TECHNICAL REPORT DATA
ffltfte rttd liutruettons on Hie rtveru before completing)
1. REPORT NO.
tPA/600/8-88/036
2.
3. RECIPIENT'S ACCESSION NO.
PB88-182852/AS
V TITLE AND SUBTITLE
Health Effects Assessment for Ethyl Chloride
6. REPORT DATE
«. PERFORMING ORGANIZATION CODE
7 AUTMOR(S)
«. PERFORMING ORGANIZATION REPORT NO.
9 PERFORMING ORGANIZATION NAME AND ADDRESS
10. PROGRAM ELEMENT NO.
11. CONTRACT/GRANT NO.
12. SPONSORING AGENCY NAME AND ADDRESS
13. TYPE OF REPORT AND PERIOD COVERED
Environmental Criteria and Assessment Office
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati. OH 45268
14. SPONSORING AGENCY CODE
EPA/600/22
15. SUPPLEMENTARY NOTES
16. ABSTRACT
This report summarizes and evaluates information relevant to a preliminary interim
assessment of adverse health effects associated with specific chemicals or compounds.
The Office of Emergency and Remedial Response (Superfund).uses these documents in
preparing cost-benefit analyses under Executive Order 12991 for decision-making under
CERCLA. All estimates of acceptable intakes and carcinogenic potency presented in
this document should be considered "as preliminary and reflect limited resources
allocated to this project. The intent in these assessments is to suggest acceptable
exposure levels whenever sufficient data are available. The interim values presented
reflect the relative degree of hazard associated with exposure or risk to the
chemical(s) addressed. Whenever possible, two categories of values have been
estimated for systemic toxicants (toxicant'; for which cancer is not the endpoint of
concern). The first, RfD$ or subchronic reference dose, is an estimate of an exposure
level that would not be expected to cause adverse effects when exposure occurs during
a limited time interval. The RfD is an estimate of an exposure level that would not
be expected to cause adverse effects when exposure occurs for a significant portion
of the lifespan. For compounds for which there is sufficient evidence of
carcinogenicity, qi*s have been computed, if appropriate, based on oral and
inhalation data if available.
7.
KEY WORDS AND DOCUMENT ANALYSIS
oucMirrofts
b. IDENTIFIERS/OPEN ENDED TERMS C. COSATI Field/Group
18. DISTRIBUTION STATEMENT
Public
19. SECURITY CLASS (This Report)
Unclassified
21. NO. OF PAGES
20. SECURITY CLASS fTHitpagej
Unclassified
22. PRICE
EPA Farm 2220-1 (R«». 4-77) pncvioui COITION i»
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EPA/600/8-88/036
July, 1987
HEALTH EFFECTS ASSESSMENT
FOR ETHYL CHLORIDE
ENVIRONMENTAL CRITERIA AND ASSESSMENT OFFICE
OFFICE OF HEALTH AND ENVIRONMENTAL ASSESSMENT
OFFICE OF RESEARCH AND DEVELOPMENT
U.S. ENVIRONMENTAL PROTECTION AGENCY
CINCINNATI, OH 45268
U.S. Environmental Protection Agency
E-.S. ion 5 , LlVvury ( 5PL - 1C *
230 S. Deaiborn bti-eefc, Hoom 1670
Chicago, IL 60604
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DISCLAIMER
This document has been reviewed • 1n accordance with the U.S.
Environmental Protection Agency's peer and administrative review policies
and approved for publication. Mention of trade names or commercial products
does not constitute endorsement or recommendation for use.
11
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PREFACE
This report summarizes and evaluates Information relevant to a prelimi-
nary Interim assessment of adverse health effects associated with ethyl
chloride. All estimates of acceptable Intakes and carcinogenic potency
presented 1n this document should be considered as preliminary reflecting
limited resources allocated to this project. Pertinent toxlcologlc and
environmental data were located through on-Hne literature searches of the
TOXLINE and the CHEMFATE/OATALOG data bases. The basic literature searched
supporting this document Is current up to Hay, 1986. Secondary sources of
Information have also been relied upon 1n the preparation of this report and
represent large scale health assessment efforts that entail extensive peer
and Agency review. The following Office of Health and Environmental Assess-
ment (OHEA) sources have been extensively utilized:
U.S. EPA. 1980a. Ambient Water Quality Criteria for Chlorinated
Ethanes. Prepared by the Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office,
Cincinnati, OH for the Office of Water Regulations and Standards,
Washington, DC. EPA 440/5-80-029. NTIS PB81-117400.
