Occupational Hearing Loss: The Interaction of Industrial Solvents and Noise
Jeffery J. Kuhn, MD, FACS Department of Otolaryngology-Head and Neck Surgery Naval Medical Center Portsmouth
Historical Perspective
Demographics
30 million workers in the U.S exposed to hazardous noise levels alone or in combination with other ototraumatic agents (organic solvents, asphyxiants, metals, ototoxic drugs)
Historical Perspective
Demographics
5 million workers in the manufacturing sector are exposed to five most common organic solvents (toluene, TCE, styrene, xylene, carbon disulfide) (1981-1983 NOES) 9 million workers have consistent combined exposures, 1 million with significant exposures (2002 NOES/NOHSM)
Historical Perspective
Cost
Veterans Administration’s annual expenditure for compensable losses due to hearing loss as the primary disability exceeds $440 M (CHPPM, 2002)
Otoneurotoxins
Classes
Drugs:
– Aminoglycosides – Loop diuretics – Anti-neoplastic agents – ASA
– Quinine compounds
Organic solvents:
– Toluene – Styrene – Carbon disulfide – Tichloroethylene(TCE)
– Xylene – n-Hexane
Otoneurotoxins
Classes
Metals:
– Arsenic – Mercury – Trimethyltin (organic
Asphyxiants:
– Carbon monoxide – Hydrogen cyanide
tin) – Lead – Manganese
Military:
– Chemical warfare
nerve agents – JP-8 fuel – Organophosphate pesticides
Toxicology
Organic Solvents
Used in industry for over 150 years and their potential toxicity reported since 1863:
– Central nervous system (psychophysiologic
testing for cognition) – Vision (impaired color discrimination) – Olfaction – Balance (central and peripheral vestibular effects)
Otoneurotoxins
Organic Solvents
Industrial solvents receiving greatest attention in animal and human studies either alone or in combination with noise:
– – – – – –
Toluene Styrene Carbon disulfide Trichloroethylene Xylene n-Hexane
Toluene
Applications
Contained in paints, thinners, lacquers, adhesives, rubber, rotogravure printing Contained in many consumer products (cosmetics) and in pharmaceuticals Abused by “glue sniffers” & spray paint sniffers
Toluene
Biomonitoring
Metabolized by the microsomal cytochrome P-450 system Excreted in the urine as hippuric acid
Toluene
Research Findings
Animal studies (toluene alone):
– Mid-frequency range (2-20 kHz) affected as
evidenced by reflex modification audiometry (RMA), OAE, and ABR testing
Pryor, et al, 1983; Rebert, et al, 1983; Johnson et al, 1988; Mattsson, et al, 1990; Yano, et al, 1992
– OHC loss in middle turn of cochlea by
histopathology
Yano, et al, 1992; Johnson & Canlon, 1994
Toluene
Research Findings
Animal studies (toluene & noise):
– Synergistic effect on audition with combined
toluene and noise in rats when toluene exposure preceded noise exposure (significant loss at 3.15 & 6.3 kHz by ABR)
Johnson, 1988
– Additive effect with combined exposure and
loss enhanced by ASA and worse in rats with age-related hereditary loss
Johnson, 1993
Toluene
Research Findings
Human studies (toluene & noise):
– Adjusted relative risks for hearing loss in
rotogravure printing plant workers were 4x for noise, 5x for toluene alone, and 11x for toluene and noise group compared to controls
Morata, et al, 1993
– Odds ratio estimates for hearing loss in
rotogravure printing factory workers (n=124) were 1.07x for each increment of 1 yr. in age and 1.76x per gm hippuric acid
Morata, et al, 1997
Styrene
Applications
Plastic manufacturing industry Synthetic rubber, resins, insulating materials Structurally similar to toluene
Styrene
Research Findings
Animal studies (styrene alone):
– Decreased behavioral and electrophysiologic
testing thresholds in 2-20 kHz range
Pryor, et al, 1987
– Decreased ABR amplitudes in rats at 8, 16, and
30 kHz and OHC loss in basal and middle turns of the cochlea
Yano, 1992
Styrene
Research Findings
Animal studies (styrene & noise):
– Threshold elevations and OHC losses
exceeding the summed loss caused by styrene and noise alone in range 8-16 kHz suggesting a synergistic effect
Lataye, et al, 2000
Styrene
Research Findings
Human studies (styrene & noise):
– No conclusive evidence for synergism between
styrene and noise in 299 workers from fiber reinforced plastics manufacturing industry with long term exposures
Sass-Kortsak, et al, 1995
– Odds ratio for hearing loss was 1.19 for noise
and 2.44 for styrene and noise in fiberglass and metal products manufacturing plant workers suggesting a synergistic effect
Morata, et al, 2002
Carbon Disulfide
Applications
General neurotoxicant Recognized as an occupational hazard since discovery of cold vulcanization in 1843 (permanent elasticity to shaped rubber goods) and later abandoned due to toxicity Used in the viscose-rayon textile industry Insecticides
