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J Am Acad Audiol 23:824-830 (2012)

Case Report

Hearing Loss Associated with Xylene Exposure


in a Laboratory Worker
DOI: 10.3766/jaaa.23.10.7

Adrian Fuente*
Bradley McPhersonf
Linda J. Hoodt

Absfracf

Background: Xylene is an organic solvent, vi/idely used in histology laboratories and other occupational
settings. Research in animals has demonstrated that xylene induces outer hair cell damage. Evidence
regarding the effects of xylene in humans is only available from studies investigating workers exposed to
mixtures of^solvents containing xylene. These data indicate that mixtures of solvents containing xylene
may induce hearing loss and central auditory dysfunction.

Purpose: To comprehensively evaluate the peripheral and central auditory system of a histology labo-
ratory worker exposed to xylene, who had presented with bilateral mild sensorineural hearing loss at an
initial assessment.

Research Design: A case report of a male histology laboratory worker who has been exposed to xylene
for over 20 yr.

Results: A diagnosis of bilateral mild sensorineural hearing loss of cochlear origin was made on the basis
of otological, neuroimaging, and audiological examinations. Results indicating the absence of transient-'
evoked otoacoustic emissions, and auditory brainstem responses as expected for a mild cochlear hear-
ing loss, were obtained.

Conclusions: The observed bilateral mild sensorineural hearing loss was considered to have been
induced by xylene exposure, due to the absence of any other etiological factors related to the onset
of hearing loss. The results found in this patient are in agreement with animal data indicating xylene-
induced ototoxicity. Xylene-exposed individuals should be audiologically monitored on a regular basis.

Key Words: Occupational hearing loss, organic solvents, xylene


Abbreviations: ABR = auditory brainstem response; [(C)AP] = (central) auditory processing; DD = Dichotic
Digits test in Spanish; FS = Filtered speech test in Spanish; HINT = Hearing-ln-Noise test; HL = hearing level;
MRI = magnetic resonance imaging; nHL = normal hearing level; OHC = outer hair cell; PEL = permissible
exposure limit; PPS = Pitch Pattem Sequence test; RGDT = Random Gap Detection test; SNR = signal-to-
noise ratio; TEOAE = transient-evoked otoacoustic emission; TWA - time-weighted average

INTRODUCTION used as a solvent (a liquid that can dissolve other substan-


ces) in paints, varnishes, degreasers, paint thinners, and
ylene (C8H10) is an organic solvent, produced pesticides. A common form of laboratory exposure occurs

X from coal tar or by the aromatization of petroleum


hydrocarbons (Johnson and Morata, 2010). It is
during the preparation of tissue specimens for histol-
ogic examinations (Baselt and Cravey, 1989). Xylene

*School of Speech and Hearing Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile; tCentre for Communication Disorders,
Faculty of Education, University of Hong Kong, Hong Kong; ^Department of Hearing and Speech Sciences, Vanderbilt University, Nashville TN

Jrian Fuente, School of Speech and Hearing Sciences, Faculty of Medicine, Universidad de Chile, Independencia 1027, Santiago, Chile; Phone:
Adrian
4-56i 2 978 6606; Fax:
I -1-56 2 978 6608; E-mail: afuente@med.uchile.cl
This work was supported by the National Fund for Scientific and Technological Development (FONDECYT), Chile, Project number 11080270.
Xylene-Induced Hearing Loss/Fuente et al

