United States
Environmental Protection
Agency
Office of Mobile Source Air Pollution Control
Emission Control Technology Division
2565 Plymouth Road
Ann Arbor, Ml 48105
EPA-460/3-81 -034
Air
&EFA
Acrolein Health Effects
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ACROLEIN HEALTH EFFECTS
with Contributions by
Bonnie L. Carson
Cecily M. Beall Larry H. Baker
Harry V. Ellis III Betty L. Herndon
FINAL TASK 6 REPORT
December 23, 1981
Contract No. 68-03-2928
Task Specification No. 6
"Health Effects Support for the Emission Control
Technology Division"
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
V- •'• i:-:.' ^
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PREFACE
This report on health effects of acrolein was prepared by Midwest
Research Institute (MRI) as Task No. 6 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 acrolein has been collected, evaluated, tabulated, and summarized so
that this report can be used to derive a range of concern for human ex-
posure to vehicular atmospheric emissions of acrolein.
Task activities were coordinated by the project leader, Mrs. Bonnie L.
Carson, Senior Chemist, and the task leader, Ms. Cecily M. Beall, Assistant
Scientist. Documents were rated and summarized by senior pharmacologists
Drs. Harry V. Ellis III and Betty L. Herndon, of MRI, and epidemiologist
Larry H. Baker, M.D., MRI consultant, who is Associate Professor of Commun-
ity Health at the University of Kansas Medical Center. Data were tabulated
by Ms. Beall, who, along with Mrs. Carson, 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 officer 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,
Center for Technoeconomic
Analysis
December 23, 1981
111
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CONTENTS
Preface.
Figures.
Tables .
111
vi
vi
Summary 1
Goals and methods 1
Bioassay tests 1
Animal exposures 3
Human exposures 7
Recommended range of concern 11
I. Introduction 13
II. Bioassays 17
III. Experimental Animal Inhalation Exposures 21
IV. Experimental Human Inhalation Exposures 75
V. Other Human Exposures 89
Bibliography 93
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FIGURES
Number
1-1
Form for report rating
TABLES
Number
S-l Summary of Studies of Animal Exposure to Acrolein Up to
2.5 mg/m3 4
S-2 Examples of Ambient Air Levels of Acrolein 8
S-3 Acrolein Levels in Cigarette Smoke 9
S-4 Summary of Acute Human Experimental Exposure to Acrolein . 10
S-5 Summary of Regulations and Recommendations for Limiting
Human Exposure to Acrolein 12
II-l Respiratory Tract Bioassays 18
III-l Mice—Acute Experimental Exposure to Acrolein 22
III-2 Mice—Repeated Dose Experimental Exposure to Acrolein. . . 30
III-3 Hamsters—Acute Experimental Exposure to Acrolein 34
III-4 Hamsters—Chronic Experimental Exposure to Acrolein. ... 35
III-5 Rats—Acute Experimental Exposure to Acrolein 37
III-6 Rats—Repeated Dose Experimental Exposure to Acrolein. . . 42
III-7 Rats—Chronic Experimental Exposure to Acrolein 52
III-8 Guinea Pigs—Acute Experimental Exposure to Acrolein ... 55
III-9 Guinea Pigs—Repeated Dose Experimental Exposure to
Acrolein 57
111-10 Chickens—Repeated Dose Experimental Exposure to
Acrolein 58
III-ll Rabbits—Acute Experimental Exposure to Acrolein 59
111-12 Rabbits—Chronic Experimental Exposure to Acrolein .... 60
111-13 Cats—Acute Experimental Exposure to Acrolein 61
III-14 Monkeys--Repeated Dose Experimental Exposure to Acrolein . 63
111-15 Dogs—Repeated Dose Experimental Exposure to Acrolein. . . 65
III-16 Summary of Animal Inhalation Exposures to Acrolein .... 67
IV-1 Humans—Acute Experimental Inhalation Exposure to
Acrolein 76
V-l Studies of Occupational Exposure to Acrolein 90
V-2 Humans--Studies of Accidental Exposures to Acrolein. ... 91
VI
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SUMMARY
This summary of the health effects of inhalation of acrolein (CH2=CH-CHO)
is organized into the following sections: Goals and Methods, Bioassays, Ani-
mal Exposure Studies, Human Exposure Studies, and Recommended Range of Con-
cern.
GOALS AND METHODS
The purpose of this compilation of data on acrolein inhalation expo-
sures is to assist the Emission Control Technology Division (ECTD) of the
U.S. Environmental Protection Agency (EPA) to establish the ranges of ex-
posure conditions that are of concern for acrolein in exhausts from vehi-
cles equipped with catalytic converters, and to be able to advise automobile
manufacturers thereof. The situations of concern are during malfunctions
and during exposures in traffic jams, parking and home garages, and other
situations where little dilution of the exhaust is expected before inhala-
tion. Most of the report is, as directed by ECTD, in the form of tables
based on the literature reviewed. Data from exposures at levels higher
than those of primary concern are included because strictly relevant infor-
mation was scarce and these related data might prove helpful in assessing
health effects at lower levels.
Documents on inhalation effects of acrolein identified from manual
and computerized literature searches were rated in a two-step process
by the project pharamacologist and epidemiologist. First, the document re-
ceived an A, B, C, or D rating according to its applicability for deriving
a range of concern for acrolein in automobile emissions. Second, if the
paper was not a low-rated, foreign language document*, a theoretical paper,
a review, or a nontoxicology experimental paper, it received a numerical
score based on itemized features that should be present in an ideal report.
For the most part, only A- and B-rated documents were tabulated; but when
C- or D- rated studies involved low-level acrolein exposures, these were
also tabulated. Blanks in the .tables should be construed as denoting
missing information in the documents.
BIOASSAY TESTS
In vitro studies show acrolein to be an inhibitor of ciliary activity
and possibly a weak mutagen. Its possible carcinogenicity is also dis-
cussed.
Most foreign language articles rated C and D were usually not translated.
Each foreign language document tentatively rated A or B from an English
language abstract or brief examination of the paper was translated in
sufficient degree to judge the experimental design and details. These
papers were numerically scored from the translation.
1
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In vitro tests on respiratory tissues: Only those tests using respira-
tory tissues and gaseous acrolein and reporting the acrolein levels used are
tabulated in Section II. This tabulation has ignored the i.n vitro studies
that evaluated the enzymatic changes brought about in animals by acrolein
exposure, because they did not fulfill these criteria. Also, there is no
adequate way to evaluate or extrapolate from the enzyme studies to an in-
halation dose level for man. A thorough description and discussion of all
types of in vitro studies is given in ECAO (1980).
Many of the tabulated (Table II-l) studies looked at irritant effects
of acrolein, using tracheal cilia motion to quantitate acrolein dose-effects.
The lowest level tested for effect on ciliary activity was 31.2 mg acrolein/
m3, causing ciliostasis in rabbit tracheal sections in ~ 36 rain (Dalhamn
and Rosengren, 1971).
Battista and Kensler (1970) interpreted their ciliary bioassay results
as showing acrolein to be one of the most potent components of cigarette
smoke. Macrophage function bioassays, however, specifically excluded acro-
lein as being a contributor to cigarette smoke toxicity (not tabulated:
Haroz and Mattenberger-Kreber, 1977; Leffingwell and Low, 1979). However,
Voisin et al. (1979, 1980) reported that ATP levels in macrophages decreased
20-70% following 30-min exposures to 18.6-81.6 mg acrolein/m3.
Other bioassays: The mutagenic, carcinogenic, and teratogenic poten-
tial of acrolein has been thoroughly reviewed in ECAO (1980) and SRC (1979)
(identical reviews).
Acrolein has shown "low," "borderline," or "moderate" mutagenicity
depending on the test system and the author's frame of reference. No base-
pair or frameshift mutations were found by two different groups using dif-
ferent test systems. Neither activated nor unactivated bacterial systems
produced point mutations. Undescribed levels produced Drosophila mutations
according to a 1945 report. One recent report described mutagenic changes
(nucleic acid chain insertions/deletions) by acrolein when Salmonella
typhimurium TA1538 and 98 were exposed (ECAO, 1980; SRC, 1979)T~ ~~
Two chronic whole-animal carcinogenicity studies using hamsters have
been performed. The results of Feron and Kruysse (1977) have been sum-
marized in Table III-4. In the study of exposure to 9.2 mg/m3 for 7 h/d,
5 d/wk, for 52 wk, acrolein gave no indication of carcinogenic activity or
co-carcinogenic activity with diethylnitrosamine, and had a minimal effect
on the carcinogenic activity of benzo(a)pyrene (BP).
The unpublished results of a bioassay sponsored by the National Cancer
Institute show no evidence that acrolein was a carcinogen or a co-carcinogen
with BP or with ferric oxide (ECAO, 1980; SRC, 1979). The hamsters had been
exposed to 11.5 mg acrolein/m3 6 h/d, 5 d/wk, throughout their lifespan.
IARC (1979) concludes that the small amount of animal data and the lack
of human data precludes an evaluation of the carcinogenicity of acrolein.
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One study exposing male and female rats to 1.24-1.31 mg acrolein/m3
for 26 d found no effect on the number of pregnant rats or the number and
average weights of the fetuses (Bouley et al., 1975 and 1976) (see
Table III-6). No longer-term studies have been done.
ANIMAL EXPOSURES
Acrolein is well known as an extremely irritating chemical, more po-
tent than either its saturated analogue, acetaldehyde (CHsCHO), or the pro-
totype aldehyde, formaldehyde (HCHO) (see standard texts, such as Amdur,
1980). Upper respiratory tract retention of acrolein in dogs is ~ 80%
(Egle, 1972), so that is the site of most of the irritation. Acrolein is a
major toxic component of fires, and is the usually cited representative of
the complex mixture of aldehydes and ketones which causes delayed deaths 6
to 72 h after "smoke inhalation." Much of the experimental data was in-
spired by this source, so most studies are of acute exposures. These stud-
ies are completely described in Section III, summarized by concentration in
Table 111-16, and summarized here in Table S-l.
Mouse studies: Most acute data (see Table III-l) are from the work of
Kane and Alarie (1977, 1978), who studied acrolein alone and with formalde-
hyde. They found effects (decrease in respiratory rate) at the lowest lev-
els tested (0.68 mg acrolein/m3 or 0.28 mg acrolein/m3 plus 0.46 mg HCHO/m3)
Repeated dose studies (Table III-2) showed similar results: some effects
during a 10-min exposure to 1.03 mg/m3 following acute exposures to 0.40 mg/
m3 in the previous days. There was some evidence of tolerance (at lower
levels of 0.4 mg/m3) and some of sensitization (at higher levels of 1.2 and
4.0 mg/m3) from repeated dosing.
Hamsters: Feron and Kruysse (1977) and Feron et al. (1978) did 52-wk
(12-mo) and 13-wk (3-mo) studies on hamsters exposed for 6 or 7 h/d, 5 d/wk
(Table III-4). Exposure to 0.93 mg/m3 produced no effects at all, while 3.3
mg/m3 caused minimal effects: sleeping and restlessness during exposure,
minimal inflammation in the nasal cavity. Higher doses were much more
toxic, with a variety of effects. Histopathologic effects were found in the
respiratory tract, basically as a reaction to inflammation.
Rat studies: The rat acute dose studies (Table III-5) were not very
useful, the lowest level tested being 4.9 mg/m3. However, there are several
interesting repeated dose studies (Table III-6). Lyon et al. (1970) exposed
rats continuously for 90 d. A concentration of 0.51 mg/m3 had no effect,
while 1.6 mg/m3 caused pulmonary inflammation and occasional emphysema, 2.3
mg/m3 affected weight gain, and higher doses caused various nonspecific in-
flammatory changes.
Bouley et al. (1975, 1976) did a variety of studies on specific
pathogen free rats exposed to 1.24 to 1.31 mg/m3 for various periods of
time (Table III-7). These exposures were toxic (decreased body weight and
food consumption), but effects decreased during exposure and recovery oc-
curred afterward, in 39 d. There were no effects on reproduction. When
challenged with an aerosol of pathogenic bacteria after exposure to this
level for 18 d, mortality increased; however, there was no increase after
63-d exposure.
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TABLE S-l
SUMMARY OF STUDIES OF ANIMAL EXPOSURE TO ACROLEIN
UP TO 2.5 mg/m3*
Level Time Species Effects
2.3 up to RAT Decreased wt. gain and vanillylmandelic
91 d acid levels; no effect on hematological
values or respiratory resistance; slight
loss of bronchial ciliation on days 7-35;
perivascular edema after 35 d.
2.3 90 d DOG Decreasing ocular and nasal discharge in
MKY DOG and MKY; no effect on wt. gain (ex-
GPG cept RAT, which decreased) or hematolog-
RAT ical values; various degrees of pulmonary
inflammation in DOG, GPG, and RAT; para-
sitic infection in MKY; occasional, slight
liver damage in DOG and GPG; kidney in-
flammation in DOG.
2.3 81 h RAT No effect on: liver-to-body-wt. ratio;
adrenal and lung wt.; and liver, lung,
and serum AP activity.
2.3 2 h GPG Significantly increased respiratory
resistance and rate and decreased tidal
volume.
1.6 8 h/d, RAT No effect on behavior, body wt. gain,
5 d/wk, GPG hematological values, various enzyme
6 wk MKY activities; mild chronic lung inflamma-
DOG tion; occasional emphysema; no definite
alteration of respiratory epithelia or
the peribronchial smooth musculature.
1.52 24 d RAT Progressive deterioration of general
condition; 7/10 died; changes in mag-
nitude and latent period of condition-
ed motor response; decreased blood cho-
linesterase activity and increased
leukocytes, returning to normal by 20 d
post-exposure; lung inflammation; myo-
cardium and liver changes.
1.23-1.47 6 mo RAT Decreased body wt.; alveolar damage;
liver cell damage; no effect on alveolar
macrophages, spleen, kidney, stomach, or
heart.
* This level, about 10 times the threshold limit value, was chosen
arbitrarily.
4
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TABLE S-l (continued)
Level Time Species Effects
1.4 2 h GPG Increased expiratory flow resistance
and tidal volume and decreased respira-
tion rate, max. change in 30-60 min.
1.24-1.31 10-180 d RAT Decreased number of alveolar macrophages
on days 10-26; no effect on relative no.
of cells, viability, and physiological
activity; no effect on days 60-180.
1.24-1.31 15,18, RAT Increased lung-to-body-wt. ratio only
21, 26 on day 77; no effect on various enzyme
32, 60, activities; decreased body wt. during
63, or 21-d exposure; no effect on no. of
77 d pregnant rats or no. and avg. wt. of
fetuses for 26-d exposure; signifi-
cantly increased mortality when a high
bacterial dose followed an 18-d expo-
sure, but not after a 63-d exposure.
0.93 6 h/d, RBT No effect on behavior, growth, food in-
5 d/wk, HAM take, hematological values, blood chem-
13 wk istry, urinalysis, organ-to-body-wt.
ratios, gross autopsy, or histopathol-
ogy of the respiratory tract.
0.9 2 h GPG Significantly increased total respira-
tory resistance; decreased respiratory
rate.
0.74 61 d RAT General state and wt. affected by 6th
wk in healthy rats and by 5th wk in rats
with experimentally induced silicosis;
changes in chronaxy of antagonistic
muscles in both groups.
0.51 90 d DOG No effect on behavior, wt. gain, hema-
GPG tological values, gross autopsy (RAT,
MKY MKY, GPG, DOG, with exceptions noted
RAT below). MKY & GPG & DOG - nonspecific
inflammatory changes in liver, lung,
kidney, and heart. DOG - some of the
following: emphysema, lung congestion,
some bronchiolar construction, hyper-
plasia of the thyroid, focal subcapsular
hemorrhage of the spleen.
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TABLE S-l (continued)
Level Time Species Effects
0.51 61 d RAT No change in behavior or general condi-
tion; lost wt.; loss of conditioned
reflexes after 10 d; disturbance of
spatial relationships; decreased urine
coproporphyrin levels and blood cholin-
esterase activity; recovery post-exposure;
some histopathologicial changes in the
bronchi.
0.47 2 h GPG Slight increase in total respiratory
flow resistance; slight decrease in res-
piratory rate and minute volume.
0.15 61 d RAT No change in behavior, general condition,
wt., magnitude or latent period of condi-
tioned motor reflexes, urine copropor-
phyrin levels, or blood cholinesterase
activity; no appreciable changes found
on autopsy.
0.14 61 d RAT Changes in chronaxy of antagonistic
muscles in healthy rats and rats with
silicosis.
0.03 61 d RAT No change in a variety of biological,
biochemical, and physiological tests in
healthy rats or rats with silicosis.
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Gusev et al. (1966) found no toxic effects after 6l-d exposure to
0.15 mg/m3, minor neurological effects after 0.51 mg/m3, and severe effects,
with 70% mortality, after 1.52 mg/m3. Sinkuvene (1970) found no effects
after 61 d at 0.03 mg/m3, minor changes (of dubious toxicological signifi-
cance) at 0.14 mg/m3, and severe toxicity at 0.74 mg/m3.
Feron et al. (1978) exposed rats 6 h/d, 5 d/wk, for 13 weeks. At
0.93 mg/m3, growth retardation was not statistically significant, but was
toxicologically important because of its consistency. Higher doses
(3.3 mg/m3 and 11.4 mg/m3) were definitely toxic with decreased weight
gain, pathologic changes in respiratory epithelia, and other effects. In-
termediate doses of 1.23 to 1.47 mg/m3 for 6 mo (Roussel et al. , 1973)
caused decreased body weight gain, alveolar damage, liver cell damage, and
had no effect on alveolar macrophage activity or other major organs.
Guinea pig studies: Murphy et al. (1963) studied respiratory physi-
ology (see Table III-8) . They found minor, possibly unimportant, changes
after 2 h of 0.47 mg/m3 of acrolein and definite respiratory effects (in-
creased resistance, decreased rate, etc.) at doses of 0.9 mg/m3 and higher.
Lyon et al. (1970) exposed guinea pigs for 90 d (see Table III-9).
The low concentration of 0.51 mg/m3 was probably nontoxic (only nonspecific
inflammatory changes in various organs were reported). Doses of 1.6 mg/m3
and up caused pulmonary pathology and other effects.
Larger animal studies: Denine (1971) gave chickens large, brief (5
min/d) doses and found dose-related toxicity, but did not determine a no-
effect dose (Table 111-10).
Feron et al. (1978) exposed rabbits 6 h/d, 5 d/wk for 13 wk (Table III-
12). They found no effects at 0.93 mg/m3, occasional sneezing and de-
creased feed intake and weight gain at 3.3 mg/m3, and histopathology of the
respiratory epithelia at 11.4 mg/m3.
Iwanoff (1911) gave cats very toxic doses (Table 111-13) of 25-210 mg/
m3. The symptoms of irritation were immediate and increased in severity
with time. All apparently recovered within a few days.
Lyon et al. (1970) exposed squirrel monkeys (Table 111-14) and dogs
(Table 111-15) to acrolein either continuously for 90 d or 8 h/d, 5 d/wk,
for 6 wk. With the monkeys, 0.51 mg/m3 had no definite effects, while
1.6 mg/m3 caused some pulmonary inflammation. Dogs were more sensitive
since the low dose of 0.51 mg/m3 did cause pulmonary pathology in two
of four dogs.
HUMAN EXPOSURES
People can be exposed to acrolein in ambient air and in cigarette
smoke. These exposures and human experimental exposures are discussed here,
followed by examples of regulations and recommendations for limiting human
exposure.
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Ambient air levels: Measured background levels of acrolein in urban
areas to which the general public can be exposed are listed in Table S-2.
They are all concentrations determined outdoors. No examples of indoor air
levels were found.
TABLE S-2
EXAMPLES OF AMBIENT AIR LEVELS OF ACROLEIN
Level (mg/m3)
0.005-0.025
0.002-0.025
0.023
0.016
0.014
0.014
Location
Reference
At street level in South
Pasadena, CA; July-November
At sixth-floor level in
Los Angeles, CA; September-
November
Urban polluted air
Downtown Los Angeles;
September-October
Urban air
Huntington Park, CA;
October
Renzetti and Bryan
(1961)
Renzetti and Bryan
(1961)
Stupfel (1976)
Altshuller (1978)
Criteria for Community
Air Quality Commit-
tee (1968)
Altshuller (1978)
Cigarette smoke: Cigarette smoke is a frequent confounding factor in
studies of human exposure to acrolein both because of the respiratory irri-
tant effects of whole smoke and the presence of acrolein in the smoke.
Estimates of acrolein levels vary with the type of cigarette and the re-
searcher. Table S-3 cites some examples found in the literature. Using the
highest reported level of 20 pg/puff (Kensler and Battista, 1963), one can
estimate that a smoker's lungs will be momentarily (but repeatedly) exposed
to air containing ~ 28.6 mg acrolein/m3 (20 |jg/0.7 L tidal lung volume).
This concentration is one hundred times greater than the TLV of 0.25 mg/m3.
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TABLE S-3
ACROLEIN LEVELS IN CIGARETTE SMOKE
Level Reference
7-12 (Jg/35 mL puff Morton and Guerin (1974)
(200 to 343 mg/m3)
2.9-8.2 |Jg/40 mL puff Newsome et al. (1965)
(72.5-205 mg/m3)
112 [jg/cigarette Haroz and Mattenberger-Kreber
(1977)
3.6 |Jg/35 mL puff Bridges et al. (1977)
(103 mg/m3)
60 ppm (138 mg/m3) Stupfel (1976)
7-74 |jg/cigarette; Rylander (1973)
9-10 puff/cigarette
20 |Jg/40 mL puff Kensler and Battista (1963)
(500 mg/m3)
Experimental studies: A wide variety of experimental studies in humans
is fully described in Table IV-1, and summarized here in Table S-4. Many
are not very useful because they involve mixtures of noxious gases. Others
show that humans will tolerate 5-10 mg/m3 of acrolein for only a minute or
two, but these are also of minimal use for our purpose.
Several important studies have, however, determined thresholds for
specific effects. Plotnikova (1960) found that 0.6 mg/m3 was the thresh-
old for an acrolein-induced increase in photosensitivity of the eye.
Weber-Tschopp et al. (1977) found a threshold of about 0.2 mg/m3 for both
subjective ("annoyance") and objective (blinking frequency) responses in
people subjected to increasing concentrations of acrolein. Odor thresholds
include 0.49 mg/m3 ("recognition"; Leonardos et al., 1969), 0.078 mg/m3
(Ubaidullaev and Abramova, 1976), and 0.07 mg/m3 (Sinkuvene, 1970).
Exposures of the general public: No useful occupational (Table V-l) or
accidental (Table V-2) studies were found.
International standards and recommendations: Many countries have regu-
lations concerning the levels of acrolein allowed in the workplace or the
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TABLE S-4
SUMMARY OF ACUTE HUMAN EXPERIMENTAL EXPOSURE TO ACROLEIN
Acrolein Level
(mg/m3) Effects
2-3-5.4 Medium to severe eye irritation in 5 min.
4 Irritation of the conjuctiva, nasal mucosa, and
nasopharyngeal region.
3-0-3.7 Medium to severe eye irritation in 5 min.
2-8 Extremely irritating to all mucous membranes in
5 min; lacrimation.
2-3 82% of the exposures caused medium or severe eye
irritation in 5 min.
1.75-2.0 Changes in amplitude of respiratory movements;
slightly increased respiratory frequency; de-
creased eye sensitivity to light; changes in
optical chronaxy.
1-88 Only just tolerable for 10 min; extremely irri-
tating to all mucous membranes.
1-5 Slight changes in amplitude of respiratory move-
ments .
0-1-5 No effect on rheobase or optical chronaxy; irrita-
tion and annoyance increasing with concentration
to severe eye and moderate nose irritation; indi-
cations of possible adaptation at lower levels
and sensitization at higher levels.
1.2 Medium or severe eye irritation, numbers of com-
plaints varying with length and type of exposure;
tear volume, pH, and lysozyrae activity changed.
0.8-1.05 Slight eye and nose irritation; no effect on res-
piratory frequency or amplitude; odor perceived.
0.8-0.83 Increased eye sensitivity to light in 5 min; eye
irritation in 70% of the subjects in 2 rain; minimum
odor perceived by 9/10 was 0.8 mg/m3.
0.7 Some eye, nose, and throat irritation for 40 mm,
then decreased; 20% decrease in respiratory fre-
quency in 40 min; subjective air quality decreased
for 20 min, then increased.
0.6-0.65 Threshold value for action on eye sensitivity to
light.
0.49-0.5 Subthreshold value for eye sensitivity to light;
lowest level at which all recognized the odor.
0.33-0.35 30% felt eye irritation in 2 min; increased an-
noyance and almost no eye or nose irritation
during repeated exposures.
0.23 50% detected the odor.
0.14 Odor threshold; slight eye irritation.
0.07-0.078 Odor threshold for most acrolein-sensitive people.
0.05 Threshold for affecting electrocortical activity.
0.03 Subthreshold for affecting electrocortical activity.
10
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ambient air. Studies have also recommended safe levels for different situ-
ations. Table S-5 summarizes this information. Allowable levels in work
environments range from 1.0 mg/m3 for a ceiling level to 0.25 mg/m3 as the
most common avg. TLV. Only one indoor recommendation was found--0.1 mg/m3
in the USSR. Ambient air standards range from 0.03 mg/m3 to a recommended
0.005 mg/m3.
RECOMMENDED RANGE OF CONCERN
From the animal data, a concentration of 1 mg/m3 is quite definitely
toxic. The most common "no-effect" level was about 0.5 mg/m3. From these
data, this would be the upper level of concern. However, acrolein appears
to have additive effects with other irritants (such as HCHO), the evidence
on sensitization/tolerance is contradictory, and few interspecies studies
were done. These problems suggest recommending a lower value for the upper
range of concern.
From the human exposure data the main noxious characteristic of acro-
lein is its sharp, irritating odor. The irritation threshold appears to
be 0.1-0.2 mg/m3, and the odor threshold somewhat below 0.1 mg/m3. No
effects at all were seen below 0.05 mg/m3. To allow for the fact that the
effects of acrolein appear to be additive with other irritants and to allow
a margin of error, we suggest a range of concern of 0.1 to 0.01 mg/m3. How-
ever, there should be some sort of an additivity system for the various ir-
ritants (HCHO, S02, NH3, etc.); the TLV system is suggested.
11
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TABLE S-5
SUMMARY OF REGULATIONS AND RECOMMENDATIONS
FOR LIMITING HUMAN EXPOSURE TO ACROLEIN
Level (mg/tn3)
1.0
0.8
0.7
0.5
0.3
0.25
0.25
0.1
0.046
0.03
0.023
0.005
Recommendation/Regulation
Standard for occupational exposure
in Czechoslovakia (ceiling).
Tentative short-term-exposure-limit
for the workplace.
Standard for occupational exposure
in Hungary and USSR.
Standard for occupational exposure
for Czechoslovakia (avg.) and
Romania (ceiling).
Standard for occupational exposure
in Romania (avg.).
Standard for occupational exposure
in Australia, Belgium, Finland, West
Germany, Japan, The Netherlands,
Sweden, Switzerland, and Yugoslavia,
and East Germany.
8-h TLV set by OSHA; time-weighted
avg. TLV recommended by ACGIH.
Max. acceptable room air concen-
tration in the U.S.S.R.
Recommended lowest concentration
necessary for TLV.
Max. immission concentration for
populated places in U.S.S.R.--both
avg. and one-time.
Recommended concentration below
which no sensory irritation will
occur.
Recommended highest concentration
for an Air Quality Standard.
Reference
SRC (1979);
ILO (1970)
ACGIH (1980)
SRC (1979)
SRC (1979);
ILO (1970)
SRC (1979)
SRC (1979);
Jermini and Weber
(1975); Bittersohl
(1974)
SRC (1979);
ACGIH (1980)
Kettner (1978)
Kane et al. (1979)
U.S.S.R. (1972);
Kettner (1978)
Criteria for Com-
munity Air Quality
Committee (1968)
Kane et al. (1979)
12
-------
SECTION I
INTRODUCTION
This report was compiled as the sixth of several tasks under Contract
No. 68-03-2928, "Health Effects Support for the Emission Control Technol-
ogy Division (U.S. Environmental Protection Agency, Ann Arbor, Michigan)."
The goal of the project is to evaluate health effects literature on spe-
cific compounds emitted from automobiles equipped with emission-control
devices (specifically catalytic converters), not for the purpose of
creating a criteria document but to identify a range of concern or a no-
observable-effect level for each compound to serve as guidance to auto-
mobile manufacturers in their development of future emission-control
devices.
The present report was meant to be largely a series of charts or
tables of pertinent data with the tests logically ordered according to ex-
posure 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 that the authors of a particular pa-
per observed may be diluted or lost when the details are spread throughout
an exceptionally large table, or between several tables. Papers described
in a largely narrative fashion, however, often are difficult to compare.
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 acrolein was collected
mainly by computer search of TOXLINE and TOXBACK and manual search through
major review articles on acrolein. Approximately 125 papers and other docu-
ments were evaluated, but only about 45 contained original data suitable for
tabulation.
