United States
Environmental Protection
Agency
FINAL DRAFT
ECAO-CIN-G049
August, 1989
Research and
Development
HEALTH AND ENVIRONMENTAL EFFECTS DOCUMENT
FOR METHYLCHLOROCARBONATE
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: 00 NOT CITE OR QUOTE HEWXJUWrttltfLIBRARY __
ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
NOTICE
This document Is a preliminary draft. It has not been formally released
IB 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 Us technical accuracy and policy Implications.
e*
1
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON. D.C. 20460
9 IOQQ
OFFICE OF
RESEARCH AND DEVELOPMENT
SUBJECT: Health and Environmental Effects Document for
FROM:
TO:
Farlawd, Ph.D.
^^Director
Office of Health and Environmental
Assessment (RD-689)
Matthew Straus
Chief, Waste Characterization Branch
Office of Solid Waste (OS-330)
I air forwarding copies of the Health and Environmental
Effects Document (HEED) for Methylchlorocarbonata.
The HEEDs support listings under RCRA, as well as provide
health-related limits and goals for emergency and remedial
actions under CERCLA. These documents represent scientific
summaries of the pertinent available data on the environmental
fate and mammalian and aquatic toxicity of each chemical at an
extramural effort of about $10K. The attached document has been
reviewed within OHEA, by staff in OPP and OTS, and by two
external scientists.
Should you wish to see any of the files related to the
development of the HEEDs, please call Chris DeRosa at
FTS: 684-7531.
Attachment
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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 c institute endorsement or recommendation for use.
11
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PREFACE
HealU and Environmental Effects Documents (HEEOs) are prepared for the
Office of Solid Waste and Emergency Response (OSHER). This document series
Is Intended to support listings under the Resource Conservation and Recovery
Act (RCRA< as well as to provide health-related limits and goals for emer-
gency and remedial actions under the Comprehensive Environmental Response,
Compensation and Liability Act (CERCLA). Both published literature and
informatkn obtained for Agency Program Office files are evaluated as they
pertain tc potential human health, aquatic life and environmental effects of
hazardous waste constituents. The literature searched for 1n this document
and the
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EXECUTIVE SUMMARY
Methylchlorocarbonate Is a colorless, flammable and corrosive liquid
(Hawley, 1981). It decomposes 1n water at 25°C (U.S. EPA, 1985), but Is
soluble 1r methanol, ethyl ether and benzene {Hawley, 1981). As of January
1988, onh two companies produced this chemical In the United States (SRI,
1988). Recent data on U.S. production and Import volume for methylchloro-
carbonate are not available, but at least 1-10 million pounds was produced
In 1977 (U.S. EPA, 1977). It 1s produced by the reaction of anhydrous
methanol
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characteristic latency period In the development of the toxic syndrome,
which Inc'udes amblyopla that may degenerate Into amaurosls (U.S. EPA, 1987;
R6e, 1982 . Laboratory nonpMmates exhibit signs that reflect the anesthetic
effects o: methanol (Roe, 198?). The syndrome 1n humans was attributed to
metabolic addosls from the accumulation of formic add, a metabolite of
methanol (U.S. EPA, 1987; Roe, 1982). Nonprlmate laboratory animals
metabolize formic add at a sufficiently rapid rate that It does not
accumulate.
Pertinent data regarding the carclnogenlclty, mutagenlclty or develop-
mental toxlclty of methylchlorocarbonate were not located In the available
literature cited 1n Appendix A.
Becair.e of a lack of data, methylchlorocarbonate 1s assigned to U.S. EPA
Group D, not classifiable as to human cardnogenldty. Data were Insuffi-
cient to derive RfDs for Inhalation exposure. RfDs for oral exposure have
been attenpted to be derived by analogy to methanol because of Insufficient
data available for methylchlorocarbonate. The NOAEL for methylchloro-
carbonate was calculated from the subchronlc toxldty data for methanol and
adjusted for the molecular weight of methylchlorocarbonate. However, the
confldenc; 1n the calculated RfD 1s very low due to the wide disparity
between Lhe calculated NOAEL and the observed LD5Q for methylchloro-
carbonate. It 1s recommended that further research be conducted on the
metabollsn and toxldty of methylchlorocarbonate before an RfD Is
established.
Data were Insufficient for derivation of RQs based either on systemic
toxldty 3r cardnogenldty.
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TABLE OF CONTENTS
1. INTRCOUCTION 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 2
2. ENVIRONMENTAL FATE AND TRANSPORT 4
2.1. SUMMARY 5
3. EXPOSURE 6
4. ENVIFONMENTAL TOXICOLOGY 7
4.1. AQUATIC TOXICOLOGY 7
4.1.1. Acute Toxic Effects on Fauna 7
4.1.2. Chronic Effects on Fauna 7
4.1.3. Effects on Flora 7
4.1.4. Effects on Bacteria 7
4.2. TERRESTRIAL TOXICOLOGY 7
4.3. FIELD STUDIES 7
4.4. AQUATIC RISK ASSESSMENT 8
4.5. SUMMARY 8
5. PHARHACOKINETCS 9
5.1. ABSORPTION 9
5.2. DISTRIBUTION 9
5.3. METABOLISM 9
5.4. EXCRETION 9
5.5. SUMMARY 9
6. EFFECTS 10
6.1. SYSTEMIC TOXICITY 10
6.1.1. Inhalation Exposure 10
6.1.2. Oral Exposure 11
6.1.3. Other Relevant Information 11
6.2. CARCINOGENICITY 16
6.3. MUTAGENICITY 16
6.4. TERATOGENICITY 17
6.5. OTHER REPRODUCTIVE EFFECTS 18
6.6. SUMMARY 18
vll
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TABLE OF CONTENTS (cont.)
Page
7. EXIST :NG GUIDELINES AND STANDARDS 20
7.1. HUMAN 20
7.2. AQUATIC. . 20
8. RISK ASSESSMENT 21
8.1. CARCINOGENICITY 21
8.1.1. Inhalation 21
8.1.2. Oral 21
8.1.3. Other Routes 21
8.1.4. Weight of Evidence 21
8.1.5. Quantitative Risk Estimates 21
8.2. SYSTEMIC TOXICITY 22
8.2.1. Inhalation Exposure 22
8.2.2. Oral Exposure 23
9. REPOR1A8LE QUANTITIES 26
9.1. BASED ON SYSTEMIC TOXICITY 26
9.2. BASED ON CARCINOGENICITY 26
10. REFERENCES 27
APPENDIX A: LITERATURE SEARCHED 34
APPENDIX B: SUMMARY TABLE FOR METHYLCHLOROCARBONATE 37
vlll
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CAS
CS
GI
Kobs
LD50
NAD
NOAEL
ppm
RfD
RQ
SGPT
LIST OF ABBREVIATIONS
Chemical Abstract Service
Composite score
Gastrointestinal
Observed hydrolysis rate constant
Concentration lethal to 50% of recipients
(and all other subscripted dose levels)
Dose lethal to 50% of recipients
Nicotine adenlne-dlnucleotlde
No-observed-adverse-effect level
Parts per million
Reference Dose
Reportable quantity
Serum glutamU pyruvlc transamlnase
1x
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1. INTRODUCTION
1.1. STRUCTURE AND CAS NUMBER
Methylchlorocarbonate 1s also known as methylchloroformate; methoxy-
carbonyl chloride; and carbonochlorldlc add, methyl ester (U.S. EPA, 1988).
