. e :1:!AL 3RAF7
'Jniten StsT-s "-in --
environmental Proteciion CV.nU^vi
Agency June. 1987
&EPA Research and
HEALTH AND. ENVIRONMENTAL EFFECTS PROFILE
FOR METHYL ACRYLATE
i
Prepared for
OFFICE OF SOLID WASTE AND
EMERGENCY RESPONSE
Prepared by
Environmental Criteria and Assessment Office
Office of Health and Environmental Assessment
U.S. Environmental Protection Agency
Cincinnati, OH 45268
DRAFT: DO NOT CITE OR QUOTE
HOTICE
This document Is a preliminary draft. It has not been formally released
by the U.S. Environmental Protection Agency and should not at this stage be
construed to represent Agency policy. It Is being circulated for comments
on Its technical accuracy and policy Implications.
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DISCLAIMER
This report 1s an external draft for review purposes only and does not
constitute Agency policy. Mention of trade names or commercial products
does not constitute endorsement or recommendation for use.
11
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DEFACE
Health and Environmental Effects Profiles (HEEPs) are prepared for the
Office of Solid Waste and Emergency Response by the Office of Health and
Environmental Assessment. The HEEPs are Intended to support listings of
hazardous constituents of a wide range of waste streams under Section 3001
of the Resource Conservation and Recovery Act (RCRA). as well as to provide
health-related limits for emergency actions under Section 101 of the Compre-
hensive Environmental Response, Compensation and Liability Act (CERCLA).
8ot.h published literature and Information obtained from Agency pngrim
office files are evaluated as they pertain to potential human health.
aquatic life and environmental effects of hazardous waste constituents. The
literature searched and the dates of the searches are Included 1n the
section titled "Appendix: Literature Searched." The literature, search
material 1s current through November, 1985.
Quantitative estimates are presented provided sufficient data are
available., for systemic toxicants, these Include Reference doses (RfDs) for
chronic exposures. An RfD 1s defined as the amount of a chemical to which
humans can be exposed on a dally basis over an extended period of time
(usually a lifetime) without suffering a deleterious effect. In the case of
suspected carcinogens, RfDs are not estimated In this document series.
Instead, a carcinogenic potency factor of q-|* 1s provided. These potency
estimates are derived for both oral and Inhalation exposures where
possible. In addition, unit risk estimates for air and drinking water are
presented based on Inhalation and oral data, respectively.
Reportable quantities (RQs) based on both chronic toxldty and cardno-
genlcHy are derived. The RQ Is used to determine the quantity of a hazard-
ous substance for which, notification Is required In the event of a release
as specified under CERCLA. These two RQs (chronic tpxldty and cardnogen-
Idty) represent two of six scores developed (the remaining four reflect
1gn1tab1l1ty, reactivity, aquatic toxldty and acute mammalian toxldty).
The first draft of this document was prepared by Syracuse Research
Corporation under EPA Contract No. 68-03-3228. The document was subse-
quently revised after reviews by staff within the Office of Health and
Environmental Assessment: Carcinogen Assessment Group, Reproductive Effects
Assessment Group, Exposure Assessment Group, and the Environmental Criteria
and Assessment Office 1n Cincinnati.
The HEEPs will become part of the EPA RCRA and CERCLA dockets.
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EXECUTIVE SUMMARY
Methyl acrylate Is a colorless liquid with an' acrid odor (IARC, 1979a).
It Is reasonably soluble In water and 1s soluble In a number of organic
solvents (Weast, 1985; Wlndholz, 1983). The chemical 1s used primarily as a
modifying monomer with other acrylates to provide, rigidity 1n resins for
leather-finishing, textile and paper coatings, and adheslves; H 1s also
used to produce acrylic fibers and plastic bottles (Celanese Chemical Co.,
1981). Currently, two U.S. manufacturers (Badlsche Corp. and Celanese
Chemical Co.) produce methyl acrylate (SRI, 1986): The current U.S.
production volume for th.1s chemical 1s not available.
Methyl acrylate 1s likely to undergo polymerization If released to the
environment 1n a spill-type situation; however, the diluted concentrations
that may be encountered 1n the environment are unlikely to polymerize
significantly. If released to water, volatfllzatlon and oxidation by
singlet oxygen and hydroxyl radical are expected to be Important removal
mechanisms. Although methyl acrylate appears to be susceptible to mlcroblal
degradation, the quantitative significance of blodegradatlon 1n the environ-
ment cannot be predicted from the available data. Direct photolysis,
adsorption to sediment, bloconcentratlon and hydrolysis (except 1f pH >9)
are not expected to be Important 1n water. If released to the atmosphere,
methyl acrylate 1s expected .to remain In the vapor phase and react rapidly
with HO radical and ozone, with an estimated half-life of 6.5 hours (U.S.
EPA, 1986a). If released to soil, methyl acrylate 1s expected to be highly
mobile based on estimated K values; therefore, significant leaching 1n
soil may occur. Methyl acrylate may volatilize significantly from soil sur-
faces. In moist alkaline soil (pH >9). hydrolysis Is potentially Important.
1v
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Pertinent amoisnt watsr monitoring jata for methyl acrylate could not :e
located In the available literature as cited In the Appendix. Methyl
acrylate was detected 1n the ambient air near Industrial sites 1n Newark,
NJ, at a concentration of 4.545 mg/m3 and at trace concentrations near
Industrial sites 1n Bound Brook. NJ (PelUzzarl, 1977). It 1s possible that
metnyl acrylate will be emitted to the atmosphere or to water from effluents
during Us Industrial manufacture or use. Leaching of residual monomer from
polymer products that have been landfllled may be possible. Since polymer
products made from methyl acrylate are permitted for various food contact
uses (IARC, 1979b), leaching of residual monomer Into foods may be
possible. Methyl acrylate has been reported to be a volatile component of
pineapple concentrate (IARC, 1979b). Incineration of acrylate polymers may
be a source of atmospheric acrylate release. A National Occupational Hazard
Survey (NOHS) conducted between 1972 and 1974 estimated that 11,803 U.S.
Workers are potentially exposed to methyl acrylate (NIOSH, 1984).
The Information concerning toxIcHy of methyl acrylate to aquatic
organisms 1s quite limited. Fish LC5Q values of 5.0 and 7.5 mg/a were
reported by Paulet and Vldal (1975) and Juhnke and Luedemann (1978), respec-
tively. A concentration of 2.4 mg/8, caused 52 and 95X mortality of two
species of planktonlc crustaceans (D'Angelo and S1gnor1le, 1978). The
lowest reported toxlclty threshold for Inhibition of culture growth among
three protozoans was 10 mg/i for Chllomonas paramedum (BMngmann and
Kuehn, 1981). The most sensitive plant species was the blue-green alga,
Hlcrocystls aeruqlnosa. with a toxlclty threshold of 1.3 mg/l (Brlngmann
and Kuehn, 1978).
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Oaia regarding :r.e rate ana .-xisni ;r 3DsorDt:o'n :r nethyi .jcryiaie ver°
not available; however, detection of urinary metabolites or radioactivity
following oral and dermal dosing of guinea pigs with unlabeled or
14C-methyl acrylate Indicate that the chemical was absorbed by the
gastrointestinal tract and skin (Seutter and Rljntjes, 1981). Whole body
autoradlography of guinea pigs following ora i oos^ng with i4C-methyl
acrylate Indicated distribution of radioactivity to the.liver, bladder and
brain 1n 2 hours. Autoradlography following dermal application Indicated
distribution to the heart, lungs and brains. Studies on the metabolism of
methyl acrylate In rats demonstrated that conjugation with glutathlone to
form mercapturlc adds and hydrolysis catalyzed by carbqxylesterase are
competing metabolic pathways (Silver and Murphy, 1S81; Oelbresslne et al.,
1981).' Guinea pigs treated orally with methyl acrylate excreted -14X of the
dose as thtoethers In the urine and an unspecified percentage of the dose In
the bile (Seutter and Rljntjes, 1981). Guinea pigs Injected
Intraperltoneally with 14C-methyl acrylate excreted 35.4% of the
radioactivity 1n the expired air as 14CO. 1n 24 hours. Urinary
excretion of radioactivity following oral dos^nq was 21% 1n 24 hours and
22.6X In 72 hours.
No carclnogenldty studies of methyl acrylate when the compound was
administered orally were available, and this chemical 1s not scheduled for
testing by the National Toxicology Program (NTP, 1987). No evidence of
carclnogenldty was found In male or female rats exposed by Inhalation to
<135 ppm (475 mg/ma), 6 hours/day, 5 days/week for up to 2 years (KHmlsch
and Re1n1nghaus, 1984; Kllmlsch and Zeller, 1979).
Methyl acrylate was not found to be genotoxlc In reverse mutation assays
using S. typhlmurlum with or without metabolic activation (Waegemaekers and
Benslnk, 1984; Florin et al., 1980). .Ishldate et al. (1981) and Sofunl et
v1
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al. (1984a) reported an increase in cnromosomai aoerratlons In a mammalian
cell line treated with the ester. Results concerning the mutagenlc
potential of methyl acrynate '.n. the mouse mlcronucleus test are ?qulvocal
(Przbo.lewska et al., 1984; Sofunl et al., 1984b). No teratogenlclty or
reproduction studies were found.
Oral in.* values 1n experimental animals range from 230-825 mg/kg
(Treon et al., 1949: Smyth and Carpenter. 1948; Tan11. and•Hashimoto, 1982).
There are no chronic oral toxldty data for methyl acrylate 1n experimental
animals. A ga.vage dose of 23 mg/kg methyl acrylate given 24 times over 33
days caused only a minor, Inhibition of growth 1n treated rabbits (Treon et
al., 1949).
In experimental animals, methyl acrylate was shown to be a potent skin
Irritant, Inducing Inflammation, edema and hemorrhaglng after dermal appli-
cation (treori et al., 1949; Delbresslne et al., 1980; Suvorov, 1973; Seutter
and Rljntjes, 1981). After 1- to 4-hour .Inhalation exposure, LC._s range
from 1000-33,500 ppm (~3500-118;000 mg/ma) (Smyth and Carpenter, 1984;
Vernot et al., 1977; Lomonova and Kllmova, 1979). Signs of Intoxication
Include severe Irritation to the mucous membranes and convulsions. Irrita-
tion of the nasal mycosa and corneal opacity were observed 1n rats exposed
by Inhalation to 15, 45 or 135 .ppm (53, 158 or 475 mg/ma). 6 hours/day. 5
days/week for up to 2 years In a cardnogenesls study (KHmlsch and
Re1n1nghaus, 1984; Kl1m1sch and Zeller, 1979). Hematology, urlnalysls, and
gross and hlstologlcal examinations revealed no systemic effects.
