solution
00
H2S04, 2 pg/ml
C particles,
100 Mg/ml in
culture solu-
tion
Mode of Exposure
Tracheal explants under sim-
ple medium containing pol-
lutant. 60 x 15 mm culture
dishes placed in a controlled
atm. chamber. Chamber rocked
at 10 cycles/min to cause
pollutants to flow continu-
ously over the epithelial sur-
face. Water-saturated atm.
contained 5% C02 in air.
Tracheal explants under sim-
ple medium containing pol-
lutants.
Kind
of Sample
CrRGH(SYR)
Syrian golden
hamster tra-
cheal explants
4 wk
No. of
Test Samples
8 tracheal rings.
2 rings/hamster
No. of
Control Samples
8 tracheal rings
2 rings/hamster,
in pollutant-
free medium
Duration
and Frequency
3 h, once
after 24-h
maintenance
period in
unpolluted
culture solu-
tion
CrRGH(SYR)
Syrian golden
hamster tra-
cheal explants
4 vk
8 tracheal rings.
2 rings/hamster
8 tracheal rings
2 rings/hamster
3 h, once
Ref-
erence
and
Rating
Schiff
et al.
(1979)
C-10
Effect
At 24 h, ciliary beat fre-
quency significantly reduced
from controls. By 48 h,
beating frequency was within
normal range. Pattern of
damage-to epithelium resem-
bled iri vivo observations.
Morphological damage immedi-
ately observable after expo-
sure. Recovery not within
72-h observation period.
Statistically similar damage
between in vivo and in vitro
exposures.
Significantly reduced ciliary Schiff
beating frequency at 24 h. et al.
By 48 h, beat frequency was (1979)
within normal range. Mor- C-10
phological damage immedi-
ately evident, persisted for
48 h. Histopathological and
scanning electron microscope
alterations similar to in
vivo exposure plus in_ vitro
maintenance changes. Damage
statistically similar between
in vivo and iji vitro exposures.
-------
SECTION III
EXPERIMENTAL ANIMAL INHALATION EXPOSURES
The essential parameters of numerous animal inhalation exposure experi-
ments are tabulated in this section. Each table includes the tests for one
species having approximately the same exposure length (that is, acute, re-
peated dose, or chronic studies). Within each table, the tests are arranged
in order of decreasing sulfuric acid concentration. Where only a range of
concentrations was specified, the highest level determined the place of the
test in the hierarchy. -
The tables, grouped by species and test duration, are arranged by ap-
proximately increasing weight of the test species. Thus, Tables II-l, -2,
and -3, give the mouse data for acute, repeated dose, and chronic inhalation
exposures to sulfuric acid, respectively. Table III-4 gives acute data for
hamsters. Tables II-5, -6, and -7 give rat data; and Tables II-8, -9, and
-10 give guinea pig data. Data for acute and repeated dose exposures of
rabbits are given in Tables III-ll and 111-12, respectively. Data on ah
acute exposure of one cat may be found in Table 111-13. Acute and repeated
dose data for monkeys are in Table 111-14. Chronic monkey tests are de-
scribed in Table 111-15. Tables 111-16, -17, and -18 report data for dogs.
A repeated dose test on an undetermined number of sheep is described in
Table 111-19. Repeated dose and chronic studies in donkeys are shown in
Tables 111-20 and 111-21, respectively. In addition, Table 111-22 summa-
rizes clearance studies performed with rats and dogs after instillation.
The tables have been arranged in the aforesaid manner for the following
reasons: (1) there were more than 400 separate tests being tabulated; (2)
there are distinct differences in lung anatomy among the laboratory species
used, and the differences seen in their relative responses may have been
largely due to these anatomical differences; and (3) by putting the highest
concentrations and worst effects first, one can more readily understand the
significance of minor or less-severe changes occurring at lower levels.
However, a composite Table S-l appears in the Summary. This table
groups the results seen in various animal species at levels less than ~ 2.5
rag H2S04/m3, a no-observable-effeet-level in some species.
19
-------
TABLE III-l. MICE—ACUTE EXPERIMENTAL EXPOSURE TO 1I2S04
KJ
o
Compound (s)
and Concen-
tration^) in
mg/m3
H2S04
1,610
H2S04
1,470
H2S04
1,040
H2S04
730
H2S04
718
H2S04 700
Carbon
Particles, 5
H2S04
699
Humidity/
Particle
Size
< 2.0 |jm
< 2.0 yin
40%
0.9 Mm
(MMAD)
40%
0.85 |Jm
(MMAD)
< 2.0 M">
60%
0.4 pm
< 2.0 M"n
Mode of
Exposure
Inhala-
tion
chamber
Static?
Inhala-
tion
chamber
Static?
Exposure
chamber
Exposure
chamber
Inhala-
tion
chamber
Static?
Inhala-
tion
chamber-
Inhala-
tion
chamber
Species/ Duration &
Strain/ Test Nos. of Frequency Total
Age/ Animals Controls of Length
Weight M F M F Exposure of Expt.
Mice 5 7 h, once
Mice 5 3.5 h, once
CDt 20 20 Not Groups of
mice, given 10 removed
6-7 wk after 1, 2,
4, and 8 h
CDt 20 20, Not Groups of
mice, given 10 removed
6-7 wk after 1, 2,
4, "and 8 h
Mice 5 3.5 h, once
-'
Mice 24 3 h, once
Sprague-
Dawley
ARS2,
CF,,
3-6 wk
Mice 5 7 h, once
Effects
Three animals died. Extensive focal hem-
orrhage and edema in lungs, degenerative
changes in surface of larynx and trachea,
and respiratory tract congestion.
Two animals died. In lungs, extensive focal
hemorrhage and edema; degenerative changes
in surface of larynx and trachea; and respira-
tory congestion.
Twenty-one deaths during first 4 h exposure;
two more deaths up to 2 wk after exposure.
No significant lesions of trachea, larynx,
or turbinates resulting from exposure. Some
lung lesions resulting from pneumonia, asso-
ciated with aspiration of foreign materials.
Eight deaths within exposure; 6 more deaths
up to 2 wk after exposure. No signficant
lesions of trachea, larynx, or turbinates re-
sulting from exposure. Some lung lesions re-
sulting from pneumonia associated with
respiration of foreign materials.
Three animals died. Focal hemorrhage and
edema in lungs.
Five deaths (21% mortality)
Two animals died. Focal hemorrhage and
edema in lungs.
.
Reference
and Rating
Treon et al .
(1950)
A-8
Treon et al.
(1950)
A-8
Runkle and Hahn
(1977a)
D-12
Runkle. and Hahn
(1977a)
D-12
Treon et al.
(1950)
A-8
Bradof et al .
(1978b)
B-12
Treon et al.
(1950)
A-8
Static?
-------
TABLE III-l. MICE—ACUTE TESTS (continued)
Compound (s)
and Concen-
tration^) in
mg/m3
H2S04
600
H2S04
600.
H2S04
550
H2S04
549
X
H2S04 500
Carbon
Particles, 5
H2S04 500
Carbon
Particles, 5
H2S04
100 & 500
Carbon
Particles, 5
H2S04 500
Carbon
Particles, 5
Humidity/
Particle
Size
60%
0.12 Mm
60%
0.12 (Jm
50%
1.2 Mm
(MMAD)
< 2.0 Mm
60%
0.4 Mm
60%
0.4 pra
60%
0.4 Mm
60%
0.4 MH>
Mode of
Exposure
Inhala-
tion
chamber
Inhala-
tion
chamber
Exposure
chamber
Inhala-
tion
chamber
Static?
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Species/ Duration &
Strain/ Test Nos. of Frequency Total
Age/ Animals Controls of Length
Weight M F M F Exposure of Expt.
Mice .101 3 h, once
Mice 60 3 h, once
CDj 20 20 Not Groups of
mice, given 10 removed
6-7 wk after 1, 2,
4, and 8 h
Mice 5 3.5 h, once
Mice 48 6 h, once
Sprague-
Uawley,
ARS2- x
CFt
3-6 wk
Mice, 44 6 h, once
Murphy
BDFj,
3-6 wk
Mice Groups of 3 h, once
48-102
Mice, 50 3 h, once
Sprague-
Dawley,
ARS2-
CF1(
3-6 wk
Effects
36 deaths (36% mortality)
12 deaths (20% mortality)
^
5/20 died during last 2 h of exposure.
One death 2 wk after exposure. No sig-
nificant lesions of trachea, larynx, or
turbinates resulting from exposure. Some
lung lesions resulting from pneumonia as-
sociated with aspiration of foreign materials
Two animals died. Focal hemorrhage and
edema in lungs.
22 deaths (46% mortality)
2 deaths (4.5% mortality)
Groups were exposed to Streptococcus 72 h
prior to exposure to various combinations
of acid and carbon. Mortality ranged from
19 to 28% of groups including controls
12 deaths (24% mortality)
Reference
and Rating
Bradof et
(1978b)
B-12
Bradof et
(1978b)
B-12
Runkle and
(1977a)
D-12
al.
al.
Hahn
Treon et al.
(1950)
A-8
Bradof et
(1978b)
B-12
Bradof et
(1978b)
B-12
Bradof et
(1978b)
B-12
Bradof et
(1978b)
B-12
al.
al.
al.
al.
-------
TABLE III-l. HICE--ACUTE TESTS (continued)
Compound (s)
and Concen-
tration^) in
mg/m3
H2S04 500
Carbon
Particles, 5
H2S04, 200-
500
H2S04, 200-
500
03, 30-80
H2S04
461
H2S04 400
Carbon
Particles, 5
H2S04 400
Carbon
Particles, 5
Humidity/
Particle
Size
60%
0.4 pm
Not given
Not given
Not given
< 2.0 pm
60%
0.4 pm
60%
0.4 pm
Mode of
Exposure
Inhala-
tion
chamber
Inhala-
tion
chamber
Static?
Inhala-
tion
chamber
Inhala-
tion
chamber
Species/
Strain/
Age/
Weight
Mice,
Murphy
BDFj,
3-6 wk
Albino
mice
Albino
mice
Mice
Mice,
Sprague-
Dawley,
ARS2-
CF1;
3-6 wk
Mice,
Murphy
BDF!,
Duration &
Test Nos . of Frequency Total
Animals Controls of Length
M F H F Exposure of Expt.
44 3 h, once
Not Not 2 h
given given
(however,
a total
of 460
mice was
used in
several
tests)
Not Not 2 h, once
given given
5 7 h, once
£
24 6 h, once
36 6 h, once
. .
--
Effects
No deaths
Elicited period of excitation (5-7 min) ,
deep sleep, lachrymation, acrid, watery
discharge from the nose, increasing
dyspnea, and disturbance of coordination
of movement. Sometimes 1 or 2 animals
died during test.
Antagonistic effect on mortality rate.
Dyspnea, disturbance of coordination,
stress, deep sleep all present. Quick
improvement after exposure. Mortality
only 27-33% up to 3 d after exposure.
No deaths. In lungs, focal hemorrhage
and edema.
5 deaths (21% mortality)
No deaths
Reference
and Rating
Bradof et al. .
(1978b)
B-12
Nevskaya and
Kochetkova (1961)
B-7
Nevskaya and
Kochetkova (1961)
B-7
Treon et al.
(1950)
A-8
Bradof et al .
(1978b)
B-12
Bradof et al.
(1978b)
B-12
3-6 wk
-------
TABLE III-l. MICE—ACUTE TESTS (continued)
Corapound(s)
and Concen-
tration^) in
mg/m3
H2S04 400
Carbon
Particles, 5
H2S04 400
Carbon
Particles, 5
H2S04 400
H2S04 400
H2S04 300
Carbon
Particles, 5
HS04 300
Carbon
Particles, 5
H2S04 300
Carbon
Particles, 5
H2S04 300
Carbon
Particles, 5
Humidity/
Particle
Size
60%
0.4 Mm
60%
0.4 Mm
60%
0.12 Mm
60%
0.12 Mm
60%
0.4 Mm
60%
0.4 Mm
60%
0.4 Mm
60%
0.4 Mm
Mode of
Exposure
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Species/ Duration &
Strain/ Test Nos . of Frequency Total
Age/ Animals Controls of Length
Weight M F M F Exposure of Expt. Effects
Mice, 24 3 h, once 4 deaths (17% mortality)
Sprague-
Dawley,
ARS2-
3-6 'wk
Mice, 36 3 h, once No deaths
Murphy
BDF,,
3-6 wk
Mice 60 3 h, once 1 death
, •
Mice 60 3 h, once No deaths
Mice, 72 6 h, once 7 deaths (10% mortality)
Sprague-
Dawley,
ARS2-
CFlt
3-6 wk
Mice, 48 6 h, once No deaths
Murphy
BDFi,
3-6 wk
Mice, 24 3 h, once No deaths
Sprague-
Dawley,
ARS2-
CFt, .
3-6 wk
Mice, 48 3 h, once No deaths
Murphy
BDFJ,
3-6 wk
Reference
and Rating
Bradof et al.
(1978b)
B-12
' •
Bradof et al.
(1978b)
B-12
Bradof et al.
. (1978b)
B-12
Bradof et al.
(1978b)
B-12
Bradof et al.
(1978b)
B-12
Bradof et al.
(1978b)
B-12
Bradof et al.
(1978b)
B-12
Bradof et al.
(1978b)
B-12
-------
TABLE III-l. MICE--ACUTE TESTS (continued)
Compound(s)
and Concen-
tration(s) in
mg/m3
H2S04
270
H2S04
218
H2S04 200
Carbon
Particles, 5
ro
-P-
H2S04 200
Carbon
Particles, 5
H2S04
191
H2S04
190
Humidity/
Particle
Size
40%
1.7 (Jra
(MMAD)
< 2.0 |jm
60%
0.4 pm
60%
0.4 pm
40%
2 . 7 pm
(MMAD)
<. 2.0 pm
,
Mode of
Exposure
27-in.
exposure
chamber
Inhala-
tion
chamber
Static?
Inhala-
tion
chamber
Inhala-
tion
chamber
Chronic
exposure
chamber
Inhala-
tion
chamber
Static?
Species/
Strain/ Test Nos. of
Age/ Animals Controls
Weight M F M F
CDj 20 20 Not
mice, given
6-7 wk
Mice 5
Mice, 24
Sprague-
Dawley ,
ARS2-
CFj,
3-6 wk
Mice, 25
Sprague-
Dawley,
ARS-
CFt,
3-6 wk
CD-I 28 30
mice,
11-13 wk
Mice 5
Duration &
Frequency Total
of Length
Exposure of Expt. Effects
Groups of No deaths during exposure. One death 2 wk
10 removed after exposure. No significant lesions of
after 1, 2, trachea, larynx, or turbinates resulting
4, and 8 h from exposure. Some lung lesions resulting
from pneumonia, associated with aspiration
of foreign materials.
7 h, once No deaths. Focal hemorrhage and edema
in lungs.
6 h, once No deaths
3 h, once 1 death (4% mortality)
6 h, once There was no change in deep lung clearance
of 137Cs-FAP* following exposure to H2S04
aerosols. No pathologic lesions noted in
tissues and no change in tissue distribution
of 137Cs-FAP following H2S04 aerosol exposure
7 h, once No deaths. Focal hemorrhage and edema in
lungs.
Reference
and Rating
Runkle and Hahn
(1977a)
D-12
Treon et al.
(1950)
A-8 .
Bradof et al.
(1978b)
B-12
Bradof et al.
(1978b)
B-12
Runkle et al.
(1977a)
C-12
Treon et al.
(1950)
A-8
-* Fused aluminosilicate particles (FAP) labeled with 137Cs.
-------
TABLE III-l. MICE—ACUTE TESTS (continued)
Ln
Compound(s)
and Concen-
tration(s) in
mg/m3
H2S04 100
Carbon
Particles, 5
H2S04 100
Carbon
Particles, 5
H2S04 100
H2S04, 100
Carbon
particles, 5
H2S04, 100
followed by
exposure to
Streptococcus
pyogenes for
15 inin
H2S04, 100
Humidity/
Particle
Size
60%
0.4 pro
60%
0.4 pm
.60%
0.12 pm.
60%
0.12 pm
0 . 4 pm
38%
60%
0.12 pm
Mode of
Exposure
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Exposure
chamber
Exposure
chamber
Exposure
chamber
Species/ Duration &
Strain/ Test Nos . of Frequency
Age/ Animals Controls of
Weight M F M F Exposure
Mice, 24 6 h, once
Sprague-
Dawley,
ARS2-
3-6'wk
Mice, 53 3 h, once
Sprague-
Dawley,
ARS2
3-6 'wk
Mice Groups of 3 h, once
45-60
Mice, ? ? 3 h, once
CDj
Charles
River
Labs,
3-4-wk-
old
CDt 20 20 3 h, once
COBS®
Charles
River
mice,
25 g
Mice, ? ? 3 h, once
CD,
Charles
River
Labs ,
3-4-wk-'
Total
Length
of Expt. Effects
No deaths
1 death (2% mortality)
After exposure, mice were challenged with
Streptococcus, Klebsiella pneumoniae, and
influenza virus 0-24 h after acid expos.
No significant increase in mortality except
with influenza exposure at 1-h interval.
One hour after exposure — nasal cavity: dam-
age, mucus, holes, tears, dying cells. No
macrophage. Damage throughout trachea; mat-
ting of cilia, mucus, holes, tears. Lung:
bronchus - slight damage, few dying cells,
alveoli - normal.
No increase in mortality.
One hour after exposure, injury to the top
and middle of the trachea. Lower portion of
the trachea was relatively free of damage,
and the lung was normal. Mucus, surface
holes .
Reference
and Rating
Bradof et al.
(1978b)
B-12
Bradof et al.
(1978b)
B-12
Bradof et al.
(1978b)
B-12
Ketels et al.
(1977)
A- 15
Gardner et al.
(1978)
A-12
Ketels et al. ,
(1977)
A-15
old
-------
TABLE III-l. MICE—ACUTE TESTS (continued)
Compound(s)
and Concen-
tration^) in
mg/m3 ,
H2S04
87
H2S04
27
H2S04, 15
£ H2S04
1.7
H2S04, 1
03, 0.5 ppm
S02, 5.0 ppm
H2S04, 0.9
followed by
03, 0.196
followed by
exposure to
Streptococcus
pyogenes for
15 min
Humidity/
Particle
Size
< 2.0 M"i
40%
1 .6 Mm
(MMAD)
70%
3.2 Mm
(CMD)
40%
1.0 Mm
(MMAD)
40 ± 5%
31 ± 1°C
0.5 Mm
MMAD
38 ± 16%
SD
0.23 Mm ±
2.4 SD
(volume
median
diameter)
Mode of
Exposure
Inhala-
tion
chamber
. Static?
Chronic
exposure
chamber
Exposure
Chamber
Chronic
exposure
chamber
Exposure
chamber
Exposure
chamber
Species/ Duration &
Strain/ Test Nos . of Frequency Total
Age/ Animals Controls of Length
Weight H F M F Exposure of Expt.
Mice 5 2.75 h,
once
CDt 40 26 6 h, once
mice,
11-13 wk
Mice 4 h
Swiss-
Webster
7-9 wks
25-29 g
CDj 24 24 6 h, once
mice,
' 11-13 wk
Swiss 20 20 2 h, once § 4 d
pathogen
free
mice,
adult
(~ 90 d) .
CDj Eleven 220? 2 h, once 15 d
COBS®, groups 3 h, once
Charles of 20 (03)
River
mice,
25 g
Effects
No deaths. Focal hemorrhage and edema
of lungs.
No change in deep lung clearance, no patho-
logic lesions noted in tissues, and no
change in tissue distribution of 137Cs-FAP*
following H2S04- aerosol exposure.
After exposure to nonviable radio-
labelled streptococcal aerosol;
reduced the rate of ciliary clearance
of bacteria from lungs and nose.
No change in deep lung clearance, no patho-
logic lesions noted in tissues, and no
change in tissue distribution of l37Cs-FAP*
following H2S04 aerosol exposure.
Ten mice from each group were killed at
day 1 postexposure and the rest at day 4.
No histological differences in lung tissues
of the 4 subgroups. No increase in numbers
of alveolar macrophages in alveolar tissues
adjacent to terminal bronchioles, indicating
no cell damage from inhaled toxicant.
No significant increase in mortality over
that of control group.
Reference
and Rating
Treon et al.
(1950)
A-8
Runkle et al.
(1977b)
C-12
Fairchild et al
(1975a)
C-12
Runkle et al.
(1977b)
C-12
Kleinman et al.
(1979) (1981)
A-14
Gardner et al.
(1977) (1978)
C-9 A-12
Fused aluminosilicate particles (FAP) labeled with 137Cs.
-------
TABLE III-l. (concluded)
Compound (s)
and Concen-
tration^) in
mg/m3
H2S04, 0.9
(~ 0.3 mg/m3
of sulfate
associated
with NH4 )
03, 0.196
followed by
H2S04, 0.9
followed by
exposure to
Streptococcus
pyogenes for
15 min
H2S04, 0.500
03) 0.1 ppm
simultaneously
H2S04, 0.500
Humidity/
Particle Mode of
Size Exposure
38 Exposure
± 16% SD Chamber
0.23 |Jm ±
2.4 SD
(geometric)
(VMD)
38% Exposure
0.23 pm ± chamber
2.4 SD
(VMD)
38% Exposure
0.23 Mm chamber
(VMD)
38% Exposure
0.23 pm chamber
(VMD)
Species/
Strain/
Age/
Weight
Mice
CDi
COBS®
25 g
CDt
COBS®,
Charles
River
mice,
25 g
CDt
COBS®,
Charles
River
mice,
25 g
CDj
COBS®,
Charles
River
mice,
25 g
Duration &
Test Nos. of Frequency Total
Animals Controls of . Length
M F M F Exposure of Expt.
Nineteen 380? 2 h, 15 d
groups once
of 20 (Filtered
air of sub-
sequent dur-
ation added
to maintain
total test
time of 5 h)
Ten groups 200? 3-h, once 15 d
of 20 (03)
2 h, once
Not Not 3 h, simul-
given given taneously
Not Not 3 h
given given
Effects
No significant increase in mortality
to a subsequent infection with Strep-
tococcus pyogenes .
.
Significant increase in respiratory infec-
tions (% mortality) when 03 preceded H2S04
where observed mortality equaled additive
effect of individual pollutants. When 03
was used alone, there was no significant
mortality increase after a subsequent in-
fection with S. pyogenes .
Significant increase in mortality rate
(7.5%).
>
No mortality.
Reference
and Rating
Gardner et al.
(1977) (1978)
C-9 A-12
Gardner et al.
(1977) (1978)
C-9 A-12
Gardner et al.
(1978)
A-12
Gardner et al.
(1978)
A-12
-------
TABLE II1-2. MICE-REPEATED DOSE EXPERIMENTAL EXPOSURE TO H2S04
Compound (s)
and Concen-
tration^) in
mg/m3
H2S04
1,160
H2S04
839
H2S04
670
a H2SO
00 383
H2S04
203
H2S04, 200
Carbon
Particles, 5
H2S04, 200
Carbon
Particles, 5
H2S04, 200
Carbon
Particles, 5
Humidity/
Particle Mode of
Size Exposure
< 2.0 pm inhala-
tion
chamber
• Static?
< 2.0 pm _ Inhala-
tion
chamber
Static?
< 2.0 pm Inhala-
tion
chamber
< 2.0 pm Irihala-'
tion
chamber
Static?
< 2.0 pm Inhala-
tion
chamber
60% Inhala-
0.4 pm tion
chamber
60% Inhala-
0.4 pm tion
chamber
60% Inhala-
0.4 pm tion
chamber
Species/ Duration &
Strain/ Test Nos. of Frequency Total
Age/ Animals Controls of Length
Weight M F M F Exposure of Expt.
Mice 5 7 h/d 4 d
Mice 5 7 h 3d
Mice 5 7 h/d 2 d
Mice 5 7 h/d 5 d
Mice 5 7 h/d 5 d
Mice Groups of 3 h/d 5 d
90-108
Mice Groups Groups 3 h/d 5 d
of 79- of 80-
274 274
Mice, 192 3 h/d 5 d
Sprague-
Dawley,
ARS2-
CF1(
7 wk
Effects
All animals died during first 2 d. Exten-
sive focal hemorrhage, edema, degenerative
changes in surface of larynx and trachea,
and respiratory congestion.
Three animals died. Focal hemorrhage and
edema in lungs .
All animals died. Focal hemorrhage and
edema in lungs .
Four animals died. In lungs, focal
hemorrhage and edema.
No deaths. In lungs, focal hemorrhage and
edema. Respiratory irritation after 3 d
indicated by animals.
Animals exposed to influenza virus <1 h
before or after acid-carbon expos. Signi-
ficant increase in mortality under both
conditions .
Animals challenged with Strepococcus
immediately before and after exposure
to acid-carbon. Significant increase
in mortality in both cases, greatest
increase in Streptococcus expos, first.
No deaths during first 3 expos, with 192
animals. 2 deaths out of 96 animals on
4th expos, and by then, animals lost avg.
20% body wt. By 5th expos., macrophages
were found in nasal cavity, very heavy
mucous coating in trachea and damaged alveoli
Reference
and Rating
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8
Bradof et al.
(1978b)
B-12
Bradof et al.
(1978b)
B-12
Bradof et al.
(1978b)
B-12
-------
TABLE III-2. MICE--REP. DOSE (continued)
Compound (s)
and Concen-
tration(s) in
mg/ra3
H2S04, 200
Carbon
Particle's, 5
H2S04( 200
Carbon
Particles, 5
H2S04, 200
Carbon
Particles, 5
H2S04, 200
Carbon
Particles, 5
H2S04
170
H2S04
154
Humidity/
Particle
Size
60%
0.4 Mm
60%
0.4 Mm
60%
0.4 pm
60%
0.12 Mm
0.4 Mm
Up to 60%
0.62 Mm
(MMAD)
0.62 Mm
(MMAD)
4.2 m3
Mode of
Exposure
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Exposure
chamber
Exposure
chamber
4.2 m3
Exposure
chamber
Species/
Strain/
Age/
Weight
Mice,
Murphy
BDF!,
6 wk
Mice,
Sprague-
Dawley,
ARS2-
CFj,
9 wk
Mice,
Murphy
BDF1(
9 wk
Mice,
CD1
•Charles
River
Labs,
3-4-wk-
old
Swiss-
Webster
mice
60 ±
3.5 d
Mice
Swiss-
Webster
60 d
Duration &
Test Nos. of Frequency Total
Animals Controls of Length
M F M F Exposure of Expt. Effects
96 3 h/d 5 d No deaths (only 48 animals used in 4th and
5th expos.) By 5th exposure, macrophages were
found in nasal cavity, very heavy mucous
coating in trachea, and damaged alveoli.
152 3 h/d 5 d One death after 1st expos., 11 after second
expos. 4 deaths after 3rd expos, (using
only 95 animals) 2 after 4th and 5 more
deaths after 5th expos. By 5th, animals
had lost 25% of avg. body wt.; and macro-
phages were found in nasal cavity, very
heavy mucous coating in trachea, and
damaged aveoli
48 3 h/d 5 d After 5th expos., two deaths and macro-
phages found in nasal cavity, very heavy
mucous coating in trachea, and damaged
alveoli.
? ? 3 h/d 5 d One hour after exposure, nasal cavity:
(Not (Not heavy damage, mucous, holes, tears, dying
given) given) "~ cells; many macrophages. Trachea: heavy
mucus making damage estimate impossible;
few cells where visible are normal. Lung:
bronchus - dying cells, holes, tears, micro-
villi missing. Lung: alveoli - thickened
alveolar walls; many emphysema-like areas.
Two weeks after exposure, nasal cavity: no
change. Trachea: no change. Lung:
bronchus - no change (possible repair).
Lung: alveoli - no change.
8 8 Continuous 10 d Lesions of larynx and trachea. Surface
epithelium ulcerated after 7 d; focal
necrotizing laryngitis observed. Lesions
characterized by ulceration, accumulation
of cellular debris, and inflammatory cell
infiltrates.
175 Continuous? 10 d 36 animals died within 2 d, 29 in the
next 3 d, and 15 during d 6-10. No
significant changes in urine or blood
except trend of a neutropenia and
lymphophilia. Interferon production
reduced.
Reference
and Rating
Bradof et al.
(1978b)
B-12
Bradof et al.
(1978b)
B-12
Bradof et al.
(1978b)
B-12
Ketels et al.
(1977)
A-15
Schwartz et al.
(1977)
A-17
Schwartz et al.
(1979)
C-12
-------
TABLE III-2. MICE--REP. DOSE (continued)
U)
o
Compound (s)
and Concen-
tration(s) in
mg/ra3
H2S04
141
H2S04
140
H2S04
125
H2S04, 100
Carbon
Particles, 5
H2S04, 100
Carbon
Particles, 5
H2S04, 100
Carbon
Particles, 5
H2S04, 100
Carbon
Particles, 5
Humidity/
Particle
Size
0.42 Mm
(MMAD)
Up to 60%
0.32 |Jm
(MMAD)
0.32 pm
(MMAD)
60%
0.4 urn
60%
0.4 (Jm
60%
0.4 pm
60%
0.4 |jm
Mode of
Exposure
Exposure
chamber
4.2 m3
Exposure
chamber
4.2 m3
Exposure
chamber
4.2 m3
Inhala-
tion
chamber
. Inhala-
tion
chamber
Inhala-
tion
chamber
•Inhala-
tion
chamber
_
Species/ Duration &
Strain/ Test Nos. of Frequency Total
Age/ Animals Controls of Length
Weight M F M F Exposure of Expt.
Mice 114 Continuous? 14 d
Swiss-
Webster
60 d
Swiss- 45 45 Continuous 14 d
Webster
mice
60 ±
3.5 d
Mice 80 Continuous? 14 d
Swiss-
Webster
60 d
Mice Groups of ' 3 h/d 5 d
40-168
Mice Groups of 3 h/d 10 wk
48-80 5 d/wk
Mice Groups Groups 3 h/d . 5 d
of 58- of 58-
60 60
Mice, 138 3 h/d 5 d
Sprague-
Dawley,
ARS2-
CF1F
9 wk
Effects
One animal died on d 3, 2 on d 5 , and
10 during d 7-14. No significant changes
in urine or blood except trend of a neutra-
penia and lymphophilia. Interferon pro-
duction reduced.
Lesions of larynx and upper trachea.
Surface epithelium ulcerated. After 7 d,
focal necrotizing laryngitis was observed.
Lesions characterized by ulceration, accumu-
lation of cellular debris, and inflammatory
cell infiltrates.
Eight animals died on d 2, 9 in the next
3 d, 8 on d 6, and 5 during d 9-12. No
significant changes in urine or blood ex-
cept trend of a neutropenia and lymphophilia.
Interferon production reduced.
Animals exposed to influenza virus at <1 to
72 h before or after expos, to acid-carbon.
No significant change except at the 24^h in-
terval. Lower mortality with acid-carbon
expos, first and higher mortality with virus
expos . first.
Animals challenged with Streptococcus imme-
diately before and after expos, to acid-
carbon. Increased mortality significant in
animals exposed to Streptococcus first.
No significant difference in mortality in
animals challenged with Streptococcus imme-
diately before or after exposure to acid-
carbon.
Two deaths after 5th expos. After 1st
expos., damage to cells in nasal cavity,
trachea, bronchus, and lungs normal.
After 3rd expos., macrophages found in nasal
cavity.
Reference
and Rating
Schwartz et al.
(1979)
C-12
Schwartz
et al. (1977)
A-17
Schwartz et al.
(1979)
C-12
Bradof et al.
(1978b)
Bradof et al.
(1978b)
B-12
Bradof et al.
(1978b)
B-12
Bradof et al.
(1978b)
B-12
-------
TABLE II1-2. MICE--REP. DOSE (continued)
Compound (s)
and Concen-
tration(s) in
mg/ra3
H2S04, 100
Carbon
Particles, 5
H2S04, 100
Carbon
Particles, 5
H2S04, 100
Carbon
Particles, 5
H2S04, 100
Carbon
Particles, 5
H2S04, 100
Carbon
Particles, 5
H2S04 50
Humidity/
Particle
Size
60%
0.4 |Jm
60%
0.4 Mm
60%
0.4 Mm
60%
0.12 Mm
0.4 Mm
60%
0.12 Mm
0.4 Mm
60%
0.4 MOI
Mode of
Exposure
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Exposure
chamber
Exposure
chamber
Inhala-
tion
chamber
Species/ Duration &
Strain/ Test Kos. of Frequency
Age/ Animals Controls of
Weight M .F M F Exposure
Mice, 358 3 h/d
Sprague-
Dawley,
ARS2-
CFi,
7 wk
Mice, 48 3 h/d
Murphy
BDFj,
6 wk
Mice, 48 3 h/d
Murphy
BDFt,-
9 wk
Mice, ? ? 3 h/d
CDt
Charles
River
Labs ,.
3-4-wk-
old
Mice, ? ? 3 h/d
CD,
Charles
River
Labs,
3-4-wk-
old
Mice Groups Groups 3 h/d
of 58 & of 58 & 5 d/wk
59 59
Total
Length
of Expt. Effects
5 d One expos. -1 death and damage to cells in
nasal cavity, trachea, bronchus, and lungs
normal. 3 expos. -1 more death and same con-
ditions. 4 expos. -2 deaths. 5 expos. -6 more
deaths, animals lost 16% avg. body wt. ; condi-
tions of tissues same.
5 d One death after 4th expos. After 1st expos.
damage to cells in nasal cavity, trachea,
bronchus, and lungs normal. After 3rd expos.
macrophages found in nasal cavity.
5 d No deaths. After 1st expos., damage to
cells in nasal cavity, trachea, bronchus,
and lungs normal.^ After 3rd expos., macro-
phages found in nasal cavity.
3 or 5 d One hour after exposure; nasal cavity: dam-
age, mucus, holes, tears, dying cells; some
macrophages. Trachea: damage throughout
trachea; matting of cilia, mucus, holes,
tears. Lung: bronchus - slight damage;
some tears. Lung: alveoli - normal. Two
weeks after exposure; nasal cavity: damage
still visible, no macrophages; most damage in
squamous cells. Trachea: some signs of
healing. Lung: bronchus and alveoli -
normal.
10 d One hour after exposure, nasal cavity: dam-
age, mucus, holes, tears, dying cells; some
macrophage. Trachea: damage throughout
trachea; matting of cilia, mucus, holes,
tears. Lung: bronchus - slight damage, some
tears. Lung: alveoli - normal. Two weeks
after exposure, nasal cavity: no change.
Trachea: no change. Lung: bronchus and
alveoli - normal.
4 wk Animals challenged with influenza virus
<1 and 24 h after acid-carbon expos.
Significant increase in mortality, pul-
Reference
and Rating
Bradof et al.
(1978b)
B-12
Bradof et al.
(1978b)
B-12
i
Bradof et al.
(1978b)
B-12
Ketels et al.
(1977)
A-15
;
Ketels et al.
(1977)
A-15
Bradof et al.
(1978)
B-12
monary consolidation, and decrease in mean
survival time at 1-h interval.
-------
TABLE III-2. MICE--RF.P. DOSE (concluded)
u>
Compound (s)
and Concen-
tration(s) in
mg/m3
H2S04, 50
Carbon
Particles, 5
H2S04> 15
H2S04( 1.5
H2S04, 1.4
Carbon
particles,
1.5
H2S04, 1.4±0.4
Carbon
Particles,
1.5±0.4
H2S04, 1.4+0.4
Carbon
Particles,
1.5+0.4
Humidity/
Particle
Size
60%
0.12 prn
0.4 pm
70%
3.2 Mm
(CUD)
70%
0.6 pro
(CMD)
0.4 |Jm
60%
0.4 pm
60%
0.4 |um
Species/
Strain/
Mode of Age/
Exposure Weight
Exposure Mice,
chamber CDj
Charles
River
Labs,
3-4-wk-
old
Exposure Mice
Chamber Swiss-
Webster
7-9 wks
25-29 g
Exposure Mice
Chamber Swiss -
Webster
7-9 wks
25-29 g
CDt
mice,
4-wk-
old
Inhala- Mice,
tion Charles
chamber River,
CD1(
4-5 wk
Inhala- Mice,
tion Charles
chamber River,
CDj,
4-5 wk
Duration &
Test Nos. of Frequency
Animals Controls of
M F M F Exposure
? ? 3 h/d
1.5 h
daily
1.5 h
daily
? ? 3 h/d,
5 d/wk
24 24 3 h/d
5 d/wk
24 24 3 h/d
5 d/wk
Total
Length
of Expt. Effects
20 d One hour after exposure, nasal cavity:
slight damage; mucus, holes, tears, dying
cells; no macrophages. Trachea: heavy
mucus making damage estimate impossible;
few cells where visible are normal. Lung:
bronchus and alveoli - normal. Two weeks
after exposure nasal cavity: no change.
Trachea: no change. Lung: bronchus and
alveoli - normal.
4 d Exposure 4 d prior to bacterial
aerosol. Clearance of nonviable
bacteria reduced in nose but not
in lungs.
4 d No significant effects. Exposure to
bacterial aerosol following H2S04
exposure.
j
1, 4, 12, Concentration of serum IgM was elevated
or 20 wk after 1 wk but significantly depressed
throughout 20 wk. Typical of other stress
exposures (abstract).
12 wk Lower avg. body wt. Damage to cells in nasal
cavity and trachea. Bronchial cells normal
but areas of fused alveoli. No significant
changes in hematological parameters except
serum levels of IgG2a and IgM remained de-
pressed. Significantly increased mortality
and pulmonary consolidation in animals chal-
lenged with influenza virus after 12 wk expos
4 wk Lower rate of growth. No changes in epithe-
lium of respiratory tract evident. No sig-
nificant changes in hematological parameters
except that serum levels of IgGj, IgG2a>
and IgM were depressed significantly. No
increased mortality in animals challenged
with influenza virus after 4 wk expos.
Reference
and Rating
Ketels et al.
(1977)
A-15
Fairchild et al.
(1975a)
C-12
Fairchild et al.
(1975a)
C-12
Bradof et al.
(1978a)
B-7
Bradof et al.
(1978)
B-12
Fenters et al.
(1979)
C-17
Bradof et al.
(1978)
B-12
Fenters et al.
(1979)
C-17
-------
TABLE III-3. MICE—CHRONIC EXPERIMENTAL EXPOSURE TO H2S04
Compound (s)
and Concen- Humidity/
tration(s) in Particle
mg/m3 Size
H2S04, 1.4 ± 60%
0.4 0.4 (Jm
Carbon
Particles ,
1.5 ± 0.4
Species/
Strain/
Mode of Age/
Exposure Weight
Inhala- Mice,
tion Charles
Chambers River,
CDj,
4-5 wk
Duration &
Test Nos. of Frequency Total
Animals Controls of Length
M F M F Exposure of Expt.
3 h/d 20 wk
24 24 5 d/wk
Reference
Effects and Rating
Slightly lower avg. body wt. Damage Bradof et al.
to respiratory tract similar but to a (1978b)
lesser degree than at 12 wk. No signi- B-12
ficant changes in hematological para-
meters except serum levels of IgM con-
tinued to be depressed, IgA was de-
pressed, too; and IgGjb was signifi-
cantly increased. Reduction in anti-
body response of spleen cells. In-
creased mortality, markedly decreased
mean survival time, and increased pul-
monary consolidation in animals challenged
with influenza virus after 20 wk expos.
-------
TABLE III-4. HAMSTERS--ACUTE EXPERIMENTAL EXPOSURE TO H2S04
Compound(s)
and Concen-
tration(s) in
mg/m3
H2S04, 700
Carbon
Particles, 5
H2S04, 700
.H2S04, 600
H2S04, 500
Carbon
Particles, 5
H2S04, 500
H2S04, 400
Carbon
Particles, 5
H2S04, 400
Carbon
Particles, 5
Humidity/
Particle
Size
60%
0.4 pm
60%
0.12 pm
60%
0.12 pm
60%
0.4 pm
60%
0.12 pm
60%
0.4 pm
60%
0.4 pm
Mode of
Exposure
Inhala-
tion
chamber
Inhala^
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Species/ Duration &
Strain/ Test Nos . of Frequency Total
Age/ Animals Controls of Length
Weight M F M F Exposure of Expt.
Hamsters, 12 3 h, once
Sprague-
Dawley,
Syrian
golden
12-14 wk
Hams'ters, 24 25 3 h, once
Sprague-
Dawley,
Syrian
golden
12-14 wk
Hamsters 36 3 h, once
v
Hamsters, 12 3 h, once
Sprague-
Dawley
Syrian
golden
12-14 wk f
Hamsters, 11 25 3 h, once
Sprague-
Dawley,
Syrian
golden
12-14 wk
Hamsters, 12 6 h, once
Sprague-
Dawley,
Syrian
golden
12-14 wk
Hamsters, 12 : 3 h, once
Sprague-
Dawley,
Syrian
golden
12-14 wk
Reference
Effects and Rating
No deaths. . Bradof et
(1978b)
B-12
Animals infected with influenza virus 72 h Bradof et
before acid expos. Significant increase in (1978b)
mortality over controls (46% vs. 12%) and B-12
reduced mean survival time.
One death (3% mortality). Bradof et
(1978b)
B-12
No deaths. Bradof et
(1978b)
B-12
Animals infected. with influenza virus 72 h Bradof et
before acid expos. Mortality 27% vs. 12% (1978b)
for control. Mean survival time also re- B-12
duced.
One death (2% mortality). Bradof et
(1978b)
B-12
•
No deaths. Bradof et
(1978b)
B-12
al.
al.
al.
al.
al.
al.
al.
-------
TABLE III-4. HAM—ACUTE TESTS (continued)
Compound (s)
and Concen-
tration(s) in
rag/m3
H2S04, 400
H2S04, 300
Carbon
Particles, 5
H2S04, 300
Carbon
Particles, 5
OJ
Ln
HZS04, 300
Carbon
Particles, 5
H2S04, 300
Carbon
Particles, 5
H2S04> 200
Carbon
Particles, 5
H2S04, 200
Carbon
Particles, 5
Humidity/
Particle
Size
60%
0.12 urn
60%
0.4 |jm
60%
0.4 pm
60%
0.4 (Jm
60%
0.4 pm
60%
0.4 pm
60%
0.4 pm
Mode of
Exposure
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Species/ Duration &
Strain/ Test Nos. of Frequency
Age/ Animals Controls of
Weight M ' F M F Exposure
Hamsters 24 3 h, once
Hamsters, Groups 44 6 h, once
Sprague- of 44
Dawley,
Syrian
golden
12-14 wk
Hamsters, Groups 40 6 h, once
Sprague- of 36-
Dawley, 42
Syrian
golden
12-14 wk
Hamsters, 12 6 h, once
Sprague-
Dawley,
Syrian
golden
12-14 wk
Hamsters, 12 3 h, once
Sprague-
Dawley,
Syrian
golden
12-14 wk
Hamsters, 12 6 h, once
Sprague-
Dawley,
Syrian
golden
12-14 wk
Hamsters, 12 3 h, once
Sprague-,
Dawley, (
Syrian
golden
12-14 wk
Total
Length Reference
of Expt. . Effects and Rating
No deaths. Bradof et
(1978b)
B-12
Animals infected with influenza virus and Bradof et
then exposed to acid and carbon at inter- (1978b)
vals of <1 to 72 h after infection. Signi- B-12
ficant increase in mortality at 24- and 48-h
intervals.
After expos., animals were challenged with Bradof et
influenza virus at < 1- to 72-h intervals (1978b)
after acid expos. No significant change in - B-12
mortality over control.
No deaths. Bradof et
(1978b)
B-12
No deaths. Bradof et
(1978b)
B-12
No deaths. Bradof et
(1978b)
B-12
No deaths. Bradof et
(1978b)
B-12
al.
al.
al.
al.
al.
al.
al.
-------
TABLE III-4. HAM--ACUTE TESTS (continued)
•
Compound (s)
and Concen- Humidity/
tration(s) in Particle
mg/m3 Size
H2S04, 100 60%
Carbon 0.4 (jm
Particles, 5
H2S04, 100 60%
Carbon 0.4 pm
Particles, 5
H2S04-coated 60%
carbon aero- 0.4 pm
sol
1.1 ± 0.3
1.5 ± 0.4
H2S04-coated 60%
Carbon aero- 0.4 |jm
sol
1.1 ± 0.3
1.5 ± 0.4
H2S04 60%
1.1 ± 0.3 0.12 pm
Mode of
Exposure
Inhala-
tion
chamber
Inhala-
tion
chamber
Exposure
chambers
in vivo-
in vitro
Exposure
chambers
in vivo
Exposure
chambers
in vivo-
in vitro
Species/
Strain/
Age/
Weight
Hamsters ,
Sprague-
Dawley,
Syrian
golden
12-14 wk
Hamsters ,
Sprague-
Dawley ,
Syrian
golden
12-14 wk
4-wk-old
CrRGH(SYR)
Syrian
golden
hamsters
4-wk-old
CrRGH(SYR)
Syrian
golden
hamsters
Test Nos. of
Animals Controls
M F M F
12
24
9 3
(All
killed
immediately
after
exposure)
12 12
(3 killed
at each
interval
after ex-
posure)
9 3
(all
killed
immediately
after
exposure)
Duration &
Frequency Total
of Length
Exposure of Expt. Effects
6 h, once No deaths.
3 h, once No deaths.
3 h, once Trachea ring cultures prepared immediately
following exposure. Ciliary beat frequency
significantly reduced immediately after ex-
posure but returned to that of the controls
by 24 h. Epithelial surface alterations
similar to those seen in hamsters exposed
and maintained in vivo. Severe loss of
ciliated cells immediately following ex-
posure.
3 h, once Animals maintained until time to observe
tracheal rings. Observed at < 1-, 24-, 48-,
and 72-h intervals. Significant decline in
cilia beat frequency, recovered within 24 h.
Immediately after exposure, tracheal epi-
thelium showed significantly greater cyto-
logical alteration than when exposed to air,
carbon, or H2S04 alone. Tracheal epithe-
lium still showed significant damage at
72 h. Loss of ciliated cells.
3 h, once Ciliary beat frequency significantly re-
duced immediately after exposure and was
still significantly lower than controls
at 24 h. Significant recovery occurred
by 48 h. Epithelial surface alterations
similar to those seen in hamsters exposed
and maintained in vivo. Loss of ciliated
cells immediately following exposure.
Reference
and Rating
Bradof et al .
(1978b)
B-12
Bradof et al.
(1978b)
B-12
Schiff et
al. (1979)
C-10
Schiff et
al. (1979)
C-10
Schiff et
al. (1979)
C-10
-------
TABLE III-4. HAM—ACUTE TESTS (continued)
OJ
Compound (s)
and Concen- Humidity/
tration(s) in Particle
mg/m3 Size
H2S04, 1.1 60%
0.12 pm
03, 0.196 48 + 11%
then SD
H2S04, 1.090 0.30 VMD
Mode of
Exposure
Exposure
cages
in vivo
Indi-
vidually
housed in
stainless
steel
cages dur-
ing ex-
posure
Species/
Strain/
Age/
Weight
4-wk-old
CrRGH(SYR)
Syrian
golden
hamsters
Syrian
hamsters/
60-70 d/
90-110 g
Test
Animals
M F
12
Duration &
Nos. of Frequency
Controls of
M F Exposure
12 3 h, once
Total
Length
of Expt.