The struc;ure, molecular formula, molecular weight and CAS Registry number
for this chemical are as follows:
0
(I
CH3-C-0-C1
Molecular formula: C-H-CIQ.
Molecular weight: 94.50
CAS Regis ;ry number: 79-22-1
1.2. PHfSICAL AND CHEMICAL PROPERTIES
Methylchlorocarbonate Is a colorless, flammable and corrosive liquid
(Hawley, 1981), which decomposes 1n water at 25°C (U.S. EPA, 1985). It 1s
soluble In methanol, ethyl ether and benzene (Hawley, 1981). A few physical
properties of this compound are listed below:
Melting paint:
Boiling point at 1 atm:
Specific gravity at 20/4°C:
Flash point:
Vapor pressure at 25°C:
not available
71°C
1.250
(tag open cup): 24.4°C
(tag closed cup): 17.8°C
113 mm Hg
Abrams, 1978
Abrams, 1978
Abrams, 1978
Abrams, 1978
U.S. EPA, 1985
Methylchlorocarbonate undergoes many reactions similar to acid
chlorides, but at a slower rate. It reacts with water particularly at
higher temperatures, with the formation of methanol, carbon dioxide and
hydrochlcrlc add. This compound Is moderately stable toward thermal
no/ii/no
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decomposition, but Us rate Increases In the presence of Iron, zinc and
aluminum :hlor1de catalysts (Abrams, 1978). Hethylchlorocarbonate will
react with water or steam to produce toxic and corrosive fumes. When heated
to decomposition, toxic fumes of phosgene are produced (Sax, 1984).
1.3. PRODUCTION DATA
According to SRI (1988), Essex Chemical Corp., Baltimore, HD, and PPG
Industries, Inc., La Porte, TX, are the only companies that manufacture this
chemical *n the United States as of January 1, 1988. USITC (1987) also
listed PPf Industries, Inc., as a manufacturer of methylchlorocarbonate 1n
the United States. Recent data on United States production and Import
volume arc not available; however, according to U.S. EPA (1977), at least
1-10 million pounds of methylchlorocarbonate was produced In the United
States In 1977. This chemical 1s prepared by the reaction of anhydrous
methanol faith a molar excess of dry, chlorine-free phosgene at low tempera-
tures and distilled to obtain methylchlorocarbonate. The specifications for
commercial methylchlorocarbonate are as follows: purity, 95-98%; phosgene,
<1X; acidity as HC1, <1X; methanol, <2X; and Iron, <10 ppm (Abrams, 1978).
1.4. USE DATA
Methylchlorocarbonate 1s used 1n organic synthesis and In the manufac-
ture of Insecticides (Hawley, 1981). It was used as a warfare agent during
World War I (Clayton, 1981).
1.5. SUMMARY
Methylchlorocarbonate Is a colorless, flammable and corrosive liquid
(Hawley, 1981). It 1s slightly soluble 1n water and decomposes at 25°C
(U.S. EPA, 1985). It Is also soluble 1n methanol, ethyl ether and benzene
(Hawley, 1981). As of January 1988, only two companies produced this
chemical 'n the United States (SRI, 1988). Recent data on U.S. production
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and Import volume for methylchlorocarbonate are not available, but at least
1-10 mlTl'on pounds was produced 1n 1977 (U.S. EPA, 1977). It Is produced
by the reaction of anhydrous methanol with dry, chlorine-free phosgene at
low temperatures (Abrams, 1978). Methychlorocarbonate Is used In organic
synthesis and In the manufacture of certain Insecticides (Hawley, 1981). It
has also been used as a poisonous gas for military purposes (Clayton, 1981).
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2. ENVIRONMENTAL FATE AND TRANSPORT
Data regarding the fate of methylchlorocarbonate 1n any environmental
medium are limited. Since the vapor pressure of this compound Is 113 mm Hg
at 25°C, Us principal environmental sink 1s expected to be air. Generally,
reaction ^Ith HO" radical Is the primary process by which most environ-
mental pollutants are removed from the atmosphere; however, kinetic data for
this reacilon for methylchlorocarbonate are not available. Based on the
method of Atkinson (1987), the rate constant for this reaction Is estimated
as 2. 16x1 )"13 cm3/molecule-sec. If the average dally concetratlon of HO
radical In the troposphere Is assumed to be 5x10' radicals/cm3 (Atkinson
et a!., 1984), the half-life of this reaction Is -74 days. Therefore, In
the absence of more rapid reaction, methylchlorocarbonate may persist In the
air for long periods of time. Hydrolysis of this compound In moist air,
however, may be a major removal process, since It Is expected to be the most
Important fate process 1n water. The rate constant for the hydrolysis of
this compiund In water Is 5.64x!0~Vsec (Queen, 1967; Castro and Hoodie,
1974), wh ch corresponds to a half-life of ~20 minutes. The hydrolysis may
become se:ond-order, however, 1n addle or basic solutions. The blomole-
cular aqueous hydrolysis of methylchlorocarbonate can be represented by the
following equation {Castro and Hoodie, 1974): CH3-C02-C1
H20 =
CHgOH * :02 * H* * Cl"; therefore, an Increase or decrease In the pH
of the so'utlon may enhance the hydrolysis rate.
The fate of this compound with respect to blodegradatlon either in
natural surface water or soil 1s unknown; however, hydrolysis of this
compound In water and wet soil may be more Important than blodegradatlon.
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The relative volatility of this compound from wet and dry soil was estimated
by U.S. IPA (1985). Compared with CS2, the evaporation rate of methyl-
chlorocarbonate from wet and dry soil Is ~3.5 times slower. Since the
evaporation rate of CS2 from soil 1s known to be fast, the evaporation
rate of methylchlorocarbonate may still be considered a significant process.
2.1. SUMMARY
Sufficient data are not available for assessing the environmental fate
of methylchlorocarbonate. Because of Its high volatility, air Is expected
to be th<> primary environmental sink for this chemical. Based on the
estimated reaction rate constant, the half-life for the reaction of methyl-
chlorocarbonate with H0~ radical 1s -7* days. Hydrolysis In moist air may
also be an Important process. The hydrolysis half-life of the compound In
water at neutral pH Is -20 minutes (Queen, 1967; Castro and Hoodie, 1974).
The rate >f hydrolysis 1s expected to be faster at higher pH (Castro and
Noodle, 1<74). Both rapid hydrolysis and evaporation may account for the
loss of significant amounts of this chemical from soil.