Exposure of small groups of experimental animals to 107 mg/m3 methyl
acrylate, 7 hours/day for 130 exposures 1n 185 days led to considerable
weight loss In rabbits, guinea pigs and monkeys, but not rats. No other
manifestations of toxldty were observed (Treon et al.. 1949). Height loss
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jr v-i:. :.v.Do^ec l.: "28
hours/day for 50 days, but rabbits had Initial signs of respiratory irrita-
tion. At higher concentrations for shorter periods of time, methyl acrylate
consistently Induced signs of respiratory distress, systemic toxlclty and
ultimate .death. Occupational studies (Suvorov, 1971; Dovzhanskll, 1976;
Khrcmov, T974) showed that methyl acrylate causes allergic contact
dermatitis 1n man. Application to the rabbit cornea led to a moderately
.Irritating response (Carpenter and Smyth, 1946.).
An RfD of 0.03 mg/kg/c!ay or 2 mg/day for a 70 kg man was derived from
the NOAEL for systemic tcxlclty 1n rats exposed by Inhalation to 53 mg/m3,
6 hours/day, 5 days/week for 2 years (converted to 3 mg/kg/day) 1n the study
by KHmlsch .and Relnlnghaus (1984) using an uncertainty factor of 100. An
RQ of 1000 was derived from the same exposure level at which corneal opacity
(considered to be a nonsystemlc effect) was observed. Negative results for
cardnogenlcHy 1n the 2-year Inhalation study In rats by KHmlsch and
Relnlnghaus (1984) and no data for cardnogenlcHy In humans constitute
Inadequate evidence to assess the. carcinogenic potential; therefore, methyl
acrylate was classified as an EPA Group D chemical (U.S. EPA, 198&b).
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TABLE OF CONTENTS
1. INTRODUCTION.
1.1. STRUCTURE AND CAS NUMBER • 1
1.2. PHYSICAL AND CHEMICAL PROPERTIES 1
•1.3'. PRODUCTION DATA. . ' . . 2
i.4. . USc JATA , t
1.5. SUMMARY.. 4
2. ENVIRONMENTAL FATE AMD TRANSPORT PROCc^S '. . . '' '
2.1. WATER. . . 5
2.1.1. Hydrolysis 5
2.1.2. Oxidation 5
2.1.3. Photolysis 6
2.1.4. M1crob1al Degradation ., 6
2.1.5. Volatilization 7
2.1.6. Adsorption. ;....•'....' 7
2.1.7. Bloconcentratlon. .... 7
2.2. AIR 8
2.3. SOIL . . . 8
2.3.1. Hlcroblal Degradation . 8
2.3.2. Adsorption : . . . 9
2.3.3. Volatilization. . 9
2.3.4. Hydrolysis , 9
2.4. SUMMARY 9
3. EXPOSURE 11
3.1. WATER 11
3.2. FOOD 11
3.3. INHALATION 12
3.4. DERMAL 12
3.5. SUMMARY 12
4. PHARMACOKINETCS 14
4.1. ABSORPTION 14
4.2. DISTRIBUTION 15
4.3. METABOLISM 16
4.4. EXCRETION. . 17
4.5. SUMMARY 17
1x
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TABLE JF C3NTEHTS tC3iu. ,
Page
—•^•-4>M«Bi
5. EFFECTS 19
5.1. CARCINOGENICITY. . . 19
5.2. MUTAGENICITY • : . . . . 19
5.3. TERATOGENICITY 21
5.-i. OTHER REPRODUCTIVE EFFECTS .'...•' 21
5.5. CHRONIC AND SUBCHRONIC TOXICITY
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LIST OF TABLcS
No. Title Page
1-1 Methyl Acrylate Production Data for 1977. . . 3
5-1 .Mutagenlclty Testing of Methyl Acrylate 20
5-2 LD"50 or LC50 Values of Methyl Acrylate 24
9-1 Inhalation ToxIcHy Summary for Methyl Acrylate 34
9-2 Inhalation Composite Scores for Methyl Acrylate
Using the Rat . 35
9-3 Methyl Acrylate: Minimum Effective Dose (MED) and
Reportable Quantity (RQ). ... 36
x1
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LIST jF ABBREVIATIONS
ADI Acceptable dally Intake
SCr 31oconcentration factor
BOO Biological oxygen demand
BOOT Biological oxycen nemana theoretical
CHL Chinese hamster lung
CIJ- Centra1! nervous system
CS Composite score
OMSO Dimethyl sulfoxlde
GRAS Generally recognized as safe,
1.p. Intraperltoneal
Koc Soil sorptlon coefficient standardized
with respect to organic carbon
Kow .Octanol/water partition coefficient
Concentration lethal to 50% of recipients
(and all other subscripted dosage levels)
Dose lethal to 50% of recipients
LOEL Lowest-observed-effect level
MED Minimum effective dose
NOAEI No-observed-adverse-effect level
NOEL No-observed-effect level
PEL Permissible exposure level
ppm Parts per million
PVC Polyvlnyl chloride
RfD Reference dose
RQ Reportable quantity
RVj Dose-rating value
RVe Effect-rating value
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LIST OF ABBREVIATIONS (com.
TLV Threshold limit value
TOTP TM-o-tolyl-phosphate
TWA Time-weighted average
JV Ultraviolet
WS Water solubility
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i. INTRODUCTION
1.1. STRUCTURE AND CAS NUMBER
Methyl acrylate Is the common name for the compound 2-orooeno1c add,
methyl ester (current CAS designation), also known as methyl 2-propenoate,
metnoxycarbonylethylene and acrylic acid, methyl ester. The structure,
molecular weight, emlplMcal formula and CAS number for methyl acrylate are
as follows:
,CH2=CH-C-0-CH3
Molecular weight: 36.1
Empirical formula: C.H60_
CAS Registry number: 96-33-3
1.2. PHYSICAL AND CHEMICAL PROPERTIES
Methyl acrylate Is a colorless liquid with an acrid odor (IARC, 1979b).
It 1s soluble 1n alcohol, ether, acetone and benzene (Weast, 1985).
Selected physical properties are listed below:
lei ting point:
Boiling point:
Density:
Refractive Index:
Water solubility:
at 20°C
at 25°C
Vapor pressure:
at 9.2°C
at 17.3°C
at 20°C
at 28°C
Log K
ow-
below -?S°C
79.9°C
0.9535 (20/4°C)
1.4040 (20°C)
6 g/100 ml water
5.2 g/100 g water
40 mm Hg
60 mm Hg
70 mm Hg
100 mm Hg
0.80
Weast. 1985
Celanese Chemical Co., 1981
Weast, 1985
Weast, 1985
Wlndholz, 1983
Klein, T981
Perry and Green, 1984
Perry and Green, 1984
Verschueren, 1983
Perry and Green, 1984
Hansch and Leo, 1985
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Vapor density: 3.0 /erjcnueren, 1983
(a1r=1.0)
Flash point: -3.3°C (closed cup) Celanese Chemical Co., 1981
Conversion factors: 1 mg/ma = 0.28 ppm Verschueren, 1983
(air) 1 ppm = 3.5 mg/m8
.'•tetnyi acry'.ate easily polymer ".zes on standing ;W1ndhoi^, "963}; :r;e
commercial' product may contain from 15-1000 ppm hydroquVnone mondmethyl
ether as an Inhibitor (IARC, 1979,b).. Polymerization is accelerated oy heat,
light and peroxides (Wlndholz,1 1983). Methyl acrylate 1s flammable and can
be a dangerous fire and explosion hazard (Hawley, 1S81).
1.3. PRODUCTION DATA
Commercial production of methyl acrylate was first reported In the
United States 1n 1944 (]ARC, 1979b). Production of methyl acrylate In 1976
(excluding any that may have been used to produce higher acrylates) was
estimated to have been 4.5 million kg (IARC, 1979b). Recent production
figures are not available. In 1984. Celanese Chemical Co. was the only
manufacturer reporting production (USITC, 1985). Current U.S. manufacturers
of methyl acrylate Include Badlsche Corp., Freeport, TX. and Celanese
Chemical Co., Pampa, TX (SRI, 1986). Production data available from the
public portion of the U.S. EPA TSCA production file for 1977 (U.S. EPA,
1977) are listed
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TABLE 1-1
Methyl Acrylate Production Data for 1977*
Producer/Location
Manufacturer
or Importer
Production Range
(millions of pounds)
Haven Chemical
Philadelphia, PA
Celanese Chemical Co.
Pampa, TX
MHJac Inc.
New Canaan, CT
Rohm and Haas Co.
Philadelphia, PA
manufacturer
manufacturer
Importer
Importer
confidential
JO-50
none
1-10
*Source": U.S. EPA, 1977
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1.4. USE DATA
Methyl acrylate Is used primarily as a modifying monomer with other
acrylates to provide rigidity Vn resins for leather-ref1n1sh1ng, textile and
paper coatings and adheslves (Celanese Chemical Co., 1981). It 1s also used.
as a component of acrylic fibers and plastic bottles (Celanese Chemical Co..
1981). Small quantities of methyl acrylate are used In the manufacture of
amphoterlc surfactants (e.g., N-dodecy1-beta-am1nooroolon1c add) for use In
special Industrial cleaners and for a variety of other applications (IARC,
1979b).
1.5. SUMMARY
Methyl acrylate Is a colorless liquid with an acrid odor {IARC, 1979b).
It 1s reasonably soluble In water and 1s soluble In a number of organic
solvents (Weast, 1985; Wlndholz, 1983). The chemical Is used primarily as a
modifying monomer with other acrylates to provide rigidity In resins for
leather-finishing, textile and paper coatings, and adheslves; H Is also
used to produce acrylic fibers, and plastic bottles (Celanese Chemical Co..
1981). Currently, two U.S. manufacturers (Badlsche Corp. and Celanese
Chemical Co.) produce methyl acrylate (SRI, 1986). Current U.S. production
volume for this chemical 1s not available.
