% jT%J^ United States
I^bTSp^ Environmental Protection
Jf % Agency
EPA/690/R-02/004F
Final
5-31-2002
Provisional Peer Reviewed Toxicity Values for
1,2-Dichloroethylene (mixture)
(CASRN 540-59-0)
Derivation of an Inhalation RfC
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

-------
Acronyms and Abbreviations
bw	body weight
cc	cubic centimeters
CD	Caesarean Delivered
CERCLA	Comprehensive Environmental Response, Compensation and Liability Act
of 1980
CNS	central nervous system
cu.m	cubic meter
DWEL	Drinking Water Equivalent Level
FEL	frank-effect level
FIFRA	Federal Insecticide, Fungicide, and Rodenticide Act
g	grams
GI	gastrointestinal
HEC	human equivalent concentration
Hgb	hemoglobin
i.m.	intramuscular
i.p.	intraperitoneal
IRIS	Integrated Risk Information System
IUR	inhalation unit risk
i.v.	intravenous
kg	kilogram
L	liter
LEL	lowest-effect level
LOAEL	lowest-observed-adverse-effect level
LOAEL(ADJ)	LOAEL adjusted to continuous exposure duration
LOAEL(HEC)	LOAEL adjusted for dosimetric differences across species to a human
m	meter
MCL	maximum contaminant level
MCLG	maximum contaminant level goal
MF	modifying factor
mg	milligram
mg/kg	milligrams per kilogram
mg/L	milligrams per liter
MRL	minimal risk level
MTD	maximum tolerated dose
MTL	median threshold limit
1

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NAAQS
National Ambient Air Quality Standards
NOAEL
no-observed-adverse-effect level
NOAEL(ADJ)
NOAEL adjusted to continuous exposure duration
NOAEL(HEC)
NOAEL adjusted for dosimetric differences across species to a human
NOEL
no-observed-effect level
OSF
oral slope factor
p-IUR
provisional inhalation unit risk
p-OSF
provisional oral slope factor
p-RfC
provisional inhalation reference concentration
p-RfD
provisional oral reference dose
PBPK
physiologically based pharmacokinetic
PPb
parts per billion
ppm
parts per million
PPRTV
Provisional Peer Reviewed Toxicity Value
RBC
red blood cell(s)
RCRA
Resource Conservation and Recovery Act
RDDR
Regional deposited dose ratio (for the indicated lung region)
REL
relative exposure level
RfC
inhalation reference concentration
RfD
oral reference dose
RGDR
Regional gas dose ratio (for the indicated lung region)
s.c.
subcutaneous
SCE
sister chromatid exchange
SDWA
Safe Drinking Water Act
sq.cm.
square centimeters
TSCA
Toxic Substances Control Act
UF
uncertainty factor

microgram
(imol
micromoles
voc
volatile organic compound
11

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5-31-2002
PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR
1,2-DICHLOROETHYLENE (mixture) (CASRN 540-59-0)
Derivation of an Inhalation RfC
Background
On December 5, 2003, the U.S. Environmental Protection Agency's (EPA's) Office of
Superfund Remediation and Technology Innovation (OSRTI) revised its hierarchy of human
health toxicity values for Superfund risk assessments, establishing the following three tiers as the
new hierarchy:
1.	EPA's Integrated Risk Information System (IRIS).
2.	Provisional Peer-Reviewed Toxicity Values (PPRTV) used in EPA's Superfund
Program.
3.	Other (peer-reviewed) toxicity values, including:
~	Minimal Risk Levels produced by the Agency for Toxic Substances and Disease
Registry (ATSDR),
~	California Environmental Protection Agency (CalEPA) values, and
~	EPA Health Effects Assessment Summary Table (HEAST) values.
A PPRTV is defined as a toxicity value derived for use in the Superfund Program when
such a value is not available in EPA's Integrated Risk Information System (IRIS). PPRTVs are
developed according to a Standard Operating Procedure (SOP) and are derived after a review of
the relevant scientific literature using the same methods, sources of data, and Agency guidance
for value derivation generally used by the EPA IRIS Program. All provisional toxicity values
receive internal review by two EPA scientists and external peer review by three independently
selected scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the
multi-program consensus review provided for IRIS values. This is because IRIS values are
generally intended to be used in all EPA programs, while PPRTVs are developed specifically for
the Superfund Program.
Because new information becomes available and scientific methods improve over time,
PPRTVs are reviewed on a five-year basis and updated into the active database. Once an IRIS
value for a specific chemical becomes available for Agency review, the analogous PPRTV for
that same chemical is retired. It should also be noted that some PPRTV manuscripts conclude
that a PPRTV cannot be derived based on inadequate data.
1