(3 killed
at each
interval)
15 with
no re-
covery
period;
9 with
72-h re-
covery
period
15; al- 3 h 03
lowed 2 h H2S04
no re-
covery
period*
5 h in
vivo; 0
or~~72-h
for main-
tenance
of tra-
cheal
ring cul-
ture
Effects
Exposed in vivo, animals maintained up to
72 h, when tracheal explants were prepared.
Observed at < 1-, 24-, 48-, and 72-h inter-
vals. Damage to ciliated epithelium less
severe than that seen in the hamsters exposed
to H2S04 + C. Mean ciliary beating frequency^
significantly lower than that of controls up
to 24 h after exposure. At 48 and 72 h, the
means were significantly lower than those of
the control, carbon alone, or H2S04 -C groups,
Recovery by 72 h. Loss of ciliated cells.
Statistically significant reduction
(P < 0.05 using Dunnett's test) in ciliary
activity immediately after exposure, but the
magnitude of the reduction was significantly
less (P < 0.05) than that in either test with
exposure to H2S04 alone. (Exposure to 0.196
Reference
and Rating
Schiff et
al. (1979)
C-10
Grose et al.
(1980)
C-8
mg 03/m3 alone did not reduce ciliary beat fre-
quency significantly.)
H2S04, 0.9
03, 0.196
H2S04, 0.9
following ex-
posure to 03
0.196 for
3 h
Syrian
hamsters
Syrian
hamsters
Not
given
Not
given
Not
given
Not
given
3 h, once
2 or 3 h,
once
Since when animals were exposed to 0.840 mg
H2S04/m3 for 2 h and allowed no recovery, the
reduction with no recovery period was 28.2%
compared to this test where the reduction
with no recovery period was 12.8% (calculated
by MRI), it appears that the hypothesis of no
antagonism between 03 and H2S04 can be re-
jected at the P < 0.05 probability level. The
fact that other workers have noted a syner-
gistic effect between 03 and H2S04 might be ex-
plained by differences in model systems, animal
species used, subsequent response of target
cells, and/or disparity in exposure regimens.
No significant difference in ciliary activ- Grose et al.
ity of exposed and unexposed animals ob- (1978)
served in tracheal ring cultures. B-6
Significant decrease in ciliary activity in
tracheal ring cultures.
Grose et al.
(1978)
B-6
-------
TABLE III-4. HAM—ACUTE TESTS (concluded)
CD
Compound (s)
and Concen-
tration(s) in
mg/m3
H2S04> 0.9
H2S04, 0880
H2S04, 0.840
Humidity/
Particle Mode of
Size Exposure
48 + 11% Indi-
SD vidually
0.27 \im housed
volume in stain-
median less
diameter steel
cages dur-
ing ex-
posure
48 + 11% Indi-
SD vidually
0.24 pro housed
VMD in stain-
less
steel
cages
during
exposure
Species/
Strain/
Age/
Weight
Syrian
hamsters
Syrian
golden
hamsters/
60-70 d/
90-110 g
Syrian
golden
hamsters/
60-70 d/
90-110 g
Test
Animals
M F
Not
given
10
per tra-
cheal
main-
tenance
duration
of 0,
24, 48,
and 72 h
15,
15,
15,
and
14 for
recov-
ery pe-
riods
0, 24,
48, and
72 h, re-
Duration &
Nos. of Frequency
Controls of
M F Exposure
Not 2 h, once
given
Controls 2 h
were ex-
posed to
filtered
air for
2 h. 10 M
at 0 and
72 h tra-
cheal
main-
tenance
duration;
9 M at
48 h, and
7 M at
72 h.*
17* 2 h
spectively
Total
Length
of Expt.
2 h
in vivo
exposure;
72 h for
tracheal
ring cul-
ture in
vitro
main-
tenance
The live
animals
breathed
clean air
for 0,
24, 48,
or 72 h
before
deter-
mination
of cili-
ary beat-
ing fre-
quency.
Tracheal
ring cul-
Effects
Significant decrease in ciliary activity
in tracheal ring cultures from controls
even after 48 h in vitro or in vivo
maintenance.
Ciliary beating frequency was initially re-
duced 29.5% from the control ciliary activ-
ity. After maintenance for 24 h, the fre-
quency was reduced -' 25%; for 48 h, ~ 26%;
and for 72 h, ~ 21%. The control and treat-
ment means were simultaneously significantly
different from each other at all time periods
(P < 0.01)
With no recovery period, the immediate cili-
ary beating frequency was 28.2% less than
that of the controls. There were also sig-
nificant (P < 0.05 using Dunnett's test) re-
ductions in ciliary beating frequency of the
Reference
and Rating
Grose et
al. (1978)
B-6
Grose et al.
(1980)
C-8
Grose et al.
(1980)
C-8
exposed hamsters at 24 and 48 h. After a 72-h
recovery period, the ciliary activity had ap-
proached the normal range.
tures were
maintained
in vitro
for 72 h
* Because of in vivo exposure, pretreatment beating frequency of the cilia could not be determined. Analysis of variance showed no interaction
between treatments and replications. Thus, treatment effects examined could be based upon pooled data.
-------
TABLE III-5. RATS--ACUTE EXPERIMENTAL EXPOSURE TO H2S04
Ul
Compound (s)
and Concen- Humidity/
tration(s) in Particle
mg/m3 Size
H2S04 < 0.2 |Jm
1,610
H2S04 < 2.0 pm
1,470
H2S04 1.2 (J"
1,090 (MMAD)
H2S04 1.1 pm
1,080 (MMAD)
H2S04 1.2 pm
800 (MMAD)
H2S04, 400- Not given
800
03, 20-50
Mode of
Exposure
Inhala-
tion
chamber
Static?*
Inhala-
tion
chamber
Static?
Exposure
chamber
Exposure
chamber
Exposure
chamber
Species/
Strain/
Age/
Weight
Rats
Rats
Fischer-
344 rats
Fischer-
344 rats
Fischer-
344 rats
Albino
rats
Duration &
Test Nos. of Frequency Total
Animals Controls of Length
M F M F Exposure of Expt.
2 7 h, once
2 3.5 h, once
16 16 Not Random
given groups of
8 removed
at 1, 2,
4, and 8 h
16 16 Not Random
given groups of
8 removed
at 1, 2,
4, and 8 h
16 16 Not Random
given groups of
8 removed
at 1, 2,
4, and 8 h
Not Not 2 h, once
given given
(however,
a total
of 190
rats was
used in
several
tests)
Effects
Both animals died. Lung edema, hyperemia,
and degeneration of surface cells.
Both animals died. Hyperemia, edema, and
degeneration of surface cells in lungs.
Nine deaths 3-21 d after exposure. Lesions
including fibrosis of larynx and broncho-
pneumonia associated with aspiration of
foreign materials.
One death during exposure; 14 deaths up to
2 wk after exposure. Lesions including fi-
brosis of larynx and bronchopneumonia asso-
ciated with aspiration of foreign materials.
Eight deaths during exposure; 10 deaths up
to 2 wk after exposure. Lesions including
fibrosis of larynx and bronchopneumonia as-
sociated with aspiration of foreign materials
Synergistic or additive effects on mor-
tality rate. Dyspnea, disturbance of
coordination, stress, deep sleep all pres-
ent. Worsened condition even 24 h after
exposure. Mortality 50-100% up to 3 d
after exposure.
Reference
and Rating
Treon et al
(1950)
A-8
Treon et al
(1950)
A-8
Runkle and
(1977a)
D-12
Runkle and
(1977a)
D-12
Runkle and
(1977a)
D-12
Hahn
Hahn
Hahn
Nevskaya and
Kochetkova
B-7
(1961)
Static as opposed to dynamic air flow conditions.
-------
TABLE III-5. RATS—ACUTE TESTS (continued)
•
Compound (s)
and Concen-
tration(s) in
mg/m3
H2S04, 400-
800
H2S04
730
H2S04
718
H2S04
699
H2S04
549
H2S04
470
H2S04
461
Humidity/
Particle Mode of
Size Exposure
Hot given
1.3 pm Exposure
(MMAD) chamber
< 2.0 |Jm Inhala-
tion
chamber
Static?
< 2.0 pm Inhala-
tion
chamber
Static?
< 2.0 |jm Inhala-
tion
chamber
Static?
1.3 pm Exposure
(MMAD) chamber
< 2.0 pm Inhala-
tion
chamber
Species/
Strain/ Test Nos . of
Age/ Animals Controls
Weight M F M F
Albino Not Not
rats given given
Fischer- 16 16 Not
344 rats given
Rats 2
Rats 2
Rats 2
Fischer- 16 16 Not
344 rats given
Rats 2
Duration &
Frequency Total
of Length
Exposure of Expt.
2 h
Random
groups of
8 removed
at 1, 2,
4, and 8 h
3.5 h, once
7 h, once
3.5 h, once
Random
groups of
8 removed
at 1, 2,
4, and 8 h
7 h, once
Effects
«
Period of excitation (5-7 min) , deep sleep,
lachrymation, acrid, watery discharge from
nose, increasing dyspnea, and disturbance
of coordination of movement. After ex-
posure, animals were sluggish, inactive,
drank poorly, and the hair became bristling
or ruffled.
Two deaths during exposure; 14 deaths 3-21 d
after exposure. Lesions including fibrosis
of the larynx and bronchopneumonia associated
with aspiration of foreign materials.
No deaths. In lungs, hyperemia, edema,
and degeneration of surface cells.
Both animals died. Lung hyperemia , edema,
and degeneration of surface cells.
No deaths. In lungs, hemorrhage, edema,
and degeneration of surface cells.
Thirteen deaths between 8-21 d after expo-
sure. Lesions including fibrosis of the
larynx and bronchopneumonia associated with
aspiration of foreign materials.
No deaths. In lungs, hyperemia, edema,
and degeneration of surface cells.
Reference
and Rating
Nevskaya and
Kochetkova (1961
B-7
Runkle and Hahn
(1977a)
D-12
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8
Runkle and Hahn
(1977a)
D-12
Treon et al.
(1950)
A-8
Static?
-------
TABLE III-5. RAT—ACUTE TESTS (continued)
Compound (s)
and Concen- .
tration(s) in
mg/m3
H2S04
240
H2S04
218
H2S04
190
H2S04
172
H2S04
100
H2S04, 94
Humidity/
Particle
Size
40%
1.4 (Jm
(HMD)
< 2.0 \im
< 2.0 pm
Up to 60%
0.45 M
(CUD)
82% 0.8 \i
(MMAD)
80%
20%
0.35-0.6
Mm (MMAD)
Mode of
Exposure
Exposure
chamber
Inhala-
tion
chamber
Static?
Inhala-
tion
chamber
Static?
Exposure
chamber
Exposure
chamber,
34-in.
Controls
in:
27-in.
chamber
Nose
only
Species/ Duration &
Strain/ Test Nos. of Frequency Total
Age/ Animals Controls of Length
Weight M F M F Exposure of Expt.
Fischer- 16 16 Not Random
344 rats given groups of
8 removed
at 1, 2,
4, and 8 h
Rats 2 7 h, once
J
Rats 2 7 h, once
Sprague- 18 18 7 d,
Dawley once
and Long-
Evans
rats, 60 ± .
3.5 d old
Fischer- 19 19 19 19 6 h, once
344 rats
COB CD
F/Crl BR,
12-14 wk
Rats, 14-17 Not Not given Not
Fischer- given given
344,
COB CD
F/Crl BR,
M-200 g,
F-140 g
Effects
No deaths during or up to 3 wk after ex-
posure. Lesions including fibrosis of
larynx and bronchopneumonia associated with
aspiration of foreign materials.
No deaths. In lungs, hyperemia, edema,
and degeneration of surface cells.
A-8
No deaths. Slight to moderate swelling of
septal cells.
No morphological evidence of pulmonary
damage .
Females showed increase in sialic acid lev-
els; males showed decreases 1 d after expo-
sure. Increase in protein in lavage fluid
of females 1 wk after exposure. Increase in
p-glucuronidase in females 3 wk after expo-
sure. Increased mucociliary clearance 3 wk
after exposure.
55% H2S04 deposited of total inhaled. No
consistent difference seen for the deposi-
tion efficiency of H2S04 when the external
relative humidity varied from 20 to 80%.
.Reference
and Rating
Runkle and Hahn
(1977a)
D-12
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8
Schwartz
et al. (1977)
A-17
Henderson et al
(1978)
A- 13
Dahl (1978)
B-14
-------
TABLE III-5. RAT—ACUTE TESTS (continued)
NJ
Compound (s)
and Concen-
tration(s) in
rag/m3
H2S04, 90
H2S04
87
H2S04) 33.3
H2S04, 24
H2S04, 20
H2S04> 13.5
Humidity/
Particle
Size
80%
0.35-0.6
Mm (MMAD)
< 2.0 pm
40%
0.92 \tm
(MMAD)
80%
0.35-0.6
pm (MMAD)
20%
0.35-0.6
Mm (MMAD)
40%
0.5 |Jm
Mode of .
Exposure
Nose
only
Inhala-
tion
chamber
Static?
Nose
only
Nose
only
Nose
only
Nose
only
Species/
Strain/ Test Nos. of
Age/ Animals Controls
Weight M F M F
Rats, 14-17 Not
Fischer- given
344,
COB CD
F/Crl BR,
M-200 g,
F-140 g
Rats 2
Rats, 17 Not
Fischer- given
344,
COB CD
F/Crl BR,
218 g
Rats, 14-17 Not
Fischer- given
344,
COB CD
F/Crl BR,
M-200 g,
F-140 g
Rats, 14-17 Not
Fischer- given
344,
COB CD
F/Crl BR,
M-200 g,
F-140 g
Rats, 16 Not
Fischer- ' given
344,
COB CD
F/Crl BR,
215 g
Duration &
Frequency Total
of Length
Exposure of Expt.
Not given Not
given
2.75 h,
once ,
0.5 h, not Not
given given
Not given Not
given
Not given Not
given
0.5 h, not Not
given given
Effects
18% H2S04 deposited of total inhaled. No
consistent difference seen for deposition
efficiency of H2S04 when external relative
humidity varied from 20 to 80%.
No deaths. Slight to moderate swelling of
septal cells.
Slightly less deposition efficiency for
0.9 M"i droplets than for 0.4 Mm- 39%
deposition efficiency.
42% H2S04 deposited of total inhaled. No
consistent difference seen for deposition
efficiency of H2S04 when external relative
humidity varied from 20 to 80%.
46% H2S04 deposited of total inhaled. No
consistent difference seen for deposition
efficiency of H2S04 when external relative
humidity varied from 20 to 80%.
Slightly greater deposition efficiency for
0.4 pm droplets than for 0.9 M"i. 52% depo-
sition efficiency.
Reference
and Rating
Dahl (1978)
B-14
Treon et al.
(1950)
A-8
Dahl (1978)
B-14
Dahl (1978)
B-14
Dahl (1978)
B-14
Dahl (1978)
B-14
-------
TABLE III-5. RAT—ACUTE TESTS (concluded)
Compound(s)
and Concen-
tration(s) in
mg/m3
H2S04, 12
H2S04
10
H2S04, 9.6
H2S04
1.0
H2S04) 0.1-1.0
alone and
with 03
0.4-0.5 ppm
Humidity/
Particle
Size
80%
0.35-0.6
Mm (MMAD)
.'
82% 0.7
Mm
(MMAD)
80%
20%
0.35-0.6
Mm (MMAD)
82% 0.6
Mm
(MMAD)
80%
Not
given
Mode of
Exposure
Nose
only
Exposure
chamber,
54-in.
Controls
in:
27-in.
chamber
Nose
only
Exposure
chamber
54-in.
Controls
in:
27-in.
chamber
Not '
given
Species/ Duration &
Strain/ Test Nos. of Frequency Total
Age/ Animals Controls of Length
Weight M F M F Exposure of Expt.
Rats, 14-17 Not Not given Not
Fischer- given given
344,
COB CD
F/Crl BR,
M-200 g,
F-140 g
Fischer- 19 19 19 19 6 h, once
344 rats
COB CD
F/Crl BR,
12-14 wk
Rats, 14-17 Not Not given Not
Fischer- given given
344,
COB CD
F/Crl BR,
M-200 g,
F-140 g
Fischer- 19 19 19 19 6 h, once
344 rats
COB CD
F/Crl BR,
12-14 wk
Rats Not Not
given given
Effects
52% H2S04 deposited of total inhaled. No
consistent difference seen for the deposi-
tion efficiency of HZS04 when external rela-
tive humidity varied from 20 to 80%.
Sialic acid level back to normal. Increase
in protein in lavage fluid, increase in
B-glucuronidase in females 1 d after expo-
sure. Increased mucociliary clearance 1 wk
after exposure.
/
43% H2S04 deposited of total inhaled. No
consistent difference seen for the deposi-
tion efficiency of H2S04 when external relar
tive humidity varied from 20 to 80%.
Increase in sialic acid 1 d after exposure.
Increased mucociliary clearance 3 wk after
exposure.
Wet to dry weight ratios; DNA, protein and
RNA content; and the activities of lysosomal
hydrolases in the lung homogenate increased
on exposure to the mixtures together with in-
Reference
and Rating
Dahl (1978)
B-14
Henderson et al
(1978)
A-13
Dahl (1978)
B-14
Henderson et al
(1978)
A-13
Last et al.
(1977b)
C-10
creases in the rate of secretion of mucus gly-
coproteins by tracheal explants of the same
rats.
-------
TABLE III-6. RATS--REPEATED DOSE EXPERIMENTAL EXPOSURE TO H2S04
Compound (s)
and Concen- Humidity/
tration(s) in Particle
mg/ra3 Size
H2S04 < 2.0 Mm
1,160
H2S04 < 2.0 Mm
839
H2S04 < 2.0 Mm
670
H2S04 < 2.0 Mm
383
H2S04 < 2.0 Mm
203
H2S04 Not
156 given
H2S04 55%
100.0 0.72 Mm
(HMD)
H2S04 (3 dif-
5-100 ferent)
Mode of
Exposure
Inhala-
tion
chamber
Static?
Inhala-
tion
chamber
Static?
Inhala-
tion
chamber
Inhala-
tion
chamber
Static?
Inhala-
tion
chamber
Static?
Inhala-
tion
chamber
Inhala-
tion
chamber
Species/ Duration &
Strain/ Test Nos. of Frequency
Age/ Animals Controls of
Weight M F M F Exposure
Rats 2 7 h/d
-
Rats 2 7 h/d
Rats 2 7 h/d
Rats 2 7 h/d
Rats 2 7 h/d
Rats, 50 135 6 h/d, al-
Wistar ternate
~60 d wkd for 6
exposures
Rats 20 20
Charles
River
Fischer,
150-200 g
Charles ? ? ? ? 6 h/d
River
(Sprague-
Dawley)
or Fischer
rats, 150-
200 g
Total
Length
of Expt. Effects
4 d One animal died during first exposure pe-
riod; other one during second period. Lung
hyperemia, edema, and degeneration of sur-
face cells.
3 d Both animals died. In lungs, edema, hyper-
emia, and degeneration of surface cells.
2 d Both animals died. In lungs, hyperemia,
edema, and degeneration of surface cells.
5 d Both animals died. In lungs, hyperemia,
edema, and degeneration of surface cells.
5 d No deaths. Slight to moderate swelling of
septal cells.
Lifetime Median survival, 710 d. No bone tumors.
observa-
tion
5 d No morphologic effects.
48 h to No exposure related pulmonary lesions were
6 mo seen in the rats at any concentration (ab-
stract).
•
Reference
and Rating
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8
Treori et al.
(1950)
A-8
Ballou et al.
(1977); (1980)
D-- B--
Cavender et al.
(1977)
B-13
Cockrell
et al. (1976)
A-10
-------
TABLE III-6. RAT—REP. DOSE (continued)
Compound (s)
and Concen-
tration^) in
mg/m3
H2S04
68
H2S04
45
"
H2S04, 30.0
H2S04
23
H2SO, 10.0
H2S04, 10.0
03, 2.0 ppm
H2S04) 10.0
03, 1.0 ppm
Humidity/
Particle
Size
Up to 60%
0.4 (jm
(MMAD)
Up to 60%
0.52 Mm
(CMD)
55%
0.83 Hm
(HMD)
Not
given
55%
0.93 pm
(HMD)
55%
0.99 \im
(HMD)
55%
1.01 Mm
(HMD)
Mode of
Exposure
Exposure
chamber
Exposure
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Species/ Duration &
Strain/ Test Nos . of Frequency
Age/ Animals Controls of
Weight M F M F Exposure
Sprague- 10 10
Dawley
and Long-
Evans
rats, 60 ±
3.5 d old
Sprague- 6 6 ?
Dawley
and Long-
Evans
rats, 60 ±
3.5 d old
Rats 20 20 ?
Charles
River
Fischer,
150-200 g
Rats, 50 135 6 h/d, al-
Wistar ternate
~60 d wkd for 6
exposures
Rats 60 20 ?
Charles
River
Fischer,
150-200 g
Rats 20 ' 20 ?
Charles
River
Fischer,
150-200 g
Rats 20 20 ?
Charles
River
Fischer,
150-200 g
Total
Length
of Expt. Effects
6 d No morphological evidence of pulmonary
damage.
11 d No morphological evidence of pulmonary
damage .
5 d No morphologic effects.
Lifetime Median survival, 755 d. No bone tumors.
observa-
tion
^
7 d No morphologic effects.
•
7 d After 2 d, epithelial hypertrophy and
hyperplasia in terminal bronchioles.
Alveolitis and pulmonary edema present.
Reduced body wt., increased lung/body
wt. ratio. Loss of cilia in bronchi.
7 d After 2 d, epithelial hypertrophy and
hyperplasia in terminal bronchioles.
Alveolitis and pulmonary edema present.
Reference
and Rating
Schwartz
et al. (1977)
A-17
Schwartz
et al. (1977)
A-17
Cavender et al.
(1977)
B-13
Ballou et al.
(1977); (1978);
(1979); (1980)
D-; B-7;
B-; B-
Cavender et al.
(1977)
B-13
Cavender et al.
(1977)
B-13
Cavender et al.
(1977)
B-13
-------
TABLE III-6. RAT--REP. DOSE (continued)
Compound (s)
and Concen-
tration(s) in
mg/m3
H2S04
6.59
^
H2S04
6.35
H2S04, 5.0
03, 2.0 ppm
H2S04> 5.0
03, 1.0 ppm
H2S04, 5.0
03 , 1.0 ppm
H2S04, 5.0
H2S04
4.05 ± 1.63
Humidity/
Particle
Size
0.31 pra
(HMD)
0.44 urn
(HMD)
55%
0.94 [im
(MUD)
55%
0.95 \an
(HMD)
55%
0.75 pm
(HMD)
55%
0.88 pm
(HMD)
33%
0.5 ±
1.0 Mm
(MUD)
Mode of
Exposure
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Species/ Duration &
Strain/ Test Nos. of Frequency Total
Age/ Animals Controls of Length
Weight M F M F Exposure of Expt.
Rats -20 ~ 20 Continuous 13 wk
except
6 h/wk
Rats ~ 20 ~ 20 Continuous 6 wk
except 6
h/wk
Rats 20 20 ? 7 d
Charles
River
Fischer,
150-200 g
Rats 20 20 ? 7 d
Charles
River "
Fischer,
150-200 g
Rats 20 20 ? 7 d
Charles
River
Fischer,
150-200 g .
Rats 60 20 ? 7 d
Charles
River
Fischer,
150-200 g
Rats 12 12 Continuous 7 wk
Effects
No significant effect on lung function,
acid-base chemistry of blood or behavior
as measured by spontaneous motor activity.
Developed metabolic alkalosis.
No significant effect on lung function acid-
base chemistry of blood or behavior, as mea-
sured by spontaneous motor activity. Devel-
oped metabolic alkalosis.
After 2 d, epithelial hypertrophy and
hyperplasia in terminal bronchioles.
Alveolitis and pulmonary edema present.
Reduced body wt., increased lung/body
wt. ratio. Loss of cilia in bronchi.
After 2 d, epithelial hypertrophy and
hyperplasia in terminal bronchioles.
After 2 d, epithelial hypertrophy and
hyperplasia in terminal bronchioles.
No morphologic effects.
No significant effects on acid-base chem-
istry of blood or learning as measured by
task performance. Significant lung changes
were higher pulmonary resistance and respira-
tory frequencies and lower tidal volumes.
Reference
and Rating
Lewkowski
et al. (1979)
A-ll
Lewkowski
et al. (1979)
A-ll
Cavender et
(1977)
B-13
Cavender et
(1977)
B-13
Cavender et
(1977)
B-13
Cavender et
(1977)
B-13
Lewkowski
al.
al.
al.
al.
et al. (1979)
A-ll
-------
TABLE III-6. RAT—REP. DOSE (concluded)
Compound (s)
and Concen-
tration^) in
mg/m3
H2S04, 4
H2S04
2.49 ± 0.4
H2S04
2
H2S04, 2
03, 0.9 ppm
S04 exhaust
emissions with
catalytic
converter
0.61
S02
4.95
Humidity/
Particle
Size
44%
< 0.24 ym
(HMD)
40-60%
0.3 (Jm
40-60%
0.3 (Jm
50%
Mode of
Exposure
Inhala-
tion
chamber
Inhala-
tion
chamber
Atmo-
spheric
exposure
chamber
Atmo-
spheric
exposure
chamber
Exposure
chambers
Species/
Strain/
Age/
Weight
Rats,
Wistar
Rats
Rats,
Sprague-
Dawley,
1 mo .
Rats,
Sprague-
Dawley,
1 mo
Sprague-
Dawley
rats
200 g
Duration &
Test Kos. of Frequency
Animals Controls of
M F M F Exposure
50 135 6 h/d,
alternate
wkd for 6
exposures
? ? Continuous
25 ? 8 h/d
25 ? 8 h/d;
exposed
4 h to
H2S04
then 4 h
to mixture
20 10 24 h/d
(10 each
nonirradi-
ated and
irradiated
exhaust)
Total
Length
of Expt. Effects
Lifetime Median survival, 730 d. Two rats with bone
observa- tumors; not considered significant compared
tion to controls.
8 wk No significant effects on acid-base chem-
istry or lung function. Performance on
forced treadmill reduced even 80 d past
exposure.
82 d Minimal evidence of hypertrophy of epi-
thelial lining cells, mainly at the
ductal level.
82 d Hypertrophic cells line the alveolar duct.
7 d Body weight changes were significantly
lower for both irradiated and nonir-
radiated exhaust exposures. Hematocrit
changes were insignificant for both as
were serum LDH levels for both groups.
Reference
and Rating
Ballou et al.
(1977); (1978);
(1979); (1980)
D— ; B-7;
B-, B-
Lewkowski
et al. (1979)
A-ll
Juhos et al.
(1978)
B-ll
Juhos et al.
(1978)
B-ll
Lee et al.
(1976)
B-10
-------
TABLE II1-7. RATS--CHRONIC EXPERIMENTAL INHALATION EXPOSURE TO H2S04
00
Compound (s)
and Concen-
tration(s) in
mg/m3
H2S04, 10.34
H2S04, 9.98
03, 0.52 ppm
H2S04, 7 ± 3
H2S04, 7
03, 0.8
S04=
5.48 ± 0.60
(almost all
existing
as H2S04)
H2S04
2.37 ± 1.13
Humidity/
Particle
Size
63%
0.83 Mi"
(50% EAD)
56%
1.38 pm
(50% EAD)
Not given
0.1-0.2
pm (HMD)
50%
0.5 ±
1.0 Mm
(HMD)
Mode of
Exposure
Inhala-
tion
Chamber
Inhala-
tion
Chamber
Exposure
chamber
Exposure
chamber
Exposure
chamber
Inhala-
tion
chamber
Species/
Strain/ Test Nos. of
Age/ Animals Controls
Weight M F M F
Rats 35 35 35 35
Charles
River
Fischer,
150-200 g
Rats 35 35 35 35
Charles
River
Fischer,
150-200 g
Albino 10 10
rats,
270-280 g
Albino 10 10
rats,
270-280 g
Crl:COBS 20 20
CD(SD)BR
rats,
130 g
Rats 10 10
Sprague-
Dawley
Duration &
Frequency Total
of Length
Exposure of Expt.
6 h/d, 6 mo
5 d/wk
6 h/d, 6 mo
5 d/wk
5 h/d, 6 4.5 mo
d/wk (100 d)
5 h/d, 6 4.5 mo
d/wk (100 d)
16 h/d, 90 d
7 d/wk
Continuous 14 wk
Effects
No pronounced respiratory tract lesions.
Weight unaffected.
2 rats showed slight hypertrophy and
hyperplasia of bronchiolar epithelium.
No pronounced respiratory tract lesions.
Weight unaffected.
Inflammation of .the lung. Increase in
excitability of the lung. Lowering of
oxygen consumption. Development of con-
nective tissue in the lungs did not ap-
pear until 5 mo, whereas this occurred
within 3-3.5 mo with 03 and 2.5 mo with
H2S04 + 03.
Increase of CNS excitability. Lowering
of 02 consumption. Catarrhal desquama-
tion, purulent tracheitis, bronchitis,
sclerosis, and evidence of pneumonia and
emphysema 5 mo after exposure. Body weight
significantly different from that of the
controls and from those of rats exposed to
H2S04 or 03 alone.
Numerous alveolar macrophages in the lungs.
Cytoplasm of these contained black granular
pigment. No indication of pathological ef-
fects due to exposure to automobile exhaust
containing sulfuric acid. No effects noted
at 45 d.
No significant effects on lung function,
acid-base chemistry of blood, or behavior
as measured by spontaneous motor activity.
Reference
and Rating
Cavender et al.
(1978c)
B-ll
Cavender et al.
(1978c)
B-ll
Nevskaya and
Kochetkova (1961)
B-7
Nevskaya and
Kochetkova (1961)
B-7
Pepelko
et al. (1979)
B-10
Lewkowski
et al. (1979)
A-ll
-------
TABLE III-8. GUINEA PIGS—ACUTE EXPERIMENTAL EXPOSURE TO H2S04
Compound (s)
and Concen- Humidity/
tration(s) in Particle
mg/m3 Size
H2S04 < 2.0 pm
218
H2S04 < 2.0 [im
206
H2S04 < 2.0 pro
190
H2S04 < 2.0 (jra
178
H2S04 < 2.0 pm
178
H2S04 0.5 Mm
174 (HMD)
Plus kero-
sene smoke
H2S04 < 2.0 pro
165
H2S04 0.5 Mm
138 (MUD)
Mode of
Exposure
Inhala-
tion
chamber
Static?
Inhala-
tion
chamber
Static?
Inhala-
tion
chamber
Static?
Inhala-
tion
chamber
Static?
Inhala-
tion
chamber
Static?
Inhala-
tion
chamber
Inhala-
tion
chamber
Static?
Inhala-
tion
chamber
Species/ Duration &
Strain/ Test Nos. of Frequency Total
Age/ Animals ' Controls of Length
Weight M F M F Exposure of Expt.
Guinea 2 7 h,
pigs once
Guinea 6 3 h,
pigs once
Guinea 3 7 h,
pigs once
Guinea 3 1 h,
pigs once
Guinea 2 0.5 h,
pigs once
Guinea 5 10 h
pigs, avg
wt, 250 g
Guinea 3 0.25 h
pigs Once
Guinea 5 10 h
pigs, avg
wt, 250 g
Effects
Both animals died. Lungs hyperemic,
enlarged, and emphysematous with de-
generative changes in surface cells
of lung, larynx, and trachea and con-
gestion of abdominal viscera.
Two animals died. Lungs hyperemic,
enlarged, and emphysematous with de-
generative changes in surface cells of
lung, larynx, and trachea and conges-
tion of abdominal viscera.
All three animals died. Lungs hypere-
mic, enlarged, and emphysematous with
degenerative changes in surface cells
of lung, larynx, and trachea and con-
gestion of abdominal viscera.
Two animals died. Lungs hyperemic,
enlarged, and emphysematous with de-
generative changes in surface cells
of lung, larynx, and trachea and con-
gestion of abdominal viscera.
One animal died. Lungs hyperemic,
enlarged, and emphysematous with de-
generative changes in surface cells
of lung, larynx and trachea and con-
gestion of abdominal viscera.
Mean death time 56 ± 9 min. Lungs dis-
tended with ruptured alveoli, areas of
edema and consolidation.
One animal died. Ataxia and prostra-
tion during exposure. Lungs hyperemic,
enlarged, and emphysematous with de-
generative changes in surface cells of
lung, larynx, and trachea and congestion
Mean death time 87 ± 39 min. Lungs dis-
tended with ruptured alveoli, areas of
edema and consolidation.
Reference
and Rating
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8- '
Salem and
Cullumbine (1961)
B-12
Treon et al.
(1950)
A-8
\
Salem and
Cullumbine (1961)
B-12
-------
TABLE III-8. GPG--ACUTE TESTS (continued)
Ln
O
Compound(s)
and Concen-
tration(s) in
ing/m3
H2S04
120
H2S04
120
H2S04
116
H2S04
111
H2S04, 109.2
NH3, 0.2-0.4
H2S04
109
Humidity/
Particle
Size
< 2.0 pm
< 2.0 prn
< 2.0 pm
0.5 pm
(HMD)
70-80%
0.41 |jm
(MMAD)
80%
0.4 pm
(MMAD)
Mode of
Exposure
Inhala-
tion
chamber
Static?
Inhala-
tion
chamber
Static?
Inhala-
tion
chamber
Static?
Inhala-
tion
chamber
Inhala-
tion
chamber
Exposure
chamber
Species/ Duration &
Strain/ Test Nos. of Frequency Total
Age/ Animals Controls of Length
Weight M F M F Exposure of Expt.
Guinea 3 1 h,
pigs once
Guinea 3 0.5 h, once
pigs
Guinea 3 ' 0.25 h,
pigs once
Guinea 5 10 h
pigs, avg
wt, 250 g;
exposed to
. kerosene
smoke for
up to 6 h
3 days
prior
Guinea 8 8 8 h,
pigs once
Hartley
strain, — *
2-3 mo
old
Charles 8 8 8 h, once
River
Hartley
strain
guinea
Pigs,
1.5-3 mo
Effects
No deaths. Degenerative changes in
surface cells of lungs, larynx, and
trachea and congestion of abdominal
viscera.
No deaths. Degenerative changes in surface
cells of lungs, larynx, and trachea and con-
gestion of abdominal viscera.
No deaths. Labored breathing developed
within 15 min.
Mean death time 111 ± 12 min. Lungs dis-
tended with ruptured alveoli, areas of
edema and consolidation.
2 animals developed labored breathing
after 1 h and died 30 min later; 3
animals became dyspneic at 6-8 h and
died within 30 min. The LCSO, therefore,
is higher for the 0.41-pm particles than
for particles ~ 2X bigger (estimated LC50
is 30 mg/m3).
Dyspnea onset shortly before death, when it
occurred.
Reference
and Rating
Treon et al.
(1950)
A-8
Treon
et al. (1950)
A-8
Treon et al.
(1950)
A-8
Salem and
Cullumbine (1961)
B-12
Wolff et al.
(1979a)
A-16
Silbaugh et al.
(1978b)
Silbaugh et al.
(to be published)
C-12
-------
TABLE III-8. GPG—ACUTE TESTS (continued)
Compound(s)
and Concen-
tration(s) in
mg/m3
H2S04
100.0
H2S04
87
H2S04
84
H2S04
83
H2S04, 82.9
NH3, 0.2-0.4
H2S04
40-80
\
Humidity/
Particle
Size
55%
0.72 Mm
(MUD)
< 2.0 pro
50%
5 0.73 Mm
80%
0.4 pin
(MMAD)
70-80%
0.47 Mm
(MMAD)
40%
0.7 M"1
(MMAD)
^-
Mode of
Exposure
Exposure
chamber
4.2 m3
Inhala-
tion
chamber
Static?
Exposure
chamber
Exposure
chamber
Inhala-
tion
chamber
Nose
only
Species/ Duration &
Strain/ Test Nos . of Frequency
Age/ Animals Controls of
Weight M F M F Exposure
Guinea 20 20 2 h
pigs
Charles
River , ,
Hartley
strain,
250-300 g
Guinea 3 2.75 h,
pigs once
Guinea 6 Not Not given
pigs given
Charles 88 8 h, once
River
Hartley
strain
guinea
pigs,
1.5-3 mo
Guinea 88 8 h,
pigs once
Hartley
strain,
2-3 mo
old
Guinea Not Not 30-55 s,
pigs, given given once
Charles
River,
Hartley
Crl:COBS(HA)
Total
Length
of Expt. , Effects
Death occurred in all animals within 2 h due
to severe pulmonary edema, hemorrhage, and
diffuse acute alveolitis. This level was
the S7-d LDSO determined by Schwartz et al.
(1979).
All animals died. Lungs hyperemic, enlarged,
and emphysema tous with degenerative changes
in surface cells of lungs, larynx, and
trachea and congestion of abdominal viscera.
S
Three guinea pigs died after 24 h.
Dyspnea onset shortly before death, when it
occurred.
2 animals developed markedly labored
breathing soon after beginning of ex-
posure and died within 2 h.
A greater proportion of the deposited H2S04
was found in the deep lungs than in the
upper respiratory tract.
Reference
and .Rating
Cavender et
(1977)
B-13
Treon et al.
(1950)
A-8
Freeman and
(1976)
D--
Silbaugh et
~
al.
Juhos
al.
(to be published)
C-12
Wolff et al.
(1979a)
A-16
Dahl (1979)
B-ll
,
-------
TABLE III-8. GPG--ACUTE TESTS (continued)
Compound (s)
and Concen-
tration^) in
mg/m3
H2S04
40-80
H2S04
40-80
H2S04
60
Ul
ro
H2S04
55
H2S04
. 50
H2S04
48.3
H2S04
43.60
Humidity/
Particle
Size
40%
0.8 pro
(MMAD)
40%
1.1 pm
(MMAD)
50%
S 0.46 pm
1.2 pm
(HMD)
40-45%
1 pm
80%
1.00 pm
(MMAD)
38% ± 7%
2.5 (Jin
(HMD)
og 1.38
Mode of
Exposure
Nose
only
Nose
only
Exposure
chamber
Inhala-
tion
chamber
Exposure
chamber
Head
only
Exposure
chamber
(head
only)
Species/
Strain/ Test
Age/ Animals
Weight M F
Guinea Not
pigs, given
Charles
River,
Hartley
Crl:COBS(HA)
Guinea Not
pigs given
Charles
River,
Hartley
Crl:COBS(HA)
Guinea 6
Pigs -
Guinea 5
pigs, avg
wt, 250 g
Guinea
pigs
18 mo
1 kg
Guinea 8
Pigs,
Hartley
strain,
1.5-3 mo
Guinea 10
Pigs,
233 g
Duration &
Nos. of Frequency
Controls of
M F Exposure
Not 30-55 s,
given once
Not 30-55 s,
given once
Not Not given
given
10 h
8 h,
once
Served 1 h, once
as own
control
Each 1 h, once
animal
served as
its own
control ;
postexpo-
sure 1-3
h; preex-
posure
0.5 h
Total
Length
of Expt. Effects
A greater proportion of the deposited H2SO
was found in the deep lungs than in the
upper respiratory tract.
A greater proportion of the deposited H2S04
was found in the deep lungs than in the upper
upper respiratory tract.
Not Three guinea pigs died after 24 h.
given
Mean death time 175 ± 46 min. Lungs en-
larged with consolidation and gross edema.
LD50
Four animals had marked increase in pulmo-
nary resistance and decrease in dynamic
compliance; two died after 25 min. Other
animals had no changes in pulmonary func-
tions .
Increased pulmonary resistance 317%; de-
creased compliance 76%. Major physiologic
effect at the level of the main bronchi.
Increased elastic work of the lungs.
Reference
and Rating
Dahl (1979)
B-ll
Dahl (1979)
B-ll
Freeman and Juhos
(1976)
D--
Salem and
Cullumbine (1961)
B-12
Amdur et al.
(1952a)
C-6
Silbaugh et al.
(1978a; 1979a ;
1979c; to be
published; 1981)
B-ll, B-ll, B-14
C-12, C-12
Amdur et al.
(1958)
D-10
-------
TABLE III-8. GPG—ACUTE TESTS (continued)
Ln
Compound (s)
and Concen-
tration^) in
mg/m3
H2S04
43
H2S04
43
HZS04
32.7-42.9
H2S04, 42.8
NH3, 0.2-0.4
H2S04) 42.7
NH3, 0.2-0.4
H2S04
31.4-42.7
Humidity/
Particle
Size
80%
0.4 Mm
(MMAD)
80%
0.8 Mm
(MMAD)
70-90%
0.9 Mm
(MMAD)
70-80%
0.36 pm
(MMAD)
70-80%
0.87 Mm
(MMAD)
70-90% .
0.80-0.97
Mm (MMAD)
Mode of
Exposure
Exposure
chamber
Exposure
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Species/ Duration &
Strain/ Test Nos. of Frequency
Age/ Animals Controls of
Weight M F M F Exposure
Charles 8 8 8 h, once
River
Hartley
guinea
Pigs,
1.5-3 mo
Charles 88 8 h, once
River
Hartley
strain
guinea
Pigs,
1.5-3 mo
Guinea 10 6 4 h, once
Pigs,
Hartley
strain,
340-400 g
Guinea 8 8 8 h,
pigs once
Hartley
strain,
2-3 mo.
old
Guinea 88 8 h,
pigs once
Hartley
strain,
2-3' mo.
old
Guinea 42 7 8 h, once
Pigs,
Hartley
strain
.
Total
Length
of Expt. Effects
Severe labored breathing prior to death for
those who died during exposure. Onset of
dyspnea was no more than 16 min before death.
Dyspnea onset up to > 3 h before death.
Three animals developed dyspnea; one died
within 2 h. Others did not respond.
Dyspneic animals had elevated whole lung
histamine levels.
No signs of respiratory distress.
15 animals developed labored breathing
within 10 min; 13 died within 2.5 h;
and 2, within 4-8 h. One animal ap-
peared unaffected throughout exposure.
, After exposure, lungs hyperinf lated, with
areas of hemorrhage, edema, and epithelial
desquamation. Gradual return to normal
6-20 d post-exposure. Using practically the
Reference
and Rating
Silbaugh et al.
(to be published)
C-12
Silbaugh et al.
(to be published)
C-12
Brownstein and
Beethe (1978)
C-13
Wolff et al.
(1979a)
A- 16
Wolff et al.
(1979a)
A-16
Silbaugh et al.
(1977b)
C-13
Brownstein et al.
(1978a)
C-12
same range and conditions, Silbaugh et al.
(1978b) found the following in lungs of ani-
mals dying of exposure (no changes in animals
sacrificed at 21 d) to 0.8-Mm particles:
diffuse hyperinflation, segments1 hemorrhagic
consolidation, and congestion with partial
atelectasis of involved segments. Bronchi-
oles .supplying hemorrhagic regions showed
early degenerative changes with epithelial
desquamation and fibrin deposition.
-------
TABLE III-8. GPG--ACUTE TESTS (continued)
Compound (s)
and Concen- Humidity/
tration(s) in Particle Mode of
rag/m3 Size Exposure
H2S04 - 38% ± 7% Exposure
42.00 0.8 pm chamber
(HMD) (head
only)
H2S04 ,80 ± 10% Exposure
4-40 1.0 pm chamber
Each animal (MMAD)
given a his-
Jj£ tamine chal-
lenge* before -"
exposure and
2 and 19 h
after
H2S04 70% Exposure
36 1pm chamber
(MMAD)
H2S04, 36 70% Exposure
preexposed to 1 pm chamber
gradually (MMAD)
increased con-
centration
H2S04 over
1.5 h (5-25)
Species/ __. Duration &
Strain/ Test^ Nos . of Frequency Total
Age/ ' Animals Controls of Length
Weight M F M F Exposure of Expt.
Guinea 5 Each 1 h, once
pigs, animal
247 g served
as its
own con-
trol;
postexpo-
sure 1-3
h; preex-
posure
0.5 h
Guinea 48 10 1 h, once ~ 20 h
Pigs,
Charles
River,
Hartley
Crl:COBS(HA)
1.5 mo
Charles 12 45 min,
River once
Hartley (3),
Camm
Hartley (3),
Camm English
shorthair (3),
NIH strain
13 (3),
guinea pigs '
Charles 12 45 min,
River once
Hartley (3),
Camm
Hartley (3),
Camm English
shorthair (3),
NIH strain
13 (3),
guinea pigs
Reference
Effects and Rating
Increased pulmonary resistance 120%; de- Amdur et al.
creased compliance 26%. (1958)
D-10
Animals exposed to < 19 mg/m3 were no dif- Silbaugh et al.
ferent from controls. Those exposed to (1979b)
> 19 mg/m3 exhibited major increases in C-12
sensitivity only if labored breathing de-
veloped during exposure. Dypsnea appeared
to be a prerequisite for sensitiEation.
Only 6 of the 48 exposed animals were es-
pecially responsive to H2S04, and then
showed the greatest increases in histamine
.sensitivity at 19 h.
NIH strain appeared more sensitive. Seem- Silbaugh et al.
ing adaptation (in all strains) to dyspnea (to be published)
producing action of H2S04 if concentration C-12
is gradually increased rather than abruptly.
NIH strain appeared more sensitive. Seem- Silbaugh et al.
ing adaptation (in all strains) to dyspnea (to be published)
producing action of H2S04 if concentration C-12
is gradually increased rather than abruptly.
Stepwise increased histamine dihydrochloridde; concentrations beginning at 0.022 mg/m3 were doubled every ~ 2 min with filtered air for 30 s
between each new concentration. The histamine exposure was stopped when the animal's dynamic compliance reached 50% of its prechallenge
value. Preexposure doses ranged from 0.12 to 6.53 mg/m3/
-------
TABLE III-8. GPG—ACUTE TESTS (continued)
Compound (s) '
and Concen-
tration(s) in
mg/m3
H2S04
36 (8.4 ppra)
H2S04
35.0
HS04
33 (7.6 ppm)
H2S04
32.6
H2S04
32.6
Humidity/
Particle
Size
80%
0.8 (jm
70-90%
0.8 pm
(MMAD)
80%
0.8 (jm
(HMD)
1.0 pra
(MMAD)
1.0 pm
(MMAD)
Mode of
Exposure
Inhala-
tion
chamber
20°C
Inhala-
tion
chamber
0°C
Exposure
chamber
Exposure
chamber
Species/
Strain/
Age/
Weight
Guinea
pigs
200-250 g
Guinea
Pigs,
Hartley
strain,
400-
450 g
Guinea
pigs
200-250 g
Hartley
strain
guinea
Pigs,
350-
450 g,
4-6 wk
Hartley
strain,
guinea
Pigs,
350-
450 g,
4-6 wk
Duration &
Test Nos. of Frequency Total
Animals Controls of Length
M F M F Exposure of Expt.