0855p -4- 04/23/87
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•HVISONMEHTAL raH AND "RANSPORT -ROCHES
Methyl acrylate Is subject to polymerization, particularly 1n the
presence of heat or light (Wlndholz, 1983). Therefore, 1n a spill-type
situation, methyl acrylate may undergo polymerization to a resin form. The
fate processes discussed below relate to dilute concentrations of methyl
acrylate that may be encountered 1n the environment; these dilute concentra-
tions are unlikely to experience significant polymerization.
2.1. WATER
2.1."!. Hydrolysis. • Hydrolysis rate data of methyl acrylate In the
neutral aqueous solution could not be located 1n the available literature as
dted 1n the Appendix; however, the hydrolysis half-life for ethyl acrylate
at 25°C and pH 7 was reported to be 3.5 years (Mabey and H111, 1978). Based
on the add- and base-catalyzed hydrolysis rate constants reported by Mabey
and .Mill (1978), hydrolysis of methyl acrylate In environmentally addle
water will be even slower. Hydrolysis 1n alkaline waters will be faster
than at pH 7 and at pH 8 and 25°C, the half-life will be on the order of 100
days; whHe .at ?H 9, the half-life will be en the order cf 10 days. Roy
(1972) reported the alkaline hydrolysis rate constant for methyl acrylate at
25°C to be 0.0779 M~\ sec"1, which Is very close to the value of 0.078
M~l sec'1 for ethyl acrylate reported by Habey and Mill (1978). Based
on the above data, the half-life of methyl acrylate resulting from
hydrolysis will be -10 days at pH 9 and therefore hydrolysis will not be
Important 1n most environmental waters. The hydrolysis products, should
hydrolysis occur, will be acrylic add and methanol.
2.1.2. Oxidation. Experimental data specific to the oxidation of methyl
acrylate In water could not be located 1n the available literature as cited
In the Appendix; however, oxidation by photochemlcally produced oxldants,
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sucn as iinglet oxygen and HO radical, is potentially an imponant removal
mechanism. The half-life for the reaction of singlet oxygen with unsubstl-
tuted or substituted oleflns In natural water was reported to be -7.3-8.0
•Jays (Mill and Mabey, 1985). The reactivity of the acrylate monomers with
singlet oxygen in vapor-phase was found to be on the same order of magnitude
as reactivity with the oleflns (Datta and Rao, 1979). Assuming that
reactivity of acrylate monomers and oleflns In water 1s similar, then
reaction with singlet oxygen Is potentially significant.
The half-life of oleflns In water that results from Us reaction with HO
radical 'Is' on the order of 13-14 days (Mill ana Mabey, 1985). Since the
acrylate monomers contain oleflnlc double bonds, they may again be suscep-
tible to this oxidation process. Oxidation of oleflns with RO^ radical In
water has a reported half-life >200 years (Mill and Mabey, 1985); therefore,
this oxldant reaction 1s not Important.
2.1.3. Photolysis. Acetonltrlle and both the ethyl and methyl esters of
acrylic and methacryllc adds In cyclohexane and methanol, respectively, do
not absorb light strongly 1n the UV spectrum >290 nm (Brunn et al., 1976).
•This suggests that direct photolysis 1n water will riot be significant
compared with Us photooxldatlon by singlet oxygen and HO radical.
2.1.4. M1crob1al Degradation. Methyl acrylats was confirmed to be
significantly biodegradable (blo-oxldatlon was >30% after 2 weeks of Incuba-
tion) by the Japanese MITI test (Sasaki, 1978). Thorn and Agg (1975) report-
ed that methyl acrylate should be degradable by biological sewage treatment
provided suitable acclimatization can be achieved; Speece (1983) suggested
that methyl acrylate should be amenable to anaerobic blodegradatlon for
Industrial wastewater treatment.
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Price ei al. (1974) measured the bioaegraaabiiity of ethyl acrylate
using an acclimated and nonacclimated sewage seed In freshwater and non-
acclimated sewage seed 1n synthetic seawater. In all three cases, 20-day
SODTs Indicated significant b1o-ox1dat1on of ethyl acrylate. By analogy,
methyl acrylate may also be blodegraded under these .test conditions. These
data are not sufficient to predict the .quantitative significance of methyl
acrylate blodegradatlon in natural water; however, H appears that methyl
acrylate may be susceptible to mlcroblal transformation In the natural
environment.
2.1.5. Volatilization. Based on a vapor pressure of 70 mm Hg
(Verschueren, 1983) and a water solubility of 60 g/J. (Ulndholz, 1983) at
20°C, the Henry's Law constant for methyl acrylate can be estimated to be
1.32x10"* atm-mVmol. This value of Henry's Law constant Indicates that
volatilization 1s significant from all environmental waters (Lyman et al.,
1982). Using the method of Lyman et al. .(1982), the volatilization
half-life from a river 1 m deep, flowing at a speed of 1 m/sec, with a wind
velocity of 3 nr/sec Is estimated to be 8.8 hours. . The volatilization
half-life from a river 10 m deep 1s estimated to be 7.9 days.
2.1.6. Adsorption. Based on a WS of 60 g/l at 20°C (Wlndholz, 1983)
and a log K of 0.80 (Hansch and Leo, 1985), partitioning from the water
column to partlculate organic matter and sedlmant 1s not expected to be
Important.
2.1.7. Bloconcentratlon. The following two equations can be used for
estimating the BCF of methyl acrylate (Lyman et al., 1982):
log BCF = 0.76 log KQW - 0.23 (2-1)
log BCf = 2.791 - 0.564 log HS (water solubility 1n ppm) (2-2)
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Based on a log X of 0.30 ana a WS of 60 g/1 'at 20°C, the 3CF values
estimated from Equations 2-1 and 2-2 for methyl acrylate are 2.4 and 1.2,
respectively. These values suggest that b1oaccumulat1on of methyl acrylate
1n aquatic organisms will not be significant.
2.2. AIR
Because of Us relatively high vapor pressure, methyl acrylate that 1s
released to the atmosphere Is expected to remain 1n the vapor phase and not
become associated with partlculate matter.
The rate constants for the vapor-phase atmospheric reaction of methyl
acrylate with HO radical and with ozone have been estimated to be
2.7xlO~11 and l.GxlCT1* cm8/molecule-sec, respectively (U.S. EPA,
1986a). Assuming average atmospheric concentrations of 8xlO» HO
rad1cal/m» and SxlO11 0_ molecules/m», the half-life of methyl
290 nm (Brunn ei al,, 1976), direct photolysis 1s not expected
to be significant compared with Its reaction to HO radical or ozone.
2.3. SOIL
2.3.1. M1crob1a1 Degradation. Pertinent data regarding the m1crbb1al
degradation of methyl acrylate could not be located In the available litera-
ture as cited 1n the Appendix. Since ethyl and methyl acrylate have been
shown to be degradable 1n various BOO tests (see Section 2.1.4.), mlcroblal
degradation 1n soil may be possible.
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'•.Z.2. • .-.asorotlon. ,( .'a'i'jes :3n :e fstlinatea jsir.a ':rse -'o
oc "
regression equations (Lyman et al., 1982):
log X = 3.64 - 0.55 log WS (In ppm) . (2-3)
log KOC = 0.544 log KQy + 1.377 (2-4)
The K va.lues calculated from Equations 2-3 and 2-4 for methyl acrylate
\iog ,< of J.60; «S or oO.uOO ppm) are 10 and 65, respecv;veiy. These
estimated K values predict high to very high soil mobility (Swann et
al., 1983). Therefore, methyl acrylate appears susceptible to significant
leaching 1n soil.
2.3.3. Volatilization. The vapor pressure of methyl acrylate (70 mm Hg
at 20°C) Indicates that It will volatilize from dry surfaces quite rapidly.
In moist soils, volatilization may be significant since methyl acrylate Is
expected to volatilize from water (see Section 2.1.5.).
2.3.4. Hydrolysis. The hydrolysis of methyl acrylate Is not expected to
become environmentally Important until pH >9 (see Section 2.1.1.). In moist
alkaline soils (pH >9), hydrolysis Is potentially Important for degradation
of methyl acrylate.
2.4. SUMMARY
Methyl acrylate 1s likely to undergo polymerization If released to the
environment in a spill-type situation; however, the diluted concentrations
that may be encountered In the environment are unlikely to polymerize
significantly. If released to water, volatilization and oxidation by
singlet oxygen and HO radical are expected to be Important removal mecha-
nisms. Although methyl acrylate appears to be susceptible to microblal
degradation, the quantitative significance of blodegradatlon 1n the environ-
ment cannot be predicted from the available data. Direct photolysis,
adsorption to sediment, bloconcentratlon and hydrolysis (except If pH >9)
are not expected to be Important In water. If released to the atmosphere.
0855p -9- 06/01/87
-------
methyl acrylate is expected i.o remain 1n ine vapor pnase ana react rapidly
with HO radical .and ozone, with an estimated half-life of 6.5 hours (U.S.
EPA. 1986a). If released to soil, methyl acrylate Is expected to be highly
mobile based on estimated K values; therefore, significant leaching In
son may occur. Methyl acrylate may volatilize significantly from soil sur-
faces. In moist alkaline soil (pH >9), hydrolysis Is potentially Important.
0855p -10- 04/24/87
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3. EXPOSURE
A National Occupational Hazard Survey conducted between 1972 and 1974
has estimated that 11.803 U.S. workers are potentially exposed to methyl
acrylate (NIOSH, 1984).
.3.1. HATER
Pertinent aquatic monitoring data 'for methyl acrylate could not be
located In the available literature as dted 1n the Appendix. The U.S. EPA
STORET Data base contained no postings for the compound.
It Is possible that methyl acrylate may be discharged with wastewater
effluents generated by manufacturing and use operations. Small amounts of
residual ethyl acrylate monomer have been found-In polymer latexes (IARC,
1979b). Leaching of residual monomer from polymer products that have been
landfllled may be possible, although no groundwater monitoring data are
available to confirm this suggestion.
3.2. FOOD
Methyl acrylate has been, reported to be a volatile component of pine-
apple concentrate (IARC,. 1979b).