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3. EXPOSURE
No monitoring data on this chemical 1n any environmental medium were
located 1r the available literature cited In Appendix A. Since almost all
of the mrthylchlorocarbonate produced Is used captlvely (other than Us
military use) (Abrams, 1978), this lack of data Is to be expected.
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4. ENVIRONMENTAL TOXICOLOGY
4.1. AQWJIC TOXICOLOGY
4.1.1. A«:ute Toxic Effects on Fauna. Pertinent data regarding the
effects of acute exposure of aquatic fauna to methylchlorocarbonate were not
located In the available literature cited 1n Appendix A.
4.1.2. Chronic Effects on Fauna.
4.1.2. . TOXICITY Pertinent data regarding the effects of chronic
exposure of aquatic fauna to methylchlorocarbonate were not located In the
available literature cited In Appendix A.
4.1.2.?. BIOACCUMULATION/BIOCONCENTRATION No measured steady-state
BCF value for methylchlorocarbonate was found In the literature. Hethyl-
chlorocarbjnate decomposes In water at 25°C (see Section 1.2.) and, there-
fore, 1s rot expected to accumulate In aquatic organisms.
4.1.3. EFfects on Flora. Pertinent data regarding the toxic effects or
bloconcent'atlon 1n aquatic flora of methylchlorocarbonate were not located
In the available literature cited In Appendix A.
4.1.4. EFfects on Bacteria. Pertinent data regarding the effects of
exposure cf aquatic bacteria to methylchlorocarbonate were not located In
the available literature dted 1n Appendix A.
4.2. TERRESTRIAL TOXICOLOGY
Pertinent data regarding the effects of exposure of terrestrial fauna or
flora to Methylchlorocarbonate were not located 1n the available literature
cited In Appendix A.
4.3. FIELD STUDIES
Pertinent data regarding the effects of methylchlorocarbonate on flora
and fauna In the field were not located In the available literature dted in
Appendix A.
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4.4. AQIMTIC RISK ASSESSMENT
There were no data available regarding the effects of exposure of
aquatic fauna and flora to methylchlorocarbonate preventing the development
of either a freshwater or saltwater criterion by the method of U.S. EPA/OWRS
(1986).
4.5. SUM1ARY
Pertinent data regarding the toxlclty of methylchlorocarbonate to
aquatic oiganlsms were not located 1n the available literature dted In
Appendix A.
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5. PHARHACOKINETICS
5.1. ABSCRPTION
Two English abstracts of a Russian study (Gurova et al., 1977a,b)
Indicate that methylchlorocarbonate easily penetrates the skin of mice, rats
and guinea pigs and manifests a "skln-resorptlve action" (not described).
5.2. DISTRIBUTION
Pertinent data regarding the tissue distribution of methylchloro-
carbonate were not located In the available literature dted 1n Appendix A.
5.3. METABOLISM
Data regarding the metabolism of methylchlorocarbonate 1n biologic
systems we-e not located. As discussed In Chapter 2, however, methylchloro-
carbonate readily undergoes hydrolysis In the presence of water or moist
air. Queen (1967) experimentally determined rate constants for hydrolysis
of methylchlorocarbonate In pure water of 3.323x10"* sec'1 at 19.569°C
and 14.05<10~« sec'1 at 35.042°C. The rate constants correspond to
half-lives of 35 and 8 minutes, respectively. These data suggest that
methylchlo-ocarbonate absorbed Into biologic systems may undergo rapid
hydrolysis to form methanol and hydrochloric add.
5.4. EXCIETION
Pertinent data regarding excretion of methylchlorocarbonate were not
located In the literature cited 1n Appendix A.
5.5. SUK1ARY
Methyl:hlorocarbonate readily penetrates the skin of mice, rats and
guinea plijs (Gurova et al., 1977a,b). In biological systems It may be
expected 1o undergo rapid hydrolysis to form methanol, carbon dioxide and
hydrochloric acid (Queen, 1967).
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6. EFFECTS
6.1. SYSTEMIC TOXICITY
6.1.1. inhalation Exposure.
6.1.1.1. SUBCHRONIC Gage (1970) studied the subchronlc Inhalation
toxldty )f methylchlorocarbonate In Alderly Park SPF rats with an average
body weight of 0.200 kg. In acute range-finding studies, a concentration of
an aerosol of methylchlorocarbonate In petroleum ether (supposedly toxlco-
logically Inert solvent) that produced overt signs was adjusted downward
until the rats could withstand 6-hour exposures. In the subchronlc experi-
ments, grcups of four male and four female rats were exposed In a chamber to
methylchlcrocarbonate at 1, 5 or 20 ppnv (4, 20 or 80 mg/m3) 6 hours/day, 5
days/week for 3 weeks. Variables evaluated were general appearance and
behavior, body weight, limited urlnalysls, hematology and blood blochemlsty
test resu ts, gross appearance at necropsy, and hlstopathologlc appearance
limited t3 lungs, liver, kidneys, spleen and adrenals and occasionally
Including heart, Jejunum, lleum and thymus.
Methylchlorocarbonate was 1 of 109 chemicals tested In this laboratory
over a period of -20 years. Gage (1970) stated that batches of control
animals were Included In the experiments about every 2 months to "check the
characteristics of the colony," but results of examination of control
animals were not reported. Control values for the blood tests were pre-
treatment values from the test animals.
Rats exposed to 20 ppm exhibited nasal Irritation, dyspnea, lethargy,
poor condition and loss of body weight. The lungs appeared to be grossly
distended and hemorrhaglc; hlstopathologlc examination revealed areas of
lung consolidation, collapse and edema, and congestion of the kidneys. At 5
ppm, rats exhibited nasal Irritation and lethargy, but the organs appeared
to be "nornal." At 1 ppm, no adverse effects were reported.
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6.1.1.2. CHRONIC Data regarding the effects of "chronic" exposure
to methylchlorocarbonate vapors are limited to abstracts of a Russian study
by Gurova et al. (1977a,c). Effects reported In rats and mice exposed to
0.64-0.72 mg/m3 were changes 1n neuromuscular excitability, body
temperature, respiratory frequency, erythrocyte content and osmotic
stability, liver antitoxic function, kidney, heart, and spleen weights, and
adrenal v tamln C content. The highest Ineffective concentrations for a
chronic 1ihalat1on study were reported to be 0.185 mg/m3 for mice and
0.197 mg/m3 for rats (Gurova, 1977a). It 1s not clear how the study was
undertaken since further Information was not available.
6.1.2. Oral Exposure. Pertinent data regarding the toxldty of oral
exposure 1o methylchlorocarbonate were not located In the available litera-
ture cited In Appendix A.
