Isopropanol
M Punja, Centers for Disease Control and Prevention, Chamblee, GA, USA
Ó 2014 Elsevier Inc. All rights reserved.
This article is a revision of the previous edition article by Michael D. Reed, volume 2, pp 653–655, Ó 2005, Elsevier Inc.
The findings and conclusions in this chapter are those of the author and do not necessarily represent the views of the Centers for Disease Control and
Prevention.
l Name: Isopropyl alcohol
l Chemical Abstracts Service Registry Number: 67-63-0
l Synonyms: 2-Propanol, 2-Propyl alcohol, Isopropyl alcohol,
Rubbing alcohol, sec-Propyl alcohol, 2-Hydroxypropane,
1-Methylethanol, 1-Methylethyl alcohol
l Molecular Formula: C3H8O
l Chemical Structure: CH3CHOCH3
OH
H3C CH3
Background
Isopropanol is a clear, colorless alcohol that is used in the
production of acetone and as a solvent in the manufacture of
various industrial and commercial products. It is used by the
public for a number of different purposes and is commonly
known as rubbing alcohol. It is flammable and miscible with
both water and many different organic solvents. Isopropanol
can be prepared via three different methods: indirect hydration
of propylene (the ‘strong acid’ method), direct hydration of
propylene, and catalytic hydrogenation of acetone.
Uses
Isopropanol is found in a number of different industrial and
commercial products that are used for different purposes. It is
used in paints, paint thinner, paint remover, inks, fuels,
disinfectants, coatings, dyes, cements, and deicers. It is used in
the production of acetone, waxes, animal and vegetable oils,
and flavorings. It can be found in variable amounts among
common household products such as medications, colognes,
perfumes, toiletries, and windshield and glass cleaning fluids.
Over-the-counter hand sanitizers and hospital hand rubs often
contain isopropanol but at low concentrations (less than 5%).
Some sanitizing wipes, usually labeled ‘rubbing alcohol wipes’
contain up to 70% isopropanol. Because of widespread avail-
ability and low price, rubbing alcohol (typically containing
70% isopropanol) is abused by ingestion in place of ethanol
by people seeking intoxication. Dermal application of iso-
propanol is an inappropriate folk remedy for fever.
Environmental Fate and Behavior
The vast majority of isopropanol in the environment origi-
nates from manufacturing processes. Small amounts are
produced by certain microbes, fungi, and yeast. The high
volatility of isopropanol ensures that when it is released
1144
into the environment in any state, it eventually ends up in
the atmosphere. There, it can be degraded by hydroxyl radicals
or it can return to soil or water through precipitation. Its
half-life in the environment is approximately 3.2 days and is
highly biodegradable; bioaccumulation in plants and animals
does not occur.
Relevant Physicochemical Properties
Molecular Weight: 60.1 g mol
1
Boiling Point: 82.5  C (180.5  F)
Melting Point:
88.5  C (
127.3  F)
Critical Temperature: 235  C (455  F)
Specific Gravity: 0.785 05 (Water ¼ 1)
Vapor Pressure: 4.4 kPa (at 20  C)
Vapor Density: 2.07 (Air ¼ 1)
Water/Oil Distribution Coefficient: equally soluble in oil and
water; log(oil/water) ¼ 0.1
Auto-ignition Temperature: 399  C (750  F)
Flammable Limits in Air (percent by volume): Lower, 2.0;
upper, 12.7 at 93  C (200  F)
Odor Threshold: 22 ppm
Refractive Index: 1.377 6
Acidity: pKa 16.5
Isopropyl alcohol is miscible in water, alcohol, ether, and
chloroform. It will dissolve ethyl cellulose, polyvinyl butyral,
many oils, alkaloids, gums, and natural resins. It is insoluble in
salt solutions. Unlike ethanol or methanol, isopropyl alcohol
can be separated from aqueous solutions by adding a salt such
as sodium chloride, sodium sulfate, or any of several other
inorganic salts, since the alcohol is much less soluble in saline
solutions than in salt-free water. The process is colloquially
called salting out, and causes concentrated isopropyl alcohol to
separate into a distinct layer.
