ACROLEIN
Ambient Water Quality Criteria
Criteria and Standards Division
Office of Water Planning and Standards
U.S. Environmental Protection Agency
Washington, D.C.
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CRITERION DOCUMENT
ACROLEIN
CRITERIA
Aquatic Life
For acrolein the criterion to protect freshwater aquatic
life as derived using the Guidelines is 1.2 ug/1 as a 24-hour
average and the concentration whould not exceed 2.7 ug/1 at any
time.
The data base for saltwater aquatic life is insufficient to
allow use of the Guidelines. The following recommendation is
inferred from toxicity data for freshwater organisms.
For acrolein the criterion to protect saltwater aquatic life
as derived using procedures other than the Guidelines is 0.88
ug/1 as a 24-hour average and the concentration should not exceed
2.0 ug/1 at any time.
Human Health
For the protection of human health from the adverse effects
of acroelin ingested through the consumption of water and contaminated
aquatic organisms a criterion of 6.5 ug/1 is suggested.
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Introduction
Acrolein has a wide variety of applications. It is directly
used as a biocide for aquatic weed control; for algae, weed and
mollusk control in re-circulating process water systems; for
slime control in the paper industry; 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 inter-
mediate in the chemical industry. Its dimer, which is prepared
by a thermal, uncatalyzed reaction, has several applications, in-
cluding use as an intermediate for crosslinking agents, humec-
tants, plasticizers, polyurethane intermediates, copolymers and
homopolymers, and Greaseproofing cotton. The monomer is utilized
in synthesis via the Diels-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, as coatings for aluminum and steel panels,
as well as other applications. Hess, et al. (1978) described
marketing aspects of acrolein. In 1975 worldwide production was
about 59 kilotons. Its largest market was for methionine
manufacture. Worldwide capacity was estimated at 102
kilotons/year of which U.S. capacity was 47.6 kilotons/year.
Acrolein (2-propenal) is a liquid with a structural formula
of CH2=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
A-l
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and its water solubility is 20.8 percent by weight at 20°C
(Standen, 1967).
A flammable liquid with a pungent odor, acrolein is an un-
stable compound that undergoes polymerization to the plastic
solid disacryl, especially under light or in the presence of
alkali or strong acid (Windholz, 1976). It is the simplest
member of the class of unsaturated aldehydes, and the extreme
reactivity of acrolein is due to the presence of a vinyl group
H 0
C-) and an aldehyde group (-C-H) 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).
.Freshwater acute toxicity values as low as 61 ug/1 have been
reported. A chronic fish value of 21.8 ug/1 has been demonstrat-
ed. Acrolein has been found to bioconcentrate 344 times in a
freshwater fish. Saltwater acute toxicity in one fish species
was found to be 240 ug/1. No bioconcentration or chronic data
are available for marine species.
Acrolein has been shown to produce a great variety of dis-
orders in mammalian animals and man. However, it has not been
shown to be a teratogen and only a mild to weak mutagen, if one
at all, depending on the test system employed. Though it has
been suspected as a carcinogen or cytotoxigen, information does
not definitively produce evidence of confirmation.
Acrolein can enter the aquatic environment by its use as an
aquatic herbicide, from industrial discharge, and from the chlor-
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ination of organic compounds in waste water 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
fires, and cigarette smoke. An evaluation of available data in-
dicates that, while industrial exposure to manufactured acrolein
is unlikely, acrolein is pervasive from nonmanufactured sources.
Acrolein exposure will occur through food ingestion and inhala-
tion. 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 samples, with concentrations
ranging from 20 to 200 yg/1 (UoS. 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 acrolein dissipated after eight days were
34 percent from the tank and 16 percent from the bottles. The
rate of disappearance of acrolein in the tank was 0.83 day"-1-
at a pH of 7.2. The lack of turbulence in the tank reduced acro-
lein loss by volatilization to 1/20 of what would be expected if
volatilization was controlled only by resistance in the gas phase
and any discrete surface layers. The authors agree with Geyer
(1962), who states that the primary degradation reaction is re-
versible hydrolysis to ^-hydroxypropionaldehyde, which is less
volatile than acrolein.
The fate of acrolein in water was observed in buffered solu-
tions and in natural channel waters (Bowmer and Higgins, 1976).
An equilibrium between dissipating acrolein and degradation pro-
ducts was reached in the buffered solution following dissipation
of 92 percent of the acrolein, but in natural waters there was no
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indication of an equilibrium, with the dissipating reaction, ap-
parently being continued to completion. In natural waters/ the
accumulation of a reaction (degradation) product was greater at
higher initial acrolein-concentration, and decay was rapid when
acrolein concentration 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 processes. Unlike
earlier works (Bowmer, et al. 1974), there was an eight- to ten-
fold increase in the observed dissipation rate as compared to the
expected 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. Higgins. 1976. Some aspects of the per-
sistence and fate of acrolein herbicide in water. Arch. Environ.
Contain. 5: 87
Bowmer, K.H., et al. 1974. Loss of acrolein from water by vola-
tilization and degradation. Weed Res. 14: 325.
Geyer, B.P. 1962. Reaction with water. In C.W. Smith, ed. Acro-
lein. John Wiley and Sons, Inc., New York.
Hess, L.B., et al. 1978. Acrolein and derivatives. In Kirk-
Othmer Encyclopedia of Chemical Technology. 3rd ed. Interscience
Publishers, New York.
Standen, A., ed. 1967. Kirk-Othmer Encyclopedia of Chemical
Technology. Interscience Publishers, New York.
U.S. EPA. 1977. Survey of two municipal wastewater treatment
plants for toxic substances. Wastewater Res. Div. Municipal
Environ. Res. Lab., Cincinnati, Ohio.
Weast, R.C., ed. 1975. Handbook of chemistry and physics. 56th
ed. CRC Press, Cleveland, Ohio.
Windholz, M., ed. 1976. The Merck Index. 9th ed. Merck and Co.,
Inc., Rahway, N.J.
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AQUATIC LIFE TOXICOLOGY*
FRESHWATER ORGANISMS
Introduction
Much of the data concerning the effects of acrolein on
freshwater aquatic organisms has been determined using static test
conditions with unmeasured concentrations. Consequently, these
data may underestimate the toxicity of this volatile, unstable
chemical. The study of Bond, et al. (1960) shows 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 (Folmar, 1976).
Acute Toxicity
Seven LC50 values for 24-, 48-, and 96-hour exposures are
available for six fish species (Table 1). All values were deter-
mined under static conditions. The adjusted values for the six
species tested showed a narrow range of toxicity (23 to 87 ug/D-
In the study of Bond, et al. (1960), the 24-hour LC50 of 80 ug/1
*The reader is referred to the Guidelines for Deriving Water
Quality Criteria for the Protection of Aquatic Life [43 FR 21506
(May 18, 1978) and 43 FR 29028 (July 5, 1978)] in order to better
understand 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 the calcula-
tions for deriving various measures of toxicity as described in
the Guidelines.
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for chinook salmon is only 1.2 times the LC50 of 65 ug/1 for rain-
bow trout. Among the adjusted LC50 values for four species tested
by Louder and McCoy (1962), the highest, 87 ug/1 for largemouth
bass, is only 3.2 times higher than the lowest, 27 ug/1 for mos-
quitofish. The geometric mean LC50, 40 ug/1? divided by the sen-
sitivity factor (3.9), results in the Final Fish Acute Value for
acrolein of 10 ug/1-
The data base for invertebrate species is limited to two
static tests with Daphnia magna (Table 2)? therefore, no compari-
son of relative species sensitivity can be made. The adjusted
LC50 values of 48 ug/1 and 68 ug/1 show that Daphnia magna has
about the same sensitivity to acrolein as fish. The geometric
mean divided by the Guideline species sensitivity factor (21)
results in the Final Invertebrate Acute Value of 2.7 ug/1 which
becomes the Final Acute Value since it is lower than the compar-
able value (10 ug/1) for fish.
Chronic Toxicity
The chronic toxicity data base consists of one value for fish
and one for invertebrate species. A life cycle test with fathead
minnows (Macek, et al. 1976) resulted in a chronic value of 21.8
ug/1 (Table 3). Survival of newly hatched second generation (F^)
fathead minnow fry was significantly reduced at 42 ug/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/lf so no second generation fish
were produced. The chronic value is about half the adjusted mean
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LC50 value for fish and the adjusted LC50 value for fathead
minnows (Table 1). The Final Fish Chronic Value is 3.3 ug/1•
Macek, et al. (1976) also 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 4). The unadjusted acute
values for this species are 57 ug/1 and 80 ug/1- These data show
that there is little difference in concentrations between the
acute and chronic effects of acrolein on Daphnia magna. The
chronic value divided by the sensitivity factor (5.1) is the Final
Invertebrate Chronic Value of 4.7 ug/1. As with the acute data,
estimated chronic values show no appreciable difference in
sensitivity between freshwater fish and invertebrate species. The
slightly lower Final Fish Chronic Value of 3.3 ug/1 is the Final
Chronic Value.
It is interesting to note that the Final Invertebrate Chronic
Value is higher than the Final Invertebrate Acute Value when both
are derived from data for Daphnia magna.. This is the result of
the small difference in the acute and chronic toxicity of this
species as discussed above and the fact that the species sensi-
tivity factor (21) for acute data is larger than that (5.1) for
chronic data. There are insufficient species tested to evaluate
the accuracy of these factors and, therefore, they are not used
for acrolein.
Plant Effects
No usable plant data were available.
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Residues
Bluegills exposed for 28 days to 13 ug/1 of 14C-acrolein
bioconcentrated acrolein 344 times (Table 5). The half-life was
greater than 7 days. Thin layer chromatography was used to verify
concentrations.
Miscellaneous
The additional information on short-term exposures of fish
agree with previously described acute data. Hartley and Hattrup
(1975) observed 32 percent mortality of rainbow trout exposed for
48 hours to 48 ug/1. The 24-hour mean time to death concentra-
tions for brown trout and bluegill were calculated to be 46 ug/1
and 79 ug/1, respectively (Burdick, et al. 1964). Macek, et al.
