Diethyl Ether
F Monticelli, Paris Lodron University Salzburg, Salzburg, Austria
Ó 2014 Elsevier Inc. All rights reserved.
This article is a revision of the previous edition article by Angelica Becaria, volume 2, pp 33–34, Ó 2005, Elsevier Inc.
l Name: Diethyl ether
l Chemical Abstracts Service Registry Number: 60-29-7
l Synonyms: Ether, Ethyl ether, Diethyl oxide, Ethyl oxide,
Ethoxyethane, Anesthetic ether
l Molecular Formula: C4H10O
l Chemical Structure: CH3CH2OCH2CH3
H3C O CH3
Background
Diethyl ether is a component of starting fluids and is used as
a solvent in the manufacture of synthetic dyes and plastics.
Because of its characteristics, diethyl ether was widely used in
many countries as an anesthetic agent, but was then replaced by
other substances in the 1960s.
Uses
Diethyl ether is used in the production of rubber, plastics,
paints, coatings, perfumes, and cosmetics. It is used as a solvent
or extractant for fats, waxes, oils, resins, dyes, and alkaloids. It is
also used as a fuel additive and alcohol denaturant as well as
a component of starting fluids in heavy engines. Although it
was the first successful surgical anesthetic agent, due to its
chemical properties and pharmacokinetic characteristics it is
not used anymore today.
Environmental Fate and Behavior
Inhalation is the main route of exposure to diethyl ether.
Occupational exposure to diethyl ether may occur through
inhalation and dermal contact with this compound at work-
places where diethyl ether is used. Exposure to this chemical
may also occur via inhalation of ambient air and ingestion
of contaminated drinking water. Although rare, intentional
(suicidal) exposure is also reported.
The industrial use of diethyl ether may result in its release to
the environment through various waste streams. In air, diethyl
ether will exist as a vapor and will be degraded in the atmo-
sphere after reacting with hydroxyl and nitrate radicals. Half-
lives of these reactions in air are estimated to be 1.2 and
5.8 days, respectively. In soil and water, diethyl ether is expected
to volatilize and biodegradation is likely to be a slow process.
Bioconcentration of diethyl ether in aquatic organisms is low.
Toxicokinetics
Diethyl ether is immediately absorbed from inhaled air into the
bloodstream and passes rapidly into the brain. More than 90%
138 Encyclopedia of Toxicology, Volume 2
of a dose of ether is exhaled unchanged after cessation of
exposure. Another 1–2% is excreted in urine. A residual amount
may deposit in fatty tissue. Radiotracer studies in rats have
shown that diethyl ether can be degraded to carbon dioxide.
After 20 min, 90% of diethyl ether applied on skin is absorbed.
Mechanism of Toxicity
The mechanism and site of action of diethyl ether are
unknown. In the past, most solvents were thought to interfere
with the bulk properties of membranes such as membrane
fluidity and permeability, thus causing a generalized pertur-
bation to neuronal membranes. In recent years, it has emerged
that specific sites such as ion channels and other receptors are
the more likely targets.
Acute and Short-Term Toxicity (or Exposure)
Animal
Inhalation of high concentrations of ether produces central
nervous system (CNS) changes, such as behavioral effects,
excitation, depression, and unconsciousness. Male mice
exposed by inhalation to 13 300–30 000 ppm of diethyl ether
for 20 min had decreased excitability, reduced muscle tone, and
reduced sensorimotor activity. Diethyl ether is a mild eye irri-
tant. The reported toxic doses for mice include the following:
LC50 (inhalation), 31 000 ppm per 30 min; LD50 (oral),
1.215 g kg 1.
Human
The target organ of ether is the CNS. Inhalation of high
concentrations may cause CNS effects including headache,
dizziness, unconsciousness, and coma. It is, however, rare to
find death due to an inhalation exposure. Ingestion poisonings
are of rapid onset, short duration, and clinically similar to
ethanol overdose. Diethyl ether is an irritant to the eye, skin,
and mucous membranes.
Chronic Toxicity (or Exposure)
Animal
Rats exposed orally to 3500 mg kg 1 per day for 13 weeks to
diethyl ether presented signs of toxicity characterized by
decrease in appetite, weight loss, and death.
Human
Repeated dermal exposure may cause the skin to become dry
and cracked due to oil extraction. Several reports have sug-
gested that long-term exposure to diethyl ether may have health
http://dx.doi.org/10.1016/B978-0-12-386454-3.00987-8

effects, but there is not enough information available to draw
firm conclusions.
Genotoxicity
Mutagenicity studies in cultured mammalian cells are ambig-
uous. Positive and negative results have been reported. Bacte-
rial mutagenicity tests have been primarily negative. Aged ether
(containing peroxides) has been shown to be mutagenic.
Clinical Management
Contact with the skin should be minimized by thoroughly
washing affected areas for at least 15 min. Symptoms of
dermatitis should be treated if necessary. If ingested, vomiting
should not be induced since ether poses an aspiration hazard
and chemical pneumonitis may occur. CNS depression may
result from ingestion. Treatment should be symptomatic. There
are no known antidotes to diethyl ether.
Ecotoxicology
The LC50 for Poecilia reticulate (guppy) is shown to be
2138 ppm for 14 days. The LC50 for Pimephales promelas
(fathead minnow) is 2560 mg l 1 for 96 h.
Other Hazards
Diethyl ether is extremely flammable. Its volatility and low
ignition temperature make it one of the most dangerous fire
Diethyl Ether 139
hazards in the laboratory. Ether vapor forms explosive mixtures
with air due to the formation of unstable peroxides. Diethyl
ether may react violently with halogens or strong oxidizing
agents.
Exposure Standards and Guidelines
The Occupational Safety and Health Administration permis-
sible exposure limit is set at 8 h time-weighted average of
400 ppm, which is equivalent to 1200 mg m 3. Fifteen minutes
short-term exposure limit is 500 ppm (equivalent to
1520 mg m 3). The ‘immediately dangerous to life or health’
concentration is 1900 ppm and is based on 10% of the lower
explosive limit for safety considerations.
See also: Anesthetics; Volatile Organic Compounds.
Further Reading
Monticelli, F., Kemmerling, R., Schulz, K., Keller, T., September 2011. Another case of
diethyl ether intoxication?: a case report focusing on toxicological analysis. Leg.
Med. (Tokyo) 13 (5), 254–258.
Toski, J.A., Bacon, D.R., Calverley, K., 2001. The history of anesthesiology. In:
Barash, P.G., Cullen, B.F., Stoelting, R.K. (Eds.), Clinical Anesthesia, fourth ed.
Lippincott Williams & Wilkins, p. 3. ISBN 978-0-7817-2268-1.
Ueda, I., 2001. Molecular mechanisms of anesthesia. Keio J. Med. 50 (1), 20–25.
Relevant Websites
http://anesthesiageneral.com/ether-effects/ – Anesthesia General: Ether effects.
http://hazard.com/msds/mf/baker/baker/files/e2340.htm – Hazard.com: Ethyl Ether.