Carbon Disulfide
Research Findings
Animal studies (carbon disulfide alone):
– Significantly prolonged absolute and interpeak
latencies and reduced amplitudes on ABR testing in exposed rats
Rebert & Beeker, 1986
– No effect on RMA for prolonged exposures in
rats (12 wks, 500 ppm)
Clerici, 1991
Carbon Disulfide
Research Findings
Human studies (carbon disulfide alone):
– ABR abnormalities were significant in workers
with the longest and most excessive exposure histories and were consistent with an affect on the ascending auditory tract in the brainstem
Hirata, et al, 1992
Carbon Disulfide
Research Findings
Human studies (carbon disulfide and noise):
– 258 Brazilian workers in viscose-rayon plant
exposed to relatively high levels of CS2 and noise (86-89 dBA); 47% incidence HFSNHL after two years and 71% incidence after three years suggesting an ototraumatic interaction between CS2 and noise
Morata, 1989
Otoneurotoxins
Mixed Exposures
Human studies (solvents & noise):
– Odds ratios for hearing loss were 2.4, 3, and 1.8
for three mixed solvent exposed groups with varying noise exposure histories, respectively (n=438, petroleum refinery workers); exposure levels for solvent mixtures and for noise in two groups were consistently below NIOSH recommended exposure levels
Morata, et al, 1997
Otoneurotoxins
Mixed Exposures
Human studies (solvents & noise):
– Increased prevalence effect on upper limit of
hearing in the combined exposure group (solvents & noise) compared to the noise alone and control groups in plastic button factory workers (n=48; solvent mixture of styrene, methanol, & methyl acetate)
Morioka, et al, 2000
Otoneurotoxins
Mechanism of Action
Histopathologic evidence from ototoxic solvent exposed rats suggests a greater vulnerability of OHCs than IHCs
– Pryor, et al, 1984; Sullivan , et al, 1989;
Yano, et al, 1992; Johnson & Canlon, 1994
Otoneurotoxins
Mechanism of Action
Aromatic hydrocarbons may penetrate the lipophilic cytoplasm of Hensen’s and Deiter’s cells influencing K+ homeostasis and ion accumulation in supporting cells causing metabolic changes in OHCs
– Merchant, et al, 1980
Otoneurotoxins
Mechanism of Action
The mid-frequency effects may be due to anatomical and/or functional processes having a non-linear distribution along the basilar membrane May be explained by a differential activity of choline acetyltransferase and Ca+2-ATPase immunoreactivity in OHCs
– Godfrey & Ross, 1985; Schulte, 1993
Historical Perspective
Co-exposure Initiatives
1990 NIH Consensus Development Conference:
– The degree of hearing loss sustained by workers
with the same noise history may differ by as much as 70 dB – Variability may be due to individual differences in susceptibility to noise and/or uncontrolled variables in the work environment (genetics, chemical exposures)
Historical Perspective
Co-exposure Initiatives
Currently no mandate to include chemical exposures in hearing conservation programs in private industry Recent NIOSH publications (1996, 1998) advise that chemical exposures be considered when monitoring noise hazards in the workplace and recommend the term “occupational hearing loss”
Historical Perspective
Co-exposure Initiatives
The US Army has included guidelines for monitoring chemical exposures in their HCP since 1998 The ACGIH recently (2000) amended their “Noise” section that states: “In settings where exposures to toluene, lead, manganese or n-butyl alcohol occurs, periodic audiograms are advised and should be carefully reviewed”
Historical Perspective
Co-exposure Initiatives
NORA (coordinated by NIOSH):
– Identified multiple exposures as a research
priority for the occupational safety and health community – Grant announcement by NIOSH/CDC (Oct. 2001) for protocols investigating hearing sensitivity and exposure to noise and/or chemicals (RFA-OH-02-003)
Historical Perspective
Co-exposure Initiatives
Combined Effects of Chemicals and Noise on Hearing Symposium (April 2002 in Cincinnati, OH) ACOEM Evidenced-based Statement (Oct. 2002):
– Co-exposure to ototoxic agents such as solvents, heavy
metals and tobacco smoke may act in synergy with noise to cause hearing loss – Research needed to identify role of cofactors in hearing loss including solvents, metals, vibration, lead and carbon monoxide
Historical Perspective
Hearing Health Initiatives
www.entnet.org/noise-hearing.html:
– Noise, Ears & Hearing Protection
AAO-HNS Foundation, Inc.:
– Guide for Conservation of Hearing in Noise (sixth ed.)
