Combined Exposures to Noise and Chemicals at Work
M Sliwinska-Kowalska, Nofer Institute of Occupational Medicine, Medical University of Lodz, Lodz, Poland
& 2011 Elsevier B.V. All rights reserved.
Introduction
Simultaneous exposure to more than one physical or
chemical hazard is common in occupational environ-
ment; however, at present each hazard is assessed indi-
vidually. Such complex exposures can potentially lead to
different types of interactions with regard to health
outcome. These interactions include additive effects in
which the combined effect of exposure represents the
sum of exposures to the individual agents. More prob-
lematic are synergistic interactions when the effect is
more than additive. In the case of hearing damage (oto-
toxicity), a major concern arises about the effects of
combined occupational exposures to noise and chemicals.
Potentially, this issue has significant socioeconomic im-
portance, because of large populations exposed to either
noise or chemicals, alone or in combination. Approxi-
mately 30 million US workers are exposed to potentially
hazardous noise levels in the workplace, and roughly
one-third of them are coexposed to ototoxic chemicals. In
Europe, similar number of workers are at risk of de-
veloping hearing loss due to occupational noise exposure,
wherein the chemical industry is the third largest one,
employing 1.7 million people directly, and additionally
3 million jobs are estimated to be dependent on it. As it
was evaluated by the World Health Organization (WHO)
in 2002, worldwide approximately 16% of disabling
hearing loss in adults is attributed to occupational noise;
however, the percentage of solvent-induced or noise and
solvent-induced hearing loss cases is still to be evaluated.
The effects of several chemical substances have been
investigated through animal and human studies and have
been proven to damage hearing. According to the current
knowledge, the major groups of chemicals that are con-
sidered to be ototoxic are organic solvents, heavy metals,
and asphyxiants. Recent studies have alluded also to
pesticides as substances exerting ototoxic effects. Poten-
tially, all these chemicals can damage hearing when
acting alone, as well as by interacting with noise.
Organic Solvents
Organic solvents are routinely used in commercial in-
dustries. These chemicals are useful because they can
dissolve oils, fats, resins, rubber, and plastics. They share
a common structure (at least one carbon atom and one
hydrogen atom); have low molecular weight, lipophili-
city, and volatility; and exist in liquid form in ambient
temperatures. Some substances produce vapors that are
heavier than air. These vapors may move on the floor or
ground toward a distant ignition source, such as sparks
caused by welding or static electricity. Vapors of solvents
can also accumulate in confined places and stay there for
a long time, thereby presenting a risk for health and a
possible source of explosion.
Solvents enter the body by inhalation and swallowing
and through the skin and have various effects on human
health. Many of them have a narcotic effect, causing fa-
tigue, dizziness, and intoxication. High doses may lead to
unconsciousness and death.
Ototoxicity
Animal studies
The ototoxicity of organic solvents was first discovered in
rats in early 1980s, when Pryor and Rebert documented
the ability of several aromatic hydrocarbons to produce
auditory impairment following subchronic inhalation
exposure. The concentration of solvents used in these
studies was relatively high as compared to the permis-
sible levels in industry. Initially, ototoxic effect was
shown for toluene, but subsequent studies by Pryor and
Rebert and several other authors demonstrated hearing
loss in rats after exposure to xylenes, ethyl benzene,
trichloroethylene (TCE), styrene, chlorobenzene, and
n-hexane.
Long-lasting inhalations of organic solvents, as it was
documented for toluene and styrene, can impair the
peripheral auditory receptors in the cochlea (organ of
Corti). After inhalation, the volatile solvents are carried
by blood, pass through the stria vascularis, and use the
lipid-rich outer sulcus cells to reach the organ of Corti.
The first cochlear targets are supporting cells, Deiters’
and Hensen’s cells. After that the chemical insult leads to
the digestion of outer hair cells (OHCs), whereas the
inner hair cells seem to stay well preserved. The initial
loss of the third row of OHCs distinguishes the effect of
organic solvent exposure from noise exposure, which
initially involves the first row of OHCs.
A functional consequence of hair cells damage is
hearing loss. Toluene- or styrene-induced hearing loss is
primarily located in the vicinity of mid (16–20 kHz) and
mid-low (4 kHz) frequency regions. This pattern is es-
pecially striking because it is quite different from high-
frequency noise-induced hearing loss (NIHL), as well as
from ‘classical’ high-frequency hearing loss produced by
other ototoxicants like aminoglycoside antibiotics or
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756 Combined Exposures to Noise and Chemicals at Work
platinum-containing chemotherapeutic drugs (e.g., cis-
platinum). These differences probably arise from various
mechanisms of hair cell loss, which in case of noise in-
volve a mechanical input, whereas in case of hydrophilic
