It remains a puzzle to observe a very large interindividual
variability in susceptibility to NIHL. Whether and how much
individual vulnerability is
dependent upon external conditions occurring at time of acoustic
trauma or internal conditions linked to the genetics and
physiological condition of the subject remains unknown.
Significant progresses have been performed recently on these
126.96.36.199. Environmental factors
Noise exposures in
combination with several chemical and physical hazards, as well
as ototoxic drugs may produce more hearing impairment than could
be expected from noise-only exposure.
Chemicals are frequent contaminants in industry, some of them
might be also common in general environment
(heavy metals) or are used
in everyday life (paints and lacquers). They are classified into
three major groups:
organic solvents, heavy
metals, and asphyxiants.
Almost all studies about association of solvent fumes
respiration with traumatizing
sound exposure confirm
their clear potentiation of NIHL, (Campo et al. 2001, Morata et
al. 2002, Morata et al. 2003, Sliwinska-Kowalska 2003,
Sliwinska-Kowalska et al. 2005, El-Shazly 2006).
Ototoxic effects of organic aromatic solvents, such as
toluene, styrene, xylene, trichloroethylene, benzene, n-hexane
and their mixtures are well recognized. These chemicals are
frequent air contaminants in industry, such as in paint and
lacquer factories, dockyards, printing industry, yacht
manufacturing, furniture making, plastics and fibers processing,
rubber tires production and many other industrial activities.
Exposure may also occur in domestic settings through processed
wood products, plastics furnishing, paints and lacquers. Animal
studies have shown that several
organic solvents, as has
been exemplified by styrene and toluene, damage the
cochlea (predominantly the
supporting and outer hair cells) in rats and the exposure
(Sliwinska-Kowalska et al. 2007). Alcohol exposure, although
alone it does not produce hearing loss, increases significantly
the degree of hearing impairment caused by styrene or toluene
(Campo et al. 1998, Campo et al. 2000). Synergistic effects
occur in rats exposed to both
noise and solvents (Campo
et al. 2001, Sliwinska-Kowalska et al. 2007)). It means that
hearing impairment is higher than the sum of hearing loss
produced by solvent exposure and noise exposure alone. In
combined exposures, the most important factor for inducing
hearing impairment is potency of noise exposure (level,
impulsiveness); concomitant exposure to organic solvents may
induce impairment where the exposure to noise alone may have
The ototoxicity of
organic solvents in
occupationally exposed human individuals is more difficult to
elucidate. This is because the concentration of chemicals is
much lower than that used in animal studies, and the workers are
usually exposed to a mixture of solvents at widely varying
compositions and concentrations, disabling the assessment of the
effect of a single substance (Sliwinska-Kowalska et al. 2001).
However, investigations on humans confirm the findings in
animals. It has been shown that organic solvents have
detrimental effects not only on peripheral, but also on central
part of the auditory pathway (Johnson et al. 2006, Fuente and
McPherson B, 2007). Thus, pure-tone audiogram might be
insufficient to monitor this effect, and central auditory tests
must be implemented. An additive or synergistic effect occurs in
case of the combined exposure to
noise and solvents,
significantly increasing the odds ratio of developing
(Sliwinska-Kowalska et al. 2003, Sliwinska-Kowalska et al.
2004). The risk for hearing loss increases with the growing
number of solvents in a mixture.
Extensive use of
heavy metals in industry
adds to the environmental exposures to these substances. Heavy
metals are not metabolised 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, air, or absorption
through the skin when they come in contact with humans in
residential and occupational settings as well as in the general
environment. Commonly encountered toxic heavy metals include
lead, mercury, cadmium and arsenic.
Most of the lead is used for batteries. The remainder is used
for cable coverings, plumbing, ammunition, and fuel additives.
It has been shown that the exposure to lead results in delayed
wave I latency of ABR,
dysfunction (Osman et al. 1999). But the findings on
lead-induced hearing loss
are inconsistent (Farahat et al. 1997, Forst et al. 1997, Baloh
et al. 1979, Counter et al. 1997, Otto et al. 1985, Buchanan et
There are very few studies exploring the effects of combined
lead and noise exposure.
Elevated hearing thresholds have not been reported for lead and
noise combined exposure (Wu et al. 2000).
Mercury is found in dental amalgams, aquatic sediments,
thermometers, vaccine preservatives, to quote a few examples. It
is present in the atmosphere, and also in shark-, sword-,
tuna-fish and other fish species. First, mercury intoxication
was reported in 1953 among persons living in the vicinity of
Minamata, Japan, where mercury-containing effluent flowing from
a chemical manufacturing plant into the local bay contaminated
shellfish. Hearing impairment and deafness were reported among
other neurological symptoms of the “Minamata disease”.
Mercury affects hearing, with central conduction time delay
(ABR I-V, III-V), but
cochlear function may be
unaffected (Counter et al. 1998a and b, Rice and Gilbert 1992;
Murata et al. 1999).
Cadmium is used e.g. in nickel-cadmium batteries, PVC
plastics, and paint pigments. Cadmium causes dose-dependent
hearing loss in rats;
wave I was delayed,
dysfunction. Zinc-enriched diet reduced the ototoxic effect of
cadmium, while noise
exposure shows a synergistic effect at 4 and 6kHz (De Abreu and
Arsenic is released into the environment by the smelting
process of copper, zinc, and lead, as well as in the manufacture
of chemicals and glass. Arsenic overexposure results in
disorders in the Organ of Corti beginning at the apex with the
greatest hearing losses in the lower
frequencies (at 125, 250,
and 500 Hz). Arsenic
produces also balance disturbances.
Carbon monoxide (CO) and hydrogen cyanide (H2S)
bind hemoglobin heme, thereby preventing oxygen transportation.
