.   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                            DRAFT: DO NOT CITE OR QUOTE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
0855p
           -1-
                   04/23/87

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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
0855p
   -3-
            06/01/87

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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,

0855p                               -5-                              06/01/87

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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.
0855p                               -6-                              04/23/87

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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)
0855p                               -7-                              04/23/87

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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.
0855p                               -8-                              04/24/87

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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

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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.
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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

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 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

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 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

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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

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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

-------
                     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

-------
                              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

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-------
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0855p                               -38-                             04/27/87

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0855p                               -45-                             04/27/87

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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

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    Clayton,  G.D.   and   F.E.  Clayton,  Ed.   1982.   Patty's  Industrial
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    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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