FINAL DRAFT
United States ECAO-CIN-P224
Erv/iror.rremai ?rctsc::on ' April. 1987
Agency
&EPA Research and
Development
HEALTH AND ENVIRONMENTAL EFF.ECTS PROFILE
FOR 2-METHOXYETHANOL ACETATE
Prepared for
OFFICE OF SOLID HASTE 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DRAFT: DO NOT CITE OR QUOTE
NOTICE
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 is 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.
II
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PSEFACE
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 1.01 of. the Compre-
hensive Environmental Response, .Compensation and Liability Act (CERCLA).
3cth published 1-Heraturs and information obta-lned from Agency program
or'fice 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 in the
action- l.1l.led "Appendix: Literature Searched." The literature search
material Is current through November, 1985.
Quantitative estimate's are presented provided sufficient .data are
available. For systemic toxicants, these Include Reference doses (RfDs) for
chronic exposures. An RfO is defined as the. amount of a cnemical 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-|* Is 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-
genlcity are derived. The RQ 1s 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 toxldty and carcinogen-
Iclty) represent two of six scores developed .(the remaining four reflect
Ignltablllty, 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 In Cincinnati.
The HEEPs will become part of the EPA RCRA and CERCLA dockets.
111
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cXECUTIVE.SUMMARY
2-Methoxyethanol acetate, also known as ethylene glycol monomethyl ether
acetate, Is a colorless liquid at room temperature, with a sweet, pleasant
odor. It Is mlsdble with water and many common organic solvents
(Verschueren, 1983; Hawley, 1981). Etnylene qlycol monomethyl ether, formed
by reacting ethylene oxide and anhydrous methanol, Is esterlfled with'acetic
acid to produce 2-,nethoxyei.nanol acetate (U.S. EPA, 1982). As o: 1934,
Union Carbide Corp., South Charleston, WV, was the sole U.S. manufacturer of
2-methoxyethanol acetate. The current U.S. production volume for this
chemical Is unavailable.
The primary use of 2-methoxyethanol acetate 1s as a solvent for oils,
greases. Inks, gums, resins, plastics, adhesive*, waxes, nitrocellulose,
cellulose acetate and other cellulose esters and ethers. 2-Methoxyethano.l
acetate Is also used In the manufacture of lacquers, enamels, adheslves,
photographic film and 1n- the textile printing Industry (U.S. EPA, 1982).
If released to water, the primary processes that may remove 2-methoxy-
ethanol are hydrolysis and blodegradatlon (Lyman et al., 1982). Bloaccumu-
latlon In aquatic organisms and adsorption to suspended solids and sediments
should not be significant. The compound Is expected to persist In aquatic
media. If released to the atmosphere, 2-methoxyethanol acetate Is expected
to exist primarily In the vapor phase and Is apparently susceptible to
oxidation by HO radical (t]/2=22.42 hours) (Yanaglhara et al.. 1977; U.S.
EPA. 1986b). Removal from the atmosphere by wet deposition may also be
significant. If released to soil, 2-methoxyethanol acetate should be highly
mobile In moist soils and may volatilize significantly from dry soil
surfaces. This compound may be degraded In moist soils by hydrolysis and
blodegradatlon.
1v
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Limixsu monitorinu and exposure uaia ryqurdinq 'i-ineihoxye.thano 1 dcsiate
were located In the available literature. 2-Methoxyethanol ace.tate has been
qualitatively Identified in drinking water (Kaol et al., 1982) and in an
effluent discharged into the Illinois River (Somani et al., 1980.). It is
likely that consumer exposure to this compound will occur during the use of
cleaning solutions, paint, ink and nail polish '.U.S. EPA,'1982).
Potential routes of 2--nethoxyethanol acetate exposure to workers include
inhalation of the vapor, ingescion and eye and sicLn contact (U.S. EPA,.
1982). A 1972-1974' National Occupational Hazard Survey estimated that'
436,989 workers are occupationally exposed to this compound during manufac-
turing, processing, use and handling of 2-methoxyethanol acetate (RTECS,
1984). A more recent survey, the National Occupational .Exposure Survey,
estimates that 2024 workers are exposed to 2-methoxyethanol acetate; how-
ever, this figure does not1 reflect exposure to tradename products containing.
2-methoxyethanol acetate (NIOSH, 1985).
Little Information Is. available concerning effects of 2-methoxyethanol.
acetate on aquatic organisms. LC... 'values of 40, 45 and 190 mg/i were
reported for tidewater sllversldes, bluegllls (Oawson et al., 1977) and
goldfish (Bridie,et al.. 1979a),respectively.
Data related to the pharmacokinetics of 2-methoxyethanol acetate are
very limited. From toxlcity studies, absorption of 2-methoxyethanol acetate
through the skin, lung and gastrointestinal tract as well as general distri-
bution throughout the body can be Inferred. 2-Methoxyethanol acetate Is
most likely hydrolyzed to 2-methoxyethanol (Stott and McKenna, 1985; Oahl
and Hadley, 1983; Hoffman, 1984; Browning, 1965). although there were no J_n
.vivo data available to support this conclusion. No excretion data were
available.
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No information ;s availaoie regarding cither, the care: noyenicl iy or
teratogenlcity of 2-methoxyethanol acetate In animals or humans. 2-Methoxy-
ethanol acetate reportedly caused aneuploldy. In yeast (Zimmerman et al.,
1985). but there Is considerable doubt as to the .relevance of these data to
actual genotoxldty.
The only study that demonstrates the In' vivo toxlclty of 2-methoxy-
ethanol acetate was conducted, by Nagano et al. (1979), who treated male
MCL-ICS ,irice at oral, doses' or bZ.5, ".25, 250, 500, 1000 or 2000 mg/kg/day, 5
days/week for 5 weeks. Significant decreases In testkular weight, and
substantial atrophy were observed In animals receiving >500 mg/kg.. In
addition, leukopenla was evident In mice In the 1000 and 2000 mg/kg groups.
No effects were observed at <250 mg/kg/day. Thes.e responses were similar
qualitatively and quantitatively (on a molar basis), to those Induced by
2-methoxyethanol 1n the same study.
Oral LD5Q values for' 2-methoxyethanol acetate range from 1.25 g/kg 1n
guinea pigs to ,3.93 g/kg 1n rats (Smyth et al., 1941).. Similar results were
obtained following subcutaneous Injection (Smyth et al., 1941; Flury and
Wlrth, 1933). Kidney lesions were common following these exposures. Three
'repeated 8-hour. Inhalation -exposures of 1000 . ppm (4831 mg/m3) .were
generally lethal to cats, rabbits, guinea pigs and mice (Gross, 1938).
