EPA-540/1-86-041
Off'ce-of Research and Development
Office of Health and Environmental
Assessment
Environmental Criteria and
Assessment Office
Cincinnati OH 45268
Superfund
vvEPA
HEALTH EFFECTS ASSESSMENT
FOR 1,2-t-DICHLOROETHYLENE
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EPA/540/1-86-041
September 1984
HEALTH EFFECTS ASSESSMENT
FOR 1.2-T-DICHLOROETHYLENE
U.S. Environmental Protection Agency
Office of Research and Development
Office of Health and Environmental Assessment
Environmental Criteria and Assessment Office
Cincinnati, OH 45268
U.S. Environmental Protection Agency
Office of Emergency and Remedial Response
Office of Solid Waste and Emergency Response
Washington, DC 20460
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DISCLAIMER
This report has been funded wholly or In part by the United States
Environmental Protection Agency under Contract No. 68-03-3112 to Syracuse
Research Corporation. It has been subject to the Agency's peer and adminis-
trative review, and It has been approved for publication as an EPA document.
Mention of trade names or commercial products does not constitute endorse-
ment 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 1.2-t-
dlchloroethylene. All estimates of acceptable Intakes and carcinogenic
potency presented 1n this document should be considered as preliminary and
reflect limited resources allocated to this project. Pertinent toxlcologlc
and environmental data were located through on-Hne literature searches of
the Chemical Abstracts, TOXLINE, CANCERLINE and the CHEMFATE/DATALOG data
bases. The basic literature searched supporting this document 1s current up
to September, 1984. 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 Assessment (OHEA) sources have
been extensively utilized:
U.S. EPA. 1980a. Ambient Water Quality Criteria for Dlchloroethy-
lenes. Environmental Criteria Assessment Office, Cincinnati, OH.
EPA 440/5-80-041. NTIS PB 83-117525.
U.S. EPA. 1982. Reportable Quantity for 1,2-D1chloroethylene.
Prepared by the Environmental Criteria and Assessment Office,
Cincinnati, OH, OHEA for the Office of Solid Waste and Emergency
Response, Washington, DC.
U.S. EPA. 1983b. Hazard Profile for trans-1,2-D1chloroethylene.
Prepared by the Environmental Criteria and Assessment Office,
Cincinnati, OH, OHEA for the Office of Solid Waste and Emergency
Response, Washington, DC.
The Intent 1n these assessments Is to suggest acceptable exposure levels
whenever sufficient data were available. Values were not derived or larger
uncertainty factors were employed when the variable data were limited 1n
scope tending to generate conservative (I.e., protective) estimates. Never-
theless, the Interim values presented reflect the relative degree of hazard
associated with exposure or risk to the chemlcal(s) addressed.
Whenever possible, two categories of values have been estimated for sys-
temic toxicants (toxicants for which cancer Is not the endpolnt of concern).
The first, the AIS or acceptable Intake subchronlc, 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). This type of
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 where lifetime exposure 1s
assumed. Animal data used for AIS estimates generally Include exposures
with durations of 30-90 days. Subchronlc human data are rarely available.
111
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Reported exposures are usually from chronic occupational exposure situations
or from reports of acute accidental exposure.
The AIC, acceptable Intake chronic, 1s similar 1n concept to the ADI
(acceptable dally Intake). It 1s 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 (1980b) for a discussion
of this concept]. The AIC 1s route specific and estimates acceptable
exposure for a given route with the Implicit assumption that exposure by
other routes Is Insignificant.
Composite scores (CSs) for noncardnogens have also been calculated
where data permitted. These values are used for ranking reportable quanti-
ties; the methodology for their development 1s explained 1n U.S. EPA (1983a).
For compounds for which there 1s sufficient evidence of carclnogenlcHy,
AIS and, AIC values are not derived. For a discussion of risk assessment
methodology for carcinogens refer to U.S. EPA (1980b). Since cancer 1s a
process that 1s not characterized by a threshold, any exposure contributes
an Increment of risk. Consequently, derivation of AIS and AIC values would
be Inappropriate. For carcinogens, q-|*s have been computed based on oral
and Inhalation data 1f available.
1v
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ABSTRACT
In order to place the risk assessment 1n proper context, the reader Is
referred to the preface of this document. The preface outlines limitations
applicable to all documents of this series as well as the appropriate Inter-
pretation and use of the quantitative estimates.
