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

-------
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

-------
                                  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

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                                         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.

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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

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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

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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

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          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

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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

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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

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          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

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          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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