is rapidly absorbed following inhalation or ingestion, ated with xylene exposure (Draper and Bamiou, 2009).
but is less well absorbed through intact skin. The highly One ofthe main symptoms was the inability to discrim-
volatile nature of xylene makes inhalation the most inate speech in the presence of background noise. Diffi-
efficient route of absorption (Horowitz, 2001). Since culties in understanding foreign accents and speaking on
systematic studies on solvent-induced hearing loss com- the telephone were also reported by the patient, who was
menced, xylene has been implicated as an ototoxic agent exposed to xylene in his workplace over a period of 6 mo,
(Gagnaire et al, 2001). with poor ventilation. The hearing difficulties were exa-
The effects of xylene on the human auditory system cerbated with aging and indeed, the auditory neuropathy
have been studied only in populations of factory workers was cUnically diagnosed 40 yr postexposure to xylene.
exposed to mixtures of solvents containing xylene, as In summary, despite evidence from animal studies
factory workers are not typically exposed to isolated that xylene induces hearing loss due to the loss of OHCs,
agents. Human studies have found that exposure to mix- there is limited understanding of whether xylene in iso-
tures of solvents is associated with hearing loss (Morata lation may also induce OHC loss in humans. As the
et al, 1997; Sliwiñska-Kowalska et al, 2000) and central industrial use of xylene seldom occurs alone, but occurs
auditory dysfunction (Fuente et al, 2011). Animal mod- rather in combination with other solvents, study of
els, on the other hand, allow study of the adverse audi- the ototoxicity of xylene in humans is difficult. Data
tory effects ofthe agents in isolation. Data from animal from human studies cannot differentiate whether the
models suggest that exposure to xylene in isolation is adverse auditory signs observed in workers exposed
associated with loss of outer hair cells (OHCs) and thus to mixtures of solvents containing xylene are due to
peripheral hearing loss (Gagnaire et al, 2007). the ototoxic effects of xylene, to the effects of other sol-
In rats, a slight loss of OHCs has been observed in the vents, or to those solvents in combination, rather than
first row, with greater loss in the second and third rows the organic solvents in isolation.
(Gagnaire and Langlais, 2005). Studies conducted in The aim of the present manuscript is to report an
rats exposed to xylene have found OHC damage, mainly unusual hearing loss associated with xylene exposure
in the midrange (8-24 kHz) ofthe rats' audible frequen- in a histology laboratory worker. The patient developed
cies (Pryor et al, 1987; Crofton et al, 1994). It is impor- a cochlear hearing loss (pure- tone thresholds worse
tant to note that the ototoxicity induced by xylene is than 25 dB hearing level [HL]) in the 1-6 kHz range
species-dependent. Gagnaire et al (2007) have demon- (based on standard pure-tone audiometry). The patient
strated that rats, but not guinea pigs, are susceptible was exposed to xylene over a long period of time. The
to the ototoxic effects of xylene. authors were unable to find any similar case report
In humans, Shwinska-Kowalska et al (2000) studied a in the literature, in which the exposure to organic sol-
population of 117 paint and lacquer factory workers who vents had been exclusively to xylene.
were exposed madnly to a mixture of xylenes and ethyl
acetate. The research design also included two nonex- METHOD
posed control groups. The results indicated that the group
of workers exposed to xylene and ethyl acetate had worse Case Report
hearing thresholds than the nonexposed workers. A
high percentage (30%) of hearing loss was found among A 46-jT-old Caucasian male visited the Audiology
exposed workers, in comparison to nonexposed workers. Laboratory of the School of Speech and Hearing Scien-
The relative risk value for hearing loss in xylene-exposed ces, Medical Faculty, University of Chile, as a research
workers was greater (9.6) when compared to that for volunteer. He was a histopathologist, who had been
workers only exposed to noise (4.2). Fuente et al (2011) working at a histopathology and cytodiagnostics labora-
studied a group of factory workers who were exposed tory in a Chilean public hospital for 23 yr. He reported
to a mixture of solvents containing toluene, methyl ethyl working directly with xylene, on an everyday basis,
ketone and xylene, and a nonexposed control group of using it for human tissue processing, staining, and
subjects. A comprehensive test battery was used to inves- cover slipping. According to the patient's report, his
tigate the central auditory system. Solvent-exposed work- most direct exposure to xylene was when samples with
ers presented with significantly worse results for most of human tissue had to be embedded in a receptacle with
the tests in comparison to control group subjects, indicat- xylene, for approximately 40 min while he remained at
ing central auditory dysfunction associated with solvent the same room as the receptacle. He then had to take
exposure. Similar results have been found in other stud- the sample from the receptacle for examination under
ies investigating workers exposed to different mixtures of microscope. He reported that no gloves were used when
solvents (Fuente et al, 2007; Johnson et al, 2006; Laukli handling the sample embedded in xylene. The level of
and Hansen, 1995; Ödkvist et al, 1987). exposure varied according to the demand for samples
A case report was recently published regarding a requiring examination. The higher the number of sam-
patient who had developed auditory neuropathy, associ- ples to be examined, the greater the amount of xylene

