AMBIENT WATER QUALITY CRITERIA FOR
ACROLEIN
Prepared By
U.S. ENVIRONMENTAL PROTECTION AGENCY
Office of Water Regulations and Standards
Criteria and Standards Division
Washington, O.C.
Office of Research and Development
Environmental Criteria and Assessment Office
Cincinnati, Ohio
Carcinogen Assessment Group
Washington, D.C.
Environmental Research Laboratories
Corvalis, Oregon
Duluth, Minnesota
Gulf Breeze, Florida
Narragansett, Rhode Island
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DISCLAIMER
This report has been reviewed by the Environmental Criteria and
Assessment Office, U.S. Environmental Protection Agency, and approved
for publication. Mention of trade names or commercial products does not
constitute endorsement or recommendation for use.
AVAILABILITY NOTICE
This document is available to the public through the National
Technical Information Service, (NTIS), Springfield, Virginia 22161.
ii
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FOREWORD
Section 304 (a)(l) of the Clean Water Act of 1977 (P.L. 95-217),
requires the Administrator of the Environmental Protection Agency to
publish criteria for water quality accurately reflecting the latest
scientific knowledge on the kind and extent of all identifiable effects
on health and welfare which may be expected from the presence of
pollutants in any body of water, including ground water. Proposed water
quality criteria for the 65 toxic pollutants listed under section 307
(a)(l) of the Clean Water Act were developed and a notice of their
availability was published for public comment on March 15, 1979 (44 FR
15926), July 25, 1979 (44 FR 43660), and October 1, 1979 (44 FR 56628).
This document is a revision of those proposed criteria based upon a
consideration of comments received from other Federal Agencies, State
agencies, special interest groups, and individual scientists. The
criteria contained in this document replace any previously published EPA
criteria for the 65 pollutants. This criterion document is also
published in satisifaction of paragraph 11 of the Settlement Agreement
in Natural Resources Defense Council, et. al. vs. Train, 8 ERC 2120
(D.D.C. 1976), modified, 12 ERC 1833 (D.D.C. 1979).~
The term "water quality criteria" is used in two sections of the
Clean Water Act, section 304 (a)(l) and section 303 (c)(2). The term has
a different program impact in each section. In section 304, the term
represents a non-regulatory, scientific assessment of ecological ef-
fects. The criteria presented in this publication are such scientific
assessments. Such water quality criteria associated with specific
stream uses when adopted as State water quality standards under section
303 become enforceable maximum acceptable levels of a pollutant in
ambient waters. The water quality criteria adopted in the State water
quality standards could have the same numerical limits as the criteria
developed under section 304. However, in many situations States may want
to adjust water quality criteria developed under section 304 to reflect
local environmental conditions and human exposure patterns before
incorporation into water quality standards. It is not until their
adoption as part of the State water quality standards that the criteria
become regulatory.
Guidelines to assist the States in the modification of criteria
presented in this document, in the development of water quality
standards, and in other water-related programs of this Agency, are being
developed by EPA.
STEVEN SCHATZOW
Deputy Assistant Administrator
Office of Water Regulations and Standards
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ACKNOWLEDGEMENTS
Aquatic Life Toxicology:
William A. Brungs, ERL-Narragansett
U.S. Environmental Protection Agency
David J. Hansen, ERL-Gulf Breeze
U.S. Environmental Protection Agency
Mammalian Toxicology and Human Health Effects:
Patrick Durkin (author)
Syracuse Research Corporation
Terence M. Grady (doc. mgr.)
ECAO-Cin
U.S. Environmental Protection Agency
Mary F. Argus
Tulane Research Laboratory
John L. Egle
Medical College of Virginia
Betty LaRue Herndon
Midwest Research Institute
Steven D. Lutkenhoff, ECAO-Cin
U.S. Environmental Protection Agency
Donna Sivulka, ECAO-RTP
U.S. Environmental Protection Agency
Woodhall Stopford
Duke University Medical Center
Jonathan Ward. •
University of Texas Medical Branch
Robert M. Bruce, ECAO-RTP
U.S. Environmental Protection Agency
Jan Connery
Energy Resources Company, Inc.
Rolf Hartung
University.of Michigan
George J. Jakab
Johns Hopkins School of Hygiene
Alan B. Rubin, CSD
U.S. Environmental Protection Agency
Anne Trontell
Energy Resources Company, Inc.
Technical Support Services Staff: D.J. Reisman, M.A. Garlough, B.L. Zwayer,
P. A. Daunt, K.S. Edwards, T.A. Scandura, A.T. Pressley, C.A. Cooper,
M.M. Denessen.
Clerical Staff: C.A. Haynes, S.J. Faehr, L.A. Wade, D. Jones, B.J. Bordicks,
B.J. Quesnell, T. Highland, R. Rubinstein.
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TABLE OF CONTENTS
Criteria Summary
Introduction
Aquatic Life Toxicology
Introduction
Effects
Acute Toxicity
Chronic Toxicity
Plant Effects
Residues
Miscellaneous
Summary .
Criteria
References
Mammalian Toxicology and Human Health Effects
Introduction
Exposure
Ingestion from Water
Ingestion from Food
Inhalation
Dermal
Pharmacokinetics
Absorption
Distribution
Metabolism
Excretion
Effects
Acute, Subacute and Chronic Toxicity
Subacute Toxicity to Experimental Mammals
Chronic Toxicity to Experimental Mammals
Effects on Humans
Synergism and/or Antagonism
Teratogenicity
Mutagenicity
Carcinogenicity
Criterion Formulation
Existing Guidelines and Standards
Current Levels of Exposure
Special Groups at Risk
Basis and Derivation of Criteria
References
Paae
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B-5
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C-4
C-4
C-8
C-13
C-20
C-20
C-20
C-22
C-22
C-24
C-24
C-24
C-33
C-38
C-39
C-43
C-43
C-44
C-45
C-50
C-50*
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CRITERIA DXUMENT
ACROLEIN
CRITERIA
Aquatic Life
The available data for acrolein indicate that acute and chronic toxicity
to freshwater aquatic life occur at concentrations as low as 68 and 21 ug/1,
respectively, and would occur at lower concentrations among species that are
more sensitive than those tested.
The available data for acrolein indicate that acute toxicity to salt-
water aquatic life occurs at concentrations as low as 55 ug/1 and would oc-
cur at lower concentrations among species that are more sensitive than those
tested. No data are available concerning the chronic toxicity of acrolein
to sensitive saltwater aquatic life.
Human Health
For the protection of human health from the toxic properties of acrolein
ingested through contaminated aquatic organisms, the ambient water criterion
is determined to be 320 ug/1.
For the protection of human health from the toxic properties of acrolein
ingested through contaminated aquatic organisms alone, the ambient water
criterion is determined to be 780 ug/l«
VI
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INTRODUCTION
-•• . -. • .
Acroleln has a wide-variety of applications. It is used directly as a
biocide for aquatic weed control; for algae, weed,.and mollusk control in
recirculating process water systems; for slime control in the paper indus-
try; and to protect liquid fuels against microorganisms. Acrolein is also
used directly for crosslinking protein collagen in leather tanning and for
tissue fixation in histological samples. It is widely used as an intermedi-
ate in the chemical industry. Its dimer, which is prepared by a thermal,
uncatalyzed reaction, has several applications, including use as an interme-
diate 'for crosslinking agents, humectants, plasticizers, polyurethane inter-
mediates, copolymers and homopolymers, and Greaseproofing cotton. The mono-
mer is utilized in synthesis via the Oiels-Alder reaction as a dienophile or
a diene. Acrolein is widely used in copolymerization, but its homopolymers
do not appear commercially important. The copolymers of acrolein are used
in photography, for textile treatment, in the paper industry, as builders in
laundry and dishwasher detergents, and as coatings for aluminum and steel
panels, as well as other applications. Hess, et al. (1978) described mar-
keting aspects of acrolein. In 1975, worldwide production was about 59 kil-
otons. Its largest market was for methionine manufacture. Worldwide capac-
ity was estimated at 102 kilotons/year, of which U.S. capacity was 47.6 kil-
otons/year.
Acrolein (2-propenal) is a liquid with a structural formula of CH_ «
CHCHO and a molecular weight of 56.07. It melts at -86.95"C, boils at*52.5
to 53.5*C, and has a density of 0.8410 at 20* C (Weast, 1975). The vapor
pressure at 20*C is 215 mm Hg, and its water solubility is 20.8 percent by
weight at 20"C (Standen, 1967).
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A flammable liquid with a pungent odor, acrolein is an unstable compound
that undergoes polymerization to the plastic solid disacryl, especially
under light or fn the .presence of alkali or strong acid (Windholz, 1976).
It is the simplest member of the class of unsaturated aldehydes, and the ex-
t
treme reactivity of acrolein is due to the presence .of a vinyl group
(HgC-H-) and an aldehyde group on such a small molecule (Standen, 1967).
Additions to the carbon-carbon double bond of acrolein are catalyzed by
acids and bases. The addition of halogens to this carbon-carbon double bond
proceeds readily (Standen, 1967).
i
Acrolein can enter the aquatic environment by its use as an aquatic her-
bicide, from industrial discharge, and from the chlorination of organic com-
pounds in wastewater and drinking water treatment. It is often present in
trace amounts in foods and is a component of smog, fuel combustion, wood,
and possibly other fire, and cigarette smoke. An evaluation of available
data indicates that, while industrial exposure to manufactured acrolein is
unlikely, acrolein from nonmanufactured sources is pervasive. Acrolein ex-
posure will occur through food ingestion and inhalation. Exposure through
the water or dermal route is less likely. However, analysis of municipal
effluents of Dayton, Ohio showed the presence of acrolein in 6 of 11 sam-
ples, with concentrations ranging from 20 to 200 ug/1 (U.S. EPA, 1977).
Bowmer, et al. (1974) described the loss of acrolein by volatilization
and degradation in sealed bottles and tanks of water. The amounts of acro-
lein dissipated after eight days were 34 percent from the tank and 16 per-
cent from the bottles. The rate of disappearance of acrolein in the tank
was 0.83 day"* at a pH of 7.2. The lack of turbulence in the tank reduced
acrolein loss by volatilization to 1/20 of what would be expected if vola-
tilization were controlled only by resistance in the gas phase and any dis-
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crete surface layers. The authors agree with Geyer (1962), who states that
.•.-
the primary degradation reaction is reversible hydrolysis to 8-hydroxypro-
pionaldehyde, which is 1-ess volatile thari acrolein.
The fate of acrolein in water was observed in buffered solutions and in
natural channel waters (Bowmer and Higgins, 1976). An equilibrium between
dissipating acrolein and degradation products was reached in the buffered
solution following dissipation of 92 percent of the acrolein, but in natural
waters there was no indication of an equilibrium, with the dissipating reac-
tion apparently being continued to completion. In natural waters, the accu-
mulation of a reaction (degradation) product was greater at higher initial
acrolein concentration, and decay was rapid when acrolein concentrations
fell below 2 to 3 mg/1. The initial period of slow decline preceding the
rapid dissipation period is thought to be the result of microbiological pro-
cesses. Unlike earlier works (Bowmer, et al. 1974), there was an 8- to
10-fold increase in the observed dissipation rate as compared to the expect-
ed rate in two of four flowing water channels, suggesting major losses in
volatilization and absorption.
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REFERENCES
Bowmer, K.H. and M.L. -Wiggins,. 1976. Some aspects of the persistence and
fate of acroleln herbicide 1n water. Arch. Environ. Contain. 5: 87.
Bowmer, K.H., et al. 1974. Loss of acroleln from water by volatilization
and degradation. Weed Res. 14: -325.
Geyer, B.P. 1962. Reaction with Water. In: C.W. Smith (ed.), Acroleln.
John Wiley and Sons, Inc., New York.
Hess, L.B., et al. 1978. Acroleln and Derivatives. In_; A. Standen (ed.),
Klrk-Othmer Encyclopedia of Chemical Technology. 3rd ed. Intersclence Pub-
Ushers, New York.
Standen, A. (ed.) 1967. Kirk-Othmer Encyclopedia of Chemical Technology.
Intersclence Publishers, New York.
U.S. EPA. 1977. Survey of two municipal wastewater treatment plants for
toxic substances. Wastewater Res. D1v. Municipal Environ. Res. Lab., Cin-
cinnati, Ohio.
Weast, R.C. (ed.) 1975. Handbook of Chemistry and Physics. 56th ed. CRC
Press, Cleveland, Ohio. *
Wlndholz, M. (ed.) 1976. The Merck Index. 9th ed. Merck and Co., Inc.,
Rahway, New Jersey.
A-4
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Aquatic Life Toxicology*
INTRODUCTION
Much of the data concerning the effects of acrolein on freshwater
aauatic organisms has been determined using static test conditions with
unmeasured concentrations. Conseauently, these data may underestimate the
toxicity of this volatile, unstable chemical. The study of Bond, et al.