58 4 h
12 4 h, once
6 given
10 mg/kg
disodium
cromogly-
cate prior
to exposure
36 4 h
20 4 h, once
10 re-
moved and
killed im-
mediately
following
exposure;
rest '
killed
24 h
later
12 12 4 h, once
6 of each
received
5 mg/kg
atropine
sulfate
30 min
prior to
exposure;
animals
sacrificed
24 h after
exposure
Effects
LCS. Median lethal concentration was 14.9
ppm or 64 mg/m3. When (NH4)2C03 was present
at the acid inlet, no deaths occurred.
Four pretreated and three untreated animals
developed dyspnea and lung lesions.
LCS. Medial lethal concentration was 11.7
ppm or 50.3 mg/m3. When (NH4)2C03 was sup-
plied at the acid inlet, no deaths occurred.
Developed varying degrees of dyspnea 10-30
min into exposure. Most cyanotic 10-20 min
after onset of dyspnea. Immediately follow-
ing exposure, gross lung changes and histo-
logic alterations were noted including hyper-
inflation, edema, and desquamation. Those
animals killed 24 h after exposure had only
slight hyperinflation, numerous alveolar
macrophages. Fibrin deposits lined the
desquamated surfaces. There were ultra-
structural alterations in both ciliated and
nonciliated secretory cells accompanying epi-
thelial desquamation.
Eleven of 12 untreated developed respira-
tory distress; 11 of 12 pretreated remained
asymptomatic during exposure. The untreated
guinea pigs had lung lesions including hyper-
inflation and edema and epithelial desquama-
tion. The pretreated animals had no histo-
logic lung changes.
Reference
and Rating
Pattle et
(1956)
C-ll
Brownstein
(1978b)
B-13
Pattle et
(1956)
C-ll
Brownstein
A-12
Brownstein
A-12
al.
et al.
al.
(1980)
(1980)
-------
TABLE II1-8. GPG--ACUTE TESTS (continued)
Ln
Coropound(s)
and Concen-
tration(s) in
mg/m3
H2S04
32.1-32.6
H2S04
32
H2S04, 32.0
preexposed to
gradually in-
creased con-
centration
H2S04 over
1.5 h (5-25)
H2S04
32
H2S04, 31.7
NH3> 0.2-0.4
Humidity/
Particle
Size
70-90%
0.9 pm
(MMAD)
80%
0.8 pm
(MMAD)
70%
1 pm
(MMAD)
0.84 pin
(MMAD)
70-80%
0.84 \tm
(MMAD)
Mode of
Exposure
Inhala-
tion
chamber
Exposure
chamber
Exposure
chamber
Inhala-
tion
chamber
Species/ Duration &
Strain/ Test Nos. of Frequency
Age/ Animals Controls of
Weight M F M F Exposure
Guinea 24 4 h, once
pigs, 12 given
Hartley 5 mg/kg
strain, atropine
400- sulfate
450 g prior to
exposure
Charles 88 8 h, once
River
Hartley
strain
guinea
Pigs,
1.5-3 mo
Charles 12 45 min,
River once
Hartley (3),
Camm
Hartley (3),
Camm English
shorthair (3),
NIH strain
13 (3),
guinea pigs
Guinea 16 8 h,
pigs once
Charles
River
Hartley
strain,
2-3 mo.
Guinea 88 8 h,
pigs once
Hartley
strain,
2-3 mo.
old
Total
Length
of Expt. Effects
Two pretreated animals developed dyspnea
and lung lesions. Eleven untreated animals
developed dyspnea and lung lesions.
Dyspnea onset up to > 3 h before death.
NIH strain appeared more sensitive. Seem-
ing adaptation to dyspnea producing action
of H2S04 if concentration is gradually in-
creased rather than abruptly (all strains).
95% mortality. Lungs of animals that
died did not collapse, inflated poorly,
were congested and hemorrhagic.
i 72 h Most animals developed distressed
breathing within 15 min; 5 died between
3-7 h; 3, within 24 h of exposure; and
1, ~ 72 h after exposure. Three ap-
peared unaffected. Silbaugh et al.
(1978b) estimated that the LC50 for an
8-h exposure to ~ 0.8-pm particles and
observation for 21 d after is 30 mg
H2S04/m3.
Reference
and Rating
Brownstein et al.
(1978b)
B-13
Silbaugh et al.
(to be published)
C-12
Silbaugh et al.
(to be published)
C-12
Wolff et al.
(1978a)
B-10
Wolff et al.
(1979a)
A-16
Silbaugh et al.
(1977b)
C-13
-------
TABLE III-8. GPG—ACUTE TESTS (continued)
Compound (s)
and Concen-
tration(s) in
mg/m3
H2S04
30.5-32.6
H2S04
30.50
H2S04
28.9-30.5
H2S04
30
H2S04
30
Species/
Humidity/
Particle
Size
70-90%
0.80-0.97
Mm (MMAD)
38% ± 7%
7.0 Mm
(HMD)
70-90%
1.2 Mm
(MMAD)
7 Mm
70%
1 MBI
(MMAD)
Mode of
Exposure
Inhala-
tion
chamber
Exposure
chamber
(head
only)
Exposure
chamber
Exposure
chambers
Strain/
Age/
Weight
Guinea
Pigs,
Hartley
strain
Guinea
Pigs,
195 g
Guinea
Pigs,
Hartley
strain,
400-
450 g
Guinea
pigs
Charles
River
Hartley
Caram
Hartley
Test
Animals
M F
12
10
24
12 given
Duration &
Nos. of Frequency
Controls of
M F Exposure
7 4 h, once
Each 1 h, once
animal
served as
its own
control;
postexpo-
sure 1-3
h; preex-
posure
0.5 h
4 h, once
12.5 rag/kg
diphenhy-
dramine
prior to
exposure
12
(3),
(3),
1 h
45 min,
once
Total
Length
of Expt. Effects
After exposure, lungs hyperinflated, with
areas of hemorrhage, edema, epithelial
desquamation. Gradual return to normal
6-20 d post-exposure.
Increased pulmonary resistance 42%; de-
creased compliance 17%. Relatively slight
increase in resistance when smaller parti-
cles produced a marked response. No sta-
tistically significant increase in respira-
tory work. Response delayed in time.
Six animals pretreated with antihistamine
developed dyspnea, and 9, lung lesions.
Eleven untreated animals developed dyspnea
and lung lesions.
Very little effect. Particles unable
to penetrate upper respiratory tract.
NIH strain appeared more sensitive. Seem-
ing adaptation to dyspnea producing action
of H2S04 if concentration is gradually in-
creased, rather than abruptly (all strains)
Reference
and Rating
Brownstein et al.
(1978a)
B-13
Amdur et al.
(1958)
D-10
Brownstein et al.
(1978b)
B-13
Amdur et al.
(1959)
B-9
Silbaugh et al.
(to be published)
C-12
Camra English
Shorthair (3),
NIH strain
13 (3),
guinea pigs
-------
TABLE III-8. GPG--ACUTE TESTS (continued)
Ul
00
Corapound(s)
and Concen-
tration(s) in
mg/m3 .
H2S04
26.1
H2S04
25
H2S04
24.3
H2S04, 21.1
NH3, 0.2-0.4
H2S04
21
Humidity/
Particle
Size
38% ± 7%
0.8 pm
(HMD)
0.84 |Jm
(MMAD)
80% .
1 . 18 |Jm
(MMAD)
70-80%
0.79 Mm
(MMAD)
80%
0.8 (jm
(MMAD)
Species/
Strain/ Test
Mode of Age/ Animals
Exposure Weight M F
Exposure Guinea 7
chamber pigs.
(head 218 g
only)
Guinea 16
pigs
Charles
River
Hartley
strain,
2-3 mo.
Head Guinea 9
only pigs,
Hartley
strain,
1.5-3 mo
Inhala- Guinea 8 8
tion pigs
chamber Hartley
strain,
2-3 mo. old
Exposure Charles 8 8
chamber River
Hartley
strain
guinea
Pigs-
1.5-3 mo
Duration &
Nos . of Frequency Total
Controls of Length
M F Exposure of Expt.
Each 1 h, once
animal
served as
its own
control;
postexpo-
sure 1-3
h; preex-
posure
0.5 h
8 h
once
Served 1 h, once
as own
controls
8 h
once
8 h, once
'r
Effects
Increased pulmonary resistance 89%; de-
creased compliance 38%.
56% mortality. Lungs of animals that
died did not collapse, inflated poorly,
were congested and hemorrhagic.
Three animals had marked increase in pul-
monary resistance and decrease in dynamic
compliance, and two died within 35 min.
Other animals had no changes in pulmonary
functions.
Two animals developed slightly labored
breathing after 35 min. Distress in-
creased with time; one died after 7.5 h
exposure, but the other one returned to
normal 30 min after exposure.
Dyspnea onset up to > 3 h before death.
;
Reference
and Rating
Amdur et al.
(1958)
D-10
Wolff et al.
(1978a)
B-10
Silbaugh et al.
(1978a; 1979a;
1979c; to be
published; and
1981)
B-ll, B-ll, B-14
C-12, C-12
Wolff et al.
(1979a)
A-16;
Silbaugh et al.
(1977b)
C-13
Silbaugh et al.
(to be published)
C-12
-------
TABLE III-8. GPG--ACUTE TESTS (continued)
Compound (s)
and Concen- Humidity/
tration(s) in Particle
mg/m3 Size
H2S04
20.0
H2S04
20.0
H2S04
20.0
H2S04
20.0
H2S04 50%
20.0 1 |jm
H2S04 5-9, 55%
10, or 20 1 pro
(not specified)
H2S04, 20.0 Not given
Mode of
Exposure
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Exposure
chamber
Exposure
chambers
Pretreat-
ment with
10 rag/ kg
chlorphen-
iramine
Species/
Strain/
Age/
Weight
Guinea
Pigs,
Hartley
strain
Guinea
pigs,
Hartley
strain
Guinea
Pigs.
Hartley
strain
Guinea
Pigs,
Hartley
strain
Guinea
pigs
18 mo
1 kg
Guinea
pigs
Guinea .
pigs
Duration &
Test Nos. of Frequency Total
Animals Controls of Length
M F M F Exposure of Expt.
? ? 1 h, once
? ? 2 h, once
? ? 4 h, once
? ? 6 h, once
12 8 h
Once
Not Not Not given
given given
Not Not 5 min, 1 h
given given (not spe-
cific)
Effects
Hemorrhage in apical lobes of lungs.
Foci of hemorrhage in apical lobes of lungs
more diffuse than at 1 h. Some alveolar
ducts swollen.
Pronounced hemorrhagic foci of distal ends of
airways, increased numbers of alveolar
macrophages, perivascular edema, swelling
and fibrin deposition in alveolar ducts.
Pronounced hemorrhagic foci of distal ends
of airways, increased numbers of alveolar
macrophages, perivascular edema, swelling
and fibrin deposition in alveolar ducts.
No mortality.
No deaths occurred, but" definite exposure-
related microscopic alterations were seen
in the lungs characterized by a diffuse
regional, nonsuppurativt alveolitis. Bron-
choconstriction occurred to the degree of
respiratory distress.
Prevented broncho-constriction with
H2S04.
Reference
and Rating
Cockrell
et al. (1977)
A-8
Cockrell
et al. (1977)
A-8
Cockrell
et al. (1977)
A-8
Cockrell
et al. (1977)
A-8
Amdur et al.
(1952a)
C-6
Cavender et al.
(1975)
C-9
Loscutoff (1978)
C-8
,
-------
TABLE III-8. GPG—ACUTE TESTS (continued)
Compound (s)
and Concen-
tration^) in
mg/m3
H2S04) 20
H2S04, 20
H2S04
4-19
H2S04
18
H2S04
16.9
H2S04
16
Humidity/
Particle
Size
Not given
Not given
80%
1.0 (Jm
(MMAD)
50%
1 (J™
40%
0.91 pm
(MMAD)
0.84 (Jm
(MMAD)
Species/
Strain/ Test
Mode of Age/ Animals
Exposure Weight M F
Parasym- Guinea Not
pathetic pigs given
blockade
with atro-
pine (5 mg/
kg)
Not Guinea Not
given. pigs given
beta-
Adrener-
gic ( . • '
blockade
with pro-
panolol
(10 mg/kg)
Exposure Guinea 48
chamber "• pigs ,
Charles
River,
Hartley
Crl:COBS(HA)
1 . 5 mo ,
Exposure Guinea
chamber pigs
1-2 mo
250 g
Nose Guinea 13
only pigs,
520 g
Guinea 16
pigs
Charles
River
Hartley
strain,
2-3 mo.
Duration &
Nos. of Frequency Total
Controls of Length
M F Exposure of Expt.
Not 5 min, 1 h
given (not spe-
cific)
Not 5 min, 1 h
given (not spe-
cific)
10 1- h, once
8 h, x
once
Not 0.5 h, not Not
given given given
8 h,
once
Effects
Decreased but did not abolish broncho-
constriction.
No inhibition; possible potentiation of
broncho-constrictive effects of H2S04.
".
Su'lfuric acid produced alterations in
sensitivity to histamine aerosols, but
not as great as concentrations 19 mg/m3
or greater, and only if labored breathing
developed during exposure.
LDso! gross areas of hemorrhage and
edema in the lungs of dead animals.
Pneumonic changes and fibrosis.
Large difference seen between the deposi-
tion efficiency of aerosols with droplets
of 0.4 and 0.9 (J™ diameters. 18% deposi-
tion efficiency.
6% mortality. Lungs of animals that
died did not collapse, inflated poorly,
were congested and hemorrhagic.
Reference
and Rating
Loscutoff (1978)
C-8
Loscutoff (1978)
C-8
Silbaugh et al.
(1979b)
C-12
Amdur et al.
(1952a)
C-6
Dahl (1978)
B-14
Wolff et al.
(1978a)
B-10
-------
TABLE III-8. GPG--ACUTE TESTS (continued)
Compound (s)
and Concen-
tration(s) -in
rag/m3
H2S04
15.40
'
H2S04, 15.4
(3.6 ppm)
H2S04, 15.4
(3.6 ppm)
H2S04
15.40
H2S04
15
Humidity/
Particle
Size
38% ± 7%
2.5 Mm
(HMD)
50%
0.8 pm
50%
2.5 Mm
38% ± 7%
0.8 (Jm
(HMD)
80%
0.9 Mm
(MMAD)
Mode of
Exposure
Exposure
chamber
(head
only)
Exposure
chamber
Exposure
chamber
Exposure
chamber
(head
only)
Head
only
Species/
Strain/
Age/
Weight
Guinea
Pigs ,
215 g
Guinea
pigs
Guinea
pigs
Guinea
Pigs,
219 g
Guinea
Pigs,
Hartley
Duration &
Test Nos. of Frequency Total
Animals Controls of Length
M F M F Exposure of Expt.
10 Each 1 h, once
animal
served as
its own
control;
postexpo-
sure 1-3
h; preex-
posure
0.5 h '
6 1 h
10 1 h
6 'Each 1 h, once
animal
served as
its own
control;
postexpo-
sure 1-3
h; preex-
posure
0.5 h
10 10 1 h, once
Effects
Increased pulmonary resistance 97%; de-
creased compliance 43%. Major physiologic
effect at the level of the main bronchi.
Increased elastic work of the lungs.
Decreased resistance; increased compliance
suggesting bronchial constriction.
Compliance decrease was proportionately
greater than the resistance increase. De-
layed reaction time; post mortem lung ap-
pearance different suggesting action by a
mechanism different from the action of 0.8 |Jm
H2S04 (probably at the level of the main
bronchi).
Increased pulmonary resistance 69%; de-
creased compliance 24%.
One animal had 190% increase in pulmonary
resistance and 90% decrease in dynamic lung
compliance. Other animals had no change in
Reference
and Rating
Amdur et al.
(1958)
D-10
Amdur et al.
(1959)
B-9
Amdur et al.
(1959)
B-9
Amdur et al.
(1958)
D-10
Silbaugh et al.
(1977c)
B-12
strain,
1-3 mo
old, 350-
460 g
pulmonary functions.
-------
TABLE II1-8. GPG--ACUTE TESTS (continued)
Compound (s)
and Concen-
tration(s) in
mg/ra3
H2S04
14.6
H2S04
10.1
(7.3-13.0)
H2S04
8.90
H2S04
8
S02, 89 ppm
H2S04
8
S02
89 ppm
H2S04
8
H2S04
8
Humidity/
Particle
Size
80%
0.87 Mm
(MMAD)
70-80%
0.5 pro
(MMAD)
38% ± 7%
2.5 pm
(HMD)
Inhalation
Chamber
0.84 pm
(MMAD)
40-45% -
1 |Jm
Mode of
Exposure
Head
only
Inhala-
tion
chamber
Exposure
chamber
(head
only)
Inhala-
tion
chamber
Guinea
Pigs
Exposure
Chamber
Species/
Strain/
Age/ .
Weight
Guinea
pigs.
Hartley
strain,
1.5-3 mo
Guinea
Pigs,
Hartley
strain,
3-mo old
Guinea
Pigs,
206 g
Guinea
pigs
Guinea
Pigs
Guinea
pigs
Charles
River
Hartley
strain,
2-3 mo.
Guinea
pigs
1-2 mo.
250 g
Duration &
Test. Nos. of Frequency
Animals Controls of
M F M F Exposure
5 5 10 1 h, once
8 8 3 8 h, once
10 Each 1 h, once
animal
served as
its own
control;
postexpo-
sure 1-3
h; preexpo-
sure 0.5 h
8 68 to 8 h, once
H2S04
only;
4 to
S02
only
4 8
Twice—
4 h apart
16 . 8 h,
once
68 8 h,
once
Total
Length
of Expt. Effects
One animal had marked response with peak-
to-peak pleural pressure and total pulmor
nary resistance increasing and dynamic com-
pliance decreasing.
No deaths or dyspnea occurred.
Increased pulmonary resistance 61%; de-
creased compliance 26%.
Respiratory distress, large areas of com-
plete consolidation and hepatization in
lungs; weight and growth depressed and slow
to resume.
_
Respiratory distress, widespread hemorrhage,
and consolidation in lungs; weight and
growth depressed
No deaths.
No mortality.
Reference
and Rating
Silbaugh et
al.
(1979c; to be
published;
1981)
B-14, C-12,
Silbaugh et
(1977b)
C-13
Amdur et al.
(1958)
D-10
Amdur (1954)
B-12
Amdur (1954)
B-12
Wolff et al.
(1978a)
B-10
Amdur et al.
(1952a)
C-6
C-12
al.
-------
TABLE III-8. GPG--ACUTE TESTS (continued)
Compound (s)
and Concen-
tration^) in
mg/m3
H2S04
5.30
H2S04
4.1
H2S04
3.020
Followed by
a 4 min ex-
posure to
33P-labeled
aerosol of
Streptococcus
Humidity/
Particle
Size
38% ± 7%
0.8 pm
(HMD)
40%
0.43 pm
(MMAD)
50-55%
1.8 pm
(CUD)
2.0 pm
(HMD)
Mode of
Exposure
Exposure
chamber
(head
only)
Nose
only
Exposure
chamber,
body
plethys-
mograph;
subjects
lightly
sedated
with Na
pento-
barbital
adminis-
tered i.p.
30 min be-
Species/
Strain/. Test
Age/ Animals
Weight M F
Guinea 11
Pigs,
205 g
Guinea 16
Pigs,
495 g
Hartley 10
strain
guinea
pigs
600-830 g
250-350 g
Duration &
Nos. of Frequency Total
Controls of Length
M F Exposure of Expt.
Each 1 h, once
animal
served as
its own
control;
postexpo-
sure 1-3
h; preex-
posure 0.5
h
Not 0.5 h, not Not
given given given
10 1 h, once
Effects
Increased pulmonary resistance 54%; de-
creased compliance 40%.
Large difference seen between the deposi-
tion efficiency of aerosols with droplets
of 0.4 and 0.9 pm diameters. 74% deposi-
tion efficiency.
Induced 60% greater total respiratory deposi-
rate tion and change in regional deposition
of Streptococcus aerosol (radiolabeled).
Although there was no change in the absolute
amount of radiolabeled aerosol in the tra-
chea or lung, the greater percent of total
radioactivity found in the nasopharynx
caused a reduction in the percent of radio-
activity in the lung.
Reference
and Rating
Amdur
(1958)
D-10
Dahl (1978)
B-14
Fairchild
et al. (1975b)
A-ll
r~
fore inser-
tion in ap-
H2S04
2.30
38% ± 7%
2.5 pm
(HMD)
paratus.
Exposure
chamber
(head
only)
Guinea 10
Pigs,
222 g
Each 1 h, once
animal
served
as its
own con-
trol;
postex-
posure
1-3 h;
.preexpo-
sure 0.5
h
Increased pulmonary resistance 39%; de-
creased compliance 16%.
'
Amdur
(1958)
D-10
-------
TABLE III-8. GPG--ACUTE TESTS (continued)
Compound (s)
and Concen-
tration^) in
mg/m3
H2S04
1.90
H2S04
1.2
H2S04
1
H2S04
1
H2S04
1
H2S04
1.0
Humidity/
Particle
Size
38% ±'7%
0.8 pm
(MMD)
40%
0.94 pm
(MMAD)
80%
0.9 Mm
(MMAD)
40%
0.9 pra
(MMAD)
40 or 80%
0.6 pm
50%
0.3 pm
(HMD)
Mode of
Exposure
Exposure
chamber
(head
only)
Head
only
Head
only
Head
only
-^
Exposure
chamber
Head
only
Species/
Strain/ Test
Age/ Animals
Weight M F
Guinea 6
Pigs,
208 g
Guinea 5 5
Pigs,
Hartley
strain,
1.5-3 mo
Guinea 10
Pigs,
Hartley
strain,
1-3 mo
old, 350-
460 g
Guinea 10
Pigs,
Hartley
strain,
1-3 mo
old, 350-
460 g
Guinea 20
pigs
350-450 g
Guinea 25
pigs
200-300 g
Duration &
Nos. of Frequency Total
Controls of Length
M F Exposure of Expt.
Each 1 h, once
animal
served as
its own
control ;
postexpo-
sure 1-3
h; pre-
exposure
0.5 h
10 1 h, once
5 at 40%
RH; 5 at
80% RH
10 1 h, once
10 1 h, once
(several) 1 h
Each 1 h, once
served as .
own con-
trol
~
Effects
Increased pulmonary resistance 51%; de-
creased compliance 35%.
No group differences in tidal volume,
respiratory frequency, minute volume, peak
inspiratory or expiratory flow, peak to
peak pleural pressure, total pulmonary re-
sistance, or dynamic compliance.
Pulmonary functions unchanged.
Pulmonary functions unchanged.
-
No changes in V , f, minute volume, Ppl,
peak inspiratory and expiratory flow,
R , and C2 dyn.* Lack of pulmonary
,cfianges contrasts with earlier reports
of effects at lower concentrations.
Increased pulmonary resistance 78%; de-
creased compliance 40%. Other pulmonary
functions unaffected. After 30 min,
postexposure resistance values were less
that at end of exposure but still elevated
above control values; postexposure compli-
ance values greater than at end of exposure
bill still less than control values.
Reference
and Rating
Amdur (1969)
A-0
Amdur (1958)
D-10
Silbaugh et
al.
(1979c; to be
published ;
1981)
B-14, C-12,
Silbaugh et
(1977c)
B-12
Silbaugh et
(1977c)
B-12
Silbaugh et
" (1977a)
A-ll
Amdur et al.
(1978)
D-10; Amdur
(1978) B-ll
C-12
al.
al.
al.
* Terms were not defined.
-------
TABLE III-8. GPG--ACUTE TESTS (continued)
Compound (s)
and Concen-
tration(s) in
mg/m3
H2S04
0.85
H2S04
0.69
H2S04
0.51
H2S04
0.40
Humidity/
Particle
Size
50%
1.0 \tm
(HMD)
50%
1.0 pin
(MMD)
50%
0.3 Mm
(MMD)
50%
1.0 Mm
(MMD)
Mode of
Exposure
Exposure
chamber
(head
only)
Head
only
Head
only
Head
only
Species/
Strain/ Test
Age/ Animals
Weight M F
Guinea 20
Pigs,
random-
bred,
200-
300 g
Guinea 20
pigs
200-300 g
"A
Guinea 20
pigs
200-300 g
Guinea 20
pigs
200-300 g
Duration &
Nos. of Frequency Total
Controls of Length
M F Exposure of Expt.
Each 1 h, once
animal
served as
its own
control;
preexpo-
sure 0.5
h; postex-
posure
0.5 h
Each 1 h, once
served
as its
own con-
trol
Each 1 h
served as
its own
control
Each 1 h
served as
its own
control
Effects
Increased pulmonary resistance 60%; de-
creased compliance 28%. Other pulmonary
functions unaffected. After 30 rain,
postexposure resistance values less than
at end of expos'ure but still elevated
above control values; postexposure compli-
ance values greater than at end of exposure
but still less than control values.
Increased pulmonary resistance 47%; de-
creased compliance 25%. Other pulmonary
functions unaffected. After 30 rain, post-
exposure resistance values less than at end
of exposure but still elevated above control
values; postexposure compliance values
greater than at end of exposure but still
less than control values.
Increased pulmonary resistance 60%; de-
creased compliance 33%. Other pulmonary
functions unaffected. After 30 min, post-
exposure resistance values less than at end
of exposure but still elevated above control
values; postexposure compliance values
greater than at end of exposure but still
less than control values.
Increased pulmonary resistance 30%; de-
creased compliance 8%. Other pulmonary
functions unaffected. After 30 min, post-
exposure resistance values less than at end
of exposure but still elevated above control
values; postexposure compliance values
greater than at end of exposure but still
less than control values.
Reference
and Rating
Amdur et al.
(1978a)
D-10; Amdur
(1978) B-ll
Amdur efc al.
(1978a)
D-10; Amdur
(1978) B-ll
Amdur et al.
(1978a)
D-10; Amdur
(1978) B-ll
Amdur et al.
(1978a)
D-10; Amdur
(1978) B-ll
-------
TABLE III-8. GPG--ACUTE TESTS (continued)
— —— ~ — . — . — __ —
Compound (s)
and Concen-
tration(s) in
mg/m3
H2S04
0.320
Followed by
a 4-min ex-
posure to
33P-labeled
Streptococcus
sp.
H2S04
0.11
H2S04
0.10
Humidity/
Particle
Size
50-55%
0.6 pm
(CMD)
50%
1.0 pm
(HMD)
50%
0.3 pm
(HMD)
Species/ Duration &
Strain/ Test Nos. of Frequency Total
Mode of Age/ Animals Controls of Length
Exposure Weight M F M F Exposure of Expt.
Exposure Hartley 10 10 1 h, once
chamber, strain
body guinea
plethys- pigs
mograph;
subjects '600-830 g
lightly 250-350 g
sedated
with Na
pento-
barbital
adminis-
tered i.p.
30 rain be-
fore inser-
tion in ap-
paratus.
Head Guinea 20 Each 1 h, once
only pigs served as
200-300 g its own
control
Head Guinea 23 Each 1 h, once
only pigs served
200-300 g as its
own con-
trol
Effects
No effect on total or regional deposition
of radiolabeled Streptococcus sp. was ob-
served.
Increased pulmonary resistance 14%; de-
creased compliance 13%. Other pulmonary
functions unaffected. Both resistance and
compliance values returned to preexposure
values by end of 30 rain postexposure period.
Increased pulmonary resistance 41%; de-
creased compliance 27%. Other pulmonary
functions unaffected. After 30 min, post-
exposure resistance values less than at end
of exposure but still elevated above control
values, postexposure compliance values
greater than at end of exposure but still
less than control values.
Reference
and Rating
Fairchild
et al. (1975b)
A-ll
Amdur et al.
(1978)
D-10; Amdur
(1978) B-ll
Amdur et al.
(1978)
D-10;
Amdur et al.
(1975)
D-0; Amdur
(1978) B-ll
-------
TABLE III-8. GPG--ACUTE TESTS (concluded)
Compound (s)
and Concen-
tration(s) in
mg/m3
H2S04
0.03
Followed by
a 4-min ex-
posure to
33P-labeled
aerosol of
Streptococcus
sp.
Species/ Duration &
Humidity/ Strain/ Test Nos . of Frequency Total
Particle Mode of Age/ Animals Controls of Length
Size Exposure Weight M F M F Exposure of Expt.
50-55% Exposure Hartley 10 10 1 h, once
0.25 Mm chamber, strain
(CMD) body guinea
plethys- pigs
mograph;
. subjects 600-830 g
lightly 250-350 g
sedated
with Ka
pento-
barbitol
adminis-
tered i.p.
30 min be-
fore inser-
tion in ap-
paratus.
Reference
Effects and Rating
A significantly greater amount of radio- Fairchild
activity was found in the trachea in the et al. (1975b)
test animals than in the controls. The A-ll
9% greater total resporatory deposition
rate was not different from control values
at the 5% level of statistical significance.
-------
TABLE III-9. GUINEA PIGS—REPEATED DOSE EXPERIMENTAL EXPOSURE TO H2S04
00
Compound (s)
and Concen- Humidity/
tration(s) in Particle
mg/m3 Size
H2S04 < 2.0 \im
1,160
H2S04 < 2.0 pro
839
H2S04 Not
220 deter-
mined
H2S04 0.33 pra
105 (MMAD)
H2S04 (3 dif-
5-100 ferent)
Mode of
•Exposure
Inhala-
tion
chamber
Static?
Inhala-
tion
chamber
Static?
Exposure
chamber
4.2 m3
Exposure
chamber
4.2 m3
Species/ Duration &
Strain/ Test Nos. of Frequency Total
Age/ Animals Controls of Length
Weight M F M F Exposure of Expt.
Guinea 2 7 h/d 4 d
pigs
Guinea 2 7 h/d 3 d
pigs
Guinea 10 Continuous 7 d?
pigs
Charles
River
Hartley
albino
51-65 d
410 g avg. wt.
Guinea 10 Continuous 7 d
pigs
Charles
River
Hartley
albino
51-65 d
410 g avg. wt.
Charles .? ? ? ? 6 h/d 48 h to
River ~ 6 mo
(Hartley
strain)
guinea
pigs
Effects
Both animals died. Lungs hyperemic,
enlarged and emphysematous with de-
generative changes in surface cells
of lung, larynx and trachea and con-
gestion of abdominal viscera.
Both animals died. Lungs hyperemic,
enlarged, and emphysematous with de-
generative changes in surface cells
of lungs, larynx, and trachea and
congestion of abdominal viscera.
Four died within 3 h. Other six
killed while in extreme respiratory
distress.
Five animals died.
Microscopic and ultrastructural lesions in
trachea and lungs at all concentrations.
Lesions varied from bronchiolitis to alveo-
litis with Type II cell hyperplasia and focal
loss of tracheal cilia. Death from pulmonary
edema and hemorrhage in those animals exposed
to 100 mg/m3 for several h. Differences in
particle size did not affect variability of
pulmonary response (abstract).
Reference
and Rating
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8
Schwartz et
(1979)
C-12
Schwartz et
(1979)
C-12
Cockrell
al.
al.
et al. (1976)
A-10
-------
TABLE III-9. GPG—REP. DOSE (continued)
vo
Compound (s)
and Concen- Humidity/
tration(s) in Particle
rag/m3 Size
H2S04 2.7 Mm
17.2 (4.0 ppm) (HMD)
23.2 (5.8 ppm)
30.8 (7.7 ppm)
40.3 (10.0 ppm)
65.6 (16.4 ppm)
89.6 (22.4 ppm)
Batch of 6 animals
exposed to first
concn. After
mortality noted,
concn. raised and
further batch (6
animals) added.
Process repeated
to 4th (with 10-
member groups) day.
2-day break and then
5, 6 & 7th days concns.
constant. 8th day concn.
raised final time.
H2S04 80%
26.2-82.1 0.8 pro
(6.1-19.1 (HMD)
ppm)
H2S04 Up to 60%
71 0.52 (Jin
(CUD)
H2S04 0.32 Mm
62 (MMAD)
Species/
Strain/ Test Nos . of
Mode of Age/ Animals Controls
Exposure Weight M F M F
Guinea 32
Pigs
200-250 g
^
Exposure Guinea 10
chamber* pigs
200-250 g
Exposure Conven- 2 2 -
chamber tional
and SPF
albino
Hartley
guinea
pigs, 400-
800 g
Exposure Guinea 10
chamber pigs
4.2 m3 Charles
River
Hartley
albino
51-65 d
4iO g avg.
wt.
Duration &
Frequency Total
of Length Reference
Exposure of Expt. Effects and Rating
8 h/d 8 d, 2 d No significant difference between the mor- Pattle et al.
break tality among previously exposed animals and (1956)
then that among fresh animals. LC50 6.8 ppm C-ll
repeat (27.2 mg/m3), LC5 (est.) 4.8 ppm (19.2 mg/m3),
LC95 (est.) 9.5 ppm (38.0 mg/m3) 2 animals
remained alive through 8th day of exposure
indicating exceptional resistance.
Up to 90 h After 20 h, 3 g-p.'s found dead (13.5 ppm Pattle et al.
H2S04). After 90 h, the remaining g.p.'s (1956)
were found dead. These animals showed C-ll
typical post-mortem appearance.
Continuous 4 d Bronchial and alveolar levels focally dam- Schwartz
aged. Regions of edema, fibrinoid necrosis et al. (1977)
of alveolar septae and inflammatory cell in- A-17
filtration were present.
Continuous 7 d One animal died. Schwartz et al.
(1979)
C-12
* Clean: Wire-mesh cages above l-in.-deep pans of 10% H2S04 to reduce concentration of NH3 present from droppings.
-------
TABLE III-9. GPG--REP. DOSE (continued)
Compound(s)
and Concen-
tration^) in
mg/m3
H2S04
58
H2S04
52
H2S04
47
H2S04
38
H2S04
38
H2S04, 30.0
Humidity/
Particle
Size
50%
S 0.73 Mm
50%
S 0.46 Mm
0.40 pm
(MMAD)
Up to 60%
0.31 Mm
(MMAD)
0.40 Mm
(MMAD)
55%
0.83 pm
(MMD)
Mode of
Exposure
Exposure
chamber
Exposure
chamber
Exposure
chamber
4.2 m3
Exposure
chamber
4.2 m3
Exposure
chamber
4.2 m3
Inhala-
tion
chamber
Species/ Duration &
Strain/ Test Nos. of Frequency Total
Age/ Animals Controls of Length
Weight M F M F Exposure of Expt. Effects
Guinea 6 Not Not given. Not Three guinea pigs died after 1 wk.
pigs given Continuous? given
Guinea 6 Not Not given Not Three guinea pigs died after 1 wk.
pigs given Continuous? given
Guinea 10 Continuous 7 d No deaths
pigs
Charles
River
Hartley
albino
51-65 d
410 g avg.
wt.
Conven- 6 6 Continuous 7 d Minimal changes in variability in density
tional and length of cilia, mainly at sites of
and SPF airway bifurcation.
albino
Hartley
guinea
pigs, 400-
800 g
Guinea 10 Continuous 7 d No deaths
Pigs •
Charles
River
Hartley
albino
51-65 d
410 g avg.
wt « '
Guinea 20 20 5 d 7 d Death occurred within 7 d due to severe
pigs pulmonary edema, hemorrhage, and diffuse
Charles acute aveolitis.
River
Hartley
strain,
250-300 g
Reference
and Rating
Freeman and
(1976)
D—
Freeman and
(1976)
D--
Schwartz et
(1979)
C-12
Schwartz et
(1977)
A-17
Schwartz et
(1979)
C-12
Cavender et
(1977)
B-13
Juhos
Juhos
al.
al.
al.
al.
-------
TABLE III-9. GPG--REP. DOSE (continued)
Compound (s)
and Concen-
tration(s) in
mg/m3
H2S04
3.87-
27.09
(0.9-6.3 ppm)
H2S04
25.0
H2S04
21.20
H2S04
20.0
Humidity/
Particle
Size
80%
0.8 pm
(HMD)
.
50-60%
1 pm
(HMD)
Not
given
(fine)
55%
0.53 Mm
(HMD)
Mode of
Exposure
Exposure
chambe r*
Inhala-
tion
chambers
Exposure
chambers
Inhala-
tion
chamber
Species/ Duration &
Strain/ Test Nos. of Frequency Total
Age/ Animals Controls of Length
Weight M F M F Exposure of Expt.
Guinea 10 96 h
pigs
200-250g
Guinea 10 10 10 10 6 h/d 2 d
Pigs,
Hartley
' strain,
3-4 wk
old
Guinea 4 old Not Continuous 45 d
pigs 6 young given
old:
>6-8 raos
young :
<6-8 mos
'
Guinea 20 20 28 d
pigs
Charles
River
Hartley
strain,
250-300 g
Reference
Effects and Rating
After 20 h, no g.p.'s dead (H2S04, 0.9 ppm). Pattle et al.
After 90 h, the animals appeared normal (1956)
(5.1 ppm free NH3 present). Survivors C-ll
were removed after 96 h and killed in 2
batches (96 & 120 h after exposure).
Autopsy revealed only one gross lung con-
gestion in one animal and some congestion in
all animals, possibly due to inhalation of
acid particles. Max. concentration of acid
was 6.3 ppm.
Segmented alveolar hemorrhage, type 1 Cockrell
pneumocyte hyperplasia, and proliferation et al. (1978)
of pulmonary macrophages. C-8
\
Of these old animals killed during exposure, Thomas et al.
histological effects included hyperemic (1958)
lungs, focal congestion, and desquamated B-ll
epithelial cells with continuum of epithe-
lium broken. The young animals killed dur-
ing exposure exhibited edematous and hyper-
emic lungs, capillary hemorrhages, cellular
exudation, and desquamation of bronchial epi-
thelium. All of these conditions were more
serious than in the older animals. For those
animals that survived, similar symptoms were
seen but as tha length of time beyond exposure
increased (before killing), the severity of
the conditions decreased. The intermediate
aerosol seemed to have a much more significant
effect than either the fine or coarse aerosols.
Diffuse, regional, non-suppurative Cavender et al.
alveolitis, septal edema, and areas (1977)
of hemorrhage in lungs. B-13
* Ordinary: Solid floor cages cleaned once a day.
-------
TABLE III-9. GPG--REP. DOSE (continued)
Compound (s)
and Concen-
tration^) in
mg/m3
H2S04
20.0
H2S04
20 . 0
H2S04
16
H2S04
12
H2S04
10.0
H2S04, 10.0
03, 2.0 ppm
Humidity/
Particle
Size
55%
0.99 Mm
(MMD)
55%
1.66 pm
(MMD)
40-45%
1 Mm
50%
1 pm
55%
0.93 Mra
(MMD)
55%
0.99 M"i
(MMD)
Mode of
Exposure
Inhala-
tion
chamber
<
Inhala-
tion
chamber
,
Exposure
chamber
Exposure
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Species/ Duration &
Strain/ Test Nos. of Frequency Total
Age/ Animals Controls of Length
Weight M F M F Exposure of Expt.
Guinea 20 20 28 d
pigs
Charles
River
Hartley
strain,-
250-300 g
Guinea 20 20 28 d
Pigs
Charles
River
Hartley
strain,
250-300 g
Guinea ,14 Continuous 72 h
pigs
1-2 mo.
250 g
Guinea 18 Continuous 72 h
pigs
1-2 mo.
250 g ,
Guinea 60 20 7 d
pigs
Charles
River
Hartley
strain,
250-300 g
Guinea 20 20 7 d
pigs
Charles
River
Hartley
strain,
250-300 g
Effects
Diffuse, regional, non-suppurative
alveolitis, septa] edema, and areas
of hemorrhage in lungs.
Diffuse, regional, non-suppurative
alveolitis, septa! edema, and areas^
of hemorrhage in lungs .
Little or no change in mortality rate
from 8-72 h.
Little change in mortality rate from
8-72 h
No effects observed.
After 2 d, epithelial hypertrophy and
hyperplasia in terminal bronchioles.
Alveolitis and pulmonary edema present.
Reduced body wt. , increased lung/body
wt. ratio. Loss of cilia in bronchi
and fewer goblet cells in trachea.
Reference
and Rating
Cavender et
(1977)
B-13
Cavender et
(1977)
B-13
Amdur et al.
(1952a)
C-6
Amdur et al.
(1952a)
.. C-6
Cavender et
(1977)
. B-13'
Cavender et
(1977)
B-13
al.
al.
al.
al.
-------
TABLE III-9. GP.G--REP. DOSE (continued)
Compound (s)
and Concen-
tration(s) in
mg/m3
H2S04, 10.0
03, 1.0 ppm
H2S04, 8.3
H2S04, 8
S02, 89 ppm
H2S04
5.0
H2S04, 5.0
03, 2.0 ppm
Humidity/
Particle
Size
55%
1.01 (Jm
(HMD)
55%
0.88 Mm
(HMD)
55%
0.94 pro
(HMD)
Mode of
Exposure
Inhala-
tion
chamber
Inhala-
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
• . •
Inhala-
tion
chamber
Species/ Duration &
Strain/ Test Nos. of Frequency Total
Age/ Animals Controls of Length
Weight M F M F Exposure of Expt.
Guinea 20 20 7 d
pigs
Hartley
strain,
250^-300 g
Guinea 4 Continuous 5 d
Pigs
1.5-2 mo.
200-270 g
Guinea 4 8 h
pigs twice--4
d apart
Guinea 60 60 7 d
pigs
Charles
River
Hartley
strain,
250-300 g
Guinea 20 20 7 d
Pigs
Charles
River
Hartley
strain,
250-300 g
. '
Effects
After 2d, epithelial hypertrophy and
hyperplasia in terminal bronchioles.
Alveolitis and pulmonary edema present.
Within 2 h, animals showed increased breath-
ing frequency, one died in 29th h. Others
survived but ate poorly and were sluggish
till end of exposure. Wt. gain significantly
less. Upper respiratory tract lesions sug-
gesting blood or lymph circulation distur-
bances, in early exposure, edema lungs, later
infiltrations around vessels and bronchi and
scleratic changes around vessels. Damage
still 3t after exposure.
Respiratory distress, widespread
hemorrhage, and consolidation in
lungs; weight and growth depressed.
No effects observed.
After 2 d, epithelial hypertrophy and
hyperplasia in terminal bronchioles.
Alveolitis and pulmonary edema present
Reduced body wt., increased lung/body
wt. ratio. Loss of cilia in bronchi
and fewer goblet cells in trachea.
Reference
and Rating
Cavender et al.
(1977)
B-13 ,
Bushtueva
(1957b)
B-10
Amdur
(1954)
B-12
Cavender et al.
(1977)
B-13
Cavender, et al
(1977)
B-13
-------
TABLE III-9. GPG--REP. DOSE (continued)
Compound (s)
and Concen- Humidity/
tration(s) in Particle
rag/ra3 Size
H2S04, 5.0 55%
03, 1.0 ppm 0.75 \im
(MMD)
H2S04) 5.0 55%
03, 1.0 ppm 0.95 pm
(MMD)
H2S04 33%
4.05 ± 1.63 0.5 ± 1.0
Mm (MMD)
H2S04
4.0
H2S04 Not
3.05 given
(medium)
Species/ Duration &
Strain/ Test Nos. of Frequency Total
Mode of Age/ Animals Controls of Length
Exposure Weight M F M F Exposure of Expt.
Inhala- Guinea 20 20 7 d
tion pigs ,
chamber Charles
River '
Hartley
strain,
250-300 g
Inhala- Guinea 20 20 7 d
tion pigs
chamber Hartley
strain, --
250-300 g
Inhala- Guinea ? ? Continuous 7 wk
tion pigs
chamber
Inhala- Guinea 4 ? Continuous 5 d
chamber pigs,
1.5-2 mo.
200-270 g
Exposure Guinea 3 old Not 45 d
chambers pigs 6 young given
old:
> 6-8 mos
"young:
< 6-8 mos
_
Effects
After 2 d, epithelial hypertrophy and
hyperplasia in terminal bronchioles.
After 2 d, epithelial hypertrophy and
hyperplasia in terminal bronchioles.
No significant effects on acid-base chem-
istry of blood or learning as measured by
task performance. Pulmonary resistance
somewhat higher.
During exposure, behavior was normal;
animals ate well and were active. Wt.
gain significantly less. Upper respiratory
tract lesions suggesting blood or lymph
circulation disturbances; in early exposure
some edema, later infiltrations around ves-
sels and bronchi and sclerotic changes
around vessels. Some regeneration 3 wk
after exposure.
Of those animals killed during exposure,
histological effects included hyperemic
lungs, focal congestion, and desquamated
epithelial cells with continuum of epi-
thelium broken. The young animals killed
during exposure exhibited edematous and
hyperemic lungs, capillary hemorrhages,
cellular exudation, and desquamation of
bronchial epithelium. All of these condi-
tions were more serious than in the older
animals. For those animals that survived,
similar symptoms were seen but as the length
Reference
and Rating
Cavender et al .
(1977)
B-13
Cavender et al.
(1977)
B-13
Lewkowski
et al. (1979)
A-ll
Bushtueva
(1957b)
B-10
Thomas et al.
(1958)
B-ll
of time beyond exposure increased (before kill-
ing), the severity of the conditions decreased
The intermediate aerosol seemed to have a much
more significant effect than either the fine
or coarse aerosols.
-------
TABLE III-9. GPG—REP. DOSE (continued)
Compound(s)
and Concen-
tration(s) in
mg/m3
H2S04
2.49 ±0.4
H2S04
2.21
^
H2S04
2.0
Species/ Duration &
Humidity/ Strain/ Test Nos. of Frequency Total
Particle Mode of Age/ Animals Controls of Length
Size Exposure Weight M F M F Exposure of Expt.
44% Inhala- Guinea ? ? Continuous 8 wk
< 0.24 Mm tion pigs
(HMD) chamber
Not given Exposure Guinea 4 old Not Continuous 45 d
(coarse) chambers pigs 2 young given
Various
ages i
old:
>6-8 mos
young:
<6-8 mos
Inhala- Guinea 4 ? Continuous 5 d
tion pigs,
chamber 1.5-2 mo,
200-270 g
Effects
No significant effects on acid-base chem-
istry of blood or lung function.
Of those old animals killed during exposure,
histological effects included hyperemic lungs
focal congestion, and desquamated epithelial
cells with continuum of epithelium broken.
The young animals killed during exposure ex-
hibited edematous and hyperemic lungs, cap-
illary hemorrhages, cellular exudation, and
desquamation of bronchial epithelium. All
of these conditions were more serious than in
the older animals. For those animals that
survived, similar symptoms were seen; but as
the length of time beyond exposure increased
(before killing), the severity of the condi-
tions decreased. The intermediate aerosol
seemed to have a much more significant effect
than either the fine or coarse aerosols.
During exposure behavior was normal, ani-
mals ate well and were active. Wt. gain •
significantly less. Upper respiratory
tract lesions suggesting blood or lymph
circulation disturbance; in early exposure
some edema, later infiltrations around
vessels and bronchi and sclerotic changes
around vessels. Some regeneration 3 wk
after exposure.
Reference
and Rating
Lewkowski
et al. (1979)
A-ll
Thomas et al.