(1976) reported a 6-day incipient LC50 of 84 ug/1 for fathead
minnows. The avoidance response seen in rainbow trout at 100 ug/1
(Folmar, 1976) is above reported acute levels. Ninety-eight per-
cent of adult snails and 100 percent of snail eggs died after a
24-hour exposure to 10,000 ug/1 (Ferguson, et al. 1961).
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CRITERION FORMULATION
Freshwater-Aquatic Life
Summary of Available Data
The concentrations below have been rounded to two significant
figures.
Final Fish Acute Value = 10 ug/1
Final Invertebrate Acute Value = 2.7 ug/1
Final Acute Value = 2.7 ug/1
Final Fish Chronic Value =3.3 ug/1
Final Invertebrate Chronic Value = 4.7 ug/1
Final Plant Value = not available
Residue Limited Toxicant Concentration = not available
Final Chronic Value = 3.3 ug/1
0.44 x Final Acute Value = 1.2 ug/1
The maximum concentration of acrolein is the Final Acute
Value of 2.7 ug/1 and the 24-hour average concentration is 0.44
times the Final Acute Value. No important adverse effects on
freshwater aquatic organisms have been reported to be caused by
concentrations lower than the 24-hour average concentration.
CRITERION: For acrolein the criterion to protect freshwater
aquatic life as derived using the Guidelines is 1.2 ug/1 as a
24-hour average and the concentration should not exceed 2.7 ug/1
at any time.
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Table 1. Freshwater fish acute values for acrolein
Adjusted
ro
i
en
Bioaeeay Test Time
prganjsp Method-- Cone .** (hrs)
Chinook salmon S U 24
(fingerling).
Oncorhynchus tshawytscha
Rainbow trout S U 24
(fingerling) ,
Salmo gairdneri
Fathead minnow, S U 48
Pimephales promelas
Mosquitofish. S U 48
Gambusla affinls
Bluegill. S U 96
Lepomis macrochirua
Bluegill, S U 96
Lepomis macrochirus
Largemouth bass, S U 96
Micropterus salmoides
LC50 LC50
juq/1) (uq/ll heference
80 29 Bond, et al.
65 23 Bond, et al.
115 51 Louder & McCoy
61 27 Louder & McCoy
100 55 Louder & McCoy
90 49 U.S. EPA. 1978
160 87 Louder & McCoy
1960
1960
, 1962
. 1962
. 1962
. 1962
* S = static
»•»• U = unmeasured
40.2
Geometric mean of adjusted values = 40.2 Mg/1 A'A = 10 Mg/1
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Table 2. Freshwater invertebrate acute values for acrolein
Adjusted
Organism
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Bicassay Test Time LC50 I.CliO
Mctnou* Cor.c.** ((IKS) (uci/ll (uq/l| Kcterence
S U 48 57 48 Macek, et al. 1976
S U 48 80 68 U.S. EPA. 19.78
* S = static
** U •= unmeasured
Geometric mean of adjusted value •» 57.2 wg/1
= 2.7
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Table 3. Freshwater fish chronic values for acrolein
Chronic
Limits Value
Organism Test* (ug/i) (ug/l) fieferenct
Fathead minnow. LC 11.4-41.7 21.8 Macek, et al. 1976
Pimephales promelas
* LC = life cycle or partial life cycle
21 fl
Geometric mean of chronic value *• 21.8 (jg/1 67 •=• 3.3 Mg/1
Lowest chronic value = 21.8
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Table 4. Freshwater invertebrate chronic values for acrolein
Organism
Cladoceran,
Daphnia magna
* LC = life cycle
Geometric mean
Teat*
LC
or partial life
of chronic value
Limits
fuq/1)
16.9-33.6
cycle
- 24 vg/l
Chronic
Value
(uq/l> Reference
•24 Macek. et al. 1976
24
-57T- 4.7 KB/1
Lowest chronic value = 24 iJg/1
00
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0)
I
Table 5. Freshwater residues for acrolein (U.S. EPA, 1978)
Organism
Bioconcentration Factor
Time
(days)
Bluegill.
Lepomis macrochlrus
344
28
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Table 6. Other freshwater data for acrolein
Teat
Result
DO
I
Organism
Snail (adult), 24 hra 98% mortality
Australorbls glabratus
Snail (egg). 24 hrs 100% mortality
Australorbts glabratus
Rainbow trout (fry),
Salmo galrdneri
Rainbow trout,
Salmo galrdnerl
Brown trout
(fIngerllng).
Salmo trutta
Fathead minnow,
Pimephales promelas
1 hr Avoidance
48 hrs 32% mortality
24 hrs Hean time to death
6 days Incipient LC50
Blueglll (flngerling), 24 hrs Mean time to death
Lepomts macrochlrus
10,000 Ferguson, et al. 1961
10,000 Ferguson, et al. 1961
100 Folmar, 1976
48 Hartley & Hattrup, 1975
46 Burdick, et al. 1964
84 Macek, et al. 1976
79 Burdick. et al. 1964
Lowest value = 46 Mg/1
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SALTWATER ORGANISMS
Introduction
Acrolein is used as a fungicide and a herbicide. It has been
applied directly to the'saltwater environment to control 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 unmeasured test concentrations.
Acute Toxicity
The longnose killifish was exposed for 48 hours to acrolein
in a flow-through test (Butler, 1965). The adjusted LC50 is 150
ug/1 (Table 7). Adjusted LC50 values for six species of fresh-
water fish ranged from 23 to 87 ug/1 (Table 1). The Final Fish
Acute Value for saltwater fish, obtained using the species
sensitivity factor (3.7), is 41 ug/1.
The adjusted LC50 values for three invertebrate species
ranged from 33.1 to 764.8 ug/1 (Butler, 1975; Dahlbergl; 1971). -
Brown shrimp and the eastern oyster were the most sensitive
species tested (Table 8). The Final Invertebrate Acute Value,
obtained using the species sensitivity factor (49) is 2.0 ug/1/
and was an order of magnitude less than the lowest LC50 value of
tested species.
Chronic Toxicity
No chronic effects of acrolein on saltwater fish and inverte-
brate species have been reported.
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Plant Effects
The effects of acrolein on saltwater and freshwater plants
have not been studied. Because acrolein is a herbicide, phyto-
toxicity to aquatic species might be expected.
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CRITERION FORMULATION - • - .
Saltwater-Aquatic Life
Summary of Available Data
The concentrations below have been rounded to two significant
figures.
Final Fish Acute Value = 41 ug/1
Final Invertebrate Acute Value = 2.0 ug/1
Final Acute Value = 2.0 ug/1
Final Fish Chronic Value = not available
Final Invertebrate Chronic Value = not available
Final Plant Value = not available
Residue Limited Toxicant Concentration = not available
Final Chronic Value = not available
0.44 x Final Acute Value = 0.88 ug/1
No saltwater criterion can be derived for acrolein using the
Guidelines because no Final Chronic Value for either fish or
invertebrate species or a good substitute for either value is
available.
Results obtained with acrolein and freshwater organisms
indicate how a criterion may be estimated.
For acrolein and freshwater organisms 0.44 times the Final
Acute Value is less than the Final Chronic Value which is derived
from results of a life cycle test with the fathead minnow. There-
fore, it seems reasonable to estimate a criterion for acrolein and
saltwater organisms using 0.44 times the Final Acute Value.
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The maximum concentration of acrolein is the Final Acute
Value of 2.0 ug/1 and the estimated 24-hour average concentration
is 0.44 times the Final Acute Value. No important adverse effects
on saltwater aquatic organisms have been reported to be caused by
concentrations lower than the 24-hour average concentration.
CRITERION: For acrolein the criterion to protect saltwater
aquatic life as derived using procedures other than the Guidelines
is 0.88 ug/1 as a 24-hour average and the concentration should not
exceed 2.0 ug/1 at any time.
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I
Table 7. Marine fish acute values for acrolein (Butler, 1965)
Adjusted
Bioaseay Test Time LC50 LCbO
Oygapism Method* Cone.** (Era) (ug/11
Longnose killifish FT U 48 240 150
(juvenile),
Fundulus similis
* FT - flow-through
** U = unmeasured
Geometric mean of adjusted values " 150 pg/1 r-j = 41 pg/1
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Tdbie 8. Marine invertebrate acute values for acrolein
03
1
H"
Organism
Eastern oyster,
Crassostrea virginica
Barnacles (adult),
Balanus eburneus
Barnacles (adult) ,
Balanus eburneus
Brown shrimp (adult),
Penaeus aztecus
biodssay
Metnoa*
FT
S
S
FT
Test
Cone .**
U
U
U
U
* S » static; FT = flow- through
** U = unmeasured
***EC50: 50% decrease in shell growth of
Time
(nts)
96
48
48
48
oyster;
i' a ..n / 1
LC50
55***
2,100
1,600
100***
or loss of
97.9 „
Adjusted
LCbO
(uq/1) hereience
42.4 Butler, 1965
764.8 Dahlberg, 1971
582.7 Dahlberg, 1971
33.1 Butler, 1965
equilibrium of brown shrimp.
n ..,. 1 1
49
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ACROLEIN
REFERENCES
Hartley, T.R., and A.R. Hattrup. 1975. Acrolein residues
in irrigation water and effects on rainbow trout. Bur.
Reclam. Rep. REC-ERC-75-8.
Bond, C.E., et al. 1960. Toxicity to various herbicidal
materials to fishes. Biol. problems in water pollut., Trans.
1959 seminar. Public Health Service. Tech. Rep. W60-3;
96-101. U.S. Dep. Health Educ. Welfare.
Burdick, G.E., et al. 1964. Toxicity of aqualin to finger-
ling brown trout and bluegills. N.Y. Fish Game Jour. 11:
106.
Butler, P.A. 1965. Commercial fisheries investigations.
Effects of pesticides on fish and wildlife, 1964 research
findings Fish Wildl. Serv. U.S. Fish Wildl. Serv. Circ.