Humans were unable to tolerate exposure to 1000 ppm (4831 mg/m3) for 1
hour, while a level of 120 ppm (580 mg/m3) for 3 minutes "provided good
warning properties" (Union Carbide, 1958).
An Inhalation study by Miller et al. (1982) was used by U.S. EPA (1986c)
to derive an RfD for 2-methoxyethanol. This RfD was based on a NOEL for
both developmental and testlcular effects. Since 2-methoxyethanol acetate
Is metabolized to 2-methoxyethanol and the Nagano et al. (1979) study
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veti srfsc^s quantitativeiy :nd qualitatively -ifnilir (an ^ -ioi£r basi;}
for both compounds, an RfD of 0.002 mg/kg/day or 0.11 mg/day for .a 70 kg man
is proposed based on analogy to 2-methoxyethanol. A CS of 23 and an RQ of
100 were derived from a chronic human MED of 28 mg/day based on neurochemi-
cal alterations in offspring of male rats exposed to 25 ppm (78 mg/m3) of
2-methoxyethanol, 7 hours/day for 6 weeks In the study by Nelson • et al.
(1984). To calculate the MED, the exposure level of 78 mg/m3 .of
2-methox.yethar,ol was adjusted to 121 mg/m3 for 2-methoxyethanol acetate.
In terms of. carcinogenic potential, 2-methoxyethanol acetate Is classified
as .a U.S. EPA Group D chemical, meaning there is Inadequate evidence or in
this case no existing data regarding the human carcinogeniclty of this
compound.
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TABLE OF CONTENTS
1. INTRODUCTION 1
1.1. STRUCTURE AND CAS NUMBER 1
1.2. PHYSICAL AND CHEMICAL PROPERTIES 1
1.3. PRODUCTION DATA. . 2
1.4. USE DATA 2
1.5. SUMMARY 4
2. ENVIRONMENTAL FATE AND TRANSPORT PROCESSES 5
2.1. WATER. '..... 5
2.1.1.. Hydrolysis . . . 5
2.1.2. H1crob1al Degradation ' 5
, 2.1.3. Transport 6
i • f
2.2. AIR. '.....'...' 6
2.3. SOIL , . • 7
2.3.'l. Hydrolysis. .....' ...'..'.. 7
2.3.2. Leaching . . . . ; . 7
2.3.3. Volatilization. ...,.........,.:.. 7
2.4. SUMMARY. 7
3. EXPOSURE 9
4. PHARMACOKINETCS ...:.... '..'..' . 10
4.1. ABSORPTION ::.... 10
4.2; DISTRIBUTION : 10
4.3. METABOLISM ....... J .:.'. 1 10.
4.4. EXCRETION. 11
4.5. SUMMARY. 11
5. EFFECTS , . 12
5.1. CARCINOGENICITY. . • 12
5.2. MUTAGENICITY ....:. 12
5.3. TERAT.OGENICITY 12
5.4. OTHER REPRODUCTIVE EFF.ECTS 13
5.5. ' CHRONIC AND SUBCHRONIC TOXICITY 13
5.6. OTHER RELEVANT INFORMATION . . . 14
5.7. SUMMARY. ...... 16
vin
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TABL; OF CONTENTS (cent.)
Page
6. AQUATIC TOXICITY 18
6.1. ACUTE : . . .. 18
6.2. CHRONIC 18
6.3. PLANTS 18.
6.4. RESIDUES . . . ' . 18
6.5. SUMMARY. , 18
7. EXISTING GUIDELINES AND STANDARDS ' 19
7.1. HUMAN .. . 19
7.2. ..AQUATIC . 19
8.. RISK ASSESSMENT . V 20
9. REPORTABLE QUANTITIES.. ....... .••••. 22
9.1. REPORTABLE QUANTITY (RQ) RANKING BASED ON CHRONIC
TOXICITY ...... . . 22
9.2. HEIGHT OF EVIDENCE AND POTENCY FACTOR ,(F=1/ED10).
FOR CARCINOGENI CITY. ....... 25
10. 'REFERENCES. .:..'.........' , . 27
APPENDIX: LITERATURE SEARCHED. ........ '. 34
1x
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LIST OF TABLES
No. Title Page
1-1 U.S. Manufacturers and Importers of 2-Methoxyethanol
Acetate for 1977 ........................ 3
5-1 Acute Toxldty of 2-Methoxyethanol Acetate
9-1 .Oral Toxlcity Summary for 2-Methoxyethanol Acetate Using
Male JCL-ICR Mice ................... ... 24
9-2 Compos Ue Scores for 2-Methoxyethanol Acetate ........ 25
9-3 Minimum. Effective Dose (MED) and Reportable Quantity (RQ) . . 27
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LIST CF /.GBREVIATIONS
ADI Acceptable dally Intake
BOO Biochemical oxygen demand
CNS Central nervous system
COD Chemical oxygen demand
CS Composite scare
ONA Deoxyr Ibonucleic acid
Koc So1l:sorptlon coefficient
Kow OctanoV water partition coefficient
LC5Q Median lethal concentra.tlon
LD5Q Median lethal dose
LOAEL Lowest-observed-adverse-effect level
MED llnlmum effective dose
MLD Minimum lethal dose
NOAEL Yo-observed-adverse-effect level
NOEL »lo-observed-effect level
PEL Permissible exposure level
ppm Parts per million
RfD Reference dose
RQ Reportable quar.tHy
RVd Dose-rating value
RVe Effect-rating value
ThOD Theoretical oxygen demand
TLV Threshold limit value
xl
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: . INTRODUCTION
1.1. STRUCTURE AND CAS NUMBER
2-Methoxyethanol acetate is also known as 2-methoxyethyl . acetate,
ethylene glycol monomethyl ether acetate, acetyl methyl cellosolve • and
methyl cellosolve acetate. The structure, molecular ' weight, empirical
formula and CAS Registry number for 2-methoxyethahol acetate are as Follows:
CH3-C-0-CH2-CH2-0-CH3 .
Molecular weight: 118.13
.Empirical formula: c5H1Q0'j
CAS Registry number: 110-49-6
1.2. PHYSICAL AND CHEMICAL PROPERTIES
2-Methoxyethanol acetate Is a colorless liquid at room temperature, with
a sweet, pleasant odor (Verschueren, 1983; Hawley, 1981). It Is mlsclble
with common organic solvents and 1s Incompatible with nitrates, strong
oxldlzers. strong acids and strong alkalies (Hawley. 1981; U.S. EPA, 1982).
