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|Year : 2008 | Volume
| Issue : 40 | Page : 74--82
Audiological findings in individuals exposed to organic solvents: Case studies
Kamakshi V Gopal
Department of Speech and Hearing Sciences, University of North Texas, Denton, Texas, USA
Kamakshi V Gopal
P.O. Box 305010, Department of Speech and Hearing Sciences, University of North Texas, Denton, TX 76203
Millions of people around the world are exposed to industrial organic solvents such as toluene and xylene in the manufacturing sectors. Solvents are neurotoxic substances that are detrimental to the functioning of the nervous system, including the central auditory nervous system (CANS). This study investigated hearing and auditory processing in seven individuals with a history of exposure to industrial solvents. A battery of audiological tests was administered to all subjects: pure tone, speech, and impedance audiometry, otoacoustic emissions tests, auditory brainstem responses, middle latency responses, as well as the SCAN-A and R-SPIN tests with low predictability sentence lists. All individuals in this study exhibited findings consistent with retrocochlear and/or central abnormality. Two of the seven subjects in this study had normal pure tone thresholds at all frequencies bilaterally, yet showed abnormal retrocochlear/central results on one or more tests. The auditory test battery approach used in this study appears to be valuable in evaluating the pathological conditions of the CANS in solvent-exposed individuals.
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Gopal KV. Audiological findings in individuals exposed to organic solvents: Case studies.Noise Health 2008;10:74-82
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Gopal KV. Audiological findings in individuals exposed to organic solvents: Case studies. Noise Health [serial online] 2008 [cited 2022 Sep 26 ];10:74-82
Available from: https://www.noiseandhealth.org/text.asp?2008/10/40/74/44345
Hearing loss remains one of the most prevalent occupational diseases in the world. In the US alone, more than five million people are exposed to organic solvents, mainly toluene and xylene, in the manufacturing sector where noise is also present at high levels.  Hearing loss observed in industrial settings with high levels of solvent and noise is often assumed to be solely due to noise. , Epidemiological evidence, however, indicates that there is a two- to five-fold increase in the risk of hearing loss among humans exposed to organic solvents. ,,,,,, Several animal studies have also shown auditory impairment in solvent-exposed animals, ,,, which is potentiated when combined with noise exposure. ,, Due to various confounding factors, it has been difficult to assess individual effects of solvents,  although some studies have tried to identify auditory insults solely from exposure to solvents. ,
Organic solvents are chemicals that contain at least one carbon and one hydrogen atom. Solvents are lipophilic and have a high affinity for lipid-rich tissues such as the brain tissue. They are known to be neurotoxic substances that are detrimental to the central nervous system (CNS), causing damage to the brainstem, cerebellum, and cerebral cortex.  A fairly large volume of the nervous system is devoted to the identification and processing of auditory information, yet a perceptive understanding of the effects of solvents on the central auditory nervous system (CANS) is still missing.
Organic solvents are contaminants in the air found mostly in industries that manufacture boats, plastic, rubber tires, paint, paint thinners, insect repellents, varnishes, perfumes, artificial leather, photogravure ink, etc. These solvents enter the body through inhalation, ingestion, or skin absorption and cause damage to several structures including the cochlea and CANS pathways. Although heavy exposure to solvents can cause solvent encephalopathy, consequences of low level exposures have not been well characterized.  Furthermore, consequences of exposure to mixtures of solvents are not known either. In fact, exposure to only one solvent at a time is extremely rare because people working in these environments are usually exposed to a mixture of solvents. 
The two main solvents that industrial workers are most often exposed to are toluene and xylene. Toluene is a clear, water-insoluble liquid that occurs at low levels in crude oil and is used as an octane booster in fuel, and as a solvent in paints, paint thinners, rubber, printing, adhesives, lacquers, leather tanning, and disinfectants. Toluene has been shown to decrease N -methyl-D-aspartate currents, and increase currents generated by Gamma-aminobutyric acid (GABA) and glycine receptors.  In a study by Rosenberg et al. ,  magnetic resonance imaging (MRI) scans showed abnormal results despite abstinence from solvent exposure for 18 months, suggesting irreversible changes in the brain.