U.S. EPA. 1980b. Hazard Profile for Chloroethane. Prepared by
the Office of Health and Environmental Assessment, Environmental
Criteria and Assessment Office, Cincinnati, OH for the Office of
Solid Waste, Washington, DC.
U.S. EPA. 1986a. Summary Review of Health Effects Associated with
Monochloroethane: Health Issue Assessment. Internal Review Draft.
Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria, and- Assessment Office, Research Triangle
Park, NC for the Office of A1r Quality Planning and Standards,
Washington, DC.
The Intent In these assessments Is to suggest acceptable exposure levels
for noncardnogens and risk cancer potency estimates for carcinogens
whenever sufficient data were available. Values were not derived or larger
uncertainty factors were employed when the variable data were limited In
scope tending to generate conservative (I.e., protective) estimates.
Nevertheless, the Interim values presented reflect the relative degree of
hazard or risk associated with exposure to the chemlcal(s) addressed.
Whenever possible, two categories of values have been estimated for
systemic toxicants (toxicants for which cancer Is not the endpolnt of
concern). The first, RfD$ (formerly AIS) or subchronlc reference dose, Is
an estimate of an exposure level that would not be expected to cause adverse
effects when exposure occurs during a limited time Interval (I.e., for an
Interval that does not constitute a significant portion of the Hfespan).
111
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,Jh- ui exposure estimate has not been extensively used, or rigorously
defined, as previous risk assessment efforts have been primarily directed
towards exposures from toxicants In ambient air or water whe»re lifetime
exposure 1s assumed. Animal data used for RFD$ estimates generally
Include exposures with durations of 30-90 days. Subchronlc human data are
rarely available. Reported exposures are usually from chronic occupational
exposure situations or from reports of acute accidental exposure. These
values are developed for both Inhalation (RfD$j) and oral (RfOgQ)
exposures.
The RfO (formerly AIC) Is similar In concept and addresses chronic
exposure. It Is an estimate of an exposure level that would not be expected
to cause adverse effects when exposure occurs for a significant portion of
the Hfespan [see U.S. EPA (1980c) for a discussion of this concept]. The
RfD Is route-specific and estimates acceptable exposure for either oral
(RfDn.) or Inhalation (RfDj) with the Implicit assumption that exposure
by other routes 1s Insignificant.
Composite scores (CSs) for noncarclnogens have also been calculated
where data permitted. These values are used for Identifying reportable
quantities and the methodology for their development Is explained 1n U.S.
EPA (1983).
For compounds for which there Is sufficient evidence of cardnogenldty
RfD$ and RfO values are not derived. For a discussion of risk assessment
methodology for carcinogens refer to U.S. EPA (1980c). Since cancer Is a
process that Is not characterized by a threshold, any exposure contributes
an Increment of risk. For carcinogens, q-j*s have been computed, If
appropriate, based on oral and Inhalation data If available.
1v
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ABSTRACT
Limited subchronlc toxlcity testing of ethyl chloride administered by
Inhalation de.flnes only free-standing NOELs. There are no carclnogenlclty
or chronic toxldty data on ethyl chloride, although the NTP (1986) Is
currently completing a chronic bloassay. Risk assessment for carcinogenic
or chronic toxldty effects may be performed on the results of this
bloassay. The liver, CNS and heart appear to be target organs.
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ACKNOWLEDGEMENTS
The Initial draft of this report was prepared by Syracuse Research
Corporation under Contract No. 68-03-3112 for EPA's Environmental Criteria
and' Assessment Office, Cincinnati, OH. Or. Christopher DeRosa and Karen
Blackburn were the Technical Project Monitors and John Helms (Office of
Toxic Substances) was the Project Officer. The final documents In this
series were prepared for the Office of Emergency and Remedial Response,
Washington, OC.