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5-31-2002
Disclaimers
Users of this document should first check to see if any IRIS values exist for the chemical
of concern before proceeding to use a PPRTV. If no IRIS value is available, staff in the regional
Superfund and RCRA program offices are advised to carefully review the information provided
in this document to ensure that the PPRTVs used are appropriate for the types of exposures and
circumstances at the Superfund site or RCRA facility in question. PPRTVs are periodically
updated; therefore, users should ensure that the values contained in the PPRTV are current at the
time of use.
It is important to remember that a provisional value alone tells very little about the
adverse effects of a chemical or the quality of evidence on which the value is based. Therefore,
users are strongly encouraged to read the entire PPRTV manuscript and understand the strengths
and limitations of the derived provisional values. PPRTVs are developed by the EPA Office of
Research and Development's National Center for Environmental Assessment, Superfund Health
Risk Technical Support Center for OSRTI. Other EPA programs or external parties who may
choose of their own initiative to use these PPRTVs are advised that Superfund resources will not
generally be used to respond to challenges of PPRTVs used in a context outside of the Superfund
Program.
Questions Regarding PPRTVs
Questions regarding the contents of the PPRTVs and their appropriate use (e.g., on
chemicals not covered, or whether chemicals have pending IRIS toxicity values) may be directed
to the EPA Office of Research and Development's National Center for Environmental
Assessment, Superfund Health Risk Technical Support Center (513-569-7300), or OSRTI.
INTRODUCTION
1,2-Dichloroethylene (CASRN 540-59-0), a mixture of cis and trans isomers, is not listed
on IRIS (U.S. EPA, 2001), and an RfC is not available in the HEAST (U.S. EPA, 1997). The
CARA list (U.S. EPA, 1991a, 1994) includes a Health and Environmental Effects Profile
(HEEP) on dichloroethenes (U.S. EPA, 1986) and a Health and Environmental Effects Document
(HEED) on 1,2-dichloroethylene (mixed isomers) (U.S. EPA, 1991b). Both documents declined
to derive an RfC due to insufficient reporting and contradictory results in the limited data
available. The ACGIH (1991, 2001) lists a TLV-TWA of 200 ppm (793 mg/m3) for all forms of
1,2-dichloroethylene based on liver toxicity of the trans isomer in a study by Freundt et al.
(1977). NIOSH (1981, 2001) established a recommended exposure limit of 200 ppm (790
mg/m3) and OSHA (1999, 2000) established a permissible exposure limit of 200 ppm (790
mg/m3) for all forms of 1,2-dichloroethylene to protect against irritation of the eye and
respiratory system, and depression of the central nervous system. ATSDR (1996, 2001) has not
established inhalation MRLs for mixed isomers of 1,2-dichloroethylene or for the cis isomer, but
2

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5-31-2002
has established an intermediate inhalation MRL of 0.2 ppm for the trans isomer based on hepatic
effects. Neither IARC (2001) nor the WHO (2001) have written toxicological review documents
on 1,2-dichloroethylene. A toxicity review on unsaturated halogenated hydrocarbons (Lemen,
2001), and the NTP (2001a, 2001b) management status report and health and safety report for
1,2-dichloroethylene were consulted for relevant information. Literature searches were
conducted from 1994 to June 2001 for studies relevant to the derivation of an RfC for
1,2-dichloroethylene. The databases searched were: TOXLINE, MEDLINE, CANCERLIT,
TOXLIT/BIOSIS, RTECS, HSDB, GENETOX, CCRIS, TSCATS, EMIC/EMICBACK, and
DART/ETICB ACK.
REVIEW OF THE PERTINENT LITERATURE
Human Studies
No pertinent data regarding the inhalation toxicity of 1,2-dichloroethylene in humans
following subchronic or chronic exposures were found in the available review documents (U.S.
EPA, 1986, 1991b; AT SDR, 1996; Lemen, 2001).
Animal Studies
The U.S. EPA (1986, 1991b) considered an available subchronic inhalation study on the
mixed isomers by Torkelson (1965) to be an inadequate basis for risk assessment because of its
lack of detail and because its negative results were discordant with those of Freundt et al. (1977)
for the trans isomer. Torkelson (1965) reported no effects in rats, rabbits, guinea pigs, and dogs
exposed to 500 or 1000 ppm of mixed isomers (60% cis, 40% trans) for 7 hrs/day, 5 days/week
for 6 months, whereas Freundt et al. (1977) reported a LOAEL of 200 ppm for pulmonary and
liver histopathology in female Wistar rats exposed to the trans isomer for 8 hours/day, 5
days/week for 16 weeks. However, a report of the Torkelson (1965) study submitted to the EPA
in 1994 (Dow Chemical, 1962) indicated that statistically significant increases in organ weights
relative to body weight were observed in the kidney of male rats and the liver of female rats at
500 and 1000 ppm, and the kidney of female rats at 1000 ppm. In addition, increased relative
liver weight was also observed in a small group of male and female rabbits. (Absolute organ
weights and histopathological results were not reported.) Rather than contradicting the Freundt
et al. (1977) results, the reported organ weight changes in the Dow Chemical (1962) report lend
some support to the histopathological observations in Freundt et al. (1977). However, too few
details of methods and results are available regarding the Torkelson/Dow study to use this study
for risk assessment. No additional subchronic or chronic duration studies of inhalation toxicity
of 1,2-dichloroethylene (mixed isomers) in animals were found in the available review
documents (ATSDR, 1996; Lemen, 2001) or in the literature search.
3

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5-31-2002
Other Studies
Acute exposures to high concentrations (>1000 ppm) of trans-1,2-dichlorocthylcnc have
been reported to cause eye irritation, nausea, vertigo, or narcosis (ACGIH, 1991; OSHA, 1999).
One human fatality, presumably from depression of the central nervous system, was reported
following exposure to an unknown quantity of 1,2-dichloroethylene vapor (isomer composition
unreported) in an enclosed area (ATSDR, 1996). 1,2-Dichloroethylene has been used as an
anesthetic in humans and animals (ACGIH, 1991; Lemen, 2001).
FEASIBILITY OF DERIVING A PROVISIONAL RfC FOR
1,2-DICHLOROETHYLENE (MIXED ISOMERS)
Quantitative data regarding the inhalation toxicity of 1,2-dichloroethylene are lacking for
humans and the available subchronic animal study is inadequate. Thus, it is not possible to
derive a provisional RfC for 1,2-dichloroethylene.
REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). 1991.
1,2-Dichloroethylene. Documentation of the Threshold Limit Values and Biological Exposure
Indices, 6th ed. ACGIH, Cincinnati, OH. p. 429-431.
ACGIH (American Conference of Governmental Industrial Hygienists). 2001. 2001 Threshold
Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices.
ACGIH, Cincinnati, OH. p. 26.
ATSDR (Agency for Toxic Substances and Disease Registry). 1996. Toxicological Profile for
1,2-Dichloroethene (Update). TP-95/04. August 1996. Atlanta, GA.
ATSDR (Agency for Toxic Substances and Disease Registry). 2001. Minimal Risk Levels
(MRLs) for Hazardous Substances. Dated April 2001. Examined July 2001. Online.
http://www.atsdr.cdc.gov/mrls.html
Dow Chemical Co. 1962. The toxicity of 1,2-dichloroethylene as determined by repeated
exposures in laboratory animals. OTS0557247.
Freundt, K.J., G.P. Liebaldt and E. Lieberwirth. 1977. Toxicity studies on trans- 1,2-
dichloroethylene. Toxicology. 7: 141-153.
IARC (International Agency for Research on Cancer). 2001. Search IARC agents and summary
evaluations. Examined July, 2001. Online, http://monographs.iarc.fr/
4