6.1.3. Other Relevant Information. Methylchlorocarbonate Is highly
Irritating and corrosive by Ingestlon, Inhalation, or eye or skin contact
(Sandmeyer and Klrwln, 1981). ID,., values for oral, Intraperltoneal and
dermal adn1n1strat!on of methylchlorocarbonate are presented In Table 6-1.
There appear to be no marked species differences 1n the acute oral toxldty
of methylrhlorocarbonate. Oral and Intraperltoneal LD,0s for mice appear
to be similar. Nice may be more sensitive than rabbits to dermal applica-
tions of nethylchlorocarbonate. Dermal application caused skin resorptlon,
hyperemla and pigmentation In mice (Gurova et al., 1977a) and skin damage In
guinea pics (Sandmeyer and Klrwln, 1981).
Vernol et al. (1977) reported 1-hour LC5Q values of 88 ppm (340
mg/m3} fo* male rats and 103 ppm (398 mg/m3) for female rats. Gurova et
al. (1977i,c) reported a 4-hour LC5Q for rats of 450 mg/m' and a 2-hour
LC.Q for mice of 185 mg/m3. Effects associated with acute Inhalation
exposure In humans Include an odor threshold of 1 mg/m' (Gurova et al..
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TABLE 6-1
Acute ToxlcHy of Methylchlorocarbonate
Rout?
Oral
Oral
Oral
Oral
Oral
Intraperl :oneal
Dermal
Dermal
Species/Sex
rat/NR
rat/M
rat/F
mouse/NR
guinea p1g/NR
mouse/NR
rabbU/NR
mouse/NR
LD50
(mg/kg)
60
190
110
67
140
40
7120
1750
Reference
Gurova et al..
Vernot et al..
Vernot et al.,
Gurova et al.,
Gurova et al..
NIOSH, 1988
Vernot et al.,
Gurova et al.,
1977a,C
1977
1977
1977a,c
1977a,c
1977
1977a
NR = Not -eported
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1977a), Iicr1mat1on resulting from 10 minutes at 10 ppm (40 mg/m3) and
death resjltlng from 10 minutes at 190 ppm (730 mg/m3) (Vedder, 1925).
Employees exposed to methylchlorocarbonate 1n a chemical plant had no asso-
ciated he<1th effects or abnormal results In liver and kidney function tests
(Sandmeyei and Klrwln, 1981). Skin sensltlzatlon may occur (Sandmeyer and
K1rw1n, 1J81). One worker accidentally exposed to 2-3 Inhalations recovered
within 6 hours from the Initial Irritation, but suffered several bouts of
severe synptoms (heavy cough, dyspnea and light cyanosis of the Ups) after
a latency period of 36 hours (Schuckmann, 1972). These recurrences
continued for 9 days until recovery was complete. Methylchlorocarbonate has
been used as a war gas (Sandmeyer and K1rw1n, 1981}.
In sdvolysls studies In water. Queen (1967) showed that methylchloro-
carbonate Is hydrolyzed In a blmolecular reaction to methanol, carbon
dioxide end HC1 (see Chapter 2). The reaction rate constant was positively
correlated with water temperature between 0.57 and 45.H°C. Half-lives of
35 and 3 minutes were estimated from rate constants of 3.323x10~« and
14.05x10"* sec"1, respectively. These data suggest that methylchloro-
carbonate may persist sufficiently long to cause toxic effects. Hethanol Is
probably the most toxic degradation product of methylchlorocarbonate
followlnu 1ngest1on. Oral ID values for methanol In rats range from
5628-13.DOO mg/kg (Sax, 1984), substantially higher than ID5Q values
(60-190 mg/kg) for methylchlorocarbonate.
In the critical study, groups of 30 male and 30 female Sprague-Dawley
rats were given dally doses of methanol 1n water of 0, 100, 500 or 2500
mg/kg/day for 90 consecutive days (TRL, 1986). Analysis confirmed that the
concentrations of methanol In solution were consistently within 10% of
target levels. Indicators of toxlclty evaluated were general appearance and
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behavior, food consumption, body weight and an ophthalmologlc examination
pretreatment and at termination. In addition, extensive hematology, serum
chemistry and urlnalysls determinations were performed pretreatment, at an
Interim sacrifice after 6 weeks of treatment and at termination. Major
organs were weighed and a comprehensive hlstopathologlc examination was
performed at termination on all rats In the control and 2500 mg/kg/day
groups; n the other treated groups, hlstopathologlc examination was
restrlctec to liver, kidney, heart and gross lesions. The appropriate
statistical analyses were performed.
There were no compound-related effects on food consumption, body weight
or the results of ophthalmologlc examination. A transient ataxla and slowed
righting "eflex were observed 1n both sexes, but only during the first 3
days of treatment, at 2500 mg/kg/day. These signs appeared soon after
treatment and abated within 3 hours. Compound-related cllnlcopathologlc
changes w?re limited to elevated SGPT and alkaline phosphatase In rats at
2500 mg/kg/day at termination. Absolute brain weights In both sexes and
relative I>ra1n weights In males were decreased at 2500 mg/kg/day. The only
hlstopathologlc observation ascribed to methanol was a higher Incidence of
colloid In the hypophyseal cleft of the pituitary of both sexes at 2500
mg/kg/day
A les; comprehensive study was performed In Swiss Webster mice by Apaja
(1980). Groups of 25 male and 25 female mice were provided drinking water
containing 0.22, 0.444 or Q.889X methanol for 120 weeks. U.S. EPA (1987}
estimated dosages of 800, 1400 and 2800 mg/kg/day, respectively. Compared
with Mstjrlc controls, all groups of female rats had significantly reduced
survival, although the effect appeared to be Inversely related to dosage
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(U.S. EPA, 1987). Other effects attributed to treatment Included hepato-
cellular necrosis In high-dose females and amyloldosls In both sexes In all
exposed groups.
U.S. EPA (1987) and Roe (1982) noted striking differences 1n the
response cf humans and laboratory nonprlmates when exposed orally to lethal
or near-lfthal doses of methanol. The human syndrome has been divided Into
three pha:es: (1) slight Intoxication followed by a latent period of 1-72
(typically 12-24) hours; (2) Increased toxlclty manifested by nausea, vomit-
Ing, Inteise GI pain, dizziness, headache, lethargy, amnesia, confusion.
Impaired '1s1on, dyspnea and cyanosis; (3) coma and semi coma, convulsions
and death resulting from respiratory or cardiac failure (Kolvusalo, 1970).
Survivors who regain full visual acuity within a week of treatment retain
1t. Thosr survivors who regain partial vision experience a gradual decline
Iri visual acuity over several months (Roe, 1982).
NonpHmate laboratory species exhibit symptoms attributable to the
general anesthetic effects of methanol (R6e, 1982); fatalities occur without
a transleit recovery period (U.S. EPA, 1987). Permanently Impaired vision
has not b;en demonstrated In these species (Roe, 1982). Monkeys, however,
may exhibit a syndrome similar to that 1n humans: a period of little
reaction followed by a latency period, followed by nausea, sickness and
semlcoma preceding death (Gllger and Potts, 1955). Although the results are
not alway; consistent between studies (U.S. EPA, 1987; Roe, 1982). acutely
Intoxicated monkeys have exhibited ocular changes similar to those observed
1n humans (Gllger and Potts, 1955; Roe, 1982).
