Ethyl ether (CASRN 60-29-7)
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Ethyl ether; CASRN 60-29-7
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 Ethyl ether
File First On-Line 09/01/1990
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 07/01/1993 |
Inhalation RfC Assessment (I.B.) | no data | |
Carcinogenicity Assessment (II.) | no data |
_I. Chronic Health Hazard Assessments for Noncarcinogenic Effects
_I.A. Reference Dose for Chronic Oral Exposure (RfD)
Substance Name — Ethyl ether
CASRN — 60-29-7
Last Revised — 07/01/1993
The oral Reference Dose (RfD) is based on the assumption that thresholds exist for certain toxic effects such as cellular necrosis. It is expressed in units of mg/kg-day. In general, the RfD is an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. Please refer to the Background Document for an elaboration of these concepts. RfDs can also be derived for the noncarcinogenic health effects of substances that are also carcinogens. Therefore, it is essential to refer to other sources of information concerning the carcinogenicity of this substance. If the U.S. EPA has evaluated this substance for potential human carcinogenicity, a summary of that evaluation will be contained in Section II of this file.
__I.A.1. Oral RfD Summary
Critical Effect |
Experimental Doses* |
UF
|
MF
|
RfD
|
---|---|---|---|---|
Depressed body Rat Oral Subchronic U.S. EPA, 1986 |
NOAEL: 500 mg/kg/day LOAEL: 2000 mg/kg/day |
3000
|
1
|
2E-1
mg/kg/day |
__I.A.2. Principal and Supporting Studies (Oral RfD)
U.S. EPA. 1986. Rat oral subchronic study with ethyl ether. Prepared by American Biogenics Corporation for the Office of Solid Waste, Washington, DC.
Four groups of male and female rats (30/sex/group) were gavaged daily with 0, 500, 2000, and 3500 mg/kg/day of ethyl ether for 13 weeks. Six weeks after the initiation of dosing, an interim sacrifice of 10 rats/sex was performed. The remaining animals continued in the experiment until the day of the final sacrifice. Data generated from this study included body weight changes; food consumption; ophthalmological examinations; clinical, biochemical, and gross morphological changes; and histopathology of target organs. An evaluation of data revealed marked toxicity of ethyl ether at the high dose (3500 mg/kg/day), including mortality, decreased food intake, and body weight loss. Body weight loss was observed in both sexes at the two highest doses; only females showed a significant reduction at the high dosage. Histopathological evaluations of tissues revealed no effects related to the administration of ethyl ether. Based on data available from this study, 500 mg/kg/day is considered a NOAEL and 2000 mg/kg/day a LOAEL (significant body weight depression in male rats).
__I.A.3. Uncertainty and Modifying Factors (Oral RfD)
UF — An uncertainty factor of 3000 reflects 10 to extrapolate from subchronic to chronic data, 10 for interspecies extrapolation, 10 to account for intraspecies variability, and an additional factor of 3 for lack of toxicity data in a second species and reproductive/developmental studies.
MF — None
__I.A.4. Additional Studies/Comments (Oral RfD)
Additional information regarding orally administered ethyl ether is essentially limited to acute toxicity data. Reported intentional consumption can result in symptoms similar to those associated with alcoholism (Moeschlin, 1965). Ether anesthesia of pregnant mice and rats has been reported to produce some embryotoxic and teratogenic effects; however, the authors did not consider ether anesthesia as "highly teratogenic" (Schwetz and Becker, 1970).
Other criteria for ethyl ether exposure include a TLV of 400 ppm (1210 mg/cu.m) (ACGIH, 1984), an OSHA standard of 400 ppm, and a NIOSH recommended IDLH of 19,000 ppm in the atmosphere (Mackinson, 1980).
__I.A.5. Confidence in the Oral RfD
Study — Medium
Database — Low
RfD — Low
The oral subchronic study was based on a well-designed experimental protocol, provided adequate toxicological endpoints, identified both a LOAEL and a NOAEL, and is considered of medium confidence. The database does not provide pertinent information on toxicity data in a second species, on reproductive or developmental studies, however, and is considered of low confidence. Low confidence in the RfD follows.