Xylene is a colorless, sweet-smelling liquid that is highly flammable. It occurs naturally in petroleum and coal tar. Xylene is found in industries that use or manufacture laboratory chemicals, paint, pesticides, printing, rubber, and leather. High levels of acute exposure or low levels of chronic exposure of xylene are known to affect the brain causing imbalance, hearing loss, and memory difficulty. ,,
Organic solvents readily cross the blood-brain barrier following inhalation and produce CNS effects similar to those of alcohol and benzodiazepines.  Positron Emission Tomography (PET) studies have indicated that solvents have rapid entry into the brain, short half-lives, and high rates of metabolism and clearance.  Memory impairment, hearing loss, eye irritation, dizziness, attention disorders, depression, and fatigue are some of the common symptoms of solvent exposure. MRI findings indicated cerebral and hippocampus atrophy, and loss of brain volume in workers chronically exposed to solvents. ,, In rats with chronic exposure to solvents, neuronal loss is reported in sensory and motor cortices, as well as in the hippocampus.  Impairment of catecholaminergic and serotonergic neurotransmission has been implicated with solvent exposures. ,,,,,, However, the exact site and mechanism of action of solvents are not fully understood.
Ameno et al .  demonstrated that in rats and in humans, the highest brain/blood concentration ratio of toluene was in the brainstem region. Whereas audiograms may not suggest any observable hearing loss in subjects exposed to solvents, these subjects may nevertheless show significant difficulty with speech understanding.  This finding suggests brainstem or central auditory system damage, a finding not seen in pure noise-induced hearing loss cases. ,,,,, Workers exposed to solvents for 9-40 years showed poor speech discrimination scores and poor cortical responses to frequency glides, indicating auditory cortex abnormalities. 
Animal studies and case reports on toluene abusers indicated peripheral as well as central hearing loss. ,, In the rat, toluene disrupted the outer hair cells and was thought to mimic the effects of cholinergic receptor antagonists.  Auditory brainstem responses (ABR) in workers exposed to an average of 99 ppm of toulene showed statistically significant prolonged latencies and longer interpeak latencies among ABR waves compared to nonexposed subjects matched for gender and age.  ABRs obtained from 49 workers occupationally exposed to low concentrations of toluene for 20 years, showed significant reduction of peak amplitudes and prolongation of peak latencies.  Prolongation of P300 (auditory cognitive evoked potential) latency along with a reduction in its amplitude was also demonstrated in toluene-exposed individuals. , Fuente et al .  found statistically significant differences in auditory processing tests in workers exposed to a mixture of solvents compared to an age-matched control group.
This clinical study intended to assess the performance of peripheral and central auditory systems in individuals with a history of exposure to solvents.
This study reports results from seven adults who were recruited via a local newspaper advertisement, which sought individuals exposed to industrial solvents such as toluene, styrene, and xylene. The advertisement and the study were approved by the University's Institutional Review Board. All seven individuals reported in this study had a history of exposure to toluene, xylene, or both, for a period of at least three years. All subjects had normal middle ear function, no known neurological or psychological disorders, were not on any prescribed or nonprescribed CNS drugs, and were all native speakers of English. The test battery [Table 1] for all subjects consisted of the following tests: Case history, otoscopy, pure tone audiometry, speech audiometry tests, i.e ., speech recognition threshold (SRT) and word recognition score (WRS), impedance audiometry, i.e ., tympanometry and acoustic reflex threshold (ART) tests, otoacoustic emissions tests, i.e ., spontaneous emissions, transient otoacoustic emissions (TEOAE), and distortion product otoacoustic emissions (DP), the SCAN-A test, the Revised Speech Perception in Noise (R-SPIN) test with the low predictability sentence list, auditory brainstem responses (ABR), and middle latency responses (MLR). ABR and MLR waveforms were analyzed for absolute peak latencies, absolute peak amplitudes, amplitude growth, and waveform morphology. Absolute latencies from subjects were compared to the normative data used in the author's laboratory [Table 2]. Amplitude growth for ABR peak V and MLR peak Na was defined as the increase in amplitude between 40 and 80 dB nHL click intensity levels [Table 2]. Waveform morphology refers to the clarity, resolution, and definition of the auditory evoked potentials. 