ototoxic drugs, intoxication within the organ of Corti.
However, each exposure to noise or to organic solvents is
responsible for the increased generation of reactive
oxygen species (ROS) in the cochlea, which in turn leads
to cell death. This can be prevented by application of
antioxidants or antiapoptotic drugs, as it has been shown
in animal models.
The ototoxic potency of organic solvents differs
widely among substances; for instance, it has been proved
in rats that styrene was much more ototoxic than toluene.
To be ototoxic, one aromatic solvent must have a single,
unbranched side chain and two methyl groups; however,
no evident structure–ototoxicity relationship was found.
Synergistic effect occurs in rats simultaneously ex-
posed to noise and organic solvents. Solvents may modify
the membranous structures of OHCs, making them more
fragile and vulnerable to noise. Thus, the same acoustic
energy entering the cochlea might be more harmful when
accompanied by an organic solvent. However, in combined
exposures, the most important factor for inducing hearing
impairment is potency of noise exposure (level and im-
pulsiveness). Concomitant exposure to organic solvents
may induce hearing loss when the exposure to noise is
relatively low and alone may exert only little effect.
As organic solvents have lipophylic and neurotoxic
properties, it is very likely that they can damage not only
the cochlea but also other central parts of the auditory
system. However, such effect has not yet been clearly
demonstrated in animals.
The ototoxic effect of organic solvents differs among
animal species. Contrary to rats, guinea pigs do not reveal
such cochlear damage due to solvent ototoxicity. The
toxic mechanisms of organic solvents are probably dif-
ferent also at high and low exposure levels. The con-
centration of solvent which can significantly contribute to
various hearing effects induced by combined exposures
to noise and solvents. This observation seems to be of
primary concern in humans, since combined exposures to
noise and low-concentration solvents are much more
common than exposures to very high levels of organic
solvents alone.
Human studies
Ototoxicity of organic solvents is more difficult to elu-
cidate in occupationally exposed human individuals than
in animals. This can be explained by several factors: the
concentration of chemicals is much lower than that used
in experimental studies; workers are usually exposed to a
mixture of solvents at widely varying compositions and
concentrations, disabling in the majority of cases the as-
sessment of the effect of a single substance; and finally, a
substantial number of workers are coexposed to noise and
chemicals.
However, over recent decades several studies in
humans have reported on the deteriorating effects of
organic solvents on the auditory and balance systems and
their interaction with noise. Most of the literature data
concerns one of the three solvent exposure categories: (1)
mixed solvent exposure (the most common type), (2)
styrene-only exposure, and (3) toluene-only exposure.
Exposures
The largest groups of workers exposed to mixtures of
solvents are painters; employees of paint and lacquer
industry, chemical plants, dockyards, and oil refinery; and
subjects exposed to jet fuel in aviation industry. These
mixtures are typically composed of xylene, toluene,
methyl ethyl ketone (MEK), methyl isobutyl ketone, and
others (ethanol, ethyl acetate, butyl acetate, ethyl ben-
zene, thinner, cyclohexane, and benzene). Occupational
exposures to styrene occur mainly in the manufacturing
of fiberglass-reinforced polyester products, for example,
reinforced plastics used in the boat-building industry.
Toluene-only exposures are selectively found in Roto-
gravure printing industry.
As reported in the literature, the concentration of
industrial organic solvents in the air and the time period
when the measurement was done differ largely among
industries as well as between countries. For instance, in
the currently assessed studies on hearing effects of styr-
ene, exposure levels ranged from below 5 up to ap-
proximately 50 ppm, whereas occupational exposure
limits (OELs) range from 10 to 100 ppm depending on
the country. The concentration of toluene was estimated
to vary from below 50 up to over 350 ppm, and the
concentration of xylenes as a main compound of mix-
tures was from few parts per million up to over 400 ppm;
these values largely exceeded the maximum world OEL
value for either of these substances.
The OELs exceed even more when calculating ex-
posure index (a ratio of the actually measured concen-
tration of a solvents to its OEL value) for a mixture (the
sum of the indexes for all solvents present in a mixture of
solvents). As for the solvent mixtures, the lowest ex-
posure indexes were found in aviation and refinery in-
dustries, whereas the highest were in a dockyard,
exceeding over 20 times the allowable value.
Although the dermal absorption of organic solvents is
negligible compared to the uptake via the lung, biologic
monitoring with assessing solvent metabolites in urine
seems to be more appropriate for their health effect
evaluation, including ototoxicity.
None of the studied populations exposed to solvents
worked in a totally quiet environment. The equivalent