(1960) showed acrolein to have a substantially greater acute toxicity to
fish than the 14 other herbicides tested. This relationship is also seen in
a toxicity bibliography of five herbicides (Folmer, 1977).
Acrolein has been applied directly to the saltwater environment to con-
trol fouling organisms in cooling water systems of coastal power plants.
The data base for toxicity of acrolein is limited to the results of acute
exposures of one fish and three invertebrate species, performed with unmea-
sured test concentrations.
EFFECTS
Acute Toxicity
The data base for freshwater invertebrate species is limited to two
values for Daphnia magna. The reported 48-hour values from static tests
with unmeasured concentrations are 57 and 80 ug/1 (Table 1).
Three 96-hour LCgg values are reported for two freshwater fish spe-
cies, bluegill and largemouth bass, both in the family Centrarchidae. These
results were also obtained from static tests with unmeasured concentrations.
*The reader is referred to the Guidelines for Deriving Water Quality Crite-
ria for the Protection of Aauatic Life and Its Uses 1n order to better un-
derstand the following discussion and recommendation. The following tables
contain the appropriate data that were found in the literature, and at the
bottom of each table are calculations for deriving various measures of tox-
icity as described in the Guidelines.
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Ninety-six-hour values of 90 and 100 ug/1 for bluegill and 160 wg/1 for
largemouth bass have been reported (Table 1).
Based on only two_ifish species, no conclusion can be drawn regarding
the relative species sensitivity to acrolein. Also because of a paucity of
data, no comparison .of relative sensitivity between freshwater invertebrate
and fish species can be made.
Among the tested saltwater species, the eastern oyster was most sensi-
tive with a 96-hour ECgg, based on decreased shell growth, of 55 ug/1,
(Table 1). Tests with other species (Table 5) were conducted for less than
the standard testing times for those species or life stages.
Chronic Toxicity
The chronic toxicity data base consists of one value for fish and one
c
for invertebrate species.
Macek, et al. (1976) conducted the only freshwater invertebrate chronic
test. Based on the cumulatively reduced survival of Daphnia magna through
three generations, a chronic value of 24 ug/1 is obtained (Table 2). The
acute value for this species by the same investigator is 57 ug/1 and this
results in an acute-chronic ratio of 2.4. These data show that there is
little difference in concentrations between the acute and chronic effects of
acrolein on Daphnia magna.
A life cycle test with the fathead minnow, also conducted by Macek, et
al. (1976), resulted in a chronic value of 21 wg/1 (Table 2). Survival of
newly-hatched second generation fathead minnow fry was significantly reduced
at 41 wg/1 but was not significantly different from control survival at 11
ug/1. A dilutor malfunction killed or severely stressed the fish at an
intermediate concentration, 21 ug/1, so no second generation fish were pro-
duced. Although no 96-hour LC5Q for this species is available, a 6-day
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incipient LCgQ for fathead minnows of 84 ug/1 was reported by the same
authors using a flow-through test with unmeasured concentrations (Table 5).
Also, Louder and McCoy (1962) reported a 48-hour LC?Q of 115 ug/l for fat-
head minnows.
No saltwater species have been tested to evaluate chronic effects.
Species mean acute and chronic values are summarized in Table 3.
Plant Effects
Although published literature does exist describing the use of acrolein
to control aauatic macrophytes and algae, no appropriate plant effect data
are available. In some cases, test methods were insufficiently described to
evaluate reported results. In others, because of the methods used, no
actual exposure concentration under field conditions could be calculated or
results were reported as control of the weeds with no quantitative measure-
ments made.
The effects of acrolein on saltwater and freshwater plants have not
been studied. Because acrolein is a herbicide, phytoxicity to aauatic spe-
cies might be expected.
Residues
Bluegills exposed for 28 days to 13 wg/1 of 14C-acrolein bioconcen-
trated acrolein 344 times (Table 4). The half-life was greater than seven
days. Thin-layer chromatography was used to verify concentrations.
Miscellaneous
Ninety-eight percent of adult snails and 100 percent of snail -embryos
died after a 24-hour exposure to 10,000 ug/1 (Ferguson, et al. 1961).
Nine short-term exposures with seven fish species yielded acute toxic-
. ;y values in the range of 46 to 115 ug/1 (Table 5). Static tests with un-
measured concentrations were run by Bond, et al. (1960), Louder and McCoy
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(1962), and Bridie, et al. (1979). The studies of Burdick, et al. (1964)
and Macek, et al. (1976) were performed under flow-through conditions with
unmeasured concentration^. That of Bartley and Hattrup (1975) reporting 32
percent mortality of rainbow trout in 48 hours at 48 ug/1 was the only flow-
through study with measured acrolein concentrations. Because of differences
in test methods and the valatility of acrolein, no meaningful comparison of
relative sensitivity among the fish species is possible.
The avoidance response of rainbow trout at 100 ug/1 is above reported
acute levels (Folmar, 1976). Folmar (1980) reported flavor impairment of
rainbow trout flesh up to four days after a four-hour exposure to 90 ug/1.
Various species of aauatic weeds were damaged or destroyed following
treatment with 500 to 25,000 ug/1 of acrolein (Table 5).
The 48-hour ICgg values for three saltwater species are in the range
from 100 to 2,100 ug/1 with the brown shrimp being the most sensitive.
Summary
Appropriate acute freshwater toxicity data for acrolein are limited to
LCgg values from five tests with one invertebrate and two fish species.
The species mean acute values are 68 ug/1 for Daphnia magna, 95 ug/1 for
bluegill, and 160 ug/1 for largemouth bass. Because these results were all
obtained from static tests with unmeasured concentrations, these data prob-
ably underestimate the toxicity of this volatile, unstable chemical.
The chronic values for acrolein, 24 ug/1 for Daphnia magna and 21 ug/1
for the fathead minnow, reveal similar sensitivity between these species.
»
No 96-hour IC-. is available for the fathead minnow but two nonstandard
tests showed acute effects at 84 and 115 ug/1. Thus, it appears that there
is little difference between acute and chronic toxicity for acrolein.
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CRITERIA
The available data for acroleln indicate that acute and chronic
toxicity to freshwater aquatic life occur at concentrations as low as 68 and
21 ug/1, respectively, and would occur at lower concentrations among species
that are more sensitive than those tested.
The available data for acrolein indicate that acute toxicity to salt-
water aquatic life occurs at concentrations as low as 55 ug/l and would oc-
cur at lower concentrations among species that are more sensitive than those
tested. No data are available concerning the chronic toxicity of acrolein
to sensitive saltwater aquatic life.
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Tab la I. Acuta valuaa for acrolala
00
Spacla*
Cladocaran,
Daphnla aagna
Cladocaran,
Daphnla aaflna
Bluaglll,
Lapoals Mcrochlrus
Blueglll,
Lapo*ls Mcrochlrus
Largaaouth bass,
Mlcroptarus salaoldas
Eastern oystar
Crassottraa vlrglnlca
Saaclac Meaa
LCM/ECM Acute Valwa
Mathod* Ipgyi)
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Tabla 2, Chronic wluac for acrolala (Macafc. at al. 19761
Spaclaa Maan
Llailts Chronic Valua
Spacla» Mathod" lug/I) luo/l)
FRESHWATER SPECIES
Cladocaran, LC 17-34 24
Daphnla a»gna
Fatttaad •Innow, LC 11-42 21
Plaaphala* proa* Iat
• LC - Ufa eye la or partial Ilia eye la
Acuta-Chronlc Ratio
Chronic Acuta
Valua Valua
Spacla« tiifl/O lug/I) Ratio
Cladocaran, 24 97 2.4
Daphnla aaona
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Table 3. Species Man acute Md chronic wlues for ecroleln
Rank* Specie*
oo
Species Mean
Acute Valua
FRESHWATER SPECIES
Large«outh bass,
Mlcroptarut sal«old«s
Bluaglll,
LapoaiU iBCfochlrus
Cladocaran,
Daphnla aagna
160
66
SALTWATER SPECIES
Eastarn oystar,
Crassostraa virginlea
Acuta-Chronlc
Ratio
2.4
* Rankod fro* least sensitive to w>st sansltlva basad on speclas moon
acut* value.
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Table 4. Raclducs for Bcrolcl* (U.S. EPA, 1978}
BloconcMtratlon Duration
Sp«cU« TUiua Factor
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Tabla 9. Otbar data for acrolaln
Spaclas
Aquatic Macrophytas,
Majas sp., CaratophylluM
sp., and Jooawa sp.
Pondvaad,
PotoMoqaton crlspus
Aquatic Macrophyta,
Elodaa dansa
Snail (adult).
Australorbls glabratus
Snail (aatryos)
Australorbls glnbratut
Chinook
(finger I Ing),
Oncorhynchus t«hatiyt«cha
ftalnboo trout
(flngarllng),
Salao aalrdnarl
Rainbow trout (fry),
Salap aalrdnarl
Ralnbo« trout,
Salao galrdnarl
RalnboM trout,
So IBO aalrdnarl
Brown trout
(finger I Ing),
Salao trutta
* Goldfish.
Carasslus auratus
Duration Effact
FRESHWATER SPECIES
RMUlt
(no/»
9 hrs
24 hri
Oastroyad or badly 29.000
Korchad ona Maak
aftar application
Oacayad In 6 days 20,000
Call
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Tabla 5. (Cofltlnuad)
tpaclas
Fathaad Minnow,
PlMaphalat pronalat
Fathaad Minnow,
PlMaphalat proaalat
Bluaglll (flngarllng),
LapoMlt Macrochlrut
Moaqultoflth,
GaMbutla afflnlt
Barnaclas (adult)
Balanut aburnaut
Barnaclat (adult)
Balanut aburnaut
Brown thrlap (adult)
Panaaut aitacut
Longnota kllllflth
(juvanlla)
Fundulut tlMlllt
Duratloa
6 dayt
48 hrt
24 hrt
48 hrt
48 hrt
48 hrt
48 hrt
48 hrt
Effact
Inclplant LC50
LC50
Maan tlMa to daath
LC90
SALTWATER SPECIES
LC90
LC50
EC50
LC50
fteault
(MQ/I)
84
115
79
61
2,100
1,600
100*
240
Rafaranca
Macak, at al. 1976
Loudar i McCoy. 1962
Burdlck, at al.
Loudar i McCoy,
Oahlbarg. 1971
Dahlbarg, 1971
Butlar, 1965
Butlar, 1965
1964
1962
• EC50 basad on lose of aqull Ibrliuu
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REFERENCES
Bartley, T.R. and A.R. Hattrup. 1975. Acrolein residues 1n Irrigation
water and effects on rainbow trout. Bur. Reelam. Rep. REC-ERC-75-8.
Bond, C.E., et al. 1960. Toxldty to various herblcldal materials to
fishes. B1ol. Problems 1n Water Pollut., Trans. 1959 Seminar, U.S. Dept.
Health, Edu., and Welfare, PHS Tech. Rep. W60-3; 96*101.
Bridle, A.L., et al. 1979. The acute toxlclty of some petro-chemlcals to
goldfish. Water Res. 13: 623.
Burdlck, 6.E., et al. 1964. Toxlclty of agualln to flngerllng brown trout
and bluegllls. N.Y. Fish Game Jour. 11: 106.
Butler, P.A. 1965. Commercial fisheries Investigations. Effects of pesti-
cides on fish and wildlife, 1964 research findings F1sh W1ldl. Ser. U.S.
F1sh WUdl. Ser. C1rc.
Dahlberg, M.D. 1971. Toxlclty of acroleln to barnacles, Sal anus eburneus.
Chesapeake Sc1. 12: 282.
Ferguson, F.F., et al. 1961. Control of Australorb1s glabratus by acro-
leln 1n Puerto R1co. Public Health Rep. 76: 461.
Ferguson, F.F., et al. 1965. Preliminary field trials of acroleln 1n the
Sudan. WHO Bull. 32:243.
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Folmar, L.C. 1976. Overt avoidance reaction of rainbow trout fry to nine
herbicides. Bull. Environ. Contain. Toxicol. 15: 509.
Folmar, L.C. 1977. Acroleln, dalapon, dlchlobenll, diquat, and endothall:
Bibliography of toxicity to aquatic organisms. U.S. Fish W1ldl. Ser., Tech.
Paper 88.
Folmar, L.C. 1980. Effects of short-term field applications of acrolein
and 2,4-0 (DMA) on flavor of the flesh of rainbow trout. Bull. Environ.
Contam. Toxicol. 24: 217.
Louder, O.E. and E.G. McCoy. 1962. Preliminary investigations of the use
of aqualin for collecting fishes. Proc. 16th Annu. Conf. S.E. Assoc. Game
Fish Comm. p. 240.