The U.S. Food and Drug Administration considers methyl acrylate to be a
GRAS (generally recognized as safe) adjuvant In food, and polymers, and
copolymers made from methyl acrylate are permitted for various contact uses
with foods (IARC, 1979b). Residual monomer 1n these polymers and copolymers
may leach Into the contacted foods, although data establishing such contami-
nation could not be located 1n the available literature.
0855p -11- 04/23/87
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3.3. INHALATION
Methyl acrylate was detected In the ambient air near Industrial sHes 1n
Newark. NJ. at a concentration of 4.545 mg/ma and at trace concentrations
near Industrial sites 1n Bound Brook, NJ (PelUzzarl, 1977). Atmospheric
emissions- may result from the commercial manufacture and use of methyl
acrylate.
The high temperature combustion (>300-800°C) of polydlmethacrylates can
result 1n the formation of ethy.l methacrylate (Lomakln et a!., 1984),
suggesting that Incineration of methacrylate polymers may produce ethyl
methacrylate as a combustion product, which may In turn be released to the
atmosphere through stack emission. Incineration of acrylate polymers may
therefore be a source of atmospheric release of acrylates.
3'. 4. DERMAL
Pertinent data regarding dermal exposure of methyl acrylate could not be
located 1n the available .literature as dted 1n. the Appendix. Exposure
potential may be greatest 1n occupational settings, and. the dermal route
leads to systemic uptake (Silver and Murphy, 1981; Delbresslne et al., 1981).
3.5. SUMMARY
Pertinent ambient water monitoring data for methyl acrylate could not be
located 1n the available literature as cited 1n the Appendix. Methyl
acryla.te was detected 1n the ambient air near Industrial sites 1n Newark,
NJ, at a concentration of 4.545 mg/m* and at trace concentrations near
Industrial sites In Bound Brook, NJ (PelllzzaM. 1977). It Is possible that
methyl acrylate will be emitted to the atmosphere or to water from effluents
during Us Industrial manufacture or use. Leaching of residual monomer from
polymer products that have been landfllled may be possible. Methyl acrylate
has been reported to be a volatile component of pineapple concentrate (IARC,
0855p -12- 06/01/87
-------
1979b). Sines polymer products made from methyl jcrylate are permittee for
various food contact uses (IARC, 1979b), leaching of residual monomer Into
foods may be possible. Incineration of acrylate polymers may be a source of
atmospheric acrylate release. A National Occupational Hazard Survey (NOHS)
conducted between 1972 and 1974 estimated that 11,803 U.S. workers are
potentially exposed to methyl acrylate (NIOSH, 1984).
0855p -13- 04/23/87
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4. PHARMACOXINETICS
4.1. ABSORPTION
Seutter and Rljntjes (1981) administered 99% pure methyl acrylate by
stomach- tube to two male guinea pigs at a dose level of 0.40 mmol/kg (34
mg/kg). Five guinea pigs received the same dose of methyl (2,3-14C)-acry-
late (specific activity 0.76 mCl/mmol). Any methyl acrylate that remained
In the stomach tube was washed down with 0.3 mi of 50% ethanol. Urinary
thloether concentrations In guinea pigs treated with the unlabeled compound
were determined for 24-hour periods, then compared with the baseline concen-
tration. Guinea pigs treated with labeled compound were sacrificed 1, 2, 4,
8 and 16 hours after dosing, sectioned and prepared for whole-body auto-
radiography.
The urinary elimination of thloether or radioactivity (Sections 4.3. and
4.4.) In guinea pigs treated with unlabeled compound or 14C-methyl
acrylate Indicated that methyl acrylate was absorbed from the gastro-
intestinal tract. This conclusion was substantiated by the finding of a
distribution of radioactivity throughout body tissues, .principally 1n the
liver, bladder and brain, 2 hours after administration.
Seutter and Rljntjes (1981) applied 0.53 rnmol/kg (46 mg/kg) methyl
acrylate to the shaved skin of eight guinea pigs. Six of the guinea pigs
received methyl (2,3-1*C)-acrylate and the other two received unlabeled
methyl acrylate. The guinea pigs were sacrificed 4, 8, 16, 28 and 40 hours
after skin application. For the guinea pigs receiving unlabeled methyl
acrylate, urinary thloether levels were measured at three 24-hour Intervals.
The finding of urinary thloether levels at all three time points 1n one
guinea pig and at one time point 1n the second guinea pig Indicated dermal
0855p -14- 06/01/87
-------
jbsorpt'on; ihese ".3ve;.s ..ere lorietheles: "ower -.han -.hose • ;een .-ftsr oral
administration (Section 4.4.). For the guinea pigs receiving dermal appli-
cation of radioactive methyl acrylate, edema was first observed at 4 hours;
complete penetration of the dermls was noted at 8 hours, and by 16 hours
radioactivity' had spread directly Into the subcutaneous tissue and the rest
of the body.
4.2. DISTRIBUTION
As discussed 1n Section 4.1., whole-body autoradlography revealed that
radioactivity spread Into the Internal organs, particularly the livers,
bladders and brains of guinea pigs 2 hours after oral administration of
14C-methyl acrylate (Seutter and Rljntjes, 1981). Hepatic levels of
radioactivity declined gradually and were negligible 16 hours after dosing.
Significant retention at 16 hours was found only 1n the mucosal linings of
the stomach. Intestines and mouth epithelium. Autoradlography 8-16 hours
after dermal application of 14C-methyl acrylate revealed gradual Increases
of radioactivity In the hearts, lungs and brains of guinea pigs.
Seutter and Rljntjes (1981) also Injected six guinea pigs l.p. with 0.40
mmo'!/kg '.24 mgAg) 1*C^ethy1 ;cry1ate 'ntraperHoneally. Guinea pigs
from this group were sacrificed 1, 2, 4, 8, 24 and 48 hours after
administration, and their tissues were analyzed by whole-body
autoradlography. Radioactivity was concentrated primarily In the liver and
peritoneum of the guinea pig sacrificed at 1 hour, but had already started
to spread to other organs. Except for the liver and bladder, radioactivity
levels decreased 1n all organs of guinea pigs sacrificed at 2. 4 or 8
hours. The liver and bladder lost their radioactivity only after 24 and 48
hours. At these time points, there was stm significant retention 1n the
mucous membranes.
0855p -15- 06/01/87
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4.3. METABOLISM
Studies on the metabolism of methyl acrylate demonstrate that conjuga-
tion with glutathlone to form mercapturlc adds and hydrolysis by carboxy!-
ase activity are competing processes.
Delbresslne et al. (1981). treated female Hlstar rats 1ntraper1toneally
with methyl acrylate 1n arachls.oll at 0.14 mmol/kg/day (12 mg/kg/day), 5
days/week for 3 weeks. Analyses of the jr'ne revealed mer*:apt'jr*c acid
formation. The mercapturlc adds were Identified as N-acetyl-S-(2-carboxy-
ethyl) cystelne as a major component and N-acetyl-S-(2-carboxyethyl)
cystelhe monomethyl ester as a minor component.
In another experiment Delbresslne et al. (1981) treated female adult
Hlstar rats with 0.14 mmol/kg (12 mg/kg) methyl acrylate In arachls oil by a
single 1.p. Injection In order to quantHate the mercapturlc add formation
by measuring urinary thloether excretion. Urine was collected for 24
hours/day for 3 days and analyzed for thloether content. The single dose
nearly doubled the amount of thloether excretion over control levels. The
Investigators also studied the effect of TOTP, a carboxylesterase Inhibitor,
on the formation of thloesters. When separate groups of rats were pre-
treated with TOTP, thloether excretion Increased dramatically 1n rats given
a single 1.p. dose of 12 mg/kg methyl acrylate, but not In the rats Injected
with the vehicle control. Thin-layer chromatographlc analysis revealed that
the ratio of excreted N-acetyl-S-(2-carboxyethyl) cystelne to Us monomethyl
ester was 20:1 without pretreatment, but 1:2 with pretreatment with TOTP.
Silver and Murphy (1981) demonstrated significant hydrolysis of methyl
acrylate by lung, kidney and especially liver carboxylesterases In rat
tissue homogenates. Pretreatment of rats with 5-125 mg/kg TOTP, 18 hours
before Inhalation exposure to methyl acrylate, reduced hydrolysis by 38-96%
1n these tissues and potentiated the toxldty of methyl acrylate.
0855p -16- 04/23/87
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Pretreatment with 125 mg/kg TOTP, before innaiation exposure to £00-1000 ppm
(704-3521 mg/m3). methyl acrylate, also significantly depleted nonproteln
sulfhydryl concsntratlons Vn rat lungs, blood and liver, an Indication that
conjugation with glutathlone was enhanced. The results of Delbresslne et
"al. (1981)~*nd S1Ner and Murphy (1981) .Indicate that the carboxylesterase-
medlated hydrolysis 1s a major detoxification mechanism. When this enzyme
Is inhibited however the pathway of metabolism shifts dramatically .toward
.glutathlone conjugation and mercapturlc add (thloether) formation.
4.4. EXCRETION
Following an oral dose of -34 mg/kg of methyl acrylate to guinea pigs,
-14% of, the dose: was excreted as thloether (mercapturlc acid conjugates) 1n
the urine collected over 72 hours, with -11X of the dose being excreted In
the first 24 hours (Seutter and Rljntjes, 1981). Guinea pigs Injected l.p.
with 22 mg/kg of methyl(2,3-l4C) acrylate excreted 35.4X of the dose of
radioactivity In expired air as 14CO. within 24 hours. Total excretion
of radioactivity 1n the 'urine was 22.6X of the dose 1n 72 hours, with 21%
being excreted In the first 24 hours. Biliary excretion of radioactivity
following an oral dose of methyl (2,3-14C) acrylate was substantial wnmn
10 hours, but the amount was not expressed as percentage of dose.
4.5. SUMHARY
Data regarding the extent of absorption of methyl acrylate were not
available; however, detection of urinary metabolites or radioactivity fol-
lowing oral and dermal dosing of guinea pigs with unlabeled or 14C-methyl
acrylate Indicate that the chemical was absorbed by the gastrointestinal
tract and skin (Seutter and Rljntjes, 1981). Whole body autoradlography of
guinea pigs following oral dosing with 14C-methyl acrylate Indicated
distribution of radioactivity to.the liver, bladder and brain 1n 2 hours.