,(1958)
B-ll
Bushtueva
"(1957b)
B-10
-------
TABLE III-9. GPG--REP. DOSE (concluded)
Compound(s)
and Concen- Humidity/
tration(s) in Particle Mode of
rag/m3 Size Exposure
H2S04, 1.91 Exposure
After 2 wk of chamber
pre-albumin -"
exposure,
each exposure
followed by anti-
gen (albumin)
aerosol, 216;
at end of expt. :
acetylcholine
spray at 0.4
rag/ml (concen-
tration chosen
to elicit asth-
ma attacks in 1
or 2 animals in
the control
groups) for 10
min.
H2S04, 1.89 Exposure
S02, 145 ppm. chamber
After 2 wk of
pre-albumin
exposure, each
exposure was
followed by
30-min albumin
aerosol, 216;
at end of
expt. : acetyl-
choline spray,
0.4 mg/ml for
10 min.
H2S04 40% Head
1.3 0.96 pm only
(MMAD)
Species/ Duration &
Strain/ Test Nos. of Frequency Total
Age/ Animals Controls of Length
Weight M F M F Exposure of Expt.
Hartley 12 12 30 min 5 wk
strain twice/wk (2 wk
adult solely
guinea H2S04)
pigs
Hartley 12 12 30 min, 5 wk
strain twice/wk (2 wk
adult solely
guinea H2S04
pigs t S02)
Hartley 5 5 10
strain
guinea
Pigs,
1.5-3 mo
Effects
Significant change in breathing patterns
on the 5th exposure. After acetylcholine
exposure, 7/12 showed some signs of
forced breathing. Apnea and/or dyspnea
occurred in 2 of the 12, whereas this oc-
curred in 1 of the 12 controls.
V
Significant change in breathing patterns
after 5th, 7th, and 8th exposures. After
acetylcholine exposure, 8/12 showed some
signs of forced breathing. Apnea and/or
dyspnea occurred in 7 of the 12
/'
,
Decrease in all pulmonary parameters, only
significant in peak expiratory flow.
Reference
and Rating
Kitabatake et al.
(1979)
A-ll;
Japanese
version:
Kitabatake
(1976)
Kitabatake et al.
(1979)
A-ll;
Japanese version
Kitabatake
(1976)
Silbaugh et al.
(1980); Silbaugh
et al. (to be
published)
C-12, C-12
-------
TABLE 111-10. GUINEA PIGS—CHRONIC EXPERIMENTAL EXPOSURE TO H2S04
Compound (s)
and Concen
tration(s) in
mg/m3
H2S04
10.34
H2S04, 9.98
03, 0.52 ppm
H2S04
2.74
H2S04
2.10
H2S04
2.06
H2S04
2.04
H2S04
1.46
Humidity/
Particle
Size
63%
0.83 Mm
(50% EAD)
56%
1.38 pm
(50% EAD)
Not
given
Not
given
(medium)
Not
given
(medium-
coarse)
Not
given
(fine)
Not
given
(fine)
Mode of
Exposure
Inhala-
tion
chamber
Inhala-
tion
chamber
Exposure
chambers
Exposure
chambers
Exposure
chambers
Exposure
chambers
Exposure
chamber
Species/ Duration &
Strain/ Test Nos. of Frequency Total
Age/ Animals Controls of Length
Weight M F M F Exposure of Expt.
Guinea 35 35 35 35 6 h/d, 6 mo
pigs 5 d/wk
Hartley
strain
250-300 g
Guinea 35 35 35 35 6 h/d, 6 mo
pigs 5 d/wk
Hartley
strain j
250-300 g
Guinea 3 old Not Continuous 140 d
pigs 7 young given
old:
>6-8 mo
young :
<6-8 mo
Guinea 8 old Not Continuous 130 d
pigs 8 young given
old:
>6-8 mo
young:
<6-8 mo
Guinea 8 young Not Continuous 130 d
pigs given
old:
>6-8 mo
young:
<6-8 mo
Guinea 8 young Not Continuous 130 d
pigs given
old:
>6-8 mo
young :
<6-8 mo
Guinea 5 old Not Continuous 139 d
pigs 10 young given
old:
>6-8 mo
young :
<6-8 mo
Effects
Mild tracheal changes, minimal prolif-
eration of alveolar macrophages.
Weight unaffected.
Lesions near terminal bronchioles of
lungs. Epithelium was hypertrophied,
hyperplastic; alveolar macrophages pre-
sent. Slight loss of cilia in bronchi
and trachea. Weight unaffected.
Number and discreteness of lymphocytic-
histocytic foci in lungs were reduced
from those of control; mucus decreased
in larynx in major bronchi. In minor
bronchi, there was less spasm than in
controls.
Slightly edematous lungs, desquamated epi-
thelial cells in minor bronchi, reduced
amount of mucus and less spasm than con-
trols in major and minor bronchi.
Slight edema of the larynx-.and trachea, de-
crease in mucus in major bronchi compared
to controls. Decrease in lymphocytes in
lymphatic channels.
Number and discreteness of lymphocytic-
histocytic foci in lungs were reduced
compared to control values. Mucus de-
creased in larynx in major bronchi.
In monor bronchi, there was less spasm
than in controls.
Number and discreteness of lymphocytic-
histocytic foci in lungs were reduced
compared to control values. Mucus de-
creased in larynx in major bronchi.
In minor bronchi there was less spasm than
in controls.
Reference
and Rating
Cavender et al.
(1978c)
B-ll
Cavender et al.
(1978c)
B-ll
Thomas et al.
(1958)
B-ll
Thomas et al.
(1958)
B-ll
Thomas et al.
(1958)
B-ll
Thomas et al.
(1958)
B-ll
Thomas et al.
(1958)
B-ll
-------
TABLE 111-10. GPG--ACUTE TESTS (concluded)
oo
Compound (s)
and Concen
tration(s) in
mg/m3
H2S04
.1.15
H2S04, 0.9 ±
0.30
H2S04
0.10
H2S04
0.08
H2S04, 0.08 ±
0.03
Fly ash,
0.46 ± 0.15
H2S04, 0.08 ±
0.03. Fly ash,
0.45 ± 0.14
Humidity/
Particle
Size
Not
given
(coarse)
50 ± 5%
0.49 ±
0.2 Mm
50% ± 5%
2.78 ±
1.07 Mm
(HMD)
50% ± 5%
0.84 ±
0.60 Mm
(MUD)
0.54 ±
0.2 Mm
3.50 ±
2.6 Mm
50 ± 5%
2.23 ±
0.5 |Jm
5.31 ±
3.2 Mm
Mode of
Exposure
Exposure
chamber
Exposure
chamber
Exposure
chamber
Exposure
chamber
Exposure
chamber
Exposure
chamber
Species/
Strain/
Age/
Weight
Guinea
pigs
old:
>6-8 mo
young:
<6-8 mo
Guinea
pigs
Guinea
pigs
Hartley
strain
Guinea
pigs
Hartley
strain
Guinea
pigs
Guinea
pigs
Duration &
Test Nos . of Frequency
Animals Controls of
M F M F Exposure
5 old Not Continuous
10 young given
50 50 50 50 22 or 23
h/d
50 50 50 50 22 or 23
h/d
50 50 50 50 22 or 23
h/d
50 50 50 50 22 or 23
h/d
50 50 50 50 22 or 23
h/d
-- -
Total
Length
of Expt. Effects
139 d Slight edema of the larynx and trachea, de-
crease in mucus in major bronchi. Decrease
in lymphatic channels.
12 mo No detrimental effects on growth rate,
survival, or organs.
12 mo No significant hematological effect. No
microscopic lung alterations after 12 or 52
wk exposure. Females had significantly
lower growth rates than controls.
12 mo No significant hematological effect.
No microscopic lung alterations after
12 or 52 wk exposure. Females had
significantly lower growth rates than
controls.
12 mo No detrimental effects on growth rate,
survival, or organs.
12 mo No detrimental effects on growth rate,
survival, or organs.
Reference
and Rating
Thomas et
(1958)
B-ll
Alarie et
(1975)
A-15
Alarie et
(1973)
A-15
Alarie et
(1973)
A-15
Alarie et
(1975)
A-15
Alarie et
(1975)
(A-15)
al.
al.
al.
al.
al.
al.
-------
TABLE III-ll. RABBITS—ACUTE EXPERIMENTAL EXPOSURE TO H2S04
Compound (s)
and Concen-
tration^) in
mg/m3
H2S04
1,610
H2S04
1,470
H2S04
718
H2S04
699
H2S04
549
H2S04
461
H2S04
218
Humidity/
Particle
Size
<2.0 pm
<2.0 pm
<2.0 pm
<2.0 pm
<2.0 pm
<2.0 pm
<2.0 pm
Species/
Strain/ Test Nos. of
Mode of Age/ Animals Controls
Exposure Weight M F M F
Inhala- Rabbits 2
tion
chamber
Static?
Inhala- Rabbits 2
tion
chamber
Static?
Inhala- Rabbits 2
tion
chamber
Static?
Inhala- Rabbits 2
tion
chamber
Static?
Inhala- Rabbits 2
tion
chamber
Static?
Inhala- Rabbits 2
tion
chamber
Static?
Inhala- Rabbits 2
tion
chamber
Duration &
Frequency Total
of Length
Exposure of Expt.
7 h,
once
3.5 h,
once
3.5 h,
once
7 h,
once
3.5 h,
once
7 h,
once
7 h,
once
Effects
One animal died. In lungs, edema,
pulmonary hemorrhage, extensive lung
damage and degenerative changes in
lung, larynx, and trachea surface cells.
One animal died. Extensive lung damage,
hemorrhage, edema; degeneration changes
in lung, larynx, and trachea surface
cells.
No deaths. Lung hemorrhage and
edema; extensive degenerative changes
in lung, larynx, and trachea surface
cells.
No deaths . Hemorrhage and edema in
lungs and extensive degenerative
changes in lung, larynx and trachea
surface cells.
No deaths. In lungs, hemorrhage and
edema and extensive degenerative changes
in lung, larynx, and trachea surface
cells.
No deaths. In lungs, hemorrhage, edema
and extensive degenerative changes in
lung, larynx, and trachea surface cells.
No deaths. Areas of hemorrhage, edema,
and degenerative changes of surface cells
of lungs.
Reference
and Rating
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8
Static?.
-------
TABLE III-ll. RBT--ACUTE TESTS (concluded)
Compound (s)
and Concen- Humidity/
tration(s) in Particle
mg/m3 Size
H2S04 <2.0 \im
190
H2S04 <2.0 (Jm
87
Mode of
Exposure
Inhala-
tion
chamber
Static?
Inhala-
tion
chamber
Static?
Species/
Strain/
Age/
Weight
Rabbits
Rabbits
Duration &
Test Nos. of Frequency Total
Animals Controls of Length
M F M F Exposure of Expt. Effects
2 7 h, No deaths. Minimal lesions and de-
once generative changes in surface cells
of lungs.
2 2.75 h, No deaths. Minimal lung lesions and
once degeneration of surface cells.
Reference
and Rating
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8
00
o
-------
TABLE 111-12. RABBITS—REPEATED DOSE EXPERIMENTAL EXPOSURE TO H2S04
00
Compound(s)
and Concen- Humidity/
tration(s) in Particle
rag/m3 Size
H2S04 <2.0 pm
1,160
H2S04 <2.0 \ua
839
H2S04 <2.0 Mm
670
H2S04 <2.0 Mm
383
H2S04 <2.0 Mm
203
Species/
Strain/
Mode of Age/
Exposure Weight
Inhala- Rabbits
tion
chamber
Static?
Inhala- Rabbits
tion
chamber
Static?
Inhala- Rabbits
tion
chamber
Static?
Inhala- Rabbits
chamber
Static?
Inhala- Rabbits
tion
chamber
Duration &
Test Hos. of Frequency Total
Animals Controls of Length
M F M F Exposure of Expt.
2 7 h/d 4 d
"2 7 h/d 3d
2 7 h/d 2 d
2 7 h/d 5 d
2 7 h/d 5 d
k
Effects
Both animals died. Extensive lung
damage, hemorrhage, edema; degener-
ation changes in lung, larynx, and
trachea surface cells.
No deaths. Extensive lung hemorrhage
and edema and degenerative changes in
lungs, larynx, and trachea surface
cells.
No deaths. Lung hemorrhage, edema, and
extensive degenerative changes in lung,
larynx, and trachea surface cells.
Both animals died. Areas of hemorrhage,
edema, and degenerative changes of sur-
face cells in lungs.
No deaths. Areas of hemorrhage, edema,
and degenerative changes in surface
cells of lungs.
Reference
and Rating
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8
Treon et al.
(1950)
A-8
Static?
-------
TABLE III-13. CAT—ACUTE EXPERIMENTAL EXPOSURE TO H2S04
Corapound(s)
and Concen-
tration(s) i
mg/m3
H2S04
461
Humidity/
Particle
Size
< 2.0
Inhala-
tion
Chamber
Static?
Species/
Strain/
Age/
Weight
.Cat
Test
Animals
Nos. of
Controls
F M
Duration &
Frequency
of
Exposure
7 h, once
Total
Length
of Expt.
Effects
Damage to lungs, areas of emphysema,
hemorrhage, edema, and degenerative
changes in surface cells.
Reference
and Rating
Treon et al.
(1950)
A-8
oo
-------
TABLE III-14. MONKEYS—ACUTE AND REPEATED DOSE EXPERIMENTAL EXPOSURE TO H2S04
00
Compound (s)
and Concen-
tration(s) in
rag/m3
H2S04
502
H2S04
361
H2S04
150
H2S04, 2.5
H2S04, ~ 1
03, 0.5 ppm
S02, 5.0 ppm
Humidity/
Particle
Size
Up to 60%
0.48 M"i
(MMAD)
Up to 60%
0.43 Mm
(MMAD)
Up to 60%
0.3-0.5 M"1
(CMD)
40%
0: 4 M>n
(MMAD)
40 ± 5%
31 ± 1°C
0.5 Mm
MMAD
Mode of
Exposure
Exposure
chamber
Exposure
chamber
Exposure
chamber
Exposure
hood
Exposure
chamber
Species/
Strain/ Test
Age/ Animals
Weight M F
Rhesus 2
monkeys
(Macaca
mulatta)
Rhesus ' 2
monkeys
Rhesus 2
monkeys
Squirrel 6
monkeys
(Saimiri
sciureus)
Squirrel 5
monkeys
(Saimiri
sciureus)
Duration &
Nos. of Frequency
Controls of
M ' F Exposure
7 d, once
7 d, once
3 d, once
Each .2 h, once
served
as its
own
control
Probably 2 h, once
served
as own
control
Total .
Length
of Expt. Effects
No morphological alterations.
No morphological alterations
No morphological alterations.
No significant changes in respiratory
' resistance.
2 d No effects noted in total respiratory re-
(sham sistance or in irritant response signs
exposure (coughing, sneezing, lachrymation, tachyp-
on day nea, agitation).
D
Reference
and Rating
Schwartz et
(1977)
A-17
Schwartz et
(1977)
A-17
Schwartz et
(1977)
A-17
Hackney et
(1978)
C-ll
Kleinman et
al.
al.
al.
al.
al.
(1979) (1981)
A-14
-------
TABLE 111-15. MONKEYS—CHRONIC EXPERIMENTAL EXPOSURE TO H2SO,,
00
-is
Compound (s)
and Concen-
tration(s) in
mg/m3
H2S04
4.79
H2S04
2.43
H2S04
1.0
N02
5 . 0 ppm
H2S04
1.0
N02
1 . 0 ppm
II2S04
•1.0
H2S04, 0.99
± 0.29
Fly ash, 0.55
±0.38
Humidity/
Particle
Size
50 ± 5%
0.73 M"i
(HMD)
-
50 ± 5%
3.0 pm
(HMD)
2-4 pm
(HMD)
2.4 pm
(HMD)
S
2-4 Mm
(HMD)
50 ± 5%
0.64 ±
0.3 pm
(MUD)
5.34 ±
2.8
Mode of
Exposure
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Species/ . Duration &
Strain/ Test Nos. of Frequency Total
Age/ Animals Controls of Length
Weight M F M F Exposure of Expt.
Cynomol- 9 9 > 23 h/d 78 wk
gus
monkeys
(Macaca
irus)/
young/
1.7-5.3 kg
Cynomol- 9 9 > 23 h/d 78 wk
gus continuous
monkeys
Cynomol- 4 54 5 22-23 h/d 26 wk
gus 7 d/wk
monkeys
(Macaca
fascicularis)
2.0-3.8 kg
Cynomol- 4 54 5 22-23 h/d 26 wk
gus 7 d/wk
monkeys
2.0-3.8 kg
Cynomol- 4 54 5 22-23 h/d 26 wk
gus 7 d/wk
monkeys
2.0-3.8 kg
Cynomol- 9 9 >23 h/d 78 wk
gus monkeys
3.0 ± 0.3 kg
Effects
No significant hematological effect. Mor-
phological changes in the lungs. At highest
concentrations, there were changes regardless
of particle size. Major findings include
Reference
and Rating
Alarie et
al. (1973)
A- 15
bronchiolar epithelia, hyperplasia, and thicken-
ing of the respiratory bronchioles.
No significant hematological effect. Mor-
phological changes in the lungs. At highest
concentrations, there were changes regard-
less of particle- size. Major findings in-
clude bronchiolar epithelia, hyperplasia, and
thickening of the respiratory bronchioles.
Alveolar walls were thickened.
No significant changes in pulmonary
function tests, hematological, serum
chemical, or blood gas measurements.
Increased microscopic lung alterations
from exposure to N02 only. Airway
disease and alveolitis present.
No significant changes in pulmonary ^
function tests, hematological, serum
chemical, or blood gas measurements.
Detrimental effects detected; increased
pulmonary flow resistance. Microscopic
alterations in the lungs.
Alarie et
al. (1973)
A-15
Coate et al.
(1975)
B-12
Coate et al.
(1975)
B-12
Coate et al.
(1975)
B-12
Alarie et al.
(1975)
A-15
-------
TABLE III-15. MKY--CHRONIC (continued)
00
Ul
Compound (s)
and Concen
tration(s) in
mg/m3
H2S04, 0.97
± 0.28
S02, 5.23
±0.45 ppm
H2S04, 0.93
S02, 0.99 ppm
H2S04, 0.88
S02, 1.01 ppm
Fly ash, 0.41
/
H2S04
0.5
N02
5.0 ppra
H2S04
0.5
N02 ^
1 . 0 ppm
H2S04
0.5
H2S04
0.48
H2S04
0.38
Humidity/
Particle
Size
50 ± 5%
0.52 ±
0.2 pm
(HMD)
50 ± 5%
0.50 pm
(MMD)
50 ± 5%-
0.54 pm
(MMD)
2-4 pm
(MMD)
2-4 pm
(MMD)
2-4 pm
(MMD)
50 ± 5%
0.54 pm
(MMD)
50 ± 5%
2.15 pm
(MMD)
Mode of
Exposure
Exposure
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber '
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Inhala-
tion
chamber
Species/
Strain/ Test Nos. of
Age/ Animals Controls
Weight M F M F
Cynomol- 4 54 5
gus or or
monkeys 5 45 4
(Macaca
irus)
3.5 ±
0.3 kg
Cynomol- 9 9
gus monkeys
3.4 ± 0.3
kg
Cynomol- '9 9
gus monkeys
3.3 ± 0.4
kg
Cynomol- 4 54 5
gus
monkeys
2.0-3.8 kg
Cynomol- 4 54 5
gus
monkeys
2.0-3.8 kg
Cynomol- 4 54 5
gus
monkeys
2.0-3.8 kg
Cynomol- 9 9
gus
monkeys
Cynomol- 9 9
gus
monkeys
Duration &
Frequency Total
of Length
Exposure of Expt.
22-24 h/d, 18 mo
7 d/wk
>23 h/d 78 wk
>23 h/d 78 wk
22-23 h/d 26 wk
7 d/wk
22-23 h/d 26 wk
7 d/wk
22-23 h/d 26 wk
7 d/wk
>23 h/d 78 wk
>23 h/d 78 wk
Effects
No difference in growth curve from con-
trols. Pulmonary function tests showed
only statistically significant time-related
increases in flow resistance. Values for
hematocrit, hemoglobin, RBC, WBC, lympho-
cytes, and segmented neutrophils were com-
parable in all' groups of monkeys and no
deleterious effect due to exposure could be
detected.
Detrimental effects detected. Micro-
scopic alterations in the lungs char-
acterized by hypertrophy, hyperplasia,
and squamous metaplasia.
Detrimental effects detected. Micro-
scopic alterations in the lungs. De-
leterious histopathological changes in
pulmonary tissues.
No significant changes in pulmonary
function tests, hematological, serum
chemical, or blood gas measurements.
Increased microscopic lung alterations
from exposure to N02 only. Airway
disease and alveolitis present.
No significant changes in pulmonary
function tests, hematological, serum
chemical, or blood gas measurements.
No significant hematological effect. Mor-
phological changes in the lungs.
No significant hematological effect. Mor-
phological changes in the lungs. Hyper-
plasia and bronchiole thickening.
Reference
and Rating
Alarie et al.
(1975)
A-15
Alarie et al.
(1975)
A-15
Alarie et al.
(1975)
A-15
Coate et al.
(1975)
B-12
Coate et al.
(1975)
B-12
Coate et al.
(1975)
B-12
Alarie et
al. (1973)
A-15
Alarie et
al. (1973)
A-15
-------
TABLE 111-15. MKY--CHRON1C (continued)
oo
Compound (s)
and Concen
tration(s) in
mg/m3
H2S04, 0.11 ±
0.09
Fly ash,
0.53 ± 0.29
S02) 5.15 ±
0.26
H2S04, 0.11 ±
0.05
S02, 0.89 ±
0.18
H2S04, 0.11 ±
0.05
S02) 0.11 ±
0.05
H2S04, 0.11 ±
0.05
Humidity/
Particle
Size
50 ± 5%
0.75 ±
0.3 Mm
(MUD)
4.11 ±
3.0 pm
(HMD)
50 ± 5%
1.07 ±
0 . 1 M"1
(MMD)
50 ± 5%"
3.11 ±
0.77 Mm
(HMD)
50 ± 5%
3.35 ±
1 . 26 Mm
(HMD)
Mode of
Exposure
Exposure
chamber
Exposure
chamber
Exposure
chamber
Exposure
chamber
Species/ Duration &
Strain/ Test Nos. of Frequency Total
Age/ Animals Controls of Length
Weight M F M F Exposure of Expt.
Cynomol- 4 54 5 22-24 h/d, 18 mo
gus or or 7 d/wk
(Macaca 5454
irus)
3.0 ±
0.4 kg
Cynomol- 454 5 22-24 h/d, 18 mo.
gus or or 7 d/wk
monkeys 5 45 4
(Macaca
irus)
3.3 ±
0.3 kg
Cynomol- 4 54 5 22-24 h/d, 18 ino.
gus or or 7 d/wk
monkeys 5 45 4
(Macaca
irus)
3.3 ±
0.3 kg
Cynomol- 4 54 5 22-24 h/d, 18 mo.
gus or or 7 d/wk
monkeys 5 45 4
(Macaca
irus)
372~±
0.3 kg
Effects
One death in control and one in exposure
group unrelated to exposure. No signifi-
cant changes in pulmonary function tests as
a result of exposure. Increase in pulmonary
resistance of time-related significance
values for hematocrit, hemoglobin, RBC, WBC,
lymphocytes, and segmented neutrophils were
comparable in all groups of monkeys, and no
deleterious effect due to the exposures could
be detected. Minimal subacute bronchiolitis ,
alveolitis, and bronchitis. No significant
difference in growth curves.
No change in growth curve. No alterations
in pulmonary functions as a result of ex-
posure. Values for hematocrit, hemoglobin,
RBC, WBC, lymphocytes, and segmented neutro-
phils were comparable in all groups of
monkeys, and no deleterious effect due to
exposure could be detected.
No significant change in growth rate.
Pulmonary function tests showed no sig-
nificant changes. A significant increase
appeared in the number of breaths to wash-
out to 1% N2, measuring distribution of
ventilation. No detrimental effect could
be attributed to this exposure. Hematologi-
cal and biochemical determinations not sig-
nificantly altered.
No change in growth curve. No change in
pulmonary function tests. Hematological
and biochemical determinations not sig-
nificantly different. Some incidental
microscopic changes in lungs.
Reference
and Rating
Alarie et
(1975)
A- 15
Alarie et
(1975)
A-15
Alarie et
(1975)
A-15
Alarie et
(1975)
A-15
al.
al.
al.
al.
-------
TABLE 111-15. MKY—CHRONIC (continued)
00
Compound (s)
and Concen
tration(s) in
mg/m3
S02, 1.04 ±
0.09
H2S04, 0.10 ±
0.03
S02) 0.11 ±
0.01
H2S04, 0.10 ±
0.04
S02, 5.29 ±
0.94
H2S04, 0.10 ±
0.04
Fly ash,
0.44 ± 0.16
S02, 0.12 ±
0.04
H2S04, 0.10 ±
0.04
Fly ash
0.46 ± 0.22
S02, 0.11 ±
0.04
H2S04, 0.10 ±
0.03
Fly ,ash,
0.44 ±
0.18
Humidity/
Particle
Size
50 ± 5%
0.53 ±
0.3 pm
(MMD)
50 ± 5%
1.00 ±
0.3 pm
(MMD)
50 ± 5%
0.54 ±
0.23 pm
(MMD)
4.87 ±
1.90 pm
(MMD)
50 ± 5%
2.73 ±
0.54 pm
(MMD)
4.87 ±
3.12 pm
(MMD)
50 ± 5%
0.71 ±
0.19 pm
(MMD)
5.24 ±
2.34 pm
(MMD)
Mode of
Exposure
Exposure
chamber
Exposure
chamber
Exposure
chamber
Exposure
chamber
Exposure
chamber
Species/ Duration &
Strain/ Test Nos. of Frequency Total
Age/ Animals Controls of Length
Weight M F M F Exposure of Expt.
Cynomol- 4 54 5 22-24 h/d, 18 mo.
gus or or 7 d/wk
monkeys 5454
(Macaca i.
irus)
3.0 ±
0.3 kg
Cynomol- 4 54 5 22-24 h/d, 18 mo.
gus or or 7 d/wk
monkeys 5454
(Macaca
irus) .
3.3 ±
0.2 kg
Cynomol- 4 54 5 22-24 h/d, 18 mo.
gus or or 7 d/wk
monkeys 54.54
(Macaca
irus)
3.6 ±
0.2 kg
Cynomol- 4 54 5 22-24 h/d, 18 mo.
gus or or 7 d/wk
monkeys 5 ,45 4
(Macaca
irus)
3.2 ±
0.3 kg
Cynomol- 4 54 5 22-24 h/d, 18 mo.
gus or or 7 d/wk
monkey 5 45 4
(Macaca
irus)
3.5 ±
0.4 kg
Effects
No change in growth rate. Statistically
significant time-related increase in pul-
monary resistance. All other pulmonary
functions unaffected. Slight microscopic
alterations in tissues and lungs were
present, characterized by minimal bron-
chiolitis, alveolitis, and bronchitis.
No significant difference in growth curves.
Significant time-related increase in pul-
monary resistance. No other pulmonary
function changes. Values for hematocrit,
hemoglobin, RBC, WBC, lymphocytes, and
segmented neutrophils were comparable in
all groups of monkeys and no deleterious
effect due to exposure could be detected.
Minimal subacute bronchitis, alveolitis,
and bronchiolitis.
, No detrimental effects or significant
changes .
No change in growth curve. Pulmonary
function changes insignificant. No
other detrimental effects.
. No significant changes except for an
elevated pulmonary resistance value that
persisted for 30 wk of exposure and began
an apparent decline toward the end of ex-
posure.
Reference
and Rating
Alarie et
(1975)
A-15
Alarie et
(1975)
A-15
Alarie et
(1975)
A-15
Alarie et
(1975)
A-15
Alarie et
(1975)
A-15)
al.
al.
al.
al.
al.
-------
TABLE II1-15. MKY--CI1RONIC (concluded)
Compound (s)
and Concen
tration(s) in
mg/m3
S02, 0.93 ±
0,22
H2S04) 0.09 ±
0.03
Fly ash,
0.48 ± 0.22
S02, 0.84 ±
0.17
H2S04, 0.09 ±
0\04
Fly ash
0.42 ± 0.18
00 H2S04) 0.09 ±
00 0.06
Fly ash,
0.45 ± 0.17
Humidity/
Particle
Size
50 ± 5%
0.64 ±
0.29 pro
(HMD)
5.18 ±
3.12 pra
(HMD)
50 ± 5%
2.37 ±
0.59 urn
4.92 ±
1.09 |Jm
50 ± 5%
2.58 ±
0.64 urn
(MMD)
5.89 ±
3.64 urn
(MMD)
Species/
Strain/
Mode of Age/
Exposure Weight
Exposure Cynomol-
chamber gus
monkeys
(Macaca
irus) •
3.1 ±
0.3 kg
Exposure Cynomol-
chamber gus
monkeys
(Hacaca
irus)
3.0 ±
0.2 kg
Exposure Cynomol-
chamber gus
monkeys
(Macaca
irus)
3.1 ±
0.3 kg
Duration &
Test Nos. of Frequency Total
Animals Controls of Length
M F H F Exposure of Expt. Effects
4 -54 5 22-24 h/d, 18 mo. No detrimental effects or significant
or or 7 d/wk changes.
5 4. 5 4
4 54 5 22-24 h/d, 18 mo No detrimental effects or significant
or or 7 d/wk changes.
5454
-^
4 545 22-24 h/d, 18 mo. No detrimental effects.
or or 7 d/wk
5454
Reference
and Rating
Alarie
(1975)
A-15
Alarie et al.
(1975)
A-15
Alarie et al.
(1975)
A-15
-------
TABLE 111-16. DOGS—ACUTE EXPERIMENTAL EXPOSURE TO H2S04
oo
Compound (s)
and Concen-
tration(s) in
mg/m3
H2S04, 60
(radiolabeled)
H2S04, 40
(radiolabeled)
H2S04
18.0
H2S04
1.6 to 9.3
H2S04
5.3±0.1
H2S04
4.0
H2S04, 1.4 ±
0.2
„
H2S04, 1.12 ±
0.18
-
Humidity/
Particle
Size
1.0 pm
1. 1 pm
0.2 (Jm
(MMAD)
Not given
80%
0.3 pm
(MMAD)
0.2 pm
(MMAD)
80%
0.3 pm
(MMAD)
80%
0.89 pm
(MMAD)
Mode of
Exposure
Nose
only
Nose
only
Not given
Predom-
inantly
nasal
Predomi
inantly
nasal
Predom-
inantly
nasal
Species/
Strain/
Age/
Weight
Dogs,
beagle
Dogs,
beagle
Dogs
-
Dogs
Dogs
Dogs
.
Dogs,
beagle,
3 V,
9.5-12.6
kg
Dogs,
beagle,
3 y,
9.5-12.6
kg
Test Nos. of
Animals Controls
M F M F
Not Not
given given
Not Not
given given
5 Not
given
.
3 5 Each
served
as own
control
3 5 Each
served
as own
control
3 5 Each
served
a s own
control
"
Duration &
Frequency
of
Exposure
57 s,
once
50 s,
once
7.5 rain
4 h
• -
1 h on day
7 of 5th
7-wk cycle
4 h, once
1 h, on
day 7 of
4th 7-wk
cycle. .
1 h, on
day 7 of
1st 7-wk
cycle
Total
Length
of Expt.
v
Not
given
Five
7-wk
cycles
with 4
real and
1 sham ex-
posure*
Five
7-wk
cycles
with 4
real and
1 sham
exposure
Five
7-wk
cycles
with 4
real
and 1
sham
exposure*
Effects
v, • "
H2S04 droplets were deposited in almost
equal amounts in the pulmonary region and
in the upper respiratory tract.
Sulfuric acid droplets were deposited
in almost equal amounts in the pulmonary
region and in the upper respiratory tracts.
No significant changes in respiratory func-
tions or in cardiovascular parameters.
No statistically significant differences
between NaCl and the sulfate aerosols in
respiratory, pulmonary, cardiovascular
parameters measured.
No significant changes at any time.
^-
No significant changes in respiratory
functions.
No significant change in tracheal mucus
clearance. Reddening of pharyngeal,
laryngeal, and tracheal mucosa seen with
0.9-m particles was seldom seen in dogs
exposed to 0.3-(Jm particles.
Tracheal mucus velocities significantly de-
pressed 0.5 h, 1 d, and 1 wk after exposure.
Greater proportion of material left at depo-
sition site than controls (47% vs. 14%) at
1 wk. Recovery at 5 wk postexposure.
Reference
and Rating
Dahl (1979)
B-ll
Dahl (1979)
B-ll
Sackner et
al. (1978b)
A-15
Sackner et al.
(1978a)
D-5
Wolff et al.
(1979c)
B-12
Sackner et
al. (1978b)
A-15
Wolff et al.
(1979c)
B-12
Wolff et al..
(1978b)
B-12; (1979b)
B-12; (1979c)
B-12
Since tracheal mucus clearance returned to normal before the same dog was exposed again, these tests are treated here as acute rather than repeated
dose tests. The sequence of exposures in mg H2S04/m3 (|am) was ~ 1 (-0.9), -0.5 (~0.9), sham, -1 (-0.3), 5.0 (-0.3).
-------
TABLE JII-16. DOG--ACUTE TESTS (concluded)
Compound (s)
and Concen- Humidity/
tration(s) in Particle
rag/m3 Size
H2S04, 0.49 ± 80%
0.18 0.87 pm
(MMAD)
Species/
Strain/ Test Nos. of
Mode of
Exposure
Predomi-
nantly
nasal
Age/ •• Animals Controls
Weight M
Dogs, 3
beagle,
3 y,
9.5-12.6
kg
F M F
5 Each
served
as its
control
Duration &
Frequency
of
Exposure
1 h, on
day 7 of
2nd 7-wk
cycle
Total
Length
of Expt.
Five
7-wk
cycles
with 4
real and
1 sham
exposure
Effects
Nonsignificant increases in mucus velocity
clearance at 0.5 h and 1 day after exposure.
1 wk after exposure significant depression
in clearance. Indication of impairment of
lung defense mechanism following exposure
to low levels of H2S04 mist.
Reference
and Rating
Wolff et al.
(1978b) B-12;
(1979b) B-12;
(1979c) B-12.
* Since tracheal mucus clearance returned to normal before the same dog was exposed again, these tests are treated here as acute rather than
repeated dose tests. The sequence of exposures in mg H2S04/m3 ((Jm) was ~1 (~0.9), -0.5 (-0.9), sham, -1 (-0.3), 5.0 (-0.3).
-------
TABLE III-17. DOGS—REPEATED DOSE EXPERIMENTAL EXPOSURE TO H2S04
Compound (s)
and Concen-
tration(s) in
mg/m3
H2S04
9.5, 11.9
H2S04
10.4, 9.5
with
increased
endogenous
NH3 by in-
fusion of
KH4OAc solu-
tion.
H2S04
6.54
Humidity/
Particle
Size
50%, 0.21,
0.22 pro
(MMAD)
50%, 0.19,
0.21 |Jm
(MMAD)
^
50%
0.19,
0.22 pm
(MMAD)
Species/
Strain/
Mode of Age/
Exposure Weight
Mask. 3-y-old
Dogs beagle
treated dogs
with 0.75
mg/kg ace-
promazine
maleate i.v.
pre-exposure.
Mask. 3-y-old
Dogs beagle
treated dogs
with 0.75
mg/kg
acepromazine
maleate i.v.
pre-exposure
Mask. 3-y-old
Dogs beagle
treated dogs
with 0.75
mg/kg
acepro-
mazine
maleate
i.v.
pre-
exposure
Test Nos. of
Animals Controls
M F M F
9 Each
served
as own
control
9 Each
served
as own
control
9 Each
served
as own
control
Duration &
Frequency Total
of Length
Exposure of Expt. . Effects
20 min/wk 6th wk During exposure, unneutralized H2S04 com-
of 6 wk* prised approximately 25% of the total ex-
haled sulfate. Functional residual capa-
city and residual volume were significantly
lower compared with the comparable exposure
with increased blood ammonia. Closing vol-
umes were increased by the same amount with
normal or increased blood NHs-
20 min/wk 5th wk Increasing the ammonia concentration in
of 6 wk* blood tenfold increased the neutralization
of inhaled H2S04 aerosols to the point that
no unneutralized H2S04 was detected in ex-
haled air during exposure. Decrease in dy-
namic compliance was only significant change
in pulmonary function. Because of the dif-
ferent response patterns seen between clos-
ing volume and measurements of other lung
volumes, the author could make no conclusion
on the effect of increased blood KH3 on the
pulmonary response to inhaled H2S04.
20 min/wk 4th wk Pulmonary function parameters most sensi-
of 6 wk* - live to changes caused by aerosol expo-
sure were closing volume, residual volume,
and functional residual capacity. H2S04 ex-
posures with and without increased blood am-
Reference
and Rating
Loscutoff
(1980a)
A- 15
Loscutoff
(1980a)
A-15
Loscutoff
(1980a)
A-15
monia resulted in nearly identical dose-related
changes in closing volume.
All dogs were exposed to each of 3 concentrations of H2S04 aerosols (0, ~ 6, ~ 12 mg/m3) at ~ 1-wk intervals.
-------
TABLE 111-17. DOG--REP. DOSE (concluded)
Compound (s)
and Concen-
tration(s) in
mg/m3
H2S04, 6.52,
6.54 with
increased
endogenous
NH3 by in-
fusion of
NH4OAc solu-
tion
H2S04
6.3
H2S04
3.5
H2S04
1.0
Humidity/
Particle
Size
50%
0.16,
0.19 (Jm
(MMAD)
Not
given
Not
given
Not
given
Mode of
Exposure
Mask.
Dogs
treated
with 0.75
mg/kg
acepro-
mazine
maleate
i.v. pre-
exposure
Inhala-
tion
chamber
No tran-
quiliza-
tion.
Inhala-
tion
chamber
No tran-
quiliza-
tion.
Inhala-
tion
chamber
No tran-
quiliza-
tion.
Species/
Strain/
Age/
Weight
3-y-old
beagle
dogs
Dogs
Dogs
Dogs
Duration &
Test Nos. of Frequency Total
Animals Controls of Length
M F M F Exposure of Expt. Effects
9 Each 20 min/wk 1st wk Increasing the ammonia concentration in
served of 6 wk* blood tenfold increased the neutralization
as own of inhaled H2S04 aerosols to the point that
control no unneutralized H2S04 was detected in ex-
haled air during exposure.
Not Not Not given During exposure, 26% of exhaled sulfate
given given ' was H2S04. Increased respiration rate,
minute volume, and pulmonary resistance
and decreased dynamic compliance during
exposure. Increased closing volume
measured after exposure.
Not Not Not given Increased pulmonary resistance. All exhaled
given given \ sulfate was an ammonium salt.
Not Not Not given No effect reported. All exhaled sulfate
given given was an ammonium salt.
Reference
and Rating
Loscutoff
(1980a)
A-15
Loscutoff et
al.
(1978) [abstract
only]
A- 6
Loscutoff et
(1978).
A-6
Loscutoff et
(1978)
A-6
al.
al.
All dogs were exposed to each of 3 concentrations of H2S04 aerosols (0, ~ 6, ~ 12 mg/m3) at ~ 1-wk intervals.
-------
TABLE 111-18. DOGS—CHRONIC EXPERIMENTAL EXPOSURE TO H2S04
Compound (s)
and Concen
tration(s) in
mg/ra3
H2S04, 0.904
± 0.288
S02, 5.1 ±
0.4 ppm
H2S04
0.889 ± 0.296
^0
u>
Humidity/
Particle
Size
43-50%
< 0.5 M">
(90%)
43-50%
< 0.5 Mm
(90%)
Mode of
Exposure
Exposure
chamber
Exposure
chamber
Species/
Strain/
Age/
Weight
Dogs ,
purebred
beagles
7-17 kg
Dogs
purebred
beagles
7-17 kg,
i y
Duration &
Test Nos. of Frequency Total
Animals Controls of Length
M
4
4
F M F Exposure of Expt.
8 8 21 h/d 620 d
impaired* and
unimpaired in
each group
4
4
8 8 21 h/d 620 d
impaired*
unimpaired
Effects
Same trends in effects as described below
when H2S04 was used alone. However, the
combination generally produced more pro-
nounced detrimental effects oh each lung
function measurement.
The average response of all pulmonary
function measurements tended to decrease
except for RV/TLC (residual volume - total
lung capacity ratio) and total expiratory
resistance, which are indexes whose in-
crease denotes dysfunction. Previously im-
paired dogs produced abnormally high nitro-
gen washout values . The conducting airways
as well as the lung parenchyma were af-
fected. Statistically significant decreases
for heart and lung weights, which were more
expressed in unimpaired animals. No effect
Reference
and Rating
Lewis et
(1973)
B-10
Lewis et
(1973)
B-10
al.
al.
was noted in hematological variables examined.
H2S04) 0.835
± 0.368
S02, 5.1 ±
0.4 ppm
H2S04
0.755 ± 0.362
•'
43-50%
< 0.5 M"i
(90%)
43-50%
< 5 pm
(90%)
Exposure
chamber
Exposure
chamber
Dogs,
purebred
beagles
7.2-17.7
kg
Dogs
purebred
beagles
7.2-17.7
kg
4
4
8 8 21 h/d 225 d
impaired* and
unimpaired in
each group
4
4
8 8 21 h/d 225 d
impaired*
unimpaired
Lungs previously impaired are less likely to
be altered physiologically by subsequent
toxicants.
Decreased diffusion capacity in both im-
paired and unimpaired dogs, decreased com-
pliance in unexposed dogs, increased lung
resistance in both groups, and decreased
residual volume more pronounced in unim-
paired dogs.
Lower CO-diffusion capacity independent of
N02 impairment. Adverse effects (not sta-
tistically significant) on pulmonary com-
pliance shown on unimpaired dogs.
Lewis et
(1969)
C-9
Lewis et
(1969)
C-9
al.
al.
* Impaired by previous daily exposure to 48.9 mg/m3 (26 ppm) N02, 191 d; verified pathologic lesions resulted.
-------
TABLE. 111-18. DOG—CHRONIC (continued)
Compound (s)
and Concen Humidity/
tration(s) in Particle
mg/m3 Size
Irradiated
auto exhaust
+S02, 1.0 +
0.56
+H2S04
0.11 ±
0.04
Nonirradiated
auto exhaust
+S02, 1.27 ±
0.61
+H2S04, 0.09 ±
0.04
Species/
Strain/ Test Nos. of
Mode of Age/ Animals Controls
Exposure Weight M F M F
Exposure Purebred 12 20
chamber female
dogs =
1 y at
onset of
test
Exposure Purebred 12 20
chamber female
dogs
= 1 y at
onset of
test.
Duration &
Frequency Total
of Length
Exposure of Expt.
16 h/d 68 mo
7 d/wk exposure
plus 32-
36 mo
after
exposure
16 h/d 68 mo
7 d/wk exposure
plus 32-
36 mo
after
exposure
Effects
Following 18 (Vaughan et al., 1969) and 36
mo, no significant changes in pulmonary
function indexes were noted. Higher ex-
piratory resistance than controls at 61 mo
(Lewis et al., 1974). Increased prolyl hy-
droxylase activity. No significant changes
in collagen-protein ratio at sacrifice
(Orthoefer et al., 1976). Carboxyhemoglo-
bin concentrations significantly elevated
after 4 y of exposure (Bloch et al., 1973).
No significant cardiovascular changes in
most dogs after 4.5 and 5 y of exposure
(Bloch et al., 1972).
i
After ~ 3 y of breathing clean air follow-
ing the exposure period, no significant
gross lesions in lungs. Airspace enlarge-
ment and nonciliated bronchiolar cell
hyperplasia in lungs (Hyde et al., 1978).
Little or no pulmonary function impairment
after 18 mo (Vaughn et al., 1969) or 36 mo
(Lewis et al., 1974). At 61 mo, signifi-
cantly higher mean residual volume than in
dogs receiving S02, H2S04, and irradiated
exhaust. Relative pulmonary hyperinfla-
tion (Lewis et al., 1974). No alteration
of prolyl hydroxylase level. No signifi-
cant changes in collagen-protein ratio at
sacrifice (Orthoefer et al., 1976). Car-
boxyhemoglobin concentrations significantly
elevated after exposure for 4 y (Bloch et
al., 1973).
No significant cardiovascular changes in
most dogs after exposure for 4.5 and 5 y
(Bloch et al. , 1972).
After ~ 3 y of breathing clean air follow-
ing the exposure period, no significant
gross lesions in lungs. Significant cili-
Reference
and Rating
Lewis et al.
(1974)
B-9
Bloch et al.
(1973)
D-0
Orthoefer et al.
(1976)
C-5
Vaughan et al.
(1969)
B-12
Bloch et al.
(1972)
B-8
Hyde et al.
(1978)
B-14
Lewis et al.
(1974)
B-9
Bloch et al.
(1973)
D-0
Orthoefer et al.
(1976)
C-5
Vaughan et al.
(1969)
B-12
Bloch et al.
(1972)
B-8
Hyde et al.
(1978)
B-14
ary loss with squamous metaplasia and air-
space enlargement and nonciliated bronchi-
olar cell hyperplasia in lungs (Hyde et
al., 1978).
-------
TABLE 111-18. DOG—CHRONIC (concluded)
Ln
Compound(s)
and Concen Humidity/
tration(s) in Particle
mg/ro3 Size
S02, 1.10 ±
0.57
H2S04, 0.09 ±
0.04
Species/ Duration &
Strain/ Test Nos. of Frequency Total
Mode of Age/ Animals Controls of Length
Exposure Weight M F M F Exposure of Expt. . Effects
Exposure Purebred 12 20 16 h/d 68 mo Little or no pulmonary function impairment
Chamber female 7 d/wk exposure after 18 mo (Vaughn et al., 1969). Follow-
dogs plus 32- ing 36 mo, no statistically significant
= 1 y at 36 mo changes in pulmonary function indexes were
onset of after noted. At 61 mo, the N2 washout value was
test exposure significantly lower than that of the con-
trols (Lewis et al.,. 1974). Minimal
changes in prolyl hydroxylase level. No
significant changes in collagen-protein
ratio at sacrifice (Orthoefer et al., 1976).
No statistically significant effects after
exposure for 4 y (Bloch et al., 1973).
No significant cardiovascular changes in
most dogs after exposure for 4.5 and 5 y
(Bloch et al., 1972).
After ~ 3 y of breathing clean air follow-
ing the 68-mo exposure period, no signifi-
cant gross lesions in lungs. Significant
increased ciliary loss without squamous
metaplasia, air space enlargement, and non-
ciliated bronchiolar cell hyperplasia in
lungs. The lung weight, total lung capac-
ity, and the displaced volume of the pro-
cessed right lung were significantly higher
than in the controls. Enlargement centering
on respiratory bronchioles and alveolar ducts
was considered analogous to an incipient
stage of human proximal acinar emphysema.
Reference
and Rating
Lewis et al.