level of noise varied greatly from below 80 up to
100 dB(A).
 Combined Exposures to Noise and Chemicals at Work
Hearing outcomes
The probability of developing hearing loss has been
shown to be significantly higher in workers exposed to
organic solvents than in individuals not exposed to
solvents. In the case of coexposure to noise and organic
solvents, the risk of hearing loss was much higher than in
solvent-only or noise-only exposed individuals, sug-
gesting an additive effect (Figure 1(a) and 1(b)). More-
over, the risk for hearing loss increased with the growing
number of solvents in a mixture.
Organic solvents and their mixtures have been dis-
covered to cause sensorineural hearing loss, retrocochlear
hearing loss, and lesions in the higher auditory pathways,
as well as vestibular disturbances, whereas noise exposure
results predominantly in sensorineural (cochlear) hearing
loss. The effects were found in different audiological
tests, such as pure-tone audiometry of standard and ex-
tended high frequencies and otoacoustic emission, cen-
tral hearing tests (evoked potentials and distorted speech
audiometry), as well as balance tests. Audiometric fre-
quency range affected by solvents in humans is not
limited to the range affected by noise.
Both extended high frequencies as well as low-middle
frequencies can be affected by solvents in addition to the
frequencies 3–6 kHz typically damaged by noise. How-
ever, the extent of damage is rather small compared to
noise-induced hearing threshold shift.
Since organic solvents affect not only peripheral
but also central auditory system, they can impair
speech comprehension even though no changes or small
hearing threshold shift is noted in conventional pure-
tone audiometry. Thus, if careful analyses are not per-
formed and attention is not given to all the exposure
conditions, the observed hearing disorders in workers
exposed to noise and chemicals can be erroneously at-
tributed to noise or can be completely unnoticed among
the subjects who are not included in the hearing con-
servation programs due to relatively moderate-level
noise exposures. In addition to pure-tone audiometry,
central auditory tests should be used in the diagnostics
of solvent-induced hearing impairment; otherwise it can
be unnoticed. An additive effect should be also con-
sidered in case of the combined exposure to noise and
solvents.
Substances Overview
Toluene
Toluene is the most frequently used solvent. It is a col-
orless liquid, with a characteristic odor. The vapor mixes
well with air and explosive mixtures are formed easily. As
a result of flow and agitation, among others, electrostatic
charges can be generated.
Toluene primarily affects the central nervous system in
both humans and experimental animals. Acute high-dose
757
exposure provokes excitability and euphoria followed
by a depressant response with disorientation, mood fluc-
tuations, hallucinations, ataxia, and coma. Long-term
effects of occupational exposure to toluene include
memory and concentration deficits and disturbance of
emotional and psychomotor functions.
Ototoxic effects
Much of what is known about toluene’s effects on hearing
comes from animal studies. It has been reported to cause
hearing loss alone and in the presence of noise.
Acute exposure to toluene causes an irreversible
hearing loss in rats at frequencies of 8–20 kHz, and
produces OHC loss spread along the cochlea with sub-
sequent inner hair cell loss. The severity of damage
depends on duration of exposure. In addition, toluene-
induced loss of auditory sensitivity is permanently po-
tentiated by simultaneous exposure to acetylsalicylic
acid. Synergistic effect occurs in case of simultaneous
exposure to toluene and noise.
The effects of occupational exposure to toluene and
noise were studied among Rotogravure printing and
paint-manufacturing workers. The results predominantly
suggested a noncochlear site of damage, perhaps with
central auditory pathway (brain stem) involvement, and
increased risk of hearing loss at high-concentration ex-
posures. Equilibrium disorders and cerebral damage have
been reported among toluene abusers.
Styrene
Styrene is a volatile liquid with a low pressure value that
is widely used in the production of various plastics,
synthetic rubber, resins, and insulating materials. It is a
building block for the manufacture of a broad range of
materials used in thousands of products throughout the
world. Probably the most recognizable material is poly-
styrene, often encountered as expanded polystyrene
foam. Other styrene-based materials include acrylonitrile
butadiene styrene, styrene acrylonitrile, styrene buta-
diene rubber, and unsaturated polyester resin, which is
better known as fiberglass.
The substance can be absorbed into the body by in-
halation and through the skin. It irritates eyes, skin, and
respiratory tract. Swallowing the liquid may cause as-
piration into the lungs with the risk of chemical
pneumonitis.
Repeated or prolonged contact with skin may cause
dermatitis, skin sensitization, and asthma. The substance
may have effects on the central nervous system. This
substance is possibly carcinogenic to humans.
Ototoxic effects
Like for toluene, evidence for styrene ototoxicity comes
mainly from animal studies although more and more
758 Combined Exposures to Noise and Chemicals at Work