Scientists from the following U.S. EPA offices provided review comments
for this document series:
Environmental Criteria and Assessment Office, Cincinnati, OH
Carcinogen Assessment Group
Office of Air Quality Planning and Standards
Office of Solid Waste
Office of Toxic Substances
Office of Drinking Water
Editorial review for the document series was provided by the following:
' Judith Olsen and Erma Durden
Environmental Criteria and Assessment Office
Cincinnati, OH
Technical support services for the document series was provided by the
following:
Bette Zwayer, Jacky Bohanon and K1m Davidson
Environmental Criteria and Assessment Office
Cincinnati, OH
vl
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TABLE OF CONTENTS
7.
2.
5.
6.
ENVIRONMENTAL CHEMISTRY AND FATE
ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS . . .
2.1. ORAL
2.2. INHALATION
TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. HUMAN
3.2. ANIMALS
3.2.1. Oral
3.2.2. Inhalation
CARCINOGENICITY
4.1. HUMAN AND ANIMAL DATA
4.2. OTHER RELEVANT DATA
4.3. WEIGHT OF EVIDENCE
REGULATORY STANDARDS AND CRITERIA
RECOMMENDATIONS
REFERENCES
Page
1
... 3
... 3
... 3
... 4
... 4
4
... 4
4
, , , 6
... 6
... 6
6
7
8
. . . 9
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NOAEL
NOEL
PEL
ppm Omissible exposure
RfO PartS "er»"Hon
RfOs ^rence dose
STEL SUbChr°n1c Deference dose
TLV S^t-term exposure level
TWA ThreSho]d "»1t value
averagi
e
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Selected physical
'"to" I" Table ,.,. ""'ronmenu, fau ^
at">osphere.
K
, ; ,r
Vo7atnizatlon of i } esed the
]
o i
cm de*P to b ] ppm
« «- .»„ „ — n '
0087h
-1-
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TABLE 1-1
Selected Physical and Chemical Properties and
Environmental Fate of Ethyl Chloride
Property
Value
Reference
CAS number:
Chemical class:
Molecular weight:
Vapor pressure:
Water solubility:
Log octanol/water
partition coefficient:
Bloconcentratlon factor;
Soil adsorption
coefficient:
75-00-3
halogenated aliphatic
hydrocarbon
64.52
1000 mm Hg at 20°C :
5710 mg/i at 20°C
1.43
5-7 (estimated)
33-143 (estimated)
Verschueren, 1983
Mackay and Sh1u, 1981
Hansch and Leo, 1985
Lyman et al., 1982
Lyman et al. ,r 1982
Half-life:
Air
Water
Soil
23-26 days
~ hours
NA
Atkinson et al
Butler et al.,
DUlIng, 1977
'.":/
., 1979;
1978
NA = Not available
0087h
-2-
06/2
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2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS
2.1. ORAL
Quantitative data regarding the rate or extent of absorption of ethyl
chloride by oral administration could not be located In the available
literature. Sax (1984) reported that ethyl chloride is rapidly absorbed
Into the body after oral intake.
2.2. INHALATION
Sax (1984) and Konletzko (1984) reported that ethyl chloride is rapidly
absorbed after inhalation.
0087h -3- 12/1
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3. TOXICITY IN HUMANS MO EXPERIMENTAL ANIMALS
3.7. HUMAN
Epldemlologlcal data on the effects of ethyl chloride exposure by any
route of administration could not be located In the available literature.
Lehmann and Flury (1943) reported that0 acute exposure to ethyl chloride
vapors has narcotic effects In man. Twelve-minute exposure to 19,000 ppm
(50 g/m3) caused weak analgesia; stupor, eye Irritation and stomach cramps
accompanied two Inhalations of 40,000 ppm (106 g/m3).