Experimental animal and human exposure studies and bioassay studies
were evaluated and summarized by senior Ph.D. pharmacologists. Occupa-
tional exposures were rated by an epidemiologist with an M.D. degree.
Figure 1-1 is the form used for rating documents by the project pharmacolo-
gist and epidemiologist. Each document was rated in a two-step procedure
according to the applicability of its subject matter and to the quality of
the experimental 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 to
or assists in establishing a range of concern for exposure to acrolein.
13
-------
Article No. 4997-6-
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 acrolein as guidance for establishing a
range of concern for acrolein in automobile exhaust.
(circle one)
a. Clearly, directly applies/assists in establishing a range of concern.
(Chronic human studies; acute exposure of humans if minimal effects.)
b. Research requires major inferences; potentially applicable.
(Chronic animal studies; acute human, maximal effect; acute animal,
minimal effects.)
c. Useful hints or suggestions; tentatively applicable.
(Acute animal, lethal effects; studies in above categories but effects
reported not appropriate.)
d. Not directly applicable (peripheral useful information).
Figure 1-1. Form for report rating.
14
-------
The second part of the rating is the methodology score. The document re-
viewer 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, theoretical papers, and low-rated foreign language documents, a
paper may have received an applicability rating (generally C or D) but none
on methodology.
Data, including the MRI-assigned rating, from the A-, B-, and some
C-rated papers were tabulated by mid-level scientists. Information for each
topic heading was carefully sought; so if blanks appear in the table, the
reader can generally assume the data were not given. Information which was
unclear in the original document but needed for tabulation is preceded in
the tables by a qualifying word such as "apparently." Sometimes a group
published several papers that described the same tests. To avoid redun-
dancy, all pertinent papers were cited and the test was described as well
as possible from all the papers' descriptions.
The final written 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 tabu-
lar material by weight. The tables reflect the amount of data generated,
and the summary puts the evaluated data in perspective 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 of same) to the study. English titles are given for foreign lan-
guage documents, and an abbreviation of the language is given in paren-
theses at the end of the citation.
The report is organized into the following chapters: II. Bioassay
Tests, III. Experimental Animal Inhalation Exposures, IV. Experimental
Human Inhalation Exposures, and V. Other Human Exposures. The Summary
precedes the entire report and the Annotated Bibliography follows it.
15
-------
SECTION II
BIOASSAYS
Only five in vitro studies using respiratory tissues and gaseous acro-
lein were found~~in the literature. The results, described in Table II-l,
appear to have little information directly useful to this task on determin-
ing a range of concern for human exposure to acrolein in automobile exhaust.
The data are discussed in the Summary.
17
-------
TABLE II-l. RESPIRATORY TRACT BfOASSAYS
Compound and
concentration
in mg/m3 (ppm)
Temperature
and
humidity
Preparation exposed
Description of tests and duration
Results
Reference
and
rat ing
Acrolein 1,250 37°C Tracheal tissue from young adult The concentration of acrolein (in air) The "8 puff ED50" was 50 ug/puff, Kensler and
New Zealand albino rabbits. per puff producing 50% inhibition in or 1,250 mg/m3. The authors' Battista (1963)
tracer particle movement, after 8-40 value for acrolein levels in D-10
mL, 12 sec "puffs" of air. cigarette smoke was 20 pg/puff.
Acrolein 875-
1,000
White Leghorn chickens.
00
The larynx of an anesthetized chicken
was lifted into its mouth. The animal
was exposed to a 40-mL puff for 4 sec,
once every minute. After each expo-
sure, the ciliary transport rate of
tracer particles was measured. The
level of acrolein/puff which would
cause a 50% inhibition after 8 puffs
was determined.
The "8 puff ED50" was 35-40 Battista and
Mg/puff, or 875-1,000 mg/m3. Kensler (1970)
Cigarette smoke is estimated C-9
to contain 8.2 - 20 pg acrolein/
40 mL puff.
Acrolein
31.2-247.8
Rabbit tracheal sections.
HCHO from an air nebulizer was added
to a moist, temperate chamber at the
rate of 54 L/h for a maximum of 60
min. Ciliary beating was monitored
(method not given) during exposure,
but no recovery period was included.
Ciliary activity stopped after
~ 6 min exposure to 247.8 mg/m3.
Decreasing concentrations
caused increasing time to
ciliostasis, ~ 36 min for
31.2 mg/m3.
Dalhamn and
Rosengren (1971)
C-5
Acrolein 140
Not explicit as to which system Ciliary activity was observed during a Ciliary movement stopped in 11
was used with acrolein: in vivo
measures on exposed canine
tracheal cilia, or in vitro mea-
sures on cilia from sheep, goat,
and rat tracheal preparations.
12-min exposure to gaseous acrolein.
min 10 sec. When mixed with
2,150 mg acetaldehyde/m3 , move-
ment stopped in 5.5 min about
the same length of exposure
required for whole cigarette
smoke .
Guillerm et al.
(1961)
C-7
Acrolein 81.6
(35)
37° C,
"satu-
rated
with
water"
Alveolar macrophages from
Hartley guinea pigs.
Macrophages were deposited on mem-
brane filters, which were then
placed on a nutrient liquid. Exposed
to acrolein in air for 30 min, then
the ATP level in the cells was mea-
sured. Authors believe this method
reproduces the bronchial and
alveolar microenvironmont.
Caused a 30-70% decrease in the
level of ATP, compared to con-
trols .
Voisin
(1979)
C-9
Voisin
(1980)
C-9
et al .
et al .
(continued)
-------
TABLE II-l (concluded)
Compound and Temperature Reference
concentration and anr'
in mg/m3 (ppm) humidity Preparation exposed Description of tests and duration Results rating
Acrolein 28 See entry in this table for exposure to 81.6 mg/m3 (Voisin et al., 1979) for details Caused a 25-50% decrease in ATP Voisin et al.
of the methodology. levels, compared to controls. (1979)
C-9
Voisin et al.
(1980)
C-9
Acrolein 18.6 See entry in this table for exposure to 81.6 mg/m3 (Voisin et al., 1979) for details Caused a 20-45% decrease in ATP Voisin et al.
(8) of the methodology. levels, compared to controls. (1979)
C-9
Voisin et al.
(1980)
C-9
Acrolein 9.3 See entry for exposure to 81.6 mg/m3 (Voisin et al., 1979) for the details of the Caused a 0-21% decrease in ATP Voisin et al.
(4) methodology. levels, compared to controls. (1979)
C-9
Voisin et al.
(1980)
C-9
-------
SECTION III
EXPERIMENTAL ANIMAL INHALATION EXPOSURES
The essential parameters of numerous animal inhalation exposure ex-
periments are tabulated in this section. The primary organization of data
is by species, in order of increasing weight (mice to dogs in this case).
Within a species, studies are divided by dosing duration: acute exposure
(S 24 h), repeated exposure, and chronic exposure (> 90 d). Within a
single table, reported results are listed in order of decreasing exposure
level. The studies are discussed in the Summary.
The tables have been arranged in the aforesaid manner for the follow-
ing reasons: (a) there were about 120 separate tests tabulated; (b) 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 (c) by putting the highest concen-
trations and worst effects first, one can more readily understand the sig-
nificance of minor or less-severe changes occurring at lower levels.
However, a condensation of the data by acrolein concentration is in
Table 111-16.
In the animal exposure tables in this section, the column headed Total
Length of Experiment includes not only the total length of exposure to
acrolein but also any recovery time observed in the study. This recovery
time was included to note the endurance or reversibility of the toxic
effects.
21
-------
TABLE III-l. MICE--ACUTE EXPERIMENTAL EXPOSURE TO ACROLETN
Compound (s) and
Concentration(s) ,
mg/m3 (ppm)
Acrolein 600
Acrolein 300
Acrolein 277
(119)
Acrolein 186
(80)
Acrolein 142
(61)
Acrolein 93.2
(40)
Mode of Species/Strain/
Exposure Age/Weight
Swiss
mice,
15-25 g,
anesthe-
tized, with
tracheal
cannula
Swiss
mice,
15-25 g,
anesthe-
tized, with
tracheal
cannula
Inhalation Mice
chamber
Inhalation Mice
chamber
Inhalation Mice
chamber
Inhalation dd strain
chamber mice, 20 + 3 g
Duration and Total
No. of No. of Frequency of Length of
Test Animals Controls Exposure Experiment Effects
5 M 5 M 5 min 5 min Decreased pulmonary resistance,
respiratory minute volume, and
respiratory frequency. No change
in respiratory compliance.
5 M Appar- 5 min 5 min Decreased pulmonary compliance,
ently pulmonary resistance, tidal volume,
served as and respiratory frequency (statis-
own con- tical significance not given).
trols
44 20 6 h 6 h 100% mortality.
24 20 6 h 6 h 75% mortality
20 20 6 h 6 h 40% mortality.
? M ? M 15 min 7 d Marked respiratory difficulty,
or 1 h decreased respiration rate. ~ 20%
(text is decrease in body wt . 2 d after ex-
unclear) posure. Then gradual wt. increase
Reference
and Rating
Watanabe and
(1974)
C-9
Watanabe and
(1974)
C-9
Philippin et
(1969)
C-8
Philippin et
(1969)
C-8
Philippin et
(1969)
C-8
Iwasaki
(1979)
D--
Aviado
Aviado
al.
al.
al.
to pre-exposure level by 5 d post-
exposure .
(continued)
-------
TABLE I1I-1. (continued)
Corapound(s) and
Concentration(s) ,
mg/m3 (ppm)
Acrolein 72.2
(31)
Acrolein 26. 1
(11.2)
Mode of
Exposure
Inhalation
chamber
Inhalation
chamber
Duration and Total
Species/Strain/ No. of No. of Frequency of Length of
Age/Weight Test Animals Controls Exposure Experiment
Mice 20 20 6 h 6 h
Swiss- 4 M Served as 10 min 10 min
Webster own con-
mice, trols
specific
pathogen
free,
Effects
No deaths.
A maximum decrease in respira-
tory rate of 80.5%. A different
group of mice with repeated pre-
vious exposures to 0.40 mg/m3
before exposure to 26.1 mg/m3
had a 73.7% decrease. The re-
Referencr
and Ra t ] n
Philippin
(1969)
C-8
Kane and
(1977)
B-12
g
et al.
Alarie
20-30 g
suits of this entire series of
expts. (see entries below and in
Table II-2.) suggest that a
slight hut definite tolerance to
acrolein develops after repeated,
low (0.40 mg/m3) exposures.
Acrolein ~ 20.63
(8.97)
HCHO ~ 12.16
(9.73)
Inhalation
chamber
Swiss-
Webster
mice,
specific
pathogen
free,
20-30 g
4 M
Served as
own con-
trols
10 min,
once
10 min
Maximum decrease of respiratory
rate was 74.4%.
Kane and Alarie
(1978)
B-10
Acrolein ~ 18.31
(7.96)
HCHO -5.61
(4.49)
Inhalation
chamber
Swiss-
Webster
mice,
specific
pathogen
free,
20-30 g
4 M
Served as
own con-
trols
10 min,
once
10 min
Maximum decrease in respiratory
rate was 71.3%.
Kane and Alarie
(1978)
B-10
(continued)
-------
TABLE III-l. (continued)
Compound (s) and
Concentration(s) ,
mg/m3 (ppm)
Acrolein ~ 18. 15
(7.89)
HCHO -0.99
(0.79)
Acrolein 13.0
(5.6)
Acrolein 12.47
(5.35)
Acrolein 7.2
(3.1)
Acrolein - 4.72
(2.05)
HCHO ~ 3.13
(2.50)
Mode of Species/Strain/
Exposure Age/Weight
Inhalation Swiss-
chamber Webster,
mice,
specific
pathogen
free,
20-30 g
Inhalation Swiss-
chamber Webster
mice,
specific
pathogen
free,
20-30 g
Inhalation Swiss-
chamber Webster
mice,
specific
pathogen
free,
20-30 g
Inhalation Swiss-
chamber Webster
mice,
specific
pathogen
free,
20-30 g
Inhalation Swiss-
chamber Webster
mice,
specific
pathogen
free,
20-30 g
Duration and
No. of No. of Frequency of
Test Animals Controls Exposure
4 M Served as 10 min,
own con- once
trols
4 M Served as 10 min
own con-
trols
4 M Served as 10 min
own con-
trols
4 M Served as 10 min
own con-
trols
4 M Served as 10 min,
own con- once
trols
Total
Length of
Experiment Effects
10 min Maximum decrease in respiratory
rate was 77.9%.
10 min A maximum decrease in respiratory
rate of 76.0%. A different
group of mice with repeated pre-
vious exposures to 0.40 mg/m3
before exposure to 13 mg/m3
had 61.5% decrease.
10 min A maximum decrease in respiratory
rate of 70.1%. A different
group of mice with repeated pre-
vious exposures to 0.40 mg/m3
before exposure to 12.47 mg/m3
had a 67.3% decrease.
10 min A maximum decrease in respiratory
rate of 65.7%. A different group
of mice with repeated previous
exposures to 0.40 mg/m3 before
exposure to 7.2 mg/m3 had a
53.0% decrease.
10 min Maximum decrease in respiratory
rate was 61 .8%.
Reference
and Rating
Kane and Alarie
(1978)
B-10
Kane and Alarie
(1977)
B-12
Kane and Alarie
(1977)
B-12
Kane and Alarie
(1977)
B-12
Kane and Alarie
(1978)
B-10
-------
TABLE 1II-1 . (continued)
Compound(s) and
Concent rat iori(
mg/m3 (ppm)
Acrolein 2.3-4.7
(1-2)
30 min, prior to
acrolein exposure,
by aerosol inhala-
tion of radio-
labeled bacterial
suspensions of
Proteus mirabilis
and Staphylococcus
aureus.
ind
.s) , Mode of
1 Exposure
(.7 Inhalation
1 chamber
•d for
to
;ure ,
Species/Strain/ No. of
Age/Weight Test Animals
Swiss 18-24 M
albino
mice
(CD-I
strain) ,
18-20 g
Duration and Total
No. of Frequency of Length of
Controls Exposure Experiment
18-24 M; 4 or 24 h 24 h
also
exposed
to the
bacteria
Effects
Mild discomfort, indicated by eye
blinking and rubbing of the nose.
Decreased pulmonary bactericidal
activity from normal (percent of
initial viable S. aureus and P.
Reference
and Rating
Jakab
(1977)
C-12
mirabilis remaining in the lungs
of the test mice was greater).
The difference was not significant
at 4 h, but was at 24 h. Bacteri-
cidal activity was more inhibited
for P. mirabilis (~ 50% remaining
versus ~ 0.3% for controls) than for
S. aureus (~ 9-20% versus ~ 0.4% for
controls).
Compare with the following results
for additional exposure to viruses.
Acrolein 2.3-4.7
(1-2)
Given an aerosol
of para-influenza 1
(Sendai) virus at
2.5 x 108 infective
dose/mL, 7 d belore
acrolein exposure.
Then a 30-min ex-
posure to an
aerosol of radio-
labeled bacterial
suspensions of
Proteus mirabilis
and Staphylococcus
aureus, immediately
before acrolein
exposure. Both
test and control
animals.
Inhalation Swiss
chamber albino
mice
(CD-I
strain),
18-20 g
18-24 M 18-24 M 4 or 24 h 24 h Discomfort to the nose and eyes.
Labored breathing. By 24 h, some
mice appeared to be moribund.
The pulmonary bactericidal activity
at 24 h was decreased for the
acrolein-exposed group for S. aureus
(proliferation to 250 + 60% versus
42 + 7% remaining in the controls).
The adverse effect was even more
pronounced for P. mirabilis (pro-
liferation to 67800 + 4,000% versus
1,400 + 350% for the controls).
Compare with the results for ex-
posure without viral infection or
with a lower viral exposure
(Jakab, 1977).
Jakab
(1977)
C-12
(continued)
-------
TABLE II I-1. (continued)
Compound(s) and
Concentration(s) ,
mg/m3 (ppm)
Acrolein 2.3-4.7
(1-2)
Given an aerosol
of para-influenza
(Sendai) virus at
107 infective
Mode of
Exposure
Inhalation
chamber
1
Species/Strain/
Age/Weight
Swiss
albino
mice
(CD-I
strain) ,
18-20 g
No. of No. of
Test Animals Controls
18-24 M 18-24 M;
also
exposed
to virus
and
bacteria
Duration and Total
Frequency of Length of
Exposure Experiment Effects
4 or 24 h 24 h Discomfort to nose and eyes.
Labored breathing.
The pulmonary bactericidal activity
at 24 h was decreased in the
acrolein-exposed group for S. aureus
Reference
and Rating
Jakab
(1977)
C-12
dose/mL, 7 d before
acrolein exposure.
Then for the 30 min
prior to acrolein
exposure were ex-
posed to an aerosol
of radiolabeled
bacterial suspen-
sions of Proteus
mirabilis and
Staphylococcus
aureus.
(82 + 22% remaining versus 8+2%
for the controls). The adverse ef-
fect was even more pronounced for
P. mirabilis (proliferation to 1,500
+ 600% versus 82 + 49% remaining for
the controls).
Compare with the results for ex-
posures with no viral infection or
with a, higher viral exposure (Jakab,
1977).
Acrolein ~ 4.30
(1.87)
HCHO -1.78
(1.42)
Inhalation
chamber
Swiss-
Webster
mice,
specific
pathogen
free,
20-30 g
4 M
Served as
own con-
trols
10 min,
once
10 min
Maximum decrease in respiratory
rate was 60.7%.
Kane and Alarie
(1978)
B-10
Acrolein 4.26
(1.83)
Inhalation Swiss-
chamber Webster
mice,
specific
pathogen
free,
20-30 g
4 M
Served as 10 min 10 min A maximum decrease in respiratory
own con- rate of 51.9%. A different group
trols of mice with repeated previous
exposures to 0.40 mg/m3 before
exposure to 4.26 mg/m3 had a
30.1% decrease.
Kane and Alarie
(1977)
B-12
(continued)
-------
TABI.F. III-l. (cont miird)
Compound(s) and
Concentration(s) ,
mg/m3 (ppm)
Acrolein 4.0
(1.7)
Acrolein ~ 4.00
(1.74)
HCHO -4.30
(3.44)
Acrolein 2.70
(1.16)
Acrolein ~ 1 .68
(0.73)
HCHO - 8.96
(7.17)
Mode of Species/Strain/
Exposure Age/Weight
Inhalation Swiss-
chamber Webster
mice,
specific
pathogen
free,
20-30 g
Inhalation Swiss-
chamber Webster
mice,
specific
pathogen
free,
20-30 g
Inhalation Swiss-
chamber Webster
mice,
specific
pathogen
free ,
20-30 g
Inhalation Swiss-
chamber Webster
mice,
specific
pathogen
free,
20-30 g
Duration and Total
No. of No. of Frequency of Length of
Test Animals Controls Exposure Experiment Effects
Groups of Served as 10 min - 20 min, This concentration causing a 50%
4 M own con- with 5-min decrease in respiration rate (RD^0)>
trols pre- and was calculated from the results of
post- exposures of groups of mice to
exposure — 0.1-~ 10 ppm. Exposure of mice
periods through tracheal cannulae caused
much smaller decreases in respira-
tion rate (e.g., one level causing
a 61% decrease in uncannulated mice
and a 3.7% decrease in cannulated
mice), indicating that the site of
reactions provoking the decreases
is in the upper respiratory tract.
4 M Served as 10 min, 10 min Maximum decrease in respiratory
own con- once rate was 62.0%.
trols
4 M Served as 10 min 10 min A maximum decrease in respiratory
own con- rate of 46.6%. A different group
trols of mice with repeated previous
exposures to 0.40 mg/m3 before
exposure to 2.7 mg/m3 had a 19.9%
decrease.
4 M 10 min, 10 min Maximum decrease in respiratory
once rate was 69.6%.
Reference
and Rating
Kane and Alarie
(1977)
B-12
Kane and Alarie
(1978)
B-10
Kane and Alarie
(1977)
B-12
Kane and Alarie
(1978)
B-10
(cont i niiod)
-------
TABLE III-l. (continued)
N3
Compound(s) and
Concentration(s) ,
mg/m3 (ppm)
Acrolein - 1 .56
(0.68)
HCHO - 3.13
(2.50)
Acrolein - 1.29
(0.56)
HCHO - 1.08
(0.86)
Acrolein 1.2
(0.52)
Acrolein 1.03
(0.44)
Duration and
Mode of Species/Strain/ No. of No. of Frequency of
Exposure Age/Weight Test Animals Controls Exposure
Inhalation Swiss- 4M Served as 10 min,
chamber Webster own con- once
mice, trols
specific
pathogen
free,
20-30 g
Inhalation Swiss- 4 M Served as 10 min,
chamber Webster own con- once
mice, trols
specific
pathogen
free ,
20-30 g
Inhalation Swiss- 4 M Served as 10 min
chamber Webster own con-
mice, trols
specific
pathogen
free,
20-30 g
Inhalation Swiss- 4 M Served as 10 min
chamber Webster own con-
mice, trols
specific
pathogen
free,
20-30 g
Total
• Length of
Experiment Effects
10 min Maximum decrease in respiratory
rate was 52.8%.
10 min Maximum decrease in respiratory
rate was 41 .4%.
10 min A maximum decrease in respiratory
rate of 28.7%. A different group
of mice with repeated previous
exposures to 0.40 mg/m3 before
exposure to 1.2 mg/m3 had a
24.1% decrease.
10 min A maximum decrease in respiratory
rate of 30.1%. A different group
of mice with repeated previous
exposures to 0.40 mg/m before
exposure to 1.03 mg/m3 had a
14.8% decrease.
Reference
and Rating
Kane and Alarie
(1978)
B-10
Kane and Alarie
(1978)
B-10
Kane and Alarie
(1977)
B-12
Kane and Alarie
(1977)
B-12
(continued)
-------
TABLE III-I . (concluded)
Compound(s) and
Concentration(s) ,
mg/m3
Acrolein
HCHO - 0,
(0,
Acrolein
Acrolein
HCHO - 0.
(0.
(ppm)
-0.85
(0.37)
.41
,33)
0.68 +
0.25
~ 0.28
(0.12)
.46
37)
Duration and Total
Mode of Species/Strain/ No. of No. of Frequency of Length of
Exposure Age/Weight Test Animals Controls Exposure Experiment
Inhalation Swiss- 4 M Served as 10 min, 10 min
chamber Webster own con- once
mice, trols
specific
pathogen
free,
20-30 g
Inhalation Swiss- 32 M; Served as 10 min - 20 min,
chamber Webster 8 groups own con- with 5-min
mice, of 4 trols pre- and
specific post-
pathogen exposure
free, periods
20-30 g
Inhalation Swiss- 4 M Served as 10 min, 10 min
chamber Webster own con- once
mice, trols
specific
pathogen
free,
20-30 g
Maximum decrease in respiratory
rate was 30.1%.
Caused a 31.1 + 3.3% decrease in
respiratory rate.
Maximum decrease in respiratory
rate was 20.2%.
Kane and Alarie
(1978)
B-10
Kane and Alarie
(1977)
B-12
Kane and Alarie
(1978)
B-10
-------
TABLE 111-2. MICE--REt'F,ATF,I) DOSE EXPERIMENTAL EXPOSURE TO ACROLEIN
Compound (s) and
Concentration(s) ,
mg/m3 (pptn)
Acrolein 14-116.5
(6-50)
Acrolein 100
Acrolein 26. 1
(11.2)
Acrolein 13.0
(5.6)
Mode of Species/Strain/
Exposure Age/Weight
Inhalation Mice
chamber
Inhalation Swiss
chamber mice,
avg.
21.2 g
Inhalation Swiss-
chamber Webster
mice,
specific
pathogen
free,
20-30 g
Inhalation Swiss-
chamber Webster
mice,
specific
pathogen
free,
20-30 g
No. of
Test Animals
47
^
5 M
8 M;
exposed to
0.4 mg/m3
for 3 h/d
for the
three
previous
days
8 M;
exposed to
0.4 mg/m3
for 3 h/d
for the
three
previous
days
Duration and Total
No. of Frequency of Length of
Controls Exposure Experiment
43 6 h/d, 6 wk
5 d/wk,
2 wk; this
schedule
1st at
14 mg/m3,
then
35 mg/m3,
then
58 mg/m3;
then one
6-h
exposure
to 116.5
8 « 30 min, 5 wk
twice daily;
5 wk
Served as 10 min 4 d
own con-
trols?
Served as 10 min 4 d
own con-
trols?
Effects
46.6% mortality after the final
exposure (6 h at 116.5 mg/m3).
In the physical performance test
(swimming), apparently a signifi-
cant change only after exposure
to 58 mg/m3 (document is unclear).
Exposed mice maintained a constant
weight, below that of the controls,
which regularly gained weight. 15
exposed (and 10 control) mice were
sacrificed 24 h after the last
exposure and the lungs examined:
atelectasis, cellular inflammation,
edematous inflammation, and
thickening of the septa.
Significantly decreased pulmonary
compliance. Significantly in-
creased serum antitrypsin activity
and lung total phospholipids .
A maximum decrease in respiration
rate of 73.7%. A group of fresh
mice exposed to this level for
10 min had a 80.5% decrease. The
results of this entire series of
expts. (see entries below and in
Table II-l) suggests that a slight
but definite tolerance to acrolein
develops after repeated, low
(0.40 mg/m3) exposures.
A maximum decrease in respiration
rate of 61.5%. A group of fresh
mice exposed to this level for
10 min had a 76% decrease.
Reference
and Rating
Philippin et al.
(1969)
C-8
Watanabe and Aviado
(1974)
C-9
Kane and Alarie
(1977)
B-12
Kane and Alarie
(1977)
I!- 12
(outi nuod )
-------
TABLE IT 1-2. (continued)
Compound (s) and
Concent ration(s) ,
mg/m3 (ppra)
Acrolein 12.47
(5.35)
Acrolein 7.2
(3.1)
Acrolein 4.26
(1.83)
Mode of Species/Strain/
Exposure Age/Weight
Inhalation Swiss-
chamber Webster
mice,
specific
pathogen
free,
20-30 g
Inhalation Swiss-
chamber Webster
mice,
specific
pathogen
free,
20-30 g
Inhalation Swiss-
chamber Webster
mice,
specific
pathogen
free,
20-30 g
Duration and Total
Wo. of No. of Frequency of Length of
Test Animals Controls Exposure Experiment
8 M; Served as 10 min 4d
exposed to own con-
0.4 mg/m3 trols?
for 3 h/d
for the
three
previous
days
8 M; Served as 10 min 4 d
exposed to own con-
0.4 mg/m3 trols?
for 3 h/d
for the
three
previous
days
8 M; Served as 10 min 4 d
exposed to own con-
0.4 mg/m3 trols?
for 3 h/d
for the
three
previous
days
Effects
A maximum decrease in respiration
rate of 67.3%. A group of fresh
mice exposed to this level for
10 mm had a 70. I"/, decrease.
A maximum decrease in respiration
rate of 53.0%. A group of fresh
mice exposed to this level for
10 min had a 65.7% decrease.
A maximum decrease in respiration
rate of 30.1%. A group of fresh
mice exposed to this level for
10 mm had a 51.9% decrease.
HP f erence
and Rat i nj>
Kane and Alarie
(1977)
B-12
Kane and Alarie
(1977)
B-12
Kane and Alarie
(1977)
B-12
(cont inued)
-------
TABLE I1I-2. (continued)
U>
NO
Compound(s) and
Concentration(s) ,
mg/m3 (ppra)
Acrolein 4.0
(1.7)
Acrolein 2.70
(1-16)
Acrolein 1.2
(0.52)
Mode of Species/Strain/
Exposure Age/Weight
Inhalation Swiss-
chamber Webster
mice,
specific
pathogen
free,
20-30 g
Inhalation Swiss-
chamber Webster
mice,
specific
pathogen
free,
20-30 g
Inhalation Swiss-
chamber Webster
mice,
specific
pathogen
free,
20-30 g
No. of
Test Animals
4 M
8 M;
exposed to
0.4 mg/m3
for 3 h/d
for the
three
previous
days
8 M;
exposed to
0.4 mg/m3
for 3 h/d
for the
three
previous
days
Duration and Total
No. of Frequency of Length of
Controls Exposure Experiment
Probably 3 h/d, 4 d
served as 4 d
own con-
trols (1st
day pre-
exposure
values) for
decrease in
respiration
values; a
comparison
group of 4
fresh mice
exposed
each day
for 10 min
Served as 10 min 4 d
own con-
trols?
Served as 10 min 4 d
own con-
trols?
Effects
One day 1, the maximum decrease in
respiration rate (~ 40%) was
reached in 5-6 min, and remained
at that level for the entire ex-
posure (the shape of a typical
response curve for 10-min expo-
sures to acrolein is this plateau).
On day 2 the maximum response was
~ 50% decrease, maintained through-
out the exposure. On days 3 and
4 the % decrease in respiration
rate increased continuously through-
out the exposure, to a maximum of
~ 70% at the end. This increase
in the maximum response and change
in the shape of the curve on days
3 and 4 indicates possible sensi-
tization.