Macek, K.J., et al. 1976. Toxicity of four pesticides to water fleas and
fathead minnows: Acute and chronic toxicity of acrolein, heptachlor, endo-
sulfan, and trifluralin to the water flea (Daphnia magna) and the fathead
minnow (Pimephales promelas). U.S. Environ. Prot. Agency, EPA 600/3-76-099.
Unrau, G.O., et al. 1965. Field trials in Egypt with acrolein herbicide-
molluscicide. WHO Bull. 32: 249.
U.S. EPA. 1978. In-depth studies on health and environmental impacts of
selected water pollutants. U.S. Environ. Prot. Agency, Contract No. 68-01-
4646.
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Van Ov.rb.ck.-O., et .1. 1959. cr,«n r contro, of
disease-carrying water snails. Science. 129: 335.
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Mammalian Toxicology and Human Health Effects
INTRODUCTION
Acrolein, a colorless volatile liquid, is the simplest of the
unsaturated aldehydes:
CH2 » CHCHO
Table 1 describes its salient physical properties. Since it is a
highly reactive organic chemical and capable of self-polymeriza-
tion, the marketed product contains an inhibitor (0.1 percent
hydroquinone) to prevent its degradation. It is extremely reactive
at high pH (Hess, et al. 1978; Smith, 1962). Methods for acrolein
analysis are summarized in Table 2.
The present technology for acrolein preparation employs cata-
lytic oxidation of propene in the vapor phase. A typical reaction
process consists of feeding propylene and air at 300°C to 400°C and
30 to 45 psi over the catalyst (usually of bismuth, molybdenum, or
antimony) (Hess, et al. 1978).
An evaluation of available data indicates that, while indus-
trial exposure to manufactured acrolein is unlikely, acrolein from
nonmanufactured sources is ubiquitous. Acrolein exposure will
occur through food ingestion and through inhalation. Exposure
through the water or dermal route is unlikely. Acrolein is often
present in trace amounts in foods and is a component of smog, fuel
combustion, wood and possibly other fires, and cigarette smoke.
C-l
-------
TABLE 1
Physical Properties of Acrolein*
Empirical Formula
Molecular Weight
Melting Point, °C
Boiling Point, °C
Vapor Pressure at 20°C, KPa (mmHg)
Refractive Index no (20°C)
Viscosity at 20°C, cS
Solubility in Water (weight %)
Critical Properties:
Temperature, °R
Pressure,atm.
Volume, cc/g-mole
*Source: Smith, 1962; Hess, et al. 1978
C3H4o
56.06
-86.95
52.69
29.3 (220)
1.4017
0.393
20.6
510
51.58
189
C-2
-------
Table 2
Methods for Acrolein Measurement*
Analytical Method
Detection Limit
Interferences
NMR (Aldehydic proton) 100 mg/1
Colorimetry
2,4-D
4-Hexylresorcinol
Fluorimetry
Direct
J-Acid
m-Aminophenol derivative
Differential pulse 30 ug/1
Polarography
Gas chromatography
Flame-ionization 500 ug/1
Mass spectral 50 ug/1
few
so ug/i
700 ug/1
20 mg/1
20 ug/i
10 ug/i
many
many
very few
very few
very few
few
very few
very few
*Source: Brady, et al. 1977; Kissel, et al. 1978; Bellar and
Sigsby, 1970
C-3
-------
EXPOSURE
Inqeation from Water
There is no evidence that acrolein is a contaminant of potable
water or water supplies. Available monitoring studies have not
noted its presence/ and acrolein is not listed in compendia on
water monitoring (Junk and Stanley/ 1975; Shackelford and Keith/
1978; AbramSr et al. 1975). Investigations on the fate of acrolein
in water suggest that it dissipates with a half-life of 4 to 5
hours. Based on these studies and its half-life in water
(Table 3), it can be assumed that acrolein is present in water sup-
plies in negligible amounts.
Acrolein is applied to canals as a biocide for the control of
harmful organisms and aquatic weeds (Van Overbeek/ et al. 1959).
This application has prompted studies to delineate the amount of
acrolein required to maintain effective pest control (Bowmer and
Sainty, 1977; Hopkins and Hattrup/ 1974). These studies have exam-
ined dilution problems and pathways for loss. Degradation and
evaporation appear to be the major pathways for loss/ while a
smaller amount is lost through absorption and uptake by aquatic
organisms and sediments. In a review of the Russian literature/
Helnikov (1971) indicates that acrolein is used as a biocide in
water reservoirs.
Kissel/ et al. (1978) have demonstrated the analytical prob-
•>
lems in a study of the effect of pH on the rate of degradation of
aqueous acrolein. Their study compared acrolein measurement by 10
analytical techniques in six pH buffer systems (pH 5, 7, and 9).
C-4
-------
TABLE 3
First Order Rate Constants of Acrolein Degradation
in Laboratory Experiments*
Watera
Supply
Supply
Drainage
Supply
Supply
Supply
Distilled
£1
7.3
7.3
7.8
7.2
7.2
7.2
Initial
Acrolein
ppm
8.0
6.8
6.4
6.1
17.5
50.5
6.4
103k
hr'1
23.7
15.9
45.1
13.3
14.2
11.4
2.7
SE
2.4
2.0
7.5
1.9
2.5
1.0
0.3
*Source: Bowmer and Biggins, 1976
^ater from canal supply, canal drainage, or distilled
water
C-5
-------
The analytical methods were:
(a) bioassay with an ATPase enzyme system,
(b) bioassay by a plate count method,
_i
(c) bioassay by fish kill (bluegill sunfish),
(d) chemical titration with bromide-bromate solution-iodide-
thiosulfate,
(e) colorimetric by the 2,4-dinitrophenylhydrazone (DNP),
(f) fluorometric analysis (m-aminophenol) with excitation at
372 run and emission at 506 run,
(g) gas-liquid chromatography (on 6' Poropak Q with injection
temperature of 250 C and column at 200 C) ,
(h) nuclear magnetic resonance using aldehyde proton at 9.44
ppm vs. tetramethylsilane,
(i) polarographic analysis,
(j) direct fluorometric analysis of acrolein with excitation
at 276 nra and emission at 370 nm.
Kissel, et al. (1978) separated the analytical techniques into
three groups: bioassay, derivatization, and direct measurement.
Differences between bioassay methods were less than for any other
group. They considered bioassay a good measure of true acrolein
concentration. Some titrimetric methods were satisfactory, but
others were poor. Among the direct methods, they considered that
GLC and direct fluorimetry were poor, but that NMR and polaro-
graphic analyses were better methods. Kissel, et al. (1978) did
not identify reasons for the large discrepancies. Also, they noted
that acrolein rapidly degraded at pH 9.
Bowiner and coworkers (Bowiner and Higgins, 1976; Bowmer and
Sainty, 1977; Bowmer, et al. 1974; O'Loughlin and Bowmer, 1975)
have measured acrolein degradation rates in laboratory and field
studies. They evaluated the possible degradation pathway in buf-
C-6
-------
fared, distilled water. At pH 5, the acrolein reacted by .a revers-
ible hydrolysis and yielded an equilibrium mixture containing
/o-hydroxypropionaldehyde:acrolein in a 92:8 ratio.
-« .
H2O + CH2 » CHCHO ^HOCH2CH2CHO
In alkali the primary reaction was consistent with a polycondensa-
tion. In natural waters they observed no evidence for an equili-
brium. They considered the initial product to be from chemical
degradation and suggested, but did not demonstrate, that it further
degraded to a carboxylic acid via a microbial pathway. Acrolein
was analyzed by colorimetry using the 2,4-DNP method and by bio-
assay. Results were conflicting, and they concluded that the ana-
lytic complication (as described by Kissel, et al. 1978) resulted
from the ability of the hydroxypropionaldehyde to form a 2,4-DNP
derivative. They resolved the analysis problem by flushing the
volatile acrolein from a sample by means of an air stream, which
left the nonvolatile hydroxypropipnaldehyde in solution. Acrolein
concentration was measured as the difference between the sum of
absorbances for acrolein and 2,4-DNP in samples before and after
air flushing (Bowmer, et al. 1974). Their laboratory, studies uti-
lized samples sealed in bottles and maintained at 20.6°C. Table 3
summarizes their results. The authors also examined acrolein loss
in field studies, using actual irrigation channels. The apparent
dissipation rate, k, was estimated at 0.16 hr , which is about an
order of magnitude faster than measured in laboratory experiments.
They suggested that the difference could result in part from*vola-
tization and absorption.
Hopkins and Hattrup (1974) examined acrolein loss in field
studies in canals of the Columbia River basin. Their analytical
C-7
-------
technique was fluorometric analysis of the m-aminophenol deriva-
tive. The work of Kissel, et al. (1978), which is discussed above,
suggested that this, analytical method could yield higher acrolein
concentrations than were actually present. Table 4 describes the
acrolein concentration in a flow-plug measured during a 48-hour
study period in two canals. Hopkins and Hattrup (1974) suggested
that dissipation resulted from acrolein degradation, volatiliza-
tion, and absorption by weed tissue.
Potable water is normally treated with a chemical oxidant,
usually chlorine or less often ozone. These oxidants will react
with olefins and are very likely to react with the olefinic portion
of acrolein. It is likely that ozone will initially yield a raalo-
nozonide. Aqueous chlorine (which exists as HOC1) will probably
degrade acrolein as follows (Hess, et al. 1978): 2(CH2"CH-CHO) +
2(HOC1)—>HOCH2CHC1CHO + C1CH2CH(OH)CHO. The relative amounts of
the two possible reaction products and their degradation products
are not known (Morris, 1975).
Ingestion from Food
Acrolein, at yg/g concentrations, is a common component of
food. It is commonly generated during cooking or other processing
and is sometimes produced as an unwanted by-product in the fermen-
tation of alcoholic beverages. The information on acrolein in
foods has been generated primarily to identify organoleptic proper-
ties, so its relevance to exposure levels is limited. '
Acrolein can be produced by cooking potatoes in water.
El'Ode, et al. (1966) investigated acrolein production in potato
extract (Katahdin variety) and synthetic mixtures of the extract.
C-8
-------
TABLE 4
Acrolein Dissipation in Two Canals of the Columbia
River Basin Over 48 Hours*
o
Canal
Potholes
-
East Low
Intended
Application
ppm
0.14
Booster application at
12.6 miles
0.11
Sampling Point
Miles Below Initial
Appl. Point
1.0
10. 0
12.5
13.5
15.0
20.0*
30.0
35.0
1.0
5.0
10.0
20.0
30.0
40.0
64.5
Acrolein
ppm
t>-
0.14
O.lfr
0.09
0.20
0.18
0.15
0.08
0.05
0.09
0.10
0.10
0.08
0.06
0.02
0.03
*Source: Hopkins and Hattrup, 1974
-------
The synthetic mixture contained amino acids (glycj.ne, glutamic
acid, lysine, methionine, and phenylalanine) and sugar (glucose,
fructose, maltose, and sucrose). Acrolein was identified by gas
chromatography (GO as a product of heating some but not all mix-
tures of amino acid and sugar. They did not identify acrolein as a
product of heating the actual potato extract (30 minutes at 180°C)
or of heating the synthetic potato mixture (60 minutes at 100°C),
As reviewed by Izard and Libermann (1978), acrolein is gener-
ated when animal or vegetable fats are subjected to high tempera-
*
tures. In these cases, acrolein is formed primarily from the dehy-
dration of glycerol.
Kishi, et al. (1975) identified acrolein production from cook-
ing potatoes or onions in edible oil. They detected acrolein at
concentrations ranging from 2.5 to 30 rag/m in the air 15 on above
the surface of the heated oil. Cooking about 20 g of potatoes or
onions in the oil yielded 200 to 400 yg of acrolein. The authors
did not determine whether the acrolein came from the oil, the pota-
toes, the onions, or from all three sources.
Hrdlicka and Kuca (1965.) examined aldehydes and ketones in
turkey before cooking and in volatiles produced by either boiling
(3 kg in 6 1 of distilled water for 3 hours) or roasting (3 kg at
170°C to 190°C for 3 hours). Raw turkey was extracted at 2°C with
75 percent ethanol for 72 hours, and volatiles were collected by
vacuum distillation. Derivatives were formed from carbonyl frac-
tion with 2,4-DNP, and these were identified by paper chromatog-
raphy. Acrolein was identified in raw turkey and in the volatile
products from both cooking methods.
C-10
-------
Love and Bratzler (1966) identified acrolein in wood smoke.
*•
Samples (whole smoke and vapor phase) were collected from commer-
cial smokehouses (operated at 48°C to 49.5°C) and from hardwood
sawdust (mainly maple) burned on a hot plate (490°C to 500°C). The
carbonyl compounds were trapped in 2,4-DNP solution, and the deriv-
atives were identified by GC. Acrolein was identified in all smoke
samples but was not quantified.