2-Methoxyethanol acetate Is a moderate fire hazard when exposed to heat or
flame and. In .case of fire, will form toxic gases.and vapors such as carbon
monoxide (Hawley. 1981; U.S. EPA, 1982). Selected physical properties of
2-methoxyethanol acetate are listed below.
Melting point: -65.TC Union Carbide, 1979
.Boiling point: 145°C (760 mm Hg) Union Carbide, 1979
Vapor pressure: 2 mm Hg at 20°C Union Carbide, 1979
Hater solubility: complete Union Carbide, 1979
Log Kow: 0.12 U.S. EPA. 1986a
0858p -1- 03/20/87
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' .dens 1 * v:
(air=n
4.Q7
.C. cpa.
Specific gravity:
Refractive index,
Flashpoint:
TLV, air:
Conversion factors
in air:
1.0067 (20/20°C)
1,4019
12TF (49.4°C)
(closed cup)
132°F (55'.6°C
(open cup)
25 ppm (skin)
1 mg/m3 = 0.207 ppm
1 ppm = 4.83 mg/m3
Union Carbide, 1979
Brown et al., .1980
Union Carbide,. 1979
Brown st al., 1980
Sax, 1984
1.3. PRODUCTION DATA
2-Methoxyethanol acetate is produced from ethylene glycol monoethyl
ether, by first reacting ethylene oxide and anhydrous methanol under a
variety of reaction conditions and with or without catalysts such as caustic
soda or boron trlfluoride. Monoethers of dlethylene, trlethylene and poly-
ethylene glycols are by-products of the reaction. The ethylene glycol mono-
methyl ether Is then esterified with acetic add to produce 2-methoxyethanol
acetate (U.S. EPA, 1982).
Since 1984, Union Carbide Corp. (Chemicals and Plastic 01v.), South
Charleston, HV, has been the only U.S. manufacturer of 2-methoxyethanol
acetate (USITC, 1985). The U.S. manufacturers and Importers of this chemi-
cal in 1977 are listed In Table 1-1. -The current production volume of
2-methoxyethanol acetate could not be located in the available literature.
1.4. USE DATA
2-Methoxyethanol acetate Is used primarily as a solvent for oils,
greases. Inks, gums, resins, plastics, adheslves, waxes, nitrocellulose,
cellulose acetate and other cellulose esters and ethers (U.S. F.PA, 1982).
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TABLE 1-1
U.S. Manufacturers and Importers of 2-Hethoxyethanol
Acetate for 1977*
Company/Location
. Manufacturer
or Importer
Volume Produced
or Imported
Union Carbide Corp.
South Charleston, UV
CPS Chemical Co.
Oldbrldge. NJ
Uglne Kuhlmann of America. .Inc,
Paramus, NJ
manufacturer'
manufacturer
Importer
confidential
none'5
confidential
aSource: U.S. EPA, 1978
bTh1s company manufactured 2-methoxyethanol before 1977
0858p
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It is also usea in the texine priming industry ana in ;he iTianuraciure or
lacquers, enamels, adhesives and photographic film (U.S. EPA. 1982).
2-Methoxyethanol acetate is used in a resin/water mixture to prevent
discoloration of dyes of thermoplastic moldings; for the control of oil
spills; as a final rinse of resist patterns; as a rinse, after the electro-
phoretic coating of metals; In th'e formation of a protective layer on X-ray
intensifying screens; for treating defective lacquer coatings on cars; to
Impart stability to organophosphate Insecticides; and as a stabilizer to
absorb nitrogen oxide's and sulfur dioxide in flue gas (U.S. EPA, 1982).
1.5. SUMMARY
2-Methoxyethanol acetate, also known as ethylene glycol monomethyl ether
acetate, is a colorless liquid at room temperature, with a sweet, pleasant
odor. It is mlscible with, water and many common organic solvents
(Verschueren, 1983; Hawley, 1981). Ethylene glycol monomethyl ether; formed
by reacting ethylene oxide and anhydrous methanol. Is esterified with acetic
acid to produce 2-methoxyethanol acetate (U.S. EPA, 1982). Since 1984,
Union Carbide Corp., South Charleston, HV, has been the only U.S. manufac-
turer oF 2-methoxyethanol acetate. The current U.S. production volume for
this chemical is unavailable.
The primary use of 2-methoxyethanol acetate is as a solvent for oils,
greases, inks, g.ums, resins, plastics, adhesives, waxes, nitrocellulose,
cellulose acetate and other cellulose esters and ethers. 2-Methoxyethanol
acetate is also used in the manufacture of lacquers, enamels, adhesives,
photographic film and in the textile printing industry (U.S. EPA, 1982).
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2. cM/lRONHEMTAL .FATE AMD TRANSPORT PROCESSES
Pertinent data regarding the environmental fate and .transport of
2-methoxyethanol acetate in water, air and soil could not be located In the
available literature as cited in the Appendix. When possible, physical'
properties anc tne limited laboratory studies of related compounds were used
to 'derive Information on the environmental fate and transport processes of
•2-niethoxye':ri<;',Tji acetate.
2.1. HATER
2.V.I. Hydrolysis. Carboxylic add esters are potentially susceptible to
hydrolysis (Lyman et al., 1982). Based on the molecular structure of
2-methoxyethanol acetate, hydrolysis may be a potential removal process In
the ambient environment; however, the hydrolysis half-lives of ethyl acetate
In water at 25°C and at pHs of 7 and 9 were estimated to be 2 years and 7
days, respectively (Lyman et al., 1982). Therefore, the hydrolysis of
2-methoxyethanol In ambient water may be Important.
2.1.2. Mlcroblal Degradation. Bridle et al. (1979a) conducted a 5-day
BOD test on 2-methoxyethanol acetate In accordance with the American Public
Health Association standard dilution methods. The BOD value determined was
0:49 g O./g compound, which Is 30X of the theoretical value. This BOD
value suggests that 2-methoxyethanol acetate Is slightly to moderately
biodegradable. Analysis of a 10-day BOD value Indicates that during Incuba-
tion of 200-1000 mg/l 2-methoxyethanol acetate In acclimated activated
sludge, removal was 15X, suggesting that only slight blbdegradatlon occurred
(Ludzack and Ettlnger, 1960). In a "dispersed seed aeration" study. Mills
and Stack (1954) measured a 10-day BOD of 1.1 g 0 /g compound (68% ThOD).
0858p -5- 10/02/86
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suggests that ^degradation was significant. The importance of
blodegradatlon In natural waters Is uncertain because of. the conflicting
results from the BOO studies and the lack of natural water studies.