0855p -17- 04/23/87
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Autoradlography following derma! application :raicatea Distribution :o :;-.='
heart, lungs and brains. Studies on the metabolism of methyl acrylate 1n
rats demonstrated that conjugation with glutathlone to form mercapturlc
adds • and hydrolysis catalyzed by carboxylesterase are competing metabolic
pathways (Silver and Murphy, 1981; Delbresslne et al.. 1981). Guinea pigs
treated orally with methyl acrylate excreted -14% of the dose as thloethers
In the urine and an unspecified percentage of the dose In the bile (Seutter
and Rljntjes, 1981). Guinea pigs Injected .1.p. with 1*C-methyl acrylate
excreted 35.4% of the radioactivity 1n the expired air as 14CO. 1n 24
hours. Urinary excretion of radioactivity following oral dosing was 2154 In
24 hours reaching 22.6X 1n 72 hours.
0855p -18- 04/23/87
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5.1. CARCINOGENICITY
No cardnogenlcHy studies by the oral route 1n animals were located.
In a 2-year Inhalation study, however, groups of 86 male and 86 female
Sprague-Oatfley rats were exposed to methyl acrylate vapor at concentrations
of 0, 15, 45 or 135 ppm (0, 53, 153 or 475 ing/'m3}, 6 nours/aay, 5
days/week (KHmlsch and Relnlnghaus, 1984; Kllmlsch and Zeller. 1979).
Interim kills of 10 rats/sex/group were performed after 12 months and .of 15
rats/sex/group after 18 months.' The remaining rats were killed after 24
months. At each sacrifice time,.gross necropsy and hlstologlcal examination
of unspecified tissues were performed. No evidence of cardnogenlcHy was
found.
Methyl acrylate Is not scheduled for testing by the National Toxicology
Program (NTP, 1987).
5.2. NUTAGENICITY
Methyl acrylate was negative for reverse mutations In several strains of
Salmonella typhlmurlum with and without metabolic activation (Waegaekens and
Senstnk', 198*; Florin et al., 1980) (Table 5-1). Methyl acrylate oroduced
chromosomal aberrations In lung flbroblasts In a CHL cell line, as
determined by metaphase analysis; a dose of 6.5 vq/mt Induced
aberrations In 20% of cells (Ishldate .et al.. 1981). Przbojewska et al.
(1984) reported dose-related Increases 1n mouse mlcronucleus assay after
Injection of 37.5-300 mg/kg of methyl acrylate with significant toxlclty
evident at 75 mg/kg and higher. As described 1n abstracts, Sofunl et al.
(1984a,b) found that methyl acrylate Induced chromosomal aberrations In
Chinese hamster cells In culture, but was negative 1n a mouse mlcronucleus
test.
0855p -19- 06/01/87
-------
o
00
TABLE 5-1
Mulagenlclty Test Ing'of-Methyl Acrylatc
O
I
o
cr
00
Assay
Reverse
mutation
Reverse
mutation
Reverse
mutation
Chromosomal
aberration
Chromosomal
aberration
House
•Icronucleus
test
House
(•Icronucleus
test
Indicator
Organism
Salmonella
typhlnuirlua
TA98. TA100,
TA1537. TA1538.
TA1535
S. typhlmur lun
TA100
S. typhlmur lun
TA98, TA100
TA1535. TA1537
CHI cells.
lung ftbro-
blast line
Chinese
hanster
f Ibroblasts
mouse bone
marrow
f/Balb/c
mouse bone
marrow cells
Purity Application
>99X plate
Incorporation
>99X liquid
suspension
NR spot test
NR liquid
suspension
NR vapor phase
NR Inhalation
NR I. p. Injection
of mice
Concentration Activating Response
or Dose SysteiTi
40-2500 ^S-9 ;
pg/plate
60-600 pg/2 ml »S-9 ;
Incubation
medium
3 n«ol/plate .S-9 . ;
various concen- »S-9 J
trat Ions, but not
reported
189 ppm none >
(666 ng/rn')
UQ UA
nn Pin
37.5-300 mg/kg NA •
Comments
NC
NC
NC
6.5 Mg/mt.
dose dt which
chruiitosomal
dberidtlons i.ere
detected In i'OX
of n.ctdphases
A cuncenlrat ion
of 3/0 ppm
(1331 tny/in' ) udS
toxic
no <
-------
5.3. TERATOGENICITY
Pertinent data regarding the teratogenldty of methyl acrylate could not
be located'1n the'available literature as cHed in the Appendix.
5.4. OTHER REPRODUCTIVE EFFECTS
Pertinent data regarding the other reproductive effects of methyl
acrylate could not be located In the available literature as cHed 1n the
Appendix.
5.5. CHRONIC AND SUBCHRONIC TOXKITY
No chronic oral studies of methyl acrylate were available; however,
Treon et al. (1949) orally administered 23 mg/kq methyl acrylate by gavage
to two rabbits, 24 times over 33 days. Besides minor growth retardation,
there were no changes 1n the gross or microscopic hlstopathology of these
rabbits.
In the previously described (see Section 5.1.) 2-year Inhalation study
1n which rats were exposed to 0, 15, 45 or 135 ppm (0, 53, 158 or 475
mg/ma), 6 hours/day, 5 days/week for up to 2 years ophthaimologlcal exami-
nations, hematology and urlnalysls tests were also conducted at each sacri-
fice. In addition to the gross and hlstologlcal examinations (KlImlsch. and
Relnlnghaus, 1984; KHmlsch and Zeller, 1979). A temporary decreased body
weight gain was observed at 135. ppm. Irritation of the nasal mucosa with
atrophy of the neurogenlc portion of the olfactory epithelium and prolifera-
tion of reserve cells was dose-related. There was also a dose-related
corneal opacity and vascularizatlon of the eyes. No signs of systemic
toxldty, however, were observed at any exposure level.
Four rabbits, two guinea pigs, two rats and one monkey were exposed to
107 mg/ma methyl acrylate, 7 hours/day for 130 exposures 1n 185 days
(Treon et al., 1949). All species except rats showed a substantial weight
0855p -21- 09/26/86
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''oss ~'om exposure. Otner^lse. th'ere 'were no ::smcai signs, = na ~o er'fec-j
on formed elements of the blood, clotting times (rabbits) or urinary
1norgan1c:total sulfate ratios (rabbits). There were also no pathological
changes 1n the tissues of affected animals, sacrificed 2 months after the
last exposure1. No weight losses were observed In four rabbits, two guinea
pigs or two rats given 50, 7-hour exposures to 328 mg/ma meihyi acryiaie,
but the rabblt.s were found to have slight conjunctiva! and nasal
Irritation. Higher exposure concentrations for shorter periods of time
(Section 5.6.), were usually lethal..
TSCA-ITC. (1985) briefly described a Soviet rat study by Oslntseva et al.
(1970) Involving 100-day Inhalation exposure to methyl acrylate. No patho-
logical changes were seen at 0.01 mg/m3, whereas unspecified hemodynamlc
shifts occurred at Oil mg/ma, and reversible structural alterations. In
various organs were noted at 1 mg/m8. Further details were not available.
5.6. OTHER RELEVANT INFORMATION
Ghanayem et al. (1985) administered methyl' acrylate In corn oil by
Ravage to male F344 rats for analysis of the dose-response and time-course
relationships fcr gastric edema Induction. In a preliminary study, a group
of eight rats that received 2 mmol/kg (172 mg/kg) methyl acrylate had
mucosal congestion, submucosal edema and superficial necrosis of the glandu-
lar stomach; the forestomachs were characterized by edema and vacuollzatlon
of the. tunica muscularls. In separate groups of rats, 2 mmol/kg (172 mg/kg)
methyl acrylate produced more severe forestomach edema than did 1 mmol/kg
(86 mg/kg), and In the time-course study, a maximum forestomach gravimetric
response was obtained I hours after 2 mmol/kg oral methyl acrylate. In both
the dose-response and the time-course studies, the amount of glandular
stomach edema produced was Insignificant.
0855p -22- 06/01/87
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LD-n and _2C~ /a iues .or methyl ,scry late 3xposur3 ar3 summarizes ;ri
J J ' -• U
Table 5-2. Lethality after high doses 1n rabbits was preceded by lethargy
and detention of ear veins, tremors, convulsions, running movements, spasms
of the diaphragm, labored breathing and cyanosis (Treon et al., 1949). In
this study. Inhalation exposure of five rabbits, two guinea pigs and two
rats co 617 ing/m3 methyl acrylate, 7 jiours/day for "ii-"i2 jays -as ~,ethal
to all animals except the two rats. Fassett (1963) characterized unsatu-
rated ester toxldty In man and animals as severely Irritating and occasion-
ally lachrymatory. Symptoms after" 1ngest1on Include collapse, respiratory
difficulty and CNS stimulation.
Methyl acrylate has been shown to be a potent skin Irritant (Treon et
al.,.1949; Delbresslne et al., 1980; Seutter and Rljntjes. 1981; Suvorov,
1971, 1973; Khromov, 1974; Dovzhansk11, 1976). In rabbits exposed dermally
to a total dose of 4.3-32.6 mg/kg, Inflammation, Intense edema and occasion-
al hemorrhaglng were observed (Treon et al., 1949). Microscopic examination
of affected skin revealed cloudy swelling of the rete and connective tissue,
with scatterings of polytnorphonuclear leukocytes and Intraeplthellal
abscesses. Suvorov (1973) noted necrotlc and dystrophlc changes In the
corlum, adventHIa and epidermis of rabbit skin treated repeatedly with IX
water solutions of methyl acrylate. After 60 days of application, there
were Increases In serum phosphatase activities, as well as accumulations of
mast cells and lymphold cells In the corlum. Seutter and Rljntjes (1981)
observed necrosis and edema of the skin of guinea pigs after dermal applica-
tion of methyl acrylate. Carpenter and Smyth (1946) found methyl acrylate
to be moderately Irritating to the rabbH cornea after topical adminis-
tration.
u855p -23- J6/01/87
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TABLE 5-2
LD50 or LC50 Values of Methyl Acrylate
Species
Rabbit
Rat
House
Rat
Rat
Rat
House
Rabbit
Route
oral
oral
oral
Inhalation
(4-hour)
Inhalation
(1-hour)
Inhalation
(time NR)
Inhalation
(time NR)
dermal
LD50 or LC50
-230 mg/kg
300 mg/kg
825 mg/kg
1000 ppm
(-3500 mg/m»)
-33,500 ppm
(-118,000 mg/ma)
7300 mg/m"
12.800 rng/m*
1.3 mi/kg
(1.2 g/kg)
Reference
Treon et al.,
1949
Smyth and
Carpenter, 1948
Tanll and
Hashimoto. 1982
Smyth and
Carpenter, 1948
Vernot et al. ,
1977
Lomonova and
KHmova. 1979
Lomonova and
Kllmova, 1979
Smyth and
Carpenter, 1948
NR = Not reported
0855p
-24-
09/26/86
-------
Humans have been 'snown :a jjffer a contact oer~Jt'!'::''.s .'c-aC'-'on *nen
exposed to methyl acrylate. Suvorov (1971) reported that 3/57 workers In
physical contact with the ester developed occupational dermatitis, which was
reversible after washing. Khromov {1974} noted that 76.1% of all workers 1n
contact with methyl acrylate showed a positive Intradermal hemagglutlnatlon
reaction; control data were not provided. Oovznansicli (1976), ooserveci cnat
acrylates are capable of Inducing epVdermatms, contact dermatitis, and,
occasionally, eczema. This Investigator found that 20% of workers given an
eplcutaneous drip test with 20 and 50% methyl acrylate were hypersensitive.