A maximum decrease in respiration
rate of 19.9%. A group of fresh
mice exposed to this level for
10 min had a 46.6% decrease.
A maximum decrease in respiration
rate of 24.1%. A group of fresh
mice exposed to this level for
10 min had a 28.7% decrease.
Reference
and Rating
Kane and Alarie
(1977)
B-12
Kane and Alarie
(1977)
B-12
Kane and Alarie
(1977)
B-12
(continued)
-------
TABU- I1I-2. ((oncliidrd)
Compound (s) and
Concent ra I ion(s) ,
mg/ra3 (ppm)
Acrolein 1 . 2
(0.5)
Acrolein 1.03
(0.44)
Mode of Species/Strain/
Exposure Age/Weight
Inhalation Swiss-
chamber Webster
mice,
specific
pathogen
free,
20-30 g
Inhalation Swiss-
chamber Webster
mice ,
specific
pathogen
free,
20-30 g
Duration and
No. of No. of Frequency of
Test Animals Controls Exposure
4 M Probably 3 h/d,
served as 4 d
own con-
trols (1st
day pre-
exposure
values) for
decrease
in respir-
ation values;
a compari-
son group
of 4 fresh
mice was
exposed
each day
for 10 min
8 H; Served as 10 min
exposed to own con-
0.4 mg/m3 trols?
for 3 h/d
for the
three
previous
days
Total
Length of
Experiment
4 d
4 d
Effects
On day 1 and 2, the magnitude of
the response (decrease in respira-
tion rate) remained constant at
~ 30% during the 3-h exposure.
(The shape of a typical response
curve to a single one-time ex-
posure is this plateau.) On day
3, the reponse continuously in-
creased to ~ 55% at 8 min, leveled
off for ~ 1 h, then continuously
decreased to ~ 40% by the end of
the exposure. On day 4, the re-
sponse rose to a maximum of ~ 60%
by ~ 10 min, and remained constant
throughout the exposure. This in-
crease in the maximum response and
change in the shape of the curve on
days 3 and 4 indicate possible
sensitization.
A maximum decrease in respiration
rate of 14.8%. A group of fresh
mice exposed to this level for
10 min had a 30.1% decrease.
Reference
arid Rating
Kane and Alarie
(1977)
B-12
Kane and Alarie
(1977)
B-12
-------
TABLE III-3. HAMSTERS--ACUTE EXPERIMENTAL EXPOSURE TO ACROLEIN
Compound(s) and
Concentration(s) ,
mg/m3 (ppm)
Acrolein 14
(6)
Acrolein < 14
(< 6)
coated on carbon
particles-
593 mg/m3
Mode of Species/Strain/
Exposure Age/Weight
Inhalation Syrian
chamber golden
hamsters ,
100 + 10 g
Inhalation Syrian
chamber golden
hamsters ,
100 + 10 g
Duration and Total
No. of No. of Frequency of Length of
Test Animals Controls Exposure Experiment
8 (M + F) None 4 h 96 h;
1-2
animals
sacrificed
at 6 h,
12 h, 1 d,
2 d, and
4 d from
the begin-
ning of
exposure
10 (M + F) None 4 h 8 d;
1-2
animals
sacrificed
at 6 h,
12 h, 1 d,
2 d, 4 d
and 8 d
from the
beginning
of the
exposure
Effects
No recruitment of polymorpho-
nuclear leukocytes to the epithe-
lium of tracheas and intrapul-
monary airways. Was cytotoxic:
50% of the ciliated cells exfol-
iated in the bronchi and cells of
all airway surfaces were pale and
swollen. Changes increased by
24 and 48 h (bleeding, cytoplasm] c
vacuoles, nuclear pallor, nuclear
vacuoles, indented basal lamina),
in both the trachea and bronchi.
By 96 h there were areas of ir-
regular epithelium with early
stratification and hyperplasia,
few ciliated cells, and reduced
no. of cilia per cell.
Caused leukocyte recruitment to
the epithelium of tracheas and
intrapulmonary airways, peaking
at 12-24 h (carbon particles or
acrolein alone caused no recruit-
ment) . No leukocytes were seen
by day 8. Macrophages and un-
ciliated epithelial cells in air-
way surfaces contained carbon
particles .
Reference
and Rating
Kilburn and
McKenzie (1978)
B-ll
Kilburn and
McKenzie (1978)
B-ll
-------
TABLE II1-4. HAMSTERS--CHRONIC EXPERIMENTAL EXPOSURE TO ACROLE1N
Compound(s) and
Concenlration(s),
mg/m3 (ppm)
Humidity/
Temperature
Mode of
Exposure
Species/Strain/
Age/Weight
No. of
Test Animals
No. of
Controls
Duration and
Frequency of
Exposure
Total
Length of
Experiment
Effects
Reference
and Rating
Acrolein 11.4
(4-9)
23-24°C,
50-70%
Exposure
chamber
Acrolein 9.2
Cages
suspended
in
inhalation
chambers
Syrian
golden
hamsters,
10 wk,
88-124 g
20
20
Syrian
golden
hamsters
(Mesocri-
cetus
auratus)
6 wk
6 h/d,
5 d/wk,
13 wk
13 wk
18 M +
18 F
exposed to
acrolein
only; 18 M
18 F
exposed to
acrolein
and weekly
intra-
tracheal
instilla-
tion of
0.9% Nad
18 M + 7 h/d,
18 F 5 d/wk,
exposed 52 wk
to air
only;
18 M *
18 F
exposed
to air
and
weekly
intra-
tracheal
instilla-
tion of
0.9% NaCl
81 wk;
3 M +
3 F of
each
group
were
sacrificed
at wk 52
Closed eyes, salivation, and nasal leron et al.
discharge. 1 M died, of causes (1978)
thought not to be treatment- B-13
related. Decreased food intake
and body weight gain. Females
showed significantly increased
hematological values. Increased
urinary sediments and decreased
urinary crystals occurred. In-
creased organ-to-body weight
ratios for lungs, heart, and
kidneys. No effect on blood
chemistry and histopathology of
the lungs and bronchi. Histo-
pathological changes were found
in the epithelial lining of the
nasal cavity, and the larynx of
a few females. Focal hyper- and
metaplasia of the tracheal
epithelium in a few males and
most females.
There were no differences between Feron and
the 2 exposure groups, so results Kruysse
were combined. Restless during (1977)
wk 1. Closed eyes, salivation, B-13
and nasal discharge occurred for
1-2 wk, then disappeared.
Slight decrease in body wt., the
difference decreasing after ex-
posure stopped. At wk 52, 8 con-
trols and 2 test animals had died.
By wk 80 a total of 23 controls and
20 test animals had died.
Hematological and blood bio-
chemical parameters unaffected.
Inflammation and epithelial
metaplasia of slight to moderate
degree in the nasal cavity. 20%
of the animals killed at wk 81
still showed treatment-related
nasal cavity lesions. Changes in
other parts of the respiratory
tract. No respiratory tract tumors
were found.
(continued)
-------
TABLE III-4. (concluded)
Compound(s) and
Concentration(s),
mg/m3 (ppm)
Humidity/
Temperature
Mode of
Exposure
Species/Strain/
Age/Weight
No. of
Test Animals
No. of
Controls
Duration and
Frequency of
Exposure
Total
Length of
Experiment
Effects
Reference
and Rating
Acrolein 3.3
(1.4)
23-24°C,
50-70%
Exposure
chamber
Syrian
golden
hamsters,
10 wk,
88-124 g
Acrolein 0.93
(0.4)
23-24°C,
50-70%
Exposure
chamber
Syrian
golden
hamsters,
10 wk,
88-124 g
20
20
A statistically insignificant in-
crease in respiratory tract tumors
was found in animals also exposed
to low benzo(a)pyrene (18.2 mg
total) compared to those exposed
only to BP. In females, co-expo-
sure to 36.4 mg BP caused increased
tumors. Co-exposure to subcutane-
ously applied diethylnitrosamine
caused no change in the incidence
of respiratory tract tumors.
20 6 h/d, 13 wk Sleeping and restlessness during
5 d/wk, exposure. No effect on growth,
13 wk food intake, hematological values,
blood chemistry, urinalysis,
organ-to-body weight ratios,
gross autopsy, and histopathology
of the larynx, trachea, bronchi,
and lungs. Minimal inflammatory
changes were found in the nasal
cavity.
20 6 h/d 13 wk No abnormal behavior. No changes
5 d/wk, in growth, food consumption,
13 wk hematological values, blood
chemistry, urinalysis, organ-to-
body weight ratios, gross autopsy,
or histopathology of the respira-
tory tract.
Feron et al.
(1978)
B-13
Feron et al.
(1978)
B-13
-------
TABLE IIJ-5. RATS--ACUTE EXPERIMENTAL EXPOSURE TO ACROLEIN
Compound (s) and
Concentration(s) ,
mg/m3 (ppm)
Acrolein 100-
5,000
Acrolein 700
Mode of Species/Strain/ No. of
Exposure Age/Weight Test Animals
Cylinder Wistar 56 M,
placed rats, for a
over 250-450 g total of
mouth of 111
and exposures
nasal
openings
Inhalation White rats, 8
chamber 110-150 g
Duration and
No. of Frequency of
Controls Exposure
Served as 1 min
own con- at each
trols of the
levels
tested
30 min
Total
Length of
Experiment Effects
Significant changes in blood pres-
sure (BP) and heart rate (HR)
which began 15 s after exposure
started, peaked at 30 s, and per-
sisted until the end of exposure.
Generally increased BP, but some
decreases. Generally increased
HR at the lower levels and de-
creased HR at higher levels. Over-
all, a pressor effect of increasing
magnitude with increasing acrolein
concentration. Rapid return to
control levels in 10 s after expo-
sure stopped. Pronounced cardio-
inhibitory effect was seen in the
majority of animals at 2,500 and
5,000 mg/m3.
4 d LD10o> deaths occurring up until the
4th day. Marked respiratory prob-
Reference
and Rating
Egle and Hudgins
(1974)
C-6
Skog (1950)
B-10
lems, animals gaping and jerking
heads backward with each breath.
Lacrimation, heavy secretion from
the nose, and some rats had large
frothy brown-colored bubbles in
front of the nose. By the end,
breathed with a snuffling sound and
appeared listless. On autopsy:
lung edema, hyperemia, and hemor-
rhages, degenerative changes in the
bronchial epithelium, hyperemia of
the heart, liver, and kidneys, and
no changes in other organs.
Acrolein 300
Inhalation
chamber
White rats,
110-150 g
30 min 3 wk LD50, deaths occurring until the Skog (1950)
4th day. B-10
(continued)
-------
TABLE I 11-5. (continued.)
Compound (s) and
Concentration(s) ,
mg/m3 (ppm)
Acrolein 105-221
(45-95)
Mode of
Exposure
Inhalation
chamber
Species/Strain/ No. of
Age/Weight Test Animals
Sprague- 7 M
Dawley
rats
Duration and
No, of Frequency of
Controls Exposure
30 min
Total
Length of
Experiment
14 d
Effects
The LCso was in this range, no
animals dying in 72 h after ex-
posure to the low level and all
Reference
and Rating
Potts et al
(1978)
C-ll
the animals dying in the 72 h
after exposure to the high level.
Those surviving had no visible
lesions when sacrificed 14 d
post-exposure.
Acrolein 100
00
Inhalation
chamber
White rats
110-150 g
30 min 3 wk No mortality. Marked respiratory
difficulty: gaping and jerking
heads backward with each breath.
Abundant lacrimation and heavy
nasal secretion. By the end of
the exposure, breathed with a
snuffling sound and appeared list-
less. Majority recovered only
after 4-5 d. On autopsy: lung
edema, hyperemia, and hemorrhages,
degenerative changes in the
bronchial epithelium, hyperemia
of the heart, liver, and kidneys,
and no changes in other organs.
Skog (1950)
B-10
Acrolein 50
Cylinder
placed
over
mouth
and
nasal
openings
Wistar
rats ,
250-450 g
9 M,
for a
total
of 17
exposures
Served as
own con-
trols
1 min
2 min Insignificant changes in blood
pressure: 14/17 had a 20.4%
increase, 3/17 had a 10.3%
decrease. Significant changes
in heart rate: 15/17 had a
7.5% increase, 2/17 had a 4.0%
decrease.
Egle and Hudgins
(1974)
C-6
(continued)
-------
TABLE III-5. (continued)
Compound (s ) and
Concent ration(s)
mg/m1 (ppm)
Aero] ein 46 . 6
(20)
Acrolein 46.6
(20)
CO
(3,700)
Acrolein 46.6
(20)
CO (3,700)
C02 (50,000)
Acrolein 28
(12)
Duration and Total
, Mode of Species/Strain/ No. of No. of Frequency of Length of
Exposure Age/Weight Test Animals Controls Exposure Experiment Effects
Long-Evans 4 4 15 min Caused a 40-50% decrease in respi-
rats ration rate within 3 mm; contin-
uing throughout the exposure
Long-Evans 4 4 -20 min Compared to CO alone: a 40-50%
rats decrease in respiration rate,
extended the time to reach 60%
carboxvhemoglobin in the blood
by almost 40%, and increased the
time to loss of avoidance response
( incapaci tat i on) by about 60%.
Long-Evans 4 4 ~ 20 min Compared to CO alone or CO plus
rats acrolein: increased respiration
rate, decreased time to reach
60% carboxyhemoglobin in the
blood, and decreased time to
loss of avoidance response
(incapacitation) .
Inhalation Sprague- 20 M Controls 4 h 52 h; During and following exposure:
chamber Dawley used, but 5 animals severe symptoms of eye and res-
rats, no. not sacrificed piratory tract irritation, gasping
"adult," given at 0, 5, and other signs of dyspnea,
200-300 g 24, and anorexia, and generalized weakness.
48 h Max. effects on enzyme activities
Same age and weight after were seen at 24 h, when the avg.
exposure alkaline phosphatase activities
were 36% and 72% of control values
for serum and lung, respectively
Reference
and Rating
Hartzel 1 el
(1976)
C-7
Hartzell et
(1977)
C-8
Hartzell et
(1976)
C-8
Hartzell et
(1977)
C-8
Hartzell et
(1976)
C-7
Hartzell et
(1977)
C-8
Murphy et a
(1964)
C-8
at.
al .
al.
al.
al.
al.
1.
(continued)
-------
TABLE III-5. (continued)
Compound(s) and
Concentration(s) ,
mg/m3 (ppm)
Acrolein
Acrolein
25
18.6
(8)
Mode of
Exposure
Cylinder
placed
over
mouth
and
nasal
openings
Inhalation
chamber
Species /Strain/
Age/Weight
Wistar
rats ,
250-450 g
Holtzman
rats,
200-300 g
No. of
Test Animals
8 M,
for a
total
of 25
exposures
14 M; 6
were
adrenal-
ectomized
Duration and Total
No. of Frequency of Length of
Controls Exposure Experiment
Served as 1 min 2 min
own con-
trols
8 M; 4 4 h 6 h
were
adrenal-
ectomized
o
Effects
Insignificant changes: 20/25 had
a 7.2% decrease in blood pressure,
15/25 had a 15.4% decrease in
blood pressure, 25/25 had a 0.4%
increase in heart rate.
Increased liver enzyme (alkaline
phosphatase and tyrosine trans-
aminase) activity and slightly
increased lung-to-body weight and
liver-to-body weight ratios in
intact animals. Adrenalectomized
animals showed small increased in
enzyme activities, increased lung-
to-body weight ratio, and no change
in liver-to-body weight ratio.
Reference
and Rating
Egle and Hudgins
(1974)
C-6
Murphy (1965)
D-9
Acrolein 14.9
(6.4)
Inhalation
chamber
Spxague-
Dawley
rats,
"adult,"
200-300
20 M 20? M
Same age and weight;
fasted 24 h before
sacrifice
4 h
96 h; Liver alkaline phosphatase (AP)
5 animals activity was significantly above
sacrificed control levels through 48 h post-
at 4, 24, exposure (a max. of ~ 325% at 24 h).
48, and Liver acetylcholine esterase ac-
96 h after tivity was below controls for 48 h,
exposure significantly so only at 4 h (~ 80%).
Liver/body weight ratio was signifi-
cantly above that of controls at
24 h (~ 110%) and 48 h (~ 130%).
Liver glutamic-oxaloacetic trans-
aminase activity was increased,
but not significantly. Mean
adrenal weight was above controls
(102-132%) for all post-exposure
times, max. at 24 h. Avg. serum
AP activity did not differ from
controls. Lung AP activity was
significantly decreased (36% lower)
only at 4 h, probably due to dilu-
tion with edema fluid, because
fresh lung/body weight ratio was
i1)0/, greater tli.in contpols.
Murphy et al.
(1964)
C-8
(cont i nued)
-------
TABLE 111-5. (loud
Compound(s) and
Concentration(s), Mode of Species/Strain/
rag/m3 (ppm) Exposure Age/Weight
No. of
Test Animals
No.
of
Controls
Duration and
Frequency of
Exposure
Total
Length of
Experiment
Effects
Reference
and Rating
Acrolein 10.3
(4.A)
Inhalation Sprague-
chamber Dawley
rats,
"adult,"
200-300
15 M
5 H
2-8 h
24 h
Groups of r> animals
removed after 2-, 4-,
or 8-h exposure; all
sacrificed at 24 h
Lung and kidney alkaline phos-
phatase (AP) activity did not
differ significantly from con-
trols for any of the exposure
groups. Those exposed for 2 h
had liver AP activities 35%
below controls but increasing
exposure to 8 h increased liver
AP to over twice control levels.
Murphy et al.
(1964)
C-8
Acrolein 10
Acrolein 9.6
(4.1)
Cylinder
placed
over
mouth
and
nasal
openings
Inhalation
chamber
Wistar
rats ,
250-4.SO g
Sprague-
Dawley
rats ,
"adult,"
200-300 g
8 M; Served as
for a own con-
total trols
of 28
exposures
6 M 6 H
1 min
2 min
20 h
20 h
Insignificant changes: 25/28 had
an 8.57o increase in blood pressure,
3/28 had a 6.6% decrease in blood
pressure, 28/28 had a 0.1% in-
crease in heart rate.
Liver/body weight ratio, weight
of adrenals, and liver alkaline
phosphatase (AP) activity all
above control values. Lung and
serum AP activity did not differ
from controls. Lung/body weight
ratio 14% greater than controls.
Egle and Hudgins
(1974)
C-6
Murphy et al .
(1964)
C-8
-------
TABU; in-6. RATS--REPEATED DOSE EXPERIMENTAL EXPOSURE TO ACROLEIN
Compound(s) and
Concentration(s),
mg/m3 (ppm)
Humidity/
Temperature
Mode of
Exposure
Durnt ion and Total
Species/Strain/ No. of No. of Frequency of Length of
Age/Weight Test Animals Controls Exposure Experiment
Effects
Ret e rence
and Rating
Acrolein 11.4
(4.9)
23-24°C,
50-70%
Exposure
chamber
-P-
KJ
Wistar rats,
specifie
pathogen
free, 7 wk,
98-124 g
12
12 6 Ii/d, 13 wk Closed eyes and bristling hair
5 d/wk, during exposure. 3 M and 3 F
13 wk died in the first 4 wk. De-
creased food intake and body
wt. gain. No effect on hema-
tological values and blood
chemistry. Increased urinary
sediments and decreased urinary
crystals. Increased relative
wt. of lungs, heart, kidneys,
and adrenals. Autopsy revealed
hemorrhages and collapsed areas
of the lungs, and chronic pleu-
ritis in 1 M. Histopathological
changes were found in the epithe-
lial linings of the nasal cavity
and larynx. Severe damage of the
trachea, lungs, and bronchi were
reported.
Feron et a I .
(1978)
B-13
Acrolein 9.3
(4.0)
Inhala-
tion
chamber
Sprague-
Dawley
rats,
"adult,"
200-300 g
6 M
6 M 4 h/d, 5 d Significantly lower liver/body
5 d wt. ratio (body wt. decreased
7% compared to a 3% increase
in the controls). Lung, liver,
and serum alkaline phosphatase
activity, and lung and adrenal
wt. did not differ from controls.
Murphy et a 1.
(1964)
C-8
Acrolein 9.1
(3.9)
Inhala-
tion
chamber
Sprague-
Dawley
rats,
"adult,"
200-300 g
6 M
6 M 4 h/d, 9 d Significantly lower liver/body
9 d wt. radio (body wt. decreased
8% compared to a 37» increase
in the controls). Lung, liver,
and serum alkaline phosphatase
activity and lung and adrenal
wt . did not differ from control-
Mu rphy e t
(1964)
C-8
a I .
(continued)
-------
TABLE III-6. (continued)
Compound(s) and
Concentration(s), Humidity/ Mode of
mg/m1 (ppm) Temperature Exposure
Species/Strain/
Age/Weight
No. of
Test Animals
No. of
Controls
Duration and
Frequency of
Exposure
Total
Length of
Experiment
Effects
Reference
and Rating
Acrolein 77 + 1°F, Inhala- Sprague-
8.6+1.9 ~50% tion Dawley
(3.7 + 0.8) chamber rats
7 M
8 F
M 8 h/d, 6 wk No effect on behavior, hema-
F 5 d/wk, tological values, and various
6 wk liver and serum enzyme activ-
ities. Rate of body wt. gain
was significantly less than that
of the controls for both males
and females. Nonspecific inflam-
matory changes in the lungs,
liver, and kidneys. Focal
calcification of renal tubular
epithelium.
Lyon et al.
(1970)
B-12
OJ
Acrolein 4.9
(2.1)
Inhala-
tion
chamber
Sprague-
Dawley
rats,
"adult,"
200-300 g
12 M
12 M
41 h
41 h Liver/body weight ratio, adrenal
weight, and liver alkaline phos-
phatase (AP) activity were all
significantly above controls.
Lung and serum AP activity and
lung weight did not differ from
controls.
Murphy et al.
(1964)
C-8
Acrolein 4.2
(1.8)
77 + 1°F,
~ 50%
Inhala-
tion
chamber
Sprague-
Dawley
rats
7 M
8 F
7 M
8 F
90 d
90 d No effect on behavior or hema-
tological values. Rate of wt.
gain was significantly lower than
that of the controls with equiv-
alent starting wts. Nonspecific
inflammatory changes in brain,
heart, lung, liver, and kidney.
Lyon et al.
(1970)
B-12
(continued)
-------
TABLE III-6. (continued)
Compound(s) and
Concentration(s) , Humidity/ Mode of
mg/m3 (ppm) Temperature Exposure
Acrolein 3.3 23-24°C, Exposure
(1.4) 50-70% chamber
Species /Strain/
Age/Weight
Wistar rats,
specific
pathogen
free, 7 wk,
98-124 g
Duration and Total
No. of No. of Frequency of Length of
Test Animals Controls Exposure Experiment
12 12 6 h/d, 13 wk
5 d/wk,
13 wk
Effects
At each exposure there was ini-
tial hyperactivity followed by
restless sleep. Decreased food
intake and body weight gain. No
effect on hematological values,
blood chemistry, urinalysis,
organ-to-body wt. ratios,
gross autopsy, or histopahology
of the larynx, trachea, bronchi,
and lungs. Squamous metaplasia
and neutrophilic infiltration of
the mucosa were found in the nasal
cavity.
Reference
and Rating
Feron et al.
(1978)
B-13
Acrolein 2.3
(1.0)
77 + 1°F,
~ 50%
Inhala-
tion
chamber
Sprague-
Dawley
rats
7 M
8 F
7 M 90 d
8 F
90 d No effect on behavior or hema-
tological values. Some showed
focal liver necrosis (minute
foci without any specific pat-
tern) and occasional pulmonary
hemorrhage. Rate of wt. gain
was significantly lower than that
of controls with equivalent start-
ing wts.
Lyon et al.
(1970)
B-12
Acrolein 2.3
(1.0)
Inhala-
tion
chamber
Sprague-
Dawley
rats,
"adult,"
200-300 g
12 M
12 M 81 h
81 h Liver/body wt. ratio, adrenal Murphy et al.
wt., lung wt., and liver, lung, <1964)
and serum alkaline phosphatase C-8
activity did not differ from
control values.
(continued)
-------
TABLE fII-6. ((-ontinni-tf)
Compound(s) and
Conrentralion(s),
mg/m' (ppnt)
Humidity/ Mode of
Temperature Exposure
Duration and Total
Species/Strain/ No. of No. of Frequency of Length of
Age/Weight Test Animals Controls Exposure Experiment
Ac: rol ein
1.6 + 0.2
(0.7 + 0.1)
77 + 1°F
~ 50%
Inhala-
tion
chamber
Sprague-
Dawley
rats
7 H
8 F
7 M
8 F
8 h/d,
5 d/wk,
6 wk
6 wk 1
1
1
Efforts
No effect on behavior, body wt.
gain, hematological values, and
various serum and liver enzyme
activities. Lungs showed mild
chronic inflammatory changes
and occasional emphysema. No
definite alteration of the
respiratory epithelium or
peribronchial smooth muscula-
ture.
Reference
and Rating
Lyon et al.
(1970)
B-12
•P-
t_n
(continued)
-------
TABLE III-6. (continued)
Compound(s) and
Concentration(s), Humidity/ Mode of
mg/ra3 (ppm) Temperature Exposure
Species/Strain/
Age/Weight
Duration and Total
No. of No. of Frequency of Length of
Test Animals Controls Exposure Experiment
Effects
Reference
and Rating
Acrolein
1.52 + 0.05
Inhala-
tion
chamber
White
rats
10 M
10 M
24 d
101 d By 10 d of exposure all were
(with a sluggish and apathetic, their
21-d pre- coats lost luster, and they had
and a poor appetites. There was
56-d progressive deterioration in
post- their general condition. 7/10
exposure died. Wt. loss up to 14% by
period) 24 d. Changes in the magnitude
of conditioned motor response
(decreased response to a bell)
and the latent period of the
response (increase in response
to light) began at 10 d, and
continued throughout exposure.
An insignificant increase in
urine coproporphyrin levels
during exposure, a significant
decrease by 5 wk post-exposure,
and back to control levels by
8-wk recovery. Blood cholines-
terase activity significantly
decreased by wk 2, and returned
to normal only 20 d post-exposure.
Statistically significant increase
in fluorescent leucocyte count
after 1 wk, continuing throughout
exposure, and began to decrease
towards normal at 11 d post-
exposure. On autopsy, the lungs
showed drastic changes of an in-
flammatory nature. Myocardium
and liver showed marked changes
(granular and fatty dystrophy,
and necrosi s).
Gusev et al.
(1966)
B-9
(continued)
-------
TABLE I I 1-6. (i on I i lined)
Compound (s) and
Concenlration(s) , Humidity/ Mode of
mg/m3 (ppm) Temperature Exposure
Acrolein 21° C, Inliala-
1-24 - 1.31 58% tion
(0.53-0.56) chamber
Dur.il i on and 'lotd 1
Species/Strain/ No. of No. of Frequency of Length of
Age/Wei ghl Test Animals Controls Exposure Experiment F.ffects
OFA rats, 163 M 163 N 15, !2, 77 d The ratio of the weight of
specific Same age and avg. or 77 d the lungs to the body weight
pathogen weight was significantly above that
free of the controls only on day
77. The ratio of the weight
of the liver to body wt . was
significantly below that of
the controls on day 15, but
there was no difference on
days 32 or 77. There were
no differences in levels of
serum alkaline phosphatase or
liver alcohol dehydrogenase
and oxidation reduction enzymes
on any days. Serum acid phos-
phatase level was below that of
the controls only on day 15
Reference
-irid Ka t i ng
Mou ley et .1 1
(1975)
B-10
Bouley et al
(1976)
B-10
Acrolein
1.24-1.31
(0.53-0.56)
21°C,
58%
Inhala-
tion
chamber
OFA rats,
specific
pathogen
free
20 M
20 M
Same age and avg.
weight
21 d
60 d Sneezing occurred between days Bouley et al.
7 and 21. Body weight was sig- (1975)
nificantly less than control R-10
value during exposure and after.
The difference began decreas- Bouley et al.
ing after the exposure stopped (1976)
and ceased to be significant B-10
by day 60. Food consumption
was significantly less than
that of the controls during ex-
posure, and above that of the
controls after the exposure
stopped.
Acrolein
1.24-1.31
(0.53-0.56)
21°C,
Inhala-
tion
chamber
OFA rats,
speci fic
pathogen
free
25 M 25 M
Same age and avg.
weight
60 d
60 d Sneezing during days 7-21,
then it stopped. Body weight
was significantly below thai
of the controls jfter (lav 7.
Bouley et a 1 .
(1975)
B-10
Bou1ey e t a 1.
