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Bis(chloroethyl)ether (BCEE)
CASRN 111-44-4
Contents
0137
Bis(chloroethyl)ether (BCEE); CASRN 111-44-4
Health assessment information on a chemical substance is included in IRIS only
after a comprehensive review of chronic toxicity data by U.S. EPA health
scientists from several Program Offices and the Office of Research and
Development. The summaries presented in Sections I and II represent a
consensus reached in the review process. Background information and
explanations of the methods used to derive the values given in IRIS are
provided in the Background Documents.
STATUS OF DATA FOR BCEE
File On-Line 03/31/1987
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) no data
Inhalation RfC Assessment (I.B.) message 10/01/1991
Carcinogenicity Assessment (II.) on-line 02/01/1994
_I. CHRONIC HEALTH HAZARD ASSESSMENTS FOR NONCARCINOGENIC EFFECTS
__I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD)
Substance Name -- Bis(chloroethyl)ether (BCEE)
CASRN -- 111-44-4
Not available at this time.
__I.B. REFERENCE CONCENTRATION FOR CHRONIC INHALATION EXPOSURE (RfC)
Substance Name -- Bis(chloroethyl)ether (BCEE)
CASRN -- 111-44-4
The health effects data for bis(chloroethyl)ether have been reviewed by
the RfD/RfC Work Group and determined to be inadequate for derivation of an
inhalation RfC. The verification status of this chemical is currently not
verifiable. For additional information on health effects of this chemical
interested parties are referred to the EPA documentation listed below.
U.S. EPA. 1980. Ambient Water Quality Criteria Document for Chloroalkyl
Ethers. Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of
Water Regulations and Standards Criteria and Standards Division, Washington,
DC. EPA 440/5-80-030. NTIS PB81-117418/AS.
U.S. EPA. 1987. Health Effects Assessment for Bis(2-chloroethyl)ether.
Prepared by the Environmental Criteria and Assessment Office, Cincinnati, OH.
EPA/600/8-88/023.
Agency Work Group Review -- 07/17/1991
EPA Contacts:
Please contact the Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513)569-7254 (phone), (513)569-7159 (FAX)
or RIH.IRIS@EPAMAIL.EPA.GOV (internet address).
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- Bis(chloroethyl)ether (BCEE)
CASRN -- 111-44-4
Last Revised -- 02/01/1994
Section II provides information on three aspects of the carcinogenic
assessment for the substance in question; the weight-of-evidence judgment of
the likelihood that the substance is a human carcinogen, and quantitative
estimates of risk from oral exposure and from inhalation exposure. The
quantitative risk estimates are presented in three ways. The slope factor is
the result of application of a low-dose extrapolation procedure and is
presented as the risk per (mg/kg)/day. The unit risk is the quantitative
estimate in terms of either risk per ug/L drinking water or risk per ug/cu.m
air breathed. The third form in which risk is presented is a drinking water
or air concentration providing cancer risks of 1 in 10,000, 1 in 100,000 or 1
in 1,000,000. The rationale and methods used to develop the carcinogenicity
information in IRIS are described in The Risk Assessment Guidelines of 1986
(EPA/600/8-87/045) and in the IRIS Background Document. IRIS summaries
developed since the publication of EPA's more recent Proposed Guidelines for
Carcinogen Risk Assessment also utilize those Guidelines where indicated
(Federal Register 61(79):17960-18011, April 23, 1996). Users are referred to
Section I of this IRIS file for information on long-term toxic effects other
than carcinogenicity.
__II.A. EVIDENCE FOR CLASSIFICATION AS TO HUMAN CARCINOGENICITY
___II.A.1. WEIGHT-OF-EVIDENCE CLASSIFICATION
Classification -- B2; probable human carcinogen
Basis -- Positive carcinogenicity results in two strains of mice and evidence
of mutagenicity
___II.A.2. HUMAN CARCINOGENICITY DATA
None.
___II.A.3. ANIMAL CARCINOGENICITY DATA
BCEE was marginally sarcomatogenic at s.c. injection sites in female
ICR/Ha mice (Van Duurren et al., 1968). Innes et al. (1969) administered BCEE
by gavage to two hybrid mouse strains, (C57Bl/6 x C3H/Anf)F1 and (C57Bl/6 x
AKR)F1. Groups of 18 mice/sex/strain began treatment with 100 mg/kg at 7 days
of age. At 4 weeks, after weaning, exposure was continued through the diet.
Concentrations in diet were calculated so as to deliver the maximally
tolerated dose (300 ppm), and treatment was continued for 18 months.
Increased evidence of hepatomas were noted in male and female (C57Bl/6 x
C3H/Anf)F1 mice and in male (C57Bl/6 x AKR)F1 mice.