8S5
Journal of the American Academy of AudiologyA^olume 23, Number 10, 2012

used, and therefore the higher the expected level of air- lOCX) 2000 8000 H!

borne xylene concentration. On average, he reported 0


performing this task approximately four times per 10
day. A recent monitoring of airborne xylene concentra- 20
• ^
A
pi"" "" "'"' '"ftLi ^—*^
tion during 70% of the work shift at the site vsfhere the 30 !]__——=^
40
patient performed his duties showed a mean xylene air- I 50
borne concentration of 60 mg/m^. The permissible expo- € 60
sure limit (PEL) for xylene in Chile is 347 mg/m^ as an 70
80
8-hr time-weighted average (TWA) concentration (Min-
90
isterio de Salud de Chile, 2000) (in the United States, 100
the current Occupational Safety and Health Adminis- 110
tration (OSHA) PEL for xylene is 435 mg/m^ as an 8- 120

hr TWA concentration (US Department of Labor, 8000 Hz


Occupational Safety and Health Administration, 2011).
B
-10
Therefore, the patient's xylene exposure was below 0
Chilean and US OSHA norms for airborne xylene expo- 10
sure levels. 20 SH K

f
No personal protection against xylene had been uti- 40
^7^ 7
lized by the patient. During the interview, he did not I 50
€ 60
complain of hearing problems; however, no previous 70
hearing assessment results were available. The patient 80
reported that the level of noise exposure at his work- 90
100
place was not high and that he did not regularly partic- 110
ipate in noisy activities such as attending night clubs, 120
live concerts, sporting events, or parties. Medically, the
patient did not report a history of diabetes, high blood Figure 1. (A) IniüeJ air-conduction hearing thresholds for the
right (O) and left ear (X), and bone-conduction hearing thresholds
pressure, kidney dysfunction, metabolic or neurologic for the right ([) and left ear (]). • denotes the expected pure-tone
diseases. The patient reported drinking alcohol and thresholds for the 10% of people with worse hearing level from an
smoking cigarettes socially. No history of past ear infec- otologically screened population between 40 and 49 yr of age (Inter-
tions or family history of hearing loss was reported. On national Standards Organization 7029, 2000). (B) Air-conduction
hearing thresholds for the right (O) and left ear (x), and bone-
the initial hearing evaluation, the patient presented conduction hearing thresholds for the right ([) and left ear (])
with bilateral mild sensorineural hearing loss (see Fig- obtained 4 mo after the initial audiogram. • denotes the expected
ure lA) and bilateral type A results (Jerger, 1970) for pure-tone thresholds for the 10% of people with worse hearing
tympanometry. The patient was referred to an otolar- level from an otologically screened population between 40 and
yngologist for medical assessment and management. 49 yr of age (International Standards Organization 7029, 2000).
Four months after the first audiological assessment,
the patient was reassessed. ported no evidence of internal auditory canal mass.
Brain imaging was also negative for infarct, hemor-
Otological Examination rhage, mass, extra-axial fluid, or hydrocephalus.

The otological examination revealed normal external Audiological Assessment


ear canals and tympanic membranes bilaterally. No
abnormalities for the nasal cavity and throat were Four months after the first hearing evaluation the
reported. There was no history of any medical condi- patient was reassessed. A double-wall sound-treated
tions that could be associated with the onset of hearing audiometric booth meeting specifications for permissible
loss, with the exception of xylene exposure. The patient ambient noise (International Standards Organization
did not present with any abnormal neurological signs or 8253-1, 1989) was utilized for pure-tone audiometry,
symptoms. The patient was referred for a comprehen- transient-evoked otoacoustic emissions (TEOAEs),
sive hearing assessment and for magnetic resonance auditory brainstem response (ABR), hearing-in-noise
imagining (MRI) examination. test (HINT), and behavioral (central) auditory process-
ing [(C)AP] assessment. A clinical audiometer (Intera-
MRI coustics AC33) delivered all stimuli via TDH-39P
headphones for air-conduction thresholds and via a
MRI of the brain and temporal bone with and without Radioear B-71 bone vibrator for bone-conduction thresh-
gadolinium contrast was obtained 4 mo after the initial olds. A compact disc player (LG 73 UN), connected to
hearing assessment. The supervising radiologist re- the audiometer specified above, delivered all recordings