Information concerning toxlcologlcal consequences of 1,2-t-dlchloroethy-
lene exposure 1s extremely limited. Data were Inadequate to estimate an AIS
or AIC for either the oral or Inhalation routes. A CS of 10.5 was derived
based on hlstopathologlcal changes 1n the liver and lungs of rats exposed
via Inhalation. This compound has not been tested for carc1nogen1dty. The
limited mutagenldty data are negative.
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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. Dr. Christopher DeRosa and Karen
Blackburn were the Technical Project Monitors and Helen Ball was the Project
Officer. The final documents In this series were prepared for the Office of
Emergency and Remedial Response, Washington, DC.
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 A1r 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:
Judith Olsen and Erma Durden
Environmental Criteria and Assessment Office
Cincinnati, OH
Technical support services for the document series was provided by:
Bette Zwayer, Pat Daunt, Karen Mann and Jacky Bohanon
Environmental Criteria and Assessment Office'
Cincinnati, OH
v1
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TABLE OF CONTENTS
1.
2.
3.
4.
5.
ENVIRONMENTAL CHEMISTRY AND FATE
ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS . . .
2.1.
2.2.
ORAL
INHALATION
TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1.
3.2.
3.3.
3.4.
SUBCHRONIC
3.1.1. Oral
3.1.2. Inhalation
CHRONIC
3.2.1. Oral
3.2.2. Inhalation
TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS. . . .
3.3.1. Oral
3.3.2. Inhalation
TOXICANT INTERACTIONS
CARCINOGENICITY '.
4.1.
4.2.
4.3.
4.4.
HUMAN DATA
4.1.1. Oral
4.1.2. Inhalation
BIOASSAYS
4.2.1. Oral
4.2.2. Inhalation
OTHER RELEVANT DATA
WEIGHT OF EVIDENCE
REGULATORY STANDARDS AND CRITERIA
Page
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. . . ' 3
. . . 3
3
4
4
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4
4
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. . . 4
. . . 5
. . . 5
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5
6
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6
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6
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TABLE OF CONTENTS (cont.)
RISK
6.1.
6.2.
6.3.
ASSESSMENT
ACCEPTABLE INTAKE SUBCHRONIC (AIS)
6.1.1. Oral
6.1.2. Inhalation
ACCEPTABLE INTAKE CHRONIC (AIC)
6.2.1. Oral
6.2.2. Inhalation
CARCINOGENIC POTENCY (q^*)
6.3.1. Oral
6.3.2. Inhalation
REFERENCES
Page
9
9
9
9
9
9
10
10
10
10
11
APPENDIX: Summary Table for 1,2-t-01chloroethylene 15
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LIST OF ABBREVIATIONS
ADI Acceptable dally Intake
AIC Acceptable Intake chronic
AIS Acceptable Intake subchronlc
BCF B1oconcentrat1on factor
CAS Chemical abstract service
CS Composite score
l.p. IntraperHoneal
ppm Parts per million
STEL Short-term exposure limit
TLV Threshold limit value
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1. ENVIRONMENTAL CHEMISTRY AND FATE
The relevant physical and chemical properties and environmental fate of
l,2-t-d1chloroethylene (CAS No. 156-60-5) are as follows:
Chemical class: halogenated aliphatic hydrocarbon
Molecular weight: 96.95
Vapor pressure at 25°C: 324 mm Hg (Torkelson and Rowe, 1981)
Water solubility at 20°C: 6300 mg/8. (Torkelson and Rowe, 1981)
Octanol/water
partition coefficient: 3 (estimated)
BCF: 0.5 (estimated)
Half-lives In
A1r: 2.1 days (Hendry and Kenley, 1979)
Water: 1-6 days (estimated)
The octanol/water partition coefficient value has been estimated from
the equation of Kenaga and Goring (1980) and the value of water solubility
data. Similarly, the value for the BCF has been estimated from the equation
of Velth et al. (1979) and the estimated octanol/water partition coefficient
value.
The half-lives of 1,2-t-d1chloroethylene, due to Us volatilization from
aquatic media, have been estimated from the reaction rate ratio (0.601) and
the oxygen reaeratlon rate of 0.19-0.96 day~ (Mabey et al., 1981).