2.1.3. Transport.
2.1.3.1. BIOACCUHULATION — The complete water solubility and
estimated log K value of 0.12 of 2-methoxyethanol acetate suggest that
significant bloaccumulatlon In aquatic organisms would not occur. The BCF
has been estimated from the K by using the equation (Lyman et al.,
1032): log BCF = 0.76 log KQW - 0.23. The calculated BCF value of 0.73
suggests' Insignificant bloaccumulatlon of 2-methoxyethanol acetate in.
aquatic organisms.
2.1.3.2. ADSORPTION — The complete water solubility and . .log KQW
value of 0.12 for 2-methoxyethanol acetate suggest that adsorption to
particulate organic matter and sediment 1n water will not be significant.
2.1.3.3. VOLATILIZATION —Although the compound has a vapor pressure
of 2 mm Hg at ambient temperatures, H Is difficult to predict Its
volatility from water because of Us complete misclbillty In water.
2.2. AIR
Because of Us vapor pressure (2 mm Hg at 20°C) under any atmospheric
conditions 2-methoxyethanol acetate should exist primarily In the vapor
phase. The compound has demonstrated moderate reactivity in smog chamber
studies In which It was Irradiated by black lights (Yanaglhara et al.,
1977). The estimated rate constant for 2-methoxyethanol acetate reacting
with photo- chemically generated- HO radical Is 1.073X10'11 cm3
molecule'1 sec'1 at 25'C (U.S. EPA. 1986b). Assuming an .ambient HO
radical concentration of 8.0xlOs molecules cm"3 (U.S. EPA, 1986b), the
HO radical reaction half-life has been estimated to be 22.42 hours.
2-Methoxyethanol acetate Is predicted to not react with ozone (U.S. EPA,
0858p 6- 04/27/87
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i986b). Considering the ' complete water ioiuoillty or .ij-neihoxyeinanoi
acetate, removal from the atmosphere by wet deposition may be significant.
2.3. SOIL
2.3.1.. Hydrolysis. Hydrolysis of 2-methoxyethanol acetate . may be a
potential removal process particularly In moist basic soils (see Section
2.1.1.).
2.3.2. Leaching. The '.complete .-water solubility .and K value of
2-methoxyethahol acetate suggest that it may leach reacily in. tne soil.
Using the molecular topology and quantitative structure-activity relation-.
ship analysis method of Sablj.lc (1984), a K of 94 can be predicted for
2-methoxyethanol acetate, Indicating high soil mobility (Swann et al.,
1983). 2-Methoxyethanol acetate may be removed by hydrolysis In moist
soils, where H Is expected to be highly mobile.
2.3.3. Volatilization. n-Butyl acetate undergoes 10054 weight loss In 8
minutes from glass surfaces during a standard evaporation test conducted at
77°F and 15% relative humidity (Dow Chemical Co.. 1981). The relative
evaporation rate (n-butyl acetate=l) for 2-methoxyethanol acetate Is 0.3
(Smith, 1984), which suggests that 2-methoxyethanol would evaporate quite
rapidly from dry soil, assuming no significant adsorption to soil.
2.4. SUMMARY
In water, the two Important processes that may remove 2-methoxyethanol
are hydrolysis and blodegradatlon (Lyman et al., 1982.). Bloaccumulatlon In
aquatic organisms and adsorption to suspended solids and sediments should
not be significant. The -compound Is expected to persist In water. In the
atmosphere. 2-methoxyethanol acetate Is expected to exist primarily In the
vapor phase and Is apparently susceptible to oxidation by HO radical
0858p -7- 04/27/87
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•, t. .,-=
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o. EXPOSURE
Limited monitoring and exposure data regarding 2-methoxyethanol acetate
were located in the available literature. 2-Hethoxyethanol acetate has been
qualitatively Identified In drinking water (Kool et al., 1982) and in efflu-
ents discharged into the I.llinois River (Somani et al., 198C). , Consumer
exposure to this compound would likely occur during the use of cleaning
solutions, paint, ink' and nail polish that contain 2-methoxyethanol acetate
(U.S..EPA. 1982').
Potential routes of 2-methoxyethanol.acetate exposure to workers Include
Inhalation of the vapor, ingestlon _ arid eye and skin contact (U.S. EPA,
1982). A 1972-1974 National Occupational Hazard .Survey estimated that
' ' ' . •
436,989 workers are occupatlonally exposed to this .compound during, manufac-
turing; processing, use and handling of 2-methoxyethanol acetate (RTECS,
1984). A more recent survey, the National Occupational Exposure Survey,
estimates that 2024 workers are exposed to 2-methoxyethanol acetate; how-
i ' •
ever, this figure does not reflect exposure to tradename, products containing
2-methoxyethanol acetate (NIOSH, 1985).
0858p -9- 10/02/86
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4. PHARMACOKINE7ICS
4.1. ABSORPTION
Pertinent data regarding the absorption of 2-methoxyethanol acetate
could not be located In the available literature as cited In the Appendix.
Systemic toxldty resulting from acute exposures (Chapter .5), however,
suggests that absorption does occur to some extent Following oral. Inhala-
tion or dermal exposure to , 2-methoxyettianol acetate. Rowe and Wolf (1982)
stated that 2-niethoxyethanol acetate can be absorbed through the skin with
prolonged contact.
4.2. DISTRIBUTION
Although "little Is known of the specific distribution of 2-methoxy-
ethanol acetate, apparently.It Is generally distributed throughout the body
since effects In the blood, testes, brain and kidney .have been reported
following exposure.
4.3. METABOLISM
The limited data available concerning the metabolism of 2-methoxyethanol
acetate pertain only to \i\ vitro experimentation. Hoffman (1984) reported
that 2-methoxyethanol acetate Is readily hy.drolyzed by rat plasma esterases.
A half-life of -10 minutes was determined for the acetate In plasma by
gas-liquid chromatography. Stott and McKenna (1985) demonstrated that
2-methoxyethanol acetate was a relatively good substrate for carboxyester-
ases present In mouse nasal mucosa, liver, kidney, lung and blood. In
addition, significant 2-methoxyethanol production resulted from Incubation
of 2-methoxyethanol acetate with nasal mucosal carboxyesterase from rats,
rabbits and dogs. Incubation of 2-methoxyethanol acetate with nasal and
liver mlcrosomes from rats did not result In appreciable formaldehyde forma-
tion (Dahl and Hadley, 1983). Browning (1965) suggested that, like other
0858p -10- 10/02/86
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acia esters or che glycol ethers, 2-
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3. c r f IC i b
5.1. CARCINOGENICITY
Pertinent data regarding the carclnogenlclty of 2-methoxyethanol acetate
could not be located 1n the available literature as cited 1n the Appendix.