[Table 1] lists the tests performed, anatomic sites targeted, criteria for normalcy, and implications of abnormal findings in these tests. All testing was done according to ASHA standards and procedures using calibrated equipment. Assessment of auditory processing capabilities was done using the SCAN-A test and the low predictability part of the R-SPIN test at 0 (zero) message-to-competing ratio (MCR). Abnormal scores indicate that the subject is at risk for central auditory processing disorders.  The test was administered at the subject's most comfortable loudness level (MCL) to account for any hearing loss. Data obtained from subjects on behavioral, electroacoustic, and electrophysiological tests were compared to the standard clinical norms adopted in the University's Speech and Hearing Clinic and the author's laboratory. Details can be found in our earlier publications. ,,,
Common findings among all subjects
Results indicated that all seven subjects had: (1) Type A tympanograms, (2) SRTs that were consistent with their pure tone averages, (3) excellent WRSs, and (4) no spontaneous otoacoustic emissions. They all, however, showed evidence of retrocochlear or central abnormalities in one or more of the electroacoustic, electrophysiological, or behavioral speech tests. [Table 3] depicts the SCAN-A and R-SPIN results in all seven subjects tested.
This subject was a 41 year-old female with a history of toluene exposure from working as a painter for ten years. There was no history of exposure to loud noise. Pure tone thresholds revealed normal hearing in both ears. ARTs, TEOAEs, and DPs were present at normal levels. Scores on the SCAN-A test were within normal limits. The scores on the R-SPIN fell below the normative range established in the laboratory, suggesting (based on the results) difficulty in perceiving speech in noisy conditions. ABR and MLR peak absolute latencies were all within normal limits. The amplitude growths of ABR wave V between 40 and 80 dB nHL stimuli were normal in both ears. The amplitude growth for MLR peak Na between 40 and 80 dB nHL stimuli was abnormally high in the right ear [Figure 1].
This 40 year-old male had a history of exposure to toluene and xylene from working in carpet installment and steel plants for 20 years. He also had a history of exposure to noise for four years. The subject reported experiencing tinnitus and difficulty in hearing and understanding conversations. Pure tone thresholds revealed normal hearing in the right ear and a mild high frequency sensorineural hearing loss in the left ear starting at 4 kHz. ARTs were present within normal limits for ipsilateral stimulation in both ears. Contralateral ARTs were elevated at 500 Hz when the left ear was the stimulus ear, and elevated at 500 Hz, 1 kHz, and 2 kHz when the right ear was the stimulus ear. TEOAEs were absent at frequencies above 1.75 kHz in the right ear, and absent at all frequencies in the left ear; DPs were present in both ears. The SCAN-A composite score and three out of four subtest scores were below normal as were the scores on the R-SPIN which were below normal bilaterally. ABR peak absolute latencies and amplitude growths for ABR peak V and MLR peak Na were within normal limits. MLR peaks Na and Pa were normal with right ear stimulation, but the left ear latencies were delayed, consistent with the high frequency hearing loss in the left ear.
This 50 year-old female subject was exposed to toluene from various industrial jobs that she had held in the past seven years. She also had a history of noise exposure for 15 years, but wore earplugs over the last 12 yrs. She complained of hearing loss, tinnitus in her right ear, and difficulty in understanding conversation in noise. The subject reported that, six years ago, she had to see a doctor after breaking out in a rash following exposure to toluene at work. It must be noted that skin rash is a side effect of toluene exposure. Pure tone thresholds revealed normal hearing except for a notch at 4 kHz with thresholds of 35 dB HL and 30 dB HL in the right and left ears respectively. Ipsilateral ART for the right ear was normal only at 500 Hz, whereas ipsilateral ARTs in the left ear were normal at all frequencies. Contralateral ARTs were bilaterally elevated or absent. TEOAEs were absent in the right ear at all frequencies and were absent in low frequencies ( Subject 4
This 29 year-old male reported exposure to toluene from working as a painter and paint stripper for the last three years. He also had a history of noise exposure, but reported the use of ear protection during noise exposure. Pure tone thresholds revealed normal hearing thresholds at all frequencies bilaterally, except for a mild hearing loss in the right ear at 250 Hz (30 dB HL threshold). ARTs were elevated or absent for all conditions, except for the ipsilateral condition when the left ear was the stimulus ear. TEOAEs were absent in both ears. DPs were absent in the low frequencies and present at frequencies ≥ 3 kHz in the right ear and at ≥ 1 kHz in the left ear. SCAN-A results were within normal limits whereas the R-SPIN scores were slightly below normal bilaterally. ABR waveforms showed poor morphology and poor repeatability, especially with right ear stimulation [Figure 3]. Peak latencies, amplitudes, and amplitude growth were generally within normal limits bilaterally for ABR and MLR waveforms.