8S6
Xylene-Induced Hearing Loss/Fuente et al

of the (C)AP tests. The (C)AP assessment comprised and contralateral acoustic (stapedius muscle) refiexes
the Dichotic Digit (DD) test in Spanish (Fuente and in both ears (see Table 1), with negative results for ipsi-
McPherson, 2006), Random Gap Detection test (RGDT) lateral and contralateral acoustic refiex decay tests for
(Keith, 2000), Pitch Pattern Sequence test (PPS) 0.5 and 1 kHz.
(Musiek, 1994), Masking Level Difference test (MLD) TEOAEs were absent bilaterally, as the whole-wave
(Wilson et al, 2003) and the Filtered Speech (FS) test in reproducibihty was 40% and 55% for the right and left
Spanish (Fuente and McPherson, 2006). The Hearing- ear, respectively. However, in some frequency bands,
in-Noise Test (HINT) (Nilsson et al, 1994) utilized the the signal-to-noise ratios [SNR] were above 0 dB. This
Latin American Spanish sentence module (Baron De was the case for 2 kHz in the right ear (4 dB SNR) and 1
Otero et al, 2008). Immittance audiometry was per- and 2 kHz for the left ear (3 and 5 dB SNR, respectively).
formed with an Interacoustics AZ7 middle-ear analyzer. ABR showed the presence of wave III with a latency of
For TEOAE assessment, a portable Echoport plus 3.67 and 3.7 ms for the right and left ears, and wave V
(Otodynamics) was used. This equipment was con- with a latency of 5.8 and 5.7 ms for the right and left
nected to a desktop computer with ILO 88 OAE analysis ears. ABR results were observed with better wave
sofbware. Stimuh were delivered to the ears via an adult reproducibihty in the left ear. All the ABR values were
B-type ILO otoacoustic emissions probe (Kemp et al, within the normal range (Hood, 1998), and overall phys-
1990). The evoking stimuh used were 80 (xs rectangular iological test results were consistent with a mild bilat-
chcks presented at 80 ± 2 dB Peak Equivalent Sound eral sensorineural hearing loss.
Pressure Level (peSPL). To control for stimulus artifact,
a "nonhnear" paradigm was used for the cHck stimuli, Behavioral Testing
where every fourth stimulus was opposite in polarity
and 10 dB higher in intensity. The response time window
Pure-tone audiometry revealed a mild bilateral sen-
was set at 2.5-20 ms and the band-pass filter was set in
sorineural hearing loss (see Figure 1). Frequencies 3, 4,'
the range from 0.5 to 5 kHz. The TEOAE was considered
and 6 kHz for both ears exhibited the worst hearing
present if a response was observed above the noisefioorin
thresholds. Hearing thresholds at 8 kHz were within
any band firom 1.0 to 5.0 kHz with whole-wave reprodu-
normal limits for both ears (equal or better than
cibiHty equal or above 65% (Glattke and Robinette, 2007).
25 dB HL). Pure-tone thresholds were similar (±5 dB
The ABR was recorded with an Interacoustics Eclipse
HL) to those ones obtained initially (4 mo previously).
Platform (EP25) instrument, using AgCl-AgCI electrodes
placed at the scalp at the vertex (Cz) and the ipsilateral For the HINT, the patient obtained an elevated
mastoid (A 1/A2), in accordance with the International speech reception threshold for sentences (31.8 dB sound
10-20 system of EEG recordings. The amplifier band pressure level [SPL]), in the binaural listening condi-
pass was set between 0.15 Hz and 3 kHz. Two trials, each tion. For noise and speech both delivered at 0° azimuth,
averaging 2000 responses, were obtained for each ear the SNR obtained was —4.3 dB; for noise delivered to
using rarefaction chck stimuh at 80 dB normal hearing the right ear and speech to the front, the SNR obtained
level (nHL), presented monaurally, at a rate of 27.7/sec was —11 dB; and for noise delivered to the left ear and
latency of wave I, latency of wave III, latency of wave speech to the front, the SNR was -11 dB. The composite
V, interpeak latencies I-III, I-V, and III-V, and absolute score for the three noise conditions was -7.7 dB. All the
amplitude (uV) of waves I, III, and V was examined. SNR scores were within the normal range (Nilsson et al,
1994).
Results for (central) auditory function tests are shown
Solvent and Noise Exposure Assessment in Table 2. All results were within normal ranges