5.2. MUTAGEJJICITY
2-Methoxyetnano? acetate strongly induced aneuploidy but not mHottc
recombination or point mutation In the yeast Saccharomyces cerevlslae strain
D.61 .M, oui only at. reiativeiy nigh concentrations that ranged from
2.91-5.66!', (Z'mmerman et al., 1985). These authors suggested that this may
not reflect 2-,-nethoxyethano] acetate-Induced changes In DNA or DNA-metabo-
Uzlng systems, but rather may be the consequence of effects on the spindle
apparatus. Further experiments were conducted on porcine brain tubulln \r\
vitro, and It was demonstrated that 2-methoxyethanol acetate accelerated
tubulln assembly at concentrations >100-fold lower than those needed to
Induce aneuploidy (Groschel-Stewart et al., 1985).. The correlation between
these two events 1s speculative, however, because of the sp.ecles difference
between porcine brain and yeast spindle tubulln and the large discrepancy In
the concentrations needed to Induce these changes. Additional data
pertinent to 2-methoxyethanol acetate mutagenlcUy were not located.
5.3. TERATOGENICITY
Information concerning the potential teratogenlc effects of 2-methoxy-
ethanol acetate could not be located In the available literature as cited In
the Appendix. Jji vitro studies have shown, however, that 2-methoxyethanol
acetate Is hydrolyzed to 2-methoxyethanol (see Section 4.3.), which Is an
established teratogen (U.S. EPA, 1986c).
G858p -12- 03/20/87
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i.4. OTHER .^PRODUCTIVE EFFECTS
Nagano et al. (1979) Investigated the testlcular' toxiclty Induced by
2-methoxyethanol in 6-week-old male JCL-ICR mice. The compound was diluted
in water ;and administered orally by stomach tube to groups of five mice, 5
days/week for 5 weeks, at dally doses of 62.5, 125, 250, 500, 1000 or 2000
mg/kg. A control group of 20 mice was. given water by the same method. A
dose-related decrease in .absolute and relative testes weight was observed;'
the decrease was sta::!s'tici"ily significant at doses >500 mg/!500 mg/kg. In the 500 mg/kg group, there was an obvious reduction in
the number of spermatocytes. In the 1000 'mg/kg group, spermatids and
spermatozoa were not present, and the diameter of the seminiferous tubules
was significantly reduced. .Spermatocytes. existed only in 'sma11 numbers in
some of the tubules. In the 2000 mg/kg group, no germ cells were observed,
although Sertoll cells were present. This response'was essentially equiva-
lent on a molar basis to .that observed with 2-methoxyethanol.
5.5. CHRONIC AND SUBCHRONIC EFFECTS
In the Nagano et al. (1979) study (see Section 5.4.), hematological data
were also obtained. A significant decrease in the white blood cell count
.occurred In the 1000 and 2000 mg/kg dose groups, while a reduction in
hemoglobin was seen only in the high dose mice. Changes in the red blood
cell count and packed cell volume were.less pronounced. No other pertinent
data regarding the chronic or subchronic effects of 2-methoxyethanol acetate
could be located in the available literature as cited in the Appendix.
0858o -13- 03/20/87
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i.j. OTHER 3ELEVANT IHF08HATION
The acute toxldty of 2-methoxyethanol acetate In animals Is summarized
In Table 5-1. LD5Q values of 3.93 g/kg for rats and 1.25 g/kg for guinea
pigs were determined by feeding 50% aqueous solutions by stomach tube (Smyth
et al., 1941). Gross pathology observations revealed effects on the kidney,
liver and a1ges.t1ve tract. Rabbits died after receiving 3 daily oral 'doses
of either 0.5 or 1.0 g/kg. and all exhibited signs of kidney Injury with
albumin and granular casts 1'n .the urine (Gross, 1938).
Gross (1938) conducted extensive studies on the acute Inhalation toxic-
Ity of 2-methoxyethanol acetate In a number of species. Kidney Injury was
observed In cats, guinea .pigs, rabbits and mice following repeated 8-hour
exposures to 500 or 1000 ppm (2416 or 4831 mg/m3). At 500 ppm, cats
showed slight narcosis and died, while at 1000 ppm, deaths occurred In all
species. Cats were able to tolerate repeated 4- to 6-hour exposures to 200
ppm (966 mg/m3), although decreases In blood pigments and In the red blood
cell count were observed. Cats were also able to survive a 7-hour exposure
to 1500 ppm (7247 mg/ra3), but did have ah Increase tn b.lood clotting time
and displayed changes In the brain. , Cats died after being exposed to 2500
ppm (12,078 mg/m3) for 9 hours. Mice and rabbits survived a 3-hour
exposure to 4554 ppm (22,000 mg/m3), an essentially saturated atmosphere.
A similar 1-hour exposure resulted only In mucous membrane .Irritation In
mice, rats, guinea pigs and rabbits.. Dogs exposed to 2-methoxyethanol
acetate vapor at a concentration of 400 ppm (1933 mg/m3). 8 hours/day for
120 days had minor disturbances In liver function. (Union Carbide, 1958).
Five drops of undiluted 2-methoxyethanol acetate produced mild Irrita-
tion In the eyes of 'a rabbit, while application to rabbit skin was not
significantly Irritating (Union Carbide. 1958).
Q858p -14- 10/02/86
-------
TABLE 5-1
0
oo
in
CD
•o
Route Species
Oral rat
rabbit
guinea pig
Inhalation rat
i. rabbit,
T guinea pig
cat
cat
Subcutaneous guinea pig
guinea pig
cat
Acute Toxlclty of 2-Hethoxyuthanol Acetate
Dose/Concentrat Ion
3.93 g/kg
0.5-1.0 g/kg,
3 dally doses
1.25 g/kg
7000 ppin (33,610 nig/m3)
for 4 hiiur-s
1000 ppm (4830 mg/ni3)
repeated 8-hour exposures
500 or 1000 ppm. (24 15 or
4830 mg/ra3) repeated
8-hour exposures
2500 ppm (12.075 mg/m3)
for 9 hours
5 g/kg
1.25 gAg
3-4 g/k.j
Response
1=050
death
L050
death In
2/6 animals
death
death
death
HLD
L050
HID
Reference
Smyth et all. 1941
Gross, 1930
Smyth et al. . 1941
Smyth and Carpenter, 1948
Gross, 193U
Gross. 193U
Gross, 193U
Flury and Utrth, 1933
S'niyth.et al. , 1941
riury and Wtrth. 1933
o
ISJ
-------
ind C-ahi i"i97i; ,"r:portea the :ase of i ;3-year-j id -woman ..'no
developed acute dermatitis on the nose from contact with her eyeglasses.