Dahlberg, M.D. 1971. Toxicity of acrolein to barnacles,
Balanus eburneus. Chesapeake Sci. 12: 282.
Ferguson, F.F., et al. 1961. Control of Australorbis glabratus
by acrolein in Puerto Rico. Pub. Health Rep. 76: 461.
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Folmar, L.C. 1976. Overt avoidance reaction of rainbow
trout fry to nine herbicides. Bull. Environ. Contain. Toxicol.
t
15: 509.
Louder, D.E., and E.G. McCoy. 1962. Preliminary investiga-
tions of the use of aqualin for collecting fishes. Proc.
16th Annu. Conf. S.E. Assoc. Game Fish Comm. 240.
Macek, K.J., et al. 1976. Toxicity of four pesticides
to water fleas and fathead minnows: Acute and chronic toxicity
of acrolein, heptachlor, endosulfan, and trifluralin to
the water flea (Daphnia magna) and the fathead minnow (Pime-
phales promelas). EPA 600/3-76-099. U.S. Environ. Prot. Agency,
U.S. EPA. 1978. In-depth studies on health and environmental
impacts of selected water pollutants. Contract No. 68-01-4646.
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ACROLEIN
Mammalian Toxicology and Human Health Effects
EXPOSURE
Introduction
Acrolein is the simplest unsaturated aldehyde:
CH2=CHCHO
It is a colorless volatile liquid. Table 1 describes its
salient physical properties. Since it is a highly reactive
organic chemical and capable of self-polymerization, the
marketed product contains an inhibitor (0.1 percent hydro-
quinone) to prevent its degradation. It is extremely reactive
at high pHs (Hess, 1978; Smith, 1962). Methods for acrolein
analysis are summarized in Table 1A.
Acrolein has a wide variety of applications. It is
directly used as a biocide for aquatic weed control; for
algae, weed and mollusk control in re-circulating process
water systems; for slime control in the paper industry; 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 intermediate in the chemical
industry. Its dimer, which is prepared by a thermal, uncat-
alyzed reaction, has several applications, including use
as an intermediate for crosslinking agents, humectants,
plasticizers, polyurethane intermediates, copolymers and
homopolymers and Greaseproofing cotton. The monomer is
utilized in synthesis via the Diels-Alder reaction as a
dienophile or a diene. Acrolein is widely used in copolymeri-
zation but its homopolymers do not appear commercially important,
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TABLE 1
Physical Properties of Acrolein
(Smith, 1962; Hess, 1978)
Empirical formula
Molecular Weight
Melting Point, °C
Boiling Point, °C
Vapor pressure at 20°C, KPa (mmHg)
Refractive Index nQ (20°C)
Viscosity at 20°C, cS
Solubility in Water (weight %)
Critical Properties:
Temperature, K
Pressure,atm.
Volume, cc/g-mole
C3H40
56.06
-86.95
52.69
29.3 (220)
1.4017
0.393
20.6
510
51.58
189
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Table 1A
Methods for Acrolein Measurement (Brady et al., 1977;
Kissel et al., 1978; Bellar and Sigsby, 1970).
Analytical Method
Detection Limit
Interferences
NMR (Aldehydic proton)
Colorimetry
2,4-D
4-hexylresourcinol
Fluorimetry
Direct
J-Acid
m-aminophenol derivative
Differential pulse
polarography
Gas chromatography
Flame-ionization
Mass Spectral
100 mg/1
80 jug/1
700 jug/1
20 mg/1
20 ng/1
30 jug/1
500 /ig/1
50 fig/I
few
many
many
very few
very few
very few
few
very few
very few
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The copolymers of acrolein are used in photography, for
textile treatment, in the paper industry, as builders in
laundry and dishwasher detergents, as coatings for aluminum
and steel panels, as well as other applications (Smith,
1962; Hess, 1978). Hess (1978) described marketing aspects
of acrolein. In 1975 worldwide production was about 59
kilotons. Its largest market was for methionine manufacture.
Worldwide capacity was estimated at 102 kilotons/year of
which U.S. capacity was 47.6 kilotons/year.
The present technology for acrolein preparation employs
catalytic oxidation of propene in the vapor phase. Typical
reaction conditions consist of feeding propylene and air
at 300 to 400°C and 30 to 45 psi over the catalyst (usually
of the bismuth-molybdenum or the antimony family) (Hess,
1978).
Acrolein inadvertently enters the environment from
natural and anthropogenic sources. It is often present
in trace amounts in foods and is a component of smog, fuel
combustion, wood and possibly other fires, and cigarette
smoke. An evaluation of available data indicates that,
while industrial exposure to manufactured acrolein is unlikely,
acrolein is pervasive from non-manufactured sources. Acrolein
exposure will occur through food ingestion and through inhala-
tion. Exposure through the water or dermal route is unlikely.
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Ingestion from Water
There is no evidence that acrolein is a contaminant
of potable water or water supplies. No available monitoring
study has noted .its presence, and acrolein is not listed
in compendia on water monitoring (Junk and Stanley, 1975;
Shackelford and Keith, 1976; Abrams, et al. 1975). Investiga-
tions on the fate of acrolein in water suggest that it dissi-
pates with a half-life on the order of four to five hours.
Based on these studies and the half-life in water (see Table
2), it can be assumed that negligible acrolein is present
in water supplies.
Acrolein is applied to the 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). The studies have examined 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 in aquatic
organisms and sediments. In a review of the Russian litera-
ture, Melnikov (1971) indicates that acrolein is used as
a biocide in water reservoirs.
Analytical difficulties complicate the measurement
of aqueous acrolein. This problem has been demonstrated
in studies on the degradation of aqueous acrolein. Some
of these analytical problems could exist in measurements
of acrolein in other media.
C-5
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TABLE 2
First Order Rate Constants of Acrolein Degradation
in Laboratory Experiments (Bowmer and Higgins, 1976)
Water3
Supply
Supply
Drainage
Supply
Supply
Supply
Distilled
EH
7
7
7
7
7
7
.3
.3
.8
.2
.2
.2
—
Initial
acrolein
ppm
8.
6.
6.
6.
17
50
6.
0
8
4
1
.5
.5
4
10
hi
23
15
45
13
14
11
3k
.7
.9
.1
.3
.2
.4
2.7
SE
2
2
7
1
2
1
0
.4
.0
.5
.9
.5
.0
.3
aWater from canal supply, canal drainage, or distilled water
C-6
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Kissel, et al. (1978) have demonstrated the analytical
problems in a study of the effect of pH on the rate of degra-
dation of aqueous acrolein. Their study compared acrolein
measurement by ten analytical techniques on six pH buffer
systems (pH 5,7 and 9). The analytical methods were:
(a) bioassay with an ATPase enzyme system,
(b) bioassay by a plate count method,
(c) bioassay by fish kill (bluegill sunfish),
(d) chemical titration with bromide-bromate solution-
iodide- thiosulf ate,
(e) colorimetric by the 2,4-dinitrophenylhydrazone (DNP),
(f) fluorometric analysis (m-aminophenol) with excita-
tion at 372 nm and emission at 506 nm,
(g) gas-liquid chromatography (on 6' Poropaks 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) fluorometric analysis directly on acrolein with
excitation at 276 nm and emission at 370 nm.
Kissel, et al. (1978) separated the analytical techniques into
three groups: bioassay, derivatization, and direct measure-
ment. 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 polarographic analyses were better.
C-7
-------
Kissel, et al. (1978) did not identify reasons for the large
discrepancies. Also, they noted that acrolein rapidly degraded
at pH 9.
Bowmer and coworkers (Bowmer and Higgins, 1976; Bowmer
and Sainty, 1977; Bowmer, et al. 1974; O'Loughlin and Bowmer,
1975) have measured acrolein degradation rate in laboratory
and field.studies. They evaluated the possible degradation
pathway in buffered, distilled water. At pH 5, the acrolein
reacted by a reversible hydrolysis and yielded an equilibrium
mixture containing^8-hydroxypropionaldehyde: acrolein in 92:8
ratio.
H20 + CH2 = CHCHO ^HOCH2CH2CHO
In alkali the primary reaction was consistent with a polycon-
densation. In natural waters they observed no evidence
for an equilibrium. They considered the initial product
\
as chemical degradation and suggested, but did not demonstrate,
that it further degraded to carboxylic acid via microbial
pathway. Acrolein was analyzed by colorimetry using the
2,4-DNP method and by bioassay. Results were conflicting,
and they concluded that the analytic complication (as described
by Kissel, et al. 1978) resulted from the ability of the
hydroxypropionaldehyde to form a 2,4-DNP derivative, but
that it was not a biocide. They resolved the analysis problem
by flushing the volatile acrolein from a sample by means
of an air stream, which left the non-volatile hydroxypropionaldehyde
ifr-solution. Acrolein concentration was measured as the
difference between acrolein-2,4-DNP absorbance in samples
before and after the flush (Bowmer, et al. 1974). Their
laboratory studies utilized samples sealed in bottles and
C-8
-------
maintained at 20.6°C. Table 2 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 volatization and absorption.
Hopkins and Hattrup (1974) examined acrolein loss in
field studies in canals of the Columbia River basin. Their
analytical technique was fluorometric analysis of the m-
aminophenol derivative. 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 3 describes the acrolein concentration
in a flow-plug measured during a 48-hour study period in
two canals. Hopkins and Hattrup (1974) suggested that dissi-
pation resulted from acrolein degradation, volatilization,
and absorption to 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. Ozone will likely initially
yield a malonozonide. Aqueous chlorine (which exists as
HOC1) will probably degrade acrolein as follows (Hess, et
al. 1978): CH2 = CH-CHO + HOC1 »HOCH2 CHC1CHO + C1CH2CH(OH)CHO.
The relative amounts of these two possible initial acrolein
derivatives and their degradation products are not .known
(Morris, 1975).