(a) Solvents only

>5 years’ exposure; questionnaire study 1.4 (1.1−1.9)

3 years’ exposure to jet fuel and noise; adjusted for age,

gender, and noise exposure 1.7 (1.14−2.41)

Oil refinery; current exposure: toluene up to 18 ppm 1.8 (0.6−4.9)

Dockyard + paint and lacquer industry; exposure

to solvent and noise; value adjusted for age, gender, and current exposure to 2.4 (1.6−3.7)
noise

12 years’ exposure to jet fuel and noise; adjusted for age,

gender, and noise exposure 2.41 (1.04−5.57)

Aviation industry; current exposure: toluene up to 3.6 ppm,

xylene up to 2.24 ppm; exposure index <1 2.57 (0.64−10.31)

Paint and lacquer industry; lifetime exposure to

xylene up to 25 ppm, toluene up to 24.7 ppm; exposure index 0.3−3.0; 28% 2.8 (1.8−4.3)
overexposed; noise <85 dB

Painters; current exposure: toluene up to 70 ppm, xylene 5.0 (1.5−17.5)

up to 40 ppm; exposure index up to 1.53

Styrene mean worklife exposure 15 ppm 5.2 (2.9−8.9)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

(b) Solvents and noise

>5 years’ exposure; questionnaire study 1.8 (1.6−2.1)

Paint and lacquer industry; solvent mixture and

noise; exposure to styrene: up to 25 ppm, toluene: up to 24.7 ppm; exposure index 2.8 (1.6−4.9)
0.3−3.0; noise 86−90 dB(A)

Oil refinery workers; current exposure: toluene up to 5.1

ppm, xylene up to 11 ppm, benzene up to 32 ppm; noise 3.0 (1.6−4.9)
≥85 dB(A)

Dockyard workers; solvent mixture and noise;

current exposure: xylene up to 245 mg m−3, toluene up to 29 mg m−3; noise 93 4.9 (3.1−7.7)
dB(A)

10.9 (4.1−28.9)
Toluene and noise; toluene 75−600 ppm; noise 88−98 dB(A)

10.9 (4.9−24.2)
Styrene and noise; styrene mean worklife
exposure 8.4 ppm; noise 88 dB(A)

21.5 (5.1−90.0)
Styrene and toluene and noise; styrene mean
worklife exposure 8.4 ppm; noise 88 dB(A)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

Figure 1 Adjusted risk/odds ratio measures of hearing loss by type of exposure. (a) Solvent-only exposures; (b) solvent and noise
exposures.