(1974)
B-9
Bloch et al.
(1973)
D-0
Orthoefer et al.
(1976)
C-5
Vaughn et al.
(1969)
B-12
Bloch et al.
(1972)
B-8
Hyde et al.
(1978)
B-14
-------
TABLE III-19. SHEEP--REPEATED DOSE EXPERIMENTAL EXPOSURE TO H2S04
Compound (s)
and Concen-
tration(s) in
rog/m3
H2S04) 14.0
Humidity/
Particle
Size
0. 12 |Jm
Species/
Strain/
Mode of Age/
Exposure Weight
Sheep
Test Nos. of
Animals Controls
M F M
F
Duration &
Frequency
of
Exposure
Short-term
Total
Length
of Expt.
Effects
No significant changes in tracheal muco-
ciliary transport rate.
Reference
and Rating
Sackner
et al. (1978b)
A- 15
-------
TABLE 111-20. DONKEYS--REPEATED DOSE EXPERIMENTAL EXPOSURE TO H2S04
Compound (s)
and Concen-
tration^) in
rag/m3
H2S04
0.071-1.364
Humidity/
Particle
Size
45%
0.3-0.6
JJ01
(AMD)
Species/
Strain/
Mode of Age/
Exposure Weight
Nasal Donkeys
catheters
(film bag
over
muzzle)
Test Nos. of
Animals Controls
M < F H F
3 1 (Each
animal
was its
own con-
trol)
Duration &
Frequency Total
of Length
Exposure of Expt.
1 h Not
Repeated given
at various
concentra-
with at
least 24 h
clearance
periods be-
tween ex-
posures.
Reference
Effects and Rating
No measurable effect on regional depo- Schlesinger et al
.sition, pulmonary resistance, or dynamic (1978)
compliance. Bronchial mucociliary clear- A-17
ance was' generally slowed. Response to
H2B04 appeared to be erratic with no clear .
dose-response pattern of progressively
lengthening mucociliary clearance rates
with increasing mass concentration of H2S04.
Variability in the degree of neutralization,
by NH3, on different test days could result
in different effective concentrations of
acid depositing in the tracheobronchial tree
of each individual animal.
-------
TABLE 111-21. DONKEYS—CHRONIC EXPERIMENTAL EXPOSURE TO H2S04
Compound (s)
and Concen-
Species/
Humidity/ Strain/ Test Nos . of
tration^) in Particle Mode of Age/ Animals Controls
mg/mj
0.102
for 2 ani-
mals
0.106
for 2 ani-
mals
Size Exposure Weight M
45% Inhala- Donkeys 3
0.5 prn tion
Chamber
F M F
1 Each
served
as own
control
Duration &
Frequency
of
Exposure
1 h/d
5 d/wk
Total
Length
of Expt. Effects
6 mo Bronchial clearance erratic within 1st
wk of exposure. Respiratory rates were
slower than for control days. Two animals
had sustained impairment of clearance with
erratic improvement during 3 mo follow-up
(not preexposed). Two. animals had been
used in previous experiments (preexposed).
Reference
and Rating
Schlesinger
et al. (1979)
A- 16
00
-------
TABLE 111-22. CLEARANCE STUDIES IN RATS AND DOGS AFTER INSTILLATION
vo
Compound (s)
and Concen- Humidity/
tration(s) in Particle
rag/ra3 Size
Rats
H2S04 (radio- Not given
labeled),
477 pmol
H2S04 (radio- Not given
labeled),
94 pmol
H2S04 (radio- Not given
labeled),
72 pmol
H2S04 (radio- 40-60%
labeled in
saline) ,
63 praoles.
1.54 x 10§
dpm
H2S04 (radio- Not given
labeled) ,
carrier-free
"3SS-labeled
\H2S04, 20 pi
for lavage
and gavage,
containing
7.6-3.8 nCi
35S (in-
stilled in
rats under
anesthesia)
Mode of
Exposure
Lung
lavage,
instil-
lation
i.v. in-
stilla-
tion
Lung
lavage,
instil-
lation
Intra-
tracheal
instil-
lation
Intra-
tracheal
instil-
lation
'
Species/ Duration &
Strain/ Test Nos. of Frequency Total
Age/ Animals Controls of Length
Weight M F M F Exposure of Expt.
'
Rats, 3 Not
Fischer- given
344,
200 g
Rat, 3 Not
Fischer- given
344,
280-310 g
Rat, 3 Not
Fischer- given
344,
160-200 g
Rat, . 1 Not
Fischer- given
344
(patho-
gen free),
12-14 wk,
174 g
Rats, 2 Not
Fischer- given
344
(patho-
gen free)
Effects
48 h after administration, the labeled sul-
fate ion was retained primarily in the
trachea, where high endogenous sulfate lev-
els occur.
48 h after administration, labeled sulfate
ion was retained primarily in the trachea,
where high endogenous sulfate levels occur.
48 h after administration, the labeled sul-
fate ion was retained primarily in the
trachea, where high endogenous sulfate lev-
els occur.
Labeled sulfate ion (in the form of H2S04)
showed no sites of concentration of label
in the lung.
- \
H2S04 deposited as a bolus in the lungs of
rats cleared more quickly than when de-
posited in the nose.
'
/
Reference
and Rating
Dahl and Furst
(1979)
B-l"2
Dahl and Furst
(1979)
B-12
Dahl and Furst
(1979)
B-12
Dahl et al.
(1979)
B-9
Dahl (1979)
B-ll
-------
TABLE 111-22. CLEARANCE (continued)
Compound(s)
and Concen- Humidity/
tratipn(s) in Particle
mg/m3 Size
H2S04 (radio-
labeled),
carrier-free
3SS-labeled
H2S04, 20 Ml
for lavage
and gavage,
containing
7.6-3.8 nCi
35S (instilled
in rats under
anesthesia)
H2S04 (radio- Not given
labeled),
carrier-free
35S-labeled
H2S04, 5 Ml
for nasal
instillation,
containing
7.6-3.8 nCi
35S (instilled
in rats under
anesthesia)
Dogs
H2S04, not 0.4 Mm
given (MMAD)
H2S04, not 0.4 M"i
given (MMAD)
Mode of
Exposure
Gavage,
stomach
Nasal
instil-
lation
7th gen-
eration,
bronchi
instil-
lation
2nd gen-
eration,
bronchi
instil-
lation
Species/ Duration &
Strain/ Test Nos. of Frequency Total
Age/ Animals Controls of Length
Weight M F M F Exposure of Expt.
Rats, 1 Not
Fischer- given
344
(patho-
gen free)
Rats, 3 Not
Fischer- given
344
(patho-
gen free)
Dogs, Not Not 8 min, not Not
beagle given given given given
Dogs, Not Not 8 min, not Not
beagle given given given • given
Effects
H2S04 deposited as a bolus in the lung of
rats cleared more quickly than when de-
posited in the nose.
Clearance of H2S04 from the nose was rela-
tively slow compared to pulmonary clearance.
'
Nearly 100% of the instillation dose
cleared to the blood within 10 min of
instillation. Deposition for the aerosol
was mostly in the upper respiratory tract
and not in the lung.
Deposition for the aerosol was mostly in
the upper respiratory tract and not in the
lung.
Reference
and Rating
Dahl (1979)
B-ll
Dahl (1979)
B-ll
Dahl et al.
(1978a);
Dahl et al.
(1978b)
B-9, B-ll
Dahl et al.
(1978a);
Dahl et al.
(1978b)
B-9, B-lt
-------
TABLE 111-22. CLEARANCE (concluded)
Compound(s)
and Concen-
tration(s) in
mg/m3
H2S04, not
given
H2S04, not
given
Humidity/
Particle
Size
0.4 pm
(MMAD)
0.4 pm
(MMAD)
Mode of
Exposure
Tracheal
instil-
ation
Nasal
instil-
lation
Species/
Strain/
Age/
Weight
Dogs,
beagle
Dogs,
beagle
Test
Animals
M F
Not
given
Not
given
Nos. of
Controls
M F
Not
given
Not
given
Duration &
Frequency
of
Exposure
8 min, not
given
8 min, not
given
Total
Length
of Expt.
Not
given
Not
given
Effects
Only 20% of H2S04 deposited above the
carina of the trachea appeared in the
blood at one time. Deposition for the
aerosol was mostly in the upper respira-
tory tract and not the lung.
10 h after exposure, a maximum of 70% of
the instilled dose could be accounted for
in urine and blood combined. In 20 h, lungs
Reference
and Rating
Dahl et al.
(1978a);
Dahl et al.
(1978b)
B-9, B-ll
Dahl et al.
(1978a);
Dahl et al.
were cleared. Deposition for the aerosol (1978b)
was mostly in the upper respiratory tract B-9, B-ll
and not the lung.
-------
SECTION IV
EXPERIMENTAL HUMAN INHALATION EXPOSURES
Tables IV-1 and IV-2 describe acute and repeated dose laboratory human
exposures to sulfuric acid mist, respectively. In Part B of the Summary,
Table S-2 condenses the information regarding exposures at levels lower than
about twice the threshold limit value. [The American Conference of Govern-
mental Industrial Hygienists gives 1.0 mg H2S04/m3 as the time-weighted-
average threshold limit value. There is no short-term-exposure limit for
sulfuric acid (ACGIH, 1979)].
103
-------
TABLE IV-1, HUMANS—ACUTE EXPERIMENTAL INHALATION EXPOSURE TO
Compound (s)
and Concen-
tration^)
in mg/m3
H2S04
~ 40
H2S04
39.4
H2S04
20.8
H2S04
S ~20
-P-
H2S04
5
H2S04
5
H2S04
4.0
H2S04
3.0
Humidity/
Particle
Size
1.0 pm
(HMD)
62%
0.99 urn
(HMD)
91%
1.54 urn
(HMD)
1.5 |Jm
(HMD)
1 Mm
Nos. of
Test Nos. of
Mode of Subjects Controls
Exposure M F M F
Inhala- ?
tion
Exposure 12
chamber
Exposure
chamber
Inhala- ?
tion
Inhala-
tion :
mask
(at rest)
Inhala- 2 Served
tion as own
face control
mask
Inhala- 5
tion
mask
(at rest)
Inhala-
tion
mask
(at rest)
Duration &
Frequency
of
Exposures
1 h
60 min
30 min
1 h
0.25 h,
once
5 min,
once
0.25 h,
once
0.25 h,
once
Total
Length
of Expt. • Effects
Highly irritant to throat; if repeated
coughing occurred, pain developed in upper
chest. Most had no long-term effects; one
"wheezed" for 2 mo.
Initial coughing upon entering chamber.
Increased resistance 35-100%.
Almost intolerable at onset. Intense cough-
ing, lacrimation, rhinorrhea. Increased re-
sistance 43-150%.
Highly irritant to throat; pain developed in
upper chest if repeated coughing occurred.
No long-term effects reported.
Very objectionable to some subjects, less to
others. A deep breath usually produced
coughing. Perceptible to all; changes not
entirely reflex.
Marked decrease in minute volume. One sub-
ject showed an increase in respiratory rate
with a marked decrease in depth of breathing.
In the 2nd subject, both respiration rate
and breathing amplitude decreased.
Tidal volume dropped after 2 min of expo-
sure, remained depressed throughout exposure.
Noticed by odor, taste, or irritation by all
subjects--"felt like breathing dusty air."
Reference
and Rating
Pattle and
Cullumbine
(1956)
A-3
Sim and Pattle
(1957)
B-9
Sim and Pattle
(1957)
B-9
Pattle and
Cullumbine
(1956)
A-3
Amdur et al.
(1952b)
A-ll
Amdur et al.
(1952b)
A-ll
Amdur et al.
(1952b)
A-ll
Amdur et al.
(1952b)
A-ll
(continued)
-------
TABLE IV-1. HUM—ACUTE EXPTL. (continued)
O
Ln
Compound (s)
and Concen-
tration(s)
in mg/m3
H2S04
2.4
H2S04
2.0
H2S04
1.8-2.0
H2S04
0.8-1.4
H2S04,
0.8-1.4
10 breaths
of broncho-
dilator
isopro-
terenol hy-
drochloride
prior to ex-
posure
H2S04
1.1-1.3
Nos. of
Humidity/ Test Nos. of
Particle Mode of Subjects Controls
Size Exposure M F M F
2
1.0 pra Inhala- 1 Served
tion as own
mask controls
(at rest)
3
4.6 (jrn Inhala- 15 Served
tion as own
from controls
mask
through
mouth
4.6 pm Inhala- 15 Served
(CUD) tion as own
from control
mask
through
mouth
Not 3
given
Duration &
Frequency Total
of Length
Exposures of Expt.
4 min &
9 min
at 15th and
60th min of
testing, re-
spectively
0.25 h,
once
5 min,
once
5 min,
once
Effects
Irritant action accompanied by reflex cough,
decreased light sensitivity at both exposures
Normal sensitivity restored in 40-50 min.
Quick increase in respiratory rate, return
to normal slow.
Reflex changes in rhythm and amplitude of
breathing motion. Two of the subjects showed
individual differences in the character of
these changes. Clearly irritant concentration
for all subjects.
Airway resistance increased 3%.
Airway resistance increased 37%.
Irritation noted at the base of the throat.
Also elicited (initially) a slight increase
.
Reference
and Rating
Bushtueva
(1957)
C-7
Amdur et al.
(1952b)
A-ll ~~
Bushtueva
(1957a)
C-7
Toyama and
Nakamura (1964)
B-13
Toyama and
Nakamura (1964)
B-13
Bushtueva
(1957a)
then a lowering in light sensitivity of the
3 subjects. In one subject, there was ob-
served another subsequent increase in light
sensitivity.
C-7
(continued)
-------
TABLE IV-1. HUM—ACUTE EXPTL. (continued)
.
Compound (s)
and Concen-
tration^)
in mg/m3
H2S04
1.2 ± 0.2
H2S04
1
H2S04
1.0
M HZS04
0 j
H2S04
1
H2S04
1.0
Humidity/
Particle
Size
50%
0.6-1.0
pm (MMD)
1 pm
3 pm
(MMD)
70 ± 5%
0.5 pm
(MMD)
~0.1 pm
Mode of
Exposure
Exposure
by mouth
inhalation
Inhala-
tion
mask (at
rest)
Exposure
chamber
Nos. of Duration &
Test Nps. of Frequency
Subjects Controls of
M F M F Exposures
1 Served Not given
as own
control
5? Subject 5 rain,
served once
as own
control
10 Subject . Not given.
served
as own
control
3
10 Each sub- 2 h
non- ject
smoking served as
his own
control
5 normal 10 min,
5 asthmatic once
5 female
5 male
Total
Length
of Expt. Effects
Expired NH3 at time of exposure was 100 ±_
± 25 pg/m3. The molar ratio of NH4+/S042~ at
this time was 0.5, implying that the parti-
cles were an equimolar mixture of NH4HS04 and
H2S04
Threshold of detection in two subjects not
detected by others. Forced expiration some-
times observed. Little change in respiratory
rate or depth of breathing.
Lung clearance was 25% faster. Expired
flow rate was reduced 1.4%.
Above threshold of perception for 2 and
clearly irritant to the 3rd.
0.5-h exercise period at onset of exposure
Half of subjects experienced increase in
respiratory clearance.
3 h No pulmonary function changes, no alterations
in gas transport
Reference
and Rating
Larson et al:
(1977)
C-8
Amdur et al.
(1952b)
A-ll
Wolff et al.
(1977)
B-4
Bushtueva
(1957a)
C-7
Newhouse et al.
(1978)
A-10
Sackner et al.
(1978b)
A-15
(continued)
-------
TABLE IV-1. HUM--ACUTE EXPTL. (continued)
Compound (s)
and Concen- Humidity/
tration(s) Particle
in mg/m3 Size
H2S04, < 25%
NaHS04, 0.5-1 M™
NH4HS04 , MMAD
(NH4)2S04 a 1.5-2.
separately at *
1 as H2S04
Carbachol* 0.8 M™
0.0, 0.025, a 2.2
0.05, 1.0, afg.
and 2.0% in MMAD
80% aqueous
propylene
/ glycol
M -^
O.
'"J
H2S04 1 Mm
< 1
H2S04
0.7-0.96
H2S04 Not given
0.6-0.85
(avg. 0.72)
* Carbachol is choline
for each subject.
the control value.
SG on day 1.
aw *
Mode of
Exposure
, Breathed
through a
respira-
2 tory
valve
Double
blind,
random-
ized
A test
exposure
comprised
5 maximal
inhala-
tions
generated
by a D-31
nebulizer,
each with
5-s breath
holds
Inhala-
tion
mask
(at rest)
Nos. of
Test
Subjects
M F
7?
19-26 y;
normals
unrespon-
sive to
carbachol
concen-
trations
< 1%
15?
2
10
Duration &
Nos . of Frequency
Controls of
M F Exposures
Served as 16 min (1-min
own con- respite halfway
trols through) on day
(NaCl ex- 3 to each test
posures) substance with
£ 3 h between
exposures.
After each
test, exposed
to day 2 level
of carbachol
to see if the
aerosol had po-
tentiating ef-
fect on the
bronchocon-
strictor.
Served 0.25 h,
as own once
con-
trols
4 min &
9 min at
15th and
60th min
respectively
.:
_
Total
Length - Reference
of Expt. Effects and Rating
3 d All of the sulfates produced small, signifi- Morrow et al.
cant changes in the maximum expiratory flow (1980)
volume (MEFR) at 60% total lung capacity B-9
(TLC) and partial expiratory flow volume
(PEFR) at 40 and 60% total lung capacity
when compared to NaCl. The bronchocon-
strictor action of carbachol was potentiated
by the sulfate aerosols in relation to their
acidity. Thus, the most significant changes
(g < 0.01) were seen with H2S04 and NH4HS04.
For H2S04, the percent decrease in SG
(specific airway conductance) was ~ 5% with
a ~ 27% decrease after the carbachol chal-
lenge. The corresponding decreases for
NH4HS04 were ~ 10% and ~ 18%, respectively.
,
Not detectable by odor, taste, or Amdur et al.
irritation. (1952b)
A-ll
Barely significant tickling at base of pharynx Bushtueva
noted by subjects. Well-defined increase in (1957a)
light sensitivity. C-7
Minimum perception accompanied by localized Bushtueva
irritation in the region of the base of the (1957a)
throat. The data support the trigeminal nerve C-7
action of HZS04 aerosol. (Average maximum con-
centration without perception 0:6 mg/m3).
chloride carbamate, a parasympathomimetic. At the start of the study, a dose-response curve to inhaled carbachol was constructed
Each concentration was
On day 2, susceptibles
used sequentially at ~ 10-min
(not yet used in this report)
intervals until the specific airway conductance (SG ) decreased by > 40A of
were reassessed at the concentration that produced a 20 to 30% decrease in
(continued)
-------
TABLE IV-1. HUM--ACUTE EXPTL. (continued)
O
00
.
Compound(s)
and Concen-
tration(s)
in rag/m3
H2S04, 0.75
S02, 1.5
H2S04
0.73-0.75
HZS04, 0.7
S02, 3
H2S04
0.7
H2S04
0.63 or
S02
0.9 or
H2S04
0.6-0.63 or
H2S04, >0.30
+S02, 0.50
Nos. of Duration &
Humidity/ Test Nos. of Frequency Total
Particle Mode of Subjects Controls of Length
Size Exposure M F M F Exposures of Expt.
3 Between 6th
and 9th min.
for 2 rain.
Optical
chronaxy
determined
in each sub-
ject at 3-min
intervals (0,
3, 6, 9, 12, 15
min)
3 Between 6th
and 9th min.
for 2 min.
Optical
chronaxy
determined
in each sub-
ject at 3-min
intervals (0,
3, 6, 9, 12, 15
min) • '
3 4.5 min
' starting at
at the 15th
min.
3 4.5 rain
starting at
the 15th min.
3 Between
6th and 9th
minutes for
2 min. Op-
Reference
Effects and Rating
Obvious synergistic effect when subthreshold Bushtueva
concentration of each combined to cause in- (1961)
crease in optical chronaxy. C-7
Increased optical chronaxy (threshold) Bushtueva
(1961)
C-7
~60% increase in light sensitivity at the Bushtueva
20th min. (1961)
C-7
25% increase in light sensitivity at the Bushtueva
20th min. (1961)
C-7
Threshold of reflex action as determined by Bushtueva
EEC. (1962)
C-6
No significant increase in optical chronaxy Bushtueva
from controls. (1961)
C-7
tical chron-
axy deter-
mined in each
subject at 3-
min inter-
vals (0, 3, 6
9, 12, 15 min)
(continued)
-------
TABLE IV-1. HUM—ACUTE EXPTL. (continued)
Compound (s)
and Concen-
tration(s)
in mg/m3
H2S04
0.6
S02, 1.2
H2S04
0.6
S02
l_i 0.8
0
VO
H2S04
0.6
H2S04
0.6
Nos. of Duration &
Humidity/ Test Nos. of Frequency Total
Particle Mode of Subjects Controls of Length
Size Exposure M F M F Exposures of Expt.
3 Between
6th and 9th
minutes for
2 min.
Optical
chronaxy
determined
in each
subject at
5-min inter-
vals (0, 3, 6
9, 12, 15 min)
3 Between
6th and 9th
minutes for
for 2 min.
Optical
chronaxy
determined
in each sub-
ject at 3 min
intervals (0,
3, 6, 9, 12,
15 min)
3
2 4 min and
and 9 min
at 15th and
60th min,
respectively
Effects
Obvious synergistic effect when subthreshold
concentrations of each combined to cause in-
crease in optical chronaxy. Detailed results
given for only one of the three subjects.
—
Obvious synergistic effect when subthreshold
concentration of each combined to cause in-
crease in optical chronaxy.
Not irritant for 2 and threshold for the 3rd.
Not perceptible to the subjects, barely de-
tectable increase followed by slight decrease
in light sensitivity occurred with 1st ex-
posure but not the 2nd. (Inference is drawn
from a graph. Bushtueva states there was no
change in sensitivity).
Reference
and Rating
Busbtueva
(1961)
C-7
Bushtueva
(1961)
C-7
Bushtueva
(1957a)
C-7
Bushtueva
(1957a)
C-7
(continued)
-------
TABLE IV-1. HUM--ACUTE EXPTL. (continued)
Compound(s)
and Concen-
tration(s)
in mg/m3
H2S04
0.35-0.5
Humidity/
Particle Mode of
Size Exposure
1.0 |Jm Inhala-
tion
mask
(at rest)
Nos. of
Test Nos. of
Subjects Controls
M F M F
15 Served
as own
controls
Duration &
Frequency
of
Exposures
0.25 h,
once
Total
Length
of Expt. Effects
Reflex reaction to irritant stimulant by
change in respiration. After 0.25 h, expo-
sure respiration rate ~ 35% higher than pre-
exposure. Maximum inspiratory and expiratory
Reference
and Rating
Amdur et al.
(1952b)
A-ll
H2S04
0.4
S02
1.2
H2S04, 0.4
S02, 1
H2S04, 0.4
or
S02, 0.6
or
H2S04, 0.30
S02, 0.25
or
H2S04, 0.15
S02, 0.50
H2S04, 0.3
S02( 0.65
Not
given
Between
6th and 9th
minutes for
2 min.
Optical
chronaxy
determined
in each sub-
ject at 3 min
intervals (0, 3,
6, 9, 12, 15 min)
4.5 min
starting
at the
15th min.
flow decreased ~ 15-20% after exposure. Within
3 min after exposure, respiration rate back to
within 13% above control value. Steady increase
in respiratory rate during exposure period. Re-
turn to control shortly after exposure. Five
subjects exhibited above symptoms at 0.35 mg/m3,
5 at 0.4 mg/m3, and 5 at 0.5 mg/m3.
Obvious (insignificant) synergistic effect
when subthreshold concentration of each com-
bined to cause increase in optical chronaxy.
Bushtueva
(1961)
C-7 .
Below odor and irritant detection.
Bushtueva
(1961)
C-7
Threshold of reflex action as determined by Bushtueva
"electrocortical" conditioned reflex response. (1962)
C-6
No change in sensitivity of eye to light at
the 20th min.
Bushtueva
(1961)
C-7
Having a history of respiratory hyperactivity to inhaled irritants.
(continued)
-------
TABLE IV-1. HUH—ACUTE EXPTL. (continued)
Compound (s)
and Concen-
tration(s)
in mg/m3
HjjS04
0.195 ±
0.035
H2S04 0.100
03 0.36 ppm
S02 0.36 ppm
Humidity/
Particle
Size
46 ± 10%
0.055 Mm
(MUD)
40 + 5%
31 + 1°C
0.5 Mm
MMAD
(bimodal
distri-
bution,
one mode
at 0.2 Mm
and a 2nd
-mode at
~ 2 Mm)
Nos. of Duration &
Test Nos. of Frequency
Mode of Subjects Controls of
Exposure M F M F Exposures
Exposure 1 pulmonary function
value. The magnitudes of the decreases were
about the same as those that have been re-
ported from exposure to Os alone, but the
frequency of the decreases was higher. Sig-
nificant decreases were seen in these pulmon-
ary functions: forced vital capacity (FVC) ;
forced expiratory volumes (FEVt, FEV2 , FEV3);
maximum flow rate, VmaxSO (50% FVC), Vmax25
(25% FVC); and vital capacity (from single-
breath N2 washout). The presence of S042
aerosol or S02 may increase the sensitivity
of subjects normally nonreactive to 03 with-
out changing the effects seen in already
reactive individuals.
Reference
and Rating
Gardner et al.
(1978)
A-12
Kleinman et al.
(1979) (1981)
A-14, A-14
(continued)
-------
TABLE IV-1. HUM—ACUTE EXPTL. (continued)
Compound(s)
and Concen-
tration(s)
in mg/m3
H2S04
0.1
H2S04
0.01-0.1
H2S04>
0.01-0.1
10 breaths
of broncho-
dilator
isopro-
terenol hy-
drochloride
prior to ex-
posure
H2S04
0.100 ±
0.014
Humidity/
Particle
Size
~0 . 1 pm
1.8 pm
(CMD)
1.8 pro
(CMD)
46% ± 10%
0.055 pm
(MUD)
Mode of
Exposure
Inhala-
tion
from
mask
through
mouth
Inhala-
tion
from
mask
through
mouth
Exposure
chamber
Nos. of
Test Nos. of
Subjects Controls
M F M F
5 normal
5 asthmatic
9 Served
as own
controls
9 Served
as own
control
10 Each
served
as his
own
control
Duration &
Frequency
of
Exposures
10 min,
once
5 min,
once
5 min,
once
2 h (al-
ternate
15 min pe-
riods of
rest and
exercise)
Total
Length Reference
of Expt. Effects and Rating
No pulmonary function changes, no alterations Sackner et al.
in gas transport. (1978b)
A-15
Airway resistance increased 18%. Toyama and
Nakamura (1964)
B-13
Airway resistance decreased 11%. Toyama and
Nakamura (1964)
B-13
Only two of 18 pulmonary function parameters Gardner et al.
significantly changed, forced expiratory (1978)
volume and airway resistance. A-12
(continued)
-------
TABLE IV-1. HUM—ACUTE EXPTL. (continued)
Compound (s)
and Concen-
tration(s)
in rag/m3
Day 1 am-
bient air
Day 2 0.100
(air for
controls)
Nos. of Duration &
Humidity/ Test Nos. of Frequency
Particle Mode of Subjects Controls of
Size Exposure M F M F Exposures
40% Groups 18 non- 17 non- 4 h/d
22°C of 3 for smokers smokers on Day 2
0.5 pm 2 d be- Avg. height 179.8
MMD ginning cm; avg. weight
at ~ 72.6 kg; avg. age
8:30 AM. 28.0 y
At 0.5
- arid 1.5
h after
exposure
was begun
the sub-
jects en-
gaged in
a 15-min
exercise -^
period:
walking
4 mph on
a tread-
mill in-
clined at
10°. Lung
function
tests
were ad-
ministered
at 0, 2,
and 4 h.
Some ex-
posure
groups
were
tested on
M and Tu,
and some
on W and
Th.
:
Total
Length Reference
of Expt. Effects and Rating
2 d (one ex- No effects were noted on the blood parameters Chaney et al.
posure to measured (serum glutathione, lysozyrae, RBC (1980a)
H2S04) glutathione reductase, serum glutamic oxalo- C-ll
acetic acid transaminase, serum vitamin E,
and 2,3-diphosphoglycerate) due to exposure to
H2S04. The significant post-exposure increase
in GSH-reductase occurring in both air- and
H2S04-exposed groups may have been a response
to [metabolic acidosis resulting from] the
moderate level of exercise required during
the exposure periods.
No effects were seen on pulmonary function
either (function residual capacity, airway
resistance, forced inspiratory volume, forced
vital capacity, vital capacity, and maximum
voluntary ventilation). These results are to
be reported in a separate paper.
Presumably, the subjects were producing suf-
ficient breath NH3 to neutralize the 0.100 mg
H2S04/m3. (Stoichiometrically all the NH3
that is required to neutralize that amount
of H2S04 to NH4HS04 is 0.017 mg/m3. Exhaled
breath of healthy humans contains 0.029 to
~ 2.200 mg NH3/m3.
(continued)
-------
TABLE IV-1. HUM—ACUTE EXPTL. (continued)
Compound (s)
and Concen-
tration(s)
in mg/m3
H2S04
0.098
Humidity/
Particle
Size
60%
0.14 Mm
(HMD)
Mode of
Exposure
Exposure
Chamber
(2-15 min
periods
of bicy-
Nos. of
Test Nos. of
Subjects Controls
M F M F
Smokers Each
11 3 served
Npnsmok- as own
ers control
86
Duration &
Frequency
of
Exposures
4 h on the
2nd of the
3 d
cle exercise
H2S04
0.066
Particulate
S042"
0.0201
Particulate
S042~
0.0165
H2S04
0.01
46 ± 10%
0.055 |Jm
(HMD)
Outside
ambient
air ex-
posure
32%
< 2.4 pin
(MMAD)
~0.1 pm
during
exposure)
Exposure
chamber
Exposure
chamber
(supplied
with pol-
luted am-
bient air)
4 Each
served
as his
own
control
12 12
26 38 26 38
5 normal
5 asthmatic
5 male
5 female
2 h (al-
ternate
15-min pe-
riods of
rest and
exercise)
2 h, once
2 h, once
10 min,
once
Total
Length
of Expt. Effects
Once Pulmonary function studies, pulmonary resi-
within tance and compliance measurements were taken.
a 6 h/d, There were no symptom complaints attributed
3-d to the exposure and no significant changes
period were found in any pulmonary function param-
eters. There were no differences between
smokers and nonsmokers in response to
H2S04 exposure.
Three of 18 pulmonary function parameters
significantly changed. Decreased forced ex-
piratory volume 3%. Increased airway re-
sistance 3.5% and increased functional re-
sidual capacity 10.9%.
Little difference between indoor and out-
door responses (this was a validation
study) .
Responses of asthmatic and normal subjects
were generally not significantly different.
In normal subjects, a small significant in-
crease in reported symptoms was seen with
ambient air exposures compared with control.
Overall, only slight effects attributable to
exposure were found.
Not No pulmonary function change's, no alterations
given in gas transport.
Reference
and Rating
Kerr et al.
(1979)
A-9
Gardner et
(1978)
A-12
Linn et al.
(1980)
C-5
Linn et al
C-5
Sackner et
(1978b)
A-15
al.
. (1980)
al.
(continued)
-------
TABLE IV-1. HUM—ACUTE EXPTL. (continued)
Compound ( s )
and Concen- Humidity/
tration(s) Particle
in Dig/m3 Size
03 35%
0.37 ppm, 88±1°F
then 03 + S02
0.37 pm 'each
(0.4 ppm
nonmethane ,
nonoxygen-
ated hydro-
carbons)
Estimated
that 0.0006
to 0.0015
mg/m3 H2S04
could have
been formed
from S02, 03,
and olefins
03+S02 50%
0.37 ppm each 70°F
(0.4 ppm
nonmethane ,
nonoxygen-
ated hydro-
carbons)
Estimated
that 0.0006 to
0.0015 could
have formed
Nos. of Duration &
Test Nos. of Frequency
Mode of Subjects Controls of
Exposure M F M F Exposures
Environ- 4 normal Served 2 h/d for 1 d
mentally 4 sensi- as own followed by
con- tive* control 2 h/d for 1 d
trolled
chamber;
exercise
0.25 h
in each
0.5 h
to in-
crease
minute
ventil-
lation
2-25 times
more than
at rest
Environ- 4 normal Served 2 h/d
mentally Canadians as own
controlled control
chamber;
exercise
0.25 h in
each 0.5 h 5 sensitives*
from Los Angeles
Total
Length Reference
of Expt. Effects and Rating
4 d (tests Although sham and 03 exposure days did not Bell et al.
preceded by produce statistically different lung function (1977)
2 d of sham values, the forced expiratory function was B-7
exposures) significantly decreased from its value upon
exposure to 03 alone.
1 d Only significant pulmonary function effect Bell et al.
seen was the decreased FEVj in the sensitives. (1977)
,
Having a history of respiratory hyperactivity to inhaled irritants.
(continued)
-------
TABLE IV-1. HUM--ACUTE EXPTL. (concluded)
Corapound(s)
and Concen-
tration(s)
in mg/ra3
03, 0.37 ppm
then
S02,0.37 ppra
then
03 + S02
0.37 ppm each
(03 + S02,
and olefins
reacted to
form 0.001
mg/m3 of
sulfate
aerosol)
Nos, of
Humidity/ Test Nos. of
Particle Mode of Subjects Controls
Size Exposure M F M F
Respir- Inhala- 8
able sul- tion
fate chamber
aerosol
produced
Duration &
Frequency Total*
of Length
Exposures of Expt.
03 for 1 h/d
for 2 d**
followed by
S02 1 h/d
for 2 d
followed by
03+S02 1 h/d
for 2 d
Reference
Effects and Rating
Pulmonary changes in 2/8 subjects. Decrease Bell et al.
in forced expiratory volume and maximum expir- (1975)
atory flow. (Decrease by mixture, greater B-7
than cumulative effect of 2 successive days
of ozone).
Data kept in this table to compare with the above test.
-------
TABLE IV-2. HUMANS—REPEATED DOSE EXPERIMENTAL INHALATION EXPOSURE TO
Compound (s)
and Concen-
tration^)
in mg/m3
H2S04 (dry)
4.1-39
H2S04
2.9-39
H2S04 with
NH3 at end
of exposure
2.9-39
H2S04
11.5-38
H2S04, 30
with
HgO, 16.6
after 50 min
H2S04
1.020
Also exposed
for 1 h/d in
random se-
quence on 4
separate days
to 0.110,
0.330, and
0.980
Humidity/
Particle Mode of
Size Exposure
1 |Jm Inhala-
tion
mask
62% Exposure
1 Mm chamber
Exposure
chamber
91% Exposure
1.5 pm chamber
Exposure
chamber
46 ± 5% Nasal
0.5 tn mask
MUD
0 1.9
2§.7 ± 1.9°C
~
Nos. of Duration &
Test Nos. of Frequency Total
Subjects Controls of Length
M F M F Exposures of Expt.
7.7 10 min
(183 expo-
sures at
least 24
h apart)
7 7 60 min (316
exposures;
no less
than 24 h
apart)
356 dif-
ferent ex-
posures
30-60 min,
40 exposures
(no less
than 24 h
apart)
0.5 h 10 expo-
sures
4 Served as 1 h 2 4 d
own con-
Healthy trols
nonsmokers
with
faster
clearance
rates than
the group
mean
.
Reference
Effects and Rating
Coughing, some bronchoconstriction, rales. Sim and Pattle
(1957)
B-9
Coughing, some bronchoconstriction, rales. Sim and Pattle
(1957)
B-9
/
Irritation disappeared when ammonia was Sim and Pattle
liberated at end of acid mist exposure. (1957)
B-9
More irritant than dry mist at same con- Sim and pattle
centration (1957)
B-9
Irritancy not diminished when magnesium Sim and Pattle
oxide was dispersed. (1957)
B-9
Three showed S threefold increases in group Leikauf et
mean tracheobroncial clearance halftime al. (1981)
(TB ). A-16;
' Lippmann et
al. (1980)
A-15
(continued)
-------
TABLE IV-2. HUM—REP. DOSE EXPTL. (continued)
00
Compound (s)
and Concen-
tration^)
in rog/m3
99raTc-tagged
Fe203
H2S04
M). 75-1. 000
H2S04
0.980
Also exposed
for 1 h/d in
random se-
quence on 4
separate days
to 0.110 and
0.330 (4 per-
sons with
fastest
clearance
also tested
with 1.000)
99m_ . .
Tc-tagged
Fe203
Nos. of
Humidity/ Test Nos. of
Particle Mode of Subjects Controls
Size N Exposure M F M F
7.5 pm Oral inha- "
MMAD lation;
o 5 1.1 each sub-
8 ject regu-
lated own
inspiratory
flow rate
(1.0 L/s),
tidal vol-
ume (1.0 L),
and respira-
tory rate
(15/min)
2-5 pm Inhala- Not Each
tion given subject
chamber* . . served
as own
control
preceding
'each test
46 ± 5% Nasal 7 3 Served as
0.5 pm HMD mask own con-
0 1.9 Healthy trols
nonsmokers;
25.7 ± 8 had never
1.9°C smoked; avg.
age 28 4 7
y
7.5 pm MHAD Oral inha-
a S i.l lation;
* each sub-
ject regu-
lated own
inspiratory
flow rate
(1.0 L/s),
tidal, volume
(1.0 L), and
respiratory
rate (15/min)
• Duration &
Frequency Total
of Length
Exposures of Expt. Effects
~ 10 min 2 min
after H2S04
exposure -
Presumably Not Too irritant for deep breaths to be taken
more than given, at all.
than once but sub-
jects
were re-
tested on
successive
days
1 h/d 2 4 d Significant transient slowing of clearance.
Group mean tracheobronchial clearance half-
time (TB ..) increased to 118 min. (4/10
showed no significant change in TB- .- at any
level, but the 6 who had shown a signifi-
cantly lower TB,._ at 0.110 mg/m3 showed a
significantly greater TB ._ at this level.)
No significant changes in Eracheal mucocili-
ary transport rate or in indices of ventila-
tory mechanics V25 (forced expiratory flow
at 25% of vital capacity), R (airway re-
sistance), and distribution olf ventilation
by N2 washout. (Ventilatory mechanics tests
required ~ 30 min and were repeated within
10 min, 2 h, and 4 h after exposure. Pre-
~ 10 min 2 min exposure control values for the ventilatory
before mechanics tests generally showed greater
H2S04 ex- differences day to day than the correspond-
posure ing differences between pre- and post-
exposure values.) Regional deposition of
tagged test aerosols not significantly af-
fected by H2S04 exposure.
Reference
and Rating
Leikauf et
al. (1981)
and
Lippmann et
al. (1980)
(continued)
Lawther (1980)
A-10
Leikauf et
al. (1981)
A-16;
Lippmann et
al. (1980)
A-15
* Small enclosures within the main chamber were used to minimize the total amount of aerosol required. A fixed number of deep breaths were
taken voluntarily by mouth. Other inhalation procedures may have been used in these pilot studies.
(continued)
-------
TABLE IV-2. HUH--REP. DOSE EXPTL. (continued)
Compound (s)
and Concen- Humidity/
tration(s) Particle
in mg/m3 Size
H2S04 1-2 M"
<0.750
H2S04 2-5 Mm
M). 500-0. 750
H2S04 0.1-1 M">
< 0.5
H2S04 46 + 5%
0.330 0.5 Mm
Also exposed HMD
for 1 h/d in a 1.9
random se- *
quence on 4
separate days
to 0.110 and
0.980 (4 per-
sons with
fastest clear-
ance also
tested with
1.000)
Mode of
Exposure
Inhala-
tion
chamber*
Inhala-
tion
chamber*
Inhala-
tion
chamber*
Nasal
mask
Nos. of
Test
Subjects
H F
Not
given
Not
given
Not
given i
7 3
Healthy
nonsmokers ;
8 had never
smoked ; avg .
age 28 ± 7
y
Nos. of
Controls
M F
Each sub-
ject
served
as own
control
preceding
each test
Each sub-
ject
served
as own
control
preceding
each test.
Each sub-
ject
served
as his
own con-
trol pre-
ceding
each test.
Served as
own con-
trols
Duration &
Frequency
of
Exposures
Presumably
more than
once
Presumably
more than
once.
Not given.
Presumably
more than
once.
1 h/d
Total
Length
of Expt.
Not
given,
but sub-
jects
were re-
tested
on suc-
cessive
days
Not
given,
but sub-
jects
were re-
tested
on suc-
cessive
days.
Not
given,
but sub-
jects
were
retested
on suc-
cessive
days.
g 4 d
>
Reference
Effects , and Rating
Slightly irritant. No consistent changes Lawther (1980)
in lung function (e.g., FVC, FEV], mea- A-10
surements of peak flow with the simple
Wright instrument, airway resistance).
Variations in response between subjects
and even for the same subject when retested
were large. Significance of changes in
lung function cannot be assessed properly
until more experiments have been done.
Very irritant. Severe coughing after deep Lawther (1980)
breaths. Erratic changes in lung functions, A-10
notably ; in, peak flow. Droplets large enough
to impact in the upper respiratory tract will
still be relatively strong acid, whereas parti-
cles small enough to penetrate deeply become
ing produced by large particles could lead to
adverse effects on lung functions, especially
in people with existing respiratory impairment.
No subjective effects. No consistent Lawther
changes in lung function. (1980)
A-10
'
The varied response in group mean tracheo- Leikauf et
bronchial halftime included 3 persons al. (1981)
showing substantially faster clearance A-16;
than in the control test and 3 showing Lippmann et
substantially slower clearance than in al. (1980)
the control test. A-15
(continued)
-------
TABLE IV-2. HUM--REP. DOSE EXPTL. (continued)
Compound (s)
. and Concen- Humidity/
tration(s) Particle
in mg/m3 Size
99mTc-tagged 7.5 Mm
Fe203 MMAD
a S 1.1
g
H2S04 2-5 pm
•v<0.250
h- '
K>
o
H2S04 46+5%
0.110 0.5 pm MUD
Also exposed a 1.9
for 1 h/d in 8
random se- 25.7 ± 1.9°C
qiience on 4
separate days
to 0.330 and
0.980 (4 per-
sons with
fastest clear-
ance also
tested with
1.000)
Nos. of
Test Nos. of
Mode of Subjects Controls
Exposure M F M F
Oral inha-
lation;
each sub-
ject regu-
lated own
inspiratory
flow rate
(1.0 L/s),
tidal volume
(1.0 L), and
respiratory
rate (15/
min)
Inhala- Not . Each
tion given subject
chamber* served
as own
control
preceding
each test
Nasal 7 3 Served as
mask own con-
Healthy trols
•nonsmokers;
8 had never
smoked; avg.
age 28 ± 7
y
Duration &
Frequency Total
of Length Reference
Exposures of Expt . Effects and Rating
~ 10 min 2 min Leikauf et
before . al. (1981)
H2S04 and
exposure Lippmann et
al. (1980)
(continued)
Presumably Not Irritant but breathable. No consistent Lawther (1980)
more than given, changes in lung function. A-10
once but sub-
jects
were re-
tested on
successive
days
1 h/d S 4 d Significant acceleration in mucociliary Leikauf et
clearance. Group mean tracheobronchial al. (1981)
clearance (TB .„) halftime decreased from A-6;
80 to 50 min. Six showed individual de- . Lippmann et
creases in TB... > 25% of control, whereas al. (1980)
other 4 showed lesser increases or de- A-15
creases in TB? ,_. Thus, the response pat-
terns fell into two distinct groups. Even
in the control test, the same six had shown
much slower tracheobronchial clearance than
the other four.
99mTc-
Fe,0,
tagged
7.5 M™
MMAD
o S 1.1
8
Oral inha-
lation;
each sub-
ject regu-
lated own
inspiratory
flow rate
(1.0 L/s),
tidal volume
(1.0 L), and
respiratory
rate (15/
min)
~ 10 min
before
H2S04
exposure
2 min
(continued)
-------
TABLE IV-2. HUM—REP. DOSE EXPTL. (concluded)
Compound (s)
and Concen-
tration^)
in mg/m3
H2S04
0.100
(Controls were
exposed to am-
bient air for
same period)
H2S04
0.075
Humidity/
Particle
Size
40%
20°C
0.5 |Jm
HMD
40% RH
0.48-0.81
Mm (MMAD)
Mode of
Exposure
Groups of
3, begin-
ning at
the same
time each
day.
Some expo-
sure groups
were tested
on M and Tu,
and some on
W and Th.
Subjects
were at rest
throughout
exposures.
Chamber
(exercise)
Nos. of Duration &
Test Nos. of Frequency Total
Subjects Controls of Length
M F M F Exposures of Expt.
20 17 4 h/d for 2 d
non- non- 2 consec-
smokers smokers utive days
avg. height 180.6 cm;
avg. weight 73.0 kg;
avg. age 22.4 y
•
'
6 normal 2 h/d 2 d
6 asth-
matic
Effects
No significant effects were seen in serum
glutathione (GSH), red blood cell gluta-
thione reductase, red blood cell glucose-
6-phosphate dehydrogenase (G6PDH) , lysozyme,
serum glutamic oxaloacetic acid transaminase
(SCOT), serum vitamin E, and 2,3-diphospho-
glycerate (2,3-DPG) measured preceding and
following both exposure days and 20 h after
day 2. This finding is consistent with pre-
vious animal studies on biochemical blood
parameters.
No significant pulmonary effects (forced
vital capacity, forced expiratory volume,
forced expiratory flow, total lung capac-
Reference
and Rating
Chaney et
(1979)
C-12;
Chaney et
(1980b)
C-12
Kleinman
Hackney (
A-13
al.
al.
and
1978
ity, residual volume, total respiratory ^_
resistance) in either group.
Avol et al.
(1978) A-ll;
(1979) A-15
-------
SECTION V
EPIDEMIOLOGY
OCCUPATIONAL EXPOSURES
Data for occupational exposures to sulfuric acid as shown in Table V-l
are not especially useful for deriving a level of concern for sulfuric acid
in automobile emissions primarily because the occupational exposures are so
much higher.
EXPOSURES OF THE GENERAL PUBLIC
Epidemiological studies of exposure of the general public (Table V-2)
do not indicate sulfuric acid concentrations, and only one (Kitagawa, 1977)
attributes specific health effects to exposure to sulfuric acid rather than
total sulfates.
123
-------
TABLE V-l. STUDIES OF OCCUPATIONAL EXPOSURE TO SULFURIC ACID
Compounds,
Concentration,
Duration
Exposed to fuming H2S04
and water during acci-
dent. Exposure lasted
~ 8 rain.
H2SO, 2.7-9.2
Dust
HF S02, 5160
S03) 48.5 during
H2S04 production
NH3 (1 plant), 48
H2S04, 26.12 to
35.02 mg/m3 in one
factory, 12.55 to
13.51 mg/m3 in other
factory. Exposure
1 to 15+ years.
Trace to 16.6 mg/m3
(measurements from
two previous studies
in same factory).