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5-31-2002
Lemen, R.A. 2001. Unsaturated halogenated hydrocarbons. In: Patty's Toxicology, 5th ed., E.
Bingham, B. Cohrssen and C.H. Powell, Ed. John Wiley, New York. Vol.5,
p. 205-297.
NIOSH (National Institute for Occupational Safety and Health). 1981. Occupational Health
Guideline for 1,2-Dichloroethylene. Version dated September 1978. Occupational Health
Guidelines for Chemical Hazards. Department of Health and Human Services (NIOSH)
Publication No. 81-123. January 1981. Examined July 2001. Online.
http://www.cdc.gov/niosh/pdfs/0195 .pdf
NIOSH (National Institute for Occupational Safety and Health). 2001. 1,2-Dichloroethylene.
CAS No. 540-59-0. NIOSH Pocket Guide to Chemical Hazards. Examined July 2001. Online.
http://www.cdc.gov/niosh/npg/npgd0195.html
NTP (National Toxicology Program). 2001a. Health and Safety Information for 1,2-
Dichloroethylene. Examined July 2001. Online.
http://ntp-server.niehs.nih.gov/htdoct/CHEM H&S/NTP Chem5/Radian540-59-0.html
NTP (National Toxicology Program). 2001b. Testing status. Examined July 2001. Online.
http://ntp-server.niehs.nih.gov/htdocs/Results Status/Resstatd/10110-X.Html
OSHA (Occupational Safety and Health Administration). 1999. Occupational Safety and Health
Guideline for 1,2-Dichloroethylene. (Developed under protocol by OSHA, the National Institute
for Occupational Safety and Health and the Department of Energy). Version dated April 1999.
Examined July 2001. Online.
http://www.osha-slc.gOv/SLTC/healthguidelines/l 2-dichloroethylene/index.html
OSHA (Occupational Safety and Health Administration). 2000. Chemical Sampling
Information for 1,2-Dichloroethylene. Version dated May 15 2000. Examined July 2001.
Online. http://www.osha-slc.gov/dts/chemicalsampling/data/CH 233600.html
Torkelson, T.R. 1965. Communication to TLV committee. Animal experiments on the toxicity
of a vinyl chloride and vinylidene chloride copolymer and of the two substances that can be used
to stabilize dispersions. Dow Chemical Co., Midland, MI. (Cited in ACGIH, 1991)
U.S. EPA. 1986. Health and Environmental Effects Profile for Dichloroethenes. 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. 1991a. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. April.
5

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5-31-2002
U.S. EPA. 1991b. Health and Environmental Effects Document for 1,2-Dichloroethylene
(mixed isomers). 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. May.
U.S. EPA. 1994. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. December.
U.S. EPA. 1997. Health Effects Assessment Summary Tables. FY-1997 Update. Prepared by
the Office of Research and Development, National Center for Environmental Assessment,
Cincinnati, OH for the Office of Emergency and Remedial Response, Washington, DC. July
1997. EPA/540/R-97/036. NTIS PB 97-921199.
U.S. EPA. 2001. Integrated Risk Information System (IRIS). Office of Research and
Development, National Center for Environmental Assessment, Washington, DC. Examined July,
2001. Online, http://www.epa.gov/iris/
WHO (World Health Organization). 2001. Online catalogs for the Environmental Health
Criteria series. Examined July 2001. Online, http://www.who.int/dsa/cat97/zehc.htm and
http ://www,who.int/dsa/justpub/add.htm
6

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5-31-2002
Provisional Peer Reviewed Toxicity Values for
1,2-Dichloroethylene (mixture)
(CASRN 540-59-0)
Derivation of an Oral Slope Factor
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

-------
Acronyms and Abbreviations
bw	body weight
cc	cubic centimeters
CD	Caesarean Delivered
CERCLA	Comprehensive Environmental Response, Compensation and Liability Act
of 1980
CNS	central nervous system
cu.m	cubic meter
DWEL	Drinking Water Equivalent Level
FEL	frank-effect level
FIFRA	Federal Insecticide, Fungicide, and Rodenticide Act
g	grams
GI	gastrointestinal
HEC	human equivalent concentration
Hgb	hemoglobin
i.m.	intramuscular
i.p.	intraperitoneal
IRIS	Integrated Risk Information System
IUR	inhalation unit risk
i.v.	intravenous
kg	kilogram
L	liter
LEL	lowest-effect level
LOAEL	lowest-observed-adverse-effect level
LOAEL(ADJ)	LOAEL adjusted to continuous exposure duration
LOAEL(HEC)	LOAEL adjusted for dosimetric differences across species to a human
m	meter
MCL	maximum contaminant level
MCLG	maximum contaminant level goal
MF	modifying factor
mg	milligram
mg/kg	milligrams per kilogram
mg/L	milligrams per liter
MRL	minimal risk level
MTD	maximum tolerated dose
MTL	median threshold limit
1

