Bis(chloroethyl)ether (BCEE) (CASRN 111-44-4)
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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 First 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
Screening-Level Literature Review Findings — A screening-level review conducted by an EPA contractor of the more recent toxicology literature pertinent to the RfC for Bis(chloroethyl)ether (BCEE) conducted in November 2001 did not identify any critical new studies. IRIS users who know of important new studies may provide that information to the IRIS Hotline at hotline.iris@epa.gov or (202)566-1676.
EPA Contacts:
Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in general, at (202)566-1676 (phone), (202)566-1749 (FAX) or hotline.iris@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 Human Carcinogenicity
__II.A.1. Weight-of-Evidence Characterization
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
Dose (mg/kg/day) |
Human Equivalent
Dose (mg/kg/day) |
Tumor
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
nhalation 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. EPA Review (Carcinogenicity Assessment)
Agency Work Group Review — 07/23/1986
Verification Date — 07/23/1986
Screening-Level Literature Review Findings — A screening-level review conducted by an EPA contractor of the more recent toxicology literature pertinent to the cancer assessment for Bis(chloroethyl)ether (BCEE) conducted in November 2001 did not identify any critical new studies. IRIS users who know of important new studies may provide that information to the IRIS Hotline at hotline.iris@epa.gov or (202)566-1676.
__II.D.3. EPA Contacts (Carcinogenicity Assessment)
Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in general, at (202)566-1676 (phone), (202)566-1749 (FAX) or hotline.iris@epa.gov (internet address).
_III.
[reserved]
_IV. [reserved]
_V. [reserved]
_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 RfC 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 |
04/01/1997 | III., IV., V. | Drinking Water Health Advisories, EPA Regulatory Actions, and Supplementary Data were removed from IRIS on or before April 1997. IRIS users were directed to the appropriate EPA Program Offices for this information. |
12/03/2002 | I.B., II.D.2. | Screening-Level Literature Review Findings message has been added. |
_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