3.2. ANIMALS
3.2.1. Oral. Data from animal studies are limited to effects from
subchronlc and acute exposures. Adams et al. (1939) found no adverse
effects of 0.5 or 1.0 g/kg ethyl chloride given to an unspecified number of
rabbits as 60 oral doses. No further details were provided. Assuming the
rabbits were c'osed 5 times/day over a 12-day period and weighed 2.0 kg, a
NOAEL of 700 mg/kg/day can be calculated.
3.2.2. Inhalation. NTP (1986) Is currently concluding toxldty and
cancer chronic Inhalation bloassays using rats and mice. Relevant toxlclty
data that would be useful In quantitative risk assessment may result from
this study.
Adams et al, (1939) found no effects In rats or rabbits during or after
Inhalation exposure to 25.4 mg/i (25.4 g/m3) ethyl chloride, 7.5-8.0
hours/day, 5 days/week for 6.5 months. Endpolnts Included weekly weights,
gross and microscopic examination, and ophthalmoscoplc examination (rabbits
only). Assuming a rat weighs 0.35 kg and Inhales 0.223 mg/m3/day (U.S.
EPA, 1980c), the concentration used corresponds to a NOAEL of -3.73 g/kg/day.
A report from tfte Russian literature, however, Indicates that adverse
effects occur at much lower levels. Troshlna (1966) exposed rats to 0.5
mg/i (570 mg/m3) 4 hours/day for 6 months and reported "changes In 11-
0087h -4- 06/'
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function"
'•""
."cre.se.,
-...«,„
""»•»«
,0
.,.„,
0087h
cjr
-Htt.tle
-5-
06/?
-------
No e»,dence for deve^enta! or reproduce twlclt, has been reported
for ethyl chloride to date.
0087h t
-*- 06/24/87
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4. CARCINOGENICITY
4.1. HUNAN AND ANIMAL DATA
Pertinent data regarding the carcinogenic potency of ethyl chloride In
humans or experimental animals, by any route of exposure, could not be
located In the available literature. The NTP (1986) completed a 2-year
bloassay of ethyl chloride using rats and mice exposed by Inhalation;
chronic quality assessment Is currently 1n progress.
4.2. OTHER RELEVANT DATA
Ethyl chloride 1n the vapor phase was mutagenlc to four strains of
Salmonella typhlmurlum, both with and without metabolic activation (Rlcclo
et al., 1983). It was, however, negative In a Balb/c-3T3 cell transforma-
tion assay (Tu et al., 1985).
4.3. HEIGHT OF EVIDENCE
Because there are no available cancer data on ethyl chloride, the com-
pound should be classified In IARC Group 3, or U.S. EPA Group D (U.S. EPA,
1986c). These categories are reserved for chemicals with Inadequate
evidence for evaluation of human carclnogenldty. Ethyl chloride should be
reclasslfled when the results from the NTP (1986) bloassay become available.
0087h -7- 06/24/87
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5. REGULATORY STANDARDS AND CRITERIA
The U.S. EPA (1980a) did not derive an ambient water quality criteria
for ethyl chloride because of the lack of sufficient mammalian toxlcologlcal
data. Based on the limited available data, the Agency stated that 1t was
one of the least toxic of the chloroethanes.
The ACGIH (1985) adopted a TLV-TWA for 8-hour exposure to ethyl chloride
of 1000 ppm (-2600 mg/m3). In Us documentation of the TLV-THA, the ACGIH
(1986) cited acute studies (Lehmann and Flury, 1943) In humans showing weak
analgesia at 19,000 ppm and slight symptoms of toxldty at 13,000 ppm. The
committee decided to delete a former STEL of 1250 ppm (-3250 mg/m3) until
better toxlcologlcal and Industrial hygiene data become available.
The OSHA PEL (OSHA, 1985) Is 1000 ppm for an 8-hour exposure.
0087h -8- 06/24/87
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6. RECOMMENDATIONS
The two subchronlc studies of ethyl chloride exposure (Adams et al.,
1939; NTP, 1981) define only free-standing NOELs, and are therefore of
limited value 1n the calculated RfD- values. The significance of slight
hepatic enlargement and narcosis In rats exposed for 2 weeks at lower
concentrations (Landry et al., 1982) Is unclear. No other available data
are useful for quantitative risk assessment.