Isopropyl alcohol forms an azeotrope with water, which
gives a boiling point of 80.37  C and a composition of 87.7
wt% (91 vol%) isopropyl alcohol. Water-isopropyl alcohol
mixtures have depressed melting points. It has a slightly bitter
taste, and is not safe to drink.
Isopropyl alcohol becomes increasingly viscous with decreas-
ing temperature. At temperatures below
70  C isopropyl
alcohol resembles maple syrup in viscosity.
Partition Behavior
Isopropanol is completely miscible in water and most organic
solvents.
Human Exposure
In occupational settings, exposure is most likely to occur by
dermal or inhalational routes. High-risk fields for occupational
Encyclopedia of Toxicology, Volume 2 http://dx.doi.org/10.1016/B978-0-12-386454-3.00741-7

exposure include nurses, assemblers, janitors, and printing
machine operators. In nonoccupational settings, the most
likely routes of exposure are dermal and ingestion, but inha-
lational and parenteral exposures have been reported.
Poisoning in the nonoccupational setting probably most often
occurs as a result of ingestion. While most ingestion is via the
oral route, there have been cases of rectal isopropanol admin-
istration resulting in death. Isopropanol has been found in
trace concentrations of some samples of drinking water in the
United States.
Exposure Monitoring
For exposure and exposure monitoring information specific to
the occupational setting refer to the ‘Exposure Standards and
Guidelines’ section. In the nonoccupational setting, exposures
that result in isopropanol poisoning are typically via oral
ingestion for purposes of intoxication or self-harm, and
monitoring usually consists of one or serial serum isopropanol
concentration measurements. However, serum isopropanol
concentrations may not correlate well with clinical symptoms
and mortality. In a nontolerant individual such as a child, any
detectable isopropanol concentration may cause adverse
health effects. In adults, patients have survived with serum
concentrations measuring as high as 200 mg dl
1, but post-
mortem serum concentrations have been reported as low as
55 mg dl
1. The reason for this poor correlation between
clinical effects and serum concentrations can probably be
explained by several factors: co-ingestion of other sedative or
toxic agents in the published case reports, time intervals of
variable duration between exposure and laboratory measure-
ment, and variability in tolerance between individuals as
cross-tolerance between ethanol and isopropanol is observed.
Laboratory testing for serum and urinary acetone may be
useful as surrogate biomarkers for exposure. Clinicians can use
a nonspecific measurement known as the osmol gap to help
determine if an isopropanol exposure occurred. Isopropanol
ingestions can increase the patient’s serum osmolality, which
can be measured via a commonly available laboratory test. The
osmol gap is the difference between the measured serum
osmolality and another, similar value calculated from the
patient’s serum electrolyte measurements (serum osmolarity).
The osmolar gap multiplied by a correction factor for iso-
propanol (1/10th the molecular weight or 6) will provide an
estimated serum isopropanol concentration assuming the
entire gap is due to isopropanol. The baseline osmol gap is
highly variable between individuals, so one should be very
careful in attributing the value of the gap to the presence, or
lack of presence, of an alcohol. Other alcohols such as ethanol,
methanol, and ethylene glycol can increase the osmol gap
when ingested as well. The use and proper interpretation of the
osmol gap can be difficult, and should occur in consultation
with a clinical toxicologist or the local poison control center
(1-800-222-1222).
Toxicokinetics
After ingestion, isopropanol is rapidly absorbed with 80%
absorption within 30 min and 100% by 3 h; the fraction that
Isopropanol 1145
reaches the systemic circulation (bioavailability) is high (70%).
Isopropanol is highly water soluble, and after ingestion it is
widely distributed throughout total body water. The volume of
distribution is 0.6–0.7 l kg
1 and there is minimal to no serum
protein binding. Isopropanol metabolism follows first-order
kinetics. The major route of metabolism is by conversion into
acetone via the enzyme alcohol dehydrogenase. Acetone can be
detected in the serum approximately 3–4 h after ingestion. The
presence of alcohol dehydrogenase enzyme inhibitors (such as
ethanol) will decrease isopropanol metabolism and prolong its
elimination half-life. The elimination half-life has been shown
to be approximately 3 h in alcohol-dependent individuals and
around 6 h in non-alcohol-dependent volunteers. Acetone’s
elimination half-life ranges from 7 to 50 h. Approximately
25–50% of isopropanol is excreted unchanged by the kidneys,
and a small amount of isopropanol is eliminated through the
lungs via exhalation.