America’s Hearing Healthcare Team Initiative (May 2002):
– Launched by several societies working in conjunction
including AAO-HNS, ANS, AOS, IHS and endorsed by the AMA and ACS
Organic Solvents and Noise
Future Considerations
Although the interaction of solvents and noise appears to have either an additive or synergistic effect on hearing loss, individual susceptibility has yet to be adequately studied
Organic Solvents and Noise
Future Considerations
Multicenter study currently underway investigating candidate genes involved in metabolism of toxic compounds (cytochrome P450 system) and genes associated with inherited hearing disorders (Univ. Buffalo, Univ. Nebraska, Univ. Cincinnati, NMC Portsmouth) Suspect that genetic variation may influence individual susceptibility to hearing loss due to combined exposures
Historical Perspective
Federal Regulations
Flurry of federal legislation beginning in 1970 that produced several acts and created several agencies to study, develop, and monitor health standards in the workplace (OSHA, NIOSH, EPA) 1983 Dept. of Labor Hearing Conservation Amendment, Final Rule:
– Required implementation of HCP when
employee exposed to 8 hr. TWA of 85 dBA
Historical Perspective
Federal Regulations
1970 OSHA:
– NIOSH established to develop health standards
in the workplace – Office of Noise Abatement and Control (EPA) established to identify and classify causes and sources of noise and determine effect on public health and welfare
Historical Perspective
Federal Regulations
1971 Department of Labor:
– Published guidelines (Bulletin #334) to the
occupational noise standards – Established permissible exposure limits to noise at 90 dBA
1972 Noise Control Act:
– Established by the EPA to regulate emission
standards for industrial equipment
Historical Perspective
Federal Regulations
1983 Department of Labor Hearing Conservation Amendment, Final Rule:
– Required the implementation of a hearing
conservation program for employees exposed to 8 hr. TWA of 85 dBA
Otoneurotoxins
Mixed Exposures
Human studies (solvents & noise):
– Adjusted relative risk for hearing loss was 4.4
and 2.8 despite noise exposure levels < 80 dBA and < 85 dBA, respectively, for two groups of workers in paint and lacquer factory (n=517; solvent mixture of toluene, xylene, ethyl acetate, butyl acetate, & ethyl benzene); no additional risk in the solvent & noise group (RR=2.8)
Sliwinska-Kowalska, et al, 2001
Trichloroethylene
Applications
Industrial degreasing operations, paint removers, dry cleaning agents, adhesives, lubricants
Trichloroethylene
Research Findings
Animal studies (TCE alone):
– Increased ABR thresholds at 8-16 kHz and
increased mid-frequency RMA thresholds in rats
Rebert, et al, 1991; Crofton & Zhao, 1993; Jaspers, et al, 1993
Trichloroethylene
Research Findings
Human studies (TCE alone):
– 26 of 40 workers with significant hearing loss in
2-4 kHz range and most prevalent in workers with long term exposures
Szulc-Kuberska, et al, 1976
There are no animal or human studies that have investigated combined exposures with noise
Xylene
Applications
Paints, varnishes, thinners Used in histology laboratories
Xylene
Research findings
Animal studies (xylene alone):
– Increased RMA thresholds at 12 kHz and ABR
thresholds at 16 kHz in long term exposed rats (1200 ppm; 10x REL)
Pryor, et al, 1987
– Elevated mid-frequency ABR thresholds in rats
exposed to mixed xylenes; additive effect found in combined exposures (TCE or chlorobenzene)
Rebert, et al, 1995
Styrene
Research Findings
Human studies (styrene alone):
– Significant difference in high frequency pure
tone thresholds between least and most exposed workers to styrene
Miujser, et al, 1988
– Abnormally depressed speech discrimination
scores and ABR amplitudes in 7 of 18 chronically exposed workers with mild HF hearing loss
Moller, et al, 1990
Otoneurotoxins
Mixed Exposures
Human studies (solvents & noise):
– Concept of interaction between chemicals and
noise introduced in 1984 following a case report review in 32 shipyard spray painters
Barregard & Axelsson, 1984
– 20-yr. longitudinal study in 319 workers revealed
23% incidence pronounced hearing loss in chemical sector employees vs. 5-8% in nonchemical sectors despite higher noise levels (8090 dBA vs. 95-100 dBA)
Bergstrom & Nystrom, 1986