__I.A.6. EPA Documentation and Review of the Oral RfD
Source Document — This assessment is not presented in any existing U.S. EPA document.
Other EPA Documentation — U.S. EPA, 1986
Agency Work Group Review — 06/11/1986, 03/19/1987, 09/19/1989, 10/19/1989, 11/15/1989
Verification Date — 11/15/1989
Screening-Level Literature Review Findings — A screening-level review conducted by an EPA contractor of the more recent toxicology literature pertinent to the RfD for Ethyl ether 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.
__I.A.7. EPA Contacts (Oral RfD)
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).
_I.B. Reference Concentration for Chronic Inhalation Exposure (RfC)
Substance Name — Ethyl ether
CASRN — 60-29-7
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — Ethyl ether
CASRN — 60-29-7
This substance/agent has not undergone a complete evaluation and determination under US EPA's IRIS program for evidence of human carcinogenic potential.
_III.
[reserved]
_IV. [reserved]
_V. [reserved]
_VI. Bibliography
Substance Name — Ethyl ether
CASRN — 60-29-7
Last Revised — 09/01/1990
_VI.A. Oral RfD References
ACGIH (American Conference of Governmental Industrial Hygienists). 1984. TLVs - Threshold Limit Values for Chemical Substances and Physical Agents in the Environment with Intended Changes for 1984-1985. Cincinnati, OH. p. 19.
Mackison, F.W. 1980. NIOSH/OSHA Pocket Guide to Chemical Hazard. U.S. Government Printing Office, Washington, DC. DHEW (NIOSH) Publ. No. 78-210.
Moeschlin, S. 1965. Poisoning: Diagnosis and Treatment. Grune and Stratton, New York. p. 294.
Schwetz, B.A. and B.A. Becker. 1970. Embryotoxicity and fetal malformations of rats and mice due to maternally administered ether. Toxicol. Appl. Pharmacol. 17: 275.
U.S. EPA. 1986. Rat oral subchronic study with ethyl ether. Prepared by American Biogenics Corporation for the Office of Solid Waste, Washington, DC.
_VI.B. Inhalation RfC References
None
_VI.C. Carcinogenicity Assessment References
None
_VII. Revision History
Substance Name — Ethyl ether
CASRN — 60-29-7
Date |
Section |
Description |
---|---|---|
09/01/1990 | I.A. | Oral RfD summary on-line |
09/01/1990 | VI. | Bibliography on-line |
07/01/1991 | I.A.7. | Primary and secondary contacts changed |
07/01/1993 | I.A.6. | Source Document and Other EPA Documentation clarified |
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.A.6. | Screening-Level Literature Review Findings message has been added. |
04/11/2003 | I.A.3. | Text updated. |
_VIII. Synonyms
Substance Name — Ethyl ether
CASRN — 60-29-7
Last Revised — 09/01/1990
- 60-29-7
- AETHER
- ANAESTHETIC ETHER
- ANESTHESIA ETHER
- ANESTHETIC ETHER
- DIAETHYLAETHER [GERMAN]
- DIETHYL ETHER
- DIETHYL OXIDE
- DWUETYLOWY ETER [POLISH]
- ETER DIETILICO [SPANISH]
- ETERE ETILICO [ITALIAN]
- ETHANE, 1,1'-OXYBIS-
- ETHER
- ETHER DIETHYLIQUE [FRENCH]
- ETHER, ETHYL
- ETHER ETHYLIQUE [FRENCH]
- ETHOXYETHANE
- ETHYL ETHER
- ETHYL OXIDE
- HSDB 70
- NSC 100036
- 3-OXAPENTANE
- 1,1'-OXYBISETHANE
- OXYDE D'ETHYLE [FRENCH]
- RCRA WASTE NUMBER U117
- SOLVENT ETHER
- UN 1155