Patch testing demonstrated the causative agents to be 2-methoxyethanol
acetate or ethyl acetate. This is the only recorded case of adverse effects
In humans following exposure to 2-methoxyethanol acetate and the results are
Inconclusive. Exposure to 1000 ppm (4831 mg/m3} 2-methoxyethanpl acetate
for 1 minute was Intolerable for volunteers, while a level of 120 ppm (580
mg/m3) for 3 minutes "provided good warning properties" (Union Carbide,
1958).
5.7. SUMMARY
No Information. Is available regarding either, the carclnogenlclty or
teratogenlclty. of 2-methoxyethanol acetate In animals or humans., 2-Methoxy-
ethanol acetate reportedly caused aneuploldy In yeast (Zimmerman et al.,
1985). but there Is considerable doubt as to the relevance of these data to
actual genotoxlclty.
The. only study that demonstrates the In vivo toxlclty of 2-methoxy-
ethanol acetate was conducted by Nagano et al. (1979), who treated male
MCL-ICR mice at oral doses of 6'2.5.. 125. 250, 500, 1000 or 2000 mg/kg/day. 5
days/week for 5 weeks. Significant decreases In testlcular weight and
substantial atrophy were observed In animals receiving >500 mg/kg. In
addition, leukopenla was evident In mice In the 1000 and 2000 mg/kg groups.
No effects were observed at <250 mg/kg/day. These responses were similar
qualitatively and quantitatively, (on a molar basis) to those Induced by
2-methoxyethanol In the same study.
0858p -16- 03/20/87
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Oral LDcQ values ror i-,netnoxyeihano'i acetate ranue from.i. 25 -j/ku in
guinea pigs to 3.93 g/kg \n rats (Smyth et al., 1941). Similar results were
obtained Following subcutaneous Injection (Smyth et al., 1941; Flury and
W1rth. 1933). Kidney lesions were common following these exposures. Three
repeated 8-hour Inhalation exposures of .1000 ppm (4831 mg/m3) were
generally lethal to cats, rabbits, guinea pigs and mice (Gross, 1938).
Humans were, unable to tolerate exposure to 1000 ppm (4831 mg/m3) for 1
hour, while.a : level of. 120, ppm (580 mg/m3) for 3 minutes '"provided good
warning properties" (Union Carbide, 1958):
0853p -17- 10/02/86
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6. AQUATIC rOXICIT'f
6.1. ACUTE
Little Information 1s available regarding the effects of 2-methoxy-
ethanol acetate on aquatic organisms. Dawson et al. (1977) reported that
.the 96-hour LC5Q value for bluegllls,1 Lepomls macrochlrus. was 45 mg/i.
No mortalities occurred at 10 mg/l, while 10, 60 and 100% mortality
occurred at 25., 50. and 100 mg/i,.respectively, tiawson et al. (1977) also
determined .a 96;-hour LC5Q value of 40 mg/i for tidewater sllversl'des,
Menldla berylllna. with 100% mortality at 75 mg/l, 70% at 50 mg/l and 0%
at 25 mg/l. Bridle et al. (1979a) reported a 24-hour LC,_ of 190 mg/i
for the goldfish, Carasslus auratus.
6.2. CHRONIC
Pertinent data regarding1 the chronic toxlclty of . 2-methoxyethanol
acetate could not be located In the available literature as cited .in the
Appendix.
6.3. PLANTS
Pertinent data regarding the effects of 2-methoxyethanol acetate on
aquatic plants could not be located In the available .literature as cited In
the Appendix.
6.4. RESIDUES
Pertinent data regarding. 2-methoxyethanol acetate residues In aquatic
biota could not be located In the available literature as cited In the
Appendix!
6.5. SUMMARY
little Information Is available concerning the effects of 2-methoxy-
ethanol acetate on aquatic organisms. LC,_ values of 40, 45 and 190
mg/i were reported for tidewater sllversldes, bluegllls (Oawson et al.,
1977) and goldfish (Bridle et al., 1979a), respectively.
0858p -18- 03/20/87
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7. ^JIDELIJiES AND STANDARDS
7.1. HUMAN
ACGIH .(1985-1986) adopted a TLV for 2-methoxyethanol acetate of 5 ppm
(24 mg/m3), based upon the reported testlcular effects and' the apparent
hydrolysis of the ester, to 2-methoxyethanol (ACGIH, 1986). OSHA (1985) has
established a PEL of, 25 ppm (120 mg/m3). the same as recommenced for the
parent glycol ether.. Both, of these recommendations are accompanied by th^
"skin" . notation, inalcating that dermal absorption is a- potentially
hazardous route of exposure.
7.2. AQUATIC
Guidelines and standards, for the protection of aquatic biota from the
effects of 2-methoxyethanol acetate could not be located In the available
•literature as cited In the Appendix.
0858p -19- 03/20/87
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SK ASSESSMENT
Pertinent data regarding either the cardnogenlcHy or teratogenlcity of,
2-methoxyethanol acetate In animals or humans could not be located. In the
available literature. Therefore, because of the lack of carcinogenic data,
:
this compound Is classified as a U.S/ EPA Group 0 chemical (I.e.. Us
carcinogenic potential Is not ascertalnable). 2-Methoxyethanql acetate
reportedly caused aneuploVdy In yeast (Zimmerman et al., 1985}, but there is
considerable doubt as to the relevance of these data'to actual genotoxlclty.
The only study that demonstrates the \n_ vivo toxlclty of 2-methoxy-
ethanol acetate was conducted by Nagano et al. (1979), who treated male
JCL-ICR mice at oral doses of 62.5, 125, 250, 500, 1000 or 2000 mg/kg/day, 5
days/week for 5 weeks. Significant decreases In testlcular weight and
substantial atrophy were observed In animals receiving >500 mg/kg. In
addition, leukopenla was .evident In mice In the 1000 and 2000 mg/kg groups.
No. significant adverse effects were observed at doses of <250 mg/kg.. These
responses were similar qualitatively and quantitatively (on a molar basis)
to those Induced by 2-methoxyethanol In the same study.
Based on the available Information, regarding, the adverse effects of
2-methoxyethanol (U.S. EPA, T986c) and the evidence that 2-methoxyethanol
acetate Is hydrolyzed to the parent glycol ether. It Is not prudent to base
an RfD for 2-methoxyethanol acetate oh the data provided by Nagano et. al.