Estimation of carcinogenic potency should be made 1f the results of the
NTP bloassay are positive In either of the two tested species. Because the
U.S. EPA (1986b) based risk assessment on the findings that methyl chloride
produced kidney tumors In mice, the Issue of the cardnogenlclty of the
related ethyl chloride Is a cause for concern.
If the results of the NTP bloassay are not sufficient for estimation of
carcinogenic potential, a threshold toxlclty-based RfD may be estimated.
The data reviewed In this document suggest that the Hver, the CNS and
possibly the heart may be target organs for the toxldty of ethyl chloride.
The high vapor pressure of this compound (-1000 mm Hg at 20°C) reflects Us
volatility and suggests that Inhalation exposure 1s probably more likely
than oral exposure.
0087h -9- 06/26/87
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7. REFERENCES
AC6IH {American Conference of Governmental Industrial Hyglenlsts). 1985.
TLVs: Threshold limit values for chemical substances In the work environment
adopted by ACGIH with Intended changes for 1985-1986. Cincinnati, OH.
p. 18.
ACGIH (American Conference of Governmental Industrial Hyglerilsts). 1986.
Documentation of the Threshold L1mH Values and Biological Exposure Indices,
5th ed. Cincinnati, OH. p. 247.
Adams, E.M., V.K. Rowe and H.C. Spencer. 1939. Experimental Investigation
of the Toxlclty of Ethyl Chloride. The Dow Chemical Company. (Cited In
Landry et al., 1982; Betso, 1986)
Atkinson, R., K.R. DarnalU A.C. Lloyd, A.M. Winer and J.N. Pitts, Jr.
1979. Kinetics and mechanisms of the reactions of the hydroxyl radical with
organic compounds In the gas phase. Adv. Photochem. 11: 375-488.
Betso, J. 1986. Letter from J. Betso, Dow Chemical Co. to Dr. Paul
Goetchlus, Syracuse Research Corporation, dated June 5, 1986.
Butler, R., 1.3. Solomon and A. Snelson. 1978. Rate constants for the
reaction of OH with halocarbons 1n the presence of 02 and N2. J. Air
Pollut. Control Fen. 28: 1131-1133.
OQ87h -10^ 06/24/87
-------
011 ling, W.U 1977. Interphase transfer processes. II. Evaporation rates
of chloromethanes, ethanes, ethylenes, propanes and propylenes from dilute
aqueous solutions. Comparisons with theoretical predictions. Environ. Scl.
Technol. 11: 405-409.
Doerlng, H.J. 1975. Reversible and Irreversible forms of contractile
failure caused by disturbances by general anesthetics In myocardlal ATP
utilization. Recent Adv. Stud. Car. Stwet. Metab. 5: 395. (Cited In U.S.
EPA, 1980a)
Hansch, C. and A.J. Leo. 1985. MedChem Project Issue #26. Pomona College,
Claremont, CA.
Konletzko, H. 1984. Chlorinated ethanes: Sources, distribution, environ-
mental Impact and health effects. In.: Hazard Assessment of Chemicals
Current Developments, J. Saxena, Ed., Vol. 3. Academic Press, Inc., New
York. p. 401-448. (Cited In U.S. EPA, 1986a)
Landry, T.D., J.A. Ayres, K.A. Johnson and J..M. Wall. 1982. Ethyl
chloride: A two-week Inhalation toxldty study and effects on liver
non-protein gulthydyl concentrations. Fund. Appl. Toxlcol. 2: 230-234.
Lehmann, K.E. and F. Flury. 1943. Toxicology and Hygiene of Industrial
Solvents. Translated by E. Keng and H.F. Smyth, Jr. The Williams and
WHklns Co., Baltimore, MD. p. 154-157. (.Cited In ACGIH, 1986)
0087h -11- 06/24/87
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Lyman, W.J., W.F. Reehl and D.H. Rosenblatt. 1982. Handbook of Chemical
Property Estimation Method. Environmental Behavior of Organic Compounds,
McGraw Hill Book Co., New York. p. 4-9, 5-5.