(1976)
B-10
-------
TABI.F, II 1-6. (continued)
Compound (s) and
Concentration(s) , Humidity/ Mode of
mg/m3 (ppm) Temperature Exposure
Acrolein 21°C, Inhala-
1.24-1.31 58% tion
(0.53-0.56) chamber
Acrolein 21°C, Inhala-
1.24-1.31 58% tion
(0.53-0.56) chamber
Followed by
00 exposure to
an aerosol of
S. enteritidis
1 x 10b/rat
The thermal Inhala-
decomposi tion tion
products of low chamber
density poly-
ethylene:
Acrolein
1.11 + 0 . 30
(avg. 0.48 + 0. 12)
HCHO 1.70 + 0.25
(avg. 1.36 + 0.20)
Total aldehydes
(17.7 + 0.6)
CO (s 20)
Part it-ill ates
8.0 + 0.6
Duration .Hid Total
Species/Strain/ No. of No. of Frequency of Length of
Age/Weight Test Animals Controls Exposure Experiment Effects
OFA rats, 3 M, 3 M, 26 d 26 d No differences in number of
specific 21 F 21 F pregnant rats, or number and
pathogen Same age and avg. avg. weight of fetuses.
free weight
OFA rats, 32 M 31 M 18 or 63+ d When the bacteria] dose was
specific Same age and avg. 63 d given after 18 d of acrolein
pathogen weight. Both re- exposure, there was a signifi-
free ceived bacterial cant increase in mortality
dose (15/16) compared to controls
(8/15). When given after
63 d of gas exposure, there
was no difference (10/16).
Wistar rats, 15 M 9 M 6 h/night, 5 wk; Animals conspicuously inactive
240 + 22 g 5 night/wk, 5 animals during exposure periods, and
2-5 wk sacri- were not easily alerted. In-
ficed at creased preening during non-
2, 3, and exposure periods. Brain
5 wk glutathione levels and lyso-
somal acid proteinase activity
were unaffected. Brain RNA
levels were above controls at
wk 2 and 5. Microsomal super-
oxide dismutase was above control
levels at wk 5. Glycosylat ion of
cerebral protein molecules in
vitro was more rapid at wk 2,
then decreasing to near control
levels. Cytosolic NADPH (reduced
n ico t i nami de-adeni ne di nuc 1 eot i do
phosphate) di.iphorase activity in
the brain was below control levels
at wks 2, '), ami 5.
Re f e rence
and Rating
Bouley et a 1
(1975)
B-10
Bouley et al
(1976)
B-10
Bouley et al
(1975)
B-10
Bouley et al
(1976)
B-10
Zitting and
Savolainen
(1979)
C-10
-------
TABLE 111-6. (tout imiod)
Compound(s) and
Concentration(s) , Humidity/ Mode of
mg/m3 (ppm) Temperature Exposure
Acrolein
0.74 + 0.13
Species/Strain/ No. of
Age/Weight Test Animals
Albino rats 10
healthy
M, 10 M
with ex-
periment-
ally
induced
silicosis
No. of
Controls
10
healthy
M, 10 M
with ex-
periment-
ally
induced
silicosis
Duration and Total
Frequency of Length of
Exposure Experiment
61 d, 61+ d
with
starva-
tion dur-
ing the
last 10 d
Effects
General state and weight was
significantly affected by the
5th wk for the "sick" animals
and by the 6th wk for the
"healthy" animals. Changes
in the chronaxy of the antag-
onistic muscles in both groups.
Change in blood cholinesterase
activity before starvation in
the "sick" rats, but became sig-
nificant only after starvation
in the "healthy" rats. Recovery
was slower in the "sick" animals.
Increase in 17-ketosteroids in
the urine in both groups, greater
in "sick" rats. Vitamin C levels
in the adrenals decreased some-
what in "healthy" animals, and
was statistically significant in
the "sick" ones.
Reference
and Rating
Sinkuvene
(1970)
B-8
Acrolein 0.51
(0.22)
77 + 1'
~ 50%
Inhala-
tion
chamber
Sprague-
Dawley
rats
15 M
15 F
15 M
15 F
90 d
90 d No effect on behavior, wt. Lyon et al.
gain, or hematological values. (1970)
Apparently no changes found B-12
on autopsy.
(continued)
-------
TABLE HI-6. (continued)
Compound(s) and
Concentration(s),
mg/m3 (ppm)
Humidity/ Mode of
Temperature Exposure
Species/Strain/
Age/Weight
No. of
Test Animals
No. of
Controls
Duration and Total
Frequency of Length of
Exposure Experiment
Effects
Reference
and Rating
Acrolein
0.51 + 0.02
Inhala-
tion
chamber
White rats,
90-130 g
10 M
10 M
61 d
103 d No changes in the behavior and
(with general condition. Lost wt
21-d Loss of conditioned reflexes
pre- and after 10 d of exposure, fol-
post- lowed by disturbance of spatial
exposure relationships (which is depen-
periods) dent on cortical activity), both
of which returned to normal after
exposure stopped. Urine copropor-
phyrin levels significantly de-
creased, especially at wk 7, then
returned to normal during recovery.
Blood cholinesterase activity de-
creased, becoming significant from
34-41 d, then began to increase,
reaching normal levels by 10 d
post-exposure. Fluorescent
leucocyte counts began increas-
ing at wk 1, and continued until
11 d of recovery, when it began
to decrease to normal. On
autopsy: proliferation of the
columnar epithelium of the
bronchi with excess production
of mucus, and marked eosinophilic
infiltration of the bronchial
wall.
Gusev et al.
(1966)
B-9
Acrolein
0.15 + 0.01
Inhala-
tion
chamber
White rats,
90-130 g
10 M
10 M
61 d
103 d No changes in: behavior, gen-
(with eral condition, wt., magnitude
21-d or latent period of conditioned
pre- and motor reflexes, urine copropor-
post- phyrin levels, or blood cholin-
exposure psterase activity. An increase
periods) (of little toxicological signifi-
cance) in fluorescent leukocyte
counts after 24 h of exposure.
No appreciable changes found on
autopsy.
Gusev et al.
(1966)
B-9
(continued)
-------
TAIU.E F I 1-6. (
-------
TABLE III-7. RATS--CHRONIC EXPERIMENTAL EXPOSURE TO ACROLEIN
Ul
Compound (s) and
Concentration(s) , Humidity/ Mode of
mg/m3 (ppm) Temperature Exposure
Acrolein 4.7 Inhala-
(2) tion
chamber
During days 61 to
63, exposure
slowly increased
to 12 mg/m3, re-
mained at that
level for ~ 15 h,
then slowly de-
creased
Species /Strain/
Age/Weight
Albino,
Sprague-
Dawley
Souche
OFA rats,
specific
pathogen
free, 3 mo,
~ 175 g
No. of No. of
Test Animals Controls
50 M 50 M
For each lot:
2 used for
ventilation
resistance
measurements ;
3 for hema-
tology; 4 for
urinary
vanillyl-
mandelic acid
(VMA) levels;
2 for pul-
monary sur-
factant
measurements
Duration and
Frequency of
Exposure
91 d;
groups
of 6
sacrificed
on days 7 ,
14, 35, and
90 of expo-
sure for
respiratory
tract histo-
pathology
Total
Length of
Experiment Effects
105 d One rat died following the ac-
cident. Decreased wt. gain
before the accident, slight
wt . decrease for ~ 3 wk fol-
lowing the accident, then de-
creased wt. gain. After 2 wk
of recovery, body wt. (~ 375 g)
still below that of the controls
(~ 525 g) and 2.3 mg/m3 group
(~ 425 g). Slight changes in
ventilatory resistance. No sig-
nificant changes in hematological
values (cell counts, hematocrit,
leukocytes, mean cell volume, and
hemoglobin level) at any time.
Decreased VMA levels after
wk 2 to the end of exposure.
The index of stability of
pulmonary surfactant was de-
creased on day 7, the differ-
ence smaller on day 28, and
normal by day 91. Loss of
cilia in the bronchi during
1st 5 wk, then normal.
Perivascular edema was seen
from day 35 to day 90. On
days 7 to 35, no change in
the surface of the alveoli,
no cellular proliferation,
no exudates, and no abnormal
levels of macrophages.
Reference
and Rating
Guillerm
et al.
(1974)
C-12
(continued)
-------
TABLE III-7. (continued)
Compound(s) and
Concentration(s), Humidity/ Mode of
mg/m3 (ppm) Temperature Exposure
Species/Strain/
Age/Weight
No. of
Test Animals
No. of
Controls
Duration and
Frequency of
Exposure
Total
Length of
Experiment
Effects
Reference
and Rating
Acrolein 2.3
(1)
Accidentally
exposed to
~ 21 mg/m3
for ~ 18 h on
day 29, then
to 0 mg/m3 for
~ 12 h
Inhala- Albino, 50 M 50 M
tion Sprague- For each lot: 2 used
chamber Dawley for ventilation resis-
Souche tance measurements; 3
OFA rats, for hematology; 4 for
specific urinary vanillyl-
pathogen mandelic acid (VMA);
free, 3 mo, and 2 for pulmonary
~ 175 g surfactant measure-
ments
91 d; 105 d 15 rats died in the 9 d fol-
groups of lowing the accident. Wt. in-
6 sacrificed crease significantly below
on days 7, controls, even before the
14, 35, and accidental exposure, which
90 of expo- caused a sharp wt. loss of
sure for ~ 25 g. By 2 wk of recovery,
respiratory wt. still below controls
tract histo- (~ 425 g vs. ~ 525 g). In-
pathology creased expiration resistance
only on day 22. No difference
in resistance (inspiration and
expiration) any other day, be-
fore or after accident. No sig-
nificant changes in hematological
values (hematocrit, cell counts,
leukocytes, mean cell volume, and
hemoglobin levels) at any time.
Changes in VMA (vanillylmandelic
acid) levels (nonspecific indi-
cation of stress), generally
reduced by day 70. In the 1st wk,
a decrease in the index of sta-
bility of the pulmonary surfac-
tant, the difference smaller by
day 28, and normal by day 91.
Slight loss of ciliation in the
bronchi by 7 d, increasing on days
14 and 35, normal after that.
Perivascular edema was seen after
day 35. On days 7-35, no change
in the surface of the alveoli, no
cellular proliferation, no exu-
dates, and no abnormal levels of
macrophages.
Guillerm
et al.
(1974)
C-12
(continued)
-------
TABLE III-7. (concluded)
Compound(s) and
Concentration(s) ,
mg/m3 (ppm)
Acrolein
1.23-1.47
(0.53-0.63)
Acrolein
1.24-1.31
(0.53-0.56)
Humidity/ Mode of
Temperature Exposure
56% Inhala-
20°C tion
chamber,
0.3 m3,
air flow
5 m3/h
21°C Inhala-
58% tion
chamber
Species/Strain/
Age/Weight
Sprague-Dawley
rats, specific
pathogen free
OFA rats,
specific
pathogen
free
Duration and
No. of No. of Frequency of
Test Animals Controls Exposure
30 M 30 M 2-6 mo
Same age and avg.
weight. Only 15
of each group
actually examined
for changes.
10 M 10 M 10-180 d
Same age and avg.
weight
Total
Length of
Experiment Effects
6 mo Avg. body weight significantly be-
low controls after day 13, accom-
panied by decreased food and water
consumption. Significantly de-
creased avg. lung weight, perhaps
due to different body development
and the lower body weight. No dif-
ferences in number or activity of
alveolar macrophages. Bronchial
ciliated epithelium unchanged. Al-
veolar changes: thickening, indi-
cating reticular hypertrophy; and
thinning, as in emphysema. Cell
damage in the liver. No damage to
kidneys, spleen, stomach, and heart.
180 d After 10-26 d of exposure, the
number of alveolar macrophages
recovered by lavage was below
that of the controls. There were
no differences in relative num-
bers of cells, viability during
lavage, and physiological activ-
ity. After 60-180 d of exposure,
there were no significant dif-
ferences.
Reference
and Rating
Roussel
et al.
(1973)
B-9
Bouley et al
(1975)
B-10;
Bouley et al
(1976)
B-10
Acrolein 0.93
(0.4)
23-24°C,
50-70%
Exposure
chamber
Wistar rats,
specific
pathogen
free, 7 wk,
98-124 g
12
12 6 h/d, 13 wk No abnormal behavior. Slight,
5 d/wk, consistent, but statistically
13 wk insignificant, growth retarda-
tion. No effect on food in-
take, hematological values,
serum enzyme activities, urin-
alysis, organ-to-body weight
ratios, gross autopsy, and
histopathology of the tracheas,
bronchi, and lungs. 1 M rat
showed metaplastic and inflam-
matory changes in the nasal
cavity.
Feron et al.
(1978)
B-13
-------
TABLE I] [-8. GUINEA PIGS--ACUTE EXPERIMENTAL EXPOSURE TO ACROLEIN
Compound(s) and
Concentration(s) ,
mg/m3 (ppm)
Acrolein 3,728
(1,600)
Acrolein 932
(400)
Acrolein 39.6
(17)
Acrolein 39.6
(17)
Mode of Species/Strain/ No. of
Exposure Age/Weight Test Animals
Tracheotomy Guinea
P'gs,
~ 250 g
Inhalation Guinea
Pigs,
~ 250 g
Tracheotomy Guinea 6
Pigs,
~ 250 g
Inhalation Guinea 6
Pigs,
~ 250 g
Duration and Total
No. of Frequency of Length of
Controls Exposure Experiment Effects
6 min 6 min Dead in ~ 6 min without any measur-
able increase in pulmonary resis-
tance.
60 min? 60+ min? Full recovery within 5 min after
the end of exposure. Duration
of exposure unclear, and symptoms
not given.
Served as 60 min 60 min No change in respiratory resistance,
own con- rate, or minute volume.
trols
Served as 60 min 60 min Significantly increased pulmonary
own con- resistance and decreased respira-
trols tory rate. No change in minute
volume according to the 1965 re-
port, but a significant decrease in
minute volume according to the 1967
report. No change in compliance.
Authors conclude that these responses
(see results of other entries for
Davis et al., 1965, 1967) indicate
stimulation of receptors in the
supraglottal passages causing re-
flex respiratory changes.
Reference
and Rating
Davis et al.
(1967)
C-6
Davis et al.
(1967)
C-6
Davis et al .
(1965)
C-5
Davis et al .
(1967)
C-6
Davis et al.
(1965)
C-5
Davis et al.
(1967)
C-6
(continued)
-------
TABLE III-8. (concluded)
Compound(s) and
Concentration(s) , Mode of
mg/m3 (ppm) Exposure
Acrolein 2.3 Face
(1.0) masks
Acrolein 1.4 Face
(0.6) masks
Acrolein ~ 0.9 Face
(~ 0.4) mask
Acrolein 0.47 Face
(0.2) masks
Species/Strain/ No. of
Age/Weight Test Animals
Random- 10 M
bred
guinea
Pigs,
300-400 g
Random- 10 M
bred
guinea
Pigs,
300-400 g
Random- 15 H
bred
guinea
pigs,
300-400 g
Random- 5 M
bred
guinea
Pigs,
300-400 g
Duration and
No. of Frequency of
Controls Exposure
Served as 2 h
own con-
trols
14 H 2 h
during
expt. , and
own pre-
exposure
values
Served as 2 h
own con-
trols
Served as 2 h
own con-
trols
Total
Length of
Experiment
3-3.5 h
(includes
a 1-1.5 h
pre-
exposure
period)
~ 4.5 h
(a 1 h
pre- and
1.5 h
post-
exposure
period)
3-3.5 h
(includes
a 1-1.5 h
pre-
exposure
period)
3-3.5 h
(includes
a 1-1.5 h
pre-
exposure
period)
Effects
Tidal volume and total respiratory
flow resistance during expiration
and inspiration increased signifi-
cantly and respiratory rate de-
creased. All changes greater than
those for exposure to 0.6, 0.4,
and 0.2 ppm.
Increased expiratory flow resis-
tance and tidal volume and de-
creased respiration rate throughout
exposure. Responses were rapid,
reaching max. in 30-60 min and
then remaining constant. After ex-
posure stopped, rapid return to
pre-exposure and control values.
Changes greater than those for 0.2
and 0.4 ppm.
Significantly increased total
respiratory resistance during in-
spiration and expiration. Res-
piratory rate decreased. Changes
greater than those for 0.2 ppm.
Slight increase in total respira-
tory flow resistance during ex-
piration and inspiration. Slight
decreases in respiratory rate
and minute volume. No change
in tidal volume.
Reference
and Rating
Murphy et al.
(1963)
B-10
Murphy et al.
(1963)
B-10
Murphy et al .
(1963)
B-10
Murphy et al .
(1963)
B-10
-------
TABLE III-9. GUINEA PTGS--REPEATEI) BOSK EXPERIMENTAL EXPOSURE TO ACKOLEIN
Compound(s) and
Concent ration(s) , Humidity/
nig/m1 (ppm) Temperature
Acrolein 8.6 + 77 + 1°F,
1.9 ~ 50%
(J.7 t 0.8)
Acroleiii 4.2 77 + 1°F,
(1.8) ~ 50%
AcroJein 2.3 77 + 1°F,
(1.0) ~ 50%
Acrolein 1.6+ 77 + 1°F,
0.2 ~ 50%
(0.7 ± 0.1)
Mode of
Exposure
Inhalation
chamber
Inhalation
chamber
Inhalation
chamber
Inhalation
chamber
Species/Strain/ No. of
Age/Weight Test Animals
Princeton 7 H
or Hartley 8 F
gu i nea
pigs
Princeton 6 H
or Hartley 9 F
guinea
pigs
Princeton 7 M
or Hartley 8 F
guinea
pigs
Princeton 7 M
or Hartley 8 F
guinea
Duration and Total
No. of Frequency of Length of
Controls Exposure Experiment
7 H 8 h/d, 6 wk
8 F 5 d/wk,
6 wk
6 M 90 d 90 d
9 F
7 M 90 d 90 d
8 F
7 M 8 h/d, 6 wk
8 F 5 d/wk,
6 wk
Effects
No eifect on behavior, hematolog-
ical values, or various serum and
liver enzyme activities. Lower
rate of body weight gain. Non-
specific inflammatory changes in
lungs, livers, and kidneys.
No effect on behavior, weight gain,
or hematological values. Non-
specific inflammatory changes in
the brain, heart, lung, liver,
and kidney.
No effect on behavior, weight
gain, or heraatological values.
Various degrees of pulmonary
inflammation and occasional
minute foci of liver necrosis
without any specific pattern.
No effect on behavior, body weight
gain, hematological values, or
various serum and liver enzyme
Reference
and Rating
Lyon et
(1970)
B-12
Lyon et
(1970)
B-12
Lyon et
(1970)
B-12
Lyon et
(1970)
B-12
al .
al.
al.
al.
pigs
activities. Lungs showed mild
chronic inflammatory changes and
occasional emphysema. No definite
alteration of the respiratory
epithelium or of the peribronchial
smooth musculature.
Acrolein 0.51 77 + 1°F, Inhalation Princeton
(0.22) ~ 50% chamber or Hartley
guinea
pigs
15 M
15 F
15 M
15 F
90 d
90 d No effect on behavior, weight gain, Lyon et al.
or hematological values. Non- (1970)
specific inflammatory changes in B-12
liver, lung, kidney, and heart.
-------
TABLE 111-10. CHICKENS—REPEATED DOSE EXPERIMENTAL EXPOSURE TO ACROLEIN
Compound(s) and
Coiicentrat Lon(s) , Mode of Species/Strain/
mg/ra3 (ppm) Exposure Age/Weight
Acrolein 466 Endo- White
(200) tracheal leghorn
cannulae chickens,
attached 1.3-1.8 kg
to a
vapor
chamber
Ul
oo
Acrolein 116.5 Endo- White
(50) tracheal leghorn
cannulae chickens,
attached 1 .3-1.8 kg
to a
vapor
chamber
Duration and Total
No. of No. of Frequency of Length of Reference
Test Animals Controls Exposure Experiment Effects and Rating
30 F 12 F 5 min/d, 27 d, First signs of toxicity occurred on Denine (1971)
for up animals day 6: reduction in percent cilia- C-12
to 27 d sacrificed tion and number of mucus glands.
on days 1, The number of goblet cells began
3, 6, 13, decreasing on day 13. All contin-
20, and 27 ued to decline, the mucus elements
most severely.
The inflammatory response was lo-
calized in the mucosa and lamina
propria, began day 1, was mani-
fested mainly by a lymphocytic
infiltrate, and increased with
time. The symptoms were more
severe in the upper than the lower
trachea .
10 F 10F 5 min/d, 17 d Upper trachea: slight decreases Denine (1971)-
for 13 in percent ciliation on days C-12
or 17 d 13 and 17. Decreased number of
mucus glands on day 13, but no
further change. Number of goblet
cells markedly decreased on both
days. Changes are less severe
than those caused by 200 ppm after
the same length of time.
Lower trachea: no effect on per-
cent ciliation. Slight decrease
in number of goblet cells. Slight
increase in mucus glands.
-------
TAIU.F. I 11-11. RAFHUTS--ACUTF. F.XI'KK 1MKNTA1, EXPOSURE TO ACROLKFN
Compound(s) and
Concent ration(s) , Mode of Species/Strain/ No. of No. of
mg/in3 (ppm)
Acrolein 28
(12)
Arrolein 21
(9)
Exposure Age/Weight Test Animals Controls
Inhalation Rabbits, 50
(perhaps anesthetized
head ex- with urethane
posure
only)
Inhalation Rabbits
(perhaps
head ex-
posure
only)
Du ra t i on and
Frequency o)
Exposure
Probab ly
~ 5 in i ri
(text
uncle. ir)
Probably
~ 5 nun
(text
unclear)
Total
Length of
Experiment Effects
Decreased heart rate, increased
arterial pressure, and inhibi-
tion of respiratory movements.
Slight decrease in heart rate
towards the end of the exposure,
of dubious importance. No
change in arterial pressure or
respiratory movement.
Reference
and Rating
Kishi et a I
( 1 9 7 r> )
C-8
Kishi et a
(n?5)
C-8
1
-------
TABLE 111-12. RARBITS--CIIRON1C EXPERIMENTAL EXPOSURE TO ACROLF.1N
Compound (s) and
Concent rat ion(s) ,
mg/m3 (ppm)
Acrolein 11.4
(4.9)
Acrolein 3.3
(1.4)
Acrolein 0.93
(0.4)
Humidity/ Mode of Species/Strain/
Temperature Exposure Age/Weight
23-24°C, Exposure Dutch
50-70% chamber rabbits,
6-9 wk,
0.66 -
1.22 kg
'
23-24°C, Exposure Dutch
50-70% chamber rabbits,
6-9 wk,
0.66-1.22 kg
23-24°C, Exposure Dutch
50-70% chamber rabbits,
6-9 wk,
0.66 -
1.22 kg
Duration and
No. of No. ot Frequency of
Test Animals Controls Exposure
4 46 h/d,
r> d/wk,
13 wk
4 46 h/d,
5 d/wk,
13 wk
4 4 6 h/d,
5 d/wk,
13 wk
Total
Length of Reference
Experiment Effects and Rating
13 wk Closed eyes, sneezing, and occa- Feron et al.
sional breathing difficulty dur- (1978)
ing exposure. Decreased food B-13
intake and body weight gain.
Increased relative weight of the
lungs. Increased urinary sedi-
ments. No effect on hematologi-
cal values, blood chemistry, gross
autopsy, and histopathology of the
larynx. Histopathological changes
were seen in the epithelial lining
of the nasal cavity, trachea,
bronchi, and lungs.
13 wk Occasional sneezing. Decreased Feron et al.
food intake and body weight gain. (1978)
No effect on hematological values, B-13
blood chemistry, urinalysis,
organ-to-body weight ratios,
gross autopsy, or histopathology
of the respiratory tract.
13 wk No abnormal behavior. 1 F control Feron et al.
and 1 M test animal died. No (1978)
effect on growth, food intake, B-13
hematological values, blood
chemistry, urinalysis, organ-
to-body weight ratios, gross
autopsy, or histopathology of
the respiratory tract.
-------
TAIif,F, [11-13. CATS--ACUTF. KXI'KR IMKNTAI, EXPOSURE TO ACROI.F.IN
Compouiul(s) and
Concentration(s) ,
mg/m1 (ppm)
Node of
Exposure
Species/Strain/
Age/Weight
No. of
Tost Animals
No. of
Controls
Duration anil
Frequency ot
Exposure
Total
Length of
Experiment
Effects
Referencr
and Rating
Acrolein avg. 210
range 180-240
Inhalation Cat, 1,750 g
2 h Few days Immediately: tearing, first thinly
40 nun; then thickly flowing salivary
1st h secretion, coughing, sneezing.
at 240 ing/m1, After 10 min: respiration 12-16
later at interrupted by swallowing, open
IRQ mg/m3 mouth, tongue outstretched,
continuous salivation. After
40 min: coughing, head on neck,
jerky respiration 20. After
80 min: head moved with each
inspiration, clearly dyspneic.
After 85 min: spasmodic sneezing,
choking, strong dyspnea.
Iwanoff
(1911)
C-8
Acrolein avg. 40
range 34-46
Inhalation Cat, 2,400 g
4 h; Several Immediately: tearing, salivation,
1st 2.5 h days sneezing. After 10 min: nasal
at 34 mg/m3, secretions, eyes closed, respira-
later at tion 16. 15-150 min: slight
46 mg/m3 retching motions without vomiting,
copious salivation, respiratory
18-20 through wide open mouth.
After 160 min: frequent retching,
no vomiting, some dyspnea, nasal
and salivary secretions.
After exposure: remained sick for
several days, but it recovered.
Iwanoff
(1911)
C-8
Acrolein avg. 25
range 20-30
Inhalation Cat, 2,000 g
9 h 10-*- h First 105 min: quiet, respiration
40 min; 14-16, copious salivation, eyes
1st 2 h closed. After 155 min: head down
at 27 mg/m3, towards neck, eyes closed, sleepy.
next 4 h After 305 min: light retching
at 30 mg/m3, motions. Toward the end: quiet,
later at in a half slumber, respiration 16.
20 mg/m3 After exposure: appeared to be
entirely normal after "several
hours."
Iwanoff
(1911)
C-8
(continued)
-------
TABLE Ul-n. (concluded)
Compound(s) and Duration and
Concentration(s) , Mode of Species/Strain/ No. of No. of Frequency of
mg/m^ (ppm) Exposure Age/Weight Test Animals Controls Exposure
Acrolein avg. 25 Inhalation Cats, 2,000 g 1 3.5 h;
range 23-27 1st 2 h
at 27 mg/m3
later at
23 mg/m3
Total
Length of
Experiment Effects
3.5+ h Immediately: tearing, viscous
salivary secretions, leaking,
sneezing. After 135 min:
respiration 19, occasional
salivation, eyes closed,
breathing through mouth, quiet,
sleepy, head on neck. After
exposure: appeared to be
normal "after a short time."
Reference
and Rating
Iwanof f
(1911)
C-8
-------
TABI.K I I (-14. MONKEYS--RI'.i'EATI'I) DOSK liXCI.R I MKN I Al, KXI'OSUKK TO ACROLKIN
Compound (s) and
Concentrations) ,
mg/m3 (ppra)
Acrolei M
8.6 ± 1.9
(,i.7 ± 0.8)
Humid i ty/
Temperature
77 ± 1°F,
~ 50%
Mode of
Exposure
Inhala-
tion
chamber
Species/Strain/ No. of
Age/Weight Test Animals
Squirrel 9 M
monkeys
(Sa imiri
sciurea)
(Jurat ion and
No. of Frequency of
Controls Exposure
9 M 8 h/d,
5 d/wk,
6 wk
Total
Length of
Experiment
6 wk
Effects
During the 1st week of expos-
ure, salivated excessively,
blinked frequently, and kept
their eyes closed. Symptoms
Reference
and Rating
Lyon et al
(1970)
B-12
were milder the 2nd wk. 1
died on d 6, and 1 on d 9.
Decreased rate of body wt.
gain. No effect on hematol-
ogical values or various
serum and liver enzyme act-
ivities. Nonspecific inflam-
matory changes in lung, liver,
and kidney. Focal calcifica-
tion of renal tubular epithe-
lium. Squamous metaplasia anil
basal cell hyperplasia of the
trachea. Necrotizing bronchi-
tis and bronchiolitis with
squamous metaplasia of the lungs.
Acroiei n 4.2
(1.8)
77 ± 1°F,
~ 50%
Inhala- Squirrel
tion monkeys
chamber (Sa^iminL
sciurea)
9 M
9 M
90 d
90 d Excessive salivation and ocu-
lar discharge. No effect on
wt. gain or hematological
values. Nonspecific inflam-
matory changes in the brain,
heart, lung, liver, and kid-
ney. All showed squamous meta-
plasia and 6/9 showed basal
cell metaplasia of the trachea.
Lyon et a 1.
(1970)
B-12
Acrolein 2.3
(1.0)
77 ± 1°F,
~ 50%
Inhala- Squirrel
tion monkeys
chamber (Saimiri
sciureaj
9 M
9 M
90 d
90 d Ocular and nasal discharge
throughout exposure, decreas-
ing in severity. Kept eyes
closed for extended periods.
1 died on day 28, probably
due to infection from a bite.
No effect on wt. gain or hema-
tological values. Parasitic
infection in some with involve-
ment of the lung, liver, heart,
nnil brain.
Lyon et al.