Levaggi and Feldstein (1970) examined acrolein concentrations
in the emissions from a commercial coffee roaster. Acrolein was
trapped in Greenberg-Smith impingers containing 1 percent sodium
bisulfite solution and was quantified by the 4-hexylresorcinol col-
orimetric method. At the emission outlet (afterburner abatement
device) they measured 0.60 mg/nr acrolein, while no acrolein was
detected in the inlet air.
Boyd, et al. (1965) measured the unsaturated aldehyde fraction
in raw cocoa beans and chocolate liquor. The 2-enols were measured
by absorbance (at 373 nm) of its 2,4-DNP derivative. Samples were
/i?\
extracted with hexane and cleaned on Celite^ prior to preparation
of derivatives. The 2,4-DNP derivatives were separated into frac-
tions prior to measurement. They measured 2-enol concentrations of
0.6 to 2.0 umol/100 g fat in raw cocoa beans and 1.3 to 5.3
umol/100 g in the chocolate liquor.
Alcoholic beverages often contain trace amounts of acrolein
(Rosenthaler and Vegezzi, 1955). It is sometimes a problem ^since
it causes an organoleptic condition called "pepper" by the alcohol
fermentation industry. According to Serjak, et al. (1954), acro-
lein is detectable in low-proof whiskey at concentrations as low as
Oil
-------
10 mg/1. This value probably represents the upper limit for acrolein,
since industry has adapted corrective procedures to reduce "pepper"
by reducing acrolein concentrations.
The chief point of entry of acrolein into the alcoholic bev-
erages has been reported to be the mash fermentation process
.'
(Serjak, et al. 1954; Sobolov and Smiley, 1960; Hirano, et al.
1962) , where if glucose levels in the mash are low, some bacterial
strains convert glycerol to acrolein.
Avent (1961) investigated the contamination of a wine, which
was initially acrolein-free, with 14 ug/g of acrolein. In this
case, the possible source was a glycerol-impregnated oak cask.
Hrdlicka, et al. (1968) identified acrolein in the volatile
fraction of a hops sample. No quantitative data were available.
Alarcon (1976a) has demonstrated the formation of acrolein
from methionine, homoserine, homocysteine, cystathionine, sper-
mine, and spermidine under conditions similar to those used in food
processing (neutral pH, 100°C).
The information reviewed herein is insufficient to develop a
conclusive measure of acrolein exposure in food, but it indicates
that acrolein is a component of many foods and that processing can
increase the acrolein content. Volatile fractions collected during
cooking suggest that some acrolein would remain in the food.
A bioconcentration factor (BCF) relates the concentration of a
chemical in aquatic animals to the concentration in the water in
which they live. The steady-state BCPs for a lipid-soluble com-
pound in the tissues of various aquatic animals seem to be propor-
tional to the percent lipid in the tissue. Thus, the per capita
C-12
-------
ingestion of a lipid-soluble chemical can be estimated from the per
.capita consumption of fish and shellfish, the weighted average per-
cent lipids of consumed fish and shellfish, and a .steady-state BCF
for the chemical.
Data from a recent survey on fish and shellfish consumption in
the United States were analyzed by SRI International (U.S. EPA,
1980). These data were used to estimate that the per capita con-
sumption of freshwater and estuarine fish and shellfish in the
United States is 6.5 g/day (Stephan, 1980). in addition, these
data were used with data on the fat content of the edible portion of
the same species to estimate that the weighted average percent
lipids for consumed freshwater and estuarine fish and shellfish is
3.0 percent.
A measured steady-state bioconcentration factor of 344 was
obtained for acrolein using bluegills (U.S. EPA, 1978). Similar
bluegills contained an average of 4.8 percent lipids (Johnson,
1980). An adjustment factor of 3.0/4.8 = 0.625 can be used to
adjust the measured BCF from the 4.8 percent lipids of the bluegill
to the 3.0 percent lipids that is the weighted average for consumed
fish and shellfish. Thus, the weighted average bioconcentration
factor for acrolein and the edible portion of all freshwater and
estuarine aquatic organisms consumed by Americans is calculated to
be 344 x 0.625 > 215.
Inhalation . .,
Acrolein is generated during oxidation of a variety of organic
substrates. It has been noted as a combustion product of fuels and
C-13
-------
of cellulesic materials (e.g., wood and cigarettes)/ as 'an inter-
mediate product in atmospheric, oxidation of propylene, and as a
component of the volatiles produced by heating organic substrates.
Actual exposure will depend on general environmental conditions and
specific behavior patterns. Thus, total inspiration is the sum of
acrolein inhalations from the ambient air, from local air (e.g.,
occupational considerations, vehicular considerations, side-stream
smoke from cigarettes), and from cigarette smoke.
Acrolein as a component of urban smog has been measured in the
atmosphere of Los Angeles (Renzetti and Bryan, 1961; Altshuller and
McPherson, 1963). Renzetti and Bryan collected ambient air in I960
using a series of vapor traps containing SD-3A alcohol and quanti-
fied acrolein by absorbance of the 4-hexylresorcinol-mercuric
chloride-trichloroacetic acid derivative (605 ran). Altshuller and
McPherson (1963) also examined the atmosphere in 1961, but col-
lected samples in bubblers containing the 4-hexylresorcinol re-
agent; their results were similar to those of Renzetti and Bryan
(1961). For 10 days during the period from September through
November 1963, Altshuller and McPherson found that acrolein aver-
aged 0.012 mg/m with a peak concentration of 0.025 mg/m , whereas
Renzetti and Bryan found that acrolein concentrations for seven
days of this period in 1961 averaged 0.018 mg/m and peaked at
0.030 mg/m . For all of 1961, acrolein averaged 0.016 mg/m and
peaked at 0.032 mg/ra . *
Graedel, et al. (1976) developed a mathematical model for
photochemical processes in the troposphere. They combined chemical
C-14
-------
kinetic measurements and assumed values, time-varying sources of
trace contaminants/ solar flux variations/ bulk air flow/ and a
geographical matrix of "reaction volumes" for Hudson County/ N.J.
•* 3
Their computed peak acrolein concentration was 0.03 mg/m . They
did not account for other sources of acrolein or for any degrada-
tion pathway (McAfee and Gnanadesikan/ 1977). That their calcu-
lated value favorably compared with the peak values measured in Los
Angeles (0.025 to 0.032 mg/m ) could be due to an artifact.
Trattner/ et al. (1977) suggested that enols are present in
the air of a subway system. They were measuring airborne particu-
lates by an infrared technique. Samples were collected on a cas-
cade impactor containing a 0.313 u back-up filter. Potassium bro-
mide pellets were prepared from each sample fraction. Evidence for
the presence of unsaturated aldehydes were the weak maxima observed
at 1,695 cm (6.90 u) in the pellets prepared from final impactor
and backup filter samples. The authors made no quantitative
assessment.
Acrolein is a common constituent of vehicle exhaust (National
Academy of Sciences (NAS)/ 1976; Tanimoto and Uehara, 1975). The
exact concentration depends upon the type of gasoline/ engine/ and
operating conditions. Acrolein concentrations have been measured
by a variety of methods/ and the consensus of the studies suggests
that the acrolein concentration usually does not exceed 23 mg/m .
Acrolein has been measured in emissions of diesel engines %t 6.7
mg/m and in the emissions of internal combustion engines at 6.0,
22.5, 16.1, 14.7, and about 11.5 mg/m3 (NAS, 1976). Day, et al.
(1971) reported acrolein in exhaust from a 1969 model truck oper-
C-15
-------
ated on a dynamometer. Acrolein was measured (by the colorimetric
2,4-DNP method) at 0.05 mg/ra3 at hot idle, 6.4 mg/m3 at 30 mph, and
4.4 mg/m at 50 mph.
Bellar and Sigsby (1970) developed a GC unit which trapped
organic substrates from air directly onto a GC cutter column (10
percent sucrose octaacetate on Gas-Chrom Z) at -55°C and then
injected the sample onto the analytical column. Their unit was
capable of measuring acrolein in the subpart per million range.
The unit was used in measuring, diesel exhaust, ambient air in an
area of traffic, and ambient air in the open field. Diesel exhaust
contained 12.4 mg/m acrolein. No acrolein was detected in the
open field sample and, at most, a trace was present in the sample
from the traffic area.
Cigarette smoke contains acrolein. While a cigarette smoker
inspires acrolein directly, some questions exist on passive expo-
sure of nonsmokers to acrolein in side-stream smoke (Kusama, et al.
1978; Horton and Guerin, 1974; Jermini, et al. 1976; Weber-Tschopp,
et al. 1976a).
Horton and Guerin (1974) measured the acrolein content of
cigarettes by cryogenically trapping smoke onto a gas chromatog-
raphy column. A 6-part smoking machine was used with puffs set at
1-minute intervals, 2-second durations, and 35 ml volume. Measured
acrolein concentrations for the tested cigarettes are described in
Table 5.
Hoffman, et al. (1975) measured acrolein in marijuana and
tobacco cigarettes using gas chromatography. Cigarettes were,
rolled to a length of 85* mm using standard cigarette paper.
C-16
-------
TABLE 5
Acrolein Delivery from Some Experimental and Some Commercial Cigarettes*
1
"4
Cigarette
Kentucky Reference
Commercial 85 mm,
Commercial 85 mm,
Experimental 85 mm
filtered
Acrolein Delivery
(IRI)
filtered
non-filtered
, charcoal
Experimental 85 mm (same as
above) , no-charcoal
-
Commercial 85 mm,
Experimental 85 mm
little cigar
, marijuana
iig/cig.
128
102
111
62
103
70
145
tig/puff
12
10
12
7
12
8
14
lig/g tobacco burned
159
153
135
97
155
107
199
^Sources Horton and Guerin, 1974
-------
Experimental details were incomplete. Hoffman, et al. (1975)
stated that smoking machines (1 or 20 channel) were employed and
contained 10 or fewer cigarettes. Error was placed at ±4 to 6 per-
cent. They reported acrolein delivery from mainstream smoke was
92 ug from marijuana cigarettes and 85 ug from tobacco cigarettes.
The potential exposure of nonsmokers to side-stream and ex-
haled cigarette smoke is an unresolved question. Holzer, et al.
(1976) suggested that passive exposure to cigarette smoke is not
important/ while Swiss workers (Weber-Tschopp, et al. 1976b; Jer-
mini, et al. 1976) have offered evidence that passive exposure is
an important inhalation route.
Holzer, et al. (1976) developed an absorption tube sampling
method to collect organic materials (volatiles and "particulate
matter associated"). The tubes (88 mm x 2.5 mm ID) were packed
with Tenax GC or Carbopack BHT. These tubes had an uncertain capa-
city for substances of lower retention than benzene, including
acrolein, so their results were only qualitative for acrolein. The
samples were desorbed and analyzed by GC-MS (mass spectral detec-
tion) using a glass capillary column. The authors compared the GC
chroma tograms of a sample of urban air (3.5,1 samples at 220
ml/min), a standard cigarette (IRI, University of Kentucky) (3 ml
of smoke taken during a puff of 2-second duration and 35 ml vol-
ume) , and air where a cigarette had been smoked under standard con-
ditions (same sampling conditions as for urban air). They sug-
gested that the volatiles in both air samples were associated with
gasoline vapor and that cigarette smoking did not appreciably add
to these volatiles. The journal editor disagreed and in a footnote
C-18
-------
stated that the chromatograms suggested that "a person breathing in
a room where one cigarette was smoked inspires the equivalent of a
3.5 ml puff of cigarette smoke".
The Swiss team (Jermini, et al. 1976; Weber-Tschopp, et al.
19765) measured acrolein concentration from cigarettes (U.S.) in
side-stream smoke in a nearly air-tight/ 30-m climatic room and in
a 272-liter plexiglass chamber. Acrolein was measured by gas
chromatography. They reported acrolein concentrations as follows:
3 33
in the 30-m room, 0.11 mg/m and 0.87 mg/m with 5 and 30 ciga-
rettes, respectively; and in the chamber, 0.85 mg/m for one ciga-
rette. These results suggested that inhalation of significant
quantities of acrolein can result from passive exposure to side-
stream smoke.
Acrolein has been identified as a component of smoke from wood
burning. Its detection in wood smoke at commercial smoke houses
(Love and Bratzler, 1966) was discussed in the Ingestion from Food
section. Bellar and Sigsby (1970) studied volatile organics by GC
(see above) in emissions from a trench incinerator burning wood.
They published chromatograms for the wood smoke emissions but did
not present quantitative data. An acrolein peak was present in the
chromatogram for wood smoke from the incinerator without forced
air. With forced air/ the chromatogram did not contain a peak for
acrolein/ and the peaks for carbonyl compounds were lower than those
for alcohols. ?