5.7. SUMMARY
No .oral cardnogenlclty studies of methyl acrylate were available, and
this chemical Is hot scheduled for testing by the National Toxicology
Program (NTP, 1986). No evidence of carclnogenlcHy was found In male or
female rats exposed by .Inhalation to
-------
lireon et ai., 1949). Irritation or tne nasai fiiucosa ana cornea! opacity
were observed In rats exposed by Inhalation to 15, 45 or 135 ppm (53. 158 or
475 mg/m3), 6 hours/day, 5 (Jays/week for up to 2 '/ears (KHmlsch and
Re1n1nghaus, 1984; KHmlsch and Zeller, 19791, Hematologlcal. urlnalysls.
gross, and hlstologlcal examinations revealed no systemic effects. Exposure
of small groups of experimental animals to 107 'mg/m3 methyl acrylate, 7
hours/day. for 130 exposures ^n 185 days led to considerable weight loss In
rabbits, guinea pigs and monkeys, but not rats. No other manifestations of
toxlclty were observed (Treon et al., 1949). Height loss was net found In
rabbits, guinea pigs or rats exposed to 328 mg/ma, 7 hours/day for 50
days, but rabbits had Initial signs of respiratory Irritation. At higher
concentrations for shorter periods of time, methyl acrylate consistently
Induced signs of respiratory distress, systemic toxlclty and ultimate death.
Oral LD.Q values In experimental animals range from 230-825 mg/kg
(Treon et al.. 1949; Smyth and Carpenter, 1948; Tan11 and Hashimoto, 1982).
After 1- to 4-hour Inhalation exposure, LCrnS range from 1000-33,500 ppm
(-3500-118,000 mg/ma) (Smyth and Carpenter, 1984; Vernot et al., 1977;
Lomonova and KHmova, 1979). Signs of Intoxication include 'severe irrita-
tion to the mucous membranes and convulsions. In experimental animals,
methyl acrylate was shown (Treon et al., 1949; Delbresslne el al., 1980;
Suvorov, 1973; Seutter and Rljntjes, 1981) to be a potent skin Irritant,
Inducing Inflammation, edema and hemorrhaglng after dermal application.
Occupational studies (Suvorov, 1971; DovzhanskU, 1976; Khromov, 1974)
showed that methyl acrylate causes allergic contact dermatitis 1n man.
Application to the rabbit cornea led to a moderately Irritating response
(Carpenter and Smyth, 1946).
0855p -26- 09/26/86
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•i. AQUATIC FOXICITY
6.1. ACUTE
LHtle Information 1s available concerning toxlclty of methyl acrylate
to fish and aquatic Invertebrates. Juhnke and Luedemann (1978) determined
the 48-hour LC,0 for the golden orfe, Leuclscus Idus. to be 7.5 mg/i.
Li- ana LC,nf. values were 5 ana "iO ing/1, .'espectively. Pauiet and
V1dal (1975) reported a 3-day LC,-n of 5 mg/j, for an unspecified fish
species.
O'Angelo and SlgnoMle (1978) found that 96 hours of exposure to 2.4
mg/i caused 95 and 52% mortality of the planktonlc crustaceans, Molna
macrocopa and Cyprla ophthalmlca. respectively. Brlngmann and Kuehn (1981)
determined toxlclty thresholds for Inhibition of culture growth for three
protozoan species. These values were 64 mg/a. for Uronema parduczl. 11
mg/i for Entoslphon sulcatum and 10 mg/i for Ch1lomonas pararneclum.
6.2. CHRONIC
Pertinent data regarding the chronic tbx1c1ty of methyl acrylate could
not be located 1n the available literature as cited 1n the Appendix.
6.3. PLANTS
Brlngmann and Kuehn (1977, 1978) determined toxlclty thresholds for
Inhibition of culture growth of certain algae and bacteria. Toxlclty
thresholds were 1.3 mg/i for the blue-green alga, HacrocystIs aeruqlnosa.
7.0 mg/a for the green alga, Scenedesmus quadrlcauda. and 100 mg/i for
the bacterium, Pseudomonas putlda.
6.4. RESIDUES
Pertinent data regarding the methyl acrylate residues In aquatic biota
could not be located 1n the available literature as cited 1n the Appendix.
0855p -27- 04/24/87
-------
6.5. SUMMARY
The Information concerning toxldty of methyl acrylate to aquatic
organisms is quite limited. Fish LC values of 5.0 and 7.5 mg/a were
reported by Paulet and V1dal (1975) and Ouhnke and Luedemann (1979), respec-
tively. A concentration of 2.4 mq/i caused 52 and 95X mortality of two
species of planktonlc crustaceans (O'Angelo and SlgnoMle, 1978), The
lowest reported tox'.c'ty threshold for Inhibition of culture growth among
three protozoans was 10 mg/i for Chllomonas parameclum (Brlngmann and
Kuehn, 1981). The most sensitive plant species was the blue-green alga,
Hlcrocystls aeruolnosa. with a toxldty threshold of 1.3 mg/i (Brlngmann
and Kuehn, 1978).
0855p -28- 09/26/86
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7.. C*ISTI;IG-GUIDELINES AND GTANDARDS
7.1. HUMAN
The ACGIH (1985-1986) adopted a TLV-TWA of 10 ppm .(-35 mg/m3) for
methyl acrylate. In their latest documentation, the ACGIH (1986) cited work
of prior Investigators [Treon et al., 1949; Smyth, 1955), suggesting that 10
ppm should be a threshold. i1mu for lacnmatory and other primary Irritant
effects. A "skin" designation .was added to the TLV-TWA because of the
ester's 1rr1tancy effects. The OSHA PEL Is also 10 ppm with a "skin"
designation (OSHA, 1985).
The U.S. FOA (1933) did not affirm methyl acrylata as a GRAS Indirect
human food Ingredient. This agency could not find evidence that the ester
was used 1n the manufacture of food-related paper and paperbound products,
except as a component of polymers already regulated by current and prior
food additive restrictions.
7.2. AQUATIC
Guidelines and standards for the protection of aquatic biota from the
effects of methyl acrylate could not be located In the available literature
as cited ^n the Aooendlt.
0855p -29- 04/23/87
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6. rtlSX ASSESSMENT
vlo jra"! -rarclnogenlcl ty studies of methyl acrylats were available, and
this- chemical Is not scheduled for testing by NTP P987). No evidence of
C3rc1nogen1c1ty was found In male or ^ercale rat3 sxoosed by Inhalation to
<135 ppm (475 mg/m3), 6 hours/day, 5 days/week for up to 2 years (Kllmlsch
'.nd Reir.lnghaus,. 1984;'Kllmlsch and Zeller. 19"»9).
Methyl acrylate was found not to be genotoxlc In reverse mutation assays
using S. typhlmuMum with or without metabolic activation (Waegemaekers and
Benslnk, 1984; Florin et al., 1980). Ishldate et al. (1981) and Sofunl et
al. (1984a) reported an Increase 1n chromosomal aberrations 1n a mammalian
cell line treated with the ester. Results concerning the mutagenlc
potential of methyl acrylate In the mouse mlcronucleus test are equivocal
(Przbojewska et al.. 1984; Sofunl et al.. 1984b). No teratogenlclty or
reproduction studies were found..
There are no chronic oral toxldty data for methyl acrylate 1n experi-
mental animals. A gavage dose of 23 mg/kg methyl acrylate given 24 times
over 33 days caused only a minor innlbition or growth \n treated raboits
(Treon et al., 1949). Irritation of the nasal mucosa and corneal opacity
were observed In rats exposed by Inhalation to 15, 45 or 135 ppm (53, 158 or
475 mg/m1), 6 hours/day, 5 days/week for up to 2 years (Kllmlsch and
Re1n1nghaus, 1984; Kllmlsch and Zeller, 1979). Hematologlcal, urlnalysls,
gross and hlstologlcal examinations revealed no systemic effects. Exposure
of small groups of experimental animals to 107 mg/m3 methyl acrylate. 7
hours/day for 130 of 185 days led to considerable weight loss 1n rabbits,
guinea pigs and monkeys but not rats. No other manifestations of toxldty
were observed (Treon et al., 1949). Weight losses were not found In
0855p -30- 04/23/87
-------
rzboUs, gillnea pigs or r^is exposes *.c .:23 ng/md, ~ nours/aay "or 50
days, but rabbits had Initial signs of respiratory Irritation. At higher
concentrations for shorter periods of time, methyl acrylate consistently
Induced signs of respiratory distress, systemic toxldty and death.
In the- absence of onccgenlclty data, H Is appropriate to derive an RfO
(formerly called ADI). The repeated oral dosing study (rabbits) Dy Treon et
al. (1949) suggests a NOAEl at a THA dose .of 16.7 mg/kg/day ' ('23 mg/kg x
24/33 days); however, the small sample, size used and short exposure duration
make the use of this study Inappropriate 1n quantitative risk assessment.