(1970)
B-12
(cont i lined )
-------
TABLE III-14. (concluded)
Compound(s) and Duration and Total
Concentration(s) , Humidity/ Mode of Species/Strain/ No. of No. of Frequency of Length of Reference
tng/m3 (ppm) Temperature Exposure Age/Weight Test Animals Controls Exposure Experiment Effects and Rating
Acrolein 77 ± 1°F, Inhala- Squirrel 9 M
1.6+0.2 ~ 50% tion monkeys
(0.7 ± 0.1) chamber (Saimiri
sciurea)
Acrolein 0.51 77 ± 1°F, Inhala- Squirrel 18 M
ON (0.22) ~ 50% tion monkeys
chamber (Saimiri
sciurea)
9 M 8 h/d, 6 wk No effect on behavior, body wt. Lyon et al
5 d/wk, gain, hematological values, (1970)
6 wk or various serum and liver B-12
enzyme activities. Lungs
showed chronic mild inflam-
matory changes and occasional
emphysema. No definite alter-
ations in the respiratory
epithelium or the peribronchial
smooth musculature.
18 M 90 d 90 d No effect on behavior. 1 Lyon et al
animal developed an eye in- (1970)
fection in the 5th wk and B-12
died in the 6th wk. No ef-
fect on wt. gain or hematol-
ogical values. Nonspecific
inflammatory changes in the
liver, lung, kidney, and
heart.
-------
TAHl.F. 111-15. DOGS--REPEATF.I) DOSE EXPERIMENTAL EXPOSURE TO ACROLEIN
Compound(s) dud
Conrentration(s) ,
mg/m3 (ppm)
Humidity/
Temperature
Mode of
Exposure
Species/Strain/
Age/Weight
No. of
Test Animals
Duration and Total
No. of Frequency of Length of
Controls F.xposure F.xperimont
Effects
Reference
and Rating
Arrolei n
8.6 ± 1.9
(3.7 ± 0.8)
77 ± 1'
~ 50%
F,
Inhala-
tion
chamber
Purebred
beagle dogs
2 K
2 M 8 h/d, 6 wk During the 1st wk: salivated
5 d/wk, excessively, blinked frequent-
6 wk ly, kept eyes closed, and had
difficulty breathing. Con-
tinued during 2nd wk, although
less severe. Eye irritation
continued the next 4 wk. De-
creased rate of body wt. gain.
No effect on hematological
values, various liver and
serum enzyme activities, or
serum sulfobromophthaleln re-
tention. Nonspecific inflam-
matory changes in lung, liver,
a«d kidney. Squamous metaplasia
and basal cell hyperplasia of
the trachea. Rronchopneumonia.
Lyon et al.
(1970)
B-12
Acrolein 4.2
(1.8)
77 ± 1'
~ 50%
'F,
Inhala-
tion
chamber
Purebred
beagle dogs
2 M
2 M
90 d
90 d Excessive salivation and ocu-
lar discharge. No effect on
wt. gain or hematological
values. Nonspecific inflam-
matory changes in the brain,
heart, lung, liver, and kid-
ney. Both animals showed
confluent bronchopneumorlia.
Lyon et al .
(1970)
B-12
Acrolein 2.3
(1-0)
77 ± 1'
~ 50%
F,
Inhala-
tion
chamber
Purebred
beagle -dogs
2 M
2 M
90 d
90 d Ocular and nasal discharge
throughout exposure, decreas-
ing in severity. No effect
on wt. gain or hematological
values. Focal inflammatory
reactions involving lung,
kidney, and liver. Bronchi-
olitis; and early broncho-
pneumonia in 1 dog.
Lyon et a 1 .
(1970)
B-12
(cent i lined)
-------
TABLE 111-15. (concluded)
Compound(s) and
Concentration(s)
rag/m3 (ppm)
Acrolein
1.6 ± 0.2
(0.7 ± 0.1)
nd
s),
Humidity/
Temperature
77 ± 1°F,
~ 50%
Mode of
Exposure
Inhala-
tion
chamber
Species/Strain/
Age/Weight
Purebred
beagle dogs
Duration and
No. of No. of Frequency of
Test Animals Controls Exposure
2 M 2 M 8 h/d,
5 d/wk,
6 wk
Total
Length of
Experiment
6 wk
Effects
No effect on behavior, body
wt. gain, hematological
values, various serum and
Reference
and Rating
Lyon et al
(1970)
R-12
liver enzyme activities,
or serum sulfobromophthalein
retention. Lungs showed mild
chronic inflammatory changes
and occasional emphysema. No
definite alterations in the
respiratory epithelium or the
peribronchial smooth musculature.
Acrolein 0.51
(0.22)
77 ± 1°F,
~ 50%
Inhala-
tion
chamber
Purebred
beagle dogs
4 M
90 d
90 d No effect on behavior, wt.
gain, or hematological values.
The lungs of 2/4 showed mod-
erate emphysema, acute con-
gestion, focal vacuolization
of the bronchiolar epithelial
cells with increased secretory
activity, and, occasionally,
some degree of bronchiolar
constriction. Focal subcapsu-
lar hemorrhage in the spleens
of the same 2. The other 2
showed hyperplasia of the thy-
roid. Nonspecific inflammatory
changes in lung, liver, and
kidney.
Lyon et al.
(1970)
B-12
-------
TABLE 111-16
SUMMARY OF ANIMAL INHALATION EXPOSURES TO ACROLEIN
Level
Time
> 100-
5,000
39.6
20-30
28
28
23-27
< 6 h
60 min
9 h
40 min
4 h
5 min
3.5 h
Species
RAT
GPG
MUS
CKN
CAT
Effects
100
93.2
72.2
50
46.6
34-46
30 min,
twice
a day,
5 wk
15 min
or 1 h
6 h
1 min
15 min
4 h
MUS
MUS
MUS
RAT
RAT
CAT
GPG
CAT
RAT
RBT
CAT
Deaths at higher levels and longer ex-
posure times;strong respiratory irrita-
tion; decreased respiratory parameters;
histopathological changes, particularly
in the upper respiratory tract; some
damage to other organs.
Decreased pulmonary compliance; increased
serum antitrypsin activity and lung total
phospholipids.
Respiratory difficulty; decreased body
wt. 2 d later; recovery by 5 d.
No deaths.
Insignificant blood pressure changes;
changes in heart rate.
40-50% decrease in respiration rate in
3 min.
Tearing, salivation, sneezing, nasal
secretions, retching, dyspnea; recovered
in several days.
Tracheotomy: no change in respiratory
resistance, rate or minute volume.
Inhalation: increased resistance; de-
creased rate; no change in compliance.
Salivation; sleepy; light retching; quiet
Severe eye and respiratory tract irrita-
tion; dyspnea; anorexia; weakness; de-
creased lung and serum alkaline phos-
phatase (AP) activities.
Decreased heart rate; increased arterial
pressure; inhibited respiratory movement.
Tearing, salivation, sneezing, sleepy,
mouth breathing.
67
-------
TABLE 111-16 (continued)
Level
Time
25
21
18.6
14.9
14
< 14 on
593 mg/m3
carbon
particle
11.4
11.4
1 min
~ 5 min
4 h
4 h
4 h
4 h
Species
RAT
RBT
RAT
RAT
HAM
HAM
Effects
6 h/d,
5 d/wk,
13 wk
HAM
6 h/d,
5 d/wk,
13 wk
RAT
Insignificant changes in blood pressure
and heart rate.
Slight increase in heart rate; no change
in arterial pressure or respiratory
movement.
Increased liver enzyme activities;
slightly increased lung-to-body-wt.
and liver-to-body wt. ratios.
Changes in liver enzyme activites; liver-
to-body wt. ratio increased.
Cytopathological changes in the respira-
tory tract; no polymorphonuclear leukocyte
recruitment.
Leukocyte recruitment to tracheal and
intrapulmonary airway epithelia.
Salivation; nasal discharge; decreased
food intake and wt. gain; increased
hematological values in females;
changes in urinary values; increased
lung-, heart-, and kidney-to-body wt.
ratios; histopathological changes in
lining of nasal cavity, and larynx of
few females; hyper- and metaplasia
in tracheal epithelium of some males
and most females.
50% died in first 4 wk; decreased food
intake and body wt. gain; no effect on
hematological values and blood chemistry;
changes in urinary values, increased
relative wt. of lungs, heart, kidneys,
and adrenals; histopathological changes
in lining of nasal cavity and larynx;
severe damage of trachea, lungs, and
bronchi.
68
-------
TABLE III-16 (continued)
Level
Time
11.4
10.3
10
9.6
9.3
9.2
9.1
6 h/d,
5 d/wk,
13 wk
Species
RBT
Effects
2-8 h
1 min
20 h
4 h/d,
5 d
7 h/d,
5 d/wk,
52 wk
4 h/d,
9 d
8 h/d,
5 d/wk,
6 wk
RAT
RAT
RAT
RAT
HAM
RAT
MKY
DOG
GPG
RAT
Sneezing and occasional breathing dif-
ficulty; decreased food intake and body
wt. gain; increased relative wt. of
lungs; no effect on hematology, blood
chemistry, gross autopsy, histopathology
of larynx; changes in lining of nasal
cavity, trachea, bronchi, and lungs.
No changes in lung and liver alkaline
phosphatase (AP) activity; changes in
liver AP activity.
Insignificant changes in blood pressure
and heart rate.
Increased liver- and lung-to-body wt.
ratio, adrenals wt., liver AP activity;
no change in lung and serum AP activity.
Decreased liver-to-body wt. ratio; no
change in lung, liver, and serum AP
activity and lung and adrenal wts.
Slight decrease in body wt.; 20/36 died
by 28 wk post-exposure; hematological
parameters unchanged; slight to moderate
epithelial metaplasia in nasal cavity;
changes in other parts of respiratory
tract; no tumors; possible slight
co-carcinogenicity with benzo(a)pyrene.
Decreased liver-to-body wt. ratio; no
change in lung, liver, and serum AP
activities and lung and adrenal wts.
Mild irritation in MKY and DOG; 2/9 MKY
died; decreased body wt. gain; no change
in behavior (RAT and GPG), hematological
values, or various enzyme activities;
nonspecific inflammatory changes in lung,
liver, kidney, brain (GPG only), and
heart (GPG only); focal renal tubular
calcification in MKY and RAT; squamous
metaplasia and basal cell hyperplasia
of the trachea in MKY and DOG; necro-
tizing bronchitis and bronchiolitis
with squamous metaplasia of the lungs
in MKY; bronchopneumonia in DOG.
69
-------
TABLE 111-16 (continued)
Level
Time
4.9
4.7
2.3-4.7
plus prior
bacterial
and viral
exposure
4.2
4.0
3.3
2.3
41 h
up to
91 d
4 or
24 h
90 d
10 min
6 h/d,
5 d/wk,
13 wk
up to
91 d
Species
RAT
Effects
RAT
MUS
GPG
RAT
DOG
MKY
MUS
RBT
HAM
RAT
RAT
Increased liver-to-body wt. ratio,
adrenal wt., liver AP activity; no
change in lung and serum AP activity
and lung wt.
Decreased wt. gain and vanillylmandelic
acid levels; slight changes in ventila-
tory resistance; no change in hematologi-
cal value; loss of bronchial cilia during
first 5 wk; perivascular edema during
days 35-90.
Mild discomfort; significant decrease in
pulmonary bactericidal activity by 24 h,
varying with type of bacteria.
Salivation and ocular discharge in DOG
and MKY; no effect on wt. gain (except
RAT, which decreased) or hematological
values; nonspecific inflammatory changes
in brain, heart, lungs, liver, and kid-
neys; confluent bronchopneumonia in DOG;
squamous metaplasia of the trachea in MKY.
50-62% decrease in respiratory rate.
Restless; decreased food intake and
body wt. gain in RAT and RBT; no effect
on hematological values, blood chemistry,
urinalysis, organ-to-body wt. ratios,
gross autopsy, or histopathology of the
larynx, trachea, bronchi, lungs, and,
in RBT only, nasal cavity; minor in-
flammation of HAM nasal cavity; squamous
metaplasia and neutrophilic infiltra-
tion of the mucosa of the RAT nasal
cavity.
Decreased wt. gain and vanillylmandelic
acid levels; no effect on hematological
values or respiratory resistance; slight
loss of bronchial ciliation on days 7-35;
perivascular edema after 35 d.
70
-------
TABLE 111-16 (continued)
Level Time Species Effects
2.3 90 d DOG Decreasing ocular and nasal discharge in
MKY DOG and MKY; no effect on wt. gain (ex-
GPG cept RAT, which decreased) or hematological
RAT values; various degrees of pulmonary in-
flammation in DOG, GPG, and RAT; para-
sitic infection in MKY; occasional, slight
liver damage in DOG and GPG; kidney in-
flammation in DOG.
2.3 81 h RAT No effect on liver-to-body-wt. ratio,
adrenal and lung wt., and liver, lung,
and serum AP activity.
2.3 2 h GPG Significantly increased respiratory
resistance and rate and decreased tidal
volume.
1.6 8 h/d, RAT No effect on behavior, body wt. gain,
5 d/wk, GPG hematological values, various enzyme
6 wk MKY activities; mild chronic lung inflamma-
DOG tion; occasional emphysema; no definite
alteration of respiratory epithelia or
the peribronchial smooth musculature.
1.52 24 d RAT Progressive deterioration of general
condition; 7/10 died; changes in mag-
nitude and latent period of condi-
tioned motor response; decreased blood
cholinesterase activity and increased
leukocytes, returning to normal by 20 d
post-exposure; lung inflammation;
myocardium and liver changes.
1.23-1.47 6 mo RAT Decreased body wt.; alveolar damage;
liver cell damage; no effect on al-
veolar macrophages, spleen, kidney,
stomach, or heart.
1.4 2 h GPG Increased expiratory flow resistance
and tidal volume and decreased respira-
tion rate, max. change in 30-60 min.
1.24-1.31 10-180 d RAT Decreased number of alveolar macrophages
on days 10-26; no effect on relative
no. of cells, viability, and physiological
activity; no effect on days 60-180.
71
-------
TABLE 111-16 (continued)
Level Time Species Effects
1.24-1.31 15, 18 RAT Increased lung-to-body-wt. ratio only on
21, 26 day 77; no effect on various enzyme
32, 60, activities; decreased body wt. during
63, or 21-d exposure; no effect on no. of
77 d pregnant rats or no. and avg. wt. of
fetuses for 26-d exposure; signifi-
cantly increased mortality when a high
bacterial dose followed an 18-d expo-
sure, but not after a 63-d exposure.
0.93 6 h/d, RBT No effect on behavior, growth, food in-
5 d/wk, HAM take, hematological values, blood
13 wk chemistry, urinalysis, organ-to-body
wt. ratios, gross autopsy, or histo-
pathology of the respiratory tract.
0.9 2 h GPG Significantly increased total respiratory
resistance; decreased respiratory rate.
0.74 61 d RAT General state and wt. affected by 6th
wk in healthy rats and by 5th wk in rats
with experimentally induced silicosis;
changes in chronaxy of antagonistic
muscles in both groups.
0.51 90 d DOG No effect on behavior, wt. gain,
GPG hematological values, gross autopsy
MKY (RAT, MKY, GPG, DOG, with exceptions
RAT noted below). MKY & GPG & DOG -
nonspecific inflammatory changes in
liver, lung, kidney, and heart.
DOG - Some of the following: emphysema,
lung congestion, some bronchiolar con-
striction, hyperplasia of the thyroid,
focal subcapsular hemorrhage of the
spleen.
0.51 61 d RAT No change in behavior or general condi-
tion; lost wt.; loss of conditioned
reflexes after 10 d; disturbance of
spatial relationships; decreased urine
coproporphyrin levels and blood cholin-
esterase activity; recovery post-exposure;
some histopathological changes in the
bronchi.
72
-------
TABLE 111-16 (concluded)
Level Time Species Effects
0.47 2 h GPG Slight increase in total respiratory
flow resistance; slight decrease in res-
piratory rate and minute volume.
0.15 61 d RAT No change in behavior, general condition,
wt., magnitude or latent period of condi-
tioned motor reflexes, urine copropor-
phyrin levels, or blood cholinesterase
activity; no appreciable changes found
on autopsy.
0.14 61 d RAT Changes in chronaxy of antagonistic
muscles in healthy rats and rats with
silicosis.
0.03 61 d RAT No change in a variety of biological,
biochemical, and physiological tests in
healthy rats or rats with silicosis.
73
-------
SECTION IV
EXPERIMENTAL HUMAN INHALATION EXPOSURES
Table IV-1 describes acute laboratory human exposures to acrolein.
Table S-4 in the Summary condenses all the information regarding experimen-
tal human exposure. The American Conference of Government Industrial Hy-
gienists gives 0.25 mg/m3 as the time-weighted-average threshold limit
value (TLV) and 0.8 mg/m3 as the short-term-exposure limit (ACGIH, 1980).
The 8-h TLV promulgated by the Occupational Safety and Health Administra-
tion is also 0.25 mg/m3 (0.1 ppm) (SRC, 1979).
75
-------
TABLE IV-1. HUMANS - ACUTE EXPERIMENTAL INHALATION EXPOSURE TO ACROLEIN
Compound (s) and
Concentration(s)
in mg/m3 (ppm)
Mode of
Exposure
No. of
Test Subjects
No. of
Controls
Duration and
Frequency of
Exposure
Total
Length of
Experiment
Effects
Reference
and Rating
Ac rolein
2.33-46.6
(1-20)
Levels in the
whole diesel
engine exhaust
gas tested
Subject's
face held
1 m down-
stream
from ex-
haust pipe
2-3 eye
blinks,
without
breathing
When 1-5 ppm acrolein was pres-
ent, little to moderate eye irri-
tation was reported. 5-10 ppm
caused moderate to strong and
intolerable eye irritation.
> 10 ppn was intolerable and
caused strong to extremely strong
irritation.
Iwai et al.
(1976)
B-7
Acrolein
12.8
(5.5)
CH3C1
1,138?
(544.5?)
(Exposure
atmosphere
made
from a 1%
acrolein-methyl
chloride mixture)
Chamber
1 min
1 min
5 s: slight odor of acrolein,
moderate nasal and eye irrita-
tion.
20 s: painful eye and nasal ir-
ritation.
1 min: marked lacrimation, prac-
tically intolerable.
Yant et al.
(1930)
C-10
Acrolein
4.7-5.4
(2.0-2.3)
Loose-
fitting
face
mask with
respirator,
so only the
eyes were
exposed
26 M
10 F
Served
as own
controls
5 min
5 min
On a scale from 0 (none) to 2 Darley et al.
(severe), the avg. maximum eye (1960)
irritation was 1.476. The values C-10
for carbon-filtered air were
0.088-0.361.
(continued)
-------
TABLE IV-1. (continued)
Compound(s) and
Concent ratron(s)
in mg/m3 (ppm)
Acrolein
2.3-4.6
(1-2)
Acrolein
4.19
(1.8)
CH3C1
372?
(178?)
(Exposure
atmosphere
made from a
1% acrolein-
methyl chloride
mixture)
Acrolein 4
Acrolein
3.0-3.7
(1.3-1.6)
Duration and
Mode of No. of No. of Frequency of
Exposure Test Subjects Controls Exposure
Eye ex- 13-20 M+F Served 5 min,
posure for a total as own repeated
only of 23 ex- controls 3 times
through posures during at unknown
snugly the 5 intervals
fitting min be-
goggles fore ex-
posure
Chamber 6 4 rain
Inhala- 10
tion
Loose- 26 M Served 5 min
fitting 10 F as own
face mask controls
with res-
pirator,
so only
the eyes
were ex-
posed
Total
Length of
Experiment Effects
20 of 23 exposures (87%) caused
eye irritation (medium or severe).
4 min 30 s: odor of acrolein.
1 min: slight eye irritation and
no nasal irritation.
2 min: slight nasal and distinct
eye irritation.
3 min: slight nasal and distinct
eye irritation, with lacrimation.
4 min: profuse lacrimation, prac-
tically intolerable.
Acute irritation of the conjunctiva
and nasal mucosa. Painful sensa-
tions in the nasopharyngeal region.
5 min On a scale of 0 (none) to 2
(severe), the avg. maximum eye
irritation was 1.182. The val-
ues for carbon-filtered air were
0.088-0.361.
Reference
and Rating
Stephens et al
(1961)
B-8
Yant et al.
(1930)
C-10
Plotnikova
(1960)
A-9
Darley et al .
(1960)
C-10
(continued)
-------
TABLE IV-1. (continued)
Compound(s) and
Concentration^ )
in mg/m3 (ppm)
Acrolein
3.5
(1.5)
Acrolein
2.80
(1.22)
Acrolein
2.33
(1)
CH3C1
207?
(99?)
(Exposure
atmosphere
made from a
1% acrolein-
methyl chloride
mixture)
Acrolein
2.3
(1)
Mode of
Exposure
Eye
irrita-
tion
booths
attached
to a
chamber
Inhala-
tion
chamber
Chamber
Eye
exposure
only,
through
snugly
fitting
goggles
Duration and Total
No. of No. of Frequency of Length of
Test Subjects Controls Exposure Experiment Effects
Not Not 5 min 5 min Caused medium to severe eye irri-
given given tation.
12 M, Controls 5 min Not Extremely irritating to all ex-
18-45-y-old; used; no. given posed mucous membranes. Lacri-
all exposed not given mation occurred within 5 s.
simultaneously Exposure for more than 5 min
would have been extremely dis-
tressing.
7 5 min 5 min 1 min: slight nasal irritation.
2 min: slight nasal and eye ir-
ritation.
3 min: slight nasal and moderate
eye irritation.
4 min: slight nasal and moderate
eye irritation with lacrimation.
5 min: moderate nasal irritation
and practically intolerable eye
irritation with lacrimation.
13-20 M+F Served 5 min, 14 of 17 exposures (82%) caused
for a total as own repeated eye irritation (medium or severe).
of 17 expo- controls twice at
sures for the an unknown
5 nun interval
before
exposure
Reference
and Rating
Schuck and
Renzetti
(1960)
C-8
Schuck and
Doyle
(1959)
C-8
Sim and Pattle
(1957)
B-9
Yant et al.
(1930)
C-10
Stephens et al .
(1961)
B-8
(continued)
-------
TABLE IV-1. (continued)
Compoimd(s) and
Concentration(s)
in rag/m3 (ppm)
Mode of
Exposure
No. of
Test Subjects
No. of
Controls
Duration and
Frequency of
Exposure
Total
Length of
Experiment
Effects
Reference
and Rating
Acrolein 2.3
(1.0)
Injecting
sample into
nostril by
a syringe
4-6
Odor threshold
Cormack
et al.
(1974)
A-8
Acrolein
2
Inhalation
Sharp changes in the amplitude Plotnikova
of respiratory movements as mea- (1960)
sures by a pneumograph, and a A-9
slight increase in respiratory
frequency.
Acrolein
3, with
odor
thresholds
of 0.8-0.9
mg/m3
Served
as own
controls
5 min,
during
min 10-15
of the
expt .
90 min
A sharp, unpleasant odor. De-
creased eye sensitivity to light
during exposure, followed by
slow recovery. Near normal,
fresh air values by 90 min.
Changes in eye sensitivity to
light may register functional
changes in the brain.
Plotnikova
(1960)
A-9
Acrolein
1.75-2.0
Inhala-
tion
Served
as own
controls
3 min
25 min Shortened the optical chronaxy*
(using the appearance of the
phosphene*- phenomenon) in 2/3
and prolonged it in 1. Returned
to normal in all cases in 3-6 min.
The rheobase*** was unaffected.
Plotnikova
(1960)
A-9
Acrolein
1.88
(0.805)
Inhala-
tion
chamber
12 M,
18-45-y-old
all exposed
simultaneously
Controls
used; no.
not given
10 min
(continued)
Not
given
Extremely irritating to all ex-
posed mucous membranes. Lacri-
mation occurred with 20 s.
Exposure for the full 10 min was
only just tolerable.
Sim and Pattle
(1957)
Optical chronaxy is the minimum time an electric current must flow at a voltage twice the rheobasc**" to cause a muscle to contract.
Phosphene is an objective visual sensation that appears with the eyes clo&rd and in the absence of visual light
The rheobase is the minimum potential of electric current necessary to produce stimulation.
-------
TABLE IV-1. (continued)
00
O
Compound(s) and Duration and
Concentration(s) Mode of No. of No. of Frequency of
in mg/m3 (ppm) Exposure Test Subjects Controls Exposure
Acrolein Inhala-
1.5 tion
Acrolein Inhala- 3 Served 3 min
0.6-1.5 tion as own
controls
Acrolein Climatic 17 M Served 7.5 min;
1.4 chamber 25 F as own 5 x 1.5-min
(0.6) controls exposures
at 8-min
intervals
Total
Length of
Experiment Effects
Slight changes in amplitude of
respiratory movements, as measured
by a pneumograph.
25 min No effect on the rheobase or op-
tical chronaxy at 0.6, 1.0, or
1.5 mg/m3 in any of the subjects.
39.5 min Subjective air quality above that
for intermittent exposure to lower
levels and below that for contin-
uous, rising exposure to 0.6 ppm.
Desire to leave the room about
equal to that for both intermit-
tent and continuous exposures.
Slight eye and nose irritation,
a little above intermittent ex-
posure to lower levels, but well
below that of continuous, rising
exposure to 0.6 ppm.
Reference
and Rating
Plotnikova
(1960)
A-9
Plotnikova
(1960)
A-9
Weber-
Tschopp
et al.
(1977)
A-U
(continued)
-------
TABLE 1V-1. (continued)
CO
Compound(s) and
Ccmcentration(s) Mode of
in mg/m3 (ppm) Exposure
Acrolein Climatic
0-1.4 chamber
(0-0.6)
Level steadily
increasing dur-
ing the first
35 min, then
constant
i Duration and
No. of No. of Frequency of
Test Subjects Controls Exposure
31 H Served 40 min
22 F; as own
all were ex- controls
posed, but
only 34 used
for blinking
frequency and
19 for respira-
tory frequency
measurements
Total
Length of
Experiment
40 rain
Effects
Reference
and Rating
Continuously increasing annoyance
(as measured by subjective judg-
ment of air quality and the de-
sire to leave the room) with
increasing acrolein level. A
significant difference from short,
discontinuous exposures to sim-
ilar levels only for 0.15 ppm
(higher for noncontiguous), indi-
cating some adaptation to acro-
lein at continuous exposure to
lower levels, which disappears
at higher levels. Eye irrita-
tion continuously increased
from none to severe, and nose
irritation from none to mod-
erate. The level of irrita-
tion was always greater than
that during short (~ 1.5 min),
individual exposures to simi-
lar levels, the difference
increasing with time and expo-
sure levels. This indicates
an increase in sensitivity of
both organs during continuous
exposure. Blinking frequency
began increasing at 0.17 ppm,
was significant at 0.26 ppm, and
continued increasing. A sig-
nificant decrease (~ 25%) in
respiratory frequency by 0.6 ppm,
with other changes such as ir-
regularity in depth and elongated
expiration.
Weber-
Tschopp
et al.
(1977)
A-14
(continued)
-------
TABLE IV-1. (continued)
Compound(s) and
Concentration^ )
in mg/m3 (ppm)
Acrolein
1.2
(0.5)
Mode of
Exposure
Eye ex-
posure
only,
through
snugly
fitting
goggles
No. of No. of
Test Subjects Controls
13-20 M+F Served
as own
controls ,
for the
5 min
before
exposure
Duration and Total
Frequency of Length of
Exposure Experiment
5 or 12 min,
each repeated
4 or 8 times,
with various
members of the
group
Effects
For 12-min exposures, 30 of 33
exposures (91%) caused eye irri-
tation (medium or severe). For
5-min dynamic exposures with 4
repetitions, 7 of 36 exposures
(19%) caused eye irritation.
For 5-min static exposures with
8 repetitions, 25 of 72 expo-
sures (35%) caused eye irritation.
Reference
and Rating
Stephens et al
(1961)
B-8
(continued)
oo
-------
TABLE IV-1. (continued)
Compound(s) and
Concentration(s)
in mg/m3 (ppm)
id
i)
Mode of
Exposure
No. of
Test Subjects
No.
of
Cont ro 1 s
Duration and
Frequency of
Exposu re
Total
Length of
Experiment
Effects
Reference
and Rating
Acrolei n 1.2
(0.5)
Eye ex-
posure
only
4 M
2 F
Served
a s own
controls
5 mi n
24 h
00
U)
pll of the tear fluid decreased in
3/6 and stayed the same in 3/6
(avg. ~ 7.1 before and ~ 6.9
after); tear volume increased Jn
3/6 and decreased in 3/6 (avg.
~ 6.5 pL/5 min before and ~ 7.5
after); lysozyme activity (volume/
min) in the tear fluid increased
in 3/6 and decreased in 3/6 (avg.
showing an overall slight de-
crease); lysozyme activity (con-
centration) decreased slightly
overall.