C-9
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TABLE 3
Acrolein Dissipation in Two Canals of the Columbia River
Basin Over 48 Hours (Hopkins and Hattrup, 1974)
Canal
Intended
Application
ppm
Sampling Point Acrolein
Miles Below Initial ppm
Appl. Point
Potholes
0.14
Booster application at
12.6 miles
East Low
0.11
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
0.14
0.10
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
C-10
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Ingestion from Foods
Acrolein is a common component of food at ug/g concentra-
tions. It is commonly generated during cooking or other
processing, and is sometimes produced as an unwanted by-product
in the fermentation of alcoholic beverages. The information
on acrolein in foods has been generated primarily to identify
organoleptic properties, 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. The synthetic mixture contained amino acids
(glycine, glutamic acid, lysine, methionine, and phenylalanine)
and sugar (glucose, fructose, maltose, and sucrose). Acrolein
was identified (by GC) as a product of heating some but
not all mixtures 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 generated when animal or vegetable fats are subjected
to high temperatures. In these cases, acrolein is formed
primarily from the dehydration of glycerol.
Kishi, et al. (1975) identified acrolein production
from cooking potatoes or onions in edible oil. They detected
2.5 to 30 mg/m acrolein in the vapors 15 cm above the surface
of the heated oil. Cooking about 20 g of potatoes or onions
in the oil yielded 200 to 400 ug of acrolein. The authors
did not determine whether the acrolein came from the oil,
C-ll
-------
the potatoes, 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 liters of distilled water for three hours)
or roasting (3 kg at 170 to 190°C for three hours). Raw
turkey was extracted at 2°C with 75 percent ethanol for
72 hours and volatiles were collected by vacuum distillation.
The carbonyl fraction was derivatized with 2,4-DNP and the
derivatives were identified by paper chromatography. Acrolein
was identified in raw turkey and in the volatile products
from both cooking methods.
Love and Bratzler (1966) identified acrolein in wood
smoke. Samples (whole smoke and vapor phase) were collected
from hardwood sawdust (mainly maple) burned on a hot plate
(490 to 500°C) and from commercial smokehouses (operated
at 48 to 49.5°C). The carbonyl compounds were trapped in
2,4-DNP solution and the derivatives were identified by
GC. Acrolein was identified in all smoke samples but was
not quantified.
Levaggi and Feldstein (1970) examined acrolein concentra-
tions in the emissions from a commercial coffee roaster.
Acrolein was trapped in Greenberg-Smith impingers containing
o.ne percent sodium bisulfite solution and was quantified
by colorimetric 4-hexylresorcinol method. At the emission
outlet (after burner abatement device) they measured 0.60
mg/m acrolein, while no acrolein was detected in the inlet
air.
C-12
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Boyde, 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 extracted with hexane and
cleaned on Celite prior to the derivatization. The 2,4-
DNP derivatives were separated into fractions prior to mea-
surement. They measured 2-enol concentrations of 0.6 to
2.0 jumoles/100 g fat in raw cocoa beans and 1.3 to 5.3 jumoles/
100 g in the chocolate liquor.
Alcoholic beverages often contain trace amounts of
acrolein (Rosenthaler and Vegezzi, 1955). It sometimes
is a problem since it causes an organoleptic condition called
"pepper" by the alcohol fermentation industry. As a means
of controlling the "pepper" character, acrolein production
has been investigated. According to Serjak, et al. (1954)
acrolein is detectable in low-proof whiskey at concentrations
as low as 10 mg/1. This value probably represents the upper
limit for acrolein, since industry adapts corrective procedures
to reduce "pepper" by reducing acrolein concentration.
The chief pathway for acrolein entry to the alcohol
has been delineated as mash fermentation (Serjak, et al.
1954; Sobolov and Smiley, 1960; Hirano, et al. 1962). When
glucose levels in the mash are low, some bacterial strains
convert glycerol to acrolein.
Avent (1961) investigated the contamination of a wine
with 14 pg/g of acrolein, which was initially acrolein-free.
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
C-13
-------
were available.
Alarcon (1976a) has demonstrated the formation of acrolein
from methionine, homoserine, homocysteine, cystathionine,
spermine, 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.
Processing can increase the acrolein content. Volatile frac-
tions collected during cooking suggest that some acrolein
would remain in the food. Based upon organoleptic factors,
it is probably reasonable to assume that acrolein would
seldom exceed 10 mg/1, if it were present.
A bioconcentration factor (BCF) relates the concentration
of a chemical in water to the concentration in aquatic organ-
isms, but BCF's are not available for the edible portions
of all four major groups of aquatic organisms consumed in
the United States. Since data indicate that the BCF for
lipid-soluble compounds is proportional to percent lipids,
BCF's can be adjusted to edible portions using data on per-
cent lipids and the amounts of various species consumed
by Americans. A recent survey on fish and shellfish comsump-
tion in the United States (Cordle, et al. 1978) found that
the per capita consumption is 18.7 g/day. From the data
on the 19 major species identified in the survey and data
on the fat content of the edible portion of these species
(Sidwell, et al. 1974) , the/relative consumption of the
four major groups and the weighted average percent lipids
for each group can be calculated:
C-14
-------
Consumption Weighted Average
Group (Percent) Percent Lipids
Freshwater fishes 12 4.8
Saltwater fishes 61 2.3
Saltwater molluscs 9 1.2
Saltwater decapods 18 1.2
Using the percentages for consumption and lipids for each
of these groups, the weighted average percent lipids is
2.3 for consumed fish and shellfish.
A measured steady-state bioconcentration factor of
344 was obtained for acrolein using bluegills containing
about one percent lipids (U.S. EPA, 1978). An adjustment
factor of 2.3/1.0 = 2.3 can be used to adjust the measured
BCF from the 1.0 percent lipids of the bluegill to the 2.3
percent lipids that is the weighted average for consumed
fish and shellfish. Thus, the weighted average bioconcentra-
tion factor for acrolein and the edible portion of all aquatic
organisms consumed by Americans is calculated to be 344
x 2.3 = 790.
Inhalation
Acrolein inhalation occurs through many exposure routes.
Acrolein is generated during oxidation of a variety of organic
substrates. It has been noted as a combustion product of
fuels and of cellulosic materials (e.g., wood and cigarettes),
as an intermediate product in atmospheric oxidation of propy-
lene, and as a component of the volatiles produced by heating
organic substrates. Actual exposure will depend on general
environmental conditions and specific behavior patterns.
Total inspiration is the sum of acrolein inhalations from
C-15
-------
the ambient air, from local air (e.g., occupational considera-
tions, vehicular considerations, side-stream smoke from
cigarettes) and from cigarette smoke.
Acrolein is a component of the urban smog; its concentra-
tion has been measured in Los Angeles atmosphere (Renzetti
and Bryan, 1961; Altshuller and McPherson, 1963). Renzetti
and Bryan collected ambient air in 1960 using a series of
vapor traps containing SD-3A alcohol and quantified acrolein
by absorbance of the 4-hexylresorcinol-mercuric chloridetri-
chloroacetic acid derivative (605 nm). Altshuller and McPherson
(1963) also examined the atmosphere in 1961, but collected
samples in bubblers containing the 4-hexylresorcinbl reagent.
Similar results were obtained with both studies. For ten
days during a September-October-November period acrolein
averaged 0.012 mg/m with a peak concentration of 0.025 mg/m .
Acrolein concentration for seven days of this period in
1961 averaged 0.018 mg/m and peaked at 0.030 mg/m . For
all 1961 acrolein averaged 0.016 mg/m and peaked at 0.032 mg/m .
Graedel, et al. (1976) developed a mathematical model
for photochemical processes in the troposphere. They combined
chemical 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. Their computed peak acrolein concen-
tration was 0.03 mg/m . They did not account for other
sources of acrolein or for any degradation pathway (McAfee
and Gnanadesikan, 1977). That their calculated value favorab-
ly compared with the peak values measured in Los Angeles
(0.025 to 0.032 mg/m3) could be an artifact.
C-16
-------
Trattner, et al. (1977) suggested that enols are present
in the air of a subway system. They were measuring airborne
particulates by an infrared technique. Samples were collected
on a cascade impactor system containing a 0.313 u back-up
filter. Potassium bromide pellets were prepared from each
sample fraction. Evidence for the unsaturated aldehyde
assignment were weak maxima observed at 1,695 cm (6.90 u)
in the pellets prepared from final inpactor and backup filter
samples. They made no quantitative assessment.
Acrolein is a common constituent of vehicle exhaust
(Natl. Acad. Sci. 1976; Tanimoto and Uehara, 1975). The
exact concentration depends upon the type of gasoline, eng-
ine, 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 . It has been measured
in diesel engines at 6.7 mg/m and in internal combustion
engines at 6.0, 22.5, 16.1, 14.7, and about 11.5 mg/m
(Natl. Acad. Sci. 1976). Day, et al. (1971) reported acro-
lein in emissions from a 1969 Chevrolet truck operated on
a dynamometer. Acrolein was measured (by the colorimetric
2,4-DNP method) as 0.05 mg/m3 for 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 (ten percent sucrose octaacetate on Gas-Chrorn 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 applied in
C-17
-------
measuring diesel exhaust, ambient air in an area of traffic
and ambient air in 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 area of traffic.
Cigarette smoking produces acrolein. While a cigarette
smoker directly inspires acrolein, some questions exist
on passive exposure of non-smokers to acrolein, from 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 acrolein content
of cigarettes by cryogenic trapping smoke onto a gas chromato-
graphy column. A six-part smoking machine was used with
puff set at one-minute intervals, two-second durations,
and 35 ml volume. Measured acrolein content for the tested
cigarettes is described in Table 4.
Hoffman, et al. (1975) measured acrolein in marijuana
and tobacco cigarettes using gas chromatography. Cigarettes
were rolled to 85 nun length using standard cigarette paper.
Experimental details were incomplete. Hoffman, et al. (1975)
stated that smoking machines (1 or 20 channel) were employed
and contained ten or fewer cigarettes. Error was placed
at +4 to 6 percent. They reported acrolein delivery from
mainstream smoke was 92 ug from marijuana cigarettes and
85 ug from tobacco cigarettes.
The potential exposure of non-smokers to side-stream
and exhaled cigarette smoke is an unresolved question.