The CO intoxication (e.g. in gas stove accidents) results in
hearing impairment, dizziness and headache. Dizziness and
headache were also noted in the prolonged intoxication with
HS2 and SO2. These gases are common air
pollutants; thus, H2S and SO2 exposures
affect the majority of individuals. CO and H2S
potentiate damaging effect of
noise to hearing in
animals. The effects of combined exposure to noise and
asphyxiants in human are not fully recognized.
hearing loss may be
developed in patients after temporal bone surgery or in subjects
working with vibrating tools. In such cases, co-exposure to
noise and vibration can
hearing threshold shift
compared to noise-only exposure.
Recent studies concerning association of body vibration with
sound trauma brought
contradictory and inconclusive results (Palmer et al. 2002a,
Silva et al. 2005).
188.8.131.52. Ototoxic drugs
Several drugs used in contemporary medicine can damage
hearing. Ototoxic effect depends on the dose, way of application
and the type of medicine. Although these drugs can damage
hearing at different levels of the auditory pathway, majority of
them exert mainly cochlear
ototoxic effect and they are competitive with
noise in damaging hair
The main groups of drugs that can cause
hearing loss are:
- antineoplastic drugs (cisplatinum, carboplatinum)
- loop diuretics (furosemide, ethacrinic acid)
(acetyl salicylate acid)
- antimalaric drugs.
The most commonly used drugs that have been reported in the
literature to result in hearing damage are aminoglycosides and
anti-neoplasmatic drugs. Aminoglycosides are used parenterally
in treating severe
bacterial infections. After
prolonged treatment with such aminoglycosides like gentymycin,
hearing loss at high
tinnitus and vestibular
disorders were noted. The changes in hearing are irreversible.
Prior exposure to noise
(and vibration) increases the risk of hearing impairment due to
aminoglycosides. The ototoxic effect depends on genetically
determined susceptibility; it increases with high concentration
of ferrum ions in the blood, and low protein diet. Anti-oxidant
substances (like Vitamins
A, C and E) have been shown to be protective.
It has been shown that
cancer chemotherapy with
hearing loss in up to 31%
of patients. As in
noise-induced hearing loss
and aminoglycoside-induced hearing loss, these chemotherapeutics
affect mainly hair cells of the basic turn in the
cochlea and result in
high-frequency (above 2
kHz) hearing impairment. Noise exposure at the time of
chemotherapy significantly increases the risk of hearing
The advance of genetic
research and associated tools triggered a series of explorations
of the human genes possibly involved in NIHL, first evidences
point to some candidate genes and seem to exclude other genes
(Fortunato et al. 2004, Heinonen-Guzejev et al. 2005, Yang et
al. 2005, Yang et al. 2006, Van Laer et al. 2006, Yang et al.
2006, Sliwińska-Kowalska et al. 2006, Konings et al. 2007, Van
Eyken et al. 2007). The mechanisms of acoustic trauma involve
both metabolic stress and micromechanical damage to the outer
hair cells, predominantly to their stereocilia. Thus, good
candidate genes are those encoding oxidative stress enzymes,
mitochondrial proteins, and proteins involved in
K+ recycling pathway. The importance of oxidative
stress genes has been shown in knockout mice, including
SOD1-/- (Ohlemiller et al. 1999), GPX1-/-
(Ohlemiller et al. 2000), and PMCA2-/- mice (Kozel et
al. 2002), all of which were more sensitive to
noise than their wild-type
littermates. However, these results have not been confirmed in
humans (Carlsson et al. 2005). A more recent study suggests a
possible role of potassium recycling pathway genes in the
susceptibility to NIHL in human workers (Van Laer et al.
Some of the differences in susceptibility to NIHL have been
attributed to various other genetically dependent factors, like
eye colour (blue-eyed more susceptible), and pigmentation
(African-Americans showed a somewhat better average in
hearing threshold levels
than Caucasians), gender (women more susceptible than men), age,
etc (Henderson et al. 1993, Pyykkö et al. 2007). Also short
stature has been recently recognized as a risk factor for
developing sensorineural hearing impairment (Barrenäs et al.
184.108.40.206. Other factors
The gender of an individual has been often considered as a
possible influencing factor with men appearing somewhat more
affected than women. The difference however seems minimal if
present (Müller 1989).
A predominance of left ear
vulnerability as compared
with right ear has been confirmed (Nageris et al. 2007) but the
difference is small and shows mostly on average data.
Cardio-vascular alteration was often studied as a possible
factor influencing NIHL but data are contradictory and the
subject remains a matter of debate. Recent studies tend to
confirm that alterations of blood pressure can be related with
NIHL but it remains unknown whether it might be a cause or a
simultaneous effect (Souto Souza et al. 2001, Toppila et al.
2001, Narlawar et al. 2006, Ni et al. 2007). A more detailed
presentation is provided further in this report.
Evidence that smoking increases the risk of NIHL were provided
long ago, all recent studies on this matter confirmed this
assertion (Mizoue et al. 2003, Ferrite and Santana 2005, Uchida
et al. 2005, Burr et al. 2005, Wild et al. 2005, García Callejo
et al. 2006, Pouryaghoub et al. 2007).
Vitamin deficiencies were
previously suspected to influence NIHL. Two recent studies
brought evidence for the involvement of vitamin B12 (Quaranta et
al. 2004, Gok et al. 2004).
The cochlear efferent
innervation has long been known to be involved in NIHL. Recent
studies further showed that assessment of cochlear efferent
functioning did not clearly relate with NIHL (Veuillet et al.
2001, Shupak et al. 2007, Wagner et al. 2005).
The production of heat shock proteins constitute a
physiological response to stress, first evidence for their
implication in NIHL was recently provided (Yang et al. 2004,
Yuan et al. 2005).