human studies prove the animal results. In rats, styrene is
more harmful to the cochlea than toluene. Elevated
auditory brain stem thresholds were found in rats after
inhalation exposure to xylene or styrene, and loss of
OHCs have been observed in rats exposed to styrene.
Chronic occupational exposures seem to influence
hearing thresholds over a wide range of frequencies.
Some workers in a plastics boat plant with chronic ex-
posure to styrene showed distorted speech and poor
performance on cortical response audiometry tests.
 Combined Exposures to Noise and Chemicals at Work
Xylenes (meta, ortho, and para)
Meta-, ortho-, and paraorthologs of xylene are known as
xylenes having similar chemical characteristics. They are
colorless liquids with a characteristic odor. Mixtures of
o-, p-, and m-xylenes are extensively used in the
chemical industry as solvents for products including
paints, inks, dyes, adhesives, pharmaceuticals, and de-
tergents. In the petroleum industry, xylenes are used as
antiknock agents in gasoline and as an intermediate in
synthetic reactions.
They can be absorbed into the body by inhalation,
through the skin, and by ingestion. They are irritating to
eyes and skin and may effect the central nervous system.
If swallowed, they can be aspirated into the lungs and
may result in chemical pneumonitis. In the liquid form
they defat the skin and may have effects on the central
nervous system. Animal tests have shown that they pos-
sibly cause toxicity to human reproduction or
development.
Ototoxic effects
There is no data in the literature concerning the occu-
pational exposure to pure xylene. Xylene as a main
compound of a mixture was shown to affect hearing in
humans.
Ethylbenzene
Ethylbenzene is a colorless liquid, with aromatic odor. It
is mainly used in the manufacture of styrene. The sub-
stance can be absorbed into the body by inhalation of its
vapor and by ingestion.
Ethylbenzene has been found to potentially cause
drowsiness, fatigue, headache, and mild eye and re-
spiratory irritations when people are exposed to levels
above the OELs for a short period of time. Long-term
exposure to ethylbenzene can cause damage to the liver,
kidneys, central nervous system, and eyes.
Ototoxic effects
Ethylbenzene was proven to be ototoxic in animal stud-
ies. The functional and histological patterns of the
hearing loss induced by ethylbenzene are very similar to
the effects of toluene or styrene. This chemical is the
most potent ototoxic organic solvent known today. No
human data is available, since in occupational exposures,
ethylbenzene constitutes usually a minor part of a mix-
ture of solvents.
Trichloroethylene
TCE is a colorless liquid, with characteristic odor. It is
mainly used as a degreaser of metal surfaces; an ex-
traction solvent for greases, oils, fats, waxes, and tars; a
chemical intermediate in the production of other
chemicals; and a refrigerant. It is used in consumer
products such as typewriter correction fluids, paint
759
removers/strippers, adhesives, spot removers, and rug-
cleaning fluids.
Its vapor is heavier than air and can irritate the re-
spiratory tract. It can affect central nervous system,
leading to visual disturbances and mental confusion, in-
coordination, headache, nausea, euphoria, and dizziness.
Inhalation of high concentrations of TCE can lead to
unconsciousness, heart effects, liver effects, kidney ef-
fects, and death.
Continued skin contact has a deflating action and can
produce rough, dry, and red skin resulting in secondary
infection. Vapors may cause severe irritation with redness
and pain. Workers chronically exposed may exhibit cen-
tral nervous system depression, intolerance to alcohol,
and increased cardiac output. TCE has been linked to
mutagenic effects in humans.
Ototoxic effects
TCE has been identified as an auditory toxicant in la-
boratory animals. It affects the cochlea and spiral gan-
glion cells, although ototoxic mechanism of TCE may
differ from that of other aromatic solvents. An interaction
of exposure to TCE and noise at the lower edge of the
range of frequencies in rats was observed.
Individual medical case histories implicate TCE as a
toxicant with possible ototoxic and vestibulotoxic prop-
erties. Workers claimed many health complaints and
suffered from high-frequency sensorineural hearing loss.
The hearing impairment was considered to be caused by
damage to the auditory nerve resulting from TCE
exposure.
n-Hexane
n-Hexane is a widely used aliphatic hydrocarbon. It is
made from crude oil that is mixed with solvents for
several uses. Several consumer products contain n-hex-
ane, such as gasoline, quick-drying glues used in various
hobbies, and rubber cement.
n-Hexane is irritating to the skin. Swallowing it may
cause aspiration into the lungs with the risk of chemical
pneumonitis. Exposure at high levels could cause de-
terioration of consciousness.
Ototoxic effects
In animal studies n-hexane has been recognized to be
ototoxic alone, whereas human studies reported the same
effect in combination with noise. n-Hexane has been
mostly studied when presented in solvent mixtures.
Jet fuel
A high proportion of aromatic solvents are often found in
fuels used in military and civil aviation, like in JP-8
common in the USA. They contain several known oto-
toxic solvents: toluene, xylenes, ethylbenzene, styrene,
and n-hexane. There is limited epidemiological evidence
760 Combined Exposures to Noise and Chemicals at Work
that jet fuel exposures may increase the risk of hearing
loss among exposed air force personnel.
Heavy Metals
Heavy metals are the stable metals or metalloids of
density greater than 4.5 g cm 3, for example, lead, copper,
nickel, cadmium, zinc, mercury, and platinum. Heavy
metals are natural constituents of the earth’s crust. They
cannot be degraded or destroyed, and therefore, they