1-24 h after exposure: significant
decrease in avg. pll of the te,ir
fluid (avg. ~ 6.8) by 2 h, then
increase to near normal value by
24 h; significant increases in
avg. tear volume by 2 h (~ 11 |JL/
5 min) and 8 h (~ 13 [JL/5 min),
then decrease by 24 h but still
above normal; avg. lysozyme activ-
ity (volume/min) increased at 2
and 5 h, was significantly in-
creased at 8 h (~ 27 Mg/mitl vs •
~ 18 pg/min), then slight decrease
at 24 h though still above normal;
avg. lysozyme concentration de-
creased for 8 h, then increased
towards normal levels. Individual
differences were seen at all
times for all parameters.
Harada
(1977)
B-8
(continued)
-------
TABLE IV-1. (continued)
Compound(s) and Duration and
Concentration(s) Mode of No. of No. of Frequency of
in mg/m3 (ppm) Exposure Test Subjects Controls Exposure
Acrolein Climatic 17 M Served 7.5 min;
1.05 chamber 25 F as own 5 x 1.5-min
(0.45) controls exposures at
8-min inter-
vals
Acrolein Inhala- 10
Oo 1 tion
**
Acrolein Inhala-
0.8-1.0 tion
Acrolein 3, with Served 5 min,
0.8-0.83 odor as own during
thresholds controls min 10-15
of 0.8-0.9 of the expt.
mg/m3
Acrolein Eye 9 M, 2 min
0.82 exposure 20-23-y-old
(0.35) only
Arrolein Inhala- 10
0.8 tion
Total
Length of
Experiment Effects
39.5 min Subjective air quality and the
desire to leave the room equal to
that of intermittent exposure to
lower levels and continuous, ris-
ing exposure to 0.45 ppm. Very
slight eye and nose irritation,
equal to that of intermittent,
lower exposures and well below
that of continuous, rising ex-
posures to 0.45 ppm.
Slight irritation of the con-
junctiva and a stinging sensation
in the nose.
No effect on respiration frequency
or amplitude (as measured by a
pneumograph) ; although the sub-
stance was clearly perceived by
the subjects.
90 min Increased eye sensitivity to
light during exposure, with re-
covery to normal, fresh air values
by 60 min.
Concentration at which 70% of the
subjects sensed eye irritation.
Minimum odor perceived by 9/10.
Reference
and Rating
Weber-
Tschopp
et al.
(1977)
A-14
Plotnikova
(1960)
A-9
Plotnikova
(1960)
A-9
Plotnikova
(1960)
A-9
Mizoguchi
et al.
(1972)
A-6
Plotnikova
(1960)
A-9
(ronti nued)
-------
TABLE IV-1. (continued)
00
Ul
Compound(s) and
Concentration(s)
in mg/ra3 (ppm)
Acrolein
0.7
(0.3)
Acrolein
0.7
(0.3)
Duration and Total
Mode of No. of No. of Frequency of Length of
Exposure Test Subjects Controls Exposure Experiment
Climatic 21 M Served 60 rain 60 min
chamber 25 F; as own
~ 31 used controls
for blinking
frequency and
16 for respira-
tory frequency
measurements
Climatic 17 M Served 7.5 min; 39.5 min
chamber 25 F as own 5 x 1.5-min
controls exposures at
8-min inter-
vals
Effects
Subjective air quality decreased
continuously for ~ 20 min, then
increased slightly. Eye, nose,
and throat irritation al] in-
creased for ~ 40 min, then leveled
off, the relative irritation de-
creasing in the order of organs
given. Increased blinking fre-
quency, correlated with eye irri-
tation. Significant decrease
(~ 20%) in respiratory frequency
by 40 min, remaining near that
level to the end. Occasional
irregularities in respiratory
depth and holding of breath.
Subjective air quality and the
desire to leave the room slightly
above values for intermittent ex-
posure to lower levels and above
those for continuous, rising
Re f erence
and Rating
Weber-
Tschopp
et al.
(1977)
A-14
Weber-
Tschopp
et al.
(1977)
A-14
exposure to 0.3 ppm. Almost no
eye or nose irritation, equal to
that at lower intermittent expo-
sure levels and well below that
during continuous, rising expo-
sure to 0.3 ppm.
Acrolein
0.6-0.65
3, with
odor
thresholds
of 0.8-0.9
mg/m3
Served
as own
controls
10 min,
during
min 10-15
and min
45-50 of
the expt.
90 min,
with a
10-min
pre-
exposure
peri od
Eye sensitivity to light increased
sharply during both exposures, and
decreased sharply at the end of
each exposure. Response was the
same as the control and fresh air
values by 60 min. The threshold
value for acrolein action on light
sens j tivity.
Plotnikova
(1960)
A-9
(continued)
-------
TABLE IV-1. (continued)
Compound(s) and
Concentration(s)
in mg/m3 (ppm)
Acrolein
0.5
Acrolein
0.49
(0.21)
Acrolein
0.35
(0.15)
Acrolein
0.33
(0.14)
Acrolein 0.23
(0.1)
Mode of No. of
Exposure Test Subjects
3, with
odor
thresholds
of 0.8-0.9
mg/m3
Odor test 4 trained
room odor analysts
Climatic 17 M
chamber 25 F
Eye 9 M,
exposure 20-23-y-old
only
Odor room, 4-6
8.9 m3
Duration and Total
No. of Frequency of Length of
Controls Exposure Experiment
Served 5 min, 90 min
as own during
controls min 10-15
of the
expt.
Served
as own
controls
Served 7.5 min; 39.5 min
as own 5 x 1.5-min
controls exposure at
8-rain inter-
vals
2 min
The minimum
time required
to make an
assessment
Effects
Subthreshold level of acrolein
action on eye sensitivity to light.
Lowest concentration at which all
the subjects positively recognized
the odor.
Increased annoyance (as measured
by subjective judgment of air
quality and desire to leave the
the room) compared to controls
and those exposed continuously
to < 0.15 ppm. Almost no eye
and nose irritation, below that
for continuous, rising exposure
to 0. 15 ppm.
Concentration at which 30% of the
subjects sensed eye irritation.
Odor threshold; level at which 50%
of the panelists detected the odor.
Reference
and Rating
Plotnikova
(1960)
A-9
Leonardos
et al.
(1969)
B-13
Weber-
Tschopp
et al.
(1977)
A-14
Mizoguchi
et al.
(1972)
A-6
Cormack
et al.
(1974)
A-8
(continued)
-------
TABLE TV-1. (concluded)
00
Comjiound(s) and
Concentration(s) Mode of No. of No. of
in mg/m3 (ppm) Exposure Test Subjects Controls
Acrolein
0. 14
Acrolein Loose- 26 H Served
°-14 fitting 10 F as own
(0.06) face controls
mask with
respirator,
so only the
eyes were
exposed
Acrolein 27,
0.078 "practically
healthy,"
18-35-y-old
Acrolein "Volunteers"
0.07
Acrolein
0.05
Acrolein
0.03
Duration and Total
Frequency of Length of
Exposure Experiment Effects
Odor threshold.
5 min 5 min On a scale of 0 (none) to 2
(severe), the avg. maximum degree
of eye irritation was 0.471. The
values for carbon-filtered air
were 0.088-0.361.
Threshold concentration for odor
detection for the most sensitive
people.
"Short-term" Odor threshold for sensitive sub-
jects.
Threshold concentration affecting
electrical activity of the cortex
of the brain.
Subthreshold level for electrical
activity of the cortex of the hu-
man brain.
Reference
and Rating
VanGemert
and
Nettenbreijer
(1977)
A--
Darley et al.
(1960)
C-10
IJbaidullaev
and
Abramova
(1976)
A-6
Sinkuvene
(1970)
B-8
Ubaidullaev
and Abramova
(1976)
A-6;
Sinkuvene
(1970)
B-8
Ubaidu i lacv
and
Abramova
(1976)
A-6
-------
SECTION V
OTHER HUMAN EXPOSURES
Only two occupational exposure studies were found. These are described
in Table V-l. Neither is useful due to the presence of confounding factors,
poor or no air measurements, and no controls.
No epidemiological studies of acrolein exposure were found.
Two case reports of accidental exposures to acrolein are described in
Table V-2. Because of the unknown and probably high levels of acrolein
involved, these are of little use in helping to determine a range of con-
cern for automotive emission of acrolein.
89
-------
TABLE V-l. STUDIES OF OCCUPATIONAL EXPOSURE TO ACROLEIN
Compounds and
Concentrations in
mg/m3 (ppm)
Population Group
Description
Exposed
Control
Effects
Remarks
Reference
and
Rating
HCHO and acrolein from
smoke developed from
cutting and sealing
polyethylene bags at
high temperatures
(presumably > 240°C) .
No concentrations
determined.
vo
O
Acrolein
(< 0.014 - < 0.04)
HCHO
(0.015 - 0.07)
CO
(< 1 - 15)
NO
TJ0.03 - 0.26)
SOZ
(< 0.01)
Total particulates
0.09 - 0.26
Four workers in two 8-h
shifts operated the
thermocutting and sealing
apparatus. One worker
nearby, sitting in the
draft, was less exposed.
Sometimes the remaining
workers also were ex-
posed.
> 5 F
Workers in the Run and
Service Building of the
Union Pacific Railroad
in Pocatello, Idaho.
Air measurements done
on April 9-10, 1972.
Medical evaluation
done on April 19-20,
1972.
90 H
in this
building;
27 M
in other
areas
(exposure
levels of
these men
not given)
Results of
a study of
10,000
industrial
workers
used for
comparison
to the
spirometry
test re-
sults
The 4 engaged in cutting and
sealing complained of symptoms
from skin and from the mucous
membranes of the eyes and
respiratory tract: burning
in the eyes, dryness and
irritation of the facial
and neck skin and less so
of the forearms. Heavy
smoke exposure produced
skin eruptions, especially
around the eyes. Drowsiness
and headache were noted at
the end of the day. The
worker sitting nearby com-
plained of same symptoms,
but lesser degree. All 5
workers gave a positive
response to a patch test
with a 40% aqueous HCHO
solution. When the other
workers in the room were
annoyed by the smoke, the
cutting operation was shut
down. The only ventila-
tion was via the windows,
which they were reluctant
to open in cold weather.
Workers and some of the men
taking air samples complained
of burning eyes. 31/114 were
classified as having symptoms
of bronchitis, as determined
by questionnaire. 12/114 had
abnormal spirograms (compared
to expected 7.2), not statis-
tically significant. No
pneumoconiotic lesions were
identified on chest x-ray.
The conclusion was that
excessive chronic respira-
tory disease probably did
not exist.
Essentially case reports
of exposure to small
amounts of smoke from
from cutting poly-
ethylene bags. No
measurements and no
follow-up after changes
in the ventilation
system.
Hovding
(1969)
D-4
Primarily a study of the
occurrence of the gases,
not a health effects
survey. For the pur-
poses of this study,
the effect of acrolein
is confounded by the
presence of several
other gases.
Apol
(1973)
D-5
-------
TABLE V-2. HUMANS —STUDIES OF ACCIDENTAL EXPOSURES TO ACROLEJN
Compounds and Duration
Concentrations in of
mg/m3 Exposure Accident Description
Acrolein not given
2 h
Inhaled the smoke from
an overheated frier.
Acrolein not given
(probably high)
Not given
(probably
very
short)
Worker in a chemical
factory. A rupture
sprayed acrolein in
his face.
No.
of
Victims
2 M
(4.5-
and 2-
y-old)
1 H,
39-y-old
Description
Reference
and
Rating
The 2-y-old was found dead. On hospitalizatlon 6 h later, Gosselin
the 4.5-y-old was somnolent and lightly cyanotic, with et al.
moderate respiratory difficulty. Oxygen therapy was ap- (1979)
plied 24 h after exposure, respiratory functions deteri- C-5
orated rapidly and the trachea was obstructed by a firm,
elastic substance. Death occurred quickly, due to
asphyxiation. On autopsy: total obstruction of the
trachea and bronchi by a thick mucus secretion, massive
cellular desquamation of the bronchial lining, and mul-
tiple pulmonary infarcts.
Immediately felt a burning in his face and eyelids. 20 h Champeix
later, presented subacute pulmonary syndrome with marked et al.
dyspnea, thoracic constriction, cough with frothy sputum, (1966)
and cyanosis. On hospitalization: pale, cyanotic, edema C-8
of the eyelids, sweating, intense dyspnea, very fast
respiration, cough with light red sputum, and pulmonary
edema. Treated with oxygen, antibiotics, and cortisone.
Left the hospital after 9 d, with a moderate cough and
light dyspnea. 2 mo later: moderate tracheal edema
and some blockage of the bronchial tube. 18 mo later:
general state good, some dyspnea on exertion, slight
opacities in the chest x-rays, and slightly increased
residual volume (respiratory) at rest. Eventually,
the subject presented signs of chronic broncho-
pneumopathy, with chronic bronchitis and emphysema.
-------
ANNOTATED BIBLIOGRAPHY
93
-------
6-046* Adamovich, G. G. , 0. V. Filippov, T N. Mikhailova, and Y. T.
Kozlova. 1977. Immunobiological Activity of Workers in Relation
to Length of Employment and Profession Under the Combined Effect
of Chlorobenzene, Acetone, Acrolein, and Glass-Fiber Dust.
Gigien. Aspekty Okhrany Zdorov'ya Naseleniya. 1977:107-108
(Russ).
D--.** This is a very brief discussion of the work described
in Lychagin et al. (1976).
6-047 Aerts, C., A. B. Tonnel, N. Dutriez, and C. Voisin. 1979. In
Vitro Sensitivity of Alveolar Macrophages to Gaseous Tobacco
Smoke Components. Colloq. - Inst. Natl. Sante Rech. Med. 84
(Lavage Broncho Alveolaire Homme):177-185 (Fre).
D-7. The acrolein data are the same as those given in Voisin et
al. (1979) [6-096] and Voisin et al. (1980) [6-099]. Studies
were also done with cigarette smoke which contained 0-0.1 mg
acrolein/unknown vol. Toxicity of the smoke appeared to be due
to N02, not acrolein.
6-123 AIHA, American Industrial Hygiene Association. 1963. Hygienic
Guide Series; Acrolein. American Industrial Hygiene Association,
Akron, Ohio. 2 pp.
C--. Brief review. The ACGIH recommends an 8-h maximum atmo-
spheric concentration of 0.5 ppm. However, it is suggested that
this may be too high by a fivefold factor.
6-001 Albin, T. B. 1962. Handling and Toxicology. In: Acrolein,
C. W. Smith, ed. John Wiley and Sons, Inc., New York, New York.
pp. 234-239.
C--. Good brief review for handling and personal safety, less
so for toxicology.
5-022 Altshuller, A. P. 1978. Assessment of the Contribution of Chem-
ical Species to the Eye Irritation Potential of Photochemical
Smog. J. Air Pollut. Control Assoc. 28(6):594-598.
D-8. A review and discussion of the results of several studies on
atmospheric samples or irradiated auto exhaust and hydrocarbon-
nitrogen oxide mixtures. The eye irritation on a moderately
smoggy day may be due 40% to HCHO and 25% to acrolein. Atmo-
spheric samples collected in California contained 30-66 ppb
HCHO and 6-7 ppb acrolein.
Numbers in the left margin are MRI acquisition numbers.
MRI rating system is described on pages 17-18.
94
-------
6-126 Amdur, M. 0. 1980. Air Pollutants. In: Toxicology, The Basic
Science of Poisons. 2nd ed. L. J. Casarett and J.Doull, Eds.
Macmillan Publishing Co., Inc., New York, New York. Chapter 24,
pp. 608-631.
C--. Brief review.
6-116 Apol, A. G. 1973. Health Hazard Evaluation/Toxicity Determina-
tion. Report 72-32-42; Union Pacific Railroad, Pocatello, Idaho.
PB-229 161, National Technical Information Service, U.S. Depart-
ment of Cmmerce, Springfield, VA. 23 pp.
D--. 117 workers were exposed to acrolein (0.014-0.04 ppm), HCHO
(0.015-0.07 ppm), CO (< 1-15 ppm), NO (0.03-0.26 ppm), S02
(< 0.01 ppm), and particulates (0.09-0.26 mg/m3). No excess of
chronic respiratory disease. Eye irritation and headaches re-
ported .
6-003 Aretinskii, B. V., S. V. Kazantseva, L. G. Fed'kina, Yu. A.
Potoskuev, N. V. Bochenina, L. E. Stepanova, A. N. Dudyreva, I. M.
Il'ina, and F. N. Gofina. 1971. Development of Silicosis under
the Effect of Quartz Dust and Diesel Exhaust Fumes on an Organism.
Tr. Tsentr. Nauchno-Issled. Proektn.-Konstr. Inst. Profil.
Pnevmokoniozov. Tekh. Bezop. Issue 5:100-110 (Russ).
D--. A more intense development of silicosis was observed in rats
that received 75 mg of quartz-containing dust once intratracheally
and then were subjected daily for 6 h for 90 d to poisoning by
diesel exhaust fumes (N oxides, 32-35 mg/m3; acrolein, 0.95-1.4
mg/m3).
5-191 Battista, S.P., and C. J. Kensler. 1970. Mucus Production and
Ciliary Transport Activity. In Vivo Studies Using the Chicken.
Arch. Environ. Health 20:326-338.
C-9. In vivo, a dose of 35-40 |Jg acrolein/40-mL puff (875-
1,000 mg/m3")for 8 puffs inhibited ciliary transport activity to
50% that of the tracheas of control hens. A log concentration-
percent inhibition curve for acrolein is given.
6-005 Beckner, J. S., P. M. Hudgins, and J. L. Egle, Jr. 1974. Effects
of Acetaldehyde, Propionaldehyde, Formaldehyde, and Acrolein on
Contractility, 14C-Norepinephrine and 45Calcium Binding in Iso-
lated Smooth Muscle. Res. Commun. Chem. Pathol. Pharmacol.
9(3):471-488.
D-16. Good , well-done pharmacology. Mechanisms of structural
congeners on isolated rat vas deferens and rabbit aorta (smooth
muscle). Does not help define inhalation exposure levels.
0.01 M HCHO and 0.001 M acrolein gave similar responses.
95
-------
6-140 Bittersohl, G. 1974. Epidemiologic Investigations on Cancer In-
cidence in Workers Contacted by Aldol and Other Aliphatic Alde-
hydes. Arch. Geschwulstforsch. 43(1):172-176 (Ger).
D--. MAC's for acrolein are 0.25 mg/m3 in the DDR, BRD, and USA
and 0.7 mg/m3 in the UdSSR.
6-006 Bouley, G. 1973. Effects of Atmospheric Pollutants on Health.
Econ. Med. Anim. 14(2):97-100 (Fre).
C-4. The exposure of animals (unclear whether rats or mice,
possibly both) to 0.5 ppm acrolein for varying lengths of time,
from 1 mo to the entire life span, caused decreasd growth and
decreased levels of liver redox coenzymes. No experimental de-
tails are given. Perhaps the same study reported in detail in
Bouley et al. (1975) [6-008].
6-008 Bouley, G. , A. Dubreuil, J. Godin, and C. Boudene. 1975. Toxic
Effects on Rats of a Continuous Inhalation of a Slight Dose of
Acrolein. Eur. J. Toxicol. Environ. Hyg. 8(5):291-297.
B-10. Exposure of rats to 0.55 ppm acrolein for up to 77 d caused
decreased weight gain and food consumption as long as the exposure
lasted. Hepatic and respiratory effects and an increase in sus-
ceptibility to respiratory infection occurred during the first
~ 3 weeks, then disappeared spontaneously although exposure
continued.
6-007 Bouley, G., A. Dubreuil, J. Godin, M. Boisset, and C. Boudene.
1976. Phenomena of Adaptation in Rats Continuously Exposed to
Low Concentrations of Acrolein. Ann. Occup. Hyg. 19(l):27-32.
B-10. An English translation of Bouley et al. (1975) [6-008].
6-119 Bridges, R. B., J. H. Kraal, L. J. T. Huang, and M. B. Chancellor.
1977. Effects of Cigarette Smoke Components on Ln Vitro Chemo-
taxis of Human Polymorphonuclear Leukocytes. Infection and
Immunity 16(1):240-248.
C-ll. The concentrations required in the liquid phase to reduce
the chemotactic responsiveness of PMN cultures by 50% of control
levels were:
cyanide 3.5 mM
sulfide 6.5 mM
acrolein 15 |jM
6-134 Brooks, S. M. , C. F. Reinhardt, F. N. Marzulli, R. C. Graham,
and J. Bender. 1981. Health Effects of Some Other Aldehydes.
In: Formaldehyde and Other Aldehydes. Committee on Aldehydes,
National Research Council. National Academy Press. Washington,
D.C. pp. 221-255.
96
-------
C--. Includes a review of acrolein toxicity through several
routes of exposure, including inhalation.
5-129 Carpenter, C. P., H. F. Smyth, and U. C. Pozzani. 1949. The
Assay of Acute Vapor Toxicity and the Grading and Interpretatjon
of Results on 96 Chemical Compounds. J. Ind. Hyg. Toxicol.
31:343-346.
D-5. Study to develop a toxicity screening method. 250 ppm HCHO
or 8 ppm acrolein for 4 h killed 2-4 of 6 albino rats.
6-120 Carson, S., R. Goldhamer, and M. S. Weinberg. 1966. Character-
ization of Physical, Chemical, and Biological Properties of Mucus
in the Intact Animal. Ann. N. Y. Acad. Sci. 130:935-943.
D--. Primarily a discussion of the effects of cigarette smoke.
Included a statement that acrolein was most effective of several
respiratory irritants in reducing mucus flow rates in cats after
short-term inhalation exposures.
6-010 Catilina, P., L. Thieblot, and J. Champeix. 1966a. A Trial
Treatment of Respiratory Diseases Induced Experimentally in the
Rat by Inhalation of Acrolein. Arch. Mai. Prof. 27(10):797-803
(Fre).
C-6. All of the 5 rats exposed to 1,000 mg acrolein/m3 for 10 min
died within 4 d of acute asphyxia. On autopsy, blocking of the
airways by membranes, pulmonary hemorrhages and infarctions, and
obstruction of the fine bronchioles by mucus and pus were noted.
When followed by repeated treatment with Dexamethasone and/or
Oxolamine, mortality was reduced.
6-095 Catilina, P., L. Thieblot, and J. Champeix. 1966b. Experimental
Respiratory Lesions in Rats from Acrolein Inhalatin. Arch. Mai.
Prof. 27(12):857-867 (Fre).
C-10. Detailed description of the anatomical and histopatholog-
ical changes in rats following 10-min exposures to high levels of
acrolein (> 600 mg/m3). A more complete report of the experiments
and results also given in Catilina et al. (1970) [6-009].
6-009 Catilina, P., J. Champeix, and G. Andraud. 1970. Experimental
Study of Pulmonary Toxic Substances. The Example of Acrolein.
Poumon Coeur 26(8):867-876 (Fre).
C-9. A detailed description of the pathological changes in rats
exposed to high levels of acrolein for 10 min: persistent
bradypnea; destruction of epithelia; intense edema of the trachea,
glottis, and bronchi; and congestion, hemorrhage, and infarction
in the lung. 800 mg/m3 (LC65) and 750 mg/m3 (LC50) were fatal
in 4 or 6-8 d, respectively. 650-700 mg/m3 caused more delayed
death.
97
-------
5-378 Chaigneau, M. 1980. Classification of Harmful Gases. Ann.
Anesthesiol. Fr. 21(6):683-688 (Fre).
D--. Very brief reviews (with no references) of the toxicity of
several gases, including HCHO. Acrolein is mentioned as being
lethal in < 10 rain at 30-100 ppm.
6-113 Champeix, J., and P. Catilina. 1967. Acrolein Poisoning. Masson
et Cie, Paris, France (Fre).
C--. Same animal experimental information given in Catilina et
al. (1970) [6-009], Catalina et al. (1966a) [6-010], and Catilina
et al. (1966b) [6-095]. Also includes reviews of properties,
sources, analysis methods, prevention, therapy, and human exposure.
6-011 Champeix, J., L. Courtial, E. Perche, and P. Catalina. 1966.
Acute Broncho-Pneumopathy from Acrolein Vapors. Arch. Mai. Prof.
27(10):794-796 (Fre).
C-8. Case history of a man accidentally exposed to an unknown
(probably high) level of acrolein for a short time. Within 20 h
he was hospitalized with cough, frothy sputum, cyanosis, and a
feeling of thoracic constriction. He developed extreme pallor
and cyanosis, edema of the eyelids, intense dyspnea, and accel-
erated breathing. He was released 9 d later, with light cough
and dyspnea. 18 mo later, dyspnea on exertion and slight opaci-
ties in the chest X-rays still existed.
5-220 Criteria for Community Air Quality Committee. 1968. Community
Air Quality Guides. Aldehydes. Am. Ind. Hyg. Assoc. J.
28(5):505-512.
C--. The toxicology and ambient concentrations of specific alde-
hydes including HCHO and acrolein were reviewed. In automobile
exhaust, ~ 70 mol-% of the carbonyl compounds, which are mainly
aldehydes, is HCHO. Acrolein and acetaldehyde comprise 3-10 mol-%.
Avg. U.S. urban air concentrations are 0.06 ppm HCHO (~ 0.09 mg/m3)
and 0.006 ppm acrolein (~ 0.014 mg/m3). Recommended levels (caus-
ing no sensory irritation) are 0.1 ppm HCHO, 0.01 ppm acrolein,
and 0.2 ppm total aldehyde as HCHO.
6-013 Dahlgren, S., and T. Dalhman. 1966. The Effect of Oxolamine
Citrate on Experimentally Produced Inflammation in the Respira-
tory Organs. ACTA Pharmacol. Toxicol. 24(2-3):286-296.
D-9. Respiratory tract irritation in guinea pigs was induced by
a 10-min inhalation of an aerosol of a 250 ppm acrolein solution.
Those animals receiving only treatment with NaCl showed fairly
severe macroscopic changes in the pulmonary parenchyma indicating
inflammation. Treatment with anti-inflammatory drugs decreased
the level of inflammation.
98
-------
6-014 Dahlgren, S. E., and T. Dalhamn. 1972. Antiinflammatory Action
of Phenyl-Methyl-Oxadiazole (PMO): An Experimental Study on the
Guinea Pig Trachea. Acta Pharmacol. Toxicol. 31(3):193-202.
D-9. Tracheal inflammation of the acute desquamating type was
induced in guinea pigs by a 5-min inhalation of an aerosol of a
5% acrolein solution. Immediate, continuing treatment with PMO
(orally or intraperitoneally administered) for 72 h significantly
reduced the inflammation.
6-012 Dalgren, S. E., H. Dalen, and T. Dalhamn. 1972. Ultrastructural
Observations on Chemically Induced Inflammation in Guinea Pig
Trachea. Virchows Arch. Abt. B Zellpathol. 11(3):211-223.
D-7. The tracheal epithelium of guinea pigs was examined by light
and electron microscopy 72 h after exposure to a 5% acrolein aero-
sol for 5 min. A great variation in the degree of epithelial
damage was seen. Damage included loss of cilia, thick layers of
heterophil granulocytes, altered organelles, and cytoplasmic
vacuoles.
5-228 Dalhamn, T. , and A. Rosengren. 1971. Effect of Different Alde-
hydes on Tracheal Mucosa. Arch. Otolaryngol. 93(5):496-500.
C-5. A study of rabbit tracheal tissue showed that HCHO appeared
to be the most ciliotoxic, followed by acetaldehyde and acrolein.
The experiments largely confirmed the results of other authors.
Acrolein was tested over the range of 31.2 to 247.8 mg/m3, caus-
ing ciliostasis in ~ 36 and ~ 6 min, respectively.
6-111 Darley, E. F., J. T. Middleton, and M. S. Garber. I960. Plant
Damage and Eye Irritation from Ozone-Hydrocarbon Reactions. J.
Agric. Food Chem. 8(6):483-485.
C-10. Exposure of only the eyes to 0.06-2.3 ppm acrolein for 5 min
caused very slight to strong irritation.
5-230 Davis, T. R. A., S. P. Battista, and C. J. Kensler. 1965. Effect
of Cigarette Smoke, Acrolein and Formaldehyde on Pulmonary Func-
tion. Fed. Proc. 24(2, Part I):518.
C-5. An abstract of work in Davis et al. (1964) [5-131]. Expo-
sure of both tracheotomized and intact guinea pigs to 17 ppm
acrolein or 50 ppm HCHO, with effect on lung function only in
intact animals.
5-131 Davis, T. R. A., S. P. Battista, and C. J. Kensler. 1967. Mech-
anism of Respiratory Effects During Exposure of Guinea Pigs to
Irritants. Arch. Environ. Health 15:412-419.
99
-------
C-6. Exposure of guinea pigs to HCHO and acrolein using both
tracheotomized and intact animals. Effect on lung function only
in intact animals.
6-015 Denine, E. P. 1971. A Histologic Assessment of the Effects of
Acrolein Inhalation on the Replacement of Mechanically Denuded
Tracheal Epithelium. Ph.D. Dissertation. University Microfilms
International, A Xerox Company, Ann Arbor, Michigan.