Hartstein and Forshey (1974) measured combustion products from
burning four classes of materials: polyvinyl chloride (PVC), neo-
prene, rigid urethane foams/ and treated wood. The materials were
C-19
-------
burned by two techniques: a sealed system (approximately 370°c)
and a stagnation burner (approximately 400°C). Cohdensible pro-
ducts were collected in a liquid nitrogen trap and analyzed by GC
(thermal conductivity detection). They noted that the acrolein,
concentrations measured were less than the actual amount present
since the tars and condensed water retain some acrolein. They
never observed acrolein in emissions from the PVC, neoprene, or
urethane foam samples. Acrolein was present in emissions from all
wood samples, as summarized in Table 6.
Dermal
Based upon the physical properties and known distribution of
acrolein in the environment, dermal exposure is judged to be negli-
gible.
PHARMACOKINETICS
Absorption
Egle (1972) has measured the retention of inhaled acrolein as
well as formaldehyde and propionaldehyde in mongrel dogs anesthe-
tized with sodium pentobarbital. In this study, dogs were exposed
to acrolein concentrations from 0.4 mg to 0.6 mg/1 for 1 to 3 min-
utes, and retention was calculated using the amount inhaled and the
amount recovered. In measurements of total respiratory tract ren-
tention at ventilatory rates between 6 and 20/rain., 81 to 84 per-
cent of inhaled acrolein was retained. An increase in tidal volume
(from 100 ml to 160 ml) resulted in a significant (p-^O.OOlf de-
crease in acrolein retention (from 86 to 77 percent). This was
consistent with findings that acrolein was taken up more readily by*
the upper than the lower respiratory tract.
C-20
-------
TABLE 6 ^_
Acrolein Produced by Burning Standard Southern Pine*
Acrolein Produced (rag/g
Wood
Treatment
None
None
Pen tachlor ophenol
Creosote
jg\
Koppers fire retardent Type Co/
Koppers waterborne preservative
co®
Sealed
Tube
0.67
0.62
1.21
0.43
unknown
0.47
wood burned)
Stagnation
Burner
0.21
0.70
1 0.59
0.22
0.68
*Source: Hartstein and Forshey, 1974
C-21
-------
Distribution
Studies that were directly relevant to the distribution of
acrolein upon oral administration were not found. Munsch, et al.
(1974b) have examined the incorporation of tritiated acrolein in
rats. Rats were injected (i.p.) with acrolein at 3.36 mg/kg 70
hours after partial hepatectomy. At 24 hours after injection,
88.66, 3.13f 1.72, 0.94, and 0.26 percentages of the recovered
radioactivity-were found in the acid-soluble, lipid, protein, RNA,
and DNA fractions of the liver, respectively. Based on measure-
ments taken 10 minutes to 24 hours after dosing, the extent of RNA
and DNA binding remained relatively constant, while protein binding
increased by about 70 percent. In vitro studies on the binding of
acrolein to nucleic acids are discussed in the Acute, Subacute, and
Chronic Toxicity section.
Metabolism
In terms of the potential toxicologic effects of acrolein in
drinking water, the instability of acrolein at acid pHs (see Inges-
tion from Water section) may be highly significant. As discussed
by Izard and Libermann (1978) and detailed in the Effects section
of this report, several of the toxic effects of acrolein are re-
lated to the high reactivity of the carbon-carbon double bond.
However, the low pHs encountered in the upper portions of the gas-
trointestinal tract would probably rapidly convert acrolein to
saturated alcohol compounds. The primary breakdown product* would
probably be beta-propionaldehyde (see Ingestion from Water sec-
tion) . If this is the case, the toxic effects of acrolein given by
oral administration would differ markedly from the effects observed
C-22
-------
following other routes of administration. No information is avail-
able on the toxic effects of the acrolein breakdown products. How-
ever, an analysis of subchronic and chronic studies suggests that
acrolein is markedly less toxic when given by oral administration
than when inhaled (see Basis and Derivation of Criterion section).
Relatively little direct information is available on the
metabolism of acrolein. Smith and Packer (1972) found that prepa-
rations of rat liver mitochrondria were capable of oxidizing sev-
eral saturated aldehydes but not unsaturated aldehydes, such as
acrolein, crotonaldehyde, and cinnamaldehyde. In vitro, acrolein
can serve as a substrate for alcohol dehydrogenases from human
liver, horse liver, and yeast with equilibrium constants of 6.5 x
10"11, 8.3 x 10'11, and 16.7 x KT11, respectively (Pietruszko, et
al. 1973). In vivo studies in rats indicate that a portion of sub-
cutaneously administered acrolein is converted to 3-hydroxypropyl-
mercapturic acid (Kaye and Young/ 1972; Kaye, 1973). Acrolein has
also been shown to undergo both spontaneous and enzymatically cata-
lyzed conjugation with glutathione (Boyland and Chasseaud, 1967;
Esterbauer, et al. 1975).
Alarcon (1964, 1970) has demonstrated that acrolein is formed
during the degradation of oxidized spermine and spermidine. Sera-
fini-Cessi (1972) has shown that acrolein is a probable metabolite
of allyl alcohol. Several investigators have demonstrated that
acrolein is a metabolite of the anti-tumor agent cyclophospfcamide
(Alarcon, 1976b; Alarcon and Meienhofer, 1971; Alaroon and Melen-
dez, 1974; Alarcon, et al. 1972; Connors, et al. 1974; Cox, et al.
1976a,b; Farmer and Cox, 1975; Gurtoo, et al. 1978; Hohorst, et al.
1976; Thomson and Colvin, 1974).
C-23
-------
Excretion
.-
In rats given single subcutaneous injections of acrolein, 10.5
percent of the administered dose was recovered in the urine as
3-hydroxypropylmercapturic acid after 24 hours (Kaye and Young,
1972; Kaye, 1973).
EFFECTS
Acute, Subacute, and Chronic Toxicity
Acute Effects on Experimental Systems: Several investigators
have described the toxic effects of acute lethal exposure to acro-
lein on experimental mammals (Boyland, 1940; Carl, et al. 1939;
Carpenter, et al. 1949; Skog, 1950; Smyth, et al. 1951; Pattle and
Cullumbine, 1956; Philippin, et al. 1969; Salem and Cullumbine,
1960). Albin (1962) has summarized some of these earlier studies
as well as unpublished reports (Table 7). Skog (1950) compared the
pathological effects of acute lethal subcutaneous and inhalation
exposures to acrolein in rats. After inhalation exposures, the
rats evidenced pathological changes only in the lungs. These
changes included edema, hyperemia, hemorrhages, and possible degen-
erative changes in the bronchial epithelium. Similar changes have
been noted in mice, guinea pigs, and rabbits (Pattle and Cullum-
bine, 1956; Salem and Cullumbine, 1960). After administering
lethal subcutaneous doses of acrolein to rats, Skog (1950) noted
less severe lung damage (edema without significant hemorrnaging)
but also found pathological changes in the liver (hyperemfm and
fatty degeneration) and kidneys (focal inflammatory changes).
Given the probable instability of acrolein on oral administra-
tion, a quantitative comparison of oral exposure with other routes
C-24
-------
TABLE 7
Acute Lethal Toxicity of Acrolein*
0
ro
in
Species
Mouse
Mouse
Dog
Rat'
Rat
Rat
Mouse
Rabbit
Rabbit
Rabbit
Rabbit
Rabbit
Rabbit
Route
Inhalation
Inhalation
Inhalation
Inhalation
Oral
Oral
Oral
Percutaneous
Percutaneous
Percutaneous
Percutaneous
Percutaneous
Percutaneous
Lethal Dose
LC5Q-875 ppra
LC50-175 ppm
LCgQ-150 ppm
I£50-8 PPm
LD5Q-46 mg/kg
LD5Q-42 mg/kg
LD50-28 mg/kg
LD5Q-200 mg/kg
LD50~562 m9/k9
LD50-335 mg/kg
LD5Q-1022 rag/kg
LD5Q-164 mg/kg
LD5Q-238 mg/kg
Exposure
Time
1 min
10 min
30 min
4 hr
• • •
• • •
• • •
• • •
• * •
• • •
• • •
• • •
* • *
Remarks
Approximate value
Approximate value
Approximate value
Approximate value
Approximate value
Undiluted acrolein
20% acrolein in water
10% acrolein in water
20% acrolein in mineral
10% acrolein in mineral
spirits
spirits
*Source: Albin, 1962
-------
would be of particular interest. In a study by Carl, et al. (1939),
rats given intraperitoneal injections of acrolein at 2.5 mg/kg/day
died on the second day. Single doses of 10 mg/kg given to two rats
by stomach tube killed both within 24 hours. However, six rats
tolerated doses of 5 mg/kg/day given by stomach tube for nine days.
Although firm conclusions cannot be made from this limited data,
these results suggest that acrolein has a greater acute lethal
potency when administered intraperitoneally than when given orally.
The sublethal effects of acute acrolein exposure on the liver
have received considerable investigation. In adult male rats,
inhalation exposures to acrolein or intraperitoneal injections of
acrolein cause increases in hepatic alkaline phosphatase activity
as well as increases in liver and adrenal weights. These effects,
however, occurred only in exposures causing dyspnea and nasal irri-
tation (e.g., 4.8 mg/m3 x 40 hours). Other hepatic enzyme activi-
ties, acetylcholine esterase and glutamic-oxalacetic transaminase,
were not affected. Since similar patterns were seen with other
respiratory irritants, the alkaline phosphatase response was
attributed to an alarm reaction rather than specific acrolein-
induced liver damage (Murphy, et al. 1964). In subsequent studies
(Murphy, 1965; Murphy and Porter, 1966), the effect of acrolein on
liver enzymes was linked to stimulation of the pituitary-adrenal
system resulting in hypersecretion of glucocorticoids and increased
liver enzyme synthesis. Although these results do not suggest that
acrolein is a direct liver toxin, Butterworth, et al. (1978) have
shown that intravenous infusions of acrolein at doses of 0.85 and
1.70 mg/kg induce periportal necrosis in rats. In further studies
C-26
-------
on the adrenocortical response of rats to acrolein, Scot and Murphy
(1970) demonstrated increased plasma and adrenal corticosterone
levels in rats given intraperitoneal injections of acrolein.
Unlike similar effects caused by DDT and parathion, the effect of
acrolein was not blocked by subanesthetic doses of phenobarbital
but was blocked by dexamethasone only at lower doses of acrolein.
The degree of increased corticosterone levels is dependent on the
state of the adrenocortical secretory cycle in which acrolein as
well as other toxins are administered (Szot and Murphy, 1971).
Since acrolein is a component of cigarette smoke, the sub-
lethal effects of acrolein on the respiratory system have been
examined in some detail. Murphy, et al. (1963) found that, in gui-
nea pigs, inhalation of acrolein at concentrations from 0.92 to 2.3
mg/ra for periods of up to 12 hours caused dose-related increases
in respiratory resistance, along with prolonged and deepened respi-
ratory cycles. In tests on guinea pigs exposed to whole cigarette
smoke from various types of cigarettes, Rylander (1973) associated
concentrations of acrolein and acetaldehyde with decreases in the
number of free macrophages. In mice exposed to acrolein in air at
concentrations from 2.3 to 4.6 mg/m for 24 hours there was evi-
dence of decreased pulmonary killing of Staphylococcus aureus and
Proteus mirabilis. This decrease in intrapulmonary bacterial kill-
ing was further suppressed in mice with viral pneumonia (Jakab,
1977). Kilburn and McKenzie (1978) have shown that acrolein*(13.8
mg/m x 4 hours) by inhalation is cytotoxic to the airway cells of
hamsters, causing both immediate and delayed exfoliation. When
administered either .with or adsorbed onto carbon particles, acro-
C-27
-------
lein induced leukocyte recruitment to the airways, mimicking the
effect of whole cigarette smoke. In a single 10-raihute inhalation
exposure of mice, acrolein caused dose-related decreases in respi-
ration attributed to sensory irritation, with an ECgg of 3.9 mg/m3
(Kane and Alarie, 1977). Formaldehyde caused the same effect and
exhibited competitive agonism in combination with acrolein (Kane
and Alarie, 1978).
Acrolein has been shown to exert pronounced ciliastatic activ-
ity in a variety of aquatic invertebrates (see review by Izard and
Libermann, 1978). As discussed by Wynder, et al. (1965), impair-
ment of ciliary function in the respiratory tract of mammals may be
involved in the pathogenesis of several respiratory diseases, in-
cluding cancer. Of several respiratory irritants examined by Car-
son, et al. (1966), acrolein was the most effective in reducing
mucus flow rates in cats after short-term inhalation exposures. In
in vivo assays of chicken trachea ciliary activity, acrolein and
hydrogen cyanide were found to be among the most potent ciliatoxic
components of cigarette smoke (Battista and Kensler, 1970). Simi-
larly, in tests on various types of cigarette smoke, Dalhamn (1972)
associated ciliastasis in cats with variations in the concentra-
tions of acrolein and tar.