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NAAQS
National Ambient Air Quality Standards
NOAEL
no-observed-adverse-effect level
NOAEL(ADJ)
NOAEL adjusted to continuous exposure duration
NOAEL(HEC)
NOAEL adjusted for dosimetric differences across species to a human
NOEL
no-observed-effect level
OSF
oral slope factor
p-IUR
provisional inhalation unit risk
p-OSF
provisional oral slope factor
p-RfC
provisional inhalation reference concentration
p-RfD
provisional oral reference dose
PBPK
physiologically based pharmacokinetic
PPb
parts per billion
ppm
parts per million
PPRTV
Provisional Peer Reviewed Toxicity Value
RBC
red blood cell(s)
RCRA
Resource Conservation and Recovery Act
RDDR
Regional deposited dose ratio (for the indicated lung region)
REL
relative exposure level
RfC
inhalation reference concentration
RfD
oral reference dose
RGDR
Regional gas dose ratio (for the indicated lung region)
s.c.
subcutaneous
SCE
sister chromatid exchange
SDWA
Safe Drinking Water Act
sq.cm.
square centimeters
TSCA
Toxic Substances Control Act
UF
uncertainty factor

microgram
(imol
micromoles
voc
volatile organic compound
11

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5-31-2002
PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR
1,2-DICHLOROETHYLENE (mixture) (CASRN 540-59-0)
Derivation of an Oral Slope Factor
Background
On December 5, 2003, the U.S. Environmental Protection Agency's (EPA's) Office of
Superfund Remediation and Technology Innovation (OSRTI) revised its hierarchy of human
health toxicity values for Superfund risk assessments, establishing the following three tiers as the
new hierarchy:
1.	EPA's Integrated Risk Information System (IRIS).
2.	Provisional Peer-Reviewed Toxicity Values (PPRTV) used in EPA's Superfund
Program.
3.	Other (peer-reviewed) toxicity values, including:
~	Minimal Risk Levels produced by the Agency for Toxic Substances and Disease
Registry (ATSDR),
~	California Environmental Protection Agency (CalEPA) values, and
~	EPA Health Effects Assessment Summary Table (HEAST) values.
A PPRTV is defined as a toxicity value derived for use in the Superfund Program when
such a value is not available in EPA's Integrated Risk Information System (IRIS). PPRTVs are
developed according to a Standard Operating Procedure (SOP) and are derived after a review of
the relevant scientific literature using the same methods, sources of data, and Agency guidance
for value derivation generally used by the EPA IRIS Program. All provisional toxicity values
receive internal review by two EPA scientists and external peer review by three independently
selected scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the
multi-program consensus review provided for IRIS values. This is because IRIS values are
generally intended to be used in all EPA programs, while PPRTVs are developed specifically for
the Superfund Program.
Because new information becomes available and scientific methods improve over time,
PPRTVs are reviewed on a five-year basis and updated into the active database. Once an IRIS
value for a specific chemical becomes available for Agency review, the analogous PPRTV for
that same chemical is retired. It should also be noted that some PPRTV manuscripts conclude
that a PPRTV cannot be derived based on inadequate data.
1

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5-31-2002
Disclaimers
Users of this document should first check to see if any IRIS values exist for the chemical
of concern before proceeding to use a PPRTV. If no IRIS value is available, staff in the regional
Superfund and RCRA program offices are advised to carefully review the information provided
in this document to ensure that the PPRTVs used are appropriate for the types of exposures and
circumstances at the Superfund site or RCRA facility in question. PPRTVs are periodically
updated; therefore, users should ensure that the values contained in the PPRTV are current at the
time of use.
It is important to remember that a provisional value alone tells very little about the
adverse effects of a chemical or the quality of evidence on which the value is based. Therefore,
users are strongly encouraged to read the entire PPRTV manuscript and understand the strengths
and limitations of the derived provisional values. PPRTVs are developed by the EPA Office of
Research and Development's National Center for Environmental Assessment, Superfund Health
Risk Technical Support Center for OSRTI. Other EPA programs or external parties who may
choose of their own initiative to use these PPRTVs are advised that Superfund resources will not
generally be used to respond to challenges of PPRTVs used in a context outside of the Superfund
Program.
Questions Regarding PPRTVs
Questions regarding the contents of the PPRTVs and their appropriate use (e.g., on
chemicals not covered, or whether chemicals have pending IRIS toxicity values) may be directed
to the EPA Office of Research and Development's National Center for Environmental
Assessment, Superfund Health Risk Technical Support Center (513-569-7300), or OSRTI.
INTRODUCTION
1,2-Dichloroethylene (CASRN 540-59-0), a mixture of cis and trans isomers, is not listed
on IRIS (U.S. EPA, 2001), in the HEAST cancer table (U.S. EPA, 1997), or in the Drinking
Water Standards and Health Advisories List (U.S. EPA, 2000). The CARA list (U.S. EPA,
1991a, 1994) includes a Health and Environmental Effects Profile (HEEP) on dichloroethenes
(U.S. EPA, 1986) and a Health and Environmental Effects Document (HEED) on
1,2-dichloroethylene (mixed isomers) (U.S. EPA, 1991b). The HEED assigned 1,2-
dichloroethylene to Group D because of a lack of data regarding its carcinogenicity in humans or
animals. Neither IARC (2001) nor the WHO (2001) have written a toxicological review
document on 1,2-dichloroethylene. A Toxicological Profile on 1,2-dichloroethylene (ATSDR,
1996), a toxicity review on unsaturated halogenated hydrocarbons (Lemen, 2001), and the NTP
(2001 a,b) management status report and health and safety report for 1,2-dichloroethylene were
also consulted for relevant information. Literature searches were conducted from 1994 to June
2001 for studies relevant to the derivation of an oral slope factor for 1,2-dichloroethylene. The
2