C-12. Exposure to 200 ppm acrolein for 5 min/d, up to 2-7 d,
caused ciliary loss and an inflammatory response in intact chick-
ens, and retarded cilia regeneration in chickens with mechanically
denuded tracheas. Similar exposure to 50 ppm caused less severe
changes in intact animals and had no effect on regeneration.
6-016 Denine, E. P., S. L. Robbins, and C. J. Kensler, 1971. The Ef-
fects of Acrolein Inhalation on the Tracheal Mucosa of the Chicken.
Toxicol. Appl. Pharmacol. 19(2):416.
D-4. Whole chickens exposed to 50 or 200 ppm acrolein through an
endotracheal cannula for 1-27 d (5 min/d) showed changes in the
tracheal mucosa increasing with exposure time and concentration.
Only an abstract of work, so few experimental details are given.
High levels are studied.
6-132 ECAO, Environmental Criteria and Assessment Office. 1980. Ambi-
ent Water Quality Criteria for Acrolein. PB81-117277, National
Technical Information Service, U.S. Department of Commerce,
Springfield, VA. 99 pp.
C--. The review of the literature included inhalation exposures.
Several new documents were acquired based on its bibliography.
5-005 Egle, J. L. 1972. Retention of Inhaled Formaldehyde, Propion-
aldehyde, and Acrolein in the Dog. Arch. Environ. Health
25:119-124.
D-9. Anesthetized dogs were exposed to 0.15-0.35 (Jg HCHO/mL or
0.4-0.6 |Jg acrolein/ml. Retention of HCHO in the total respira-
tory tract was nearly 100%; upper tract retention alone exceeded
95%. Retention of acrolein on the total respiratory tract was
81-84%, upper tract retention was 75-80%. Variations in concen-
tration, ventilatory rate, or tidal volume had little effect on
retention of the chemicals.
5-183 Egle, J. L., and P. M. Hudgins. 1974. Dose Dependent Sympatho-
mimetic and Cardioinhibitory Effect of Acrolein and Formaldehyde
in the Anesthetized Rat. Toxicol. Appl. Pharmacol. 28:358-366.
100
-------
D-6. Primarily a study of i.v. exposure. Anesthetized rats were
exposed by inhalation for 1 min to 0.01-5.00 (Jg acrolein/mL. As
concentration increased a pressor effect of increasing magnitude
was observed. Cardioinhibitory concentrations up to 2.50 and
5.00 pg/mL. HCHO concentrations up to 2.0 (Jg/mL did not produce
any significant cardiovascular effects.
5-174 Fassett, D. W. 1963. Aldehydes and Acetals. In: Industrial
Hygiene and Toxicology, 2nd revised ed. F. A. Patty, D. W.
Fassett, and D. D. Irish, Eds. Interscience Publishers, New York,
New York. Vol. 2, pp. 1959-1989.
C--. Contains little information specifically about acrolein.
The 30-min LCso for acrolein in rats was 130 ppm.
6-052 Feron, V. J., and A. Kruysse. 1977. Effects of Exposure to Acro-
lein Vapor in Hamsters Simultaneously Treated with Benzo(a)pyrene
or Diethylnitrosamine. J. Toxicol. Environ. Health 3(3):379-394.
B-13. Exposure of hamsters to 4 ppm acrolein 7 h/d, 5 d/wk, for
52 wk caused slightly decreased body weights, increased nasal
lesions, and no respiratory tract tumors. Co-exposure to
benzo(a)pyrene caused slightly increased tumor incidence and to
diethylnitrosamine caused no increase. A very good study, with
good control groups. Numbers too small for use as a study on
the carcinogenicity of acrolein.
6-053 Feron, V. J., A. Kruysse, H. P. Til, and H. R. Immel. 1978. Re-
peated Exposure to Acrolein Vapour: Subacute Studies in Hamsters,
Rats and Rabbits. Toxicology 9(1-2):47-58.
B-13. A good study; rats, hamsters, and rabbits were exposed to
0, 0.4, 1.4, or 4.9 ppm acrolein for 6 h/d, 5 d/wk, for 13 wk.
Irritation, decreased growth, and histopathological changes oc-
curred in all species at the higher levels. At 0.4 ppm, rats
showed abnormalities, but the other species seemed unaffected.
6-054 Fischer, T. , A. Weber, and E. Grandjean. 1978. Air Pollution
Due to Tobacco Smoke in Restaurants. Int. Arch. Occup. Environ.
Health 41(4):267-280 (Ger).
D--. Levels of acrolein, CO, N02, and NO due to tobacco smoke
were determined in the air of five restaurants. The acrolein
values were 5 to 10 ppb. Because the threshold of irritation of
acrolein is 100 ppb, it was not considered further in this study.
6-056 Gosselin, B., F. Wattel, C. Chopin, P. Degand, J. C. Fruchart, D.
Van der Loo, and 0. Crasquin. 1979. Case of Acute Acrolein
Poisoning. Nouv. Presse Med. 8(30):2469-2472 (Fre).
101
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C-5. A 4.5-y-old boy was hospitalized with acute respiratory
failure following inhalation of the smoke (containing acrolein)
from an overheated frier for 2 h. Asphyxia developed after 24 h.
Tracheal destruction, massive cellular desquamation of the bron-
chial lining, and multiple pulmonary infarcts were found on
autopsy. A 2-y-old boy died before treatment.
6-104 Guillerm, R., R. Badre, and B. Vignon. 1961. Inhibitory Effects
of Tobacco Smoke on Epithelial Ciliary Activity and the Nature of
the Responsible Components. Bull. Acad. Nat. Med. (Paris) 145
(20-21):4l6-423 (Fre).
C-7. 140 mg acrolein/m3 (the level found in cigarette smoke)
caused the complete inhibition of tracheal ciliary activity in
12 min. A mixture of acrolein (140 mg/m3) and acetaldehyde
(2,150 mg/m3) caused cessation in 5.5 min, the same time as
whole smoke.
6-018 Guillerm, R., A. Saindelle, P. Faltot, and J. Hee. 1967. Activ-
ity of Cigarette Smoke and Some of its Constituents on the
Respiratory Resistance of Guinea Pigs. Arch. Int. Pharmacodyn.
Ther. 167(1):101-114 (Fre).
D-9. The threshold level of acrolein causing increased ventila-
tory resistance in paralyzed and artificially ventilated guinea
pigs was 19 ± 5 ppm. The level of acrolein measured in cigarette
(Gauloise) smoke was ~ 200 ppm. A mixture of ethanol and acro-
lein at the levels found in the smoke caused the same respiratory
changes as whole smoke.
6-105 Guillerm, R., J. Hee, M. Bourdin, H. Burnet, and G. Siou. 1974.
Contribution to the Determination of the TLV Concentration of
Acrolein. Cahiers INRS. No. 77:527-535 (Fre).
C-12. Groups of 50 rats were exposed to 1 or 2 ppm acrolein for
91 d. Changes in wt. gain, pulmonary resistance, hematology,
pulmonary surfactant, urinary vanillylmandelic acid, and lung
histology were reported for both levels.
6-019 Gumerov, N. K., and L. V. Virpsha. 1976. Physiological-Hygienic
Appraisal of Working Conditions on Experimental Machines in the
Construction of Main Pipelines. Gig. Tr. Okhr. Zdorov'ya Rab.
Neft. Neftekhim. Prom-sti. 9:19-22 (Russ).
D--. Operators of pipe-laying machines were exposed to 368°C,
95 dB of noise, and cabin air concentrations of CO, gaseous hydro-
carbons, and acrolein in concentrations of 3.8-70.6, 3.3-102.3,
and 8.5-20.5 mg/m3, respectively. Eight hours of work on this
machine raised the operator's skin temperature significantly,
prolonged the latent period of the visual motor reaction, and
decreased the tolerance of static effort.
102
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6-106 Gusev, M. I, A. I. Svechnikova, I. S. Dionov, M. D. Grebenskova,
and A. I. Golovnia. 1966. Determination of the Daily Average
Maximum Permissible Concentration of Acrolein in the Atmosphere.
Hyg. Sanit. 31(1-3):8-13.
B-9. A nice study. Exposure of rats for 24 or 61 d showed
1.52 mg/m3 to be a lethal dose (24 d), 0.51 mg/m3, a toxic dose;
and 0.15 mg/m3, a safe dose. A wide range of physiological and
biochemical parameters were considered. Recommends an avg. per-
missible concentration of 0.1 mg acrolein/m3.
6-057 Harada, M. 1977. Photochemical Smog and Tear Fluid. Effects
[of Smog] on pH, Volume, and Lysozyme Activity of Tear Fluid.
Nippon Ganka Gakkai Zasshi 81(3):275-286 (Japan).
B-8. Much methods development. Includes a short section on
5-min exposure to 0.5 ppm acrolein and the subsequent analysis
of tear fluid. Immediate changes occurred, but returned to near
normal by 24 h. Eye irritation due to smog is measured, and the
possible role of acrolein discussed.
6-020 Harke, H-P., A. Baars, B. Frahm, H. Peters, and C. Schultz. 1972.
The Problems of Passive Smoking: Concentration of Smoke Consti-
tuents in the Air of Large and Small Rooms as a Function of
Number of Cigarettes Smoked and Time. Int. Arch. Arbeitsmed.
29(4):323-339 (Ger).
C--. Concentrations of smoke constituents when 30 cigarettes
were smoked in 13 min in a 38.2 m3 room were 0.51 mg nicotine/m3,
0.46 mg acrolein/m3, 64 ppm CO, and 6.5 mg acetaldehyde/m3. When
5 cigarettes were smoked in 13 min in a 38.2 m3 room values were
0.06 mg nicotine/m3, 0.07 mg acrolein/m3, 11.5 ppm CO, and 1.3 mg
acetaldehyde/m3. When 150 cigarettes were smoked in 30 min in a
170 m3 room: 0.69 mg nicotine/m3, 0.38 mg acrolein/m3, 53 ppm CO,
and 4.2 mg acetaldehyde/m3.
6-058 Haroz, R. K., and L. Mattenberger-Kreber. 1977. Effect of Ciga-
rette Smoke on Macrophage Phagocytosis. In: Pulmonary Macrophage
and Epithelial Cells. ERDA Symp. Ser. Vol. 43. CONF 760927,
National Technical Information Service, U.S. Department of Com-
merce, Springfield, VA. pp. 36-57.
D-6. Method development paper. Only whole cigarette smoke tested.
Various components of smoke and their levels in mg per cigarette
were: HCN (272), NH3 (24), H2S (51), and acrolein (112). Acro-
lein did not appear to be implicated in the effect of whole smoke
on alveolar macrophage function.
6-021 Hartzell, G. E., S. C. Packham, F. D. Hileman, S. C. Israel,
M. L. Dickman, R. W. Mickelson, and R. C. Baldwin. 1976. Physio-
logical and Behavioral Responses to Fire Combustion Products. In:
Proc. 4th SPI Int. Cell. Plast. Conf. Nov 15-19, 1976. Technomic
Publishing Co., Inc., Westport, Connecticut, pp. 264-270.
103
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C-8. Various physiological and behavioral responses in rats dur-
ing acute exposure to combinations of CO, C02, and acrolein. The
addition of 20 ppm acrolein to 2,700 ppm CO appeared to increase
the time to incapacitation. Minimal data given.
6-059 Hartzell, G., S. C. Packham, F. D. Hileman, S. C. Israel, M. L.
Dickman, R. W. Mickelson, and R. C. Baldwin. 1977. Physiological
and Behavioral Responses to Fire Combustion Products. In: Tox-
icity and the Products of Combustion; Fire Retard. Chem. Assoc.
Annu. Meet, 4th, Washington, D.C., 1977. pp. 175-202.
C-8. Same information given in Hartzell et al. (1976) [6-021].
6-065 Heino, M. , R. Ketola, P. Makela, R. Makinen, R. Niemela, J.
Starck, and T. Partanen. 1978. Work Conditions and Health of
Locomotive Engineers: I. Noise, Vibration, Thermal Climate,
Diesel Exhaust Constituents, Ergonomics. Scand. J. Work Environ.
Health 4(Suppl. 3):3-l4.
D-7. Exposure data only, no health effects information. The
mean levels in the atmosphere of roundhouses and locomotive cabs
were: acrolein (0.03 and 0.01 ppm, respectively), HCHO (0.16 and
0.01), NO (0.13), and dust (1.99 and 0.38 mg/m3).
X
6-022 Horton, A. D., and M. R. Guerin. 1974. Determination of Acetal-
dehydes and Acrolein in the Gas Phase of Cigarette Smoke Using
Cryothermal Gas Chromatography. Tob. Sci. 176(4):45-48.
C—. An analytical methodology paper. Commercial and exptl.
cigarettes (including a little cigar and a marijuana cigarette)
contained 7-14 (Jg acrolein per puff.
5-140 Hovding, G. 1969. Occupational Dermatitis from Pyrolysis Prod-
ucts of Polythene. Acta Derm. Venereol. 49:147-149.
D-4. Case report of exposure to small amounts of smoke (presum-
ably containing HCHO and acrolein) from cutting polyethylene bags.
Symptoms of the skin and the mucous membranes of the eyes and
upper respiratory tract were described. No measurements and no
follow-up study after changes in the ventilation system.
6-066 IARC, International Agency for Research on Cancer. 1979. Mono-
graphs on the Evaluation of the Carcinogenic Risk of Chemicals
to Humans, Vol. 19, Some Monomers, Plastics and Synthetic Elasto-
mers, and Acrolein. World Health Organization, Geneva,
Switzerland, pp. 479-494.
C--. Authoritative review of properties, uses, occurrence, tox-
icity, mutagenicity, and carcinogenicity of acrolein. States
that the data are inadequate for an evaluation of carcinogenicity.
104
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1-0172 ILO, International Labor Office. 1970. Permissible Levels of
Toxic Substances in the Working Environment. Occupational Safety
and Health Series 20, International Labor Office, Geneva,
Switzerland, pp. 194-198.
C--. Maximum acceptable concentrations in Czechoslovakia:
Normal Short, Single Exposure
MAC (mg/m3) MAC (mg/m3)
Acrolein 0.5 1.0
NH3 40 80
HCHO 2 5
HCN 3 15
MeOH 100 500
H2S 30
6-097 Iwai, T. , K. Furui, A. Yoshida, and M. Tashiro. 1976. Measure-
ment of Irritating Odor from Direct Injection Diesel Engines and
Its Reduction Methods. In: 16th Int. Automob. Tech. Congr. Pap.
No. 2-11. Tokyo, Japan, pp. 93-99.
B-7. Increasing acrolein (1-20 ppm) and aldehyde levels in
diesel engine exhaust caused increasing eye and nose irritation
in humans.
5-142 Iwanoff, N. 1911. On Some Aldehydes of Practical Importance.
Arch. Hyg. 73:307-340 (Ger).
C-8. Acute exposure of cats to HCHO and acrolein. Study is of
interest but of limited value because of the high dose levels
used (> 260 mg HCHO/m3 and > 25 mg acrolein/m3).
6-067 Iwasaki, K. 1979. Combustion Gas Toxicity of Textiles. Sangyo
Igaku 21(l):36-46 (Japan).
D—. Primarily a study of the combustion gases of different fab-
rics (gases contained trace to 500 ppm acrolein). Brief (< 1 h)
exposure to 40 ppm acrolein caused decreased wt. for several days
following exposure.
6-068 Jakab, G. J. 1977. Adverse Effect of a Cigarette Smoke Component,
Acrolein, on Pulmonary Antibacterial Defenses and on Viral-
Bacterial Interactions in the Lung. Am. Rev. Respir. Dis.
115(l):33-38.
C-12. Exposure of mice to 1-2 ppm acrolein for 24 h, following
brief bacterial exposure, suppressed pulmonary bactericidal mech-
anisms, the extent varying with the type of bacteria. The same
exposure of mice already compromised by viral pneumonitis caused
an even greater suppression of intrapulmonary bactericidal activ-
ity, proliferation of one bacteria occurring. A synergistic in-
teraction between viral infection and acrolein exposure occurred.
Results suggest a possible increase in frequency and severity of
pulmonary infections following acrolein exposure.
105
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6-024 Jermini, C., and A. Weber. 1975. Air Pollution by Cigarette
Smoke. Soz.-Praeventivmed. 20(5):213 (Ger).
C--. Smoking 10 tobacco cigarettes in a 30 m3 room produced the
following concentrations of irritating substances: acrolein,
0.120 ppm; HCHO, 0.450 ppm; CO, 24 ppm; and NO, 0.678. The
corresponding MAC's are 0.1, 2, 50, and 25 ppm, respectively.
5-208 Jermini, C. , A. Weber, and E. Grandjean. 1976. Quantitative
Determination of Various Gas-Phase Components of the Side-Stream
Smoke of Cigarettes in the Room Air as a Contribution to the
Problem of Passive-Smoking. Int. Arch. Occup. Environ. Health
36(3):169-181 (Ger).
D--. An unventilated 30 m3 room in which 30 cigarettes were
smoked contained 0.37 ppm acrolein. The unpolluted air in the
room contained 0.036 ppm HCHO and 0.06 ppm HCHO after one ciga-
rette was smoked. Other components were also measured.
5-010 Kane, L., and Y. Alarie. 1977. Sensory Irritation to Formalde-
hyde and Acrolein During Single and Repeated Exposures in Mice.
Am. Ind. Hyg. Assoc. J. 38:509-522.
B-12. Mice exposed to low levels of HCHO and acrolein in single
and repeated acute exposures with decreases in respiration rate.
Kane and Alarie recommend a TLV of 0.03 to 0.3 ppm HCHO, and
accept the TLV of 0.1 ppm acrolein.
6-069 Kane, L. E., and Y. Alarie. 1978. Evaluation of Sensory Irrita-
tion from Acrolein-Formaldehyde Mixtures. Am. Ind. Hyg. Assoc.
J. 39(4):270-274.
B-10. A mathematical model applied to the data on the effects of
acrolein and HCHO, alone and in 11 combinations, on the respira-
tory rate of mice indicates that competitive agonism exists be-
tween acrolein and HCHO when both are present.
6-070 Kane, L. E., and Y. Alarie. 1979. Interactions of Sulfur Dioxide
and Acrolein as Sensory Irritants. Toxicol. Appl. Pharmacol.
48(2):305-316.
D-ll. A study of mice exposed to mixtures of S02 (9-140 ppm) and
acrolein (0.85-3.4 ppm). The results indicate the S02 can inac-
tivate the effects of acrolein, and that a second sensory irri-
tation occurs at the termination of exposure expressed as a
post-exposure decrease in respiratory rate.
3-134 Kane, L. E., G. S. Barrow, and Y. Alarie. 1979. A Short-Term
Test to Predict Acceptable Levels of Exposure to Airborne Sensory
Irritants. Am. Ind. Hyg. Assoc. J. 40(3):207-229.
106
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C-6. A discussion using the previous results of a short-term
test with mice (effect on respiratory rate) to recommend exposure
levels for many gases. Recommended highest concentrations for
Air Quality Standards are: 0.002 ppm, acrolein; 0.3 ppm, NH3;
and 0.003 ppm HCHO. A TLV for acrolein in the range of
0.02-0.2 ppm is recommended.
6-026 Kantemirova, A. E. 1975. Illness with Temporary Work Disability
in Workers Engaged in Acrolein and Methylmercaptopropionaldehyde
(MMP) production. Tr. Volgogr. Cos. Med. Inst. 26(4):79-85
(Russ).
D--. Workers in the title industry were exposed to HCHO (0.05-
8.1mg/m3), acrolein (0.1-8.2 mg/m3), MeCHO (0.48-22 mg/m3),
methyl mercaptan (0.003-5.6 mg/m3), and MMP (0.1-6.0 mg/m3).
Women working for < 1 or > 7 y had the most catarrhal diseases
and the highest sick rates.
6-103 Kensler, C. J. , and S. P. Battista. 1963. Components of Ciga-
rette Smoke with Ciliary Depressant Activity. New Eng. J. Med.
269(22):1161-1166.
D-10. Ciliary transport rate of tracer particles in excised
tracheal tissue was reduced 50% following exposure to 8 puffs
containing 50 |Jg acrolein each. Requires major extrapolations
to an in vivo exposure, but is a good mechanism for comparing
compounds:
8 puff ED50
Gas (|jg/puff)
HCN 20
HCHO 6
NH3 70
Acrolein 50
Acetaldehyde 1,300
5-367 Kettner, H. 1978. Indoor Contamination by Chemical Substances
of Daily Use and Their Hygienic Significance. In: Org.
Verunreinig. Umwelt: Erkennen, Bewerten, Vermidern, K. Aurand,
V. Haesselbarth, E. Lahmann, G. Muller, and W. Neimitz, Eds.
Erich Schmidt Verlag, Berlin, Germany, pp. 448-453 (Ger).
C--. Maximum allowable indoor air levels in the USSR:
Acrolein 0.1 mg/m3
NH3 0.2
HCN 0.002
HCHO 0.01
MeOH 0.5
107
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5-072 Kilburn, K. H., and W. N. McKenzie. 1978. Leukocyte Recruitment
to Airways by Aldehyde-Carbon Combinations that Mimic Cigarette
Smoke. Lab. Invest. 38(2):134-142.
B-ll. Exposure of hamsters to HCHO and acrolein, alone and with
carbon particles. Effect only from the combination of two and
very high levels of HCHO. Significant in relation to exhaust
mixtures, especially diesel.
6-027 Kishi, M. , S. Satoh, H. Tsuchiya, Y. Horiguchi, and Y. Wada.
1975. Effects of Inhalation of the Vapor from Heated Edible Oil
on the Circulatory and Respiratory Systems in Rabbits. Shokuhin
Eiseigaku Zasshi 16(5):318-323 (Japan).
C-8. Primarily a study of the effects of the vapors of heated
oil on rabbits. Vapors contained up to 200 ppm acrolein, which
apparently was the cause of the changes reported. Exposure to 9
or 12 ppm acrolein alone for ~ 5 min cause respiratory, heart
rate, and blood pressure changes only at the higher level. Few
experimental details of these studies given.
5-353 LaBelle, C. W., J. E. Long, and E. E. Christofano. 1955. Syner-
gistic Effects of Aerosols. Particulates as Carriers of Toxic
Vapors. A. M. A. Arch. Ind. Health 11:297-304.
C-6. Acute exposure of mice to HCHO and acrolein in combination
with various aerosols. In general, aerosols increased the tox-
icity of HCHO and had no effect on acrolein.
6-071 Le Bouffant, L., J. C. Martin, H. Daniel, J. P. Henin, and C.
Normand. 1980. Action of Intensive Cigarette Smoke Inhalations
on the Rat Lung: Role of Particulate and Gaseous Cofactors. J.
Natl. Cancer. Inst. 64(2):273-284.
D-7. A comparison of the effects of chronic exposure to high
doses of cigarette smoke alone or in combination with coal dust
or acrolein (level not given). The acrolein alone caused dyspnea
and hypersecretion of mucus, with eventual adaptation, and had no
effect on body wt.
6-072 Leffingwell, C. M. , and R. B. Low. 1979. Cigarette Smoke Com-
ponents and Alveolar Macrophage Protein Synthesis. Arch. Environ.
Health 34(2):97-102.
D-ll. A comparison of the effects of acrolein (in solution) and
aqueous cigarette smoke extracts on amino acid incorporation into
protein by rabbit pulmonary alveolar macrophages. At 6 pg/mL in-
hibition begain in ~ 1 h. The 60-min EC5o was 5.5 |Jg/mL, about
four times the amount in the level of cigarette smoke (aqueous
extract) causing 50% inhibition.
108
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3-059 Leonardos, G., D. Kendall, and N. Barnard. 1969. Odor Threshold
Determinations of 53 Odorant Chemicals. J. Air Pollut. Control
Assoc. 19:91-95.
A-ll. Definitive paper on the subject. Odor recognition thresh-
olds were (ppm):
Acrolein 0.21
NH3 46.8
HCHO 1.0
H2S (from Na2S) 0.0047
H2S gas 0.00047
Methanol 100.0
6-075 Low, R. B., and C. A. Bulman. 1977. Substrate Transport by the
Pulmonary Alveolar Macrophage: Effects of Smoke Components. Am.
Rev. Respir. Dis. 116(3):423-432.
D-10. A mechanism study. The incubation of rabbit pulmonary
alveolar macrophages with 0.6-60.0 |Jg acrolein/flask (vol. not
given) for 1 h caused some inhibition of the transport of
a-aminoisobutyrate, inhibition of cycloleucine transport at the
longer exposure times and higher acrolein concentrations, and no
effect on the transport of 3-0-methyl-D-glucose.
6-077 Low, E. S., R. B. Low, and G. M. Green. 1977. Correlated Effects
of Cigarette Smoke Components on Alveolar Macrophage Adenosine
Triphosphatase Activity and Phagocytosis. Am. Rev. Respir. Dis.
115(6 part 1):963-970.
D-10. A mechanism study. The incubation of rabbit lung alveolar
macrophages with acrolein (3.45 \ig/mL in solution) caused a 10%
decrease in Ca-ATPase activity and a ~ 50% decrease in phagocytic
ability and cell adhesion.
6-028 Lychagin, V. V., G. G. Adamovich, T. N. Mikhailova, Yu. G. Kozlova,
Zh. V. Kinzhibalova, and O.V. Filippov. 1976. Assessment of Im-
munological Reactivity in Workers of Glass Insulation and Enamel-
ling Departments in a Cable Plant. Gig. Tr. Prof. Zabol.
No. 11:24-26 (Russ).
D--. In a cable plant, female workers were exposed in the insu-
lation department to acrolein (0.1-1.0 mg/m3), chlorobenzene,
acetone, and glass fiber dust, and in the enameling department
to acrolein (0.4-3.2 mg/m3), chlorobenzene, and phenol. The
respiratory, infectious, and immunological changes, seen more
often in the insulation workers, were ascribed to the glass fiber
dust and acetone.
6-029 Lyon, J. P., L. J. Jenkins, R. A. Jones, R. A. Coon, and J.
Siegel. 1970. Repeated and Continuous Exposure of Laboratory
Animals to Acrolein. Toxicol. Appl. Pharmacol. 17:726-732.
109
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B-12. Good study of the exposure of rats, guinea pigs, dogs, and
monkeys to 0.21-3.7 ppm for 8 h/d, 5 d/wk, for 6 wk, or contin-
uously for 90 d. Only slight changes seen in most species at the
lowest levels tested (0.22 and 0.7 ppm).
6-114 Masek, V. 1972. Aldehydes in the Air in Coal and Pitch Coking
Plants. Staub-Reinhalt Luft. 32(8):335-336 (Ger).
D--. The maximum HCHO concentration measured was 1.972 mg/m3,
and the maximum acrolein level was 0.611 mg/m3.
•
6-031 Meerson, E. A. 1975. Job Classification of Instrument Operators
in Relation to Automatization. Tr. Volgogr. Gos. Med. Inst.
26(4):11-16 (Russ).
D--. The frequencies of heart contractions, gas exchange, and
energy consumption were measured in four groups of plant per-
sonnel engaged in the production of S-containing compounds and
exposed to acrolein, CH3SH, CS2, methylmercaptopropionaldehyde,
methionine, Altax, Captax, thiuram E, and thiuram D. The groups
were divided into extent of automation of their work, but concen-
trations of the compounds to which the groups were exposed were
not given.
6-032 Mizoguchi, I., K. Makino, Y. Sato, M. Ohsawa, M. Chigusa, and H.
Yagyu. 1972. Experimental Studies on Eye Irritation Due to
Photochemical Smog. Tokyo Toritsu Eisei Kenkyusho Kenkyu Nempo
23:309-313 (Japan); English translation available from John Crerar
Library, Chicago, Illinois. Order No. 73-14686-06F.
A-6. Good data for a threshold for eye irritation of
0.14-0.35 ppm acrolein.
6-108 Munsch, N. , A. M. de Recondo, and C. Frayssinet. 1973. Effects
of Acrolein on DNA Synthesis In Vitro. F. E. B. S. Letters
30(3):286-290.
D-9. Acrolein at high levels (^ 0.002 M) inhibited the action of
partially purified regenerating rat liver DNA polymerase. Acti-
vation occurred at lower acrolein levels.
6-033 Murphy, S. D. 1965y. Mechanism of the Effect of Acrolein on Rat
Liver Enzymes. Toxicol. Appl. Pharmacol. 7(6):833-843.
D-9. Both the intraperitoneal injection (1-6 mg/kg) and the in-
halation (8 ppm) of acrolein caused increased liver enzyme activ-
ity. For i.p. exposure, a dose-response relationship was found
and the enzyme increases were much smaller when the animals were
pretreated with protein synthesis inhibitors. An overly sophis-
ticated study of local irritation after intraperitoneal injection.
110
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6-117 Murphy, S. D., D. A. Klirigshirn, and C. Ulrich. 1963. Respira-
tory Response of Guinea Pigs During Acrolein Inhalation and Its
Modification by Drugs. J. Pharmacol. Exp. Ther. 141:79-83.
B-10. Guinea pigs exposed to 0.2, 0.4, 0.6, or 1.0 ppm acrolein
for 2 h had increased total respiratory resistance and tidal vol-
ume and decreased respiratory rate, the degree of change increas-
ing with increasing concentration. Treatment with one of several
different drugs during acrolein exposure entirely reversed the
increased respiratory resistance.
