Cyclohexane
Toxic Tips
INTRODUCTION
Chemical Description
Cyclohexane is also named hexahydrobenzene,
hexamethylene, and hexanaphthen. It is
obtained in the distillation of petroleum crude
oil or by hydrogenation of benzene at 150 8C
using Raney Nickel catalyst and at 10 atmo-
spheres H2 pressure. Cyclohexane can exist in
two interconvertible conformations—the boat
and the chair.1 The Occupational Safety and
Health Administration (OSHA) identifies
cyclohexane as a benzene hexahydride.2 Cyclo-
hexane is a colorless solvent with a pungent
odor and an odor threshold of about 25 ppm.
Its molecular weight is 84.16; the freezing point
is 6.47 8C; the boiling point is 80.7 8C; the vapor
pressure is 95 Torr at 20 8C; and its closed cup
flash point is at 8 8C. It is soluble in water,
alcohol, ether, acetone, and benzene.3 Cyclo-
hexane is a dangerous fire hazard; its flamm-
ability limits are between 1.3% and 8.4% by
volume in air, and its auto ignition temperature
is at 245 8C.2 Its identification numbers include
the Chemical Abstracts Service (CAS) Registry
number (110-82-7), the OSHA IMIS code num-
ber (0810), and NIOSH Registry of Toxic Effects
(RTECS) number (GU6300000).4
Uses and Typical Exposure Situations
Cyclohexane is mainly used as a solvent to
dissolve substances such as cellulose ethers,
lacquers, resins, fats, waxes, oils, bitumen,
and crude rubber. It is also used in the perfume
industry and in the production of nylon, paint,
and varnish remover. It is involved in the
synthesis of benzene, cyclohexanol, and cyclo-
hexanone. It is an important factor in manu-
facturing of leather, where it has replaced the
more toxic benzene.3 The general population
may be exposed to cyclohexane due to it being
present in gasoline.5
METABOLISM AND PHARMACOKINETICS
Absorption by inhalation and urinary excretion
of cyclohexane were studied in eight workers in
a shoe factory, where cyclohexane was used as
a glue solvent. A total of 23% of the respiratory
dose and 34% of the alveolar dose were
absorbed in the pulmonary blood. Urinary
metabolites included cyclohexanol and cyclo-
hexanone, which did not exceed 0.5–1% of the
absorbed dose.6 In another study, volunteers
were exposed to 300 ppm cyclohexane for 8 h.
1871-5532/$36.00 ß Division of Chemical Health and Safety of the American Chemical Society
doi:10.1016/j.jchas.2010.03.009
Of the absorbed dose, only 0.5% cyclohexanol,
23.4% 1,2-cyclohexanediol and 11.3% 1,4-
cyclohexanediol were excreted in the urine
72 h after exposure.7
CLINICAL PRESENTATION
Effects Following Inhalation
Cyclohexane is a central nervous system depres-
sant. When inhaled, it can cause headache, nau-
sea, dizziness, narcosis and even death at high
levels of exposure.2 Acute extreme exposure can
cause nausea, vomiting, incoordination, and
coma.8 Exposure to lower concentrations, such
as 250 ppm for 4 h, did not cause any observable
neurobehavioral effects.3
Effects Following Skin and Eye Exposure
Cyclohexane is an irritant to the eyes and
mucous membranes. Chronic exposure to the
skin can cause dry, scaly, and fissured derma-
titis.2 Cyclohexane vapor at or above 300 ppm
is irritating to the skin and eyes.5
Carcinogenicity
Cyclohexane has not been thoroughly tested
for its ability to cause cancer.9 However, it has
been found to be a weak promoter of skin
tumors caused by carcinogenic polycyclic aro-
matic hydrocarbons in a mouse skin bioas-
say.10 Be that as it may, sufficient data is not
available to assign a carcinogenicity notation.3
FIRST AID
If a worker has become incapacitated due to
inhalation of cyclohexane, the victim should be
removed from further exposure and medical
care obtained. If splashed in the eyes, cyclo-
hexane should be immediately flushed from the
eyes with water and medical evaluation
obtained. Skin contact requires removing the
contaminated clothing followed by washing
the skin with soap and water.2
HANDLING AND STORAGE
Accidental Release Measures
After a spill or leak, all workers should be
notified, and the sources of heat or ignition
removed. Stopping a leak while ventilating
should be considered. Water spray may be used
to reduce the vapors. All the spilled or leaked
33
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cyclohexane should be absorbed in ver-
miculite, dry sand, or earth, and placed
into sealed containers for appropriate
disposal. If the accidental release
involves a fire, use dry chemical, carbon
dioxide, alcohol-resistant foam or other
foam-extinguishing agents, to fight the
fire. In case of fire, an isolation distance
of a half-mile should be taken.9
Reactivities and Incompatibilities
The proper handling and storage of
cyclohexane are essential because
cyclohexane reacts explosively with
nitrates, nitrogen dioxide, and dinitro-
gen tetraoxide. It is not compatible
with oxidizing agents such as perchlo-
rates, peroxides, permanganates, chlo-
rates, nitrates, chlorine, bromine, and
fluorine. In addition, explosion-proof
electrical equipment and fittings
should be used in areas where cyclo-
hexane is handled.9
Storage Guidelines