Population Group
Description
Worker in phenol
area of chemical
plant.
Exposed
M F
Controls
M F
Workers in 2
superphosphate
plants. Those
who had worked
< 5 y comprised
34.3%; > 5 y,
65.7%.
Workers in
storage battery
factories.
173 super-
phate work-
ers and 142
H2S04 plant
workers
33
None
20
Workers in stor-
age battery fac-
tory exposed to
H2S04 mist.
133
228
Description
Remarks
References
Immediate effects were
laryngeal, tracheal,
bronchial, and pulmonary
edema followed in 18 mo by
multilobe bronchiectasis,
interstitial fibrosis,
and pulmonary emphysema.
Respiratory difficulty re-
quired 10 d of 02 therapy
and 6 wk of hospitalization.
Goldman and Hill
(1953).
Adverse effects seen more
often in H2S04 plant
workers included pharyn-
gitis, nasal discharge,
sneezing, vasomotor and
allergic changes of up-
per respiratory tract,
lower olfaction, and
eye irritation.
Exposure did not increase
and/or cause chronic
bronchitis and/or asth-
matic bronchitis, didn't
lower forced expiratory
volume. Increased den-
tal erosion with increased
work years. No signifi-
cant differences in bron-
chopulmonary disease be-
tween smokers and non-
smokers.
Slight increase in num-
bers of "spells" of re-
spiratory disease in
workers, especially
bronchitis. Appeared
to be increased num-
ber of spells in
attacked men rather
than increased pro-
portion of men attacked.
Air levels rela-
tively high; same
effects may be pre-
sent at lower expo-
sures of long dura-
tion.
Tadzhibaeva and
Gol'eva (1976).
C-9
Not a good epide-
mology study, but
raises some inter-
esting questions.
El-Sadik et al.
(1972).
B-6
Study has flaws:
levels of H2S04
weren't measured,
duration of expo-
sure not reported,
and actual days of
illness/spell not
reported.
Williams (1970).
C-10
(continued)
-------
TABLE V-l. OCCUPATIONAL (continued)
NJ
Ul
Compounds ,
Concentration,
Duration -
H2S04 2-9 mg/m3
HC1 26-60 mg/m3.
Population Group
Exposed Controls
Description M F M F ' Description
Workers 63 49 Salivary levels of im-
munoglobulin A higher
arad serum, immunoglob-
ulin G levels lower.
Remarks References
Polish article was Scheller et al.
not fully trans- (1977).
lated because ex-
posure was to both
H2S04 and HC1. Com-
ments from summaries/
charts only.
Rating
B-3
H2S04 <0.8 to 2.5 mg/m3
H2S04 3.0 to 16.6 mg/m3
HN03, H2S04, H3P04, and
HF; concentration un-
reported. Duration
< 1 to > 15 y.
HC1, H2S04; concentra-
tion unreported; dura-
tion < 1 to > 15 y.
Workers in sto-
rage battery
factory.
Workers in sto-
rage battery
factory.
Workers in nine
plating firms.
15
63
76
Workers in 17
galvanizing
firms.
107
117 47% of men had tooth ero-
sion and etching. Six
men's teeth were unaf-
fected. Degree of ero-
sion increased with
length of exposure.
117 87% of men had tooth ero-
sion or etching. Six
men's teeth were unaf-
fected. Degree of ero-
sion increased with
length of exposure.
293 85% had no tooth ero-
sion; 7 workers had
etching and 4 had grade
1 tooth erosion; 7.3%
of workers showed pro-
gressing erosion. Con-
trol workers were free
of tooth erosion.
293 Picklers directly exposed
to acid; 43% had no tooth
erosion; 25% had etching;
22% had grade 1 erosion;
4%, grade 2; and 6%,
grade 4. Workers indi-
rectly exposed to acid:
80% had no tooth erosion;
9% had etching; 9% had
grade 1 erosion; and 3%,
grade 2; 25% showed pro-
gressing erosion. Con-
trol workers were free of
tooth erosion.
Good; some needed
study parameters
missing. Exposure
levels high.
Good; some needed
study parameters
missing. Exposure
levels high.
Usefulness limited
by lack of acid
measurements.
Usefulness limited
by lack of acid
measurements.
Malcolm and Paul
(1961).
Malcolm and Paul
(1961).
ten Bruggen Cate
(1968).
C-14
C-14
C-9
ten Bruggen Cate
(1968).
C-9
(continued)
-------
TABLE V-l. OCCUPATIONAL (concluded)
Compounds ,
Concentration,
Duration
HC1, HN03, H2S04( and
HF; concentration
unreported; duration
Population Group
Exposed Controls
Description M F M F
Workers in 13 132 293
acid pickling
firms .
Description
71% had no tooth erosion;
15% had etching; 12%,
grade 1 erosion; 1 worker
Remarks
Usefulness limited
by lack of acid
measurements .
References
ten Bruggen Cate
(1968).
Rating
C-9
each had grade 2 and 3
erosion, 22% showed pro-
gressing erosion. Con-
trol workers were free
of tooth erosion.
Isj
ON
H2S04; concentration
unreported; duration
< 1 to > 15 y.
Workers in 3
battery manufac-
turing firms.
86
H2S04; concentration
unreported; duration
10-20 y.
H2S04 produc-
tion department
workers.
57
293 Formation workers (great-
est exposure to acid):
40% had no erosion; 25%
had etching; 17% had
grade 1 erosion; 14%,
grade 2; 4%, grade 3.
Charging/Inspection work-
ers (light exposure to
acid): 63% had no ero-
sion; 15% had etching; and
20% had grade 1 erosion.
50% showed progressing
erosion. Control workers
were free of tooth erosion.
No evidence of increased.
occurrence of bronchial
or lung diseases nor of
conjunctival or pharyn-
geal irritation. Numer-
ous cases of gastritis,
gastro-duodenitis, gas-
tric ulcers, and digestive
troubles.
Usefulness limited
by lack of acid
measurements.
ten Bruggen Cate
(1968).
C-9
Gastrointestinal
effects have not
been corroborated
by other studies
in the last 25 y.
Morando (1956)
B-8
-------
TABLE V-2. EPIDEMIOLOGICAL STUDIES RELEVANT TO SULFURIC ACID EXPOSURE
(Exposure of the General Public)
Compounds and
Concentration
(Mg/m3)
Population
Studied
Duration and
Period of
Study
Description of Adverse Effects
\
Remarks on Value of Study
Reference and
Rating
Suspended sul-
fates, 20-50
Range of mean
pollution con-
centrations .
NJ
Suspended sulfates
Peak of 36.0 in
December fell to a
minimum of 12.7 by
April 1, 1961.
Particulate sul-
fate 5.4 - 29.1
Range of annual
'mean concentra-
tion of particulate
sulfate within 38
different city at-
mospheres.
New York City 27 y,
parents of ele- 1970
mentary school
children, 6,000
1944-
Female indus-
trial plant
workers re-
porting symp-
toms of infec-
tious respira-
tory disease in
Harrison, Camden,
and Woodbridge,
New Jersey;
Indianapolis,
Bloomington, and
Marion, Indiana;
Cincinnati, Ohio;
and Lancaster,
Pennsylvania.
Annual mortal-
ity rates for
total popula-
tion of 37 dif-
ferent city
atmospheres
July 1960-
December 31,
1961
4 V,
1965
1962-
Excess of chronic bronchitis among men
and smokers. Effects of smoking and
pollution very significant for both
mothers and fathers. Effects of smok-
ing and pollution seemingly additive.
Influence of pollution nearly as great
as effect of moderate smoking on the
development of chronic bronchitis.
There is a high correlation (Y = 0.96)
between the mean concentration of sus-
pended particulate sulfates and the
incidence rates of respiratory disease
lasting more than 7 d in women working
in 5 of the cities.
Some suggestive indicators of interest-
ing relationships between diseases and
S02, NOa, and particulate sulfate are
apparent. The correlation between par-
ticulate sulfate concentrations and
mortality rates for cancer of respira-
tory system, or hypertensive heart
disease is greater than the same com-
parison between S02 and these chronic
diseases. However, the comparison of
these relationships is reversed with
respect to leukemia-aleukemia. For most
other disease categories, S02 and parti-
culate sulfate generate similar correla-
tions to the same diseases. -
CHESS monitoring sites being same
as air pollution control programs
indicate some representativeness.
But it is not meaningful to draw
conclusions from S0;> exposure
levels (high) and sulfate levels
(low) since a varied combination
of concentrations could^produce
the same effects (EPA, 1980). These
studies not capable of associating
urban health differences with speci-
fic air pollutants.
Fails to do multiple regressions;
considers sulfates only, ignoring
co-varying pollutants and other
factors.
Chapman et al.
(1973)
C-7
Dohan et al.
(1962)
C-8
These authors have looked at the
negative side of a two-sided
epidemiologic hypothesis, in that
very low long-term exposure to
certain chemicals (including S02
according to these authors) can
change DNA. They have associated
exposure to disease.
Mickey et al.
(1970)
B-9
(continued)
-------
TABLE V-2 (continued)
Compounds and
Concentration
(Mg/m3)
Population
Studied
Duration and
Period of
Study
Description of Adverse Effects
Remarks on Value of Study
Reference and
Rating
Suspended sul-
fates
Urban core, 15-20
Outlying areas,
< 8
Suburbs-unknown
Suspended sul-
fates, 14.5-16.0
N3
00
Suspended sul-
fates, 11.1-13.7
(average daily
. values over 34 wk)
Range values, 8-55
Suspended sul-
fates, 10.2-14.3
Chicago mili-
tary inductees,
38,000 white,
3,200 black
Chicago, 1-12-
y-old children
and parents,
2,705
New York City
elderly; well
with heart
and/or lung
disease; over
300
~ 8 mo,
July 1969-
February
1970
1 Y,
December
1969-
November
1970
~ 8 mo,
October 17,
1971, through
June 10,
1972
New York City ~ 8 mo,
1-12-y-old September
children and 1970-May
parents, 3,000 1971
Bronchitis elevated among whites in pol- Exposure estimates questionable.
luted regions but not significantly
among blacks. Smoking significantly
affected prevalence of bronchitis.
Additive effect of smoking and pollu-
tion evident among whites but not
blacks where ratio of prevalence due
to air pollution over prevalence to
smoking was < 1.
Increased relative risk in all family
members for acute respiratory disease
in high pollution areas (with residence
time > 3 y).
Increasing temperatures aggravated heart
disease symptoms. Elevated levels of
suspended nitrates, sulfates, S02, and
total suspended particulates (TSP) were
associated with increased symptoms in
the "well" category. Similar but weaker
effects on the lung disease symptoms.
No support for the hypothesis that the
more severely afflicted would be more
sensitive to air pollution.
Increased relative risk in all family
members for acute respiratory disease
in high pollution areas (with residence
time > 3 y).
Chapman et al.
(1973)
C-7
Sampling sites did not necessarily
reflect actual exposures of the
inductees (EPA, 1980). These
studies not capable of associating
urban health differences with speci-
fic air pollutants.
No differentiation between effects French et al.
of current levels of pollution and (1973)
higher levels occurring earlier. C-9
Only average concentrations were con-
sidered, not peak or episode concen-
trations (EPA, 1980). EPA's (CHESS)
program's focus is acute respiratory
disease attack rates. Pollutants re-
sponsible for such may not be those
reported.
No threshold for suspended sulfates Stebbings and
effects can be established from Hayes (1976)
these data. Note: no greater sus- C-10
ceptibility present in the panelists
with chronic illness.
No differentiation between effects
of current levels of pollution and
higher levels occurring earlier.
Only average concentrations were con-
sidered, not peak or episode concen-
trations (EPA, 1980). EPA's (CHESS)
.program's focus is acute respiratory
disease attack rates. Pollutants re-
sponsible for such may not be those
reported.
French et
(1973)
C-9
al.
(continued)
-------
TABLE V-2 (continued)
Compounds and
Concentration
(pg/m3)
Suspended sul-
fates, 3.7-5.8
4.7-10.6
8.6-14.0
12.4-28.0
range of average
values
S02, 131-435
Suspended par-
ticulates, 75-200
Suspended sul-
fates, 5-25
,
M
N>
Suspended sul-
fates
3.3
4.9
7.6-19.5
8.4-8.6
13.0-20.4
range of average
values
Suspended sul-
fates, 2.8-20.3
Population
Studied
Four Utah com-
munities;
parents of
children,
kindergarten
to 12th grade,
7,635
Elementary
school chil-
dren in three
New York City
communities
Idaho-Montana
five communi-
ties (three
with smelters,
two without) ;
parents of ele-
mentary school
children, 5,300
Idaho-Montana
(Rocky Moun-
tain), 1-12-y-
old children,
5,776
Duration and
Period of
Study
32 y, 1940-
1971
,
November-
December 1970,
January 1971,
February-
March 1971,
April 1971
31 y, 1940-
1970
j
38 mo,
September
1967-
November
1970
Description of Adverse Effects
Chronic bronchitis prevalent in fathers.
(Reversed for ex-smokers.) Smokers,
higher prevalence rates than both groups
mentioned above. Chronic bronchitis
from high exposure community equaled
ratio of bronchitis among smokers to
bronchitis among nonsmokers (in clean
air)
Small but significant impairment in
ventilatory function.
.
Elevated bronchitis rates for fathers
and a marked increase among smokers.
Effects of smoking and pollution very
nearly additive.
Children (residence greater than 3 y)
in high pollution areas had higher at-
tack rates of single and repeated epi-
sodes of lower-respiratory disease
than those in cleaner areas (croup
and laryngotracheobronchitis most
common) .
'
* Not rated. Critique from the Congressional Investigative Report (1976) - Commentary on U.
Particulate Matter and Sulfur Oxides, Volume IV
.Health Effects, Appendix A, April 1980
Remarks on Value of Study
No mention of estimated concentra-
tions and erroneous table entries
(EPA, 1980). These studies not cap-
able of associating urban health
differences with specific air pol-
lutants
It is implied that the lower levels
given may be threshold values. Ac-
tually, they are annual average con-
centrations for 1969 and 1970. The
observed health effects may have
been result of exposure to much
higher concentrations (in earlier
years) or to some other cause.
Sources of suspended sulfate inade-
quately determined. Incomplete
findings (EPA, 1980).
No differentiation between effects
of current levels of pollution and
higher levels occurring earlier.
Only average concentrations were con-
sidered, not peak or episode concen-
tration (EPA, 1980). EPA's (CHESS)
program's focus is acute respiratory
disease attack rates. Pollutants re-
sponsible for such may not be those
reported.
Reference and
Rating
Chapman et al.
(1973)
C-7
May et al.
(publication
not identifi-
able from EPA,
1980)
*
Chapman et al. '
(1973)
C-7
French et al.
(1973)
C-9
x
S. EPA CHESS Program - in Air Quality Criteria for
(EPA, 1980).
(continued)
-------
TABLE V-2 (continued)
u>
o
Compounds and
Concentration
(MR/m3)
Suspended sulfates
24-h average on
cooler days
12
24-h average on
warmer days
7.3
SO levels
100-180 (90% of
days)
S02 <52
Suspended sulfates
8.9-rlO.l in pol-
luted lower middle
white community;
8.3 in cleanest
area.
Total suspended
particulates, 131
in polluted sector,
61-92 in clean
sector
Suspended sulfates,
5.6-12.4
~
Duration and
Population Period of
Studied Study
Panelists in 3 ~ 7 mo
New York City Oct. 1970 -
communities May 1971
Cincinnati ele- 3 mo
mentary school Nov. 1967,
children, 60-75 Feb. and May
children in 1968
each of six
study sectors.
Salt Lake Basin September
1-12-y-old 1967-November
children, 1970
8,991
-•
Description of Adverse Effects
Sulfate levels given are reported as
threshold levels for the induction of
excessive asthma attacks. No associa-
tion of increased SO levels with
asthma attack rates.
Ventilatory performance of children
(measured 12 times) did not appear to
be affected by variations of pollutant
levels on the test days.
Children (residence time > 3 y) in high
pollution areas had higher attack rates
of single and repeated episodes of
lower-respiratory disease than those
in cleaner areas (croup and laryngo-
tracheobronchitis most common).
Reference and
Remarks on Value of Study Rating
Study focused on effects of minimum Finklea et al.
temperature. Other meteorological (publication
variables might have been considered, not identifiable
Temperature differences within the from EPA, 1980)*
studied communities should have
been noted. Conclusions that attack
rates and suspended sulfate levels
follow each other is erroneous.
3 of the 5 attack rate increases
precede increases in suspended sul-
fate concentrations.
No details on the lack of correla- Shy et al.,
tion between pollution levels and (1973)*
pulmonary function test values.
Unknown psychological interaction
between children and team members,
who could anticipate outcome of
the experiment. (Curves for black
children especially interesting.)
No differentiation between effects French et al.
of current levels of pollution and (1973)
higher levels occurring earlier. C-9
Only average concentrations were
considered, not peak or episode
concentration (EPA, 1980). EPA's
(CHESS) program's focus in acute
respiratory disease attack rates.
Pollutants responsible for such
may not be those reported.
Not rated. Critique from the Congressional Investigative Report (1976) - Commentary on U.S. EPA CHESS Program - in Air Quality Criteria for
Particulate Matter and Sulfur Oxides. Volume IV, Health Effects, Appendix A, April 1980 (EPA, 1980).
(continued)
-------
TABLE V-2 (continued)
Compounds and
Concentration
(Mg/m3)
Population
Studied
Duration and
Period of
Study
Description of Adverse Effects
Remarks on Value of Study
Reference and
Rating
0.051 ppra SO-
yearly seasonal
ranges
0.75 to
1.75 ppm (SO )
1.3 t/km2/moxH,SO,
(1967-acid mist
collector in-
stalled reducing
emissions to 1% of
above)
S02
0.209-0,461
nig/cm2
1961
Suspended parti-
culates, 180
Lead peroxide
candle
rag SO,/100 cm2/d
0.731 + 0.241
1967
Suspended parti-
culates
131.5
Lead peroxide
candle
rag S03/100 cm2/d
0.469 + 0.111
Average rural sul-
fate deposit
50 g/100 mi2/mo
Hospital pa-
tients ,
Yokkaichi City
1961-1967 and
beyond
White men, 50 y
and older (no
location given)
Berlin,
New Hampshire
adults
25 to 74-y-old
541 male,
626 female
(1961)
371 male,
477 female
(1967 - of the
1961 group)
Not given
1961 and 1967
surveys
General popula-
lation,
53 county and
metropolitan
burroughs in
England,
Scotland, and
Wales.
5 y,
1950-1954
Incidence of respiratory diseases and
complaints (bronchitis, pharyngitis,
bronchial asthma, and eye irritation)
uniformly worse for urban rather than
suburban patients (<6 km, <12 km).
Respiratory problems worse for those
living near Ti02 plant whose H-SO^
emissions are more damaging than the
H-SO, formed from oxidized SO- pollu-
tion. After installation of the acid
mist collector, respiratory symptoms be-
gan to decrease.
No association between "sulfation" and
total mortality from cancer of bronchus,
trachea, and lung. Positive association
between mortality from chronic respira-
tory diseases and "sulfation" in lowest
two of five economic levels.
Shortness of breath, wheezing in the
chest and chest illness increased over
the 6 y between surveys. Cough, phlegm,
(or both), and pulmonary function values
decreased slightly (somewhat as a result
of aging). Changes in smoking habits,
decrease in pollution, and other crude
prevalences may be factors in the de-
crease of symptoms.
Urban death rate from pneumonia 30%
higher than rural (logarithmic mean).
The only air pollution component with
any relation to pneumonia mortality is
sulfate deposit. >
Interesting observation needs care-
ful confirmation and more appro-
priate controls.
Kitagawa (1977)
B-8
Winkelstein
et al. (1968)
C-10
Ferris et al.
(1973)
C-9
No shown association of total mor-
tality with atmospheric oxides of
sulfur. Lack of information on
smoking and occupation variables.
Undefined method of determining the
oxides of sulfur, including controls
of temperature and humidity.
Methodology satisfactory. High re-
sponse rate. Because of surveys
being taken at two different times
of the year, it is invalid to com-
pare the two. Other studies have
shown that frequency of symptoms and
levels of lung function are related
to season. Result reports are un-
clear as to which periods and sites
are being compared (Holland, 1979).
This study does not implicate H.SO,
or atmospheric sulfates as the cause
of the respiratory disease in this
study.
Simple correlation of pneumonia mor- Gorham (1959)
tality rates and atmospheric sulfate C-8
deposit.
(continued)
-------
TABLE V-2 (concluded)
Compounds and
Concentration
(pg/m3)
No information
given
Population
Studied
Seven south-
eastern states
in salt marsh
belt, white
males
Duration and
Period of
Study
Hot given
Description of Adverse Effects
Statistical relationship between lung
cancer mortality and biogenic (and
other) sources of hydrogen sulfide.
Some evidence that risk of lung cancer
is more strongly influenced by geolog-
Remarks on Value of Study
Preliminary report; conjecture prob-
ably based on Mason's (NCI) maps of
cancer mortality. Data need careful
validation for occupation, smoking,
and cause of death.
Reference and
Rating
Hitchcock
(1979)
C-6
ical factors than by distribution of
urban centers or industry. "These re-
sults are compatible with the results of
earlier workers who observed that high
risk of cancer is associated with poorly
drained soils with high organic content,
and are compatible with the hypothesis
that H»SO, mist may be causally related
to lung cancer and perhaps to other can-
cers associated with smoking."
U)
-------
SECTION VI
HUMAN AND ANIMAL STUDIES IN PROGRESS
Although nearly every principal investigator who had pertinent research
in progress was contacted by letter for information, not every one responded.
On the other hand, a few investigators sent several reports each. Data from
every written report received in response to these letters were included in
the appropriate tables in preceding chapters. However, a few studies that
were rated only from brief research project notices are summarized in Table
VI-1. These current studies include occupational epidemiology and experi-
mental human and animal studies. All address important aspects of inhala-
tion toxicity. It is too early to judge whether these efforts will corrob-
orate the tentative conclusion based on epidemiology, occupational, and
experimental studies that a level of concern for human H2S04 exposure is
probably 0.066 to 1.0 mg/m3.
133
-------
TABLE VI-1. SUMMARY OF PERTINENT RESEARCH IN PROGRESS ON H2S04 INHALATION
Exposure
Species '
Objectives
Reference
and Rating
Occupational H2S04
H2S04 battery manufacturing
Human
Humans
Inhaled H2S04 without sedation
or rigid restraint
0.1 mg/m3 H2S04 (0.3 (Jm diameter)
1 h/d, 5 d/wk
Donkeys
Two donkeys
To conduct a retrospective cohort
mortality study of a population occu-
pationally exposed to H2S04 mist.
To develop dose-response relation-
ships of both an acute and chronic
nature for various species of sulfur
and nitrogen in support of health
standards development. Worker re-
sponses and environmental measures
will be acquired concurrently.
Changes in pulmonary function, muco-
ciliary clearance, and regional dep-
osition will be observed and this
experiment will serve as a human
analogue.
In progress.
Beaumont and Young
(1980)
A-?
Gamble (1979)
B-?
Lippmann and
Albert (1979)
A-8
Lippmann and
Albert (1979)
A-8
6 mo of dosing as above after
baseline measurements
6 or 12 mg/m3 H2S04 and in
combination with increased levels
of exogenous or endogenous NH3
Two donkeys
Male beagle dogs
1 h to 0.1 and 1.0 mg/m3 of
0.5 Mm H2S04
Guinea pigs and
dogs
H2S04 mists
Fischer-344 rats;
\ beagle dogs
H2S04 with pretreatment by
specific pharmocologic block-
ing agents
Guinea pigs
Bronchial clearance rates have been
noted.
To determine the degree of neutrali-
zation of inhaled H2S04 by endogenous
or exogenous NH3, to determine the
effect of neutralization on toxicity,
and to estimate minimal levels of
H2S04 required to alter pulmonary
function with no NH3 present in the
lung. . •
Species comparison of breathing pat-
terns and pulmonary mechanics for
characterization of sensitive and
insensitive populations. Further
experiments will be designed for
chronic exposures with serial, com-
prehensive physiological evaluation
during and after exposure to aid in
defining risks of continuous low-
level inhalation of sulfates.
To examine toxicant distribution in
the lung after inhalation of H2S04
mist and to determine the distribution
and retention of inhaled monodisperse
inert particles after inhalation of
H2S04 mist.
To define biochemical agents responsi-
ble for changes in pulmonary function1
caused by exposure to sulfur pollut-
ants. Possible beneficial effects of
inhibiting responsible agents will be
evaluated to determine whether highly
sensitive humans can be protected.
(continued)
Lippmann and
Albert (1979)
A-8
Loscutoff (1980b)
C-9
Mauderly (1979)
C-4
Snipes (1980)
C-2
Loscutoff (1979)
A-6
134
-------
TABLE VI-1. (concluded)
Exposure
Species
Objectives
Reference
and Rating
H2S04 and other pollutants
related to energy consumption
Aged aerosol of S02-03-olefin
mixture, which produces substan-
tial quantities of submicron-
size H2S04
H2S04
Rats
Small lab
mammals
To determine qualitative and quantita- Mustafa (1980)
tive biochemical changes in the lungs B-10
of animals using sensitive biochemical
parameters.
Animals not
specified
To measure changes in pulmonary func-
tion and metabolism which are indica-
tive of tissue damage produced in the.
lungs by pulmonary toxicants using
methods similar to those used in hu-
mans but adapted and developed for
lab animals.
With the use of advanced morphological
and histochemical methodology, infor-
mation will be sought on the relative
sensitivity of specific lung cell
types, the nature of cell injury, and
the sequence of events leading to
cell repair.
Oneil et al.
(1979)
C-12
Halliwell (1979)
C-6
135
-------
ANNOTATED BIBLIOGRAPHY
137
-------
C—* AIHA, American Industrial Hygiene Association. 1964. Hygienic
Guide Series, Sulfuric Acid. American Industrial Hygiene Associa-
tion, Akron, Ohio.
The AIHA reviewed in 2 pp. with seven references industrial hy-
giene aspects of H2S04 exposure and recommended 1 mg H2S04/m3 as
the maximum 8-h concentration in workplace air.
A-15. Alarie, Y., W.M. Busey, A.A. Krumm, and C.E. Ulrica: 1973. Lorig-
Term Continuous Exposure to Sulfuric Acid Mist in Cynomolgus Mon-
keys and Guinea Pigs. Arch. Environ. Health. 27:16-24.
Guinea pigs exposed for 52 wk to 0.10 mg/m3 (2.78 Mm) or °-°8
mg/m3 (0.84 (Jm) showed no change in biochemical values, slight
temporary lung function changes, and slightly decreased growth
rates among females. Monkeys exposed for 78 wk to 0.48 mg/m3
(0.54 (Jm) had slight changes, to 0.38 mg/m3 (2.15 |Jm) had more
change, and to 2.43 mg/m3 (3.60 fjm) or 4.79 mg/m3 (0.73 |Jm) had
definite structural and function damage.
A-15. Alarie, Y.C., A.A. Krumm, W.M. Busey, C.E. Ulrich, and R.J. Kantz.
1975. Long-Term Exposure to Sulfur Dioxide, Sulfuric Acid Mist,
Fly Ash, and Their Mixtures. Results of Studies in Monkeys and
Guinea Pigs. Arch. Environ. Health. 30:254-262.
Monkeys and guinea pigs were exposed for 78 and 52 wk, respec-
tively, to mixtures of ~l-5 ppm of S02, ~0.1-1 mg H2S04/m3, and
~0.5 mg/m3 of fly ash. No synergistic action was noted between
the components of the mixture; H2S04 was responsible for the ef-
fects observed.
0.1 mg H2S04/m3 and ~0.5 mg/m3 fly ash had no adverse functional
or morphological effect on monkeys or guinea pigs.
Combinations of ~1 mg H2S04/m3 (<1 |Jm) and ~0.5 mg/m3 fly ash, or
0.99 ppm S02 and 0.93 mg H2S04/m3, or 1.01 ppm S02, 0.88 mg H2S04/
m3, and 0.41 mg fly ash/m3 caused lung changes in monkeys.
Well done chronic work—some indication that transient effects
occur that would not show up only at endpoint chronic measures.
B-12. Amdur, M.O. 1954. Effect of a Combination of S02 and H2S04 on
Guinea Pigs'. Pub. Health Reports 69:503-506.
Original but old. Too few animals; "historic" controls only.
MRI rating. See pp. 16 and 17 for description of methodology.
138
-------
D-10. Amdur, M.O. 1958. The Respiratory Response of Guinea Pigs to Sul-
furic Acid Mist. Arch. Ind. Health. 18:407-414.
At low concentrations (1-10 mg/m3), 0.8 pm particles were more
toxic [Increased resistance, airway]. At 10-50 mg/ra3, 2.5 (Jm
particles gave most effect.
200 mg/m3 .= LD10o in 1 h.
B-9. Amdur, M.O. 1959. The Physiological Response of Guinea Pigs to At-
mospheric Pollutants. Int. J. Air Pollut. 1:170-183.
Synergistic toxic action was seen in a mixture of 863 and 0.8 (Jm
particles, but not between SO^ and 2.5 (Jm HgSC^ particles. Stud-
ies with other irritant gases and aerosols also indicate that par-
ticle size is an important factor in the potentiation of a toxic
response. Possible reasons and mechanisms are discussed.
D-6. Amdur, M. 0. 1961a. The Effect of Aerosols on the Response to
Irritant Gases. In: Inhaled Particles and Vapors. C.N. Davies,
ed., Pergamon Press, Oxford, pp. 281-294,
A study of the potentiation of a toxic effect (increased airway
resistance) of several irritant gases by an aerosol. H2S04 is
not included. The theories and principles discussed may be poten-
tially applicable to this project.
A-- Amdur, M.O. 196lb. Report on Tentative Ambient Air Standards for
Sulfuric Acid and Sulfur Dioxide. Ann. Occup. Hyg. 3:71-83.
Three air standards are proposed for 1 hour or less "peaks":
H2S04 = "adverse" 1 mg/m3
"serious" 3 mg/m3
"emergency" 5 mg/m3
An average, chronic, permissible level of 0.02 mg/m3 is proposed,
based on her work with synergistic effects of pollutants and a se-
lective literature review to prove 10 premises made on toxicology.
C-6. Amdur, M.O. 1964. The Effort of High Flow-Resistance on the Re-
sponse of Guinea Pigs to Irritants. J. Am. Inc. Hyg. Assoc.
25:564-568.
Guinea pigs with control pulmonary flow resistance values above
the average show a greater increase in resistance than the average
animal upon exposure to irritant aerosols (e.g., H2S04), espe-
cially at low concentrations.
139
-------
A-0. Amdur, M.O. 1969. Toxicologic Appraisal of Particulate Matter,
Oxides of Sulfur, and Sulfuric Acid. J. Air Pollut. Control
Assoc. 19:638-646.
An early researcher in inhalation toxicology cites early papers
with useful data for setting standards. A summary, but no useful
tables.
A-0. Amdur, M.O. 1971. Aerosols Formed by Oxidation of Sulfur Dioxide.
Review of Their Toxicology. Arch. Environ. Health. 23:459-468.
Review of other papers; mostly her own early work.
^
A-12. Amdur, M.O. 1973. Animal Studies. In: Proceedings of the Con-
ference on Health Effects of Air Pollutants. Washington, B.C. A
Report Prepared for the Committee on Public Works, United States
Senate. Serial No. 93-15. U.S. Government Printing Office,
Washington, B.C. pp. 175-205.
A review that contains fresh approaches, relationships, and even
some unpublished data that may not be obtainable elsewhere.
D-0. Amdur, M.O. 1975. Toxicological Guidelines for Research on Sulfur
Oxides and Particulates. Proc. 4th Symposium on Statistics and
the Environment, pp. 48-55.
This article summarizes many experiments but contains little new
information. Clearly shows that the percent increase in airway
resistance (acute, guinea pig) is a function of particle size and
is progressively worse with particles over a range of 0.1 (Jm to
2.5 pm.
B-ll. Amdur, M. 0. 1978. Physiological Response to Atmospheric Pollut-
ants. PB-280 413. National Technical Information Service, U.S.
Department of Commerce, Springfield, Virginia. 44 pp.
Guinea pigs exposed to 0.1-1.0 mg/m3 (1 |jm or 0.3 |Jm) showed a
dose-related increase in pulmonary flow resistane, the smaller
particles having more effect. Only the 0.1 mg/m3, l-|Jm exposure
group had recovered in the half-hour post-exposure period.
D-0. Amdur, M.O. , and J. Mead. 1955. A Method for Studying the Mechan-
ical Properties of the Lungs of Unanesthetized Animals. In: Proc.
3rd National Air Pollution Symposium. National Air Pollution Sym-
posium, Pasadena, CA. pp. 150-159.
Old "methods" paper which has little current value.
140
-------
D-0. Amdur, M.O. , and J. Mead. 1958. Mechanics of Respiration in Un-
anesthetized Guinea Pigs. Am. J. Physiol. 192:364-368.
A description of a technique for determining several lung func-
tions \ The method is out of date now. Includes a comparison of
normal and tracheotomized guinea pigs.
C-6. Amdur, M.O., R.Z. Schulz, and P. Drinker. 1952a. Toxicity of
Sulfuric Acid Mist to Guinea Pigs. AMA Arch. Inc. Hyg. Occup.
Med. 5:318-329.
Age 'differences in test animals were not great enough (both were
rather young adults) to form conclusions. More useful data can
be obtained from later papers.
A-ll. Amdur, M. 0., L. Silverman, and P. Drinker. 1952b. Inhalation of
Sulfuric Acid Mist by Human Subjects. Arch. Ind. Hyg. Occup. Med.
6:305-313.
Facemask inhalation in 15 subjects with retention values/dose-
effect comments. Main problems deal with equipment: particle
size by estimate, no humidity control, and quantitation of dose
gave problems.
D-10. Amdur, M.O. , M. Dubriel, and D.A. Creasia. 1978a. Respiratory Re-
sponse of Guinea Pigs to Low Levels of Sulfuric Acid. Environ.
Res. 15:418-423.
This contains similar data to those in Amdur (1958) but a smaller
H2S04 spray was used.
A-12. Amdur, M.O. , J. Bayles, V. Ugro, and D.W. Underbill. 1978b. Com-
parative Irritant Potency of Sulfate Salts. Environ. Res. 16:1-8.
Pulmonary resistance and compliance in guinea pigs are used as a
measure of the toxicity of 4 sulfate salts, the response to the
irritants generally increasing with decreasing particle size. The
combination of S02 and copper sulfate acted synergistically. The
potentiation of S02 by metallic salts due to its conversion to
sulfuric acid, and the possibility of a sulfite or bisulfite being
formed instead is discussed.
A-16. Amdur, M. 0., V. Ugro, and D. W. Underbill. 1978c. Respiratory
Response of Guinea Pigs to Ozone Alone and with Sulfur Dioxide.
J. Am. Ind. Hyg. Assoc. 39:958-961.
141
-------
The highly-sensitive guinea pig (in vivo) lung assay indicated
that ozone and sulfur dioxide together in aerosol do not produce
sulfuric acid.
A-ll. Avol, E. L., M. P. Jones, R. M. Bailey, N. N. Chang, M. J.
Kleinman, W. S. Linn, J. D. Hackney, and K. A. Bell. 1978. Aero-
sol Characterization and Health Effects of Ammonium Sulfate, Am-
monium Bisulfate, and Sulfuric Acid Aerosols in Controlled Human
Exposures. Proc. 71st Annu. Meet. Air Pollut. Control Assoc.,
Texas 1978. Paper No. 51.6, 24 pp.
This paper gives "no respiratory function effect" levels for acute
(2-h) human exposure. The complete description of this experiment
can be found in Kleinman and Hackney (1978).
A-14. Avol, E. L., M. P. Jones, R. M. Bailey, N. N. Chang, M. T.
Kleinman, W. S. Linn, K. A. Bell, and J. D. Hackney. 1979. Con-
trolled Exposures of Human Volunteers to Sulfate Aerosols. Health
Effects and Aerosol Characterization. Am. Rev. Respir. Dis. 120:
319-327.
Small groups of people were exposed to H2S04 aerosol (75 |Jg/m3,
0.3 [Jm MMAD) at 40% R.H. for 2 h. Normal subjects were unaf-
fected. Asthmatic subjects showed increased respiratory resis-
tance during the actual exposure, but no significant change over
a 24-h period (as studied for the other group).
D— Ballou, J. E., R. A. Gies, and F. G. Burton, Exposure of Rats to
Acid Aerosols. 1977. In: Pac. Northwest Lab. Annu. Rep. 1977
ERDA Assist. Admin. Environ. Safety Pt. 1: Biomedical Science.
PNL-2100 PT1/UC-48. p. 87.
Additional methodology data for Ballou et al. (1978).
B-7. Ballou, J. E., R. A. Gies, G. E. Dagle, F. G. Burton, and 0. R.
Moss. 1978. Late Effects of Acid Inhalation. In: Pac. North-
west Lab. Annu. Rep. 1977 DOE Assist. Seer. Environ. Pt. 1:
Biomedical Science. PNL-2500 Pt. 1. pp. 6.1-6.2 1-0064.
Interim report gives good data on bone tumors (only) after sub-
acute exposure to H2S04 mist.
B-- Ballou, J. E., R. A. Gies, and G. E. Dagle. 1979. Late Effects
Following Exposure to Graded Doses of HN03, HC1, and H2S04 Aero-
sols. In: Pac. Northwest Lab. Annu. Rep. 1978 DOE Assist. Seer.
Environ. Pt 1: Biomedical Sciences. PNL-2850 PT1/VC-48. pp.
6.1-6.2.
See Ballou et al. (1978).
142
-------
B-- Ballon, J.E., R.A. Gies, and G.E. Dagle. 1980. Late Effects Fol-
lowing Exposure to Graded Doses and HN03, HC1, and H2S04. In: Pac.
Northwest Lab. Annu. Rep. 1979 DOE Assist. Seer. Environ. Pt. 1:
Biomedical Sciences. PNL-3300PT1, UC-48. pp. 254-255.
Additional data for Ballou et al. (1978); no change of conclusion.
Final report (to include histopathology in progress) will probably
be useful.
Barrow, C. S., and W. H. Steinhagen. 1980. Ammonia Concentra-
tions in the Expired Air of the Rat: Importance to Inhalation
Toxicology. Toxicol. Appl. Pharmacol. 53 (1): 116-121.
No rating. The premise was used in discussing H2S04 toxicity.
The article quantitates breath NH3 in the rat and discusses the
significance of this NH3 in low-level, chronic inhalation of chem-
icals. "
A-9. Battigelli, M. C., and J. F. Gamble. 1975. Review of Inhala-
tion Toxicology of Sulfuric Acid and Sulfates. Air Qual. Monogr.
No. 75-25., American Petroleum Institute, Washington, D.C. 89 pp.
A good review.
A--. Battigelli, M.C., and J.F. Gamble. 1976. From Sulfur to Sulfate:
Ancient and Recent Considerations. J. Occup. Med. 18:334-341.
This critical review was followed by clinical case reports. It
noted that 300 employees of a sulfuric acid plant had changes in
respiratory function that were related to smoking habits rather
than plant exposure. A case history suggesting rapid adaptation
to H2S04 aerosol was given.
A-- Beaumont, J., and M. Young. (NIOSH). 1980. Mortality and Indus-
trial Hygiene Study of Workers Exposed to Sulfuric Acid-EPA.
Toxicol. Res. Proj. Dir. 5(3):SSIE/DR; Beaumont, J., M. Young,
and R. Goldsmith, op. cit. 4(9): SSIE/DR 545; Beaumont, J.
1979. 0£ cit. 4(6):SSIE/GMA 5406.
The cohort has not yet been located. It will be 1990 before re-
sults will be obtained.
B-7. Bell, K.A., W.S. Linn, and J.D. Hackney. 1975. Effects on Pulmo-
nary Function of Humans Exposed to Mixtures of Ozone, Sulfur Di-
oxide and Their Reaction Products. Fed. Proc. 34(3):428.
143
-------
Pulmonary changes were seen in 2 of 8 subjects exposed to 0.37 ppm
03, 0.37 ppm S02, and finally 0.37 ppm each 03 + S02 for l_h/d for
2 d of each regime. Authors calculated that 0.001 mg S042 /m3
could have been present.
B-7. Bell, K.A., W.S. Linn, M. Hazucha, J.D. Hackney, and D.V. Bates.
1977. Respiratory Effects of Exposure to Ozone Plus Sulfur Oxide
in Southern Californians and Eastern Canadians. Am. Ind. Hyg.
Assoc. J. 38:696-706.
Small groups of normal and sensitive people briefly exposed to
0.37 ppm 03 plus 0.37 ppm S02 showed only slight changes in pul-
monary function test results. Forced expiratory function was
significantly decreased from the value when exposure was to 03
alone. Calculations indicated that ~ 1 |jg H2S04/m3 could have
been present in the exposure chambers.
B-8. Bloch, W.N., Jr., T.R. Lewis, K.A. Busch, J.G. Orthoefer, and J.F.
Stara. 1972. Cardiovascular Status of Female Beagles Exposed to
Air Pollutants. Arch. Environ. Health. 24:343-353.
Highly complex results are reported for beagle dogs exposed chron-
ically to H2S04 and S02 with or without irradiated or nonirradi-
ated auto exhaust. Generally, there were no significant cardio-
vascular changes for the entire groups.
D-0. Bloch, W.N., Jr., S. Lassiter, J.F. Stara, and T.R. Lewis. 1973.
Blood Rheology of Dogs Chronically Exposed to Air Pollutants.
Toxicol. Appl. Pharmacol. 25:576-581.
Dogs exposed for 4 y to combinations of auto exhaust, SOx, or NOx
had no significant changes in hematocrit values, plasma viscosi-
ties, or methemoglobin levels. Some groups had high carboxyhemo-
globin levels.
B-7. Bradof, J.N., J.D. Fenters, and R. Erhlich. 1978a. Effects of
Long-Term Exposure of Mice to Carbon and Acid Carbon Mists on Im-
muno Globulin M Forming Cells and Serum Immuno Globulin M Concen-
trations. Abstr. Annu. Meet. Am. Soc. Microbiol. 78:326.
Exposure to 1.4 mg/m3 H2S04 + carbon 3 h/d, 5 d/wk for 1 to 20 wk
caused immunoglobin M levels to increase after 1 wk, then a de-
crease. This type of change is a common stress response and
doesn't necessarily mean an immune effect unless other tests are
run.
144
-------
B-12. Bradof, J. N. , J. D. Fenters, and R. Ehrlich. 1978b. Respirable
Particles and Mists in Mouse Pulmonary Infectivity Model. Effect
of Chronic or Intermittent Exposure. PB-284904, National Techni-
cal Information Service, U.S. Department of Commerce, Springfield,
Virginia. 94 pp.
Mice exposed 3 h/d for 5 d to 200 rag H2S04/m3 mist and C particles
had alveolar damage, increased mortality, and decreased bacterial
clearance after being challenged with Streptococcus species. In-
creased mortality and pulmonary consolidation was seen in mice
challenged with a virus aerosol and exposed to 50 mg/m3 acid mist
and C particles for 3 h/d, 5 d/wk for 4 wk. Includes the details
of the study abstracted in Bradof et al. (1978a).
A-12. Brownstein, D.G. 1980. Reflex-Mediated Desquamation of Bronchi-
olar Epithelium in Guinea Pigs Exposed Acutely to Sulfuric Acid
Aerosol. Amer. J. Pathol. 98(3):577-590.
Eleven of twelve atropinized guinea pigs had no "regional desqua-
mation of airway epithelium" seen in 11/12 animals dosed with 32.6
H2S04 mg/m3 without the atropine pretreatment. Authors involve
parasympathetic effector blockage in H2S04 aerosol pathology.
They have not used another blocking agent to be sure this "protec-
tion" is not drying of airway or other atropine effect. Otherwise
(if this is real), it is a unique concept to follow further. Is
guinea pig a good human model in this?
C-13. Brownstein, D.G. and R.L. Beethe. 1978. Effects of Acute Exposure
to Sulfuric Acid Aerosol on Guinea Pig Lung Histamine. Annu. Rep.
Inhalation Toxicol. Res. Inst. pp. 382-384.
Histamine is involved in the reflex airway constriction response
to H2S04 to a small degree--(only in guinea pigs that get edema).
This paper is a very small part of a large study and has little
importance alone.
C-12. Brownstein, D.G., S.A. Silbaugh, and G.L. Christiansen. 1978a.
Evolution and Repair of Lung Lesions in Guinea Pigs Exposed Acutely
to Sulfuric Acid Aerosol. Annu. Rep. Inhalation Toxicol. Res.
Inst. pp. 378-381.
This is essentially a pathology report. Survivors had epithelial
desquamation in bronchioles after exposure to about 30 mg/m3 of an
average size (somewhat less than 1 |Jm MMD) aerosol. These are
baseline data, but adequate for what they cover.
145
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B-13. Brownstein, D.G., S.A. Silbaugh, and G.L. Christiansen. 1978b.
Effects of Anticholinergic, Antihistaminic, and Mast Cell Degranu-
lation Inhibiting Drugs on Acute Sulfuric Acid Induced Lung Injury
in Guinea Pigs. Annu. Rep. Inhalation Toxicol. Res. Inst. pp.
385-387.
Guinea pigs were pretreated with one of 3 airway-smooth-muscle con-
traction-inhibiting compounds, then exposed to ~29-35 mg H2S04/m3
(0.8-1.2 |Jm MMAD) for 1-4 h. The differences in the abilities of
these compounds to inhibit I^SC^-induced damage .(dyspnea and lung
lesions) indicate that, in guinea pigs, H2S04 toxicity is due to
parasympathetic effects. The question still remains of the appli-
cability of this finding to humans.
A-6. Busey, W.M., and T.T. Frankenberg. 1973. Physiological Responses
to Sulfur Dioxide, Sulfur Trioxide, Fly Ash, and Their Mixtures.
Proc. Amer. Power Conf. 35:504-509.
A review of work done at the Hazleton Laboratories, Inc., Vienna,
Virginia, includes a discussion of Alarie et al. (1973) and (1975).
C-7. Bushtueva, K. A. 1957a. The Determination of the Limit of Allow-
able Concentration of Sulfuric Acid in Atmospheric Air [Materialy
k Ustanovleniyu Predel'no Dopustimoi Kontsentratsii Aerozolya
Sernoi Kisloty Atmosfer nom Vozdukhe]. Predel'no Dopustimye
Kontsentratsi Atmosfernykh Zagryaznenii [Limits of Allowable Con-
centrations of Atmospheric Pollutants]. 33:23-43.
Several studies with small numbers of people on their local reflex
response (e.g., light sensitivity of the eye, cough) to H2S04 in-
dicate that the threshold of irritation by H2S04 was 0.6-0.86
mg/m3.
. . . i
B-10. Bushtueva, K. A. 1957b. Toksikologii Aerozolya Sernoi Kisloty
[The Toxicity of H2S04 Aerosol]. Gig. Sanit. 22:17-22.
v.