In in vitro studies on the effects of cigarette smoke compo-
nents on rabbit lung alveolar macrophages, acrolein has been shown
to inhibit phagocytosis, adhesiveness, and calcium-dependant ATP-
ase activity (Low, et al. 1977) and to inhibit the uptake of cyclo-
leucine and cfc-aminoisobutyrate but not 3-0-methylglucose (Low and
C-28
-------
Bulman, 1977). However/ acrolein has been shown to inhibit the
uptake of glucose by rabbit erythrocytes (Riddick, et al. 1968).
Egle and Hudgins (1974) noted that low doses (0.05 mg/kg) of
acrolein administered by intravenous injection to rats caused an
increase in blood pressure/ but higher doses (0.5 to 5.0 mg/kg)
caused marked decreases in blood pressure and bradycardia. The
pressor response was attributed to increased catecholamine release
from sympathetic nerve endings and the adrenal medulla/ while the
depressor response was attributed to vagal stimulation. Depressor
effects were noted after 1-minute inhalation exposures to acrolein
at 2.5 and 5.0 mg/1. Acrolein elicited significant cardiovascular
effects at concentrations below those encountered in cigarette
smoke. Basu/ et al. (1971) have also examined the effects of acro-
lein on heart rate in rats. Tachycardia was induced in animals
under general (sodium pentobarbital) anesthesia/ while bradycardia
was induced in animals receiving both general anesthesia and local
ocular anesthesia (2 percent tetracain hydrochloride) prior to
acrolein exposure. Pretreatment with atropine (0.5 mgAg? i.v.)
along with local and general anesthesia blocked the bradycardia
response. Tachycardia was attributed to increased sympathetic dis-
charge caused by eye irritation. Since the bradycardia response
was blocked by atropine/ parasympathetic involvement was suggested.
*,
Several groups of investigators have examined the .general
cytotoxic effects of acrolein. Alarcon (1964) determine^ the
inhibitory activities of spermine/ spermidine/ and acrolein to
S-180 cell cultures. The concentrations of these compounds causing
50 percent inhibition were 1.4 to 1.5 x 10" mmol/ml for spermine/
C-29
-------
2.8 to 3.1 x 10 mmol/ml for spermidine, and 2.6 to 3.5 x 10~5
iranol/ml for acrolein. Since the inhibitory potencies, of these com-
pounds were similar- and since only the two amines required amine
oxidase in exerting the inhibitory effect, Alarcon (1964) proposed
that the inhibitory activity of the two amines was due to the in
vitro formation of acrolein. Two groups of investigators have
examined the role of acrolein in the viricidal effects of oxidized
spermine (Bachrach, et al. 1971; Bachrach and Rosenkovitch, 1972;
Nishimura, et al. 1971, 1972). Both groups determined that the
antiviral potency of acrolein was substantially less than that of
oxidized spermine and that the antiviral effects of oxidized sper-
mine are not attributable to the generation of acrolein.
Koerker, et al. (1976) have examined the cytotoxicity of acro-
lein and related short-chain aldehydes and alcohols to cultured
neuroblastoma cells. Aldehydes were consistently more toxic than
the corresponding alcohols. Based on viability of harvested cells
and increase in the number of sloughed cells after exposure, acro-
lein was more potent than formaldehyde and much more potent than
acetaldehyde or propionaldehyde. Based on decreases in neurite
formation and viability of sloughed cells, formaldehyde was some-
what more potent than acrolein and substantially more potent than
either acetaldehyde or propionaldehyde. In ir\ vitro tests on
Ehrlich-Landschutz diploid ascites tumor cells, Holmberg and Malm-
fors (1974) found acrolein to be substantially more toxic th|in for-
maldehyde over incubation periods of 1 to 5 hours. Both of these
aldehydes, however, were among the more toxic organic solvents
assayed in this study. Similarly, in in vitro tests of tobacco
C-30
-------
smoke constituents on mouse ascites sarcoma BP8 c'ells (48-hour
exposure periods), Pilotti, et al. (1975) found aldehydes to be
among the most toxic group of compounds studied. At a concentra-
tion of 100 uM, acrolein caused substantially greater inhibition
(94 percent) than formaldehyde (15 percent).
Several of the cytotoxicity studies on acrolein have addressed
the role of acrolein in the antineoplastic effects of cyclophospha-
mide. Sladek (1973) determined the cytotoxicity of cyclophospha-
mide and various cyclophosphamide metabolities, including acro-
lein, to Walker 256 ascites cells. In this study, ascites cells
were exposed to the various compounds jin vitro for one hour, then
injected into host rats. The proportion of viable ascites cells
was estimated from survival times of the rats. Based on this
assay, acrolein was found to be only marginally cytotoxic (LC9Q of
8.75 uM) and did not account for a substantial proportion of the
cytotoxicity of cyclophosphamide metabolites generated iri vivo.
Cyclophosphamide itself was virtually nontoxic (LCgo of^»100 uM).
Similar results on the cytotoxicity of acrolein to Walker ascites
cells was obtained by Phillips (1974) using an _in vitro test system
in which cells were exposed to cytotoxic agents for one hour, then
transferred to fresh culture medium. .Cytotoxicity was expressed as
a 72-hour ICgQ — the exposure concentration causing a 50 percent
decrease in cell number compared to untreated cells 72 hours after
treatment. The ICg0 for acrolein was 1.0 ug/ml (approximately 18
uM) and the IC5Q for cyclophosphamide was 6,000 ug/ml. Lelieveld
and Van Putten (1976) measured the cytotoxic effects of cyclophos-
phamide and six possible metabolites, including acrolein, to normal
C-31
-------
hcmatopoietic stem cells of mice/ osteosarcoraa cells, and L1210
leukemia cells. Acrolein was inactive against normal hematopoietic
stem cells and osteosarcoma cells, and less active than cyclophos-
phamide against leukemia cells. Similarly/ Brock (1976) has found
that acrolein is less active than cyclophosphamide against Yoshida
ascitic sarcoma of the rat.
The cytotoxic effects of acrolein may be attributed/ at least
in part/ to direct damage of nucleic acids or impaired nucleic acid
or protein synthesis. Using primary cultures of mouse-kidney tis-
sue exposed to a total of 70 ug acrolein/ Leuchtenberger/ et al.
(1968) noted a progressive decrease in the uptake of tritiated uri-
dine/ decreased RNA, and pycnosis of cell nuclei. Similarly/ in
cultures of polyoma-transformed cells from cell lines of Chinese
hamsters exposed to acrolein at concentrations of 0.8 to 2.5 x
10" M for one hour, Alarcon (1972) found concentration-related
decreases in the uptake of tritiated uridine/ tritiated thymidine,
and tritiated leucine. Using similar methods/ Rimes and Morris
(1971) have also demonstrated inhibition of DMA/ RNA/ and protein
synthesis by acrolein in Escherichia coli.
In jin vitro studies on the kinetics of acrolein inhibition of
rat liver and E. coli RNA-polymerases/ Moule, et al. (1971) found
that inhibition was unaffected by the amount of DNA in the medium
but was partially offset by increased levels of RNA-polymerase,
suggesting that acrolein acts on RNA-polymerase rather than DNA.
In parallel studies on rat liver and S. coli DNA-polymerase/
Munsch, et al. (1973) noted that acrolein inhibited rat liver DNA-
polymerase but stimulated E. coli DNA-polymerase. Since the active
032
-------
site of rat liver DNA-polymerase is associated with a functional
sulfhydryl group but E. coli DNA-polymerase is not and since acro-
lein's inhibitory effect on rat liver DNA-polymerase could be
antagonized by 2-raercaptoethanol (see Synergism and/or Antagonism
section), these investigators concluded that, acrolein acts on rat
liver DNA-polymerase by reacting with the sulfhydryl group. Subse-
quently, Munsch, et al. (1974a) demonstrated that tritiated acro-
lein binds 20 to 30 times more to rat liver DNA-polymerase than to
E. coli DNA-polymerase. In partially hepatectomized rats given
intraperitoneal injections of acrolein at doses of 0.1 to 2.7
rag/kg, DNA and RNA synthesis was inhibited in both the liver and
lungs (Munsch and Frayssinet, 1971).
Subacute Toxicity to Experimental Mammals: Most studies on
the subacute toxicity of acrolein have involved inhalation expo-
sures. In 1-month inhalation exposures of rats to acrolein at
1.2 mg/m , Bouley (1973) noted decreases in growth rates and in the
levels of oxidation-reduction coenzymes in the liver (additional
details not given). Rats continously exposed to acrolein in the
air at 1.27 mg/m3 for up to 77 days evidenced decreased food intake
accompanied by decreased body weight gain. Between days 7 and 21
of exposure, animals evidenced nasal irritation. Changes in rela-
tive lung and liver weights, as well as serum acid phosphatase
activity, are summarized in Table 8. Respiratory tract irritation,
a decrease in the number of alveolar macrophages, and increased
susceptibility to respiratory infection by Salmonella enteritidis
were noted only during the first three weeks of exposure (Bouley,
et al. 1975, 1976). Philippin, et al. (1969) also noted decreased
C-33
-------
TABLE 8
Relative Weights of Lungs and Liver, and Serum Level of Acid Phosphatases*
Parameters
Time
Control rats
Test Rats
Statistical
Analysis
o
ui
Lungs weight x 100
Body weight
15th and 32nd days
77th day
no significant difference between 2 x 10 control
and 2 x 10 test rats
n « 10
ra * 0.489
s.d. > 0.087
n * 15
m * 0.588
s.d. » 0.111
t « 2.67
0.02>P>0.01
Liver weight x
body weight
100
15th day
n - 10
m * 5.00
s.d. « 0.14
n - 10
m - 4.55
s.d. » 0.14
t = 7.12
0.001>P
32nd and 77th days
no significant difference between 10 and 15 con-
trol, and 10 and 15 test rats
mil of acid phosphatases
per ml of serum
15th day
32nd and 77th days
n * 10
m - 77.87
s.d. = 10.59
n - 10
m * 62.11
s.d. « 6.72
t = 3.91
P » 0.001
no significant differences between 10 and 11 con-
trol, and 10 and 11 test rats
*Source: Bouley, et al. 1976
n = number of rats; m = mean value; s.d. * standard deviation
-------
body weight in mice exposed to airborne acrolein at 13.8 rag/m and
34.5 mg/m , six hours per day/ five days per week, for six weeks.
Although the decreased body weight was significant (p 0.01), the
extent of the decrease was neither substantial (approximately
€ percent) nor dose-related.
Lyon, et al. (1970) exposed rats, guinea pigs, monkeys, and
dogs to acrolein concentrations of 1.6 and 8.5 rag/m in the air for
eight hours per day, five days per week, for six weeks. In addi-
tion, continuous exposures were conducted at 0.48, 0.53, 2.3, and
4.1 mg/m for 90 days using the same animals. The following bio-
logical endpoints were used to assess the effects of exposure:
mortality, toxic signs, whole body weight changes, hematologic
changes (hemoglobin concentration, hematocrit, and total leuko-
cytes) , biochemical changes (blood urea nitrogen, alanine and
aspartate aminotransferase activities), and pathological changes
in heart, lung, liver, spleen, and kidney. Gross effects were not
noted in the continuous exposures to acrolein at 0.48 and 0.53
mg/m or in the repeated exposures to 1.6 mg/m . In continuous
exposures to 2.3 and 4.1 mg/m and in repeated exposures to 8.5
mg/m , dogs and monkeys displayed signs of eye and respiratory
tract irritation and rats evidenced decreased weight gain. All
animals exposed repeatedly to acrolein at 1.6 mg/m developed
chronic inflammatory changes of the lung. These changes were more
pronounced in dogs and monkeys than in rats and guinea pigs, /ft 8.5
mg/m squamous metaplasia and basal cell hyperplasia of the tra-
cheas of dogs and monkeys were attributed to acrolein exposure. In
addition, this exposure induced necrotizing bronchitis and bron-
C-35
-------
chiolitis with squambus metaplasia in the lungs of 7 of 9 monkeys.
;•
Similar pathological results were noted in continuous exposures of
rats, guinea pigs, dogs, and monkeys to 2.3 and 4.1 mg/ra^.
Feron, et al. (1978) exposed hamsters, rats, and rabbits to
acrolein vapor at 0.4, 3.2, and 11.3 mg/nr six hours per day, five
days per week, for 13 weeks. At the highest concentration, all
animals displayed signs of eye irritation, decreased food consump-
tion, and decreased weight gain. In rats and rabbits, no abnormal
hematological changes were noted. Female guinea pigs at the high-
est dose, however, showed statistically significant increases in
the number of erythrocytes, packed cell volume, hemoglobin concen-
tration, number of lymphocytes, and a decrease in the number of
neutrophilic leukocytes. Additional changes noted in this study
are summarized in Table 9.