Pertinent data regarding the fate of 1,2-t-d1chloroethylene 1n soil
could not be located 1n the available literature. Based on the behavior of
this compound In aquatic media, evaporation 1s expected to be the predomi-
nant loss process from the soil surface. In subsurface soil, blodegradatlon
of this compound 1s likely to be a slow process (Tabak et al., 1981), and
the compound 1s not likely to be sorbed strongly to soil because of Us low
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octanol/water partition coefflcent value. Therefore, the compound 1s expec-
ted to_Jeach from subsurface soil Into groundwater. Page (1981) reported
1,2-t-d1chloroethylene 1n groundwaters from New Jersey at a frequency of 51%.
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2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS
2.1. ORAL
Pertinent data regarding the oral absorption of 1,2-t-d1chloroethylene
could not be located In the available literature. The U.S. EPA (1980a)
estimates that "virtually 100 percent of ingested OCE may be absorbed
systemlcally," based on the studies of Daniel (1963) and Monster et al.
(1976) using trlchloroethylene.
2.2. INHALATION
Pertinent data regarding the absorption of 1,2-t-d1chloroethylene from
the respiratory tract could not be located In the available literature. The '
U.S. EPA (1980a) estimates that "35-50 percent of inhaled DCE may be
absorbed systemically," based on the studies of Daniel (1963) and Monster et
al. (1976) using trlchloroethylene.
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3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
3.1.1. Oral. Springer (1965) administered a mixture of 1,2-c-and
l,2-t-d1chloroethylene to rats for 7 weeks (0.05, 0.25, 0.5 or 1.0 g/kg).
It was not clear from the review 1f these were dally, weekly or total doses.
No adverse effects were reported at any dose. Pertinent data regarding the
subchronlc oral toxldty of pure 1,2-t-d1chloroethylene were not located In
the available literature.
3.1.2. Inhalation. In an unpublished study, Torkelson (1965) exposed
rats, rabbits, guinea pigs and dogs to atmospheres containing 60% 1,2-c- and
40% l,2-t-d1chloroethylene (500 or 1000 ppm) 7 hours/day, 5 days/week for 6
months. No adverse effects were observed on growth, mortality, organ
weights, body weight, hematology, clinical chemistry, gross pathology or
hlstopathology.
Freundt et al. (1977) exposed groups of six female Wlstar rats to atmo-
spheres containing 200 ppm 1,2-t-d1chloroethylene 8 hours/day, 5 days/week
for 1, 2, 8 or 16 weeks. The liver and lungs were examined hlstologlcally
at the end of each of these time periods. Progressive damage to the lungs
and fatty changes 1n the liver were observed. By 16 weeks, 3/6 animals
developed "severe" fatty changes 1n the liver, and 2/6 developed "slight"
fatty changes.
3.2. CHRONIC
3.2.1. Oral. Pertinent data regarding the chronic oral toxlclty of
1,2-td1chloroethylene were not located 1n the available literature.
3.2.2. Inhalation. Pertinent data regarding the chronic Inhalation toxldty
of 1,2-t-dlchloroethylene were not located In the available literature.
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3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
3.3.1. Oral. Pertinent data regarding the teratogenlcHy or other repro-
ductive effects of l,2-t-d1chloroethylene could not be located In the
available literature.
3.3.2. Inhalation. Pertinent data regarding the teratogenlcHy or other
reproductive effects of 1,2-t-d1chloroethylene could not be located 1n the
available literature.
3.4. TOXICANT INTERACTIONS
Pertinent data regarding the Interaction of 1,2-t-dlchloroethylene with
other toxicants could not be located 1n the available literature.
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4. CARCINOGENICITY
4.1. HUMAN DATA
4.1.1. Oral. Pertinent data regarding the cardnogenlcHy of orally
administered 1,2-t-d1chloroethylene 1n humans could not be located 1n the
available literature.
4.1.2. Inhalation. Pertinent data regarding the cardnogenlcHy of
Inhaled 1,2-t-dlchloroethylene 1n humans could not be located 1n the
available literature.
4.2. BIOASSAYS
4.2.1. Oral. Pertinent data regarding the carclnogenlclty of orally
administered 1,2-t-d1chloroethylene 1n experimental animals could not be
located In the available literature.
4.2.2. Inhalation. Pertinent data regarding the carclnogenlclty of
Inhaled 1,2-t-dlchloroethylene 1n experimental animals could not be located
1n the available literature.