The metabolism of methanol In all species appears to Involve progressive
oxidation to formaldehyde, formic acid and eventually to carbon dioxide
(Kolvusalo, 1970; U.S. EPA, 1987). Oxidation of methanol to formaldehyde 1n
nonprlmates Involves a catalase-peroxldatlve enzyme system (U.S. EPA, 1987)
0130d
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and In monkeys and humans Involves an NAD-dependent alcohol dehydrogenase
system (Gcodman and Tephly, 1970). In all species, formaldehyde appears to
be oxidized rapidly to formic acid (U.S. EPA, 1987), probably by an NAD-
dependent formaldehyde dehydrogenase system (R5e, 1982). Formic acid then
enters the one-carbon pool, folate-dependent pathway for oxidation to carbon
dioxide (3a1ese and Tephly, 1975). This pathway Is considerably less
efficient In the monkey than 1n the rat (Black et al., 1985), so that
monkeys treated with large doses of methanol accumulate formic add and
suffer fron metabolic acldosls.
Acute Intoxication of humans Is typically accompanied by severe acldo-
sls, attrbuted to the accumulation of formic acid (Smith et al., 1981).
Acldosls has also been reported 1n several studies with monkeys, but has not
been reported In experiments with nonpMmates (Roe, 1982). Rats provided
with folate-defldent diets exhibit a marked reduction In rate of conversion
of formic acid to carbon dioxide (Palese and Tephly, 1975). Folate-
deflclent rats Intoxicated with methanol accumulate formic acid, suffer
metabolic acldosls, and exhibit ocular lesions similar to those seen In
primates {tekar and Tephly, 1977; Lee et al., 1987).
6.2. CAR:INOGENICITY
Pertinent data regarding the carclnogenldty of methylchlorocarbonate
were not located 1n the available literature cited In Appendix A. Data
regarding the carclnogenldty of methanol are unclear (U.S. EPA, 1987).
6.3. NUnGENICITY
Pertinent data regarding the mutagenlclty of methylchlorocarbonate were
not located In the available literature cited In Appendix A. Methanol has
tested consistently negative 1n prokaryotes, eukaryotes and mammalian
systems (U.S. EPA, 1987).
0130d
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6.4. TEfATOGENICITY
The developmental effects of methylchlorocarbonate are unknown, although
there Is evidence that methanol Is associated with morphologic
teratogen'clty (Nelson et a!., 1985) and behavioral toxldty (Infurna and
Weiss, 19(6) In rats.
Nelsor et al. (1985) Investigated the potential teratogenlc effects of
methanol In pregnant Sprague-Dawley rats. Methanol was administered by
Inhalatlor for 7 hours/day during days 1-19 of gestation at concentrations
of 5000, 10,000 and 20,000 ppm {6530, 13,070 and 26,900 mg/m3). Following
exposure, the dams were sacrificed on day 20, the entire uterus removed and
the numbers of corpea lutea resorptlons and live fetuses counted. Methanol,
even at 20,000 ppm, was not very toxic to the dams although some Initial
unsteadiness of gait observations were made. There were no effects on
corpea lutea. Fetal teratogenlc effects were observed 1n a dose-related
manner. Congenital malformations such as extra or rudimentary ribs and
urinary or cardiovascular defects were observed In the treatment groups
receiving 10,000 and 20,000 ppm methanol. However, the effects observed at
10,000 ppm were not significantly different from control. No adverse
effects were noted 1n the 5000 ppm treated group.
In tie latter study (Infurna and Weiss, 1986), Long-Evans dams were
offered 2K (v/v) methanol In distilled water on days 15-17 or 17-19 of
gestation. Maternal toxldty was not detected as measured by weight gain,
gestation;1 duration or dally fluid Intake. Litter size, birth weight and
Infant moitalHy did not differ from controls. Postnatal growth and date of
eye opening were unaffected although methanol-treated pups required more
time to begin suckling on postnatal day 1. On postnatal day 10, methanol-
treated pips required more time to locate nesting material from their home
cages. Tie behavioral changes were unaccompanied by overt toxldty.
0130d -17- 08/30/89
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6.5. OTHER REPRODUCTIVE EFFECTS
The reproductive effects of methylchlorocarbonate are unknown, although
there 1s evidence that methanol 1s associated with reduced testlcular
testosterone production 1n rats (Cameron et al., 1984).
Mature, male Sprague-Dawley rats were subjected to methanol vapor for up
to 6 weeks at doses ranging from ?00-10,000 ppm (260-13,070 mg/m3).
Critical effects were observed at the 200 ppm dose level. By 6 weeks, this
treatment group had serum testosterone concentrations at levels 32% of
control. The effect was postulated to be due to decreased testlcular
formation of testosterone.
6.6. SUMMARY
Methylchlorocarbonate Is highly Irritating and corrosive by Ingestlon,
Inhalatlor, or eye or skin contact and has been used as a war gas (Sandmeyer
and Klrwli, 1981). Oral LD5Q values for laboratory rodents range from
60-190 mg/kg (Gurova et al., 1977a,c; Vernot et al., 1977), with no gender-
or specie;-related differences apparent. Inhalation LC5Q values have been
reported .it 88 ppm (340 mg/m3) for male rats and 103 ppm (387 mg/m3) for
female ra;s exposed for 1 hour (Vernot et al., 1977), 117 ppm (450 mg/m3)
for rats exposed for 4 hours and 48 ppm (185 mg/m3) for mice exposed for 2
hours (Gurova et al., 1977a,c). In rats exposed Intermittently for 3 weeks,
IrrHatlor and lung and kidney lesions were observed at 20 ppm (80 mg/m3)
and lethargy and nasal Irritation were observed at 5 ppm (20 mg/m3) (Gage,
1970). Nc effects were observed at 1 ppm (4 mg/m3).
Upon exposure to moisture, methylchlorocarbonate degrades rapidly to
methanol Queen, 1967), which Is probably the most toxic metabolite follow-
ing hydrolysis of methylchlorocarbonate. Secondary Inhalation effects may
result from exposure to HC1 vapor 1f threshold levels are reached (Flnkel,
0130d
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08/31/89
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1983). Ii the critical study with methanol, no adverse effects were
reported :n rats treated by gavage with 500 tng/kg/day for 90 days (TRL,
1986). Elevated SGPT and alkaline phosphatase levels, reduced brain weights
and mild lesions of the pituitary were observed at 2500 mg/kg/day.