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5-31-2002
databases searched were: TOXLINE, MEDLINE, CANCERLIT, TOXLIT/BIOSIS, RTECS,
HSDB, GENETOX, CCRIS, TSCATS, and EMIC/EMICBACK.
REVIEW OF THE PERTINENT LITERATURE
Human Studies
No data regarding carcinogenicity of 1,2-dichloroethylene in humans following oral
exposure were found in the available review documents (U.S. EPA, 1986, 1991b; ATSDR, 1996;
Lemen, 2001). The literature search located one relevant human epidemiological study. A case-
control study of 63,097 persons who died from pancreatic cancer between 1984 and 1993 found
no association between occupational exposure to 1,2-dichloroethylene and death from pancreatic
cancer (Kernan et al., 1999). No human studies were located that reported levels of exposure to
1,2-dichloroethylene.
Animal Studies
No data regarding carcinogenicity in animals following oral exposure to
1,2-dichloroethylene were located in the available reviews (U.S. EPA, 1986, 1991b; ATSDR,
1996; Lemen, 2001) or the literature search.
Other Studies
1,2-Dichloroethylene did not produce reverse mutations in Salmonella typhimurium
(strains TA98, TA100, TA1535, TA1537) or Saccharomyces cerevisiae D7 with or without
metabolic activation, and did not produce reverse or forward mutations in Escherichia coli K12
with activation (U.S. EPA, 199 lb). At a high concentration, it was weakly positive for mitotic
recombination in Saccharomyces cerevisiae D7 (U.S. EPA, 1991b). 1,2-Dichloroethylene
altered chromosomal segregation, resulting in aneuploidy, in Aspergillus nidulans diploid strain
PI (Crebelli et al., 1992, 1995; Rosenkranz and Klopman, 1996). This effect of
1,2-dichloroethylene and other haloalkanes was attributed to a direct or indirect interaction with
spindle microtubules (Crebelli et al., 1992). In freshly isolated human lymphocytes with or
without metabolic activation, 1,2-dichloroethylene induced micronucleus formation and also
caused DNA breakage in the alkaline single cell gel electrophoresis (comet) assay (Tafazoli and
Kirsch-Volders, 1996). 1,2-Dichloroethylene also induced micronucleus formation in 2 out of 3
human cell lines that stably express cytochromal enzymes: positive in parental human B
lymphoblastoid line AHH-1 Tk+/- and line h2El, but negative in line MCL-5 (Doherty et al.,
1996; Parry et al., 1996). At injected doses high enough to elicit clinical signs in CD-I mice,
1,2-dichloroethylene (purity 98%) did not induce micronucleus formation in bone marrow cells
(Crebelli et al., 1999).
3

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5-31-2002
FEASIBILITY OF DERIVING A PROVISIONAL ORAL SLOPE FACTOR FOR
1,2-DICHLOROETHYLENE
Since the available literature contains no information regarding carcinogenicity in humans
or animals following oral exposure to 1,2-dichloroethylene, there is no basis for the derivation of
an oral slope factor.
REFERENCES
ATSDR (Agency for Toxic Substances and Disease Registry). 1996. Toxicological Profile for
1,2-Dichloroethene (Update). August 1996. Atlanta, GA.
Crebelli, R., C. Andreoli, A. Carere et al. 1992. The induction of mitotic chromosome
malsegregation in Aspergillus nidulans. Quantitative structure activity relationship (QSAR)
analysis with chlorinated aliphatic hydrocarbons. Mutat. Res. 266: 117-134.
Crebelli, R., C. Andreoli, A. Carere et al. 1995. Toxicology of halogenated aliphatic
hydrocarbons: Structural and molecular determinants for the disturbance of chromosome
segregation and the induction of lipid peroxidation. Chem.-Bio. Interact. 98: 113-129.
Crebelli, R.C., A. Carere, P. Leopardi et al. 1999. Evaluation of 10 aliphatic halogenated
hydrocarbons in the mouse bone marrow micronucleus test. Mutagenesis. 14: 207-215.
Doherty, A.T., S. Ellard, E.M. Parry and J.M. Parry. 1996. An investigation into the activation
and deactivation of chlorinated hydrocarbons to genotoxins in metabolically competent human
cells. Mutagenesis. 11:247-274.
IARC (International Agency for Research on Cancer). 2001. Search IARC agents and summary
evaluations. Examined July, 2001. Online, http://monographs.iarc.fr/
Kernan, G.J., B.-T. Ji, M. Dosemeci et al. 1999. Occupational risk factors for pancreatic cancer:
A case-control study based on death certificates from 24 U.S. states. Am. J. Ind. Med. 36: 260-
270.
Lemen, R.A. 2001. Unsaturated halogenated hydrocarbons. In: Patty's Toxicology, 5th ed., E.
Bingham, B. Cohrssen and C.H. Powell, Ed. John Wiley, New York. Vol.5,
p. 205-297.
NTP (National Toxicology Program). 2001a. Health and Safety Information for 1,2-
Dichloroethylene. Examined July 2001. Online.
http://ntp-server.niehs.nih.gov/htdoct/CHEM H&S/NTP Chem5/Radian540-59-0.html
4