Holzer, et al. (1976) suggested that passive exposure to
cigarette smoke is not important, while Swiss workers (Weber-
C-18
-------
TABLE 4
Acrolein Delivery from some Experimental and some
Commercial Cigarettes (Horton and Guerin, 1974)
Cigarette
Acrolein Delivery
jjg/cig. ug/puff jug/g tobacco burned
Kentucky Reference (IRI)
Commercial 85 mm, filtered
Commercial 85 mm, non-filtered
Experimental 85 mm, charcoal
filtered
Experimental 85 mm (same as
above) , no-charcoal
Commercial 85 mm, little cigar
Experimental 85 mm, marijuana
128
102
111
62
103
70
145
12
10
12
7
12
8
14
159
153
135
97
155
107
199
C-19
-------
Tschopp, et al. 1976b; Jermini, 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 capacity for substances of
lower retention than benzene, including acrolein, so their
results were only qualitative for acrolein. The sample
tubes were directly desorbed and analyzed by GC-MS (mass
spectral detection) using a glass capillary column. They
compared the GC chromatograms of a sample of urban air (3.5
liter samples at 220 ml/min), a standard cigarette (IRI,
University of Kentucky) (3 ml of smoke taken during a puff
of two-second duration and 35 ml volume), and air where
a cigarette had been smoked under standard conditions (same
sampling conditions as for urban air). They suggested that
the volatiles in both air samples were associated with gasoline
vapors and that cigarette smoking did not appreciably add
to these volatiles. The journal editor disagreed and in
a footnote stated that the chromatograms suggested "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. 1976b) measured acrolein concentration from cigarettes
(U.S.) in side-stream smoke within 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: in the 30-m room,
C-20
-------
0.11 mg/m and 0.87 mg/m with 5 and 30 cigarettes, respect-
ively; and in the chamber, 0.85 mg/m for one cigarette.
These results suggested that inhalation of significant quanti-
ties of acrolein can result from passive exposure to side-
stream smoke.
Acrolein has been identified as a component in 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. The 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,
neoprene, rigid urethane foams, and treated wood. The materi-
als were burned by two techniques: a sealed system (approxi-
mately 370°C) and a stagnation burner (approximately 400°C).
Condensible products 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 will retain some acrolein. They never observed
acrolein in emissions from the PV, neoprene, and urethane
foam samples. Acrolein was in emissions from all wood samples.
C-21
-------
Table 5 summarizes their results.
Dermal
Based upon the physical properties and known distribution
of acrolein in the environment, dermal exposure is judged
negligible.
PHARMACOKINETICS
Absorption
Egle (1972) has measured the retention of inhaled acrolein
as well as formaldehyde and propionaldehyde in mongrel dogs
anesthetized with sodium pentobarbital. In this study,
dogs were exposed to acrolein concentrations of 0.4 mg to
0.6 mg/1 for one to three minutes, and retention was calculated
using the amount inhaled and the amount recovered. In mea-
surements of total respiratory tract rentention at ventilatory
rates between 6 and 20, 81 to 84 percent of acrolein was
retained. An increase in tidal volume (from 100 ml to 160
ml) resulted in a significant (p 0.001) decrease in acrolein
retention (from 86 to 77 percent). This was consistent
with finding that acrolein was taken up more readily by
the upper than the lower respiratory tract.
Distribution
No studies were found that were directly relevant to
the distribution of acrolein upon oral administration.
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, 3.13, 1.72, 0.94, and
0.36 percent of the recovered radioactivity was found in
the acid-soluble, lipid, protein, RNA, and DNA fractions
C-.22
-------
TABLE 5
Acrolein Produced by Burning Standard Southern Pine
(Hartstein and Forshey, 1974)
Wood
Treatment
Acrolein Produced (mg/g wood burned)
Sealed Stagnation
Tube Burner
None
None
Pentachlorophenol
Creosote
Koppers fire retardent Type C
Koppers waterborne preservative
CCA
0.67
0.62
1.21
0.43
unknown
0.47
0.21
0.70
0.59
0.22
0.68
C-23
-------
of the liver. Based on measurements taken ten 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 Effects
on Experimental System" section.
Metabolism
In terms of the potential toxicologic effects of acrolein
in drinking water, the instability of acrolein at acid pH's
(see "Ingestion 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 related to the high reactivity
of the carbon-carbon double bond. However, the low pH's
encountered in the upper portions of the gastrointestinal
tract would probably rapidly convert acrolein to saturated
alcohol compounds. The primary breakdown product would
probably be beta propionaldehyde (see "Ingestion from Water"
section). If this is the case, the toxic effects of acrolein
given by oral administration would differ markedly from
the effects observed following other routes of administration.
No information is available on the toxic effects of the
acrolein breakdown products. However, an analysis of subchro-
nic and chronic studies suggest that acrolein is markedly
less toxic when given by oral administration than when in-
haled (see the "Basis and Derivation of Criterion" section).
Relatively little direct information is available on
the metabolism of acrolein. Smith and Packer (1972) found
that preparations of rat liver mitochrondria were capable
C-24
-------
of oxidizing several saturated aldehydes but not unsaturated
aldehydes such as acrolein, crotonaldehyde, and cinnamaldehyde.
Iri 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~ , 8.3 x 10~ ,
and 16.7 x 10 M, respectively (Pietruszko, et al. 1973).
As cited above, jji vivo studies in rats indicate that a
portion of subcutaneously administered acrolein is converted
to 3-hydroxypropylmercapturic acid (Kaye and Young, 1972;
Kaye, 1973). Acrolein has also been shown to undergo both
spontaneous and enzymatically catalyzed 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. Serafini-Cessi (1972) has shown that acrolein
is a probable metabolite of allyl alcohol. Several investiga-
tors have demonstrated that acrolein is a metabolite of
the anti-tumor agent cyclophosphamide (Alarcon, 1976b; Alarcon
and Meienhofer, 1971; Alarcon and Melendez, 1974; Alarcon,
et al. 1972; Conners, et al. 1974; Cox, et al. 1976a,b;
Farmer and Cox, 1975; Gurtoo, et al. 1978; Hohorst, et al.
1976; and Thomson and Colvin, 1974.)
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) .
C-25
-------
EFFECTS
Acute, Sub-acute, and Chronic Toxicity
Acute Effects on Experimental Systems: Several investi-
gators have described the gross toxic effects of acute lethal
exposure to acrolein 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 unpub-
lished reports (Table 6). Skog (1950) compared the patho-
logical 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 degenerative changes in the bronchial epithelium.
Similar changes have been noted in mice, guinea pigs, and
rabbits (Pattle and Cullumbine, 1956; Salem and Cullumbine,
1960). After administering lethal subcutaneous doses of
acrolein to rats, Skog (1950) noted less severe lung damage
(edema without significant hemorrhaging) but also found
pathological changes in the liver (hyperemia and fatty degen-
eration) and kidneys (focal inflammatory changes).
Given the probable instability of acrolein on oral
administration, a quantitative comparison of oral exposure
with other routes 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
C-25
-------
TABLE 6
Acute Lethal Toxicity of Acrolein (Albin, 1962)
Species
Mouse
Mouse
Dog
Rat
Rat
n Rat
^j Mouse
Rabbit
Rabbit
Rabbit
Rabbit
Rabbit
Rabbit
Route
Inhalation
Inhalation
Inhalation
Inhalation
Oral
Oral
Oral
Percutaneous
Percutaneous .
Percutaneous
Percutaneous
Percutaneous
Percutaneous
Ex?°:r
LCcQ-875 ppm 1 min
LC50-175 ppm 10 min
LC5Q-150 ppm 30 min
LCcQ-8 ppm 4 hr
LD5Q-46 mg/kg
LD5Q-42 mg/kg
LD5Q-28 mg/kg
LD5Q-200 mg/kg
LDcQ-562 mg/kg " " *
LD5Q-335 mg/kg
LD5Q-1022 mg/kg
LD5Q-164 mg/kg
LD5Q-238 mg/kg
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
-------
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 irritation (e.g., 4.8 mg/m x
40 hours). Other hepatic enzyme activities - acetylcholine
esterase and glutamic-oxalacetic transaminase - were not
affected. Since similar patterns were seen with other res-
piratory 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 on the adrenocortical response of rats to
acrolein, Szot and Murphy (1970) demonstrated increased
plasma and adrenal corticosterone levels in rats given
C-28
-------
intraperitoneal injections of acrolein. Unlike similar effects
caused by DDT and parathion, the effect of acrolein was
not blocked by subanesthetic doses of phenobarbital and
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
sublethal effects of acrolein on the respiratory system
have been examined in some detail. Murphy, et al. (1963)
found that inhalation of acrolein at concentrations of 0.92
to 2.3 mg/m for periods of up to 12 hours caused dose-related
increases in respiratory resistance, along with prolonged
and deepened respiratory cycles in guinea pigs. In tests
on guinea pigs exposed to whole cigarette smoke from various
types of cigarettes, Rylander (1973) associated concentra-
tions of acrolein and acetaldehyde with decreases in the
number of free macrophages. Mice exposed to acrolein in
air at concentrations of 2.3 to 4.6 mg/m for 24 hours evi-
denced decreased pulmonary killing of Staphylococcus aureus
and Proteus mirabilis. This decrease in intrapulmonary
bacterial killing was aggravated in mice with viral pneumonia
(Jakab, 1977). Kilburn and McKenzie (1978) have shown that
inhalation of acrolein (13.8 mg/m x 4 hours) is cytotoxic
to the airway cells of hamsters, causing both immediate
and delayed exfoliation. When administered with or adsorbed
onto carbon particles, acrolein induced leukocyte recruitment
to the airways, mimicking the effect of whole cigarette
C-29
-------
smoke. In single ten-minute inhalation exposure to mice,
acrolein caused dose-related decreases in respiration attri-
buted to sensory irritation, with an EC5Q of 3.9 mg/m (Kane
and Alarie, 1977). Formaldehyde causes the same effect
and exhibits competitive agonism in combination with acrolein
(Kane and Alarie, 1978).