Guinea pigs showed a dose-response relationship to 120-h exposure
to 2, 4, or 8 mg H2S04/m3. Decreased weight gain and macro- and
microscopic pulmonary changes were seen at all exposure levels.
There was some recovery in the 3 wk after exposure.
C-7. Bushtueva, K. A. 1960. Threshold Reflex Effect of S02 and Sul-
furic Acid Aerosol Simultaneously Present in the Air [Porog
Reflektornogo Deistviya Sernistogo Gaza i Aerozolya Sernoi Kisloty
pri Sovmestnom Prisustvii]. Predel'no Dopustimye Kontsentratsii
Atmosfernykh Zagryaznenii [Limits of Allowable Concentrations of
Atmospheric Pollutants]. 4:92-101.
146
-------
The methods of dark adaptation and optical chronaximetry were used
to determine the subthresholds of reflex action: 0.6-0.63 H2S04/
m3 alone, 1-1.2 mg S02/m3 alone, and 1.2 mg S02/m3 plus 0.4 mg
H2S04/m3 together. The 2 compounds act synergistically at sub-
threshold levels.
C-6. Bushtueva, K. A. 1962. New Studies of the Effect of Sulfur Diox-
ide and of Sulfuric Acid Aerosol on Reflex Activity of Man [Novye
Dannye o Reflektornom Deistvii Sernistogo Gaza i Aerozolya Seriioi
Kisloty na Cheloveka]. Predel'no Dopustimye Kontsentratsii At-
mosfernykh Zagryaznenii [Limits of Allowable Concentrations of At-
mospheric Pollutants]. 5:118-125.
A discussion of the use of several different neurological, reflex
tests to determine the threshold of reflex action of H2S04, in-
cluding EEG (0.63 mg/m3) and "electrocortical" conditioned reflex
(0.4 mg/m3).
D— Bustueva, K. A. 1966. Toksichnost1 Okislov Sery v Usloviyakh
Dlitel'nogo Nepreryvnogo Deistviya. [The Toxicity of Sulfur Ox-
ides Under Conditions of Continuous Exposure]. In: Biol. Deistvie
i Gigien. Znachenie Atm. Zagryazenii [The Biological Effect and Hy-
gienic Significance of Atmospheric Pollutants], pp. 142-172; Chem.
Abstr. 1966. 65:11223a.
Rats exposed to 2-|Jm particles of H2S04 at 1.04 and 1.8 mg/m3
showed slight elevations in serum gamma-globulin.
A-0. Bushtueva, K.A. 1976. Health Effects of Sulfur Dioxide and Sul-
furic Acid Aerosols. Proc. Int. Conf. Environ. Sensing Assess.
1:1-3.
Review for a standard. Nothing new but good tabulations of the
papers the author considered important, both Russian and world
literature.
C-- California State Department of Public Health. 1960. Technical
Report of California Standards for Ambient Air Quality and Motor
Vehicle Exhaust. California Department of Public Health, Berkeley,
California, pp. 61-68.
Chronic exposures to 0.25 mg H2S04/m3 of particle size ~ 1 pm are
assumed unlikely to have an ill effect upon healthy humans.
147
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C-14. Campbell, K. I., E. L. George, and I. S. Washington, Jr. August
1980 (expected publication date). Enhanced Susceptibility to In-
fection in Mice After Exposure to Dilute Exhaust from Light Duty
Diesel Engines. In: Proc. Int. Symp. on Health Effects of Diesel
Engine Emissions. Sponsored by U.S. Environmental Protection
Agency, Cincinnati, Ohio. December 3-5, 1979. 14 pp.
Data were not tabulable because there was no indication of what
the sulfate or sulfuric acid concentration in the diesel exhaust
was (although H2S04 is known to be the major soluble sulfate spe-
cies in diesel exhaust [Truex et al. 1980. Sulfate in Diesel Ex-
haust. Environ. Sci. Technol. < 14(9):1118-1120.]). Female albino
CR/CD-1 mice, 4-8 weeks old, were exposed to diesel exhaust con-
taining 6-7 mg particulate/m3 for from 2 h once to 8 h/d, 7d/wk
for 46 wk and also exposed to Streptococcus pyogenes or A/PR8-34
influenza virus for 0.25-0.5 h each time. Mortality among the
rats exposed to diesel exhaust and then S. pyogenes was signifi-
cantly higher than among rats exposed to clean air for the corre-
sponding periods.
C-0. Cavender, F.L., and W.J. Steinhagen. 1976. Sulfuric Acid Mist
Toxicity Based on the Irritant Response versus Subacute Studies.
Am. Rev. Respir. Dis. 113:90.
An abstract of work in progress, and a discussion of the impor-
tance of relative humidity to H2S04 toxicity. No data are given.
C-9. Cavender, F. L., W. H. Steinhagen, C. E. Ulrich, W. M. Busey, and
R. T. Drew. 1975. Subacute Studies of Ozone and Sulfuric Acid
Mist and Their Mixtures. AMRL-TR-125, National Technical Infor-
mation Service, Springfield, Virginia, pp. 297-304.
Preliminary for 03/H2S04 synergism study.
B-13. Cavender, F.L., W.H.-Steinhagen, C.E. Ulrich, W.M. Busey, B.Y.
Cockrell, J.K. Baseman, M.D. Hogan, and R.T. Drew. 1977. Effects
in Rats and Guinea Pigs of Short-Term Exposures to Sulfuric Acid
Mist, Ozone, and Their Combination. J. Toxicol. Environ. Health.
3:521-533.
Rats exposed to 5-20 mg H2S04/m3 (1 (Jm) were unaffected. Guinea
pigs had definite microscopic lung alterations at 20 mg/m3. In
combination with 02 the effects seemed to be due essentially to
03. The use of some nonparametric statistics with this large a
sample size indicates large variability or other problems in test
replicability.
148
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A-13. Cavender, F.L., W.M. -Busey, and B.Y. Cockrell. 1978b. Sulfuric
Acid Mist: A Pulmonary Irritant in Guinea Pigs. Toxicol. Appl.
Pharmacol. 45:286.
More information is in Cavender et al. (1978c) and Cockrell et al.
(1977).
The implication from this paper is that the acute effect seen in
guinea pigs in response to H2S04 is a reversible histamine effect,
and that long-term exposure (after histamine depletion) produces
much less toxicity.
B-ll. Cavender, F.L., B. Singh, and B.Y. Cockrell. 1978c. Effects in
Rats and Guinea Pigs of Six-Month Exposures to Sulfuric Acid
Mist, Ozone, and Their Combination. J. Toxicol. Environ. Health.
4:845-852; practically the same article appeared in J. Environ.
Pathol. Toxicol. 2(2):485-492 (1978a).
Rats and guinea pigs exposed to 10 mg H2S04/m3 and/or 0.5 ppm 03
for 6 h/d, 5 d/wk for 6 mo showed only microscopic lung changes
for the guinea pigs exposed to 03 or 03 + H2S04.
Good for what it does cover, but no airflow measures or labile
smooth muscle or hormonal effects (histamine) measured as a mea-
sure of toxicity, only body weight and histopathology at terminal
necropsy. This approach could miss toxic effects of most impor-
tance to humans.
C-12. Chaney, S., W. Blomquist, K. Muller, and P. DeWitt. 1979. Bio-
chemical Effects of Inhalation of Sulfuric Acid Mist by Human Sub-
jects at Rest. PB80210552, National Technical Information Ser-
vice, U.S. Department of Commerce, Springfield, VA. 21 pp^
No significant effect was seen on seven blood parameters in young
human males at rest exposed to 0.100 mg H2S04/m3 for 4 h/d for two
consecutive days. Elegant methods and equipment are coupled with
the best in statistical analysis. However, the results are nega-
tive, and the rationale and discussion are not clear-cut. Find-
ings are consistent with previous lack of effect on blood biochem-
istry of H2S04-exposed animals.
C-ll. Chaney, S., W. Blomquist, K. Muller, and G. Goldstein. 1980a.
Biochemical Changes in Humans upon Exposure to Sulfuric Acid Aero-
sol and Exercise. Arch. Environ. Health 35(4):211-216.
Innovative paper. (See remarks on Chaney et al., 1979). Exer-
cised humans exposed to 0.100 mg H2S04/m3 for 4 h showed no ef-
fects on several blood or lung function parameters. (The latter
data are to be reported in a separate paper.)
149
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C-12. Chancy, S., W. Blomquist, K. Muller, and P. DeWitt. 1980b. Bio-
chemical Effects of Inhalation of Sulfuric Acid Mist by Human Sub-
jects at Rest. PB80210552, National Technical Information Ser-
vice, U.S. Department of Commerce, Springfield, VA. 21 pp.
Same data as reported by Chaney et al. (1979).
C-7. Chapman, R.S., C.M. Shy, J.F. Finklea, D.E. Hoose, H.E. Goldberg,
and C.G. Hayes. 1973. Chronic Respiratory Disease in Military in-
ductees and Parents of Schoolchildren. Arch. Environ. Health. 27:
138-142.
An EPA Community Health and Environmental Surveillance Study
(CHESS) correlates urban pollution with chronic respiratory dis-
ease prevalence as measured by questionnaire. Although measure-
ments of suspended sulfates were made, deficiencies in analysis
of the sulfate estimates are not reliable. [See reference 107
cited at page 14-260, EPA (1980).] These studies are not capable
of associating urban health differences with specific air pollut-
ants. Exposure estimates are crude at best. These studies also
characterized by extremely high nonresponse rates (> 60%) in ques-
tionnaire data. (Therefore, probable selection bias.) The mili-
tary recruit study referred to at page 14-260 of EPA (1980) may be
more useful for determining a sulfate criteria. A technical cri-
tique of this study is given on page 92 of Appendix A in EPA
(1980).
B-12. Coate, W., W. Busey, and W. S. Schoensisch. 1975. Interactive
effects of sulfuric acid mist and nitrogen dioxide on cynomolgus
monkeys. Report ISS EPRI-201. Hazleton Lab. America, Inc.,
Vienna, Virginia. 64 pp.
Monkeys exposed almost continuously for 26 wk to ~0.5-1 mg H2S04/
m3 and/or ~1 or 5 ppm N02 did not show any compound-related ef-
fects in measurements of pulmonary function, blood, or serum.
However, a possible synergism was indicated. Microscopic lung
changes were seen in monkeys exposed to the highest concentrations
of H2S04 + N02 but not in monkeys exposed to those concentrations
of each alone.
A-10. Cockrell, B.Y., W.M. Busey, F.L. Cavender, W.H. Steinhagen, arid
R.T. Drew. 1976. Light Microscopic and Electron Microscopic Pul-
monary Changes in Rats and Guinea Pigs Exposed to Sulfuric-Acid
Mist. Am. Rec. Respir. Dis. 113:91.
This looks like a good study, but data are insufficient.
150
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No rats had lung effects. Even electron microscope detectable le-
sions were absent after 5-100 mg/m3 for 48 h to 6 mo. [No study
design was given.]
All guinea pigs, on the other hand, showed effects at these expo-
sures. They used three different particle sizes and got the same
effects.
B-8. Cockrell, B. Y., N. J. Woodside, W. M. Busey, and H. W. Sugg.
1977. Correlation of Light and Electron Microscopic Pulmonary Le-
sions in Guinea Pigs Exposed to Sulfuric Acid Mist. Lab. Invest.
36:334.
An abstract of work in progress, so some data such as R.H. are not
given. Careful histopathological examination was done. These re-
sults corroborate Cavender et al. (1978b) in that acute exposure
to 20 mg/m3 is toxic: hemorrhage spots, edema, and macrophage in-
filtration were reported here. [If Wolff is correct that the
Hartley strain of guinea pig produces an all-or-none response; 1-h
ED100 is 20 mg/m3.]
D-8. Cockrell, B.Y., W.M. Busey, and F.L. Cavender. 1978. Respiratory
Tract Lesions in Guinea Pigs Exposed to Sulfuric Acid Mist. J.
Toxicol. Environ. Health. 4:835-844.
The guinea pigs were given an adequate dose (25 mg H2S04/m3 for 6
h/d for 2 d) to produce lesions, then the histopathology was very
well described. This type of data will be very limited in helping
to determine the level of concern for H2S04 in automobile emis-
sions .
C-8. Committee on Sulfur Oxides, National Research Council. 1978.
Sulfur Oxides. National Academy of Sciences. Washington, D.C.
209 pp.
Sulfuric acid and acid sulfates in this review are left without
a firm suggestion for a standard level.
B-14. Dahl, A.R. 1978. Deposition of Sulfuric Acid Aerosols in Rats
as Affected by Ambient Relative Humidity, Aerosol Droplet Size
and Concentration of the Aerosol. Annu.< Rep. Inhalation Toxicol.
Res. Inst. pp.-319-322.
This paper found that humidity was not important in 0.4 (Jm drop-
lets' deposition, but size was important.
151
-------
B-ll. Dahl, A. R. 1979. Deposition and Clearance of Sulfuric Acid Mist
in Rats, Guinea Pigs and Dogs. Annu. Rep. Inhalation Toxicol.
Res. Inst. LF-69:462-468.
Deposition patterns studied.
B-12. Dahl, A. R., and G. M. Furst. 1979. Pulmonary Retention of Sul-
fur Oxo Anions. Toxicol. Lett. 4:425-431.
35S administered as sulfate was retained by the trachea more
readily than when administered as sulfite. This may have no
toxicological significance because of abundant endogenous sul-
fate in trachea.
B-9. Dahl, A.R., B.A. Muggenburg, and S.A. Felicetti. 1978a. Deposi-
tion and Clearance of Sulfuric Acid From the Respiratory Tract of
Beagle Dogs. Annu. Rep. Inhalation Toxicol. Res. Inst. pp.
328-331.
Nose-only exposure of a dog to 25.7 mg H2S04/m3 (0.4 (Jm MMAD) in-
dicated that deposition of the aerosol was mostly in the upper
respiratory tract and not the lung. Blood clearance studies were
done on an unknown number of dogs following nasal or bronchial
instillation.
B-ll. Dahl, A.R., B.A. Muggenburg, and S.A. Felicetti. 1978b. Deposi-
tion and Clearance of Sulfuric Acid from the Respiratory Tract of
Beagle Dogs. Aniiu. Rep. Inhalation Toxicol. Inst. LF-60:328-331.
A dog exposed to 0.4-|Jm-MMAD droplets of 35S-labeled H2S04 mist
showed blood clearance similar to that for nasal instillation.
B-9. Dahl, A.R., G.M. Furst, and F.F. Hahn. 1979. Retention and Fate
of Sulfur Compounds Deposited in the Respiratory Tract of Rats.
Annu. Rep. Inhalation Toxicol. Res. Inst. LF-69:469-472.
Intratracheal instillation of labelled sulfuric acid in one rat
indicated no sites of concentration of the label in the lung 48
h later.
C-- Dalbey, W. E. 1980. Laboratory Studies of Biological Effects of
Sulfur Oxides. In: Atmospheric Sulfur Deposition: Environmental
Impact and Health Effects, 2nd ed., D. S. Shriner, C. R. Richmond,
and S. E. Lindberg, Eds. Ann Arbor Science Publishers, Inc., Ann
Arbor, Michigan. pp._ 69-75.
A brief review of animal studies.
152
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D-4. Dautrebande,~L., J. Shaver, and R. Capps. 1951. Studies on Aero-
sols. XI Influence of Particulate Matter on the Eye Irritation
Produced by Volatile Irritants and Importance of Particle Size in
Connection with Atmospheric Pollution. Arch. Int. Pharm. 85:
17-48.
Sulfuric acid toxicity cannot be evaluated due to the use of a
mixture (artificial Los Angeles Air): formaldehyde, organic
peroxides, S02, nitrous oxides, etc. (H2S04 = 0.001 to 0.033
mg/m3 as constituent).
Equipment and scoring techniques for human subjects' eye exposure
were good.
^
D-12. Demerec, M., E. M.,Witkin, B. W. Catlin, J. Flint, W. L. Belser,
C. Dissoway, F. L. Kennedy, N. C. Meyer, A. Schwartz. 1950. The
Gene. Carnegie Institute Washington Yearb. 49:144-157.
Methods development paper for Demerec et al. (1951).
C-12. Demerec, M., G. Bertani, and J. Flint. 1951. A Survey of Chemi-
cals for Mutagenic Action on E. Coli. Am. Naturalist 85:119-136.
Negative results for mutagenesis study with 0.002-0.005% H2S04 and
Escherichia coli.
C-8. Dohan, F. C., G. S. Everets, and R. Smith. 1962. Variations in
Air Pollution and the Incidence of Respiratory Disease. Journal
of the Air Pollution Control Association. 12:418-422, 436.
There is evidence from several studies that there is a correlation
between the concentration of suspended particulate sulfates (<~25
(Jg/m3) in the air and the incidence of respiratory disease. Fails
'. to do multiple regression; considers sulfates only, ignoring co-
varying pollutants and other factors.
B-6. El-Sadik, Y.M., H.A. Osman, and R.M. el-Gazzar. 1972. Exposure
to Sulfuric Acid in Manufacture of Storage Batteries. J. Occup.
Med. 14:224-226.
This study of 33 exposed workers showed:
(1) exposure to H2S04 does not increase/cause chronic
bronchitis and or asthmatic bronchitis.
(2) exposure to H2S04 does not cause decrease in forced
expiratory volume.
153
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(3) data indicated a relationship between work time and
dental erosion and'salivary pH.
The variation in some measures is quite high!
D-- EPA, U.S. Environmental Protection Agency, Office of Air and Waste
Management, Office of Air Quality Planning and Standards. 1975.
Position Paper on Regulation of Atmospheric Sulfates. PB-245 760.
National Technical Information Service, U.S. Department of Com-
merce, Springfield, Virginia. 86 pp.
, A review; state of the art, regulations and standards establish-
ment. This review concluded that more study would be necessary
before anything could be decided on the regulation of atmospheric
sulfates.
EPA. 1980i Environmental Protection Agency. Air Quality Criteria
for Particulate Matter and Sulfur Oxides.
An excellent comprehensive review. Chapters 12-14 were used as a
source for many references. This is a review draft not to be
cited.
C-12. Fairchild, G.A., P. Kane, B. Adams, and D. Coffin. 1975a. Sul-
furic Acid and Streptococci Clearance from Respiratory Tracts of
Mice. Arch. Environ. Health. 30:538-545.
Exposure to 15 mg H2S04/m3 after exposurd to Steptococci slowed
bacterial clearance from nose and lungs. Exposure to 15 mg H2S0
m3 before bacterial exposure slowed clearance in the nose only.
1.5 mg/m3 had no effect on clearance.
Four-day pre-bacterial H2S04 exposure data unconvincing in toxic
effect--large anatomical differences in nose of mouse and man.
Post-bacterial exposure to H2S04 strengthens the idea of a tran-
sient effect that may disappear in longer exposures.
A-ll. Fairchild, G.A. , S. Stultz, and D.L. Coffin. 1975b. Sulfuric Acid
Effect on the Deposition of Radioactive Aerosol in the Respiratory
Tract of Guinea Pigs. Am. Ind. Hyg. Assoc. J. 36:584-594.
Nicely done study. The high dose arid low dose of H2S04 aerosol
to anesthetized guinea pigs caused radioactive 1.8 (Jm particles
to be deposited higher in respiratory tract in a dose-response
mode. No tidal volume respiratory rate or minute volume change oc-
curred. It is a complicated assessment, but is probably another
measure of increased airway resistance and of the big particles
caught up higher in the respiratory tract.
154
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C-17. Fenters, J.D., J. N. Bradof, C. Aranyi, K. Ketels, R. Ehrlich,
and D.E. Gardner. 1979. Health Effects of Long-Term Inhalation
of Sulfuric Acid Mist - Carbon Particle Mixtures. Environ. Res.
19:244-257.
Alterations of the immune defense system suggest that prolonged
exposure to carbon-acid mixtures reduces the ability of mice to
resist respiratory infection. See Bradof et al. (1978a) and
(1978b).
C-9. Ferris, B.C., Jr., I.T.T. Higgins, M.W. Higgins, and J.M. Peters.
1973. Chronic Nonspecific Respiratory Disease in Berlin, New
Hampshire, 1961 to 1967. Am. Rev. Resp. Dis. 107:110-122.
Comparison of two cross-sectional studies for prevalence of re-
spiratory symptoms and disease suggests relating small differences
when effects of possible conformity by age, smoking, occupation,
etc., are considered. (See Holland et al., 1979.) Possibility of
selecting out healthier cohort exists due to possible loss of per-
sons with respiratory illness (change of climate, etc.). Holland
suggests the two surveys may not be comparable, since the 1967
study was undertaken during the summer and the 1961 study during
the winter when respiratory symptoms are more prevalent. In any
case, this study does not specifically implicate sulfuric acid or
atmospheric sulfates as the cause of the respiratory illness in
1961.
D-9. Finelli, V. N., M. Karaffa, M. Malanchuk, R. M. Banner, L.
McMillan, and S. D. Lee. 1976. Biological Effects of Carbon Mon-
oxide Versus Whole Emissions from Engineer with Catalyst. Air
Pollut. Control Assoc. J. 26(3):231-233.
The avg. S0| level in the exhaust without a catalytic converter,
from fuel containing 500 ppm sulfur, was 0.08 mg/m3. Exhaust
from a converter contained 0.61 rag S0| /m3 (fuel had 500 ppm sul-
fur) or 11.3 mg S0|~/m3 (fuel had 1,000 ppm). Only a slightly
elevated serum triglyceride level was noted in rats exposed for
4 wk to the exhaust emissions (both irradiated and nonirradiated).
B-5. Finelli, V.N., S.D. Lee, R.M. Banner, J. Boiano, L. McMillan, and
G.P. Cooper. 1978. Inhalation of Sulfate Particulates. II: Pul-
monary Biochemical Effects. Toxicol. Appl. Pharmacol. 45:246.
This paper presented the concept that edema and inflamation oc-
curred in rats exposed to H2S04, but infiltrating cells remained
normal, as opposed to aluminum sulfate (positive control), which
produced macrophage swelling and granulation. It concluded that
toxicity was due to Al3 and not to SOf .
155
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D-5. Firket, J. 1936. Fog Along the Meuse Valley, Trans. Faraday Soc.
32:1192-1197.
Historical interest only. The fog itself could not be analyzed.
Soil deposits could not be analyzed, so chemists conjectured that
S02 was oxidized to S03 and sulfuric acid in the fog. Yet this is
one of the first suggestions that sulfuric acid mist may be a
factor in the excessive mortality associate with "polluted fog."
D-6. Flury, F., and F. Zernik. 1931. Schwefelsa'ure [Sulfuric Acid].
In: Scha'dliche Case [Harmful Gases]. Julius Springer. Berlin.
1931 (1969 Printing), pp. 145-146.
Review cites dissertation of Dorsch, Wflrzburg, 1913, which gave
the following manifestations after inhalation of sulfuric acid-
containing air in a battery workplace (in mg/m3):
0.5 Scarcely noticeable annoyance
0.5-2 Slight annoyance
3-4 Significant annoyance
6-8 Strong annoyance
D-- ^ Freeman, G., and L. T. Juhos. 1976. Effects of Oxidant and Sul-
fate Interaction on Production of Lung Lesions. PB-251 729. Na-
tional Technical Information Service, Springfield, Virginia.
29 pp.
All the experiments with H2S04 were preliminary ones, determining
a 24-h LC50 (60-84 mg/m3) and a 1-wk LC50 (52-58 mg/m3).
C-9. French, J.G., G. Lowrimore, W.C. Nelson, J.F. Finklea, T. English
and M. Hertz. 1973. The Effect of Sulfur Dioxide and Suspended
Sulfate on Acute Respiratory Disease. Arch. Environ. Health.
27:129-133.
Results of research conducted under EPA's Community Health and En-
vironmental Surveillance Study (CHESS) program demonstrate that
families exposed to high levels of urban pollution experience
higher acute respiratory disease attack rates than do those less
exposed. S02 and sulfates are markers of pollution in these
studies, along with suspended particulates. It is not possible
to be certain that the correct pollutant is even being measured.
B— Gamble, J. (NIOSH). 1979. Morbidity and Industrial Hygiene Study
Workers Exposed (SO , H2S04, NO , N03)-EPA. Toxicol. Res. Proj.
Dir. 4(1):SSIE/DI.X X
156
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Acute and chronic exposure to the named aerosols will be studied
among appropriate occupational groups. Dose-response effects will
be studied for respiratory symptoms, chest x-rays, pulmonary func-
tion, and dental erosion. H2S04 exposure will be studied in bat-
tery workers.
C-0. Gardner, D.E. 1979. Alteration in Host-Bacteria Interaction by
Environmental Chemicals. In: Assessing Toxic Effects of Environ-
mental Pollutants, S.D. Lee and J.B. Mudd, eds. Ann Arbor Science
Publishers Inc., Ann Arbor, Michigan, pp. 87-103.
A review plus a brief comment on their own results. Their tra-
cheal organ culture detected toxicity from only 900 |jg H2S04/m3 in
hamsters exposed in vivo.
C-9. Gardner, D.E., F.J. Miller, J.W. Illing, and J.M. Kirtz. 1977.
Increased Infectivity with Exposure to Ozone and Sulfuric Acid.
Toxicol. Lett. 1:59-64.
The effect was observed only when 03 exposure immediately preceded
H2S04 exposure. Is it a measure of a weakened animal? (03 + air
killed more animals than H2S04 + air) Is it a faster respiration
rate; deeper breaths or more shallow breaths? The percent deaths
from subsequent respiratory infection is a highly labile end point.
A-12. Gardner, D.E., M. Hazucha, J.H. Knelson, and F. Miller. 1978. The
Effects of Sulfuric Acid on Men and Sulfuric Acid and Ozone on
Laboratory Animals. In: Energy/Environment III. Proceedings of
3rd National Conference on the Interagency R&D Program Held at
Washington, B.C., on June 1 and 2, 1978. EPA-600/9-78-022, PB-
290 558, National Technical Information Service, U.S. Department
of Commerce, Springfield, Virginia, pp. 51-60.
In the human exposure studies, those exposed to 66 pg H2S04/m3 had
the most changes (particularly increased airway resistance), com-
pared to 100 |Jg/m3 and 195 (Jg/m3. This could be due to different
particle sizes (not given). It is also characteristic of a trig-
gered hormone effect--histamine, SRSA, bradykinin? There was no
increase in deaths after mice were exposed to 900 (Jg sulfate/m3
for 2 h then Streptococcus, compared to those just receiving bac-
terial exposure. There was a depression of ciliary activity in
hamsters seen for 72 h following a 2-h exposure to 1 mg H2S04/m3.
D-9. Goldman, A., and W.T. Hill. 1953. Chronic Bronchopulmonary Dis-
ease Due to Inhalation of Sulfuric Acid Fumes. A.M.A. Arch. Ind.
Hyg. Occup. Med. 8:205-211.
157
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Case Report: A 40-year-old man was exposed accidentally to fuming
sulfuric acid and for 8 minutes to a heavy concentration of sul-
furic acid mist following use of a safety water shower. Immediate
effects were laryngeal, tracheobronchial, and pulmonary edema,
followed later by multilobe bronchiectasis, interstitial fibrosis,
and pulmonary emphysema. The lesions described have been produced
in guinea pigs exposed to sub-lethal doses of sulfuric acid mist.
C-8. Gorham, E. 1959. Pneumonia and Atmospheric Sulfate Deposit.
Lancet. 2:287-288.
Simple correlation analysis of pneumonia mortality rates and at-
mospheric sulfate deposit (g/100 mi2/month). Confirms well-known
observation that pneumonia mortality rates are higher in urban
areas and that sulfate deposits are better markers of urban pol-
lution than tar, ash, or other combustible material.
B-6. Grose, E., F. Miller, and D.E. Gardner. 1978. The Effects of
Ozone and Sulfuric-Acid on Ciliary Activity of Syrian Hamsters.
Pharmacologist. 20:211.
Exposure of hamsters in vivo to 0.9 mg H2S04/m3 plus 0.196 mg 03/
m3 for 3 h did not cause significant differences between tracheal
ring cultures of exposed and control animals. However, if the
H2S04 exposure followed a 3-h 03 exposure or if exposure was to
H2S04 alone, the test tracheal ring cultures exhibited significant
ciliary activity decreases.
/
C-8. Grose, E. C., D. E. Gardner, and F. J. Miller. 1980. Response
of Ciliated Epithelium to Ozone and Sulfuric Acid. Environ. Res.
22(2):377-385.
Results show apparent antagonism between 03 and H2S04 on ciliary
activity. The reduction in ciliary beating frequency in an in
vitro model upon acute exposure of hamsters in. vivo to ~0.84 or
0.88 mg H2S04/m3 was greater than when the hamsters were exposed
to 0.196 mg 03/m3 followed by 1.09 mg H2S04/m3. The hamsters were
allowed 0-, 24-, 48-, or 72-h recovery periods before their tra-
cheal explants were cultured for 72 h.
C-ll. Hackney, J.D. 1978. Effects of Sulfate Aerosols Upon Cardiovas-
cular Function in Squirrel Monkeys. Final Report. APRAC Project
CAPM-20-74, Coordinating Research Council, Inc., New York.
Acute exposure of monkeys to 2.5 mg H2S04/m3 (40% R.H. , 0.4 [jm
MMAD) appeared to cause an increase in respiratory resistance.
The text is primarily on methods development.
158
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C-ll. Hackney, J.D. 1980. Effects of Sulfate Aerosols Upon Cardiovas-
cular Function in Squirrel Monkeys. Final Report. APRAC Project
CAPM-20-74, Coordinating Research Council, Inc., New York.
Acute exposure of monkeys to 2.5 rag H2S04/m3 (40% R.H., 0.4 MMAD)
appeared to cause an increase in respiratory resistance. The
text is primarily on methods development.
C-- Hackney, J.D., W.S. Linn, M.P. Jones, R.M. Bailey,"D.R. Julin,
and M.T. Kleinman. 1980. Short-Term Respiratory Effects of
Sulfur-Containing Pollutant Mixtures: Some Recent Findings from
Controlled Clinical Studies. In: Atmospheric Sulfur Deposition:
Environmental Impact and Health Effects, 2nd ed., D.S. Shriner,
C.R. Richmond, and S.E. Lindberg, Eds. Ann Arbor Science Publish-
ers, Inc., Ann Arbor, Michigan, pp. 77-84.
This review includes a presentation of results published by
Kleinman et al. (1979; 1981).
C-6. Halliwell, W. H. (Lovelace Foundation for Medical Education and
Research; Inhalation Toxicology Research Institute). 1979. In-
jury and Repair After Inhalation Exposure to Particulate Acid Sul-
fate. Toxicol. Res. Proj. Div. 4(1):SSIE/ZPE 12493 1.
The histopathology of animal lungs after exposure to sulfuric acid
mist or ammonium sulfate are being studied by light and electron
microscopy.
A-13. Henderson, R. F., R. K. Wolff, A. H. Rebar, D. B. Denicola, and
R. L. Beethe. 1978. Early Indicators of Lung Damage from Inhaled
Sulfuric Acid Mist. Annu. Rep. Inhalation Toxicol. Res. Inst.
pp. 352-355.
Changes reported as a result of sulfuric acid mist in this study
were at a rate that physiological repair functions occurred (fi-
brin changes, ciliary clearance rate, etc.). This may give clues
to long-term effects seen in similar designs. With no particu-
lates, H2S04 at 10 and 100 mg/m3 did not produce biochemical
changes in rat lung but did increase clearance rate of a test par-
ticle significantly. This publication was made before histopatho-
logical results were obtained.
B-9. Hickey, R., D. E. Boyce, E. B. Harner, and R. C. Clelland. 1970.
Ecological Statistical Studies on Environmental Pollution and
Chronic Disease in Metropolitan Areas of the United States. Re-
gional Science Research Institute Discussion Paper Series 35,
October 1970; IEEE Trans. Geosci. Electronics GE-8(4):186-202.
159
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These authors have looked at the negative side of a two-sided epi-
demiologic hypothesis, in that very low long-term exposure to cer-
tain chemicals (including S02 and particulate sulfate according to
these authors) can cause cumulative damage to DMA. They have as-
sociated exposure to disease mortality in 38 metropolitan areas
during 1957-1964, using multivariate analysis. SC>2 levels used
ranged from 12 to 450 [Jg/m3.
D-- Hinners, R.G., J.K. Burkart, and G.I. Contner. 1966. Animal Expo-
sure Chambers in Air Pollution Studies. Arch/Environ. Health.
13:609-615.
This paper presented no health effects data, but contained infor-
mation on the design of animal exposure chambers. It considered
almost everything but had no mention of:
1. How do they assure that the drinking water stays
acid free with H2S04 aerosols?
2. Will breath and urinary ammonia be monitored and
controlled for input on results?
C-6. Hitchcock, D.R. 1979. Lung Cancer Mortality and Hydrogen Sulfide
Sources in Southeastern Coastal States. Fed. Proc. 38:1270.
Preliminary report: Interesting observation. Conjecture probably
based on Mason's (NCI) maps of cancer mortality by county. Death
certificate data of this type, needs careful validation for occupa-
tion, smoking, etc., as well as for cause of death. Measurements
of exposure specific to this region will need to be made.
C-9. Hoffman, D.J., and K.I. Campbell. 1977. Embryotoxicity of Irradi-
ated and Nonirradiated Catalytic Converter-Treated Automobile Ex-
haust. J. Toxicol. Environ. Health. 3:705-712.
The study design included a H2S04 aerosol control chamber (6.06
mg/m3 0.20-0.30 \im MMAD). This exposure had a slight effect on
survival of chicken embryos, and significantly decreased embryonic
weight and serum LDH activity levels.
Holland, W. W., A. E. Bennett, I. R. Cameron, C. du V. Florey,
S. R. Leeder, R. S. F. Schilling, A. V. Swan, and R. E. Waller.
1979. Health Effects of Particulate Pollution: Re-appraising
the Evidence. Am; J. Epidemiol. 110:525-659.
No rating. Review.
160
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B-14. Hyde, D., J. Orthoefer, D. Dungworth, W. Tyler, R. Carter, and
H. Lum. 1978. Morphometric and Morphologic Evaluation of Pul-
monary Lesions in Beagle Dogs Chronically Exposed to High Ambient
Levels of Air Pollutants. Lab. Invest. 38:455-469.
The chronic experiments with beagle dogs begun by Vaughan et al.
(1969) were concluded here with the necropsy of the remaining
dogs, which had been exposed to H2S04 and S02 with or without
irradiated or nonirradiated auto exhaust followed by 32-36 mo of
exposure to clean air. The 8 animals exposed to S02 (1.10 rrig/m3)
and H2S04 (0.09 mg/m3) showed ciliary loss without squamous meta-
plasia, nonciliated bronchiolar cell hyperplasia, and air space
enlargement primarily in the region of respiratory bronchioles
and alveolar ducts [which the authors consider to be analogous to
an incident stage of human proximal acinar (centrilobular) emphy-
sema] . Similar changes were seen when automobile exhaust was in-
cluded in the exposure except that the ciliary loss was not sig-
nificant in the dogs exposed to irradiated auto exhaust, S02, and
H2S04; and the ciliary loss in the dogs exposed to nonirradiated
exhaust, S02, and H2S04 was accompanied by squamous metaplasia.
D— Hysell, D. K., W. Moore, R. Hinners, M. Malanchuk, R. Miller, and
J. F. Stara. 1975. Inhalation Toxicology of Automotive Emissions
as Affected by an Oxidation Exhaust Catalyst.
Sulfuric acid was suspected to be the major component of the par-
ticulate from catalytic converter exhausts, but accurate measure-
ments of its concentration were not made. There were no demon-
strable biological effects in any of the animals exposed for 7 d
to these exhausts containing up to 6.53 mg particulate/m3.
D-4. John, J.A., F.J. Murray, J.S. Murray, B.A. Schwetz, and R.E.
Staples. 1979. Evaluation of Environmental Contaminants, Tetra-
chloroacetone, Hexachlorocyclopentadiene, and Sulfuric Acid Aero-
sol for Teratogenic Potential in Mice and Rabbits. Teratology
19:32A-33A.
When 5 and 20 mg/m3 H2S04 aerosols, were administered to pregnant
CFj mice and New Zealand rabbits during days 6-16 and 6-18 of ges-
tation, there were no teratogenic effects seen in the offspring.
There were no data on controls or aerosol size.
B-ll. Juhos, L.T., M.J. Evans, R. Mussenden-Harvey, N.J. Furriosi, C.E.
Lapple, and G. Freeman. 1978. Limited Exposure of Rats to H2S04
with and without 03. J. Environ. Sci. Health C13:33-48.
Rats exposed to 2 mg H2S04/m3 (0.3 pm MMD), H2S04 +0.9 ppm 03,
or 0.9 ppm 03 for 82 d showed slight respiratory tract injury.
161
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D-8. Kaizu, T., and J.A. Last. 1978. Characterization of Mucus Glyco
Proteins Secreted by Tracheal Explants from Rats and Monkeys.
Clin. Res. 26:136A.
This is an abstract of work in progress, a methods and character-
ization study, not an effects paper. While not relevant to this
project on health effects, the information could be used in other
investigations of pollutant effects on mucus.
A-9. Kerr, H. D., T. J. Kulle, B. P. Farrell, L. R. Sauder, J. L. Young,
D. L. Swift, and R. M. Borushok. 1979? Effects of Sulfuric Acid
Aerosol on Pulmonary Function in Human Subjects. An Environmental
Chamber Study. Report submitted in fulfillment of Grant No.
803804-01 by the University of Maryland School of Medicine, Divi-
sion of Pulmonary Diseases to the U.S. Environmental Protection
Agency, Office of Research and Development, Health Effects Re-
search Laboratory, Research Triangle Park, North Carolina. 17 pp.
Modified double blind study. At very low levels of H2S04 aerosol
exposure, no difference was noted between cigarette smokers and
nonsmokers. Prolonged H2S04 exposure was not judged, but was sus-
pected of being toxic.
A-15, Ketels, K.V., J.N. Bradof, J.D. Fenters, and R. Ehrlich. 1977.
Scanning Electron Microscope Studies of the Respiratory Tract of
Mice Exposed to Sulfuric Acid Mist-Carbon Particle Mixtures. In:
Scanning Electron Microscopy 1977. O.M. Johari and R.P. Becker,
eds. IIT Research Institute, Chicago, Illinois. 2:519-526.
Exposure to H2S04 mist alone (100 mg/m3) caused damage near the
top and middle of the trachea. The addition of C particles (5 mg/
m3) at several mist concentrations and exposure schedules appeared
to enhance the toxicity of the H2S04 farther down the trachea and
into the bronchus. Damage was related to acid concentration and
not to the frequency and overall duration of exposure. Limited
control data were furnished, which makes the possibility of elec-
tron microscopic artifact difficult to evaluate.
Kitabatake, M. 1976. The Effect of Air Pollutants on Experimental
Provocation of Asthma Attacks in Guinea Pigs. I. The Effects of
Sulfur Dioxide and Sulfuric Acid Mist. Taiki Osen Kenkyu. 10:
700-711.
See Kitabatake et. al. (1979).
162
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A-ll. Kitabatake, M., M. Imai, K. Kasama, I. Kobayashi, Y. Tomita, and
K. Yoshida. 1979. Effects of Air Pollutants on the Experimental
Induction of Asthma Attacks in Guinea Pigs. Sulfuric Acid Mist
and Mixture of the Mist and Sulfur Dioxide. Mie. Med. J.
29:29-36.
Guinea pigs exposed twice a week for 30 min/wk to ~1.9 mg H2S04,
sometimes plus albumin, for 5 wk did not show as severe signs of
forced breathing upon acetylcholine challenge as when the exposure
regime also included 145 ppm S02. Significant breathing pattern
changes were seen when the albumin exposures started in the 3rd
wk.
B-8. Kitagawa, T. 1977. Air Pollution by Concentrated Sulfuric Acid
Mist and Respiratory Diseases in Yokkaichi City. Anzen Kogaku
16:290-301.
This is an interesting observation which needs careful confirma-
tion and more appropriate controls. There was a greater incidence
of respiratory problems in the general population exposed to sul-
furic acid mist emissions of the titanium dioxide industry.
A-13. Kleinman, M. T., and J. D. Hackney. 1978. Effects of Sulfate
Aerosols upon Human Pulmonary Function. APRAE Project CAPM-27-75,
PB-296656, National Technical Information Service, U.S. Department
of Commerce, Springfield, Virginia. 80 pp.
This is a repeated-dose study, on normal and asthmatic people, of
the mechanical physiological effects of H2S04 (~75 pg/m3, 0.4
pm MMAD, 40% R.H.). No convincing data on lung dysfunction were
found. Background NH3 levels of ~12 ppb were also present.
A-14. Kleinman, M. T., R. M. Bailey, Y. C. Chang, K. W. Clark, M. P.
Jones, W. S. Linn, and J. D. Hackney. 1979. Task II. Controlled
Studies of Mxed Pollutants. Effects of Exposure to Mixed Ozone,
Sulfur Dioxide and Sulfuric Acid. In: Effects of Aerosols, Ox-
ides of Nitrogen, and Oxidants on Human Health. PB80-184583, Na-
tional Technical Information Service, U.S. Department of Commerce,
Springfield, Virginia.
Fourteen of 19 humans exposed for 2 h with four 15-min exercise
periods to 0.100 mg H2S04/m3 (MMAD 0.5 pm) and 0.37 ppm each 03
and S02 showed significant decreases in ^1 pulmonary function
value. These decreases were about the same in magnitude but more
frequent than when humans are exposed to 03 alone. Apparently,
the sulfate or S02 increased the sensitivity of persons normally
nonreactive to 03 but did not change the effects seen in already
reactive individuals. No effects were observed in respiratory
resistance or irritant responses in monkeys exposed to about 10X
higher levels of these pollutants. No lung histological changes
were noted in mice exposed to 1 mg H2S04/m3 and 0.5 ppm each 03
and S02.
163
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A-14. Kleinman, M. T., R. M. Bailey, Y. C. Chang, K. W. Clark, M. P.
Jones, W. S. Linn, and J. D. Hackney. 1981. Exposures of Human
Volunteers to a Controlled Atmospheric Mixture of Ozone, Sulfur
Dioxide, and Sulfuric Acid. Am. Ind. Hyg. Assoc. J. 42(l):6l-69.
Same data as reported by Kleinman et al. (1979).
D-10. Krishnan, B. , T.K.. Nambinarayanan, and V.P. Sivasankaran. 1974.
Effect of Sulfuric Acid Fumes on Lung Surfactant. Indian J. Exp.
Biol. 12:524-527.
Rats were exposed to 703 ppm H2S04 of <2-[Jm droplet size for 5 h,
6 d, or 5 wk at 5 h/d, and the activity of lung surfactant (a sur-
face active material at the alveoli essential for the stability
of the air spaces in normal lungs) was measured. Short-term ex-
posure increased it (perhaps by increased secretion of material),
long-term decreased it (perhaps by inhibiting production).
C-8. Larson, T. V., D. S. Covert, R. Frank, and R. J. Carlson. 1977.
Ammonia in the Human Airways: Neutralization of Inspired Acid
Sulfate Aerosols. Science. 197(4299):161-163.
Some experiments, much theory on ammonia breath being responsible
for individual differences in response to inhaled sulfuric acid.
Generally shows that: (a) people are different; (b) rapid inhala-
tion/slow inhalation determines the lung deposition at least as
much as breath pH; (c) only few subjects and much discussion.
D-8. Larson, T. V., D. S. Covert, and R. Frank. 1978. Respiratory Am-
monia: A Possible Defense Against Inhaled Acid Sulfate Compounds.
Proc. Symp. Environ. Stress, pp. 91-99.
Looks at human production of NH3, plus theoretical analysis of its
effects.
D-10. Last, J. A., and C. E. Cross. 1978. A New Model for Health Ef-
fects of Air Pollutants: Evidence for Synergistic Effects of Mix-
tures of Ozone and Sulfuric Acid Aerosols on Rat Lungs. J. Lab.
Clin. Med. 91:328-339.
Tracheal cultures from 03 and H2S04 - exposed rats showed biochem-
ical changes at 10 to 50 |Jg/m3 sulfate concentrations, and appear
to show synergistic effects between 0^ and H2S04. The experimen-
tal model has many problems in mechanics, exposure, extrapolation,
however.
164
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D--. Last, J. A., and T. Kaizu. 1980. Mucus Glycoprotein Secretion by
Tracheal Explants: Effects of Pollutants. Environ. Health Per-
spect. 35:131-137.
Valuable anatomy and physiology. Paper was cited to make a point
in the summary.
D-8. Last, J.A. , M. Jennings, L'.'W. Schwartz, and C.E. Cross. 1977a.
Glyco Protein Synthesis by Tracheal Explants Derived from Rats
Exposed to Sulphuric Acid Aerosols. Clin. Res. 25:133A.
The authors were seeking a more sensitive system that would show
sulfuric acid effects. They suggest that the tracheal explant is
it.
C-10. Last, J. A., M. Jennings, and C. E. Cross. 1977b. Exposure of
Rats to Combinations of Ozone and Sulfuric Acid Aerosols: Syner-
gistic Effects of TWO Air Pollutants. . Am. Rev. Resp. Dis. 115(4
part 2):226. [abstract].
In vitro assays with rat tracheal explants and lung horaogenates
demonstrate potential synergism between H2S04 (0.1-1.0 mg/m3) and
63 (0.4-0.5 ppm). Increased mucus glycoprotein secretion and en-
zyme activities.
A-ll. Lawkowski, J.P., M. Malanchuk, L. Hastings, A. Vinegar, and G.P.
Cooper. 1979. Effects of Chronic Exposure of Rats to Automobile
Exhaust, Sulfuric Acid, Sulfur Dioxide, Aluminum Sulfate, and Car-
bon Monoxide. Assessing Toxic Eff. Environ. Pollut. S. D. Lee and
J. B. Mudd, eds. Ann Arbor Science Publishers, Inc., Ann Arbor,
Michigan, pp.187-217.
Rats, breathing 4-8 mg H2S04/m3 for 6 or 14 weeks, had metabolic
alkalosis but no effect on: lung function, acid-base chemistry
of blood, and behavior as measured by spontaneous motor activity.
C-4. Lawther, P.J. 1963. Compliance with the Clean Air Act: Medical
Aspects. J. Inst. Fuel 36:341-344.
This review casts doubts on the synergistic effects of sulfur di-
oxide, and states that no effects have been seen in lung function
after "realistic" levels of sulfuric acid exposure. The following
hypothetical mechanism is presented: H2S04 particles are diluted
by gathering moisture except when the acid is on a particle and
then it is "protected."
Good ideas given but short on data.
165
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A-10. Lawther, P. J. 1980. The Effects of Sulfur Dioxide, Sulfuric
Acid, and Particulate Matter on Lung Function. Comm. Eur. Commu-
nities, [Rep.] EVR 6388, Environ. Res. Programme, pp. 390-394.
Humans, inhaling deeply by mouth, were exposed to a range of H2S04
aerosols: 0-1,000 \ig/m3 (0.1-5 |Jm). No changes were seen at the
smaller size and concentration range, but the aerosols became in-
creasingly irritating as both increase. A good, tight study.