(1979). A NOEL of 250 mg/kg/day, 5 days/week (179 mg/.kg/day). as estab-
lished by this study. Is not adequately, protective If 2-methoxyethanol
acetate produces teratogenlc, fetotoxic and reproductive effects at doses
equlmolar to those of 2-methoxyethanol producing such effects. Thus, an RfD
for 2-methoxyethanol acetate can be derived based on the RfO for 2-methoxy-
0853p . -20- 04/?7/37
-------
•ethanoi. This1 procedure vi j'.rm'iar Lo :fiat 'proposes :y ACGIK ',1936) i:::r
establishing a TLV for 2-methoxyethanol acetate. No chronic oral or Inhala-.
tlon studies on 2-methoxyethanol are available; also no studies regarding
the subchronlc oral toxldty are available. Oral studies regarding the
teratogenlc and reproductive effects of. 2-methoxyethanol are . available;
however, a NOEL or NOAEL could not be established from these studies (U.S..
EPA. 1986c). Subchronlc Inhalation, studies by Miller e.t al. (1982, 1983),
nowever, established .a. NOEL of 10 ppm, 6 hours/day, 5 days/week ',ri rabbits
(converted to 1.46 mg/kg/day) and a LOAEL of 30 ppm. 6 hours/day, 5
days/week In rabbits (converted to 4.57 mg/kg/day) for testlcular lesions
and developmental effects. Dividing the NOEL by an uncertainty factor of
1000 resulted. In an RfD for 2-methoxyethahol of 0.001 mg/kg/day or 0.01
mg/day for a 70 kg man.
An RfD of 0.002 mg/kg/day or 0.11 mg/day for a 70 kg man can be derived
for 2-methoxyethanol acetate by analogy to 2-methoxyethanol by multiplying
the RfD for 2-methoxyethanol by the molecular weight ratio of 2-methoxy-
ethanol to 2-methoxyethanol acetate.
08£8p -21- 04/27/87
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•':. 3EPORTABLE OUANTITIES
9.1. REPORTABLE QUANTITY (RQ) RANKING BASED ON CHRONIC TOXICITY
Only one subchronic toxidty study of 2-methoxyethanol acetate was
available (Nagano et al., 1979). This study was discussed in Section 5.4.
and Is summarized 1n Table 9-1. The 500 mg/kg/day, 5 days/week (357 mg/kg/
day) exposure was the lowest dose In the study io cause reduced spermato-
genesls. Multiplying the dose of 357 mg/kg/day by the cube root of the
ratio of the mouse body weight (0.03 kg) to the reference human body weinht
to convert to an equivalent human dose and by 70 kg to express the dose In
mg/day and dividing by 10 to approximate chronic exposure results in an MED
of 188 mg/day (Table 9-2). The MED corresponds to an RV. of 2.1. The
effect of reduced spermatogenesls warrants an RV of 8. which when
multiplied by the RV. yields a CS of 17, corresponding to an RQ of 1000.
Mice at >1000 mg/kg/day also had hematologlcal effects, but. since these
effects warranting lower RV s were observed at higher doses, calculation
of CSs Is not necessary.
Since 2-methoxyethanol has been studied for teratogenlc and reproductive
effects more extensively than 2-methoxyethanol acetate, and since 2-methoxy-
ethanol acetate is believed to produce similar effects as 2-methoxyethanol
on an equlmolar basis, It Is more appropriate to derive the RQ for the
acetate by analogy to the more studied compound. U.S. EPA (1986c) derived
an RQ of 100 for 2-methoxyethanol based on a 6-week Inhalation study by
Nelson et al. (1984) using Sprague-Oawley rats. In this study, the 21 -day
offspring of male rats exposed to 25 ppm (78 mg/m3) of 2-methoxyethanol, 7
hours/day, 7 days/week for 6 weeks had neurochemlcal deviations In the
brain. An RV of 7 was assigned. The exposure level of 25 ppm (78
mg/m3) corresponds to 121 mg/m3 of 2-methoxyethanol acetate. Expanding
0858p -22- 03/20/87
-------
o
to
00
TABLE 9-1
Oral Toxlclty Sumiiary for 2-Nethoxyethanol Acetate Using Hale JCL-1CR Mtcea>b
No. at
Start
Average
Uelght
(kg)
Vehicle/
Physical
State
Exposure
Transformed
Animal Dose
(ing/kg/day)
Kesponsc
S/group
0.03
water 62.5, 125. 250
500. 1000 or
2000 mg/kg/day.
5 days/week for
5 weeks
45. 89. 179.
357, 714 or
1429
Significantly reduced absolute
and relative testes weight at
>500 niy/kij; dose-related atrophy
of seminiferous epithelium at 500
mg/kg; at 500 nig/kg reduction In
number of spermatocytes; at 1000
mg/kg no spermatlds or sperma-
tozoa present; at 2000 nig/kg.
Sertoli cells only were present;
leukopenla at >1000 mg/kg/day;
reduced hemoglobin at 2000
mg/kg/day
aSource: Nagano et al.. 1979
bPurlty of compound was not reported
o
CJ
I\J
o
CD
-------
en
CD
•o
1ABLE 9-2
Compos tie Scores for ?-Hcthoxyethanol Acetate
Route
Chronic
Species Animal Dose Human MED RVd Effect
kVe CS KQ Reference
(mg/kg/day) (mg/day)
Oral
Inhalation
mouse/
JCL-ICR
rat/Sprague-
Oawley
357 188a 2.1 depressed
spermatogenes is
23b 2Ba 3.3 neurochemlcal
deviations In
offspring
B 17 1000 Nagano
el al..
7 23 100 Nelson
et al..
1979
19U4
aAn uncertainty factor of 10 was Incorporated to extrapolate to a chronic human MHO
blhe administered compound was 2-methoxycthanol. but the dose Is expressed as 2-methoxyethanol acetate.
o
CO
ro
o
CO
-------
the exposure or 121 mq/m-' over a <:
-------
TABLE 9-3
2-Methoxyethanol Acetate
Minimum Effective Dose (MED) .and Reportable Quantity (RQ)a
Route: i.-halation
Ooseb: 28 mg/day
Effect: neurochemlcal deviations In offspring
Reference: Nelson et al., 1984
RVd: 3.3
RVe: 7
Composite Score: 23
RQ: 100
aThe derivation Is based on data for 2-methoxyethanol. The dose 1s expressed
as 2-methoxyethanol acetate.
bEqu1valent human dose
0858p -26- 03/20/87
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iO. RErESEHCES
ACGIH (American Conference of Governmental Industrial Hygienists).