Watanabe and Aviado (1974) have demonstrated that repeated
inhalation exposures of mice to acrolein (100 mg/ra3 for 30 minutes,
twice a day for five weeks) cause a reduction in pulmonary com-
pliance.
The subacute oral toxicity of acrolein has been examined in
less detail. Albin (1962) found that rats exposed to acrolein in
drinking water at concentrations up to 200 mg/1 for 90 days evi-
denced only slight weight reduction at the highest level tested.
This was attributed to unpalatability of the drinking water. Simi-
*
lar results have been reported by Newell (1958) (summarized in NAS,
1977). In one study, acrolein was added to the drinking water of
male and female rats at 5, 13, 32, 80, and 200 mg/1 for 90 days. No
hematologic, organ-weight, or pathologic changes could be attrib-
uted to acrolein ingestion. At the highest concentration, water
C-36
-------
TABLE 9
Summary of Treatment-Related Effects in Hamsters, Rats and Rabbits
Repeatedly Exposed to Acrolein for 13 Weeks*
O
Criteria
Affected
Effects
a
Hamsters
Acrolein (ppm)
Rats
Acrolein (ppm)
Rabbits
Acrolein (ppm)
Symptoraa tology
Mortality
Growth
Food intake
Haema tology
Urinary amorphous
material
Urinary crystals
Organ weights
Lungs
Heart
Kidneys
Adrenals
Gross pathology
Lungs
Histopathology
Nasal cavity
Larynx
Trachea
Bronchi + lungs
0.4
0
0
0
NE
0
0
0
0
0
0
0
0
0
0
0
0
1.4
X
0
0
NE
0
•
0
0
0
0
0
0
0
X
0
0
0
4.9
XXX
0
«-.
NE
X
+
. -
ft
+
+
0
0
XXX
X
XX
0
0.4
0
0
-
0
0
0
0
0
0
0
0
0
X
0
0
0
1.4
X
0
—
-
0
0
0
0
0
0
0
0
XX
0
0
0
4.9
XX
+++
—
0
+
-
•n-
+
+
+++
X
XXX
XX
XXX
XXX
0.4
-fl
0
0
0
0
0
0
0
0
0
0
0
0
NE
0
0
1.4
X
0
-
-
0
0
0
0
0
0
0
0
0
NE
0
0
j'9
XXX
.0
_._
—
0
•f
0
++
0
0
0
0
XX
NE
X
XX
*Source: Feron, et al. 1978
0 =• not affected; x = slightly affected; xx = moderately affected;
xxx = severely affected; + = slightly increased; ++ = moderately increased;
+++ - markedly increased; - = slightly decreased;— - moderately decreased;
= markedly decreased; NE - not examined
-------
consumption was reduced by one-third for the first three weeks. By
the 12th week, the rats had apparently adapted to'the odor and
taste of acrolein. . In a subsequent study, acrolein was added to
-*
the drinking water of male rats at concentrations of 600, 1,200,
and 1,800 mg/1 for 60 days. All animals died at, the two higher
concentrations, and 1 of 5 animals died at 600 mg/1 concentration.
Death was apparently due to lack of water intake. Tissues from the
animals surviving 600 mg/1 did not show any gross or micropatho-
logic abnormalities.
Chronic Toxicity to Experimental Mammals: The only published
chronic toxicity study on acrolein is that presented by Feron and
Rruysse (1977). In this study, male and female Syrian golden ham-
sters were exposed to acrolein at 9.2 mg/m in the air, seven hours
per day, five days per week, for 52 weeks. During the first week of
exposure, animals evidenced signs of eye irritation, salivated, had
nasal discharge, and were very restless. These signs disappeared
during the second week of exposure. During the exposure period,
males and females had reduced body weight gains compared to the
control animals but the survival rate was unaffected. Heraatologi-
cal changes, i.e., slight but statistically significant increased
hemoglobin content and packed cell volume, occurred only in fe-
males. Similarly, significant (p
-------
Effects on Humans: As summarized in Table 10, considerable
information is available on the irritant properties of acrolein to
humans. In studies on photochemical smog, Altshuller (1978) has
estimated that acrolein could cause 35 to 75 percent as much irri-
tation as formaldehyde. Schuck and Renzetti (1960) indicated that
acrolein and formaldehyde account for most of the eye irritation
caused by the photooxidation of various hydrocarbons. Acrolein is
also involved in the irritant effect of cigarette smoke (Weber-
Tschopp, et al. 1976a,b, 1977).
Relatively little information, however, is available on the
toxic effects of acrolein in humans. Henderson and Haggard (1943)
state that vapor concentrations of 23 mg/m are lethal in a short
time.
In a study on irritant dermatitis induced by diallylglycol
carbonate monomer, Lacroix, et al. (1976) conducted patch tests on
humans with acrolein. In these tests, acrolein solutions in etha-
nol caused no irritation at concentrations (v/v) of 0.01 to 0.1
percent. At a concentration of 1 percent, 6 of 48 subjects showed
a positive response (two erythemas and four serious edemas with
bullae). At a concentration of 10 percent, all eight subjects had
positive responses. Histological findings of a second series of
tests with 10 percent acrolein are summarized in Table 11.
Kaye and Young (1974) have detected 3-hydroxypropylmercap-
turic in the urine of patients receiving cyclophosphamide ,prally
(50 mg tvice or three times daily) but not in the urine of untreated
humans. Based on analogies to the metabolic patterns of
C-39
-------
TABLE 10
Irritant Properties of Acrolein to Humans
Exposure
Effect
Reference
0.58 mg/m x 5 min.
2.3 mg/ra^ x 1 min.
2.3 mg/ra x 2 to 3 min.
2.3 mg/m3 x 4 to 5 min.
4.1 mg/nu x 30 sec.
4.1 ag/nu x 1.0 min.
n 4.1 mg/ra x 3 to 4 min.
i
*»
0 i
12.7 mg/m x 5 sec.
12.7 mg/m3 x 20 sec.
12.7 mg/ra x 1 min.
50.1 mg/m3 x 1 sec.
0.48
2.3 mg/m3
9.2 mg/mj
1.8 mg/ra x 10 min.
2.8 mg/m x 5 min.
moderate irritation of sensory
organs
slight nasal irritation
slight nasal and moderate eye
irritation
moderate nasal irritation and
practically intolerable eye
irritation
odor detectable
slight eye irritation
profuse lachrymation; practically
intolerable
slight odor; moderate nasal and
eye irritation
painful eye and nasal irritation
marked lachrymation; vapor prac-
tically intolerable
intolerable
odor threshold
highly irritating
lacrimation
lacrimation within 20 seconds,
irritation to exposed mucosal
surfaces
lacrimation within 5 seconds,
irritation to exposed mucosal
surfaces
Albin, 1962
Reist and Rex, 197?
Pattie and
Culluntbine, 1956
Sim and Pattle,
1957
-------
TABLE 11
Patch Tests with Ten Percent Acrolein in Ethanol on
Control Subjects (Biopsied at 48 Hours)*
No. of
Biopsy
CM 375
CM 376
CN 74
CN 88
CN 89
CN 90
CN 91
CN 178
CN 179
CN 346
CN 347
CN 348
Polymorph. Papillary
Infiltrate Edema Epidermis
+++ ++ 0
+ ++ Necrosis
!,• ^^ Q
•M. ++ Necrosis
+ + 0
* + Necrosis
++ + : 0
+ . •«• Necrosis
* + Necrosis
0 + Bullae
•i»i-* •»• - 0
•M. *+• Bullae
Result
Irritation
Irritation
Irritation
Irritation
Irritation
Irritation
Irritation
Irritation
Irritation
Irritation
Irritation
Irritation
*Source: Lacroix, et al. 1976
C-41
-------
cyclophosphamide in rats, these investigators concluded that acro-
lein is probably a metabolite of cyclophosphamide in man.
In studies 014 human polymorphonuclear leukocytes (PMNs),
Bridges, et al. (1977) found that acrolein was a potent iri vitro
inhibitor of PMN chemotaxis (EC5Q of 15 urn) but had no significant
effect on PMN integrity (measured by beta-glucurbnidase release,
lactic acid dehydrogenase release, and cell viability) or glucose
metabolism (measured by glucose utilization, lactic acid produc-
tion, and hexose monophosphate activity). Cysteine, at a concen-
tration of 10 mM, completely blocked the inhibitory effect of
160 urn acrolein on PMN chemotaxis. These results are consistent
with the assumption that acrolein inhibits chemotaxis by reacting
with one or more essential thiol groups on cellular proteins in-
volved in chemotaxis. These proteins, however, do not appear to be
involved in glucose metabolism.
Schabort (1967) demonstrated that acrolein inhibits human lung
lactate dehydrogenase. Inhibition appeared to be noncompetitive
with respect to both NAOH and pyruvate.
Little information is available on the chronic effects of
acrolein on humans. An abstract of a Russian study indicates that
occupational exposure to acrolein (0.8 to 8.2 mg/nr), methylmercap-
tan (0.003 to 5.6 mg/m3), methylmercaptopropionaldehyde (0.1 to
6.0 mg/m3), formaldehyde (0.05 to 8.1 mg/m3), and acetaldehyde
(0.48 to 22 mg/m ) was associated with irritation of the mucous
membranes. This effect was most frequent in women working for less
than one year and greater than seven years (Kantemirova, 1975).
C-42
-------
Synerqism and/or Antagonism
Acrolein is highly reactive toward thiol groups. Acrolein
rapidly conjugates with both glutathione and cysteine (Esterbauer,
Jf ,
et al. 1975, 1976). Cysteine has been shown to antagonize the
cytotoxic effects of acrolein on ascites tumor cells of mice (Til-
lian, et al. 1976). Cysteine also antagonizes the inhibition of
X
acrolein on rabbit alveolar macrophage calcium-dependent ATPase,
phagocytosis, and adhesiveness (Low, et al. 1977). Both cysteine
and ascorbic acid have been shown to antagonize the acute lethal
effects of orally administered acrolein in male rats (Sprince, et
al. 1978). Munsch, et al. (1973, 1974a) have demonstrated that
2-raercaptoethanol antagonizes the inhibitory effect of acrolein on
rat liver DNA-polymerase. The irritant effects of acrolein in-
jected into the footpad of rats were blocked by N-acetyl-cysteine,
penicillamide, glutathione, 0-mercaptopropionylglycine, 2-mercap-
toethanol, and ^^.^dimethylcysteamine (Whitehouse and Beck,
1975).
The effects of acrolein, unlike those of ODT and parathion, on
the adrenocortical response of rats is not inhibited by pretreat-
raent with phenobarbital and is only partially inhibited by dexa-
methasone (Szot and Murphy, 1970).
Pretreatment of rats with acrolein (3 mg/kg, i.p.) signifi-
cantly prolongs hexobarbital and pentobarbital sleeping times
(Jaeger and Murphy, 1973).
V
Teratogenicity
Reports have not been encountered on the potential teratogeni-
city of acrolein.
C-43
-------
Bouley, et al. (1976) exposed male and female rats to acrolein
vapor at 1.3 mg/m for 26 days and found no significant differences
either in the number, of pregnant animals or in the number and mean
weight of fetuses.
Mutagenicity
In the dominant-lethal assay for mutagenicity in ICR/Ha Swiss
mice, acrolein did not cause a significant increase in early fetal
deaths or pre-implantation losses at doses of 1.5 and 2.2 mg/kg
given in single intraperitoneal injections to male mice prior to an
8-week mating period (Epstein, et al. 1972).
As summarized by Izard and Libermann (1978) , Rapoport (1948)
assayed several olefinic aldehydes for their ability to induce sex-
linked mutations in Drosophila melanogaster. Acrolein had the
highest activity, causing 2.23 percent mutations (IS mutations
among 671 chromosomes).
Using a strain of DNA-polymerase deficient Escherichia coli,
Bilimoria (1975) detected mutagenic activity in acrolein as well as
cigar, cigarette, and pipe smoke. In a strain of E. eoli used for
detecting forward mutations (from gal Rs to gal* and from 5-methyl-
tryptophan sensitivity to 5-methyltryptophan resistance) and
reverse mutations (from arg~ to arg"1") , acrolein demonstrated no
mutagenic activity with or without activation by mouse liver homo-
genates (Ellenberger and Mohn, 1976, 1977).