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5-31-2002
NTP (National Toxicology Program). 2001b. Testing status. Examined July 2001. Online.
http://ntp-server.niehs.nili.gov/litdocs/Results Status/Resstatd/10110-X.Html
Parry, J.M., E.M. Parry, R. Bourner et al. 1996. The detection and evaluation of aneugenic
chemicals. Mutat. Res. 353:11-46.
Rosenkranz, H.S. and G. Klopman. 1996. A study of the structural basis of the ability of
chlorinated alkanes and alkenes to induce aneuploidy and toxicity in the mold Aspergillus
nidulans. Mutat. Res. 354:183-193.
Tafazoli, M. and M. Kirsch-Volders. 1996. In vitro mutagenicity and genotoxicity study of 1,2-
dichloroethylene, 1,1,2-trichloroethane, 1,3-dichloropropane, 1,2,3-trichloropropane and 1,1,3-
trichloropropene, using the micronucleus test and the alkaline single cell gel electrophoresis
technique (comet assay) in human lymphocytes. Mutat. Res. 371:185-202.
U.S. EPA. 1986. Health and Environmental Effects Profile for Dichloroethenes. 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. 1991a. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. April.
U.S. EPA. 1991b. Health and Environmental Effects Document for 1,2-Dichloroethylene
(mixed isomers). 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. May.
U.S. EPA. 1994. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. December.
U.S. EPA. 1997. Health Effects Assessment Summary Tables. FY-1997 Update. Prepared by
the Office of Research and Development, National Center for Environmental Assessment,
Cincinnati, OH for the Office of Emergency and Remedial Response, Washington, DC. July
1997. EPA/540/R-97/036. NTIS PB 97-921199.
U.S. EPA. 2000. Drinking Water Standards and Health Advisories. Office of Water,
Washington, DC. Summer, 2000. EPA 822-B-00-001. Examined July, 2001. Online.
http://www.epa. gov/ost/drinking/standards/dwstandards.pdf
U.S. EPA. 2001. Integrated Risk Information System (IRIS). Office of Research and
Development, National Center for Environmental Assessment, Washington, DC. Examined
June, 2001. Online, http://www.epa.gov/iris/
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5-31-2002
WHO (World Health Organization). 2001. Online catalogs for the Environmental Health
Criteria series. Examined July 2001. Online, http://www.who.int/dsa/cat97/zehc.htm and
http ://www,who.int/dsa/justpub/add.htm
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5-31-2002
Provisional Peer Reviewed Toxicity Values for
1,2-Dichloroethylene (mixture)
(CASRN 540-59-0)
Derivation of an Inhalation Unit Risk
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

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Acronyms and Abbreviations
bw	body weight
cc	cubic centimeters
CD	Caesarean Delivered
CERCLA	Comprehensive Environmental Response, Compensation and Liability Act
of 1980
CNS	central nervous system
cu.m	cubic meter
DWEL	Drinking Water Equivalent Level
FEL	frank-effect level
FIFRA	Federal Insecticide, Fungicide, and Rodenticide Act
g	grams
GI	gastrointestinal
HEC	human equivalent concentration
Hgb	hemoglobin
i.m.	intramuscular
i.p.	intraperitoneal
IRIS	Integrated Risk Information System
IUR	inhalation unit risk
i.v.	intravenous
kg	kilogram
L	liter
LEL	lowest-effect level
LOAEL	lowest-observed-adverse-effect level
LOAEL(ADJ)	LOAEL adjusted to continuous exposure duration
LOAEL(HEC)	LOAEL adjusted for dosimetric differences across species to a human
m	meter
MCL	maximum contaminant level
MCLG	maximum contaminant level goal
MF	modifying factor
mg	milligram
mg/kg	milligrams per kilogram
mg/L	milligrams per liter
MRL	minimal risk level
MTD	maximum tolerated dose
MTL	median threshold limit
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NAAQS
National Ambient Air Quality Standards
NOAEL
no-observed-adverse-effect level
NOAEL(ADJ)
NOAEL adjusted to continuous exposure duration
NOAEL(HEC)
NOAEL adjusted for dosimetric differences across species to a human
NOEL
no-observed-effect level
OSF
oral slope factor
p-IUR
provisional inhalation unit risk
p-OSF
provisional oral slope factor
p-RfC
provisional inhalation reference concentration
p-RfD
provisional oral reference dose
PBPK
physiologically based pharmacokinetic
PPb
parts per billion
ppm
parts per million
PPRTV
Provisional Peer Reviewed Toxicity Value
RBC
red blood cell(s)
RCRA
Resource Conservation and Recovery Act
RDDR
Regional deposited dose ratio (for the indicated lung region)
REL
relative exposure level
RfC
inhalation reference concentration
RfD
oral reference dose
RGDR
Regional gas dose ratio (for the indicated lung region)
s.c.
subcutaneous
SCE
sister chromatid exchange
SDWA
Safe Drinking Water Act
sq.cm.
square centimeters
TSCA
Toxic Substances Control Act
UF
uncertainty factor