Mechanism of Toxicity
Isopropanol is similar to other alcohols in its ability to induce
central nervous system (CNS) depression by enhancing
inhibitory neuronal activity and antagonizing excitatory
neuronal activity. It also can cause localized irritation upon
contact with skin and mucous membranes after dermal expo-
sure and ingestion, respectively.
Acute and Short-Term Toxicity (Animal/Human)
The toxicity of isopropanol depends on the route of exposure.
Isopropanol exposure to mucous membranes can cause irrita-
tion of the eyes, nose, and throat. Though rare, there are case
reports of hypotonia and lethargy occurring after widespread
coverage of skin (such as sponge baths) in a small child, sug-
gesting systemic absorption can be significant after dermal
application. After ingesting isopropanol, patients may develop
nausea and vomiting, and in severe cases, gastrointestinal
bleeding. There are case reports of hemorrhagic gastritis asso-
ciated with topical and intravenous isopropanol exposures, so
a mechanism of toxicity other than direct irritation from con-
tact with tissues for this complication is possible. The most
commonly reported adverse health effect after oral exposure is
CNS depression manifesting as inebriation that appears similar
to ethanol intoxication. Sedation and slurred speech can prog-
ress to ataxia, loss of consciousness and even coma in a dose
dependent fashion. In general, isopropanol is believed to be
more sedating than ethanol at similar serum concentrations.
Chronic Toxicity (Animal/Human)
Prolonged or repetitive dermal contact may lead to rash and
sensitization. Long-term use may induce fatty changes in the
liver, which over time can lead to fibrosis and signs and
symptoms of liver cirrhosis. Compared to ethanol, chronic
ingestion of isopropanol is more likely to cause irritation of the
gastric mucosal lining, which can potentially lead to hemor-
rhagic gastritis.
1146 Isopropanol
Carcinogenicity
There are two International Agency for Research on Cancer
(IARC) classifications for isopropanol. Isopropanol is Group 3,
not classifiable as to its carcinogenicity in humans, because
there is inadequate evidence in both humans and experimental
animals. However, observational studies have noted an
increased incidence of paranasal sinus and laryngeal cancer in
workers at factories where isopropanol is manufactured using
the strong-acid process. Therefore, manufacture of isopropyl
alcohol by the strong acid method is classified as IARC I
(carcinogenic) for cancer of the nasal cavity.
Animal Carcinogenicity Data
Carcinogenicity has been tested in mice and rats by exposing
them to volatilized isopropanol. In these small studies, there
was no statistical increase in overall tumors observed but there
was a slight increase in interstitial cell adenomas of the testis
in male rats. Regardless, the IARC has determined there is
inadequate evidence for the carcinogenicity of isopropanol in
experimental animals.
Clinical Management
Management options for isopropanol ingestions resulting in
poisoning are limited. Traditional gastrointestinal decon-
tamination practices (orogastric lavage and activated charcoal
administration) to decrease systemic absorption are unlikely
to be of clinical benefit and not routinely recommended due
to the rapid absorption of isopropanol and an unfavorable
risk to benefit ratio. There is no antidote for isopropanol
toxicity; therefore, care is mainly supportive and consists of
managing the effects of sedation, hypotension, metabolic
abnormalities, and gastritis. Patients with very large inges-
tions causing severe cardiovascular effects such as hypoten-
sion may require extracorporeal elimination techniques such
as hemodialysis to enhance elimination. Hemodialysis can
remove significant quantities of serum isopropanol and
acetone but is not routinely recommended. Typical laboratory
findings are dependent on dose, route of exposure, and time
interval since exposure. Early after moderate to large inges-
tions, an increased measured serum osmolality and increased
osmol gap can be seen. As time elapses and isopropanol is
metabolized to acetone, the osmol gap decreases and keto-
nemia and ketonuria can develop. The anion gap, a measure
of the difference between serum cation and anion concen-
trations, is usually normal or minimally elevated and meta-
bolic acidosis is not a prominent feature of oral isopropanol
poisoning. Isopropanol poisoning lacks the metabolite-
mediated, end-organ specific poisoning seen in other toxic
alcohol ingestions such as methanol (blindness) and ethylene
glycol (acute kidney injury). As discussed, the osmol gap can
be used to help assess the extent of exposure, but should be
interpreted in consultation with a clinical toxicologist or local
poison control center (1-800-222-1222). A small or ‘normal’
osmol gap should not be used to exclude isopropanol
poisoning. In addition, a mild to moderate lactic acidosis may
occasionally be seen. Unlike other volatile alcohols like
methanol or ethylene glycol that produce toxic metabolites,
severe morbidity or mortality from most isopropanol inges-
tions is rare, and most patients do well with supportive care.