In the 2-year Inhalation study . using rats, no evidence' of systemic
toxldty was observed at exposures of 15, 45 or 135 ppm (53, 158 or 475
mg/m3), 6 hours/day, 5 days/week (KT.mlsch and Re1n1nghaus, 1984). The
only effects were dose-related Irritation of the nasal mucosa and corneal
opacity. Since these effects are a direct consequence of, exposure to the
vapor they would not be expected to occur after 1ngest1on. The exposures
can be converted to. equivalent oral, doses by multiplying by 6 hours/24
hou.rs, 5 days/7 days, by 0.223 mVday (the reference breathing rate of a
0.35 kg rat), by 0.5 {the absorption factor) and by dividing by 0.35 kg.
Thus, the 53, 158 and 475 mg/m3 levels are equivalent to 3, 9 and 27
mg/kg/day, respectively. These doses could be considered NOELs for oral
exposure; however, Treon et al. (1949) reported weight loss In rabbits,
guinea pigs and monkeys exposed to 107 mg/m3, 7 hours/day for 130
exposures 1n 185 days. The exposure can be converted to equivalent doses by
multiplying by 7 hours/24 hours, by 130/185 days, by 0.5 (absorption
factor), by the animal breathing volumes of 2.0 mVday for rabbits, 0.40
mVday for guinea pigs and 5.4 mVday for monkeys (U.S. EPA, 1985), and
0855p -31- 04/23/87
-------
dividing by the animal body ^e'gnt: :f 2.2 :cg cor -abbit:. 3.34 ;cg for
guinea pigs and 8.0 kg for monkeys. The doses, thus calculated are: 6
mg/kg/day for rabbits, 5 mg/kg/day for guinea pigs and 7 mg/kg/day for
monkeys. These doses can be considered LOAELs; therefore, the exposure of
53 mg/m3, 6 hours/day, 5 days/week for 2 years, equivalent to 3 mg/kg/day,
Is the highest NOEL below which there 1s no LOAEL (Kllmlsch and Re1n1nghaus,
1984). Dividing by an uncertainty factor of 100 (10 for Interspedes
extrapolation and 10 to protect sensitive Individuals) yields an RfD of 0.03
mg/kg/day or 2 mg/day for a 70 kg man.
0855p -32- 04/23/87
-------
3. .IEPORTABLE QUANTITY
9.1. REPORTABLE QUANTITY (RQ) RANKING BASED ON CHRONIC TOXICITY
No chronic or subchronlc oral studies of methyl acrylate were located,
but one subchronlc and one chronic Inhalation study was available. These
studies were discussed 1n Section 5.5. and are summarized 1n Table 9-1. In
che presence or cne wei 1-conductea chronic study by K1 lumen una rteiningnaui
(1984), the subchronlc study by Treon et al. (1949) will not be considered
for RQ derivation. Furthermore, the subchronlc study used very small
numbers of animals.
The only effects observed 1n the rats exposed to methyl acrylate vapors
for 2 years were oose-related Irritation of the nasal mucosa witn atrophy of
the epithelium and proliferation of reserve cells, which would warrant an
RV of 4, and dose-related corneal opacity and eye vascularlzatlon, which
would warrant an RV of 7. Multiplying the lowest transformed dose at
which these effects occurred (6 mg/kg/day) by the cube root of the ratio of
the rat body weight to the human body weight (TO kg) and by 70 kg results 1n
an MEO of 71.8 mg/day, which corresponds to an RV of 2.7 (Table 9-2).
Multiplying the RVd by the higher RVg of 7 yields & CS of 19. which
corresponds to an RQ of 1000 (Table 9-3).
9.2. WEIGHT OF EVIDENCE AND POTENCY FACTOR (F=1/ED1()) FOR CARCINOGENICITY
KHmlsch and Relnlnghaus (1984) found no evidence of cardnogenlclty In
groups of 36 male and 86 female rats exposed to methyl acrylate vapor at 53,
158 or 475 mg/m», 6 hours/day, 5 days/week for up to 2 years. No other
Information regarding the carclnogenlclty of methyl acrylate to animals was
available. Existing animal data are not adequate to evaluate the car-
cinogenic potential of methyl acrylate. Since no data regarding the
carclnogenlclty to humans were available, methyl acrylate 1s classified as
an EPA Group D chemical (U.S. EPA, 1986b).
0855p -33- 06/t)i/87
-------
o
CD
in
in
Vecles/
Strain Sex
Kit/ N.f
Sprague-
l);iw)ey
h.bblt/NR NR
i Guinea NR
% plg/NR
i
K.nkey/NR .NR
Inhalation foxtclty Sunnary for
No. at Average Vehicle/
Start Height0 Physical Exposure
(kg) State
86/sex/ 0.35 vapor IS. 45 or 135 ppra
group (S3. 1S8 or 47S mg/ra*).
6 hours/day, 5 days/week
for ? years
4 3.8 vapor 107 mg/m1, 7 hours/day
for 130 exposures. In
IBS days
2 O.B4 vapor 107 mg/ra*. 7 hours/day
for 130 exposures In
185 days
1 B.O vapor 107 mg/m*, 7 hours/day
for 130 exposures In
IBS days
Methyl Acrylate3
Transformed
Animal Ousec Response
(mg/kg/day)
6.0. 18.1 Dose-related Irritation of
or 54.3 nasal raucosa with atrophy of
olfactory epithelium and
proliferation of reserve
cells: dose-related cornea)
opacity and vascular liat Ion
of the eyes
11.5 weight loss
10.4 weight loss
14.8 weight loss
Reference
Kltmlsch and
Relnlinjhaus ,
1984
Treon et al . ,
1949
freon et al . ,
1949
Treon et al . ,
1949
arur1ty of compound was not reported
Lt/day for guinea pigs and S.4 n>/day for ntunkeys (U.S. EPA. 1985) and dividing by the
animal body weight
kit = Not reported
o
V.
(V
^
CD
-------
TABLE 9-2
Inha;lat1on Composite Scores for Methyl Acrylate Using Rat Data1
Chronic
Animal Dose Human HE0 RVd . Effect RVe CS RQ
(mg/kg/day) . (mg/day)
6 71,8 2.7 corneal. 7 19 1000
opacity
•Source: Kllmlsch and Relnlnghaus. 1984
0855p -35- 04/24/87
-------
TABLE 9-3
Methyl Acrylate
Minimum Effective Dose (MED) and Reportable Quantity (RQ)
Route: Inhalation
Dose*: 71.8
Effect: corneal opacity
Reference: KHmlsch and Relnlnghaus, 1984
RVd: 2.7
RVe: 7
Composite Score: 19
RQ: 1000
•Equivalent human dose
0855p -36- 09/26/86
-------
10. SErcREHCES
ACGIH (American Conference of Governmental Industrial Hyg1en1sts).
1985-1986. TLVs: Threshold limit values and biological exposure Indices for
1985-1986-.- Cincinnati, OH. p. 26.
ACGIH (American Conference of Governmental Industrial Hyg1en1sts). 1986.
Documentation of the, Threshold Limit Values and Biological- Exposure Indices,
5th ed. Cincinnati, OH. p, 369.
Brlngmann, G. and R. Kuehn. 1977. Limiting values for the damaging action
of water pollutants to bacteria (Pseuciomonas put Ida) and green algae (Scene-
desmus quadrlcauda) , In the cell multiplication Inhibition test. 'Z. 'Wasser
Abwasser Forsch. 10(3-4): 87-98. (Ger.)
Brlngmann, G. and R. Kuehn. 1978. Testing of substances for their tox1c1ty
threshold: Model organisms Mlcrocystls (Dlplocystls) aeruqlnosa and Scene-
desmus quadMcauda. Mitt. Internal. Vereln. Umnol.. 2"<: 275-28*.
Brlngmann, G. and R. Kuehn. 1981. Comparison, of the effect of harmful
substances on flagellates and dilates as well as on bacteMovorous and
saprozolc protozoans. GasHasserfach: Wasser/Abwasser. 122(7): 308-313.
(Ger.)
Brunn, J., F. Peters and M. Dethloff. 1976. UV Spectra of a, B-unsatu-
rated esters and the effects of solvents and complex formation. J. Prakt.
Chem. 318: 745-755.
0855p -37- 06/01/87
-------
Carpenter, C.P. and H.F. Smyth. 1946. Chemical burns of the rabbit cornea.
Am,. J. Ophthal. 29: 1363-1346.
Celanese Chemical Co. 1981. The 1982 Product Index. Celanese Chemical
Co.. Inc., Dallas. TX.
D'Angelo, A.M. and G. Slgncrlle. 1978. Study on t^e tox'cHy of methyl
acrylate and acrylon1tr1le 1_n vitro on some planktonlc Crustacea. Ig. Hod.
71(8): 973-979. (Hal.) (CA 90:1465990)
Datta, R.K, and K.N. Rao.. 1979. Kinetics of reactions pf singlet moelciilar
oxygen (a) with organic compounds. Ind. J. Chem., Sect. A. 18A: 102-105.
Delbresslne, L.P.C., E. Seutter and F. Seutter-Berlage. 1980. Metabolism
and- toxlclty of acrylates and methacrylates. Br. J. Pharmacol. 68(1):
165P-166P.
Oelbresslne, L.P.C., F. Seutter-Berlage and E. Seutter. 1981. Identifica-
tion of urinary mercapturlc adds formed from acrylate, methacrylate and
crotonate 1n the rat. Xenob1ot1ca. 11(4): 241-247.
Dovzhansk11, I.S. 1976. Dermatosls sickness rate of workers having contact
with acrylates. G1g. Tr. Prof. Zabol. 1: 40-41. (Rus.) (CA 86:8195P)
Fassett, O.H. 1963. Esters. In.: Patty's Industrial Hygiene and Toxicol-
ogy, Vol. 2, 2nd ed., G.D. Clayton and F.E. Clayton, Ed. John Wiley and
Sons Inc., New York. p. 1847-1934.
0855p -38- 04/27/87
-------
F.lorln, I., '-. Sutberg, *. 'Ijrvail :na '-.A. EnzsVi. '930. screening or
tobacco smoke constituents for mutagenlcHy using the Ames' test. Toxicol-
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Ghanayem, 3.L., R.R. Maronpot ' and H.B. Hathews. 1985. Ethyl acrylate-
Induced gastric tox.ldty: 2.. Structure-toxldty relationships and mecha-
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Hansch, C. and A.J. Leo. 1985. Medchem Project. Issue No. 26. .Pomona
College, Claremont, CA.