microgram
(imol
micromoles
voc
volatile organic compound
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5-31-2002
PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR
1,2-DICHLOROETHYLENE (mixture) (CASRN 540-59-0)
Derivation of an Inhalation Unit Risk
Background
On December 5, 2003, the U.S. Environmental Protection Agency's (EPA's) Office of
Superfund Remediation and Technology Innovation (OSRTI) revised its hierarchy of human
health toxicity values for Superfund risk assessments, establishing the following three tiers as the
new hierarchy:
1.	EPA's Integrated Risk Information System (IRIS).
2.	Provisional Peer-Reviewed Toxicity Values (PPRTV) used in EPA's Superfund
Program.
3.	Other (peer-reviewed) toxicity values, including:
~	Minimal Risk Levels produced by the Agency for Toxic Substances and Disease
Registry (ATSDR),
~	California Environmental Protection Agency (CalEPA) values, and
~	EPA Health Effects Assessment Summary Table (HEAST) values.
A PPRTV is defined as a toxicity value derived for use in the Superfund Program when
such a value is not available in EPA's Integrated Risk Information System (IRIS). PPRTVs are
developed according to a Standard Operating Procedure (SOP) and are derived after a review of
the relevant scientific literature using the same methods, sources of data, and Agency guidance
for value derivation generally used by the EPA IRIS Program. All provisional toxicity values
receive internal review by two EPA scientists and external peer review by three independently
selected scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the
multi-program consensus review provided for IRIS values. This is because IRIS values are
generally intended to be used in all EPA programs, while PPRTVs are developed specifically for
the Superfund Program.
Because new information becomes available and scientific methods improve over time,
PPRTVs are reviewed on a five-year basis and updated into the active database. Once an IRIS
value for a specific chemical becomes available for Agency review, the analogous PPRTV for
that same chemical is retired. It should also be noted that some PPRTV manuscripts conclude
that a PPRTV cannot be derived based on inadequate data.
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Disclaimers
Users of this document should first check to see if any IRIS values exist for the chemical
of concern before proceeding to use a PPRTV. If no IRIS value is available, staff in the regional
Superfund and RCRA program offices are advised to carefully review the information provided
in this document to ensure that the PPRTVs used are appropriate for the types of exposures and
circumstances at the Superfund site or RCRA facility in question. PPRTVs are periodically
updated; therefore, users should ensure that the values contained in the PPRTV are current at the
time of use.
It is important to remember that a provisional value alone tells very little about the
adverse effects of a chemical or the quality of evidence on which the value is based. Therefore,
users are strongly encouraged to read the entire PPRTV manuscript and understand the strengths
and limitations of the derived provisional values. PPRTVs are developed by the EPA Office of
Research and Development's National Center for Environmental Assessment, Superfund Health
Risk Technical Support Center for OSRTI. Other EPA programs or external parties who may
choose of their own initiative to use these PPRTVs are advised that Superfund resources will not
generally be used to respond to challenges of PPRTVs used in a context outside of the Superfund
Program.
Questions Regarding PPRTVs
Questions regarding the contents of the PPRTVs and their appropriate use (e.g., on
chemicals not covered, or whether chemicals have pending IRIS toxicity values) may be directed
to the EPA Office of Research and Development's National Center for Environmental
Assessment, Superfund Health Risk Technical Support Center (513-569-7300), or OSRTI.
INTRODUCTION
1,2-Dichloroethylene (CASRN 540-59-0), a mixture of cis and trans isomers, is not listed
on IRIS (U.S. EPA, 2001), in the HEAST cancer table (U.S. EPA, 1997), or in the Drinking
Water Standards and Health Advisories List (U.S. EPA, 2000). The CARA list (U.S. EPA,
1991a, 1994) includes a Health and Environmental Effects Profile (HEEP) on dichloroethenes
(U.S. EPA, 1986) and a Health and Environmental Effects Document (HEED) on
1,2-dichloroethylene (mixed isomers) (U.S. EPA, 1991b). The HEED assigned 1,2-
dichloroethylene to Group D because of a lack of data regarding its carcinogenicity in humans or
animals. Neither IARC (2001) nor the WHO (2001) have written a toxicological review
document on 1,2-dichloroethylene. A Toxicological Profile on 1,2-dichloroethylene (ATSDR,
1996), a toxicity review on unsaturated halogenated hydrocarbons (Lemen, 2001), and the NTP
(2001 a,b) management status report and health and safety report for 1,2-dichloroethylene were
also consulted for relevant information. Literature searches were conducted from 1994 to June
2001 for studies relevant to the derivation of an inhalation unit risk for 1,2-dichloroethylene. The
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5-31-2002
databases searched were: TOXLINE, MEDLINE, CANCERLIT, TOXLIT/BIOSIS, RTECS,
HSDB, GENETOX, CCRIS, TSCATS, and EMIC/EMICBACK.
REVIEW OF THE PERTINENT LITERATURE
Human Studies
No data regarding carcinogenicity of 1,2-dichloroethylene in humans following inhalation
exposure were found in the available review documents (U.S. EPA, 1986, 1991b; ATSDR, 1996;
Lemen, 2001). The literature search located one relevant human epidemiological study. A case-
control study of 63,097 persons who died from pancreatic cancer between 1984 and 1993 found
no association between occupational exposure to 1,2-dichloroethylene and death from pancreatic
cancer (Kernan et al., 1999). No human carcinogenicity study was located that reported levels of
exposure to 1,2-dichloroethylene.
Animal Studies
No data regarding carcinogenicity in animals following inhalation exposure to
1,2-dichloroethylene were located in the available reviews (U.S. EPA, 1986, 1991b; ATSDR,
1996; Lemen, 2001) or the literature search.
Other Studies
1,2-Dichloroethylene did not produce reverse mutations in Salmonella typhimurium
(strains TA98, TA100, TA1535, TA1537) or Saccharomyces cerevisiae D7 with or without
metabolic activation, and did not produce reverse or forward mutations in Escherichia coli K12
with activation (U.S. EPA, 199 lb). At a high concentration, it was weakly positive for mitotic
recombination in Saccharomyces cerevisiae D7 (U.S. EPA, 1991b). 1,2-Dichloroethylene
altered chromosomal segregation, resulting in aneuploidy, in Aspergillus nidulans diploid strain
PI (Crebelli et al., 1992, 1995; Rosenkranz and Klopman, 1996). This effect of
1,2-dichloroethylene and other haloalkanes was attributed to a direct or indirect interaction with
spindle microtubules (Crebelli et al., 1992). In freshly isolated human lymphocytes with or
without metabolic activation, 1,2-dichloroethylene induced micronucleus formation and also
caused DNA breakage in the alkaline single cell gel electrophoresis (comet) assay (Tafazoli and
Kirsch-Volders, 1996). 1,2-Dichloroethylene also induced micronucleus formation in 2 out of 3
human cell lines that stably express cytochromal enzymes: positive in parental human B
lymphoblastoid line AHH-1 Tk+/- and line h2El, but negative in line MCL-5 (Doherty et al.,
1996; Parry et al., 1996). At injected doses high enough to elicit clinical signs in CD-I mice,
1,2-dichloroethylene (purity 98%) did not induce micronucleus formation in bone marrow cells
(Crebelli et al., 1999).
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FEASIBILITY OF DERIVING A PROVISIONAL INHALATION UNIT RISK FOR
1,2-DICHLOROETHYLENE
Since the available literature contains no information regarding carcinogenicity in humans
or animals following inhalation exposure to 1,2-dichloroethylene, there is no basis for the
derivation of an inhalation unit risk.
REFERENCES
ATSDR (Agency for Toxic Substances and Disease Registry). 1996. Toxicological Profile for
1,2-Dichlorothene (Update). August 1996. Atlanta, GA.
Crebelli, R., C. Andreoli, A. Carere et al. 1992. The induction of mitotic chromosome
malsegregation in Aspergillus nidulans. Quantitative structure activity relationship (QSAR)
analysis with chlorinated aliphatic hydrocarbons. Mutat. Res. 266: 117-134.
Crebelli, R., C. Andreoli, A. Carere et al. 1995. Toxicology of halogenated aliphatic
hydrocarbons: Structural and molecular determinants for the disturbance of chromosome
segregation and the induction of lipid peroxidation. Chem.-Bio. Interact. 98: 113-129.
Crebelli, R.C., A. Carere, P. Leopardi et al. 1999. Evaluation of 10 aliphatic halogenated
hydrocarbons in the mouse bone marrow micronucleus test. Mutagenesis. 14: 207-215.
Doherty, A.T., S. Ellard, E.M. Parry and J.M. Parry. 1996. An investigation into the activation
and deactivation of chlorinated hydrocarbons to genotoxins in metabolically competent human
cells. Mutagenesis. 11:247-274.
IARC (International Agency for Research on Cancer). 2001. Search IARC agents and summary
evaluations. Examined July, 2001. Online, http://monographs.iarc.fr/
Kernan, G.J., B.-T. Ji, M. Dosemeci et al. 1999. Occupational risk factors for pancreatic cancer:
A case-control study based on death certificates from 24 U.S. states. Am. J. Ind. Med. 36: 260-
270.
Lemen, R.A. 2001. Unsaturated halogenated hydrocarbons. In: Patty's Toxicology, 5th ed., E.
Bingham, B. Cohrssen and C.H. Powell, Ed. John Wiley, New York. Vol.5,
p. 205-297.
NTP (National Toxicology Program). 2001a. Health and Safety Information for 1,2-
Dichloroethylene. Examined July 2001. Online.
http://ntp-server.niehs.nih.gov/htdoct/CHEM H&S/NTP Chem5/Radian540-59-0.html
4