This 48 year-old male had a history of exposure to toluene and xylene for four years while working as a fabrication specialist. He also reported of noise exposure for 15 years with the use of earplugs for 12 years. He reported intermittent tinnitus and difficulty hearing in noisy conditions. Pure tone thresholds revealed normal hearing in both ears. ARTs were normal for ipsilateral conditions and bilaterally elevated or absent for contralateral conditions. TEOAEs were present at normal levels in the right ear and absent in the left ear at high frequencies above 2.5 kHz; DPs were normal bilaterally. Scores obtained on the SCAN-A and R-SPIN tests were within normal limits. ABR waveforms exhibited poor morphology and poor repeatability [Figure 4A]. The MLR amplitude growth was abnormal in both ears (especially with left ear stimulation), indicating an exaggerated amplitude growth for Na in this subject [Figure 4B].
This was a 54 year-old male with exposure to toluene and xylene through paint fumes and welding fumes for 20 years, and to noise for four years. Pure tone thresholds revealed a mild to moderately severe high frequency sensorineural hearing loss in the right ear, starting at 3 kHz. The subject exhibited a mild high frequency sensorineural hearing loss in the left ear, starting at 4 kHz. ARTs were normal for ipsilateral conditions, and bilaterally absent or elevated for the contralateral conditions. TEOAEs were absent in the right ear, and present in the left ear. DPs were absent at frequencies ≥ 3 kHz in the right ear, and were normal in the left ear. The composite score and the subtest scores obtained on the SCAN-A were below normal. The R-SPIN scores were below normal in both ears. ABR waveforms were noisy with poor morphology and poor repeatability [Figure 5]. ABR and MLR peak latencies, amplitudes and amplitude growths were normal bilaterally.
This was a 42 year-old male with a history of exposure to toluene for three years from working as a painter and floor stripper. He was also exposed to noise for five years, but had worn earplugs. He reported experiencing tinnitus, and his pure tone thresholds revealed a mild to moderate high frequency bilateral sensorineural hearing loss starting at 3 kHz. ARTs were present at normal levels for the ipsilateral conditions, and bilaterally absent or elevated in the contralateral conditions. TEOAEs were absent above 2.5 kHz in the right ear, and absent at all frequencies in the left ear. DPs were absent above 3 kHz in both ears. Scores obtained on the SCAN-A composite and two of the four subtests were below normal. The R-SPIN score was below normal in the right ear and normal in the left ear. ABR waveforms were noisy with poor morphology [Figure 6]. ABR and MLR absolute latencies, amplitudes, and amplitude growths were normal bilaterally.
CANS damage typically displays abnormal results for one or more behavioral, electroacoustic, or electrophysiological tests. Studies have demonstrated that exposure to neurotoxic substances such as solvents (toluene, xylene, etc) can show auditory behavioral and electrophysiological alterations. Depending on the site, nature, and the extent of the lesion, ipsilateral and/or contralateral effects can be anticipated even in early stages of chemical exposure.
In this study, abnormal retrocochlear/central findings were found in one or more auditory test measures among solvent-exposed individuals. Furthermore, some of these subjects had normal hearing thresholds, but revealed poor speech processing scores, elevated or absent acoustic reflex thresholds, and abnormal auditory evoked potential test results. These findings suggest retrocochlear and/or central involvement from possible exposure to solvents.
Six out of seven subjects in this investigation showed abnormal ARTs (elevated or absent) with ipsilateral and/or contralateral stimulation despite normal pure tone thresholds at the corresponding frequencies (subjects 2, 3, 4, 5, 6, and 7). All subjects in this study revealed normal tympanograms, thus ruling out middle ear disorders. In the presence of normal thresholds and absence of conductive impairment, abnormal ARTs (ipsilateral or contralateral) are considered to be uncharacteristic. Hence, these subjects are considered to be at risk for retrocochlear pathology in the stimulus ear.