Patients with large dermal exposures should be decontami-
nated with soap and water; exposed eyes should be irrigated
with water or normal saline.
Other Hazards
The National Fire Protection Association has assigned iso-
propanol a flammability rating of 3, which signifies a severe fire
hazard. Thus, appropriate precautions should be used when
handling and during transport. For small fires, use dry chem-
ical, carbon dioxide, or alcohol-resistant foam. Use water spray,
fog, or alcohol-resistant foam to fight large fires.
Exposure Standards and Guidelines
There is no currently accepted biological test for monitoring
isopropyl alcohol exposure in the occupational setting. The
current Occupational Safety and Health Administration
(OSHA) permissible exposure limit (PEL) for isopropyl alcohol
is 400 ppm (980 mg m
3) as an 8 h time-weighted average
(TWA). The National Institute for Occupational Safety and
Health (NIOSH) has established a recommended exposure
limit (REL) for isopropyl alcohol of 400 ppm (980 mg m
3) as
a TWA for up to a 10 h workday and a 40 h workweek and
a short-term exposure limit (STEL) of 500 ppm (1225 mg m
3)
for periods not to exceed 15 min. The American Conference of
Governmental Industrial Hygienists (ACGIH) has assigned
isopropyl alcohol a threshold limit value (TLV) of 200 ppm
(492 mg m
3) as a TWA for a normal 8 h workday and a 40 h
workweek and a STEL of 400 ppm (983 mg m
3) for periods
not to exceed 15 min. Values similar to the OSHA PEL and
NIOSH REL are used by most countries except for Denmark
(490 mg m
3) and Sweden (350 mg m
3), which use values
similar to the ACGIH TLV. The immediately dangerous to life
and health level is 2000 ppm.
See also: Occupational Toxicology; Ethanol; Methanol; Ethylene
Glycol.
Further Reading
ACGIH, 2001. Isopropanol. In: Documentation of the Threshold Limit Values and
Biological Exposure Indices, seventh ed. 2006 Supplement. American Conference
of Government Industrial Hygienists, Cincinnati, OH.
Haviv, Y.S., Safadi, R., Osin, P., May, 1998. Accidental isopropyl alcohol enema
leading to coma and death. Am. J. Gastroenterol. 93 (5), 850–851.
Hoffman, R.S., Smilkstein, M.J., Howland, M.A., Goldfrank, L.R., 1993. Osmol gaps
revisited: normal values and limitations. J. Clin. Toxicol. 31 (1), 81–93.
Litovitz, T., 1986. The alcohols: ethanol, methanol, isopropanol, ethylene glycol.
Pediatr. Clin. North Am. 33 (2), 311–323.
Pappas, A.A., et al., 1991. Isopropanol ingestion: a report of six episodes with
isopropanol and acetone serum concentration time data. Clin. Toxicol. 29 (1),
11–21.
Zaman, F., Pervez, A., Abreo, K., 2002. Isopropyl alcohol intoxication: a diagnostic
challenge. Am. J. Kidney Dis. 40 (3), E12.
 Isopropanol 1147

Relevant Websites http://monographs.iarc.fr/ENG/Monographs/vol100F/mono100F-32.pdf – International

Agency for Research on Cancer monographs.
http://www.osha.gov/SLTC/healthguidelines/isopropylalcohol/recognition.html –
http://monographs.iarc.fr/ENG/Monographs/vol71/mono71-45.pdf – International Occupational Safety and Health Administration Guidelines.
Agency for Research on Cancer monographs.