4.3. OTHER RELEVANT DATA
Grelm et al. (1975) reported negative results for 1,2-t-d1chloroethylene
using Escherchla coll K12 as the Indicator organism. Cerna and Kypenova
(1977) ^.found 1,2-t-d1chloroethylene to be nonmutagenlc 1n Salmonella tester
strains, and this compound failed to Induce chromosomal aberrations as Indi-
cated by cytogenic analysis of bone marrow cells 1n mice following repeated
1.p. Injections.
4.4. WEIGHT OF EVIDENCE
Pertinent data regarding the carclnogenlclty of 1,2-t-d1chloroethylene
1n humans or animals could not be located 1n the available literature.
Using the criteria for evaluating the overall weight of evidence for car-
clnogenlclty to humans proposed by the Carcinogen Assessment Group of the
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U.S. EPA (Federal Register, 1984), 1,2-t-d1chloroethylene is most approprl
ately designated a Group D - Not Classified chemical.
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5. REGULATORY STANDARDS AND CRITERIA
The ACGIH (1980, 1981) has established a TLV of 200 ppm (-790 mg/m3)
and a STEL of 250 ppm (-1000 mg/m3), based upon the unpublished study by
Torkelson (1965). This standard does not distinguish between the c1s and
trans Isomers.
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6. RISK ASSESSMENT
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS)
6.1.1. Oral. The available data were Inadequate for the derivation of a
subchronlc oral AIS for 1,2-t-dlchloroethylene.
6.1.2. Inhalation. Two studies (Torkelson, 1965; Freundt et al., 1977)
were located 1n which 1,2-d1chloroethylene was administered to experimental
animals. Torkelson (1965) observed no effects of subchronlc Inhalation
exposure to 1000 ppm of a mixture of 1,2-d1chloroethylene Isomers (-400 ppm
of the trans Isomer) for 6 months. In contrast, Freundt et al. (1977)
reported fatty changes In the liver and minor changes In the lungs following
exposure to 200 ppm 1,2-t-dlchloroethylene for 16 weeks. Because of these
contradictions, the data are not considered suitable for the derivation of
an AIS.
A CS was calculated for the effects of fatty liver changes and
progressive pulmonary hlstopathologlcal lesions observed by Freundt et al.
(1977) 1n rats exposed to 200 ppm 1,2-t-dlchloroethylene 8 hours/day, 5
days/week for 16 weeks. A human MED was obtained by expanding to continuous
exposure and applying the assumptions that the human Inhalation rate 1s 20
m3 of air/day with an absorption factor of 0.5. Additionally, an
uncertainty factor of 10 was applied because the Freundt et al. (1977) study
was subchronlc In duration. The resulting human MED of 189 mg/day corre-
sponds to an RV. of 2.1. The hlstopathologlc changes In the liver and
lungs were rated an RVg of 5. A CS of 10.5, the product of RVd and
RV , was derived.
6.2. ACCEPTABLE INTAKE CHRONIC (AIC)
6.2.1. Oral. The available data were Inadequate for the derivation of an
oral AIC 1,2-t-dlchloroethylene.
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6.2.2. Inhalation. The available data were Inadequate for the derivation
of a chronic Inhalation AIC for l,2-t-d1chloroethylene.
6.3. CARCINOGENIC POTENCY (q^)
6.3.1. Oral. Pertinent data regarding the cardnogenlclty of
1,2-t-dlchloroethylene following oral exposure could not be located 1n the
available literature. Therefore, no q^* could be derived.
6.3.2. Inhalation. Pertinent data regarding the Inhalation
cardnogenlclty of 1 t2-t-d1chloroethylene could not be located 1n the
available literature. Therefore, no q could be derived.
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7. REFERENCES
ACGIH (American Conference of Governmental Industrial Hyg1en1sts). 1980.
Documentation of the Threshold Limit Values for Substances 1n Workrook A1r,
4th ed. Cincinnati, OH. p. 130-131. (Cited in U.S. EPA, 1983b)
ACGIH (American Conference of Governmental Industrial Hyg1en1sts). 1981.
Documentation of the TLV. p. 130-131. (Cited 1n U.S. EPA, 1982)
Cerna, M. and H. Kypenova. 1977. Mutagenlc activity of choroethylenes
analyzed by screening system tests. Mutat. Res. 46: 214. (CHed 1n U.S.
EPA, 1983b)
oc
Daniel, J.W. 1963. The metabolism of C1-labeled trichloroethylene and
tetrachloroethylene In the rat. Blochem. Pharmacol. 12: 795-802. (CHed
1n U.S. EPA, 1980a)
Federal Register. 1984. Environmental Protection Agency. Proposed guide-
lines for carcinogenic risk assessment. Federal Register 49:46294-46299.