By contrast to the above, Theiss et al. (1977) saw no increases in
pulmonary tumors in strain A mice given repeated i.p. injections of BCEE.
Futhermore, an NCI study (for which statistical analyses were not available)
indicated that BCEE was not carcinogenic for Charles River rats by the oral
route (Ulland et al., 1973; U.S. EPA, 1980).
___II.A.4. SUPPORTING DATA FOR CARCINOGENICITY
BCEE is a direct-acting mutagen producing base pair exchange mutations in
E. coli, S. typhimurium, and B. subtilis (Shirasu et al., 1975). Vapor-phase
exposure of Salmonella frameshift mutant strains TA1538 and TA98 also resulted
in a weak positive response (Fishbein, 1977). BCEE is mutagenic in S.
cerevisiae (Fishbein, 1977) but did not induce heritable translocations in
mice (Jorgenson et al., 1977). BCEE is structurally related to
bis(chloromethyl)ether (BCME), a human carcinogen.
__II.B. QUANTITATIVE ESTIMATE OF CARCINOGENIC RISK FROM ORAL EXPOSURE
___II.B.1. SUMMARY OF RISK ESTIMATES
Oral Slope Factor -- 1.1E+0 per (mg/kg)/day
Drinking Water Unit Risk -- 3.3E-5 per (ug/L)
Extrapolation Method -- Linearized multistage procedure, extra risk
Drinking Water Concentrations at Specified Risk Levels:
Risk Level Concentration
-------------------- -------------
E-4 (1 in 10,000) 3E+0 ug/L
E-5 (1 in 100,000) 3E-1 ug/L
E-6 (1 in 1,000,000) 3E-2 ug/L
___II.B.2. DOSE-RESPONSE DATA (CARCINOGENICITY, ORAL EXPOSURE)
Tumor Type -- hepatomas
Test Animals -- mouse/(C57B1/6 x C3H/AnF)F1, male
Route -- gavage followed by diet
Reference -- Innes et al., 1969
Administered Human Equivalent Tumor
Dose (mg/kg/day) Dose (mg/kg/day) Incidence
---------------- ---------------- ---------
0 0 8/79
39 2.94 14/16
___II.B.3. ADDITIONAL COMMENTS (CARCINOGENICITY, ORAL EXPOSURE)
The tumor incidence in control mice is derived from pooling the tumor
incidence of four untreated control groups (8/63) and one treated (gavaged
with gelatin suspension) control group (0/16).
The unit risk should not be used if the water concentration exceeds 3E+2
ug/L, since above this concentration the unit risk may not be appropriate.
___II.B.4. DISCUSSION OF CONFIDENCE (CARCINOGENICITY, ORAL EXPOSURE)
A small number of animals was treated at only one dose.
__II.C. QUANTITATIVE ESTIMATE OF CARCINOGENIC RISK FROM INHALATION EXPOSURE
___II.C.1. SUMMARY OF RISK ESTIMATES
Inhalation Unit Risk -- 3.3E-4 per (ug/cu.m)
Extrapolation Method -- Linearized multistage procedure, extra risk
Air Concentrations at Specified Risk Levels:
Risk Level Concentration
-------------------- ---------------
E-4 (1 in 10,000) 3E-1 ug/cu.m
E-5 (1 in 100,000) 3E-2 ug/cu.m
E-6 (1 in 1,000,000) 3E-3 ug/cu.m
___II.C.2. DOSE-RESPONSE DATA FOR CARCINOGENICITY, INHALATION EXPOSURE
The inhalation risk estimates were calculated from the oral exposure data
in Section II.B.2.
___II.C.3. ADDITIONAL COMMENTS (CARCINOGENICITY, INHALATION EXPOSURE)
The unit risk should not be used if the air concentration exceeds 3E+1
ug/cu.m, since above this concentration the unit risk may not be appropriate.
___II.C.4. DISCUSSION OF CONFIDENCE (CARCINOGENICITY, INHALATION EXPOSURE)
See II.B.4.
__II.D. EPA DOCUMENTATION, REVIEW, AND CONTACTS (CARCINOGENICITY ASSESSMENT)
___II.D.1. EPA DOCUMENTATION
Source Document -- U.S. EPA, 1980
The 1980 Ambient Water Quality Criteria Document for Chloroalkyl Ethers
received extensive peer and public review.
___II.D.2. REVIEW (CARCINOGENICITY ASSESSMENT)
Agency Work Group Review -- 07/23/1986
Verification Date -- 07/23/1986
___II.D.3. U.S. EPA CONTACTS (CARCINOGENICITY ASSESSMENT)
Please contact the Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513)569-7254 (phone), (513)569-7159 (FAX)
or RIH.IRIS@EPAMAIL.EPA.GOV (internet address).