tend to accumulate in soils and sediments. In addition to
environmental exposures, they are extensively used in the
industry. The principal man-made sources of heavy
metals are, for example, mines, foundries and smelters,
and diffuse sources such as combustion by-products and
traffic. Relatively volatile heavy metals and those that
become attached to airborne particles can be widely
dispersed on very large scales.
Heavy metals are not metabolized by the body and
accumulate in the soft tissues or in the bones, causing
toxic effects. They may enter the human body through
food, water, or air, or through the skin when they come in
contact with humans in residential and occupational
settings as well as in the general environment. Commonly
encountered heavy metals that could be ototoxic are
lead, mercury, arsenic, and cadmium.
Lead
Every year, industry produces approximately 2.5 million
tons of lead throughout the world. In most of the cases,
lead is used for batteries, but it is also used for cable
coverings, plumbing, ammunition, and fuel additives.
Other sources of lead are paint pigments, PVC plastics,
X-ray shielding, crystal glass production, pencils, pesti-
cides, glazing ceramics, foods packed in cans with lead–
solder joints, ethnic foods, herbal remedies, dietary
supplements, lead emissions from fossil fuels, metals
smelting, and lead gasoline.
In 1972 approximately 400 000 tons of tetraethyl lead
were consumed throughout the world to improve the
octane rating of petrol. Since then this application has
declined dramatically because of restrictions imposed
through environmental legislation. The tetraethyl lead
market now accounts for only 1% of lead use, most of
which is in developing countries. In Europe a small
amount is still used to provide the leaded petrol re-
quirements of old vehicles, but the application will
eventually disappear.
The primary routes of human exposure to lead are
inhalation and ingestion (of water, food, air, soil, and
dust). The relative importance of any single source of
exposure is difficult to predict and will vary with geo-
graphic location, climate, and local geochemistry.
Similarly, the intensity of exposure experienced by an
individual can vary as a function of age, sex, occupation,
socioeconomic status, diet, and cultural practices. In
addition, the amount of lead taken up into the body is
believed to vary depending on the concentration and
composition (e.g., particle size and chemical form) of the
lead inhaled or ingested. Lead is causing concern in
particular due to the possible impacts on children.
Lead exposure primarily affects neurobehavioral and
endocrine systems. It results in learning disabilities,
hyperactivity, and diminished cognitive development.
Slowed growth, headaches, neuropathies, reduced dermal
sensitivity, as well as renal damage have been reported.
Ototoxic effects
Some studies of adults, children, and laboratory animals
suggest an association between lead exposure and hearing
loss. However, the findings on hearing loss from lead
exposure are contradictory, and auditory sensitivity may
not be a reliable marker of lead intoxication. One study
has shown that lead levels in blood of 5–14-year-old
children living in the contaminated Andes village were
three to twelve times greater than the US limits; however,
normal hearing thresholds and normal otoacoustic
emission were observed, proving no damage to the
cochlea. There was no correlation between hearing
threshold and lead levels in the blood. Another study
reported that the auditory brain stem response wave I
latency was delayed in children exposed to lead, sug-
gesting cochlear deficit.
There are very few studies exploring the effects of
combined lead and noise exposure. A significant correl-
ation with high long-term lead exposure (duration of
employment and ambient lead concentration) with
hearing threshold at 4 kHz, but no correlation with short-
term lead exposure (blood lead level), was found in lead
battery factory workers. No enhancement of hearing
threshold was reported with combined lead and noise
exposures.
Mercury
Mercury is found in dental amalgams, aquatic sediments,
thermometers, vaccine preservatives, fungicides, topical
antiseptics, mercury-based skin creams, gold mining, and
chlor-alkali industry, to quote the most representative
examples. It is also present in shark, swordfish, tuna fish,
and other fish species.
Mercury may occur in several stable forms. In the
environment it is mainly found as elemental mercury and
methyl mercury. In ambient air, elemental mercury vapor
is the most common compound. Owing to its long life-
time in the atmosphere, mercury is transported over
large distances. Deposition plays a major role in the
transfer of mercury from the atmosphere to surface
waters and soil or vegetation, and there is now steady
 Combined Exposures to Noise and Chemicals at Work
accumulation of mercury in soils. In the aquatic en-
vironment, mercury is transformed into methyl mercury.
The impact of mercury on human health depends on
the chemical form, that is elemental mercury, and organic
and inorganic mercury compounds. The major exposure
route to mercury is via ingestion. Chronic exposure to
mercury through any route can produce central nervous
system damage and have adverse effects on the kidneys.
It may damage developing fetuses and decrease fertility
in males and females. Mercury may cause muscle tre-
mors, personality and behavior changes, memory loss,
metallic taste, loosening of the teeth, digestive disorders,
skin rashes, brain and kidney damage, and skin allergies
and it can accumulate in the body. Methyl mercury is
classified as a possible human carcinogen by the Inter-
national Agency on the Risks of Cancer (IARC).
Ototoxic effects
Mercury intoxication causes hearing loss in humans and
animals. Mercury intoxication was first reported in 1953