Acrolein has been shown to exert pronounced ciliastatic
activity in a variety of aquatic invertebrates (see review
by Izard and Libermann, 1978). As discussed by Wynder,
et al. (1965) , impairment of ciliary function in the respira-
tory tract of mammals may be involved in the pathogenesis
of several respiratory diseases, including cancer. Of several
respiratory irritants examined by Carson, 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). Similarly, in tests on various types of cigarette
smoke, Dalhamn (1972) associated ciliastasis in cats with
variations in the concentrations of acrolein and tar.
In in vitro studies on the effects of cigarette smoke
components on rabbit lung alveolar macrophages, acrolein
has been shown to inhibit phagocytosis, adhesiveness, and
calcium-dependent ATP-ase activity (Low, et al. 1977) and
to inhibit the uptake of cycloleucine and -aminoisobutyrate
but not 3-0-methyglucose (Low and Bulman, 1977). However,
acrolein has been shown to inhibit the uptake of glucose
by rabbit erythocytes (Riddick, et al. 1968).
Egle and Hudgins (1974) noted that low doses (0.05 mg/kg)
-. . . J 030
-------
of acrolein administered by intravenous injection to the
rat caused an increase in blood pressure but that 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. Similar effects were
noted- in one-minute inhalation exposures to acrolein in
which concentrations of 2.5 and 5.0 mg/1 induced depressor
effects. Acrolein elicited significant cardiovascular effects
at concentrations below those encountered in cigarette smoke.
Basu, et al. (1971) have also examined the effects of acrolein
on heart rate in rats. Tachycardia was induced in animals
under general (sodium pentobarbital) anesthesia, while brady-
cardia 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 mg/kg i.v.) along with local and general anesthesia
blocked the bradycardic response. Tachycardia was attributed
to increased sympathetic discharge caused by eye irritation.
Since the bradycardic response was blocked by atropine,
parasympathetic involvement was suggested.
Several groups of investigators have examined the gen-
eral cytotoxic effects of acrolein. Alarcon (1964) determined
the inhibitory activities of spermine, spermidine, and acro-
lein to S-180 cell cultures. The concentrations of these
compounds causing 50 percent inhibition were 1.4 to 1.5
x 10" m moles/ml for spermine, 2.8 to 3.1 x 10~ m moles/ml
for spermidine, and 2.6 to 3.5 x 10~ m moles/ml for acrolein.
C-31
-------
Since the inhibitory potencies of these compounds 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 investi-
gators have examined the role of acrolein in the virucidal
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 spermine are not
attributable to the generation of acrolein.
Koerker, et al. (1976) have examined the cytotoxicity
of acrolein and related short-chain aldehydes and alcohols
to cultured neuroblastoma cells. Aldehydes were consistantly
more toxic than the corresponding alcohols. Based on viabil-
ity of harvested cells and increase in the number of sloughed
cells after exposure, acrolein was more potent than formalde-
hyde, and much more potent than acetaldehyde, or propionalde-
hyde. Based on decreases in neurite formation and viability
of sloughed cells, formaldehyde was somewhat more potent
than acrolein and substantially more potent than either
acetaldehyde or propionaldehyde. In j.n vitro tests on Ehrlich-
Landschutz diploid ascites tumor cells, Holmberg and Malmfors
(1974) found acrolein to be substantially more toxic than
formaldehyde over incubation periods of one to five hours.
Both of these aldehydes, however, were among the more toxic
organic solvents assayed in this study. Similarly, in J.TI
vitro tests of tobacco smoke constituents on mice ascites
C-32"
-------
sarcoma BP8 cells (48-hour exposure periods)/ Pilotti, et
al. (1975) found aldehydes to be among the most toxic group
of compounds studied. At a concentration of 100 juM, 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 cyclophosphamide. Sladek (1973) determined the cytotoxic
activities of cyclophosphamide and various cyclophosphamide
metabolities, including acrolein, to Walker 256 ascites
cells. In this study, ascites cells were exposed to the
various compounds in vitro for one hour, then injected into
host rats. The proportion of viable ascites cells was esti-
mated from survival times of the rats. Based on this assay,
acrolein was found to be only marginally cytotoxic (LCgQ
of 8.75 juM) and did not account for a substantial proportion
of the cytotoxicity of cyclophosphamide metabolites generated
iH ZJLZ2* Cyclophosphamide itself was virtually non-toxic
(LCg0 of > 100 /iM). 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 transfered
to fresh culture medium. Cytotoxicity was expressed as
a 72-hour ICcQ - the exposure concentration causing a 50
percent decrease in cell number compared to untreated cells
72 hours after treatment. The ICcn for acrolein was 1.0
>ug/ml (approximately 18 uM) and the IC5Q for cyclophosphamide
was 6,000 /ig/ml. Lelieveld and Van Putten (1976) measured
the cytotoxic effects of cyclophosphamide and six possible
metabolites, including acrolein, to normal hematopoietic
C-33
-------
stem cells of mice, osteosarcoma cells, and L1210 leukemia
cells. Acrolein was inactive against normal hematopoietic
stem cells and osteosarcoma cells, and less active than
cyclophosphamide against leukemia cells. Similarly, Brock
(1976) has found that acrolein is less active than cyclophos-
phamide 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 im-
paired nucleic acid or protein synthesis. Using primary
cultures of mouse-kidney tissue exposed to a total of 70
ug acrolein, Leuchtenberger, et al. (1968) noted a progres-
sive decrease in the uptake of tritiated uridine, 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 concentra-
tion-related decreases in the uptake of tritiated uridine,
tritiated thymidine, and tritiated leucine. Using similar
methods, Kimes and Morris (1971) have also demonstrated
inhibition of DNA, RNA, and protein synthesis by acrolein
in Escherichia coli.
In in vitro studies on the kinetics of acrolein inhibi-
tion 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 E. coli DNA polymerase, Munsch, et al.
(1973) noted that acrolein inhibited rat liver DNA polymerase
but stimulated E. coli DNA polymerase. Since the active
C-34
-------
site of rat liver DNA polymerase is associated with a functional
sulfhydryl group but E. coli DNA polymerase is not; and
since acrolein's inhibitory effect on rat liver DNA polymerase
could be antagonized by 2-mercaptoethanol (see the "Synergism
and/or Antagonism" section), these investigators concluded
that acrolein acts on rat liver DNA polymerase by reacting
with the sulfhydryl group. Subsequently, Munsch, et al.
(1974a) demonstrated that tritiated acrolein 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 mg/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 inhala-
tion exposures. In one-month inhalation exposures of rats
to acrolein at a concentration of 1.2 mg/m , Bouley (1973)
noted decreases in growth rates and in the levels of oxida-
tion-reduction coenzymes in the liver (additional details
not given). Rats continously exposed to acrolein in the
air at a concentration of 1.27 mg/m for up to 77 days evi-
denced decreased food intake accompanied by decreased body
weight gain. Between days 7 and 21 of exposure, animals
evidenced nasal irritation. Changes in relative lung and
liver weights, as well as serum acid phosphatase activity,
are summarized in Table 7. Respiratory tract irritation,
a decrease in the number of alveolar macrophages, and in-
creased susceptibility to respiratory infection by Salmonella
enteritidis were noted only during the first three weeks
C-35
-------
of exposure (Bouley, et al. 1975, 1976). Philippin, et
al. (1969) also noted decreased body weight in mice exposed
to acrolein in the air at concentrations of 13.8 mg/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 six percent) nor dose-related.
Lyon, et al. (1970) exposed rats, guinea pigs, monkeys,
and dogs to acrolein concentrations of 1.6 and 8.5 mg/m
in the air for eight hours per day, five days per week,
for six weeks. In addition, continuous exposures were con-
ducted at 0.48, 0.53, 2.3, and 4.1 mg/m for 90 days. The
following biological end points were used to assess the
effects of exposure: mortality, toxic signs, whole body
weight changes, hematologic changes (hemoglobin concentration,
hematocrit, and total leukocytes), biochemical changes (blood
urea nitrogen, alanine and aspartate aminotransferase activi-
ties) , and pathological changes in heart, lung, liver, spleen,
and kidney. No gross effects were noted in the continuous
exposures to 0.48 and 0.53 mg/m or in the repeated exposures
to 1.6 mg/m acrolein. 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 1.6 mg/m acrolein developed chronic inflammatory
changes of the lung. These changes were more pronounced
in dogs and monkeys than in rats and guinea pigs. At 8.5
mg/m squamous metaplasia and basal cell hyperplasia of
the trachea from dogs and monkeys were attributed to acrolein
C-36
-------
TABLE 7
Relative Weights of Lungs and Liver, and Serum Level of Acid
Phosphatases (n = number of rats, m = mean value,
s.d. = standard deviation) (Bouley, et al. 1976)
Parameters
Time
Control rats
Test rats Statistical analysis
lungs weight x 100
body weight
15th and 32nd days no significant difference between 2 x 10 control
and 2 x 10 test rats
77th day
n = 10
m = 0.489
n = 15
m = 0.588
t = 2.67
0.02>P>0.01
n .
i
u>
liver weight x 100
body weight
s.d. =
15th day n =
m =
s.d. =
0.087
10
5.00
0.14
s.d.
n
m
s.d.
= 0.111
= 10
= 4.55
= 0.14
t
0
= 7.12
.001>P
32nd and 77 days no significant difference between 10 and 15
control, and 10 and 15 test rats
mU of acid phosphatases
per ml of serum
15th day
n = 10
m = 77.87
s.d. = 10.59
n = 10
m = 62.11
s.d. = 6.72
t = 3.91
P = 0.001
32nd and 77th days no significant differences between 10 and 11
control, and 10 and 11 test rats
-------
. exposure. In addition, this exposure induced necrotizing
bronchitis and bronchiolitis with squamous metaplasia in
the lungs of seven of nine monkeys. Similar pathological
results were noted in continuous exposures to 2.3 and 4.1
rag/m .
Feron, et al. (1978) exposed hamsters, rats, and rabbits
to acrolein vapor at concentrations of 0.4, 3.2, and 11.3
mg/m six hours per day, five days per week, for 13 weeks.