_VI. BIBLIOGRAPHY
Substance Name -- Bis(chloroethyl)ether (BCEE)
CASRN -- 111-44-4
Last Revised -- 10/01/1991
__VI.A. ORAL RfD REFERENCES
None
__VI.B. INHALATION RfD REFERENCES
U.S. EPA. 1980. Ambient Water Quality Criteria Document for Chloroalkyl
Ethers. Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of
Water Regulations and Standards Criteria and Standards Division, Washington,
DC. EPA 440/5-80-030. NTIS PB81-117418/AS.
U.S. EPA. 1987. Health Effects Assessment for Bis(2-chloroethyl)ether.
Prepared by the Environmental Criteria and Assessment Office, Cincinnati, OH.
EPA/600/8-88/023.
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
Fishbein, L. 1977. Potential industrial carcinogens and mutagens. U.S. EPA,
Office of Toxic Substances, EPA 560/5-77-005. Washington, DC.
Innes, J.R.M., B.M. Ulland, M.G. Valerio, et al. 1969. Bioassay of
pesticides and industrial chemicals for tumorigenicity in mice: A preliminary
note. J. Natl. Cancer Inst. 42: 1101-1114.
Jorgenson, T.A., C.J. Rushbrook, G.W. Newell and R.G. Tardiff. 1977. Study
of mutagenic potential of bis(2-chloroethyl) and bis(2-Chloroisopropyl)ethers
in mice by the heritable translocation test. Toxicol. Appl. Pharmacol.
41: 196.
Shirasu, Y., M. Moriya, K. Kato and T. Kada. 1975. Mutagenicity screening of
pesticides in microbial systems. Mutat. Res. 31: 268.
Theiss, J.C., G.D. Stoner, M.B. Shimkin and E.K. Weisburger. 1977. Test for
carcinogenicity of organic contaminants of United States drinking waters by
pulmonary tumor response in strain A mice. Cancer Res. 37: 2717.
Ulland, B., E.K. Weisburger and J.H. Weisburger. 1973. Chronic toxicity and
carcinogenicity of industrial chemicals and pesticides. Toxicol. Appl.
Pharmacol. 25: 446.
U.S. EPA. 1980. Ambient Water Quality Criteria Document for Chloroalkyl
Ethers. 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 440/5-80-030. NTIS PB
81-117418.
Van Duuren, B.L., B.M. Goldschmidt, C. Katz, L. Langseth, G. Mercado and A.
Sivak. 1968. Alpha-haloethers: A new type of alkylating carcinogen. Arch.
Environ. Health. 16: 472.
_VII. REVISION HISTORY
Substance Name -- Bis(chloroethyl)ether (BCEE)
CASRN -- 111-44-4
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
03/01/1988 II.B.4. Text revised
03/01/1988 II.C.4. Text revised
02/01/1989 IV.C.1. Reference added
11/01/1989 VI. Bibliography on-line
01/01/1991 II. Text edited
01/01/1991 II.C.1. Inhalation slope factor removed (global change)
08/01/1991 I.B. Inhalation RfC now under review
08/01/1991 IV.F.1. EPA contact changed
10/01/1991 I.B. Inhalation RfC message on-line
10/01/1991 VI.B. Inhalation RfC references added
01/01/1992 IV. Regulatory actions updated
02/01/1994 II.D.3. Primary contact's phone number changed
VIII. SYNONYMS
Substance Name -- Bis(chloroethyl)ether (BCEE)
CASRN -- 111-44-4
Last Revised -- 03/31/1987
111-44-4
BCEE
beta,beta'-DICHLOROETHYL ETHER
Bis(chloroethyl)ether
BIS(2-CHLOROETHYL) ETHER
BIS(beta-CHLOROETHYL) ETHER
CHLOREX
1-CHLORO-2-(beta-CHLOROETHOXY)ETHANE
CHLOROETHYL ETHER
CLOREX
DCEE
2,2'-DICHLOORETHYLETHER
2,2'-DICHLOR-DIAETHYLAETHER
2,2'-DICHLORETHYL ETHER
beta,beta-DICHLORODIETHYL ETHER
DICHLOROETHER
DICHLOROETHYL ETHER
DI(2-CHLOROETHYL) ETHER
2,2'-DICHLOROETHYL ETHER
DI(beta-CHLOROETHYL)ETHER
sym-DICHLOROETHYL ETHER
DICHLOROETHYL OXIDE
2,2'-DICLOROETILETERE
DWUCHLORODWUETYLOWY ETER
ENT 4,504
ETHANE, 1,1'-OXYBIS(2-CHLORO-
ETHER, BIS(2-CHLOROETHYL)
ETHER DICHLORE
1,1'-OXYBIS(2-CHLORO)ETHANE
OXYDE DE CHLORETHYLE
RCRA WASTE NUMBER U025
UN 1916
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0137.HTM
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