Humans and nonprlmate laboratory species appear to respond quite dif-
ferently 1o large lethal or near lethal doses of methanol. Humans exhibit a
characteristic latency period In the development of the toxic syndrome,
which Includes ocular lesions (U.S. EPA, 1987; Roe, 1982). Laboratory
nonprlmatts exhibit signs that reflect the anesthetic effects of methanol
(Roe, 198?). The syndrome 1n humans was attributed to metabolic acldosls
from the accumulation of formic add, a metabolite of methanol (U.S. EPA,
1987; Roe, 1982). Nonprlmate laboratory animals metabolize formic acid at a
sufficiently rapid rate that It does not accumulate.
Pertinent data regarding the carclnogenlclty, mutagenlclty, develop-
mental or reproductive toxldty of methylchlorocarbonate were not located In
the available literature cited 1n Appendix A.
0130d
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08/31/89
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7. EXISTING GUIDELINES AND STANDARDS
7.1. HUMAN
The or.ly guideline located for methylchlorocarbonate has been withdrawn
pending firther consideration by the RfD Workgroup (U.S. EPA, 1989).
7.2. AQIATIC
Guidelines and standards for the protection of aquatic life from
exposure ;o methylchlorocarbonate were not located In the available litera-
ture c1te( In Appendix A.
0130d
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8. RISK ASSESSMENT
Statements concerning available literature 1n this document refer to
published, quotable sources and are In no way meant to Imply that
confldent'al business Information (CBI), which this document could not
address, ire not In existence. From examination of the bibliographies of
the CBI dita, however, It was determined that CBI data that would alter the
approach :o risk assessment or the risk assessment values presented herein
do not exist.
8.1. CAFCINOGENICITY
8.1.1. Inhalation. Pertinent data regarding the carclnogenlclty of
Inhalatlor exposure to methylchlorocarbonate were not located In the
available literature cited In Appendix A.
8.1.2. Cral. Pertinent data regarding the carclnogenlclty of oral
exposure to methylchlorocarbonate were not located In the available
literature cited In Appendix A.
8.1.3. Cther Routes. Pertinent data regarding the carclnogenlclty of
exposure :o methylchlorocarbonate by other routes were not located In the
available literature cited In Appendix A.
8.1.4. height of Evidence. There were neither human nor animal data
regarding the carclnogenlclty of methylchlorocarbonate by any route of
exposure; therefore, by applying the U.S. EPA (1986) guidelines for cancer
risk assessment, methylchlorocarbonate Is assigned to EPA Group D: not
classifiable as to human carclnogenlclty.
8.1.5. Quantitative Risk Assessments. The lack of Inhalation or oral
data regarding the carclnogenlclty of methylchlorocarbonate precludes
estimation of carcinogenic potencies for the chemical.
OlSOd
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08/28/89
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8.2. SYSTEMIC TOXICITY
8.2.1. Inhalation Exposure.
8.2.1.1. LESS THAN LIFETIME EXPOSURES (SU8CHRONIC) Gage (1970)
Intermittently exposed rats to 1, 5 or 20 ppm (4, 20 or 80 mg/ma) methyl-
chlorocartonate for 3 weeks. Adverse effects were not reported at 1 ppm,
nasal Irr tatlon and lethargy were reported at 5 ppm, and severe signs of
irritation and toxldty accompanied by hlstopathologlc lesions of the lungs
and kidneys were reported at 20 ppm. The experimental protocol did not
Include ccncurrent controls and used a very small number of animals and an
experimental period of Insufficient duration; therefore, this study should
not be usej In risk assessment.
Upon contact with moisture, methylchlorocarbonate Is expected to undergo
rapid hydrolysis to methanol and hydrochloric acid. Although methanol 1s
likely to be the more toxic product of degradation In the GI tract (Section
8.2.2.), It Is likely that hydrochloric acid may be at least as toxic as
methanol \»hen formed In the respiratory tract. Therefore, It 1s Inappro-
priate to derive an Inhalation RfD for methylchlorocarbonate by analogy to
either hydrochloric add or methanol. Data are Inadequate for derivation of
an RfD for subchronlc exposure to methylchlorocarbonate.
The ct.rrent methodology for generating dose/duration-response graphs
(Crockett et al., 1985} using the computer program by Durkln and Meylan
(1988) 1s not appropriate for Inhalation exposure, because exposure Is
expressed
-------
8.2.2. (ral Exposure.
8.2.2.1. LESS THAN LIFETIME EXPOSURES (SUBCHRONIC) Subchronlc oral
exposure Jata for methylchlorocarbonate were not located 1n the available
literature. U.S. EPA (1989) derived an RfD for subchronlc oral exposure to
methylchlcrocarbonate by analogy to methanol, based upon a 90-day gavage
study 1n -ats (TRL, 1986). In this study, no adverse effects were reported
with meth
-------
may occur U suggested by oral L05Q data. Oral LQ^Q values for methanol
In rats ringe from 5628-13000 mg/kg (Sax, 1984), about 2 orders of magnitude
higher than for methylchlorocarbonate. The acute oral toxldty of methyl-
chlorocart'onate In rats, therefore, appears not to be due to Us conversion
to metharol. This Inference supports the disparity between the oral
reported ID5Q and calculated NOAEL for methylchlorocarbonate.
The metabolism of methanol appears to be species-dependent. At least
for acute exposure to large dosages, nonprlmates apparently metabolize
methanol :o carbon dioxide more rapidly than do primates (U.S. EPA, 1987;
Roe, 1982 . These differences 1n metabolism appear to play a major role 1n
the type of toxic syndrome displayed. Primates accumulate formic add,
develop metabolic addosls and exhibit a latency period In the development
of the tcxlc sydrome. Nonprlmates simply display anesthesia followed by
recovery or death. It Is not known If the metabolic differences between
primates
-------
Data were not sufficient to generate dose/duration-response graphs for
methylchlcrocarbonate.
8.2.2.2. CHRONIC EXPOSURES -- U.S. EPA (1989) attempted to derive an
RfD for chronic oral exposure to methylchlorocarbonate by analogy to
methanol see Section 8.2.2.1.). For the reasons outlined therein, H was
withdrawn pending further experimental toxldty evaluation of methylchloro-
carbonate.
0130d -25- 08/31/89
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9. REPORTABLE QUANTITIES
9.1. BASED ON SYSTEMIC TOXICITY
The tuxldty of methylchlorocarbonate was discussed 1n Chapter 6. The
only longer-term study located was a 3-week Inhalation experiment by Gage
(1970) 1n which rats Intermittently exposed to 20 ppm (80 mg/m3) had
severe Irritation and lung and kidney lesions, and rats exposed to 5 ppm (20
mg/m3) had nasal Irritation and lethargy. Concurrent controls were not
malntalnec, small numbers of rats were used and the experimental period was
too short for this study to be used In derivation of an RQ.