At the highest concentration, all animals displayed signs
of eye irritation, decreased food consumption, and decreased
weight gain. In rats and rabbits, no abnormal hematological
changes were noted. Female guinea pigs at the highest dose,
however, showed statistically significant increases in the
number of erythrocytes, pack cell volume, hemoglobin concen-
tration, and the number of lymphocytes and a decrease in
the number of neutrophilic leukocytes. Additional changes
noted in this study are summarized in Table 8.
Watanabe and Aviado (1974) have demonstrated that re-
peated inhalation exposures of mice to acrolein (100 mg/m
for 30 minutes, twice a day for five weeks) cause a reduc-
tion in pulmonary compliance.
The subacute oral toxicity of acrolein has been examined
in less detail. Albin (1962) indicates that rats exposed
to acrolein in drinking water at concentrations up to 200
mg/1 for 90 days evidenced only slight weight reduction
at the highest level tested. This was attributed to unpala-
bility of the drinking water. Similar results have been
reported by Newell (1958) (summarized in Natl. Acad. Sci.
1977). In one study, acrolein was added to the drinking
water of male and female rats at concentrations of 5, 13,
C-38
-------
TABLE 8
Summary of Treatment-Related Effects in Hamsters, Rats and Rabbits
Repeatedly Exposed to Acrolein for 13 Weeks (Feron, et al. 1978)
o
i
OJ
vo
Criteria
affected
Effects'
Hamsters
Acrolein (ppm)
Rats
Acrolein (ppm)
Rabbits
Acrolein (ppm)
.Symptomatology
Mortality
Growth
Pood intake
Haematology
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
+
-
++
+
+
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 4.9
X XX
0 +++
_ —
0 0
0 +
0
0 ++
0 +
0 +
0 +++
0 x
XX XXX
0 xx
0 xxx
0 xxx
0.4.
0
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
4.9
xxx
0
—
—
0
+
0
++
0
0
0
0
XX
NE
X
XX
aO = 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.
-------
32, 80, and 200 mg/1 for 90 days. No hematologic, organ-
weight, or pathologic changes could be attributed to acrolein
ingestion. At the highest concentration, water 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 one of five 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 micropathologic abnor-
malities.
Chronic Toxicity to Experimental Mammals: The only
published chronic toxicity study on acrolein is that pre-
sented by Feron and Kruysse (1977). In this study, male
and female Syrian golden hamsters 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 disap-
peared during the second week of exposure. During the expo-
sure period, males and females had reduced body weight gains
compared to the control animals but the survival rate was
unaffected. Hematological changes - slight, but statistically
significant increased hemoglobin content and packed cell
volume - occurred only in females. Similarly, significant
(p 0.05) decreases in relative liver weights (-16 percent)
and increases in lung weights (+32 percent) occurred only
C-40
-------
in females. In both sexes, pathologic effects included
inflammation and epithelial metaplasia in the nasal cavity.
No other pathological changes in the respiratory tract were
attributable to acrolein.
Effects on Humans: As summarized in Table 9, consider-
able 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 irritation as formaldehyde, Schuck
and Renzetti (1960) indicated that acrolein and formaldehyde
account for most of the eye irritation caused by the photooxi-
dation 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 diallyl-
glycol carbonate monomer, Lacroix, et al. (1976) conducted
patch tests on humans with acrolein. In these tests, acrolein
solutions in ethanol caused no irritation at concentrations
(v/v) of 0.01 to 0.1 percent. At a concentration of one
percent, six of 48 subjects evidenced a positive response
(two erythemas and four serious edemas with bullae). At
a concentration of ten percent, all eight subjects evidenced
a positive response. Histological findings of a second
series of tests with ten percent acrolein are summarized
in Table 10.
C-41
-------
TABLE 9
Irritant Properties of Acrolein to Humans
Exposure
Effect
Reference
n
i
^
M
0.58 mg/m x 5 min.
2.3 mg/m3 x 1 min.
2.3 mg/m x 2 to 3 min.
2.3 mg/m x 4 to 5 min.
4.1 mg/m3 x 30 sec.
4.1 mg/nu x 1.0 min.
4.1 mg/m x 3 to 4 min.
12.7 mg/m x 5 sec.
12.7 mg/nu x 20 sec,
12.7 mg/m x 1 min.
50.1 mg/m x 1 sec,
0.48 mg/m3
2.3 mg/m
9.2 mg/m
1.8 mg/m 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 irritation
lacrimation
lacrimation within 20 seconds,
irritation to exposed mucosal
surfaces
lacrimation within 5 seconds,
irritating to exposed mucosal
surfaces
Albin, 1962
Reist and Rex, 1977
Pattle and
Cullumbine, 1956
Sim and Pattle,
1957
-------
TABLE 10
Patch Tests with ten percent Acrolein in Ethanol on
Control Subjects (Biopsied at 48 Hours) (Lacroix, et al. 1976)
CM
CM
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
No of Polymorph. Papillary
biopsy infiltrate edema
375 +++ ++
376 + ++
74 ++ ++
88 ++ ++
89 + +
90 + +
91 ++ +
178 . + +
179 + +
346 0 +
347 +++ +
348 ++ ++
Epidermis
0
necrosis
0
necrosis
0
necrosis
0
necrosis
necrosis
bullae
0
bullae
Result
Irritation
Irritation
Irritation
Irritation
Irritation
Irritation
Irritation
Irritation
Irritation
Irritation
Irritation
Irritation
C-43
-------
Kaye and Young (1974) have detected 3-hydroxypropylmer-
capturic in the urine of patients receiving cyclophospharaide
orally (50 mg twice or thrice daily) but not in the urine
of untreated humans. Based on analogies to the metabolic
patterns of cyclophosphamide in rats, these investigators
concluded that acrolein is probably a metabolite of cyclophos-
phamide in man.
In studies on human polymorphonuclear leukocytes (PMN's),
Bridges, et al. (1977) found that acrolein was a potent
in vitro inhibitor of PMN chemotaxis (EC5Q of 15 jam) but
had no significant effect on PMN integrity (measured by
beta-glucuronidase release, lactic acid dehydrogenase release,
and cell viability) or glucose metabolism (measured by glucose
utilization, lactic acid production, and hexose monophosphate
activity). Cysteine, at a concentration of 10 mM, completely
blocked the inhibitory effect of 160 /am 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 involved
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 non-competitive with respect to NADH and uncompetitive
with respect to pyruvate.
Little information is available on the chronic effects
of acrolein on humans. An abstract of a Russian study indi-
cates that occupational exposure to acrolein (0.8 to 8.2
mg/m ), methylmercaptan (0.003 to 5.6 mg/m ), methylmercaptor-
-------
propionaldehyde (0.1 to 6.0 mg/m ), formaldehyde (0.05 to
8.1 mg/m ), 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 and greater
than seven years (Kantemirova, 1975).
Synergism and/or Antagonism
Acrolein is highly reactive with thiol groups. Acrolein
rapidly conjugates with both glutathiohe and cysteine (Ester-
bauer, et al. 1975, 1976). Cysteine has been shown to antago-
nize the cytotoxic effects of acrolein on ascites tumor
cells of mice (Tillian, et al. 1976). Cysteine also antago-
nizes the inhibition of acrolein on rabbit alveolar macrophage
calcium-dependent ATPase, phagocytosis, adhesiveness (Low,
et al. 1977). Both cysteine and ascorbic acid have been
shown to antagonize the acute lethal effects of orally admin-
istered acrolein in male rats (Sprince, et al. 1978). Munsch,
et al. (1973, 1974a) have demonstrated that 2 mercaptoetha-
nol antagonizes the inhibitory effect of acrolein on rat
liver DNA polymerase. The irritant effects of. acrolein
injected into the footpad of rats was blocked by N-acetyl-
cysteine, penicillamide, glutathione, 2P-mercaptopropioriyl-
glycine, 2-mercaptoethanol, and ,^,^-dimethylcysteamine (White-
house and Beck, 1975).
The effects of acrolein, unlike those of DDT and para-
thion, on the adrenocortical response of rats is not inhibited
by pretreatment with phenobarbital and is only partially
inhibited by dexamethasone (Szot and Murphy, 1970).
Pretreatment of rats with acrolein (3 mg/kg i.p.)
significantly prolongs hexobarbital and pentobarbital sleeping
time (Jaeger and Murphy, 1973).
C-45
-------
Teratogenicity
No reports have been encountered on the potential terato-
genicity of acrolein.
Bouley, et al. (1976) exposed male and female rats ;
to 1.3 mg/m acrolein vapor for 26 days and found no signifi-
cant differences in the number of pregnant animals as well
as 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 injec-
tions to male mice prior to an eight-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 (15 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. coli used for detecting forward mutations (from gal
Rs to gal and from 5-methyltryptophan sensitivity to 5-
methyltryptophan resistance) and reverse mutations (from
arg" to arg ), acrolein demonstrated no mutagenic activity
with or without activation by mouse liver homogenates (Ellen-
berger and Mohn, 1976, 1977).
C~46
-------
Bignami, et al. (1977) found that acrolein induced
mutagenic effects in Salmonella typhimurium strains TA1538
and TA98 (insertions and deletions), but showed no activity
in strains TA1535 or TAlOO (base-pair substitutions). Anderson,
et al. (1972) were unable to induce point mutations in eight
histidine requiring mutants of S. typhimurium. This system
also gave negative results of 109 other herbicides but was
positive for three known mutagens: diethyl sulfate, N-methyl-
N1-nitro-N-nitrosoguanidine, and ICR-191.
Izard (1973) determined the mutagenic effects of acrolein
on three strains of Saccharomyces cerevisiae. In strain
N123, a histidine auxotroph, acrolein at 320 mg/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 substitutions in
S. cerevisiae. However, this lack of activity could be
due to the high toxicity or instability of acrolein or to
the inability of these strains to convert acrolein to some
other active molecule.
Carcinogenicity
Ellenberger and Mohn (1976) indicated that acrolein
is "known as (a) cytotoxic and carcinogenic compound."