among persons living in the vicinity of Minamata, Japan,
where mercury-containing effluents of a chemical-
manufacturing plant contaminated shellfish in the local
bay. Hearing impairment and deafness were reported as
some of the neurological symptoms of the ‘Minamata
disease.’ Findings consistent with Minamata disease have
been reported in other instances of accidental mercury
intoxication in Japan and Iraq.
Mercury affects hearing, with central conduction time
delay of auditory brain stem responses (ABR) (prolonged
intervals I–V, III–V), but cochlear function may be un-
affected. Interwave I–V, III–V latencies were related to
blood level of HgS and MeHg. Wave III of ABR delay has
been proposed to be used as a biomarker of prenatal
methyl mercury toxicity from contaminated seafood.
Exposures to methyl mercury seem to be more toxic than
those to mercuric chloride.
Arsenic
Arsenic is a metalloid that forms a variety of inorganic
and organic compounds.
It is released into the environment by the smelting
process of copper, zinc, and lead, as well as in the
manufacture of chemicals and glass. Its gas is a common
by-product of the manufacturing of pesticides that con-
tain arsenic.
Arsenic may be also found in water supplies world-
wide, thereby constituting a risk for shellfish, cods, and
haddocks. Other sources of arsenic are paints, rat poisons,
fungicides, and wood preservatives.
Arsenic in ambient air has important effects on human
health, leading especially to abnormalities of blood, skin,
kidneys, central nervous system, and digestive system.
761
In addition to noncarcinogenic effects, the most sig-
nificant adverse effects from prolonged exposures to ar-
senic are lung and skin carcinogens. The IARC classifies
arsenic as a known human carcinogen. Oral uptake of
arsenic is of minor importance compared to carcinogenic
effects due to inhalation.
Ototoxic effects
Arsenic overexposure damages the organ of Corti be-
ginning at the apex, with the greatest hearing losses in
the lower frequencies (at 125, 250, and 500 Hz). Analysis
of hair, blood, and urine of children living near a power
plant burning coal with high arsenic content (900–1200
grams per ton) revealed elevated arsenic levels. Signifi-
cant hearing threshold losses were also observed. Hearing
loss in industry workers is most commonly found in the
manufacturing of parasite and microorganism inhibitors.
Arsenic also causes balance disturbances.
Cadmium
Cadmium is used, for example, in nickel–cadmium bat-
teries, PVC plastics, and paint pigments. Lesser-known
sources of exposure are dental alloys, electroplating,
motor oil, and exhaust. In the general environment it can
be found in soils because insecticides, fungicides, sludge,
and commercial fertilizers that are composed of cad-
mium are used in agriculture. Cadmium may be found in
reservoirs containing shellfish, as well as in cigarettes
containing this metal.
Inhalation accounts for 15–50% of absorption through
the respiratory system; 2–7% of ingested cadmium is
absorbed in the gastrointestinal system.
Cadmium is considered to be carcinogenic and related
to occupational lung cancer.
Other health effects include kidney damage (tubular
dysfunction) causing chronic renal failure, skeletal dam-
age, and hearing dysfunction.
Ototoxic effects
Cadmium causes dose-dependent hearing loss in rats.
Increased blood and renal cortical cadmium levels have
been associated with high cadmium accumulation in ear
ossicles and labyrinth in rats exposed to cadmium. It has
been suggested that hair cells are more sensitive to
cadmium than kidney tubule cells and that the cochlear
component of hearing is more vulnerable to cadmium
toxicity than other parts of the auditory system. In fact,
wave I latency of ABRs was shown to be delayed, im-
plying cochlear dysfunction, whereas interpeak I–III la-
tencies were unchanged, confirming unaltered function
of other parts of the auditory system. Zinc-enriched diet
reduced the ototoxic effect of cadmium. Cadmium and
noise exposure have been shown to have a synergistic
effect at 4 and 6 kHz.
762 Combined Exposures to Noise and Chemicals at Work
Asphyxiants
Chemical asphyxiants are commonly used chemicals in
industry. Well-recognized asphyxiants that promote the
development of hearing loss alone or in combination with
noise are carbon monoxide (CO) and hydrogen cyanide
(HCN). They bind hemoglobin heme, thereby pre-
venting oxygen transportation.
Carbon Monoxide
CO is a colorless, practically odorless, and tasteless gas or
liquid. It results from incomplete oxidation of carbon in
combustion, thereby constituting the major combustion-
related pollutant of the air. All workers whose employ-
ment involves proximity with vehicles using internal
combustion engines have potential exposure to CO. They
included drivers of buses or trucks, mechanics and garage
attendants, and so on. In addition, CO exposure occurs in
acetylene workers, steel and coke oven workers, and pulp
and paper workers, among others. Carbon monoxide is
also produced as a metabolic by-product of the paint
stripper methylene chloride. Roughly approximately
1 million workers are exposed to significant levels of CO
in their workplaces.
CO low-concentration exposures result in fatigue in
healthy people and chest pain in people with heart dis-
ease. At higher concentrations they cause impaired vision
and coordination, headaches, dizziness, confusion, and
nausea and very often have fatal consequences.
Ototoxic effects
CO intoxication (e.g., in gas stove accidents) results in
hearing impairment, dizziness, and headache. Dizziness
and headache have been also noted in prolonged in-
toxication with H2S and SO2. These gases are common
air pollutants; thus, H2S and SO2 exposures affect the
majority of individuals. CO and H2S potentiate the
damaging effect of noise on hearing in animals. In