Freundt, K.J., G.P. Llebaldt and E. Lleberwlrth. 1977. Toxldty studies on
trans-1.2-d1chloroethylene. Toxicology. 7: 141-153. (Cited 1n U.S. EPA,
1982)
Grelm, H., G. Bonse, Z. Radwan, D. Relchert and D. Henschler. 1975. Muta-
genldty jjn vitro and potential cardnogenlclty of chlorinated ethylenes as
a function of metabolic oxlran formation. Blochem. Pharmacol. 24:
2013-2017. (Cited In U.S. EPA, 1980a, 1983b)
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Hendry, D.G. and R.A. Kenley. 1979. Atmospheric reaction products of
organic compounds. U.S. EPA, Office of Chemical Control, Office of Toxic
Substances, Washington, DC. EPA 560/12-79-001.
Kenaga, E.E. and C.A.J. Goring. 1980. Relationship between water solu-
bility, soil sorptlon, octanol-water partitioning and concentration of
chemicals 1n biota. In: Aquatic Toxicology, ASTM STP707, J.G. Eaton, P.R.
Parrlsh and A.C. HendMcks, Ed. American Society for Testing and Materials,
Philadelphia, PA. p. 78-115.
Mabey, W.R., J. H. Smith and R.T. Podoll, et al. 1981. Aquatic Fate
Process Data for Organic Priority Pollutants. U.S. EPA, Office of Water
Regulations and Standards, Monitoring and Data Support D1v., Washington, DC.
EPA 440/4-81-014.
Monster, A.C., G. Boersma and W.C. Duba. 1976. Pharmacok1net1cs of
tMchloroethylene 1n volunteers, Influence of workload and exposure concen-
tration. Ind. Arch. Occup. Environ. Health. 38: 87-102. (Cited 1n U.S.
EPA, 1980a)
Page, G.W. 1981. Comparison of groundwater and surface water for patterns
and levels of contamination by toxic substances. Environ. Sc1. Techno!.
15: 1475-1481.
Tabak, H.H., S.A. Quare, C.T. Mashnl and E.F. Broth. 1981. Blodegrad-
abllHy studies with organic priority pollutant compounds. J. Water Pollut.
Control Fed. 53: 1503-1518.
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Torkelson, T.R. 1965. Communication to TLV Committee, Dow Chemical Co.
December, 1965. (Cited 1n ACGIH, 1981; U.S. EPA, 1982)
Torkelson, T.R. and V.K. Rowe. 1981. Halogenated Aliphatic Hydrocarbons.
In.: Patty's Industrial Hygiene and Toxicology, 3rd rev. ed., Vol. 28, 6.D.
Clayton and F.E. Clayton, Ed. John Wiley and Sons, NY. 3551 p.
U.S. EPA. 1980a. Ambient Water Quality Criteria for Dlchloroethylenes.
Environmental Criteria and Assessment Office, Cincinnati, OH.
EPA-440/5-80-041. NTIS PB 83-117525.
U.S. EPA. 1980b. Guidelines and Methodology Used 1n the Preparation of
Health Effects Assessment Chapters of the Consent Decree Water Quality
Criteria. Federal Register. 45:79347-79357.
U.S. EPA. 1982. Reportable Quantity for 1,2-D1chloroethylene. Prepared by
the Environmental Criteria and Assessment Office, Cincinnati, OH, OHEA for
the Office of Solid Waste and Emergency Response, Washington, DC.
U.S. EPA. 1983a. Methodology and Guidelines for Reportable Quantity
Determinations Based on Chronic Toxldty Data. Prepared by the Environ-
mental Criteria and Assessment Office, Cincinnati, OH, OHEA for the Office
of Solid Waste and Emergency Response, Washington, DC.
U.S. EPA. 1983b. Hazard Profile for trans-1,2-D1chloroethylene. Prepared
by the Environmental Criteria and Assessment Office, Cincinnati, OH, OHEA
for the Office of Solid Waste and Emergency Response, Washington, DC.
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Velth, G.O., D.L. Defoe and B.V. Bergstedt. 1979. Measuring and estimating
the bioconcentratlon factor of chemicals 1n fish. J. F1sh Res. Board Can.
36: 1040-1048.
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APPENDIX
O Ni PJ
rr co
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