Mabey, W. and T. Mill. 1978. Critical review of hydrolysis of organic
compounds In water under environmental conditions. J. Phys. Chem. Ref.
Data. 7: 383-415.
Mackay, D. and W.Y. Shlu. 1981. A critical review of Henry's Law Constant
for chemicals o'f environmental Interest. J. Phys. Chem. Ref. Data. 19:
1175-1199.
NTP (National Toxicology Program). 1981. Prechronlc (90-day) test phase
review for ethyl chloride. NIH, Bethesda, MD. (Cited In Landry et-al..
1982)
NTP (National Toxicology Program). 1986. Management Status Report.
3/-12/86.
OSHA (Occupational Safety and Health Administration). 1985. OSHA Safety
and Health Standards (29 CFR 1910.1000).
R1cdo, F., A. Griffin, K. Mortelmous and H.A. Mllaran. 1983. A compara-
tive mutagenldty study of volatile hulogenated hydrocarbons using different
metabolic activation systems. Environ. Mutagen. 5: 472.
0087h -12- 06/24/87
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Sax, N.I., Ed. 1984. Dangerous Properties of Industrial Materials, 6th ed.
Van Nostrand Relnhold Co., New York. p. 1328.
Sayers, R.R., W.P. Yant, B.G. Thomas and L.B. Berger. 1929. No title pro-
vided. U.S. Publ. Health Bull. No. 185. (CHed 1n Torkelson and Rowe, 1981)
Torkelson, T.R. and V.K. Rowe. 1981. Ethyl chloride. Irt: Patty's Indus-
trial Hygiene and Toxicology, Vol. 28, 3rd ed., G.O. Clayton and F.E.
Clayton, Ed. John Wiley and Sons Inc., New York. p. 3480-3483.
Troshlna, M.M. 1966. Determination of maximum permissible concentration of
ethyl chloride In the atmosphere of work premises. Glglena Truda 1 Prof
Zaboleganla. 10: 37-42. (From B1ol. Abstr. translation) (CHed In Landry
et al., 1982)
Tu, A.S., T.A. Murray, K.M. Hatch, A. S1vak and H.A. Mllman. 1985. In
vitro transformation of 8AL8/C-3T3 cells by chlorinated ethanes and
ethylenes. Cancer Lett. 28: 85-92.
U.S. EPA. 1980a. Ambient Water Quality Criteria for Chlorinated Ethanes.
Prepared by the Office of Health and Environmental Assessment, Environmental
Criteria and Assessment Office, Cincinnati, OH for the Office of Water
Regulations and Standards, Washington, DC. EPA 440/5-80-029. NTIS
PB81-117400.
0087h -13- 06/24/87
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U.S. EPA. 1980b. Hazard Profile for Chloroethane. Prepared by the Office
of Health and Environmental Assessment, Environmental Criteria and
Assessment Office, Cincinnati, OH for the Office of Solid Waste, Washington,
DC.
U.S. EPA. 1980c. Guidelines and Methodology Used In the Preparation of
Health Effect Assessment Chapters of the Consent Decree Hater Criteria
Documents. Federal Register. 45(231): 49347-49357.
U.S. EPA. 1983. Methodology and Guidelines for Reportable Quantity Deter-
minations Based on Chronic Toxlclty Data. 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. 1986a. Summary Review of Health Effects Associated with Mono-
chloroethane: Health Issue Assessment. Internal Review Draft. Prepared by
the Office of Health and Environmental Assessment, Environmental Criteria
and Assessment Office Research Triangle Park, NC.
U.S. EPA. 1986b. Health and Environmental Effect Profile for Methyl
Chloride. Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH for the Office
of Solid Haste and Emergency Resp.onse, Washington, DC.
U.S. EPA. 1986c. Guidelines for Carcinogen Risk Assessment. Federal
Register. 51(185): 33992-34003.
0087h -14- 08/06/87
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Verschueren, K. 1983. Handbook on Environmental Data or Organic Chemicals,
2nd ed. Van Nostrand Relnhold, New York. p. 631.
p,~. ••-<-,, + -, 11
0087h -15- 08/03/87
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