The outer hair cells are the most vulnerable in the peripheral auditory system  and damage to these cells leads to a reduction or absence of evoked otoacoustic emissions (TEOAEs and DPs). Earlier animal and human studies have shown that several aromatic solvents, including toluene, induce irreversible cochlear hearing loss.  In this study, six out of seven individuals had a history of exposure to noise. Yet, several of them (subjects 2, 3, 4, and 5) showed normal pure tone thresholds at some or all frequencies, but abnormal OAEs, signifying the increased sensitivity of OAE measures to peripheral (cochlear) damage. OAEs have been reported to be more sensitive in detecting early symptoms of ototoxicity than conventional pure tone audiometry. , In this investigation, several subjects showed absence of TEOAEs, but presence of DPs. This is not an uncharacteristic finding as TEOAEs are typically absent in frequency regions in which the hearing loss is greater than 25-30 dB HL, whereas DPs are typically absent only when the degree of hearing loss extends to moderate or moderately severe levels.
An abnormal score on the SCAN-A test indicates that the subject is at risk for central auditory processing disorders.  The test was administered at the subject's most comfortable loudness level to account for any hearing loss. In this study, poor or abnormal SCAN-A scores were found in four subjects (subjects 2, 3, 6, and 7). The R-SPIN test was not administered in its entirety due to time constraints; only the most difficult part with the low predictability sentence list was used at 0 message-to-competing ratio. Based on the normative data set in the author's laboratory, four subjects (1, 2, 6, and 7) were found to exhibit abnormally low scores. These findings indicating difficulty in processing auditory signals are comparable to the findings of Fuente et al .,  who found statistically significant differences in auditory processing skills in workers who had been exposed to a mixture of solvents.
ABRs and MLRs are widely used in the objective evaluation of the performance of the auditory pathway from the auditory nerve in the cochlea to the auditory cortex. Abnormalities of absolute latency, interpeak latency, amplitude, amplitude growth measures, and waveform morphology (noisy, poor repeatability, shallow, or less sharply peaked responses) are considered as indicators of aberration of the auditory nerve, brainstem, thalamus, or the cortex. In this study, the ABR waveforms were abnormal in four subjects (4, 5, 6, and 7), as were MLR measures (1, 2, 3, and 5). A direct comparison between this study and earlier auditory evoked potential studies is not prudent due to numerous disparities in subject and recording parameters between the studies. The abnormal auditory evoked potential findings in this study were not totally unforeseen as auditory evoked potential abnormalities have been documented in earlier studies. ,,,, It was, however, intriguing to note that all seven subjects with solvent exposure, whether exposed to noise or not, showed aberrations of ABR measures, MLR measures, or both.
Our earlier studies on clinically depressed, serotonin-deficient individuals ,,, showed abnormal results for auditory behavioral and electrophysiologic tests that were somewhat similar to the current study's findings. Future investigations evaluating the actual serotonin levels and their role in auditory measures in solvent-exposed individuals would be valuable.
Solvents such as toluene and xylene are widely used in industries. Millions of people all over the world are exposed to industrial solvents, yet there is very limited human data on the adverse effects of solvents. This study was aimed at characterizing audiological features in individuals exposed to industrial solvents. All seven individuals examined in this study had some degree of retrocochlear and/or central auditory abnormalities.
The approach used here appears to be useful in evaluating the pathological conditions of the CANS in solvent-exposed individuals. The exposures are sufficiently long to induce permanent changes in the CNS. Our audiological test battery with behavioral, psychoacoustic, and electrophysiological measures seems to be sensitive for the identification of retrocochlear and central abnormalities. Any single measure such as the ABR, for example, may not be sufficiently sensitive to uncover the underlying conditions. However, when ABRs are combined with MLR, ART, and APD evaluations, the resulting test battery appears robust for global assessment of central auditory structures.
This study was supported by a grant awarded to KVG by the Faculty Research Grants Program at the University of North Texas.
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