Cyclohexane containers must be kept
away from sources of ignition, such as
smoking and open flames. In addition,
metal containers involved in the trans-
fer of cyclohexane should be
grounded.9 Cyclohexane should be
stored in a cool, dry, well-ventilated
area in tightly sealed containers away
from oxidizing agents.2
EXPOSURE CONTROLS
Control Methods
Four methods can be used to prevent
or reduce the exposure of workers to
cyclohexane: process enclosure, local
exhaust ventilation, general dilution
ventilation, and personal protective
equipment. Furthermore, the health
care professional can consider the
probable frequency, intensity, and
duration of exposure as well as the
applicable medical condition of the
worker. Monitoring the urinary quan-
tity of cyclohexanol can be used as a
biological method of evaluating the
exposure to cyclohexane.2
Sampling and Analysis
As specified by National Institute for
Occupational Safety and Health
(NIOSH) Method 1500, determina-
34
tion of airborne cyclohexane concen-
tration is accomplished by using a solid
sorbent (charcoal) tube. Samples are
collected at a maximum flow rate of
0.2 L/min until a maximum collection
volume of 5 L is reached. The sample is
desorbed with carbon disulfide. The
analysis is conducted by gas chroma-
tography using a flame-ionizing detec-
tor (GC/FID).11
Exposure Guidelines
The American Conference of Govern-
mental Industrial Hygienists (ACGIH)
has a Threshold Limit Value-Time
Weighted Average (TLV-TWA) of
100 ppm for cyclohexane to prevent
central nervous system (CNS) impair-
ment.12 The OSHA Permissible Expo-
sure Limit (PEL) for cyclohexane is
300 ppm (1050 mg/M3) as an 8-h time
weighted average (TWA) concentra-
tion. NIOSH has established the
Recommended Exposure Limit
(REL) of 300 ppm for cyclohexane as
a TWA for up to a 10-h workday and a
40-h work week.2 The NIOSH Imme-
diately Dangerous to Life or Health
Concentration (IDLH) is 1300 ppm.4
PERSONAL PROTECTION
Personal protective equipment (PPE)
is based on the duration and concen-
tration to which a worker is exposed to
cyclohexane. Any chemical-resistant
clothing should be periodically evalu-
ated for its efficacy to prevent dermal
contact. Safety showers and eye wash
stations should be located close to
operations involving cyclohexane.
Workers should wear splash-proof
chemical safety goggles. Workers
may also wear protective outer apparel
such as aprons or encapsulating suits
made of nitrile rubber.2
REFERENCES
1. O’Neil, M. J., Heckelman, P. E., Koch,
C. B., & Roman, K. J. (Eds.). (2006).
The Merck Index—An Encyclopedia of
Chemicals, Drugs, and Biologicals,
Fourteenth Edition; Merck Research
Laboratories. Division of Merck &
Co., Inc.: Whitehouse Station, NJ,
2006, p. 456.
2. Occupational Safety and Health Ad-
ministration (OSHA). Occupational
Journal of Chemical Health & Safety, May/June 2010
Safety and Health Guidelines for Cy-
clohexane, accessed from http://
www.osha.gov/SLTC/healthguide-
lines/cyclohexane/recognition.html on
September 13, 2009.
3. American Conference of Governmen-
tal Industrial Hygienists (ACGIH).
Documentation of the Threshold Limit
Values for Chemical Substances, 7th
ed.; Documentation for Cyclohexane,
ACGIH, Cincinnati, OH, 2002.
4. Occupational Safety and Health Ad-
ministration (OSHA). Chemical Sam-
pling Information for Cyclohexane,
accessed from http://www.osha.gov/
dts/chemicalsampling/data/
CH_230600.html#monitoring on Sep-
tember 13, 2009.
5. National Library of Medicine. Hazar-
dous Substances Data Bank (HSDB).
Fact Sheet for Cyclohexane, accessed
from http://toxnet.nlm.nih.gov/cgi-
bin/sis/search/r?dbs+hsdb:@term+
@rn+110-82-7 on September 13, 2009.
6. Mutti, A. S.; Lucertini, M.; Falzoi, M.;
et al. Organic solvents and chronic
glomerulonephritis: a cross-sectional
study with negative findings for alipha-
tic and alicyclic C5–C7 hydrocarbons. J.
Appl. Toxicol. 1981, 1(4), 224–226.
7. Mraz, J.; Galova, E.; Nohova, H.;
Vitkova, D. Markers of exposure to
cyclohexanone, cyclohexane, and cy-
clohexanol: 1,2 and 1,4-cyclohexane-
diol. Clin. Chem. 1994, 40, 1466–1468.
8. Hathaway, G. J.; Proctor, N. H.;
Hughes, J. P.; Fischman, M. L. Proctor
and Hughes’ Chemical Hazards of the
Workplace, 3rd ed. Van Nostrand Re-
inhold; New York, NY, 1991.
9. New Jersey Department of Health and
Senior Services. Hazardous Substance
Fact Sheet for Cyclohexane, accessed
from http://nj.gov/health/eoh/rtkweb/
documents/fs/0565.pdf on September
13, 2009.
10. Gupta, K. P.; Mehrotra, N. K. Mouse
skin ornithine decarboxylase induction
and tumor promotion by cyclohexane.
Cancer Lett. 1990, 15, 227–233.
11. National Institute for Occupational
Safety and Health (NIOSH). Manual
of Analytical Methods (NMAM)—
Method 1500 for Hydrocarbons (Cyclo-
hexane), accessed from http://
www.cdc.gov/niosh/nmam/method-
c.html on September 19, 2009.
12. American Conference of Governmental
Industrial Hygienists (ACGIH). 2009
TLVs and BEIs Based on Documenta-
tion of the Threshold Limit Values for
Chemical Substances and Physical
Agents & Biological Exposure Indices.
ACGIH, Cincinnati, OH, 2009.