Hawley, G.G. 1981. The Condensed Chemical Dictionary. 10th ed. Van
Nostrand Relnhold Co., New York. p. 666.
IARC (International Agency for Research on Cancer). 1979a. Monographs on
the ' Evaluation of the Carcinogenic Risk of. Chemicals to Humans. Some
Monomers, Plastics and Synthetic Elastomers and Acroleln. WHO, IARC, Lyon,
"ranee. Vol. ZS, p. 57-"1.
IARC (International Agency for Research on Cancer). 1979b.. IARC Monographs
on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Acrylic
add, methyl acrylate, ethyl acrylate and polyacryllc add. WHO, IARC,
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Ishldate, M. T. Sofunl and K. Yoshlkawa. 1981. Chromosomal aberration
tests in v1tro as a primary screening tool for environmental mutagens and/or
carcinogens. Gann Monogr. Cancer Res. 27: 95-108.
0855p -39- 04/27/87
-------
Juhnke, I. and 2. Ljedemann. 1973. Result3 of t.le :tudy of 200 •r.'i
compounds on acute fish toxldty using the Golden Orfe test. Z, Wasser
Abwasser Forsch. 11(5): 161-164. (Ger.)
Khromov, V.E. 1974. Detection of circulating and fixed antibodies In the
diagnosis of allergies of chemical etiology. Vrach. Delo. 12: 115-116.
(Rus.) (CA 82:174771K)
K1ne, B.B: and R.H. Novak. 1978. Acrylic ester polymers. Irr. K1rk-0thmer
Encyclopedia of Chemical Technology, Vol 1, 3rd ed., M. Grayson and D.
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Klein, A. 1981. Latex technology. IJK Klrk-Othmer Encyclopedia of
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WHey & Sons, Inc., New York. .p. 83.
KTImlsh, H.J. and W. Relnlnghaus. 1984. Carc1nogen1c1ty of acrylates:
Long-term 'inhalation studies on methyl acrylats (MA) and n-butyl scrylate
(BA) In rats. Tox1colog1st. 4(1): 53. Abstract No. 211.
Kllmlsch, H.J. and Zeller. 1979. Two-year vapor Inhalation study of methyl
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Bethesda, MO. Toxicology Information Program. 685952 NTISUB/E/150.
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0855p -40- 04/27/87
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Lomonova. 3.V. ina -E.I. . K1 ":mcva. ",975. Oat a on :ne toxicology of methyl
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NIOSH (National Institute for Occupational Safety and Health). 1984.
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NTP (National Toxicology Program). 1987. Management studies report,
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OSHA (Occupational Safety and Health Administration). 1985. Occupational
Standards Permissible Exposure Limits. Code of Federal Regulations. 29:
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Osintseva, V.P., L.E. Bespalko and A.M. Zubets. 1370. Heinyi acryiaie
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PelUzzarl, E.O. 1977. The measurement of carcinogenic vapors In. ambient
atmospheres. U.S. EPA, Gulf Breeze, FL. EPA-600/7-77-055. ,
Perry, R.H. and 0. Green. 1984. Perry's Chemical Handbook. Physical and
Chemical Data, 6th ed. McGraw-Hill, New York. p. 3-57.
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Seutter, E. and N.V.H. Rljntjes. 1981. Whole-body autoradlography after
systemic and topical administration of methyl acrylate 1n the guinea pig.
Arch. Dermatol. Res. 270(3): 273-234.
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Sofunl, T.t M. Hawashl, A. Hatsuoka, M. Sawada, M. Hatanaka and M.J.
Ishldate. 1984a. Cytogenetlc effects of gaseous and volatile chemicals on
mammalian cells j_n vitro and ±n vivo. I. Chromosome aberration tests In
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Sofunl, T., H. Hawashl, A. Matsuoka, H. Sawada, H. Hatanaka and H.J.
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mammalian cells _1_n vitro and j_n vivo. II. Mlcronucleus tests In mice.
Elsel Shlkensho Hokoku. 102: 84-90. (CA 103:18162j)
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acrylate. 1971. Gig. Tr. Prof. Zabol. 15(10): 49-50. (Taken from HEEP
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on the skin. Farmakol. Tokslkol. (Moscow). 36(1): 107-109. (CA 78:119846F)
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ratio and water solubility. Residue ,
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T5CA-ITC (Toxic Substance and Control Act - Interagency 7e's;ing Committee).
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Partition Coefficients (CLOGP) and/or Fate of Atmospheric Pollutant (FAP)
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U.S. EPA. 1386b. Guideline's for Carcinogen Risk Assessment. Federal
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i/ernot, E.H., J.O. HacEwen, C.C. Haun and E'.S. /Onicead. 1977. Acuie
toxldty and skin corrosion data for some organic and Inorganic compounds
and aqueous solutions. Toxlcol. Appl.. Pharmacol. 42(2): 417-A24.
Verschueren, K. 1983. Handbook of Environmental data on Organic Chemicals,
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Hlndholz, H., Ed. 1983. The Merck Index, 10th ed. Merck & Co., Inc.,
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0855p -46- 04/27/87
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APPENDIX
LITERATURE SEARCHED
This profile Is based on data Identified by computerized literature
searcne--. :* the roilowlna:
GLOBAL
7:CATS
CASK online (U.S. EPA Chemical Activities Status Report)
CAS online STN International
TOXLINE
TOXBACK 76
TOXBACK 65
RTECS
OHM TADS
STORET
SRC Environmental Fate Data Bases
SANSS
AQUIRE
TSCAPP
NTIS
Federal Register
These searches were conducted In April, 1986. In addition, hand searches
were made of Chemical Abstracts (Collective Indices 6 and 7), and the
following secondary sources were revleyed:
ACGIH (American Conference of Governmental Industrial Hyglenlsts).
1986. Documentation of the Threshold Limit Values and Biological
Exposure Indices, 5th ed. Cincinnati, OH.
ACGIH (American Conference of Governmental Industrial Hyglenlsts).
1985-1986. TLVs: Threshold Limit Values for Chemical Substances
and Physical Agents In the Workroom Environment with Intended
Changes for 1985-1986. Cincinnati, OH. 114 p.
Clayton, G.D. and F.E. Clayton, Ed. 1981. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed.. Vol. 2A. John Wiley and
Sons, NY. 2878 p.
Clayton, G.D. and F.E. Clayton, Ed. 1981. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2B. John Wiley and
Sons, NY. p. 2879-3816.
0855p
-47-
09/26/86
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Clayton, G.D. and F.E. Clayton, Ed. 1982. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2C. John Wiley and
Sons, NY. p. .3817-5112.
Grayson. H. and D. Eckroth. Ea. 1973-1983. Klrk-Otrimer Encyclo-
pedia of Chemical Technology, 3rd ed. John Wiley and Sons, NY. 23
Volumes.
Hamilton, A. and H.L. Hardy. 1974. Industrial Toxicology, 3rd ed.
Publishing Sciences Group, inc., Littleton, HA. 575 p.
IARC (International Agency for Research on Cancer). IARC Mono-
graphs ^n the' Evaluation cf Carcinogenic Risk of Chemicals to
Humans. WHO, IARC, Lyons, France.
Jaber, H.M., W.R. Mabey, S.T. Liu, T.W. Chow and H.L. Johnson.
1984. Data aqulsltlon for environmental transport and fate screen-
ing for compounds of Interest 1n the Office of Solid Waste. EPA
600/6-84-010. NTIS PB84-243906. SRI International, Menlo Park, CA.
NTP (National Toxicology Program). 1986. Toxicology Research and
Testing Program. Chemicals on Standard Protocol. Management
Status.
Ouellette, R.P. and J.A. King. 1977. Chemical Week Pesticide
Register. McGraw-Hill Book Co., NY.
Sax, N.I. 1979. Dangerous Properties of Industrial Materials, 5th
ed. Van Npstrand Relnhold Co., NY.
SRI (Stanford Research Institute). 1984. Directory of Chemical
Producers. Henlo Park, CA.
U.S. EPA. 1985. Status Reoort on RebuttabTe Presumption Against
Registration (RPAR) or Special Review Process. Registration Stan-
dards and the Data Call 1n Programs. Office of Pesticide Programs,
Washington, DC.
U.S. EPA. 1985. CSB Existing Chemical Assessment Tracking System.
Name and CAS Number Ordered Indexes. Office of Toxic Substances,
Washington, DC.
USITC {U.S. International Trade Commission). 1985. Synthetic
Organic Chemicals. U.S. Production and Sales, 1984, USITC Publ.
1745. Washington. DC.
Verschueren, K. 1983. Handbook of Environmental Data on Organic
Chemicals, 2nd ed. Van Nostrand Relnhold Co., NY.
Wlndholz, M.t Ed. 1983. The Merck Index, 10th ed. Merck and Co.,
Inc., Rahway, NJ.
Worthing, C.R. and S.B. Walker, Ed. 1983. The Pesticide Manual.
British Crop Protection Council. 695 p.
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In addition, approximately 30 compendia of aquatic toxUHy data were
reviewed, Including the following:
Battelle's Columbus Laboratories. 1971. Water Quality Criteria
Data Book. Volume 3. Effects of Chemicals on Aquatic Life.
Selected Data from the Literature through 1968. Prepared for the
U.S. EPA under Contract No. 68-01-0007. Washington, DC.
Johnson, U-.U. and M.T. Flnley. 1980. Handbook of Acute Tpxlclty
of Chemicals to F1sh and Aquatic Invertebrates. Summaries of
Toxlclty Tests Conducted at Columbia Nationa1 Fisheries Research
Laboratory. 1965-1978. U.S. Dept. ' Inferior, F1.sh.and Wildlife
Serv. Res. Pub!. 137., Washington, DC.
HcKee, J.E. and H.W.. Wolf. 1963. Water Quality Criteria, 2nd ed.
Prepared for the Resources Agency, of California, State Water
Quality Control Board. Publ. No. 3-A.
Plmental, D. 1971. Ecological Effects of Pesticides on Non-Target
Species. Prepared for the U.S. EPA, Washington,. DC.. PB-269605.
Schneider, B.A. 1979. Toxicology Handbook. Mammalian and Aquatic
Data. Book 1: Toxicology Data. Office of Pesticide Programs, U.S.
EPA. Washington, DC. EPA 540/9-79-003. NTIS PB 80-196876.
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