U.S. EPA (1989) was unable to derive an RfD for methylchlorocarbonate by
analogy to methanol, on the basis that Ingested methylchlorocarbonate
degrades -apldly to methanol (and hydrochloric add) In the presence of
water and that methanol 1s likely to be the more toxic metabolite In the GI
tract. Additionally It Is Inappropriate to derive a CS by analogy to
methanol >ecause CSs are not route-specific, and It Is likely that both
methanol ;.nd hydrochloric add would contribute to toxlclty associated with
Inhalatlor of methylchlorocarbonate. Therefore, no RQ 1s derived for the
chronic tcxlclty of methylchlorocarbonate.
9.2. BASED ON CARCINOGENICITY
There are neither human nor animal data regarding the carclnogenldty of
methylchlorocarbonate, which has therefore been assigned to U.S. EPA Group
D, not classifiable as to human carclnogenldty. U.S. EPA Group D compounds
are not given a hazard ranking and no RQ for carclnogenldty can be derived.
0130d -26- 08/31/89
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10. REFERENCES
Abrams, E. 1978. Carbonic and chloroformlc esters. In: Klrk-Othmer
Encyclopedia of Chemical Technology, 3rd ed., H. Grayson, Ed. John Wiley
and Sons, New York, NY. Vol. 4, p. 758-771.
Apaja, M. 1980. Evaluation of toxIcHy and cardnogenlclty of malonalde-
hyde. Acti Univ. Ouluensls Ser. D 55. (Cited In U.S. EPA, 1987)
Atkinson, R. 1987. A structure-activity relationship for the estimation of
rate consiants for the gas-phase reactions of OH radicals with organic
compounds. Int. J. Chem. Kinetics. 19: 799-828.
Atkinson, R., S.R. Aschmann and J.N. Pitts. Jr. 1984. Kinetics of the
reactions of naphthalene and blphenyl with OH radicals and Q~ at 294°K.
Environ. Scl. Techno!. 18: 110-113.
Black, K.A., J.T. Eells. P.E. Noker et al. 1985. Role of hepatic tetra-
hydrofolat< In the species difference In methanol toxlclty. Proc. Natl.
Acad. Scl. U.S.A. 82: 3854-3858. (Cited In U.S. EPA, 1967)
Cameron, A.M.. O.G. Nllsen, E. Haug and K.8. Elk-Nes. 1984. Circulating
concentrations of testosterone, lutelnlzlng hormone and follicle stimulating
hormone In male rats after Inhalation of methanol. Arch. Toxlcol. Suppl.
7: 441-443. (Cited 1n U.S. EPA, 1987)
0130d -27- 08/28/89
-------
Castro, E.A. and R.B. Hoodie. 1974. Kinetics of hydrolysis and amlnolysls
of methyl chloroformate 1n aqueous solution. J. Chem. Soc., Perkln Trans.
2(6); 658 661.
Clayton, i.O. and F.E. Clayton, Ed. 1981. Patty's Industrial Hygiene and
Toxicology, 3rd ed. John Wiley & Sons, New York. p. 2384-2390.
Crockett, P.M., B. KlUan, K.S. Crump and R.B. Howe. 1985. Descriptive
methods for using data from dissimilar experiments to locate a no-adverse-
toxlc-effect region 1n the dose-duration plane. Prepared by K.S. Crump and
Company, :nc., under Contract No. 6807-007 for Environmental Criteria and
Assessment Office, U.S. EPA, Cincinnati, OH.
Durkln, P and M. Meylan. 1988. User's guide for D2PLOT: A program for
dose/duration graphs. Prepared by Chemical Hazard Assessment Division,
Syracuse Fesearch Corporation under Contract No. 68-0004 for Environmental
Criteria aid Assessment Office. U.S. EPA, Cincinnati, OH.
Eells, J.I., K.A. Black, C.E. Tedford and T.R. Tephly. 1983. Hethanol
toxlclty n the monkey: Effects of nitrous oxide and methlonlne. J.
Pharmacol. Exp. Ther. 227: 349-353. (Cited In U.S. EPA, 1987)
Flnkel, A.J., Ed. 1983. Hamilton and Hardy's Industrial Toxicology, 4th
ed. John IIMght, Boston, MA. p. 179.
Gage, J.C. 1970. Subacute Inhalation toxIcUy of 109 Industrial chemicals.
Br. J. Ind. Hed. 27(1): 1-18.
0130d -28- 08/30/89
-------
GUger, A.P. and A.M. Potts. 1955. Studies on the visual toxldty of
methanol: V. The role of addosls \n experimental methanol poisoning. Am.
J. Ophthaniol. 39: 63-86. (Cited In U.S. EPA, 1987)
Goodman, ;.I. and T.R. Tephly. 1970. Peroxldatlve oxidation of methanol In
human I1v?r: The role of hepatic mlcrobody and soluble oxldases. Res.
Commun. Chem. Pathol. Pharmacol. 1: 441-450. (Cited In U.S. EPA, 1987)
Gurova, A.I., N.P. Alekseeva and O.E. Gorlova. 1977a. Data for the assess-
ment of the toxldty of methylchloroformate. Gig. SanH. 5: 97-99. (Taken
from PESTA3 77:2417)
Gurova, A.I., N.P. Alekseeva and O.E. Gorlova. 1977b. Data on the assess-
ment of mfthylchloroformate toxldty. Gig. SanH. 5: 97-99. (Taken from
HEEP 78:59U5)
Gurova, A.I., N.P. Alekseeva and O.E. Gorlova. 1977c. Data on assessing
the toxlclvy of methylchloroformate. G1g. SanH. 5: 97-99. (CA 87:0168787)
Hawley, G.G. 1981. The Condensed Chemical Dictionary. 10th ed. Van
Nostrand Rdnhold Co., New York, NY. p. 673-674.
Infurna, R. and B. Weiss. 1986. Neonatal behavioral toxldty 1n rats
following prenatal exposure to methanol. Teratology. 33: 259-265. (Cited
1n U.S. EPJ, 1987)
0130d -29- 08/28/89
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Kolvusalo. H. 1970. Hethanol. In: International Encyclopedia of Pharma-
cology anJ Therapeutics: Vol. 2, Alcohols and Derivatives. Pergamon Press,
New York. p. 465-505. (CHed 1n U.S. EPA, 1987)
Lee, E.W., C.D. Garner and W.M. Dereskl. 1987. A rat model for the study
of methane! visual neurotoxlclty. lexicologist, 7: 97. (Cited 1n U.S.
EPA, 1987]
Makar, A.E. and T.R. Tephly. 1977. Methanol poisoning. VI: Role of follc
add In :he production of methanol poisoning 1n the rat. J. Toxlcol.
Environ. Health. 2: 1201-1209. (Cited In U.S. EPA, 1987)
Nelson, B.K., U.S. BMghtwell. M.S. Mackenzie, et al. 1985. Teratologlcal
assessment of methanol and ethanol at high Inhalation levels In rats. Fund.