workers, the prolonged intoxication with CO increases
the risk of hearing loss.
Asphyxiants appear to have a synergistic effect on
NIHL. The mechanism of synergism involves increased
ROS generation. In rats, statistically significant elevations
in NIHL are observed with CO exposure of 500 ppm,
whereas OSHA ceiling admissible level is 200 ppm.
Hydrogen Cyanide
HCN is a colorless gas or bluish-white liquid with a
bitter almond odor. Cyanides are used in the extraction
of low-grade ores, in electroplating, and as chemical
intermediates. Among exposed populations are those
engaged in fumigating, electroplating, mining, metal
leaching operations, metal cleaning, and analytical
chemistry, and also in producing synthetic fibers, plastics,
dyes, and pesticides. Cyanide is a significant breakdown
product of acrylonitrile – a compound used in man-made
fibers and in certain plastics.
Exposures to HCN can occur through inhalation,
ingestion, eye or skin contact, and absorption through the
skin, eyes, and mucous membranes.
Acute exposures to cyanides can result in weakness,
headache, confusion, vertigo, fatigue, anxiety, dyspnea,
and occasionally nausea and vomiting. Coma and con-
vulsions occur in some acute cases with the danger of
death. Chronic exposures to cyanides can result in
symptoms similar to those reported after acute ex-
posures, for example, weakness, nausea, headache, and
vertigo. Dermatitis, itching, scarlet rash, and severe nose
irritation have also been reported in addition to thyroid
abnormalities.
Ototoxic effects
In rats, potassium cyanide was shown to cause impair-
ment of cochlear function, which corresponded with
blood cyanide level, and stria vascularis disruption.
Potentiation of NIHL was observed from HCN at a
concentration of 30 ppm, whereas, for example, the rec-
ommended exposure limit in the USA is approximately
5 ppm, and permissible ceiling exposure limit is 10 ppm
(averaged over 15 min). No data on occupationally ex-
posed workers is currently available.
Safety Policy Implications
The use of exposure limits and the integration of workers
in health surveillance program are nowadays the most
efficient international tools in controlling and assessing
workplace exposures. However, OELs for chemicals such
as organic solvents, heavy metals, and asphyxiants have
been established based on their toxic effects other than
hearing impairment. Enlarging the knowledge on
chemicals ototoxicity will allow to change this state in
the near future, as it is currently observed for organic
solvents.
Although no evidence for dose–response relationship
for organic solvent ototoxicity has been established so far,
in the light of the findings yielded by animal studies, it
has been suggested that current OELs for these chemicals
should be updated. Recent experiments have shown that
a 300 ppm exposure to styrene is already ototoxic to
active rats. Extrapolating this data to humans reveals that
the lowest observed adverse effect level (LOAEL) for
styrene is 30 ppm, whereas in several countries, the OEL
for styrene is set above this value. Additionally, occu-
pational exposures to styrene at levels below the lowest
accepted threshold limit value in the world (20 ppm)
were shown to affect the peripheral and central auditory
functions. It should also be underlined that current OELs
 Combined Exposures to Noise and Chemicals at Work
established for each single solvent might not be satis-
factory for hearing protection when the solvents are
mixed or combined with noise. As for other ototoxic
industrial chemicals, up to now there is no sufficient
research data whether current OELs are appropriate
regarding hearing protection.
Apart from setting exposure limits, the other kinds of
prevention should be highly recommended. They involve
avoiding/reducing exposure to chemical agents, re-
visiting the means of medical surveillance. Also raising
public awareness plays a key role in better protection of
exposed individuals at workplace, as well as in general
environment.
See also: Cadmium Neurotoxicity, Measuring Noise for
Health Impact Assessment, Mercury Toxicity, Noise and
Health: Annoyance and Interference.
Further Reading
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Mechanisms and prevention strategy. International Journal of
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Counter SA, Buchanan LH, Laurell G, and Ortega F (1998) Blood
mercury and auditory neuro-sensory responses in children and
adults in the Nambija gold mining area of Ecuador. Neurotoxicology
19: 185--196.
Counter SA and Buchanan LH (2002) Neuro-ototoxicity in Andean
adults with chronic lead and noise exposure. Journal of
Occupational and Environmental Medicine 44(1): 30--38.
Counter SA, Vahter M, Laurell G, Buchanan LH, Ortega F, and
Skerfving S (1997) High lead exposure and auditory sensory-neural
function in Andean children. Environmental Health Perspectives 105:
522--526.
de Abreu MT and Suzuki FA (2002) Audiometric evaluation of noise and
cadmium occupationally exposed workers. Brazilian Journal of
Otorhinolaryngology 68(6): 488--494.
El-Shazly A (2006) Toxic solvents in car paints increase the risk of
hearing loss associated with occupational exposure to moderate
noise intensity. B-ENT 2(1): 1--5.
Fechter LD, Cheng GD, and Rao D (2000) Characterising conditions
that favour potentiation of noise induced hearing loss by chemical
asphyxiants. Noise & Health 3(9): 11--21.
Fechter LD (2004) Promotion of noise-induced hearing loss by
chemical contaminants. Journal of Toxicology and Environmental
Health 67(8–10): 727--740.
763
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by solvent exposure. International Journal of Occupational Safety
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Johnson AC and Nylén PR (1995) Effects of industrial solvents on
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