B-10, Lee, S. D., M. Malanchuk, and V. N. Finelli. 1976. Biologic Ef-
fects of Auto Emissions. I. Exhaust from Engine With and Without
Catalytic Converter. J. Toxicol. Environ. Health. 1:705-712.
The sulfate levels encountered were very low: 0.08 mg/m3 (exhaust
without converter) and 0.61 mg/m3 (exhaust with converter). Hema-
tocrit values and serum LDH enzyme activity were elevated in the
rats exposed for 7 d to exhaust emissions without a converter.
D-9. Lee, S. D., M. Malenchuk, W. Moore, K. I. Campbell, J. Burkart,
T. Cody, L. Michael, and V. N. Finelli. 1977. Chemical and Bio-
logical Characterization of Automobile Emissions With and Without
Catalytic Converter: A Review. Int. Clean Air Congr. 4:71-73.
Review of effects of catalytic converter on auto emissions.
A-16. Leikauf, G., D.B. Yeates, K.A. Wales, D. Spektor, R.E. Albert,
and M. Lippmann. 1981. Effects of Sulfuric Acid Aerosol on Re-
spiratory Mechanics and Mucociliary Particle Clearance in Healthy
Nonsmoking Adults. Am. Ind. Hyg. Assoc. J. 42(4):273-282.
More details of the same experiment reported by Lippmann et al.
(1980a). Respiratory mechanical function was assessed in 10
healthy nonsmokers who inhaled (via a nasal mask) for 1 h/d a
0.5-(Jm H2S04 aerosol at 0, 0.110, 0.330, and 0.980 mg/m3 in ran-
dom sequence on four separate days. The individual responses of
the 10 subjects patterns fell into two groups. Four showed no
significant change in tracheobronchial clearance half-time (TB.. ,?)
from their own control values, but the TB ,~ was significantly
lower than the control for six subjects at 6.110 mg H2S04/m3 and
significantly higher at 0.980 mg/m3. The TB ,„ showed ^ threefold
increases from the group mean TB.. ,„ control value in three of
those four when the exposure to I.620qmg H2S04/m3 preceded rather
than followed the 10-min exposure to Tc-tagged Fe203.
C-9. Lewis, T.R., D.E. Campbell, and T.R. Vaughan, Jr. 1969. Effects
on Canine Pulmonary Function via Induced N02 Impairment, Particu-
late Interaction and Subsequent SO . Arch. Environ. Health.
18:596-601. X
166
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Exposing beagle dogs to 0.755 mg H2S04/m3 or 0.835 mg H2S04/m3
plus 5.1 ppm S02 for 21 h/d for 225 d generally produced more ad-
verse lung effects in dogs that had not been pre-exposed to 48.9
mg N02/m3 (26 ppm) for 191 d. CO-diffusion capacity, however, was
lowered in both unimpaired and impaired dogs from both test expo-
sures .
B-10. Lewis, T.R., W.J. Moorman, W.F. Ludmann, and K.I. Campbell. 1973.
Toxicity of Long-Term Exposure to Oxides of Sulfur. Arch. Environ.
Health. 26:16-21.
Female beagles were exposed to 0.889 mg H2S04/m3 or 0.904 mg
H2S04/m3 plus 5.1 ppm S02 for 21 h/d for 225 d. Half of each
group had been pre-exposed for 191 d to 48.9 mg N02/m3. All pul-
monary function measurements tended to decrease except those whose
increase denotes dysfunction. The conducting airways as well as
the lung parenchyma were affected. Poor reporting of histopathol-
ogy. Baselines on the animals pre-exposed to N02 are lacking.
B-9. Lewis, T.R., W.J. Moorman, Y. Yang, and J.F. Stara. 1974. Long-
Term Exposure to Auto Exhaust and Other Pollutant Mixtures. Ef-
fects on Pulmonary Function in the Beagle. Arch. Environ. Health.
29:102-106. *•
Beagle dogs (12 females/test group) were exposed for 21 h/d for
61 mo "to 0.100 mg H2S04/m3 and 0.5 ppm S02 with or without nonir-
radiated or irradiated auto exhaust. Pulmonary effects were not
seen at 36 mo; but at the end of 61 mo, certain lung function
tests revealed impairment.
C-5. Linn, W.S., M.P. Jones, E.A. Bachmayer, C.E. Spier, S.F. Mazur,
E.L. Avol, and J.D. Hackney. 1980. Short-Term Respiratory Ef-
fects of Polluted Ambient Air: A Laboratory Study of Volunteers
in a High-Oxidant Community. Am. Rev. Respir. Dis. 121:243-252.
Normal and asthmatic subjects,were exposed to polluted ambient air
from a severely polluted area and purified air for 2 h each, with
intermittent light exercise. Mean particulate S042 levels were
16.5 and 0.9 |Jg/m3 respectively. Only slight changes in lung
function and symptomology were found. Both groups had similar re-
sults. The control group had high levels of respiratory allergy,
and effects appear to be those of ozone anyway.
A-8. Lippmann, M., and R. E. Albert (New York University School of
Medicine, Department of Environmental Medicine). 1979. Effects
of Sulfur Oxide Pollutants on Respiratory Function, Particle Depo-
sition and Bronchial Clearance. Toxicol. Res. Proj. Dir. 4(4):
SSIE/GMA 2885 2. <-
167
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Experiments are being conducted with humans and donkeys at ^ 1.0
rag H2S04/m3 for 1 h to 6 mo.
/
C-- Lippmann, M. 1980. Health Significance of Exposure to Sulfur
Oxide Air Pollutants. In: Atmospheric Sulfur Deposition: Envi-
ronmental Impact and Health Effects, 2nd ed., D. S. Shriner, C. R.
Richmond, and S. E. Lindberg, Eds. Ann Arbor Science Publishers,
Inc., Ann Arbor, Michigan, pp. 85-97.
Lipmann concludes a review of the more significant clinical and
laboratory studies by stating that they demonstrate that H2S04 in
the ambient air could contribute to the pathogenesis of chronic
bronchitis and cause airway constriction sufficient to affect in-
dividuals with reactive airways. Additional concern is generated
by animal studies that indicate that H2S04 plus 03 can enhance
mortality in animals infected with bacterial aerosols.
A-15. Lippmann, M. , R.E. Albert, D..B. Yeates, K. Wales, and G. Leikauf.
1980. Effect of Sulfuric Acid Mist on Mucociliary Bronchial
Clearance in Healthy Non-smoking Humans. In: Aerosols in Science,
Medicine and Technology. The Biomedical Influence of the Aerosol.
W. StSber and R. Jaenicke, Eds. Gesellschaft fifr Aerosolforschung.
Mainz, Federated Republic of Germany, 'pp. 157-162.
Ten humans were exposed for 1 h to 107, 325, or 983 |Jg H2S04/m3
(0.5 |Jm MMD). Ventilatpry mechanics were unaffected. Mucociliary
bronchial clearance was changed at all levels: increased rate for
107 JJg/m3 exposure, decreased clearance rate for 983 (Jg/m3 expo-
sure, and variable response for 325 |Jg/m3 exposure. See also
Leikauf et al. (1981).
C-8. Loscutoff, S.M. 1978. Inhibition of Bronchoconstriction Caused
by Exposure of Guinea Pigs to Sulfuric Acid Aerosols. In: Pac.
Northwest Lab. Annu. Rep. 1977 DOE Assist. Seer. Environ. Pt.
1:Biomedical Science. PNL-2500-Pt. 1. pp. 1.7-1.8.
This is an investigation of the mechanisms of bronchoconstriction
with H2S04 mist, 20 mg/m3, of 2-pm sized particles. Atropine
partly blocked this effect (so acetylcholine is partly responsi-
ble); chlorpheniramine prevented the effect (histamine is mostly
responsible); and propranolol didn't help at all (so catecholamine
beta receptors aren't involved).
A-6. Loscutoff, S. M. (Battelle, Pacific Northwest Labs.). 1979.
Toxicity of Sulfur Pollutants. Toxicol. Res. Proj. Dir. 4(1):
SSIE/ZPE 12351 1.
168
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Guinea pigs are being pretreated with specific pharmacologic
blocking agents before H2S04 exposure to deterniine whether pro-
tection of highly sensitive humans is feasible.
A-15. Loscutoff, S.M. 1980a. Effects of Endogenous Ammonia on Neutrali
zation of Inhaled Sulfuric Acid Aerosols. EPA-600/ 1-79-045.
Health Effects Research Laboratory, Cincinnati, Ohio. 37 pp.
In this study, blood ammonia was increased in dogs to neutralize
inhaled H2S04 — it did neutralize, but there was no change in tox-
icity of H2S04 (many other measures done).
s ^
C-9. Loscutoff, S. M. (Battelle, Pacific Northwest Labs). 1980b. The
Effects of Endogenous Ammonia Upon the Neutralization of Inspired
Sulfuric Acid. Toxicol. Res. Proj . Dir. 5(2) :SSIE/GMA 5790.
Beagles will be exposed to 6 or 12 mg H2S04/m3 alone or in combi-
nation with endogenous or exogenous NH3. The degree of neutrali-
zation by NHs, the effect of this on H2S04 toxicity, and the mini
mum levels affecting pulmonary function in the absence of lung NH
will be determined.
A-6 Loscutoff, S.M., F.G. Burton, and B.W. Killand. 1978. Neutraliza-
tion of Inhaled Sulfuric Acid Aerosols by Ammonia in the Lung.
Fed. Proc. 37:867.
Fewer data than acceptable, even for an abstract. Method used?
'- Number of animals?
C-5. Lynch, J.B. and J. Bell. 1947. Dental Erosion in Workers Exposed
to Inorganic Acid Fumes. Brit. J. Ind. Med. 4:84-86.
Poor ventilation in wartime industry produced dental erosion in
as little as 3 months in employees working near baths containing
70% sulfuric acid and 22% nitric acid. No quantitation of levels
in the air was given.
C-14. Malcolm, D., and E. Paul. 1961. Erosion of the Teeth Due to Sul-
phuric Acid in the Battery Industry. Brit. J. Ind. Med. 18:63-69.
The industrial air levels to which the workers^were exposed were
much higher than will be considered for a level of concern: 3-16.6
mg/m3. ^
169
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Standard epidemiologic parameters have not been employed to
clearly define risk ratios in terms of (1) age at first exposure
(2) dose-duration exposure ratios, etc. (include time on the job
as well as employment duration). Primary focus is on the clini-
cal picture and objective documentation (uniform, repeatable clas-N
sification) of the condition of teeth.
Advantages of this study:
(1) Uniform, replicable classification of dental erosion,
although later modified by ten Bruggen Gate (1958).
(2) Relevant control groups: mean age and economic status
are statistically comparable.
C-4. Mauderly, J. L. (Lovelace Foundation for Medical Education and
Research, Inhalation Toxicology Research Inst.). 1979. Cardio-
plumonary Injury and Repair After Inhaling Acid Sulfate Aerosols.
Toxicql. Res. Proj. Dir. 4(2):SSIE/ZPE 12486 1.
Breathing patterns and pulmonary mechanics of guinea pigs and dogs
will be compared for characterization of sensitive and insensitive
populations to 0.1 and 1.0 mg/m3 of 0.5 (Jin H2S04. Thereafter,
dogs will be exposed chronically to low levels of H2S04.
B-8. Morando, A. 1956. Experimental and Clinical Contribution to the
Pathology of Sulfuric Acid Fumes in Man. Med. Lav. 47:557-561..
The suggestion that more gastrointestinal effects occur than re-
spiratory effects following industrial H2S04 exposure has not been
corroborated by other studies in the last 25 years.
Exposure to 0.35-5.0 mg/m3 increased respiratory resistance "for
several minutes after exposure ceased."
\
B-9. Morrow, P. E., M. J. Utell, F. R. Gibb, and R. W. Hyde. 1980.
Studies of Pollutant Aerosol Simulants in Normal and Susceptible
Human Subjects. In: Aerosols Sci., Med. Technol.-Biomed. Influ-
ence Aerosol-Conf., 7th 1979. W. Stoeber and R. Jaenicke, Eds.,
Ges. Aersolforschung, Mainz, Fed. Rep. Ger. pp. 11-20.
Normals exposed for ~ 15 min to H2S04, NaHS04, NH4HS04, and
(NH4)2S04 at 1 mg/m3 with ^ 3 h between exposures showed small,
but significant, decreases in maximum expiratory flow volume and
partial expiratory flow volume at 40 and/or 60% of total lung ca-
pacity. For H2S04, the decrease in specific airway conductance •
was ~ 5%; after a carbachol challenge following the H2S04 expo-
sure, ~ 27%.
170
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D-12. Murray, F. J., B. A. Schwetz, K. D. Nitschke, A. A. Crawford,
J. F. Quast, and R. E. Staples. 1979. Embryotoxicity of Inhaled
Sulfuric Acid Aerosol in Mice and Rabbits. J. Environ. Sci.
Health [C]. 13(3):251-266.
Routine teratology study with negative results. Animals were ex-
posed to 5 or 20 mg H2S04/m3 for 7 h/d during the period of major
organogenesis.
B-10. Mustafa, M. G. (University of California at Los Angeles, School of
Medicine). 1980. Effect of Pollutants from Energy Consumption
and Environmental Trace Metals on Lung Metabolism. Toxicol. Res.
Proj. Dir. 5(1):SSIE/GMA 4494 2; cf. Mustafa, M. G., D. F.
Tierney, A. D. Hacker, J. J. Ospital, and N. Elsayed. 1979. Op.
cit. 4(6):SSIE/GMA 4494 1.
Qualitative and quantitative biochemical changes studied in lungs
of rats upon exposure to H2S04 and other energy-related air pollut-
ants. Oxidant pollutants generally cause a depression of lung en-
zymatic activities, except 03 at <1 ppra and N02 at 5 ppm, both
causing stimulation.
B-7. Nevskaya, A.I., and Kochetkova. 1961. K Toksikologii Ozona i
Aerozolya Sernoi Kisloty pri Kombinirovannom Deistvii. [On the
Combined Effects of Ozone and Sulfuric Acid Aerosol.] Gigiena
Truda i Prof. Zabolevaniya [Labor Hygiene and Occupational Dis-
eases] 5(2): 20-29.
A study of the synergism between H2S04 and 03 at USSR's maximum
permissible concentration (MPC) level. It reported an early
stage of "lowered tissue excitability, then later increased CNS
excitability" with the mixture. There was no blood change. H2S04
alone took 5 months to produce connective tissue in lungs. It
took 2.5 months for the mixture to show effects. A small number
of animals was used.
A-10. Newhouse, M.T., M. Dolovich, G. Obminski, and R.K. Wolff. 1978.
Effect of TLV Levels of S02 and H2S04 on Bronchial Clearance in
Exercising Man. Arch. Environ. Health. 33:24-32.
In this study, ten exercising non-smoking subjects were exposed to
1 mg H2S04/m3 (0.5 pm MMD) after an albumin radio aerosol. Re-
sults showed high variability in 10 of 10, and an increase in
clearance rate in 5 of 10.
C-4. NIOSH, National Institute for Occupational Safety and Health.
1974. Criteria for a Recommended Standard.... Occupational Expo-
sure to Sulfuric Acid. HEW Pub. No. 74-128, Rockville, Maryland.
A review with a defined scope of coverage.
171
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C-12. Oneil, J. J., S. Stultz, and R. Slade (U.S. EPA, ORD, HERL, Clini-
cal Studies Div., Biomed. Res. Branch). 1979. Changes in Pulmo-
nary Physiologic, Biochemical, and Metabolic Function Following
Exposure to Simple or Complex Mixtures. Toxicol. Res. Proj. Dir.
4(4):SSIE/ZMA 1273 1.
Primarily methods development for inhalation parameters in experi-
mental animals, to be applied to exposure to an aged aerosol of
S02-03-olefin mixture (which produces substantial quantities of
submicron size sulfuric acid).
C-5. Orthoefer, J.G., R.S. Bhatnagar, A. Rahman, Y. Yang, S.D. Lee, and
J.F. Stara. 1976. Collagen and Prolyl Hydroxylase Levels in
Lungs of Beagles Exposed to Air Pollutants. Environ. Res. 12:299-
305.
Five beagles exposed 68 months to 1.10 mg S02/m3 plus 0.09 mg
H2S04/m3 had no collagen content increase. The slight increase in
enzyme levels of collagen-synthesizing enzymes cannot be inter-
preted.
A-3. Pattle, R.E., and H. Cullumbine. 1956. Toxicity of Some Atmo-
spheric Pollutants. Brit. J. Med. 2:913-915.
Preliminary reporting of human exposure—an unknown number of hu-
mans had highly differing responses to H2S04—10 ppm 1 (Jm MMD
particles were irritating, but "with prolonged exposure (the re-
sponse) decreased." The experiment was described in detail in
Sim and Pattle (1957). They exposed many animals to all types of
uncontrolled exhausts and aerosols.
C-ll. Pattle, R. E., F. Burgess, and H. Cullumbine. 1956. The Effects
of a Cold Environment and of Ammonia on the Toxicity of Sulphuric
Acid Mist to Guinea Pigs. J. Path. Bact. 72:219-232.
The Lego's for sulfuric acid with 0.8 (jm MMD were 14.9 ppm at room
temperature and 11.7 ppm at 0°C. When ammonium carbonate was pre-
sent so that there was an excess of NHs, H2S04 concentrations >LC50
caused no mortality. There appeared to be no adaptation to previ-
ous exposure at low H2S04 levels — fatalities still occurred.
B-10. Pepelko, W.E., J. G. Orthoefer, and Y.-Y. Yang. 1979. Effects of
90 Days Exposure to Catalytically Treated Automobile Exhaust in
Rats. Environ. Res. 19:91-101.
Good study. It is well controlled, but uses such a mixture that
the sulfuric acid effect cannot be separated out except in that
the level was higher than earlier work and there was no increase
in toxicity.
172
-------
Rinsky, R. (NIOSH). 1979. Mortality and Industrial Hygiene Study
of Workers Exposed to Sulfuric Acid-EPA. Toxicol. Res. Proj. Dir.
4(1):SSIE/DH 394.
See Beaumont and Young (1980).
D-12. Runkle, B.K. and F.F. Hahn. 1977. The Toxicity of Sulfuric Acid
Aerosols to CD-I Mice and Fischer-344 Rats. Annu. Rep. Inhala-
tion Toxicol. Res. Inst. pp. 435-439.
Very high concentrations (250-1,000 mg H2S04/m3). Results are
discussed on the basis of the LC50 as a function of exposure time.
Animals died of upper respiratory tract lesions before H2S04 af-
fected the deep lung.
C-12. Runkle, B.K., P.L. Bryant, and F.F. Hahn. 1977. The Effect of
Sulfuric Acid Aerosol Exposure on Pulmonary Clearance of Insoluble
Particles in CD-I Mice. Annu. Rep. Inhalation Toxicol. Res. Inst.
pp. 440-444.
Mice exposed to labeled fused aluminosilicate particles were then
exposed 8 d later to 191, 27, or 1.7 mg H2S04/m3 (<3 \*m MMAD) for
6 h. There were no changes in the deep lung"clearance of the par-
ticles or in tissue distribution of the particles, and no patho-
logic lesions were noted in the tissues following any of the H2S04
aerosol exposures.
Sackner, M.A., M. Reinhardt, and D. Ford. 1977. Effect ofxSul-
furic Acid Mist on Pulmonary Function in Animals and Man. Am. Rev.
Respir. Dis. 115:240.
No rating; this is reported in more detail in Sackner et al.
(1978b).
D-5. Sackner, M.A., D. Perez, M. Brito, and R.M. Schreck. 1978a. Ef-
fect of Moderate Duration Exposures to Sulfate and Sulfuric Acid
Aerosols on Cardiopulmonary Function of Anesthetized Dogs. Am.
Rev. Respir. Dis. 117:257.
An abstract of a study in which submicronic aerosols of many com-
pounds, including H2S04, were administered at 1.6-9.3 mg/m3 levels
to anesthetized dogs for 4 h. Several pulmonary and cardiac func-
tions were analyzed and no differences between sodium chloride and
sulfate aerosols were seen.
173
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A-15. Sackner, M.A., D. Ford, R. Fernandez, J. Cipley, D. Peroz, M.
Kwoka, M. Reinhardt, E.G. Michaelson, R. Schreck, and A. Wanner.
1978b. Effects of Sulfuric Acid Aerosol on Cardiopulmonary Func-
tions in Dogs, Sheep and Humans. Am. Rev. Respir. Dis. 118:497-
510.
This study reported that breathing dynamics were not affected in
normal or asthmatic subjects breathing 0.1 (Jm diameter aerosols of
H2S04 at 1, 10, or 1,000 MS/™3 for 10 min. [It also reports dog
lung measures and sheep mucociliary measures.]
B-12. Salem, H., and H. Cullumbine. 1961. Kerosine Smoke and Atmospheric
Pollutants. Arch. Environ. Health. 2:641-647.
LD50 study concluded that sulfuric acid works on guinea pigs by
bronchiolar spasm. Mice and rats are not susceptible to bronchi-
olar spasm, so sulfuric acid is not as acutely toxic. This was
shown by pre-exposing the animals to kerosene smoke (which hits
bronchioles) thereby increasing toxicity in susceptible animals
but not in resistant animals.
B-3. Scheller, S., A. Posz, J. Tustanowski, L. Ilewicz, and Z.
Paradowski. 1977. Certain Factors of Nonspecific Immunity and
Immunoglobulins in the Oral Cavity and Blood of Subjects Exposed
to Chemical Stress. Czas. Stomatol. 30:11-16.
Salivary immunoglobulin A (IgA) (high in saliva) increases and
serum IgG decreases on industrial exposure to 2-9 mg/m3 H2S04 and
26-60 me HCl/m3 compared to a control erouo.
L>CJ.IUII -Lgu ucv_ 4. c:a&ca uii j.iiuua ui. xa j. c&puou.i.c L
26-60 mg HCl/m3 compared to a control group.
C-10. Schiff, L.J. M.M. Bryne, J.D. Fenters, J.A. Graham, and D.E.
Gardner. 1979. Cytotoxic Effects of Sulfuric Acid Mist, Carbon
Particulates, and Their Mixutres on Hamster Tracheal Epithelium.
Environ. Res. 19:339-354.
Hamsters exposed for 3 h to 1.1 mg/m3 of 0.12-|Jm H2S04 particles
had damage to the tracheal epithelium.
A-17. Schlesinger, R.B., M. Lippmann, and R.E. Albert. 1978. Effects
of Short-Term Exposures to Sulfuric Acid and Ammonium Sulfate
Aerosols Upon Bronchial Airway Function in Donkeys, J. Am. Ind.
Hyg. Assoc. 39:275-286.
Two of four donkeys showed chronic slowing of bronchial clearance
rate after 1 h exposure to 194-1,364 |jg H2S04/m3 (0.3-0.6 (Jm) ,
when H2S04 exposure preceded inert test aerosol exposure. These
H2S04 exposure levels caused no measurable change in compliance,
resistance, or regional deposition. Equine lung is a good anatom-
ical model of man, which may allow comparisons of these results to
human data.
174
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A-16. Schlesinger, R. B., M. Halpern, R. E. Albert, and M. Lippmann.
1979. Effect of Chronic Inhalation of Sulfuric Acid Mist Upon
Mucociliary Clearance from the Lungs of Donkeys. J. Environ.
Pathol. Toxicol. 2:1351-1367.
Four donkeys were exposed to ~100 |Jg H2S04/m3 for 1 h/d,.5 d/wk,
for 6 mo. Bronchial clearance became erratic within the first wk,
usually slower. Two animals had sustained impairment towards the
end of the 6 mo, and continued to be erratic for a 3-mo follow-up
period. Individual variabilities in rates and susceptibility
were seen. Possible adaptation because of previous H2S04 expo-
sure. The author hypothesized that alterations in bronchial muco-
ciliary clearance may be a first indication of potential lung dam-
age.
A-17. Schwartz, L.W., P.F. Moore, D.P. Chang, B.K. Tarkington, D.L.
Dungworth, and W.S. Tyler. 1977. Short-Term Effects of Sulfuric
Acid Aerosols on the Respiratory Tract. A Morphological Study in
Guinea Pigs, Mice, Rats, and Monkeys. In: Biochemical Effects of
Environmental Pollutants (Symp.), S. D. Lee, ed. Ann Arbor Science
Pub. Inc., Ann Arbor, Mich. pp. 257-271.
A good job. They tried very hard to find toxicity. This study
measured species sensitivity and morphological change in animals
exposed to H2S04 aerosols in 0.3-0.6 (Jm ranges. Monkeys, sug-
gested as good human models by authors, showed no effect at 502
mg/m3 for 7 days. Monkeys and rats were most resistant, guinea
pigs and mice most sensitive. "The respiratory system appears to
be well shielded against H2S04-induced damage." They warn that
synergism with other toxicants or potentiation by metals could
occur.
C-12. Schwartz, L.W., Y.C. Zee, B.K. Tarkington, P.F. Moore, and J.W.
Osebold. 1979. Pulmonary Responses to Sulfuric Acid Aerosols.
Ch. 10 In: Assessing Toxic Eff. Environ. Pollut., S.D. Lee, and
J.B. Mudd, eds. Ann Arbor Science Pub. Inc., Ann Arbor, Mich.
pp. 173-186.
The H2S04 LD50 in guinea pigs was 100 mg/m3 with 0.3 to 0.4 }Jm
diameter particle size. Mice were exposed at very high levels of
H2S04 aerosol, and the urine and blood analyzed. The unrealistic-
ally high exposure levels make this rather well-done study of lit-
tle use to this project.
A-11. Silbaugh, S.A., J.L. Mauderly, R.L. Carpenter, and R.K. Wolff.
1977a. Effects of Sulfuric Acid and Histamine Aerosols on Pulmo-
nary Function of Guinea Pigs. Physiologist. 20:87.
175
-------
The acute response of guinea pigs to H2S04 did not differ from
a histamine response. No effect on pulmonary function in 20
animals exposed to 1 mg/m3, 0.6 |Jm at 40% to 80% R.H.
f
C-13. Silbaugh, S.A., R.K. Wolff, and D.G. Brownstein. 1977b. Effects
of Eight-hour Exposures to Sulfuric Acid Mist on Guinea Pigs.
1978. Annu. Rep. Inhalation Toxicol. Res. Inst. pp. 426-428.
Guinea pigs have all-or-none type responses to 15+ mg/m3. Expo-
sure to 10-43 mg/m3 for 8 h either caused severe dyspnea and death
or had no effect. The LC50 for 21 d after exposure was 31 mg/m3.
B-12. Silbaugh, S.A., R.K. Wolff, R.L. Carpenter, and J.L. Mauderly.
1977c. Effects of Sulfuric Acid and Histamine Aerosols on Pulmo-
nary Function of Guinea Pigs. Annu. Rep. Inhalation Toxicol. Res.
Inst. pp. 429-434.
Exposure for 1 h to 1 mg H2S04/m3 (0.9 Mm MMAD) caused no change
in 7 respiratory functions measured. Exposure to 15 mg/m3 caused
significant change in only 1 animal, which was also far more sen-
sitive to histamine than the other animals.
B-ll. Silbaugh, S.A., D.G. Brownstein, R.K. Wolff, and J.L. Mauderly.
1978a. Airway Response of the Hartley Guinea Pig to Sulfuric
Acid Aerosol. Annu. Rep. Inhalation Toxicol. Res. Inst. pp.
360-363.
Data show large individual differences in response to H2S04 in
guinea pigs. Further mechanistic studies on the "all or none"
response. Three of 9 at 24 mg/m3 and 4 of 8 at 48 mg/m3 (0.9-
1.3 pm MMAD) had changes in pulmonary resistance and compliance,
and 4 of those 7 later died. Other animals had near-baseline
pulmonary function values.
A-16. Silbaugh, S.A., R.K. Wolff, D.G. Brownstein, R. Loretto, and
J.L. Mauderly. 1978b. Toxicity of 0.4 and 0.8 (Jm Sulfuric Acid
Aerosols in the Guinea Pig. Annu. Rep. Inhalation Toxicol. Res.
Inst. pp. 364-367.
The 0.4-|jm aerosol was less toxic than the 0.8-|Jm aerosol at le-
thal H2S04 concentrations (17.4-144.0 mg/m3)..
Regional deposition and particle size may be mechanisms most in-
volved. The report was formally published as Wolff et al. (1979a),
which see.
176
-------
C-12. Silbaugh, S.A., C.A. Macken, and W.K. Johnson. 1979a. Factors
Affecting the Pulmonary Response of the Guinea Pig to Sulfuric
Acid Aerosols. Ann. Rep. Inhalation Toxicol. Res. Inst. LF-69:
515-518.
Individual variations described. Guinea pig sensitivity to the
H2S04-induced airway constriction may be related to detectable
pre-exposure factors such as transpulmonary pressures, pulmonary
resistance, and dynamic lung compliance.
C-12. Silbaugh, S.A., C.A. Macken, and J.L. Mauderly. 1979b. Effect of
H2S04 and N02 on Airway Responsiveness of the Guinea Pig. Annu.
Rep. Inhalation Toxicol. Res. Inst. LF-69:519-523.
An interaction study with histamines. Animals were exposed for
1 h to 4-40 mg H2S04/m3 (~1 [Jm MMAD). Increased histamine sensi-
tivity was seen only at ^ 19 mg/m3 and only if labored breathing
developed during exposure. This suggests that dyspnea is a pre-
requisite for sensitization.
B-14. Silbaugh, S.A., R.K. Wolff, and J.L. Mauderly. 1979c. Acute Pul-
monary Function Effects of Sulfuric-Acid Inhalation in Hartley
Guinea Pigs. Fed. Proc. 38:1324. [meeting abstr.J
Hartley guinea pig may be unique (and not a good model of man, in-
ferred) in that it has an all-or-none response to sulfuric acid in
their tests.
C-12. Silbaugh, S.A., R.K. Wolff, W.K. Johnson, J.L. Mauderly, and C.A.
Macken. 1981. Effects of Sulfuric Acid Aerosols on the Pulmonary
Function of Guinea Pigs. J. Toxicol. Environ. Health. 7(3-4):
339-352.
Guinea pigs were exposed to 1.2-48.3 mg H2S04/m3 (~1 (Jm MMAD) for
1 h.
Individual differences were found, probably attributable to
differences in airway caliber or the lung's elastic properties.
C-12. Silbaugh, S.A., R.K. Wolff, J.L. Mauderly, and W.K. Johnson. [To
be published.] Pulmonary Effects of Inhaled Sulfuric Acid Aero-
sols in Guinea Pigs. Pulmonary Toxicology of Respirable Parti-
cles. Symp. Proc., Department of Energy, Richland, Washington.
October 22-24, 1979.
Reviews several high-dose studies by Silbaugh and co-workers.
177
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B-9. Sim, V. M., and R.E. Pattle. 1957. Effects of Possible Smog
Irritants on Human Subjects. J. Am. Med. Assoc. 165:1980-1913.
Gaps in the reporting methods make analysis of these data diffi-
cult. Later experiments report some coughing and airflow resis-
tance increase from 35.5-100% over normal in 12 males receiving
H2S04 mist at 39.4 mg/m3 and 0.99 pm diameter particles at 62%
R.H. for 60 min. The effects were worse at 91% R.H. The two au-
thors report that personal sensitivity increased on repeated ex-
posure.
C-2. Snipes, M. B. (Lovelace Center for the Health Sciences; Lovelace
Inhalation Toxicology Research Institute). 1980. Deposition,
Retention, and Dosimetry of Inhaled Sulfates. Toxicol. Res. Proj
Dir. 5(5):SSIE/ER 1154.
An abstract of work in progress, using rats and beagle dogs to
examine toxicant distribution in the lung, the distribution and
retention of inhaled monodisperse inert particles after inhal-
ation of sulfuric acid mist. This study of a three-dimensional
distribution is a good idea, but there are no comments on the
very difficult methods.
Stara, J. F., D. L. Dungworth, J. G. Orthoefer, and W. S. Tyler.
1980. Long-Term Effects of Air Pollutants in Canine Species.
EPA-600/8-80-014, PB 81-144875, National Technical Information
Service, U.S. Department of Commerce, Springfield, Virginia.
287 pp.
The chronic beagle dog exhaust studies are recapitulated in this
document, which was received too late to incorporate chapter cita-
tions alongside data tabulated from earlier publications.
State of California Air Resources Board. February 20, 1976.
Regulations Concerning a 24-Hour Sulfate Ambient Air Quality Stan-
dard or Significant Harm Level.
Not rated, but was consulted during preparation of the summary.
The strict S02 and sulfate standards may be rescinded (Chem. Eng.
News 1980. 58:16).
C-10. Stebbings, J., and C. Hayes. 1976. Panel Studies of Acute Health
Effects of Air Pollution. I. Cardiopulmonary Symptoms in Adults,
New York, 1971-1972. Environ. Res. 11:89-111.
No threshold effects can be established from these data for sus-
pended sulfates.
178
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A human subject with chronic illness showed no greater effect than
other subjects in the study. Reviewer questions arbitrary divi-
sion of exposure levels; variation in exposure parameters appeared
too great to bracket readily. Data do not indicate that suspended
sulfates are the most cardiotoxic component of air pollution.
D— Sterekhova, N. P., S. N. Khalevina, L. N. Kruchinina, and N. P.
Yakhimovich. 1979. Health Status of Workers in the Sulfuric
Acid Shop. Vopr. Gigieny, Org. Zdravookhr., Obshch. i Prof. j
Patol. Raboch. Medeplavil'n. Komb., Sverdlovsk, pp. 55-62
(Russ).
An epidemiological occupational study that is too confounded to
be of any value for this task. The major contaminant in the air
of a sulfuric acid plant installed to purify the off-gases of cop-
per smelting is S02; but the workers are also exposed to As203,
AsH3, H2S04 aerosols, and Pb.
C-9. Tadzhibaeva, N.S., and I.V. Gol'eva. 1976. Industrial Hygiene
and Condition of the Upper Respiratory Track of People Working in
the Production of Superphosphate in Uzbekistan. Med. Zh. Uzb.
pp. 57-59.
Essentially a clinical comparison of workers exposed primarily to
^3864, SC>2, and S03 to workers exposed to ammoniated superphos-
phate dust. Industrial air levels are relatively high (5.2-9.2
mg/m3), but health effects described here may still be present at
lower exposures of long duration, i.e.,
pharyngitis, nasal discharge, sneezing,
vasomotor and allergic changes of upper respiratory tract,
lowered olfaction,
eye irritation.
It is interesting that no mention of teeth erosion is present
despite relatively high exposures.
C-9. ten Bruggen Gate, H.J. 1958. Dental Erosion in Industry. Brit.
J. Ind. Med. 25:249-266.
This is a controlled study of 555 "acid workers" of which 101
workers were exposed to surfuric acid alone. Other workers were
exposed to hydrochloric, nitric, or phosphoric acids in "a multi-
industry study (48 firms). Controls were selected from acid-free
departments of participatory firms. It has most of the problems
179
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of a multi-institutional study in terms of comparability of rele-
vant conditions. A classification of dental erosion was developed
which was improved over the system utilized by Malcom and Paul
(1961) in terms of replicability between participatory firms. The
main contribution is in the observation of length of exposure (em-
ployment) at the onset and advance of erosion (initial or Grade I
erosion observed after only 4 to 6 mo). The study attempts to ex-
amine age at first exposure, but did not show any particular sus-
ceptibility of a specific age group. Only limited analysis of
data is presented and no environmental measurements of sulfuric
acid were made.
B-ll. Thomas, M. D., R. H. Hendricks, F. D. Gunn, and J. Critchlow.
1958. Prolonged Exposure of Guinea Pigs to Sulfuric Acid Aerosol.
Arch. Ind. Health. 17:70-80.
, Animals were exposed for up to 5 mo to mainly 1-4 mg H2S04/m3,
with 2 experiments at 21-26 mg/m3. Three ranges of aerosol size
were tested. There was some damage at all exposure levels, al-
though apparently not irreversible except at a few accidental
high exposures. The 0.9-(Jm aerosols were the most effective.
Age of the animals was considered.
B-13. Toyama, T., and K. Nakamura. 1964. Synergistic Response to Hy-
drogen Peroxide Aerosols and Sulfur Dioxide to Pulmonary Airway
Resistance. Ind.,Health. 2:34-45.
This is a complicated design that assumed that all the airway re-
sistance seen in 24 subjects exposed to 03 + S02 was due to sul-
furic acid. However, bronchodilated subjects decreased the re-
sponse with all particle sizes. Either the synergism produces
limited H2S04, or they have shown no change in effects due to
change in site of aerosol impingement.
A-8. Treon, J.F., F.R. Dutra, J. Cappel, H. Sigmon, and W. Younker.
1950. Toxicity of Sulfuric Acid Mist. Arch. Ind. Hyg. Occup.
Med. 2:716-734.
Guinea pigs died at 86.6 mg ^SC^/m3, while rats, mice, and rab-
bits survived 2.75 h exposure. Mice died at 549 mg/m3 for 3.5 h,
rats at 699 mg/m3 for 7 h, and rabbits survived until 1,220 mg/m3.
Extensive respiratory damage was seen.
The samples .are small (too small), the particle-aerosol size not
very uniform, and the cage badly homemade, but it works! Observa-
tions are as good on individual animals and their physiology as
that from the latest 200-animal, sophisticated cage. As long as
the conclusions do not overstep individual observation, this is
an important species response paper.
180
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C-- USSR State Committee of the Ministers for Construction. 1972.
Sanitarnyye Normy Proyektirovaniya Promyshlennykh Predpriyatiy
[Sanitary Norms for Industrial Enterprise Design]. Izdatel'stvo
Literatury po Stroitel1stvu [Publishing House of Literature on
Construction]. Moscow. 96 pp.
In the USSR, the MAC for H2S04 in workplaces was 1 mg/m3 and in
populated places was 0.3 and 0.1 mg/m3 (one-time and avg., respec-
tively) .
B-12. Vaughan, T.R., Jr., L.F. Jennelle, and T.R. Lewis. 1969. Long-
Term Exposure to Low Levels of Air Pollutants: Effects on Pulmo-
nary Function in the Beagle. Arch. Environ. Health. 19:45-50.
A series of reports followed this initial one wherein beagle dogs
(12/group) were exposed chronically for 16 h/d to ~0.100 rag H2S04/
m3 and ~0.5 ppm SOz with or without irradiated or nonirradiated
auto exhaust. After 18 mo, analysis of variance showed no signif-
icant effects on the lung functions measured.
B-- Wanner, A. 1977. Clinical Aspects of Mucociliary Transport.
Am. Rev. Respir. Dis. 116(1):73-125,
Review on anatomical feature involved in particulate toxicity.
Basic background information.
A+- WHO, World Health Organization. 1979. Sulfur Oxides and Suspended
Particulate Matter. United Nations Environment Programme and WHO,
Geneva. 107 pp.
Recent review. Authoritative—see pp. 86-93: "insufficient data
for guidelines."
C-10. Williams, M.K. 1970. Sickness Absence and Ventilatory Capacity
of Workers Exposed to Sulfuric Acid Mist. Br. J. Ind. Med.
27:61-66.
Sickness absence rates, expressed as "spells" of sickness per
man-year exposure were compared in plate-forming workers exposed
to sulfuric acid mist, with workers in the same plant unexposed
to acid who served as controls. Exposed workers had a slight ,
excess of spells of respiratory disease (especially bronchitis).
There appeared to be an increased number of spells in attacked
men, rather than an increased proportion of men attacked. The
proportion of men attacked (prevalence) was, similar in study and
control groups. Despite adequate numbers for stratification and
statistical analysis, comparability of study and control groups
and the study of ex-workers. This study has several flaws that
limit its applicability:
181
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(1) No environmental measures of sulfuric acid levels were made
expressly for this study. Only those of Malcom and Paul
(1961) (3-16.0 mg/m3) and 6 y later, Anfield and Warner
(1968) a measurement of 1.4 mg/m3.
(2) Rates were not stratified by duration of exposure. Exposure
length varied from a few days to greater than 40 y. This
analysis would have been quite useful!
(3) Only "spells" per man-year exposure and not actual man-days
absent per disease category were calculated. Hence, the
confusion between period prevalence and spells/man-year.
This technique would not detect chronic respiratory disease.
The so-called increased spells of bronchitis are most likely
exacerbation of chronic bronchitis in the same persons.
Since the technique utilized does not distinguish between one-day
spells and 2- or 3-week spells of absenteeism, it is not surpris-
ing that the prevalence rates of the two groups are similar.
C-10. Winkelstein, W., Jr., S. Kantor, E.W. Davis, C.S. Maneri, and
W.E. Mosher. 1968. The Relationship of Air Pollution and Economic
Status to Total Mortality and Selected Respiratory System Mortal-
ity in Men. -II. Oxides of Sulfur. Arch. Environ. Health. 16:
401-405.
Mortality-based geographic study which shows no association of
total mortality with atmospheric oxides of sulfur. Relationships
between mortality from chronic respiratory disease and sulfation
are confounded by lack of information as to occupation and smoking
variables. Questions also have been raised concerning the "sulfar
tion" method used in determining the oxides of sulfur in terms of
controlling for variations in temperature and humidity.
B-4. Wolff, R.K. M. Dolovich, G. Obminski, and M.T. Newhouse. 1977.
Sulfur Dioxide and Sulfuric-Acid Mist Effects on Bronchial Clear-
ance in Man. Phys. Med. Biol. 22:116.
The irritant effect of 1'mg H2S04/m3 (3.0 (Jm MMD) produces in-
crease in clearance rate from large airways.
B-10. Wolff, R.K., S.A. Silbaugh, J.L. Mauderly, and F.F. Hahn. 1978a.
Sulfuric-Acid Mist Toxicity in Hartley Guinea Pigs. Fed. Proc.
37:870.
The LC50 was 23 mg/m3 for 8 h. Near lethal concentrations were
reached before functional changes were found in contrast to other
studies at low levels with different strains.
182
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Inference that guinea pig response to H2S04 may be unique—all or
none—which raises questions on data extrapolation to man.
B-12 Wolff, R.K., B.A. Muggenburg, and S.A. Silbaugh. 1978b. Sulfuric
Acid Mist and Mucous Clearance in Beagle Dogs. Annu. Rep. Inha-
lation Toxicol. Res. Inst. pp. 372-377.
Method demonstrates good quantitation of mucus clearance after
exposure to H2S04 mist. One-hour exposure to ~1 or ~0.5 mg/m3
(~0.9 pro MMAD) caused a significant depression in mucociliary
transport up to a week after exposure. The same dogs were used
in further studies reported by Wolff et al. (1979c).
A-16. Wolff, R.K., S.A. Silbaugh, D.G. Brownstein, R.L. Carpenter, and
J.L. Mauderly. 1979a. Toxicity of 0.4 and 0.8 |Jm Sulfuric Acid
Aerosols in the Guinea Pig. J. Toxicol. Environ. Health. 5:1037-
1047.
This report is practically identical to that of Silbaugh et al.
(1978b). Guinea pigs were exposed for 8 h to graded concentra-
tions of H2S04 aerosols (0.4 or 0.8 |Jm MMAD). The LC50 at 21 d
after exposure of the 0.4-|jm aerosol was >109 mg/m3, but the LCso
of the 0.8-|Jm aerosol was 30 mg/m3.
\
A-16. Wolff, R.K., B.A. Muggenburg, and S.A. Silbaugh. 1979b. Effects
of sulfuric Acid Mist on Tracheal Mucous Clearance in Awake Beagle
Dogs. Am. Rev. Respir. Dis. 119:242.
This is an abstract of the study reported more fully by Wolff et
al. (1978b).
B-12. Wolff, R.K., B.A. Muggenburg, and S.A. Silbaugh. 1979c. Effect of
0.3 and 0.9 |Jm Sulfuric Acid Aerosols on Tracheal Mucous Clearance
in Beagle Dogs. Ann. Rep. Inhal. Tox. Res. Inst. pp. 506-510.
Dogs exposed for 1 h to ~0.9-|Jm particles at ~1 mg H2S04/m3.and 7
wk later to 0.5 mg H2S04/m3 showed significant depression in tra-
cheal mucus clearance ~1 wk after each exposure. Recovery required
5 wk after the first exposure. (These same tests were also des-
cribed by Wolff et al., 1978b and 1979b.) After a 7-wk period in-
cluding a sham exposure, the same dogs were exposed to 0.3-|Jm parti-
cles at ~1 mg/m3 and 7 wk later to 0.3-|Jm particles at 5.0 mg/m3.
In these tests, no significant change was seen in the tracheal mucus
clearance rate.
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TECHNICAL REPORT DATA
(Please read Instructions on the reverse before completing)
1. REPORT NO.
EPA 460/3-8/-025
2.
3. RECIPIENT'S ACCESSION-NO.
4. TITLE AND SUBTITLE
Sulfuric Acid Health Effects
5. REPORT DATE
August 1981
6. PERFORMING ORGANIZATION CODE
Harry V. Ellis III
Larry H. Baker
Eileen M. Horn
Joy L. McCann
Cecily M. Beall
Carol Hopkins
7. AUTHOR(S)
Bonnie L. Carson
Betty L. Herndon
8. PERFORMING ORGANIZATION REPORT NO.
9. PERFORMING ORGANIZATION NAME AND ADDRESS
Midwest Research Institute
425 Volker Boulevard
Kansas City, Missouri 64110
10. PROGRAM ELEMENT NO.
11. CONTRACT/GRANT NO.
68-03-2928
12. SPONSORING AGENCY NAME AND ADDRESS
Environmental Protection Agency
Office of Mobile Source Air Pollution Control
Emission Control Technology Div., 2565 Plymouth Road
Ann Arbor, Michigan 48102
13. TYPE OF REPORT AND PERIOD COVERED
Final Report
14. SPONSORING AGENCY CODE
15. SUPPLEMENTARY NOTES
16. ABSTRACT • .
Health effects literature primarily related to inhalation exposures to sulfuric
acid was collected, evaluated, tabulated, and summarized. Approximately 300 documents
were collected from computerized and manual literature searches covering the period
1931-1981. Pharmacologists and an M.D. epidemiologist rated the documents according
to their applicability to the study and their methodology. Those (~ 150) documents
considered useful for deriving a range of concern for human exposure to sulfuric acid
from automotive emissions were tabulated. The 110 pages of tables detail the results
of acute, repeated dose, and chronic testing of mice,.hamsters, rats, guinea pigs,
rabbits, cats, monkeys, dogs, sheep, donkeys, and humans as well as human occupational
and epidemiological studies. Most of the documents evaluated are described in an an-
notated bibliography.
7.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.lDENTIFIERS/OPEN ENDED TERMS
c. COSATI Field/Group
Toxicity
Sulfuric Acid
Occupational Diseases
Epidemiology
Respiratory System
Bibliographies
Toxic Tolerances
Mammals
Inhalation Health Effects
06T
3. DISTRIBUTION STATEMENT
Release Unlimited
19. SECURITY CLASS (This Report)
Unclassified
21. NO. OF PAGES
186
20. SECURITY CLASS (Tins page/
Unclassified
22. PRICE
EPA Form 2220-1 (9-73)
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