The carcinogenicity of acrolein has not been confirmed in
our review of the literature. In the chronic inhalation
study by Feron and Kruysse (1977), summarized in the "Chronic
C-47
-------
Toxicity to Experimental Animals" section, acrolein gave
no indication of carcinogenic activity, had no effect on
the carcinogenic activity of diethylnitrosamine, and had
a minimal effect on the carcinogenic activity of benzo(o^)
pyrene. Detailed tumor pathology from this study is pre-
sented in Table 11.. Based on these results, Feron and Kruysse
(1977) concluded 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 (1979). In this
study, hamsters were exposed to 11.5 mg/m acrolein vapor,
six hours per day, five days per week, throughout their
lifespan. No evidence was found that acrolein was a carcin-
ogen or a cocarcinogen with either benzo(o«.)pyrene or ferric
oxide. DiMacco (1955) summarizes a study by Savoretti (1954)
indicating that acrolein resulted in an increase 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
increase.
Boyland (1940) found that acrolein, at daily oral doses
of 0.25 mg/mouse, had a marginal (p<0.1) inhibitory effect
on the growth of spontaneous skin carcinomas and a signifi-
cant (p<0.05) inhibitory effect on the growth of grafted
sarcomas.
C-48
-------
TABLE 11
Site, Type, and Incidence of Respiratory Tract Tumors in Hamsters Exposed to Air
or Acrolein Vapor and Treated Intratracheally with
BP or Subcutaneously with DENA
(Feron and Kruysse, 1977)
Incidence of tumors
Inhalation of
Site and type
of
tumors
No of animals
examined
o Larynx
',. Papilloma
o Trachea
Polyp
Papilloma
Squamous cell
carcinoma
Bronchi
Polyp
Papilloma
Adenocarc inoma
Squamous cell
carcinoma
Lungs
Papillary
adenoma
Acinar adenoma
Adenosquamous
adenoma
Squamous cell
carcinoma
Oat cell-like
carcinoma
-a 0.9%
NaClb
14 14
\/
28
0
0
0
0
0
0
0
0
0
0
0
0
0
BPC
(18.2
mg)
27
1
0
0
0
0
1
0
0
0
0
1
0
0
air
BPd
(36.
mg)
24
0
0
1
2
0
0
1
0
3
2
0
0
0
Inhalation of acrolein
4
DENA6
Females
27
3
0
8
0
0
2
0
0
0
0
0
0
0
_a 0.9%
NaClb
14 13
V
27
0
0
1
0
0
0
0
0
0
0
0
0
0
BPC
(18.2
mg)
29
0
1
3
0
0
0
0
0
2
2
0
0
0
BPd
(36.4
mg)
30
0
0
6
2
0
0
0
1
4
5
2
1
1
DENA6
28
5
0
8
0
1
1
0
0
0
0
0
0
0
-------
TABLE 11 (Cont.)
i-n
O
Incidence of tumors
Inhalation of
Site and type
of
tumors
No of animals
examined
Nasal cavity
Polyp
Papilloma
Adenocarc inoma
Larynx
Papilloma
Trachea
Polyp
Papilloma
Squamous cell
carcinoma
Anaplastic
carcinoma
Sarcoma
Bronchi
Polyp
Papilloma
Adenoma
Adenocarcinoma
Lungs
Papillary adenoma
Acinar adenoma
Adenosquamous
adenoma
Adenocarcinoma
-a 0.9%
NaClb
15 15
V
30
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
BPC
(18.2
mg)
29
0
0
0
0
0
2
0
0
0
0
1
0
0
0
1
1
0
air
BPd
(36.4
mg)
Males
30
0
0
0
1
0
5
1
1
1
0
2
0
1
6
3
2
2
Inhalation of acrolein
DENAe
29
1
0
1
7
2
1
0
0
0
1
2
0
0
0
0
0
0
a 0.9%
NaClb
15 15
V
30
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
BPC
(18.2
mg)
30
0
0
0
0
1
1
0
0
1
0
1
0
0
0
1
1
0
BPd
(36.4
mg)
29
0
0
0
1
2
3
3
2
1
2
0
1
2
4
3
1
0
DENA6
30
0
1
0
4
1
5
0
0
0
0
0
0
0
0
0
0
0
-------
TABLE 11 (Cont.)
Site and type
of
tumors
Adenosquamous
carcinoma
Squamous cell
o carcinoma
^ Oat cell-like
^ carcinoma
Anaplastic
carcinoma
.No further treatment.
Given intratracheally
oGiven intratracheally
Given intratracheally
^Given subcutaneously
Incidence of tumors
Inhalation of air Inhalation of acrolein
BPC BPd BPC BPd
-a 0.9% (18.2 (36.4 _a 0.9% (18.2 (36.4
NaClb mg) mg) DENAe NaClb mg) mg) DENAe
Males
00000010
0 0 1 00 1 1 0
00000010
0 0 10 0 0 0 0
(0.2 ml) weekly during 52 wk.
in 52 weekly doses of 0.35 mg.
in 52 weekly doses of 0.70 mg.
in 17 three-weekly doses of 0.125 ul.
.n.*** 4» A. WL v> s^.t i x"f V% ^i — * VN w ^ Vv -* 1 ^ e-*m *~i *- •*« i ^ 4- XN T • » r* ^ r*
-------
CRITERION FORMULATION
Existing Guidelines and Standards
The current time-weighted average TLV for acrolein
established by the American Conference of Governmental Indus-
trial Hygienists (ACGIH, 1977) is 0.1 ppm ( 0.25 mg/m3).
The same value is recommended by the Occupational Safety
and Health Administration (39 FR 23540). The ACGIH standard
was designed to "minimize, but not entirely prevent, irrita-
tion to all exposed individuals" (ACGIH, 1974). Kane and
Alarie (1977) have reviewed the basis for this TLV in terms
of both additional data on human irritation and their own
work on the irritant effects of acrolein to mice (summarized
in the "Acute, Subacute, and Chronic Toxicity" section).
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 paperboard 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
concentration of acrolein in the atmosphere is 0.1 mg/m
(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
c-52
-------
estimates of current levels of human exposure cannot be
made based on the available data. Acrolein has not been
monitored in ambient raw or finished waters.
Special Groups at Risk
Since acrolein is a component of tobacco and marijuana
smoke, people exposed to cigarette smoke are a group at
increased risk from inhaled acrolein. In addition, acrolein
is generated by the thermal decomposition of fat, so cooks
are probably also at additional risk (see "Exposure" section)
Since acrolein has been shown to suppress pulmonary antibac-
terial 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 "Mutagenicity" section) and can bind to mammalian DNA
(see "Acute Effects on Experimental Systems" section), cur-
rent information indicates that acrolein is not a carcinogen
or cocarcinogen ("Carcinogenicity" section). Water quality
criteria for acrolein could be derived from the TLV, chronic
inhalation studies, and subacute oral studies using non-
carcinogenic biological responses.
Stokinger and Woodward (1958) have described a method
for calculating water quality criteria from TLV's. Essen-
tially, 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 parti-
tioned 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
C-53
-------
exposures, such a criterion would have little, if any, validity.
A criterion could also be estimated based on chronic
inhalation data. As summarized in the "Chronic Toxicity
to Experimental Animals" section, female hamsters exposed
to acrolein at 9.2 mg/m in the air, seven hours per day,
five days per week, for 52 weeks evidenced slight hemato-
logic 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 calculated. The average body weight for the hamsters
at the end of the exposure was about 100 g. Assuming a
mean minute volume 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 jug/animal (9.2 mg acrolein/m x 0.033
1/min x 1 m /1000 liters x 60 min/hour x 7 hours/day x 5
days/7 days x 0.75) or 683 pg/kg. Using an uncertainty
factor of 1,000 (Natl. Acad. Sci. 1977), an estimated
"unacceptable" daily dose for man is 0.683 jug/kg or 47.8
/jg/man, assuming a 70 kg body weight.
A criterion based on this daily dose level would be
unsatisfactory for two reasons. First, the dose data used
to derive the standard are not based on a 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 inhala-
tion data may not be suitable for deriving a criterion.
C-54
-------
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 effects (see "Subacute Toxicity
to Experimental Animals" section). Because this study did
not involve a chronic exposure, the National Academy of
Sciences (1977) declined to derive an acceptable daily intake
for man based on this study. However, McNamara (1976) has
suggested that subacute exposures can be used to estimate
chronic no-effect levels. Based on an extensive review
of the literature comparing subacute and chronic toxicity
tests, McNamara (1976) noted that "for 95 percent of chemical
compounds...(on which data were available)...a three-month
no-effect dose divided by a factor of ten will produce no
effects in a lifetime." Using this approximation for acrolein,
the no-observable-effect level for acrolein on rats can
be estimated at 20 mg/1 of water. 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
is estimated at 1.56 mg/kg. This value may be converted
into an ADI for man by applying an uncertainty factor.
Since the chronic no-effect dose is merely an estimate based
on observed relation-ships between subacute and chronic
toxicity, an uncertainty factor of 1,000 is recommended
(Natl. Acad. Sci. 1977). Thus, the estimated ADI for man
is 1.56/ag/kg or 109 jug/man, assuming a 70 kg body weight.
Therefore, consumption of 2 liters of water daily and 18.7
grams of contaminated fish having a bioconcentration factor
C-55
-------
of 790, would result in, assuming 100 percent gastrointestinal
absorption of acrolein, a maximum permissible concentration
of 6.50^ug/1 for the ingested water:
109 jag
= 6.50 jug/1
(2 liters + (790 x 0.0187) x 1.0
This calculation assumes that 100 percent of man's exposure
is assigned to the ambient water pathways of ingesting water
and contaminated fish/shellfish products. Although it is
desirable to develop a criterion based on total exposure
analysis, the data for other exposure is not sufficient
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 1000, the criterion
level corresponding to the calculated acceptable daily intake
of 1.56 jug/kg, is 6.50 jug/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 7.38 jug/1
if exposure is assumed to be from the consumption of fish
and shellfish products alone.
C-56
-------
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