Noise dosimetry was conducted during a whole work Table 1. Ipsilateral and Contralateral Acoustic Reflexes,
shift (8 hr/1 day). To assess xylene exposure, methyl Pure-Tone Thresholds, and Difference between
hippuric acid (a metabolite of xylene) concentration Ipsilateral Acoustic Reflex Thresholds and Pure-Tone
per gram of creatinine in urine was analyzed. The urine Thresholds for 0.5, 1, 2, and 4 kHz
sample was taken at the end of the work shift on a Fri-. Right Ear Left Ear
day and sent to the Chilean Institute of Public Health
kHz 0.5 1 2 4 0.5 1 2 4
for further analysis.
Ipsi AR 90 100 90 80 90 90 90 80
Contra AR 90 90 90 100 100 90 90 90
RESULTS TH 25 30 35 40 25 35 35 45
A 65 70 55 40 65 55 55 35
Physiological Testing Note: Ipsi AR = ipsilateral acoustic reflex (dB HL); Contra AR =
contralateral acoustic reflex (dB HL); TH = air-conduction pure-tone
Immittance audiometry showed bilateral normal type threshold (dB HL); A = difference between Ipsi AR and pure-tone
A results for tympanometry and the presence of ipsuateral threshold in dB HL.

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Journal of the American Academy of Audiology/Volume 23, Number 10, 2012