5-157 Murphy, S. D. , H. V. Davis, and V. L. Zaratzian. 1964. Bio-
chemical Effects in Rats from Irritating Air Contaminants.
Toxicol. Appl. Pharmacol. 6:520-528.
C-8. Study of effect of acrolein (1-4 ppm, 20-81 h) and HCHO
(18-h, 35 ppm) exposure on rat organ weight and alkaline phos-
phatase activity. The same values of concentration x time for
acrolein had different effects, the continous exposures to the
higher concentrations causing increased liver weight and enzyme
activity.
6-124 Newsome, J. R., V. Norman, and V. L. Zaratzian. 1965. Vapor
Phase Analysis of Cigarette Smoke. Tob. Sci. 9:102-110; or
Tobacco 161(4):24-32.
D--. Levels in tobacco smoke (|Jg/40 mL puff):
Unfiltered Filtered
Methanol 13 10
HCHO 4.1 3.6
Acrolein 8.2 7.9
HCN 32 29
H2S 3.4 3.1
NH3 12 13
5-352 NRC. National Research Council. Panel on Vapor-Phase Organic
Pollutants. 1976. Vapor-Phase Organic Pollutants. Volatile
Hydrocarbons and Oxidation Products. Printing and Publishing
Office, National Academy of Sciences, Washington, D.C. 411 pp.
C--. An authoritative, but brief, review of various aspects of
acrolein and HCHO health effects literature is included in ap-
propriate chapters of this book, which was used as a source of
additional pertinent original papers.
6-073 Patel, J. M., J. C. Wood, and K. C. Leibman. 1980. The Bio-
transformation of Allyl Alcohol and Acrolein in Rat Liver and
Lung Preparations. Drug Metab. Dispos. 8(5):305-308.
Ill
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D-8. An in vitro study of the metabolism of acrolein by different
lung and liver fractions, the mechanism and the end products
(acrylic acid or glycidaldehyde) varying with the preparation.
6-074 Patel, J. M., E. Ortiz, and K. C. Leibman. 1981. Selective In-
activation of Rat Liver Cytochrome P-450 and of NADPH-cytochrome
£ Reductase by Acrolein. Personal Communication.
D--. The addition of acrolein to rat liver microsomal prepara-
tions caused the conversion of 50% of the cytochrome P-450 to
cytochrome P-420, regardless of the acrolein concentration, and
the total inactivation of NADPH-cytochrome c_ reductase activity
in a concentration- and time-dependent manner.
1-0196 Pattle, R. , and H. Collumbine. 1956. Toxicity of Some Atmo-
spheric Pollutants. Br. Med. J. 2:913-916.
D-7. The exposure of mice, guinea pigs, and rabbits to 24.4 mg
acrolein/m3 for 6 h caused the death of ~ 50% in each species,
due to severe tranceobronchitis with pulmonary edema, consolida-
tion, congestion, and emphysema.
6-121 Philippin, C. L., E. Grandjean, and A. Gilgen. 1969. Physiolog-
ical Effect of Acrolein on the Mouse. Praeventivmedizin
14(5):317-318 (Fre).
C-8. A study of 6-h exposure of mice to 31, 61, 80, or 119 ppm
acrolein, and repeated exposure to 6, 15, 25, and 50 ppm. Deaths
occurred only at > 50 ppm exposures. Repeated exposure caused
decreased body weight gain and swimming endurance, and lung path-
ology indicating inflammation.
6-034 Pinigin, M. A. 1972. New Approaches to the Solution of Urgent
Problems in the Theory and Practice of Setting Hygienic Standards
for Harmful Substances. PB-220-229T, National Technical Informa-
tion Service, U.S. Department of Commerce, Springfield, VA.
30 pp.
D--. Data on animal mortality following acrolein inhalation were
used as one example illustrating the author's views on setting
hygienic standards.
6-088 Plotnikova, M. M. 1961. Basic Investigations for the Deter-
minations of the Limit of Allowable Acrolein Concentration in
Atmospheric Air. In: Limits of Allowable Concentrations of
Atmospheric Pollutants No. 4. V. A. Ryazonov, Ed., B. S. Levine,
translator. Office of Technical Services, U.S. Department of
Commerce, Washington, D.C. pp. 59-71.
A-9. Several threshold levels were determined:
112
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odor - 0.8 mg/m3
optical chronaxy - 1.75 mg/m3
respiratory amplitude and frequency - 1.5 mg/m3
reflex effect on eye sensitivity to light - 0.6 mg/m3
Author recommends a maximum single limit of allowable concentra-
tion in atmospheric air of 0.3 mg/m3.
6-098 Potts, W. J., T. S. Lederer, and J. F. Quast. 1978. A Study of
the Inhalation Toxicity of Smoke Produced Upon Pyrolysis and
Combustion of Polyethylene Foams. Part I. Laboratory Studies.
J. Combust. Toxicol. 5(4):408-433.
C-ll. The smoke from the pyrolysis (nonflaming) of polyethylene-
based materials was lethal to rats in the 48 h following a 30-min
exposure. Gasping, strong eye irritation, salivation, and loss
of coordination were observed during exposure. Authors believe
the toxicity was due to the presence of acrolein (19-98 ppm from
5 1 g samples). This belief was strengthened by a study on pure
acrolein giving a 30-min LC50 of 45-95 ppm.
6-110 Prentiss, A. 1937. Chemicals in War. McGraw Hill, New York,
New York. pp. 139-140.
C--. A review with a nice summary of high dose effects:
7 mg/m3 - severe irritation
50 mg/m3 - intolerable
350 mg/m3 - lethal in < 10 min
6-115 Protsenko, G. A., V. I. Danilov, A. N. Timchenko, A. V.
Nenartovich, V. I. Trubilko, and V. A. Sauchenkov. 1973. Work-
ing Conditions When Metals to Which Primer Has Been Applied Are
Welded Evaluated from the Health and Hygiene Aspect. Avtom.
Svarka 26(2):65-68.
D--. Levels of many gases were determined under several different
welding conditions: acrolein, 0.11-1.04 mg/m3; and HCHO, 0.31-
0.83 mg/m3.
5-195 Renzetti, N. , and R. Bryan. 1961. Atmospheric Sampling for
Aldehydes and Eye Irritation in Los Angeles Smog. J. Air Pollut.
Control Assoc. 11(9):421-424 and 427.
D-10. An attempt at correlating eye irritation and aldehyde lev-
els in smog. Total aldehydes ranged from 0.02 to 0.40 ppm; HCHO
from 0 to 0.13 ppm, and acrolein from 0.002 to 0.011 ppm. Good
correlation was found for a log-probit relationship with total
aldehydes, but the fit for HCHO was not as good.
113
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6-082 Retnev, V. M. , E. L. Sinitsyna, and V. N. Solov'ev. 1977.
Physiological-Hygienic Labor Aspects of Repair-Setup Workers in
the Machine Building Industry. Gig. Tr. Prof. Zabol. 5:46-47
(Russ).
D--. All exposures to acrolein (0-1.24 mg/m3) were confounded by
the presence of oil aerosols (0.5-39.5 mg/m3) and CO (4.8-
49.2 mg/m3) and sometimes by S02 (0-10.3 mg/m3) and alkaline
aerosols (< 0.5 mg/m3).
6-083 Richter, M. , and I. Erfurth. 1979. Gas Chromatographic Deter-
mination of Acrolein in its Original State in the Main Stream
Smoke of Cigarettes. Description of an Analysis Method for
Serial Determinations. Ber. Inst. Tabakforsch., Dresden
26:36-45 (Ger).
D--. Acrolein levels in six cigarette brands were 125.7-
289.2 m|Jg/g tobacco solids.
6-036 Rickert, W. S., J. C. Robinson, and J. C. Young. 1980. Estimat-
ing the Hazards of Less Hazardous Cigarettes: 1. Tar, Nicotine,
Carbon Monoxide, Acrolein, Hydrogen Cyanide, and Total Aldehyde
Deliveries of Canadian Cigarettes. J. Toxicol. Environ. Health
6(2):351-366.
C—. Canadian cigarettes (102 brands purchased in March and April
1978) smoked usually to a 30-mm butt length contained 4-269 pg
HCN/cigarette and 3-85 pg acrolein per cigarette. At 20 cigarettes
per day, the average values per cigarette (168 and 65 |Jg, respec-
tively) could contribute 4 and 68% of the exposure at the OSHA
limits. It is not clear how the values of 432 ppm HCN and 78 ppm
acrolein were calculated for deliveries per cigarette.
6-109 Roussel, A., G. Bouley, R. Roudier, A. Dubreuil, J. Godin, and C.
Boudene. 1973. Prolonged Action of Low Doses of Acrolein in
Rats. In: Proc. 3rd Int. Clean Air Cong., Dusseldorf, Germany.
October 8-12, 1973. VDI-Verlag, Dusseldorf, Germany.
pp. A17-A18 (Fre).
B-9. Rats exposed to ~ 0.6 ppm acrolein for 2-6 mo showed de-
creased food and water consumption, decreased lung and body
weight, and some changes in the lungs and liver.
2-0051 Rylander, R. 1973. Toxicity of Cigarette Smoke Components.
Free Lung Cell Response in Acute Exposures. Am. Rev. Resp.
Dis. 108:1279-1282.
D-5. Guinea pigs were briefly exposed to cigarette smoke con-
taining 7-74 fjg acrolein/cigarette. The numbers of free macro-
phages and leukocytes in the lungs after exposure to the smoke
from unfiltered cigarettes were inversely correlated to acrolein
and other smoke components except NO.
114
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5-264 Saindelle, A., F. Ruff, N. Flavian, and J. L. Parrot. 1968.
Histamine Release by Short-Chain Aldehydes. C. R. Hebd. Seances
Acad. Sci., Ser. D. 266(2):139-140.
D-7. 15,000 mL of gaseous acrolein (200 mL/m3) was bubbled
through 20 mL of liquid containing guinea pig lung fragments for
15 min. The amount of histamine released was 0-1.1 [Jg/g of tis-
sue. This is less than that induced by a comparable volume of
whole cigarette smoke.
5-161 Salem, H. , and H. Cullumbine. 1960. Inhalation Toxicities of
Some Aldehydes. Toxicol. Appl. Pharmacol. 2:183-187.
C-6. Exposure of mice, guinea pigs and rabbits to HCHO and
acrolein in both vapor and aerosol form for up to 10 h. HCHO
concentrations of 19-20 mg/m3 caused few deaths during exposure,
but a number of the animals died later. Acrolein at mean con-
centration of 4,624 to 5,225 mg/m3 was lethal to all the animals
in < 1 h. Mice were more susceptible to both HCHO and acrolein
than other animals.
5-307 Schuck, E., and N. Renzetti. 1960. Eye Irritants Formed During
Photooxidation of Hydrocarbons in the Presence of Oxides of Ni-
trogen. Air Pollut. Control Assoc. J. 10:389-392.
C-8. Moderate to severe eye irritation was caused by 5-min ex-
posure to 1.5 ppm acrolein or 4 ppm HCHO. These two irritants
accounted for most of the observed eye irritation caused by the
products of the photooxidation of hydrocarbons with oxides of
nitrogen. 3 ppm propionaldehyde and 10 ppm acetaldehyde caused
no eye irritation.
6-038 Shmakov, A. A., G. A. Levit, A. N. Dudyrev, V. K. Agapova, V. S.
Pridvizhkin, G. G. Nizhnikov, and B. V. Aretinskii. 1971. Sani-
tary and Hygienic Working Conditions after Introducing New Self-
Propelled Equipment at the Mines of the Dzheskazgan Mining and
Metallurgical Plant. Tr. Tsentr. Nauchno-Issled. Proektn.-Konstr.
Inst. Profil. Pnevmokoniozov. Tek. Bezop. Issue 5:97-99 (Russ).
D--. Truck, bulldozer, and excavator drivers were exposed to
~ 14 mg acrolein/m3 and ~ 10.4 mg NO /m3, as well as noise, vibra-
tion, dust, and other fumes. Apparently no health evaluations
were performed.
6-093 Silvestrini, B., and G. Maffii. 1959. Antitussive Activity
Among Laboratory Animals and the Relation Between the Coughing
Action and Other Pharmacological Properties. Farmaco (Sci. Ed.)
!4(6):440-464 (Ital).
115
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D--. A method of surveying the antitussive (anticough) activity
of up to 16 substances by inducing coughing in rats, dogs, and
guinea pigs with unknown (probably high) levels of NH3, H2S04, or
acrolein.
6-094 Silvestrini, B., and C. Pozzatti. 1960. Antitussive Activity
and Other Pharmacological Properties of Six Oxadiazoles. Arch.
Int. Pharmacodyn. Ther. 129(3-4):249-263.
D-5. Acrolein was used at an unknown level as a standard irri-
tant to cause coughing in guinea pigs. Subsequent treatment with
different oxadiazoles resulted in different degrees of ameliora-
tion. Treatment of other problems, not caused by acrolein, was
also tested.
1-0055 Sim, V. ML, and R. F. Pattle. 1957. Effect of Possible Smog
Irritants on Human Subjects. J. Am. Med. Assoc. 165:1908-1913.
B-9. A study of acute (£ 30 min) human exposure to several com-
pounds of interest. HCHO at 17.3 mg/m3 was slightly irritating;
acrolein at 1.88 or 2.80 mg/m3 was extremely irritating; acetal-
dehyde at 240 mg/m3 was mildly irritating; propionaldehyde at
324 mg/m3 was mildly irritating. A more complex study of H2S04
exposure was done.
6-040 Sinkuvene, D. S. 1970. Hygienic Assessment of Acrolein as an
Air Pollutant. Hyg. Sanit. 35:325-329.
B-8. Thresholds for odor (0.07 mg/m3) and cerebral cortex reflex
activity (0.05 mg/m3) are given. Exposure of rats, both sick and
healthy, to 0.74, 0.14, or 0.03 mg/m3 for 61 d caused changes in
biological, biochemical, and physiological parameters at the two
highest levels.
5-165 Skog, E. 1950. A Toxicological Investigation of Lower Aliphatic
Aldehydes--!. Toxicity of Formaldehyde, Acetaldehyde, Propional-
dehyde, and Butyraldehyde; As Well As of Acrolein and Crotonal-
dehyde. Acta Pharmacol. Toxicol. 6:299-318.
B-10. Acute exposure of rats to 600-1,700 mg HCHO/m3 led to an
LD5o of 1,000 mg/m3. Rats exposed to 100-700 mg acrolein/m3
had an LD5o of 300 mg/m3. This is a solid acute, lethal dose
study.
3-091 Smyth, H. 1956. Improved Communication--Hygienic Standards for
Daily Inhalation. Am. Ind. Hyg. Assoc. Q. 17:129-185.
D--. Brief reviews of the toxicity of ~ 200 compounds, including
acrolein, NH3, HCN, H2S, MeOH, HCHO, and H2S04. Cites unpublished
information that 8-h exposure to 8 ppm acrolein killed 1 of 6 rats.
116
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6-133 Smyth, H. F. , C. P. Carpenter, and C. S. Weil. 1951. Range-
Finding Toxicity Data: List IV. AMA Arch. Ind. Hyg.Occup. Med.
4(2):119-122.
D--. Brief mention of acrolein with the same rat data as Smyth
(1956).
6-089 Soriano, M. Experimental Asthma Produced by Acrolein. Arch. Med.
Exp. 23(l):85-94 (Span).
C--. Guinea pigs exposed to 10% acrolein vapors suffered asthma
characterized by bradypnea, spasmodic inspiration, and prolonged
and difficult expiration rhonchus. Nasal and lacrimal secretion
also occurred. Exposure for 1-2 min caused reversible symptoms,
and normalization within 48 h. Exposure for 3-4 min caused ir-
reversible asthma, and death due to acute emphysema and respira-
tory paralysis.
5-104 Sprince, H., C. M. Parker, and G. G. Smith. 1979. Comparison of
Protection by L-Ascorbic Acid, L-Cysteine, and Adrenergic-Blocking
Agents Against Acetaldehyde, Acrolein, and Formaldehyde Toxicity:
Implications in Smoking. Agents Actions 9(4):407-414.
D-12. Rats were orally intubated with ~ 90% of the 24-h LD50 of
HCHO or acrolein. Both groups gradually showed lethargy, tremors,
respiratory distress, and death which suggested that the primary
toxic effect, even through oral dosing, was on the repiratory
system. Lung congestion and pulmonary edema at death are men-
tioned, but there is no description of histopathology or even
gross necropsy.
6-118 SRC, Syracuse Research Corporation. 1979. Potential Occupational
Hazards, Volume I, Single Chemicals; Acrolein. PB81-147951, Na-
tional Technical Information Service, U.S. Department of Commerce,
Springfield, VA. 23 pp.
A--. Extensive review.
5-306 Stephens, E., E. Darley, 0. Taylor, and C. Scott. 1961. Photo-
chemical Reaction Products in Air Pollution. Int. J. Air Water
Pollut. 4(l-2):79-100.
B-8. Eye exposure only to 0.5-2 ppm acrolein for 5 or 12 min
caused eye irritation in 19-91% of the people, the percentage in-
creasing with increasing concentration, exposure time, or number
of repetitions.
5-338 Stupfel, M. 1976. Recent Advances in Investigations of Toxicity
of Automotive Exhaust. Environ. Health Perspect. 17:253-285.
117
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D--. Summary of levels of various components of exhaust: HCHO
in gasoline exhaust (10-300 ppm), HCHO in diesel exhaust (5-30 ppm),
HCHO in urban polluted air (0.05-0.12 ppm), HCHO in tobacco smoke
(120 ppm), acrolein in urban polluted air (0.01 ppm), acrolein in
tobacco smoke (60 ppm), and HCN in tobacco smoke (300-1,500 ppm).
Extensive review of epidemiology and human and animal experimental
results of exposure to exhaust.
6-131 Tanimoto, M., and H. Uehara. 1975. Detection of Acrolein in En-
gine Exhaust with Microwave Cavity Spectrometer of Stark Voltage
Sweep Type. Environ. Sci. Technol. 9(2):153-154.
D--. The exhaust of an automobile engine connected with a dyna-
mometer contained ~ 5 ppm acrolein.
6-041 Ubaidullaev, R. , and N. S. Abramova. 1976. Hygienic Standard-
ization of the Combination of Acrolein, Acetone, and Phthalic
Anhydride in the Air. Gig. Sanit. No. 10:6-10 (Russ).; English
translation available from John Crerar Library, Chicago, Illinois.
Order No. 80 13783-06J.
A-6. Primarily a study of mixtures of the three compounds, show-
ing additive effects on odor perception and electrocortical activ-
ity. Acrolein alone had an odor threshold level of 0.078 mg/m3
and an electrocortical activity threshold level of 0.05 mg/m3.
6-091 Underbill, F. P. 1926. Chapter XIII. The Physiological Action
of Miscellaneous Gases. In: The Medical Department of the
United States Army in the World War. Vol. 14. Medical Aspects of
Gas Warfare. U.S. Government Printing Office, Washington, D.C.
pp. 407-420.
C—. Review of the toxicity of several compounds, including
acrolein. Animal data were primarily about acute, lethal expo-
sures. For human exposure:
~ 2.8 mg/m3 odor threshold
7.7 mg/m3 prominent eye and nose irritation
10.0 mg/m3 pronounced lacrimation
3-094 U.S.S.R. State Committee of the Council of Ministers for Con-
struction. 1972. Sanitary Norms for Industrial Enterprise De-
sign. Publishing House of Literature on Construction, Moscow.
92 pp. (Russ).
C--. In the USSR, the MAC for acrolein in the workplace was
0.7 mg/m3, and in populated places was 0.03 mg/m3 (one-time and
avg.).
118
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5-413 Van Gemert, L. J. , and A. H. Nettenbreijer. 1977. Compilation
of Odor Threshold Values in Air and Water. National Institute
for Water Supply. Leidschendam, The Netherlands, and Central
Institute for Nutrition and Food Research, TNO, Zeist, The
Netherlands, pp. 11, 23, 25, 33.
A--. Compilation of odor threshold values reported by different
researchers, for many compounds, including:
ammonia 0.03 - 37 mg/m3
HCN < 1.1 - 6
H2S 0.001 - 2
HCHO 0.033 - 2.2
Methanol 4.3 - 11,700
Acrolein 0.05 - 4.1
6-096 Voisin, C., C. Aerts, A. B. Tonnel, and N. Dutriez. 1979. Gas-
eous Aerocontaminants and Phagocytic Defense of the Respiratory
Tract. Cytotoxicity of N02, of Ozone and Acrolein for Alveolar
Macrophages in Gaseous Phase. Nouv. Presse Med. 8(25):2089-2094
(Fre).
C-9. Same data reported in Voisin et al. (1980) [6-099].
6-099 Voisin, C., F. Erba, N. Pommery-Dutriez, and C. Aerts. 1980.
The Effects of Toxic Gases on Phagocytic Defenses of the Respira-
tory System; In Vitro Approach. Ann. Anesthesiol Fr. 21(6):639-
643 (Fre).
C-9. Alveolar macrophage cultures from guinea pigs were exposed
to gaseous acrolein (4-35 ppm) for 30 min. Decreased ATP levels
were measured. Same data reported in Voisin et al. (1979)
[6-096].
6-101 Von Oettingen, W. F. 1958. Poisoning; A Guide to Clinical Diag-
nosis and Treatment. 2nd ed., W. B. Saunders Co., Philadelphia,
Pennsylvania, p. 216.
D--. Very brief review of symptoms, with no correlation to acro-
lein levels.
6-042 Watanabe, T., and D. M. Aviado. 1974. Functional and Biochemical
Effects on the Lung Following Inhalation of Cigarette Smoke and
Constituents: II. Skatole, Acrolein, and Acetaldehyde. Toxicol.
Appl. Pharmacol. 30(2):201-209.
C-9. Exposure of mice to 100 mg acrolein/m3 for 60 min/d for
5 wk or to 300 or 600 mg/m3 for 5 min caused decreases in lung
function values.
119
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5-348 Weber, A., C. Jermini, and E. Grandjean. 1976a. Irritating
Effects on Man of Air Pollution Due to Cigarette Smoke. Am. J.
Public Health 66(7):672-676.
D-ll. Exposure is confounded for the purposes of this report, but
worth a mention as an interaction study with HCHO and acrolein as
probably the primary irritants. The sidestream smoke from 30 cig-
arettes added to a 30 m3 room for 26 min resulted in ~ 71 ppm CO,
-1.32 ppm HCHO, and ~0.30 ppm acrolein. The results of self-
rated intensity of eye irritation paralleled the increases in
irritants with time. Nose and throat irritation, respiratory
and general complaints, and poor air quality judgments also in-
creased with time, although weaker and less obviously parallel-
ing irritant concentration. Nonsmokers were slightly more
sensitive.
5-280 Weber, A., T. Fischer, E. Sancin, and E. Grandjean. 1976b. Air
Pollution Due to Cigarette Smoke: Physiological and Irritating
Effects. Soz.-Praeventivmed. 21(4):130-132 (Fre).
D-4. A group of 33 subjects was exposed to an increasing concen-
tration of cigarette sidestream smoke for 28 min (containing
0.03-0.64 ppm HCHO, 1-43 ppm CO, 0.08-1.5 ppm NO, and 0-0.2 ppm
acrolein). Eye irritation and subjective annoyance (the more
sensitive criterion) increased with time, smokers and nonsmokers
apparently equally sensitive. No significant differences in lung
function were observed.
6-086 Weber-Tschopp, A., T. Fischer, R. Gierer, and E. Grandjean. 1977.
Experimentally Induced Irritating Effects of Acrolein on Men.
Int. Arch. Occup. Environ. Health 40(2):117-130 (Ger).
A-14. Short (1.5 min) exposures to 0.15, 0.30, 0.45, and 0.60 ppm
acrolein, 35-min exposures to continuously rising (0-0.60 ppm)
acrolein levels, and 60-min exposures to 0.30 ppm acrolein were
studied. Significant changes were seen at the following concen-
trations :
Annoyance 0.09 ppm
Eye Irritation 0.09
Nose Irritation 0.15
Blinking Frequency 0.26
Respiratory Frequency 0.30
Throat Irritation 0.30
Exposures for the longer times generally caused more irritation,
indicating lack of adjustment or desensitization to the irritat-
ing effects of acrolein.
6-112 Weissbecker, L. , R. D. Carpenter, P. C. Luchsinger, and T. S.
Osdene. 1969. In Vitro Alveolar Macrophage Viability, Effect of
Gases. Arch. Environ. Health 18(5) :756-759.
120
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D-8. Exposure of a "hanging drop" cell mixture to 36-3,600 ppm
acrolein, 373-3,700 ppm acetaldehyde, or 607-30,170 ppm HCN for
1 h caused no decrease in cell viability. The results section
furnishes data indicating that these results are not properly
reproducible, and therefore of little value.
6-044 Weissbecker, L., R. M. Creamer, and R. D. Carpenter. 1971.
Cigarette Smoke and Tracheal Mucus Transport Rate. Isolation
of Effect of Components of Smoke. Am. Rev. Resp. Dis.
104(2):182-187.
D-7. Anesthetized cats exposed to smoke from carbon-filtered
cigarettes plus isoprene, NO, and acrolein had a 32% decrease in
tracheal mucus flow. Little usefulness to this task because of
the confounding presence of other gases and the lack of concen-
tration information.
5-282 Wynder, E. L., D. A. Goodman, and D. Hoffman. 1965. Ciliatoxic
Components in Cigarette Smoke. II. Carboxylic Acids and Aldehydes.
Cancer 18(4):505-509.
C-8. The methods of this clam gill cilia study are not fully
described. The lowest level of HCHO tested was 0.05% (500 ppm)
and this produced almost immediate complete stasis of ciliary
activity with eventual recovery. 0.1-1.0% (1,000-10,000 ppm)
acrolein caused immediate arid complete ciliastasis, while 0.05%
(500 ppm) caused immediate lose of metachronic wave in the
lateral cilia and partial stasis at ~ 1 min with no further
effect.
6-092 Yant, W. P., H. H. Schrenk, F. A. Patty, and R. R. Sayers. 1930.
Acrolein as a Warning Aent for Detecting Leakage of Methyl Chlo-
ride from Refrigerators. Report of Investigations 3027, Bureau
of Mines, U.S. Department of Commerce. 11 pp.
C-10. The lowest concentration of acrolein tested (1 ppm) caused
intolerable eye irritation in 5 min. A good time-to-effect study,
but confounded by the presence of CH3C1 (99 ppm).
5-121 Zitting, A., and H. Savolainen. 1979. Neurotoxic Effects of the
Oxidative Thermal Degradation Products from Low Density Polyethyl-
ene. Fire Mater. 3(2):80-83.
C-10. Repeated exposure of rats to polyethylene combustion prod-
ucts containing 1.4 ppm HCHO, 0.5 ppm acrolein, ash, CO, and mixed
aldehydes for 6 h/d, 5 d/wk for 2-5 wk led to undesirable neural
effects.
121
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TECHNICAL REPORT DATA
(Please read Instructions on the reverse before completing)
. REPORT NO.
EPA 460/3-81-034
3. RECIPIENT'S ACCESSION-NO.
I. TITLE AND SUBTITLE
Acrolein Health Effects
5. REPORT DATE
6. PERFORMING ORGANIZATION CODE
. AUTHOR(S) ' ~ ~~
Bonnie L. Carson, Cecily M. Beall, Harry V. Ellis III,
Larry H. Baker, and Betty L. Herndon
8. PERFORMING ORGANIZATION REPORT NO
IZATION NAME AND ADDRESS
Midwest Research Institute
425 Volker Blvd.
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 Division
Plymouth Road. Ann Arbor. Michigan 48102
13. TYPE OF REPORT AND PERIOD COVERED
Final Report
14. SPONSORING AGENCY CODE
5. SUPPLEMENTAF
NOTES
Health effects literature primarily related to inhalation exposures to acrolein
was collected, evaluated, tabulated, and summarized. Approximately 125 documents
were collected from computerized and manual literature searches covering the period
1911-1981. Pharmacologists and an M.D. epidemiologist rated the documents according
to their applicability to the study and their methodology. The approximately 45
documents considered useful for deriving a range of concern for human exposure to
acrolein from automotive emissions were tabulated. The pages of tables detail
the results of acute, repeated dose, and chronic testing of mice, hamsters, rats,
guinea pigs, chickens, rabbits, cats, monkeys, dogs, and humans as well as human
occupational and accidental studies. Most of the documents evaluated are described
in an annotat-d bibliography.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.lDENTIFIERS/OPEN ENDED TERMS
c. COSATI Field/Group
Toxicity Bibliographies
Acrolein Toxic Tolerances
Aldehydes Occupational Diseases
Mammals Respiratory System
Inhalation Health Effects
06T
Release Unlimited
19 SECURITY CLASS (ThisReport)
Unclassified
21. NO. OF PAGES
122
>0. SECURITY CLASS (Thispage)
Unclassified
22. PRICE
EPA Form 2220-1 (9-73)
122
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