1985-1986. TLVs: Threshold Limit Values for Chemical .Substances in the Work
Environment with Intended Changes for 1985-1986. Cincinnati, OH. p. 23.
ACGIH '(American Conference of Governmental . Industrial Hygienists}, 1986.
Documentation of. the Threshold Limit 'Values and Biological Exposure Indices,
5th ed. Cincinnati, OH. p. 366.
Bridle. A.L., C.J.H. Wolff and M. Winter. 1979a. The acute toxlclty of
.some petrochemicals to goldfish. Water Res. .13(7): 623-626.
Bridle, A.L.. C.J.H. Wolff and M. Winter. 1979b. BOD and COD of some
petrochemicals. Water Res. 13(7):.627-630.
Brown. E.S., C.F. Mauser. B.C. Ream and R.V. Berthold. 1980. Ethylene
glycol and propylene glycol. I_n: Klrk-Othmer Encyclopedia of Chemical
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Sons, Inc., New York. p. 933-956.
Browning, E. 1965. Toxlclty and Metabolism of Industrial Solvents.
Elsevler Publishing Company, New York. p. 621-623.
Cook, R.R., K.M. Bodner, R.C. Kolesar, et al. 1982. A cross-sectional
study of ethylene glycol monomethyl ether process employees. Arch. Environ.
Health. 37(6.): 346-351.
0858p -27- 03/20/87
-------
pan!. A..",. -:na 1-i.M. Hadley. ".983. Formaldehyde production nroT.otc-d by .-.it
nasal cytochrome P-450-dependent monooxygenases with nasal decongestants,
essences, solvents, air pollutants, nicotine and cocaine as substrates.
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Dawson, G.W., A.L. Jennings, 0. Drozdowskl and E. Rider. 1977. The acute
toxlcity of 47 industrial chemicals to -fresh and salt water fishes. J..
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Dow Chemical Co. 1981. The Glyc.ol . Ethers Handbook. Dow Chemical Co.,
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1985. Aprotic polar solvents Inducing chromosomal ma 1 segregation In yeast
Interfere with the assembly of porcine brain tubulln Ui vitro. Mutat. Res.
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Gross, E. 1938. In.: Toxicology and Hygiene of Industrial Solvents, K.B.
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0858p -28- 03/20/87
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Hawley, G.G. _ 1-981. The Conaensea Chemical ;)icr.ionary, IQth ed. Van
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0858p -29- 03/20/87
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0858p -30- 03/20/87
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0858p -31- 03/20/37
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Swann, • i-i.L., u.A. LdSKOwsx'i, ,-.J. McCu i"i, £. Vdnaerxuy -^na ri.u. uisriDurtjer.
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ethanol Acetate. OTS, U.S. EPA, Washington, DC.
U.S. EPA. 1986a. Medchem Software Release 3.32, CLOGP, Graphical Exposure
Modeling System (GEMS). On-line. OTS, U.S. EPA, Washington. DC.
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0858p -32- 03/20/87
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U.S.- c?A. 1336c. Health ana iinvironmentd"! Effectj rrofiie on i--'
ethanol. Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria.and Assessment Office, Cincinnati, OH for the Office
of Solid Waste and Emergency Response, Washington, DC.
U.S. EPA. 1986d. Guidelines for Carcinogen .Risk Assessment. Federal
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Chemicals. U.S. Production and Sales. 1984. USITC Publ. 1745. Washington.
DC. p. 288.
Verschueren, K. 1983. Handbook of Environmental Data on Organic Chemicals,
2nd ed. Van Nostrand Relnhold Co:. New York.
Yanaglhara, S., I. Shi ma da, E. Shinoyama, F. Chlsaka and K. Salto. 1977.
Photochemical reactivities of hydrocarbons. In: Proc. 4th Int. Clean Air
Congr.. p. 472-477.
Zimmerman. F.K., V.W. Mayer, I. Scheel and M.A. Resnlck. 1985. Acetone,
methyl ethyl ketone, ethyl acetate. acetonltrUe and other polar aprotlc
solvents are strong Inducers of aneuploldy In Saccharomyces cerevisiae.
Mutat. Res. 149: 339-351.
0858p . -33- 03/20/87
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APPENDIX
LITERATURE SEARCHED
This profile 1s based on data Identified by computerized1 literature
searches of the following:
GLOBAL
TSCATS
CASR online (U.S. EPA Chemical Activities1Status 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 reviewed:
ACGIH (American Conference of Governmental Industrial Hygle.nlsts.).
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.O. 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.
0858p -34- 03/20/87
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"-ytbn-, ;"!.;..• end F .£. Clayton, ' Ed. 1932. ^iiy1- Ir.dustr-al
Hygiene and Toxicology,' 3rd rev. =d., Vol. 2C. ]ohn . Wiley 2nd
Sons, NY. p. 3817-5112.
Grayson, N. and 0. Eckroth, Ed. 1978-1983. Kirk-Othmer 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 on the Evaluation of 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.
. 198'4. Data aqulsltlon for environmental transport and fate screen-'
Ing for compounds of Interest in 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 Nostrand Relnhold Co., NY.
SRI .(Stanford Research Institute).1, 1984. Directory of Chemical
Producers. Henlo Park, CA.
U.S. EPA.. 1985. Status Report on Rebuttable Presumption Against
Registration (RPAR) or Special Review Process. Registration 'Stan-.
•dards and the Data Call l.n 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). 1983. Synthetic
Organic Chemicals. U.S. Production and Sales, 1982, USITC Publ.
1422, Washington, DC.
Verschueren, K. 1983. Handbook of Environmental Data on Organic
Chemicals, 2nd ed. Van Nostrand Relnhold Co., NY.
Wlndholz, M., 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.
0858p -35- 03/20/87
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In 'adaition, approximately 20 compendia :f :quat:c "-.oxk'ty 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, W.W. and M.T. Finley.' 1980. Handbook of Acute ToxIcHy
of Chemicals to F1sh and Aquatic Invertebrates. Summaries of
Toxicity Tests Conducted at Columbia National Fisheries Research
Laboratory. 1965-1978. U.S. Dept. Interior. .Fish and' Wildlife
Serv. 2es. Pub!. 137, Washington, DC.
McKee, J.E. and H.W. Wolf.-' 1963. ' Water Quality Criteria, 2nd e'd,.
Prepared for the Resources Agency of California, State Water
Quality Control Board. Pub!.. 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, 8.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.
0858p -36- 03/20/87
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