Appl. Tox1:ol. 5(4): 727-736. (CHed 1n U.S. EPA, 1987)
NIOSH (National Institute for Occupational Safety and Health). 1988. RTECS
(Registry Df Toxic Effects of Chemical Substances). Hethylchlorocarbonate,
CAS Registry No. 79-22-1. Online.
Palese, H. and T.R. Tephly. 1975. Metabolism of formate 1n the rat. J.
Toxlcol. Ervtron. Health. 1: 13-24. (CHed In U.S. EPA, 1987)
Queen, A. 1967. Kinetics of the hydrolysis of acyl chlorides In pure
water. Car. 0. Chem. 45(14): 1619-1629.
R5e, 0. 1)82. Species differences 1n methanol poisoning. CRC Crlt. Rev.
Toxlcol. 10(4): 275-286.
0130d -30- 08/30/89
-------
Sandmeyer, E.E. and C.J. Klrwln, Jr. 1981. Esters. IJK. Patty's Industrial
Hygiene and Toxicology, IIA, 3rd ed, 6.D. Clayton and F.E. Clayton, Ed.
John W1lej and Sons, Inc., New York. p. 2384-2390, 2400-2412.
Sax, N.I., Ed. 1984. Dangerous Properties of Industrial Materials, 6th ed.
Van Nostrand Relnhold Co., New York. p. 1764-1765.
Schuckmann, P. 1972. Symptomatic* of methylchloroformate Intoxication.
Zentralbl Arbeltsmed Arbeltsschutz. 22(3): 74-76. (Taken from HEEP
73:00365)
Smith, S.I., S.J.M. Smith and B.M. Buckley. 1981. Combined formate and
lactate acldosls In methanol poisoning (letter). Lancet. 8258: 1295-1296.
(Cited In J.S. EPA, 1967)
SRI (Starrord Research Institute). 1988. 1988 Directory of Chemical
Producers. United States of America. SRI International, Menlo Park, CA.
p. 777.
TRL (ToxUlty Research Laboratory). 1986. Rat Oral Subchronlc ToxicHy
Study with Methanol. Office of Solid Waste, U.S. EPA, Washington, DC.
U.S. EPA. 1977. TSCAPP (TSCA Plant and Production) Database. On-line: Hay
13, 1988.
U.S. EPA. 1980. Guidelines and Methodology Used In the Preparation of
Health Effect Assessment Chapters of the Consent Decree Water Criteria
Documents. Federal Register. 45(231): 79347-79357.
0130d -31- 08/28/89
-------
U.S. EPA. 1984. Methodology and Guidelines for Ranking Chemicals Based on
Chronic Toxlclty Data. Prepared by the Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for
the Off1c< of Emergency and Remedial Response, Washington, DC.
U.S. EPA. 1985. Physical-chemical properties and categorization of RCRA
wastes ac:ord1ng to volatility. U.S. EPA, Office of A1r Quality Planning
and Standards RTP, NC. EPA 450/3-85-007. NTIS, PB85-204527, p. 35, 43.
U.S. EPA. 1986. Guidelines for Carcinogen Risk Assessment. Federal
Register. 51(185): 33992-34003.
U.S. EPA. 1987. Summary Review of Health Effects Associated with Methanol:
Health Issue Assessment. Prepared by the Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office, Research Triangle
Park, NC =or the Office of Air Quality Planning and Standards, Washington,
DC.
U.S. EPA. 1988. SANSS (Structure and Nomenclature Search System). Data
base. On-Hne: May 13, 1988.
U.S. EPA. 1989. Integrated Risk Information System (IRIS). Online.
Office of Health and Environmental Assessment, Environmental Criteria and
Assessment Office, Cincinnati, OH.
0130d -32- 08/31/89
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U.S. EPA/3WRS (Environmental Protection Agency/Office of Nater Regulations
and Standards}. 1985. Guidelines for Deriving Numerical National Water
Quality Criteria for the Protection of Aquatic Organsms and Their Uses.
EnvUonmer tal Protection Agency, Washington, DC. 106 p.
USITC (U.S. International Trade Commission). 1987. Synthetic Organic
Chemicals. United States Production and Sales, 1986. USITC Publ. 2009,
Washlngtor, DC. p. 229.
Vedder, E.B. 1925. Medical Aspects of Chemical Warfare. Hill lams and
W1lk1ns, Balltmore, MD. (Cited 1n Sandmeyer and Klrwln, 1981)
Vernot, E.H., J.D. HacEwen, C.C. Haun and E.R. Klnkead. 1977. Acute
toxlclty i nd skin corrosion data for some organic and Inorganic compounds
and aqueous solutions. Toxlcol. Appl. Pharmacol. 42(2): 417-424.
0130d -33- 08/31/89
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APPENDIX A
LITERATURE SEARCHED
This HEED Is based on data Identified by computerized literature
searches cf the following:
CHEMLINE
TSCATS
CASR online (U.S. EPA Chemical Activities Status Report)
TOXLINE
TOXLIT
TOXLIT 65
RTECS
OHM TADS
STORET
SRC Environmental Fate Data Bases
SANSS
AQUIRE
TSCAPP
NTIS
Federal Register
CAS ONLINE (Chemistry and Aquatic)
HSDB
SCISEARCH
Federal Research In Progress
These sear:hes were conducted In October, 1987, and the following secondary
sources we*e reviewed:
ACGIH (American Conference of Governmental Industrial Hyglenlsts).
1986. Documentation of the Threshold Limit Values and Biological
Exposure Indices, 5th ed. Cincinnati. OH.
ACGIH (American Conference of Governmental Industrial Hyglenlsts).
1987. TLVs: Threshold Limit Values for Chemical Substances In the
Work invlronment adopted by ACGIH with Intended Changes for
1987-l
-------
Clayton, 6.0. and F.E. Clayton, Ed. 1982. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed.t Vol. 2C. John Wiley and
Sons, NY. p. 3817-5112.
Grays<
-------
In adiltlon, approximately 30 compendia of aquatic toxiclty 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.
Johnscn. W.W. and M.T. Flnley. 1980. Handbook of Acute Toxiclty
of Chemicals to Fish and Aquatic Invertebrates. Summaries of
Toxiclty Tests Conducted at Columbia National Fisheries Research
Laboratory. 1965-1978. U.S. Dept. Interior, Fish and Wildlife
Serv. Res. Publ. 137, Washington, DC.
HcKee, J.E. and H.W. Wolf. 1963. Water
Prepared for the Resources Agency of
Quality Control Board. Publ. No. 3-A.
Quality Criteria, 2nd ed.
California, State Water
Plmental, 0. 1971. Ecological Effects of Pesticides on Non-Target
Species. Prepared for the U.S. EPA, Washington, DC. PB-269605.
SchneUer, B.A. 1979. Toxicology Handbook. Mammalian and Aquatic
Data. Book 1: Toxicology Data. Office of Pesticide Programs, U.S.
EPA, WiShlngton, DC. EPA 540/9-79-003. NTIS PB 80-196876.
0130d
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08/28/89
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