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5-31-2002
NTP (National Toxicology Program). 2001b. Testing status. Examined July 2001. Online.
http://ntp-server.niehs.nili.gov/litdocs/Results Status/Resstatd/10110-X.Html
Parry, J.M., E.M. Parry, R. Bourner et al. 1996. The detection and evaluation of aneugenic
chemicals. Mutat. Res. 353:11-46.
Rosenkranz, H.S. and G. Klopman. 1996. A study of the structural basis of the ability of
chlorinated alkanes and alkenes to induce aneuploidy and toxicity in the mold Aspergillus
nidulans. Mutat. Res. 354:183-193.
Tafazoli, M. and M. Kirsch-Volders. 1996. In vitro mutagenicity and genotoxicity study of 1,2-
dichloroethylene, 1,1,2-trichloroethane, 1,3-dichloropropane, 1,2,3-trichloropropane and 1,1,3-
trichloropropene, using the micronucleus test and the alkaline single cell gel electrophoresis
technique (comet assay) in human lymphocytes. Mutat. Res. 371:185-202.
U.S. EPA. 1986. Health and Environmental Effects Profile for Dichloroethenes. 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. 1991a. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. April.
U.S. EPA. 1991b. Health and Environmental Effects Document for 1,2-Dichloroethylene
(mixed isomers). 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. May.
U.S. EPA. 1994. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. December.
U.S. EPA. 1997. Health Effects Assessment Summary Tables. FY-1997 Update. Prepared by
the Office of Research and Development, National Center for Environmental Assessment,
Cincinnati, OH for the Office of Emergency and Remedial Response, Washington, DC. July
1997. EPA/540/R-97/036. NTIS PB 97-921199.
U.S. EPA. 2000. Drinking Water Standards and Health Advisories. Office of Water,
Washington, DC. Summer, 2000. EPA 822-B-00-001. Examined July, 2001. Online.
http://www.epa. gov/ost/drinking/standards/dwstandards.pdf
U.S. EPA. 2001. Integrated Risk Information System (IRIS). Office of Research and
Development, National Center for Environmental Assessment, Washington, DC. Examined
June, 2001. Online, http://www.epa.gov/iris/
5

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5-31-2002
WHO (World Health Organization). 2001. Online catalogs for the Environmental Health
Criteria series. Examined July 2001. Online.
http://www.who.int/dsa/cat97/zehc.htm and http://www.who.int/dsa/justpub/add.htm
6

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