Table 2. Results of (Central) Auditory Processing Tests Age could also have affected the hearing loss. Figure 1
and Normative Values shows the expected pure-tone thresholds for the 10% of
Normative Values for people with worse hearing level from an otologically
Spanish-Speaking screened population between 40 and 49 yr of age
Adults (Fuente and (International Standards Organization 7029, 2000).
Test Results McPherson, 2006) As can be observed from Figure 1, most of the hearing
DD right ear (%) 98 '96.3 thresholds are worse than the levels expected for the
DD left ear (%) 95 96.3 patient's age. Thus, we believe that age may partially
DD both ears combined (%) 97 96.3 account for the observed hearing loss in this patient. A
RGDT 500 Hz (ms) 10 15 possible interaction between age, xylene exposure, and
RGDT 1000 Hz (ms) 2 15 smoking (Cruickshanks et al, 1998) may also account
RGDT 2000 Hz (ms) 2 15 for the hearing loss.
RGDT 4000 Hz (ms) 2 15 We conclude that this hearing loss has a cochlear ori-
RGDT clicks (ms) 2 10
gin. This conclusion relies on absent TEOAEs, absence
PPS right ear (%) 100 80
80
of consistent signs of central auditory dysfunction as
PPS left ear (%) 85
PPS both ears combined (%) 93 80
measured with behavioral auditory processing tests,
MLD (dB) 16 6.2 the presence of acoustic reflexes (ipsilateral and con-
FS right ear (%) . 48 70 tralateral), the negative acoustic reflex decay test,
FS left ear (%) 44 70 and ABR latencies within normal ranges for 80 dB
FS both ears combined (%) 46 70 nHL click stimuli. The presence of hearing loss in a per-
Note: DD = Dichotic Digits test in Spanish (Fuente and McPherson, son exposed to. solvents such as xylene is in agreement
2006); RGDT = Random Gap Detection test (Keith, 2000); PPS = with previous human cross-sectional studies (Morata
Pitch Pattern Sequence test (Musiek, 1994); MLD = Masking Level et al, 1997; Shwiñska-Kowalska et al, 2000; Sliwiñska-
Difference test (Wilson et al, 2003); FS = Filtered speech test in Spanish Kowalska et al, 2001; Chang et al, 2006), indicating
(Fuente and McPherson, 2006); ms = millisecond. the association of hearing loss with exposure to mixtures
of solvents. The cochlear type of hearing loss observed in
previously reported for Spanish-speaking adults (Fuente this patient is in agreement with previous experimental
and McPherson, 2006), with the exception of the filtered studies in rats, which have shown loss of OHCs associ-
speech test. ated with xylene exposure (Crofton et al, 1994; Gagnaire
and Langlais, 2005) and thus, cochlear-related hearing
Noise and Solvent Exposure Assessment loss induced by xylene exposure. In this patient TEOAEs
were absent, suggesting loss of OHCs.
Noise dosimetry for a whole-day work shift revealed It is important to note that the cochlear hearing loss
an equivalent noise exposure of 67.5 dBA Leq. Methyl observed in this patient is dissimilar to that noted in the
hipuric acid in urine was found at a concentration of previously mentioned case report of a person exposed
152 mg per gram of creatinine (1500 mg per gram of cre- to xylene, who had developed auditory neuropathy
atinine is the biologic tolerance limit). (Draper and Bamiou, 2009). Previous cross-sectional
human and experimental animal studies have revealed
mid- and high-frequency range hearing loss induced by
DISCUSSION solvents such as xylene (Crofton et al, 1994; Sliwiñska-
Kowalska et al, 2001; Gagnaire and Langlais, 2005;

P ure-tone audiometric results showed a mild bilat-


eral sensorineural hearing loss. Pure-tone thresh-
olds, including 8 kHz, between the first and second
Chang et al, 2006). There is, however, a case report
of a painter exposed to solvents and noise who devel-
oped a hearing disorder with maximum loss at the
assessment did not reveal differences more than 5 low- and mid-frequency range (Polizzi et al, 2003).
dB which are within the test-retest reliability previ- The.authors suggested that the unusual pattern of
ously reported (Rendell and Miller, 1983; Schmuziger hearing loss was induced by the combined effect of sol-
et al, 2004). According to the medical case history, the vents and noise. In the present case report, the patient
audiological and otological assessment and the occupa- did not have a history of occupational or recreational
tional history, xylene exposure appears to be the only noise exposure. Noise dosimetry for a typical work
etiological factor for the observed hearing loss. There- day revealed 67.5 dBA Leq. The patient in the present
fore, the hearing impairment of this patient is most case report had been exposed to xylene for over 20 jn:
likely associated with xylene exposure. However, no and reported that, during this time, he had never worn
past hearing assessments were available. Thus, the any protective equipment or clothing, such as masks or
observed hearing loss could be part of a previous hear- gloves. He also mentioned having had frequent dermal
ing loss of unknown etiology, plus the effect of xylene. contact with xylene and regularly eating in the same
Xylene-Induced Hearing Loss/Fuente et al

laboratory facilities where xylene was being used. The report, we suggest that questions concerning history
laboratory facilities were visited, where it was possible of solvent exposure should be part of the routine patient
to observe the absence of ventilation systems, extractors, examination undertaken by audiologists and otolaryng-
and other systems that would serve to diminish airborne ologists. Finally, considering thefindingsfromthe present
xylene concentrations. Airborne xylene concentrations case report, xylene-exposed persons shoxold be audiologi-
and methyl hippuric acid in urine revealed rather low caUy evaluated on a regular basis.
levels of xylene exposure; however, this must be taken
with caution. The patient had been exposed to xylene
for more than 20 JT and the assessment of xylene expo-
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T he novel aspects of the present case report are that


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Journal of the American Academy of Audiology/Volume 23, Number 10, 2012

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