Bignami, et al. (1977) found that acrolein induced mutagenic
B
effects in Salmonella typhimurium strains TA1538 and TA98 (inser-
tions and deletions), but showed no activity in strains TA1535 or
TA100 (base-pair substitutions). Anderson, et al. (1972) were
C-44
-------
unable to induce point mutations in eight histidine-requiring
mutants of S. typhimurium. This system also gave negative results
for 109 other herbicides but was positive for three known mutagens:
diethyl sulfate, N-methyl-N'-nitro-N-nitrosoguanidine, and ICR-
Izard (1973) determined the mutagenic effects of acrolein on
three strains of Saccharomyces cerevisiae. In strain N123, a his-
tidine auxotroph, acrolein at 320 rag/1 induced twice the control
incidence of respiratory-deficient mutants. In two methionine
auxotroph haploid strains used to assay for frameshift mutations
and base-pair substitutions, acrolein was inactive. As discussed
by Izard and Libermann (1978), these results suggest that acrolein
is not a strong inducer of respiratory deficient mutants and does
not appear to induce frameshift mutations or base-pair substitu-
tions in S. cerevisiae. However, this lack of activity could be
due to the high toxicity or instability of acrolein or to the in-
ability of these strains to convert acrolein to some other active
molecule. . .
Carcinogenic!ty
Ellenberger and Mohn (1976) indicated that acrolein is "known
as (a) cytotoxic and carcinogenic compound." The carcinogenicity
of acrolein has not been confirmed in this review of the litera-
ture. In the chronic inhalation study by Feron and Kruysse (1977)
acrolein gave no indication of carcinogenic activity, had ho effect
»
on the carcinogenic activity of diethylnitrosamine (DENA), and had
a minimal effect on the carcinogenic activity of benzo(
-------
Table 12. Based on these results, Feron and Kruysse (1977) con-
cluded that "...the study produced insufficient evidence to enable
acrolein to be regarded as an evident cofactor in respiratory tract
carcinogenesis." Similar results have been obtained in a not-yet-
published bioassay sponsored by the National Cancer Institute
(Sharon Feeney, personal communication). In this study, hamsters
were exposed to acrolein vapor at 11.5 mg/ra , six hours per day,
five days per week, throughout their life span. Evidence was not
found that acrolein was a carcinogen or a cocarcinogen with either
benzo(<7*>)pyrene or ferric oxide. DiMacco (1955) summarizes a study
by Savoretti (1954) indicating that acrolein resulted in an in-
crease in the incidence of benzopyrene-induced neoplasms. This
summary does not provide information on the species tested, doses,
routes of administration, or the significance of the observed in-
crease.
Boyland (1940) found that acrolein, at daily oral doses of
0.25 mg/mouse, had a marginal (p^O.l) inhibitory effect on the
growth of spontaneous skin carcinomas and a significant (p-^0.05)
inhibitory effect on the growth of grafted sarcomas.
C-46
-------
TABLE 12
Sit*. Type, and Incidence of Respiratory Tract Tumor » In Haaatera Eipoaed to
Air or AeroleIn Vapor and Treated Intratracheally with BP or Subcutaneously with DENA*
Incidence
of TiMora
Inhalation of Air
Site and Type
of TuMora
I
* No of anlMala
xj t
examined
Larynx
Papllloaa
Trachea
Polyp
PaplllMa
Squaaoua cell
carcinoma
lUonch!
Polyp
Papiiioma
' Adenocarclnoaia
Squaaioua cell
carcinoma
Lung a
Papillary
adenoaia"
Aclnar adenoaia
Adenoaquaaous
adenoaa
SquaHoua cell
carclnoaa '
Oat cell-like
carcinoma
* 0.91
NaClb |
V
21
0
0
0
0
s
0
0
0
0
0
.9 **
0
0
BPC
1«. 2 •?>
27
1
0
0
0
0
1
0
0
0
0
1
0
0
BP*
|1C. 4
24
0
0
1
2
0
0
1
0
1
2
0
0
0
•g) OBNA*
Feaale*
27
3
0
•
0
0
2
0
0
0
0
0
0
0
* O.M
NaCl"
V
27
0
0
1
0
0
0
0
0
0
0
0
0
0
Inhalation of Acroleln
BPC
(U.2 •«.!
29
0
1
3
Q
0
0
0
0
2
2
0
0
0
BP*
(3C.4 M9>
30
0
0
C
2
0
0
0
1
4
5
2
1
1
DENA*
20
S
0
•
0
1
1
0
0
0
0
0
0
0
-------
TABLE 12 (continued)
Incidence of Tuarora
Inhalation of Air
0
I
4k
OB
-
Site and Type
of Tuaora
No of anl.fla
eiMlned'
Naaal cavity
Polyp
Papllloaa
Adenocarc 1 noaa
taryni
PapllloM
Trachea
Polyp
PaptlloM
Squftaoua cell
carclno.a
Anaplestle
carcinoma
Sarcoaa
Bronchi
Polyp
PapilloM
Adenoaa
Adenocarclno»a
l.ungi
Papillary adendfta
Acinar adeno.a
Adenosqua.oua
adenoaa
Adenocarc Inoaa
8 0.9«
BPC
NaClb (11.2 .9!
V
10
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
29
0
0
0
0
0
2
0
0
0
0
I
0
0
0
1
1
0
BPd
, (!«.« .91
DBNA*
Nalea
10 29
0
0
0
1
0
5
1
1
I
0
2
0
I
C
1
2
2
1
0
1
7
2
1
0
0
0
1
2
0
0
0
0
0
0
* 0.9»
NaClb
V
10
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
*«•-
Inhalation of Acroleln
BPC
I1-.2 .91
10
0
0
0
0
1
1
0
0
1
0
1
0
0
0
1
I
0
BP*
(1C. 4 *9l
29
0
0
0
1
2
1
1
2
1
2
0
1
2
4
1
1
0
DBMJt*
10
0
1
0
4
1
S
0
0
0
0
0
0
0
0
0
0
0
-------
TABLE 12 (continued)
Incidence
of TiMora
Inhalation of Air
O
I
Site >and Type
of Tiworp
AdenoequaMoua
carcinoaia
SquMoui cell
carcinoma
Oat cell-like
carclnoM
Anaplaatlc
carcinoaa
* 0.91
MaCl"
0
0
0
0
BPC
III. 2 my}
0
0
0
0
tt*
(16.4 »gj
0
1
0
1
OBHA*
0
0
0
0
* 0.9%
MaClb
0
0
0
0
Inhalation of Acroleln
Hi. 2 B9)
0
1
0
0
(16.4 Kg)
1
1
1
0
DEN A*
o t
0
0
0
•Sources Peron and Kruyaae. 1977
*Ho further treatment
Given Intratracheally (0.2 all «eek!y during 52 wb
C0lven Intratracheatly In S2 weekly doaea of 0.15 mg
Given intratracheally In 52 weekly doaea of 0.70 mq
'Given aubcutaneoualy In 17 three-weekly doaea of 0.125 ul
*A few haaaters were loat through canniballa« or autolyala
-------
CRITERION FORMULATION
Existing Guidelines and Standards
Th« current time-weighted average threshold limit value (TLV)
for acrolein established by the American Conference of Governmental
Industrial, Hygienists (ACGIH, 1977) is 0.1 ppm (0.25 mg/m3). The
same value is enforced by the Occupational Safety and Health Admin-
istration (39 FR 23540). The ACGIH standard was designed to "mini-
mize, but not entirely prevent, irritation to all exposed individ-
uals" (ACGIH, 1974). Kane and Alarie (1977) have reviewed the
basis for this TLV in terms of both additional data on human irri-
tation and their own work on the irritant effects of acrolein to
mice (summarized in the Acute, Subacute, and Chronic Toxicity sec-
tion) . These investigators concluded that "the 0.1 ppm TLV for
acrolein is acceptable but is close to the highest value of the
acceptable 0.02 to 0.2 ppm range predicted by this animal model"
(Kane and Alarie, 1977).
The Food and Drug Administration permits the use of acrolein
as a slime-control substance in the manufacture of paper and paper-
board for use in food packaging (27 FR 46) and in the treatment of
food starch at not more than 0.6 percent acrolein (28 FR 2676).
In the Soviet Union, the maximum permissible daily concentra-
tion of acrolein in the atmosphere is 0.1 mg/ra (Gusev, et al.
1966). This study did not specify whether this level is intended
as an occupational or ambient air quality standard.
Current Levels of Exposure
As detailed in the Exposure section, quantitative estimates of
current levels of human exposure cannot be made based on the avail-
able data. Acrolein has not been monitored in ambient raw or
finished waters.
C-50
-------
Special Groups at Ri^<
Since acrolein is a component of tobacco and marijuana smoke,
people exposed to these smokes are a group at increased risk from
inhaled acrolein. In addition, acrolein is generated by the ther-
mal decomposition of fat, so cooks are probably also at additional
risk (see Exposure .section). since acrolein has been shown to sup-
press pulmonary antibacterial defenses, individuals with or prone
to pulmonary infections may also be at greater risk (Jakab, 1977).
Basis and Derivation of Criterion
Although acrolein is mutagenic in some test systems (see Muta-
genicity section) and can bind to mammalian DNA (see Acute Effects
on Experimental Systems section), current information indicates
that acrolein is not a carcinogen or cocarcinogen (see Carcino-
genicity section). Water quality criteria for acrolein could be
derived from the TLV, chronic inhalation studies, or subacute oral
studies using noncarcinogenic biological responses.
Stokinger and Woodward (1958) have described a method for cal-
culating water quality criteria from TLVs. Essentially, this
method consists of deriving an acceptable daily intake (ADI) for
man from the TLV by making assumptions on breathing rate and
absorption. The ADI is then partitioned into permissible amounts
from drinking water and other sources. However, because the TLV is
based on the prevention of the irritant effects of acrolein on
inhalation exposures, such a criterion would.have little, if any,
«
validity.
A criterion could also be estimated based on chronic inhala-
tion data. Female hamsters exposed to acrolein at 9.2 mg/m3 in the
C-51
-------
air, seven hours per day, five days per week, for 52 weeks evi-
denced slight hematologic changes, significant decreases in liver
weight, and significant increases in lung weights (Feron .and
Kruysse, 1977). By making assumptions of respiratory volume and
retention, the exposure data from this study can be., converted to a
mg/kg dose and an "equivalent" water exposure level can be calcu-
lated. The average body weight for the hamsters at the end of the
exposure was about 100 g. Assuming a mean minute volume (amount of
air exchanged per minute) of 33 ml for a 100 g hamster (Robinson,
1968) and a retention of 0.75, the average daily dose is estimated
at 68.3 ug/animal (9.2 mg acrolein/m x 0.033 1/min x 1 m /1,000
liters x 60-min/hour x 7 hours/day x 5 days/7 days x 0.75) or 683
ug/kg. Using an uncertainty factor of 1,000 (NAS, 1977), an esti-
mated "unacceptable" daily dose for man is 0.683 ug/kg or 47.8
ug/man, assuming a 70 kg body weight.
A criterion based on this daily dose level would be unsatis-
factory for two reasons. First, the dose data used to derive the
standard are not based on a no-observed-effect level (NOEL). In
this respect, the derived criterion could represent an undesirably
high level in water. Secondly, the estimation is based on an
inhalation study. Given the probable instability of acrolein in
the gastrointestinal tract, the use of inhalation data may not be
suitable for deriving a criterion.
In Drinking Water and Human Health, the National Academy of
Sciences (NAS, 1977) summarized the study by Newell (1958) in which
acrolein was added to the drinking water of rats at concentrations
of 5, 13, 32, 80, and 200 mg/1 for 90 days without apparent adverse
C-52
-------
effects (see Acute, Subacutae, and Chronic Toxicity - section) .
Assuming a daily water, consumption of 35 ml/day and a body weight
of 450 g (ARS Sprague-Dawley, 1974), the chronic no-effect dose for
rats based on 200 mg/1 in water is estimated at 15.6 mg/kg. This-
value may be converted into an ADI for man by applying an uncer-
tainty factor. Since the study involved only 90-day exposures, an
uncertainty factor of 1,000 is recommended (NAS, 1977). thus, the
estimated ADI for man is 15.6 ug/kg or 1.09 mg/man, assuming a 70 kg
body weight. Therefore, consumption of 2 liters of water daily and
6.5 grams of fish having a bioconcentration factor of 215 would
result in, assuming 100 percent gastrointestinal absorption of
acrolein, a maximum permissible concentration of '0.32 ug/1 for the
ingested water:
0.321 mg/1
21+ (215 x 0.0065) x 1.0
This calculation assumes that 100 percent of man's exposure is con-
tributed by ingesting water and contaminated fish/shellfish prod-
ucts. Although it is desirable to develop a criterion based on
total exposure analysis, the data for other exposure are not suffi-
cient to support a factoring of the ADI level.
In summary, based on the use of acute toxicologic data for
rats and an uncertainty factor of 1,000, the criterion level cor-
responding to the calculated acceptable daily intake of 15.6 ug/kg
is 0.32 mg/1. Drinking water contributes 12 percent of the assumed
*
exposure while eating contaminated fish products accounts for 88
percent. The criterion level for acrolein can alternatively be
expressed as 0.78 mg/1 if exposure is assumed to be from the con-
sumption of fish and shellfish products alone.
C-53
-------
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C-55
-------
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C-56
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C-57
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