Noise has traditionally been considered the primary risk factor for hearing loss. However, due to the complexity of industrial environments, the 1996 NIOSH publication “Preventing Occupational Hearing Loss—A Practical Guide” estimated that a worker may be exposed to up to three hazardous agents simultaneously in the workplace; for this reason, it may be inappropriate to restrict occupational hearing loss to only a noise-induced origin. Recent evidence suggests that exposures to chemicals commonly found in industrial environments may affect hearing alone or in combination with noise exposure.

A 2010 report from The Nordic Expert Group for Criteria Documentation of Health Risks from Chemicals defines the term “ototoxicant” as any substance, including drugs or industrial chemicals, that is toxic to the auditory system. Very little data is available on the dose response of ototoxicants; research in humans has been epidemiological in nature and has focused on the presence or absence of an ototoxicant. As occupational hygienists, we are interested in understanding which stressors may result in deleterious health effects, but we also need to understand what concentrations lead to adverse health effects—an idea encapsulated in the popular paraphrase of Paracelsus’s adage that “the dose makes the poison.” Specifically, we need to know what concentrations lead to hearing impairment when workers are exposed to single chemicals, when a chemical and noise exposure occurs in combination, and when multiple chemicals and noise exposures occur simultaneously. This discussion will summarize the positions of occupational health organizations on ototoxicants and discuss several studies of concentrations associated with adverse audiological effects.
GUIDANCE FROM OCCUPATIONAL HYGIENE ORGANIZATIONS Several occupational hygiene-associated organizations have released guidance applicable to practitioners regarding ototoxicants. OSHA and NIOSH released a joint safety and health bulletin in 2018 to raise awareness of ototoxicants. The bulletin summarizes the hazards, including effects on hearing, and provides a list of ototoxicants, identifies industries commonly affected by ototoxicants, and discusses methods of controlling exposure to prevent adverse health effects.  While there are no compulsory regulations targeted toward ototoxicants, OSHA has recognized the risk associated with combined exposures to noise and ototoxic substances. An appendix in the chapter on noise in the OSHA Technical Manual summarizes the epidemiological literature and concludes that physiological interactions with some mixed exposures to chemical and physical factors can increase the severity of harmful effects on the auditory system. OSHA recognizes there is “good evidence” of adverse effects from solvents such as toluene, ethylbenzene, xylene, and styrene, among others, and from chemicals that demonstrate interactive effects with noise including lead, carbon monoxide, and other solvents.  Guidance from the Department of the United States Army identifies 21 chemicals classified as ototoxicants, including metals such as arsenic, lead, mercury, and manganese, and solvents such as carbon disulfide, ethylbenzene, toluene, and xylene, among others. Any exposure to these ototoxicants, either in combination with noise or alone, that is greater than 50 percent of each chemical’s respective occupational exposure limit would trigger enrollment in a hearing conservation program.  With its 2019 Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices, ACGIH adopted a new “OTO” notation to highlight a chemical’s ability to cause hearing impairment either alone or in combination with noise. The OTO notation is intended to focus attention on exposure reduction using engineering, administrative, and PPE controls and to highlight the need to consider placing affected employees in hearing conservation and medical surveillance programs to monitor auditory capacity. Specifically, ACGIH recommends periodic audiograms in settings with combined exposures to noise and carbon monoxide, hydrogen cyanide, lead, and solvent mixtures and recommends audiograms when ethylbenzene, styrene, toluene, or xylene exposures occur in the absence of noise.  Australian safety regulations, recognizing that exposure standards do not take ototoxicants into account, recommend reduction of noise exposure to 80 dBA and audiometric testing when there are exposures to solvents such as toluene, xylene, styrene, and fuel mixtures; metals such as arsenic, lead, and manganese; and other ototoxicants such as hydrogen cyanide and carbon monoxide in combination with noise exposure.  As detailed by the European Agency for Safety and Health at Work, scientists from France’s Institut national de la recherche scientifique (INRS) recommended lowering the exposure limit for styrene from 50 to 30 ppm and adopting an eight-hour noise OEL of 80 dBA. The European Union’s noise directive (2003/10/EC) requires the employer to assess the occupational risk not only from exposure to noise at work but also from the combined exposure to noise and occupational ototoxic compounds. CONCENTRATIONS ELICITING ADVERSE AUDIOLOGICAL EFFECTS Researchers have sought to identify which industrial chemicals demonstrate ototoxicant potential. While not exhaustive, this discussion will focus on the individual chemicals, chemical combinations, and chemicals combined with noise that exhibit the most evidence for ototoxicity.  Metals A suggestive association between lead exposure and hearing loss is not new. A 2013 feature in The Laryngoscope reported high levels of lead in Beethoven’s bones at the time of his death. His autopsy identified shrunken cochlear nerves consistent with axonal degeneration. While Beethoven’s physicians believed he had alcohol dependence, lead exposure was suspected to have been a result of consuming lead-contaminated wine. A 2009 paper in Science of the Total Environment investigated the effects of manganese, copper, zinc, arsenic, cadmium, lead, and noise exposure for steelworkers. Analysis showed lead levels greater than 7 µg/dL of blood were significantly associated with hearing loss at 3,000-8,000 Hz. The biological monitoring requirements in OSHA’s lead standard (29 CFR 1910.1025) begin with semiannual evaluations at an action level of 30 µg/dL, evaluations every two months at 40–100 µg/dL, and removal of workers from the lead environment when blood lead levels reach 60 µg/dL. The Nordic Expert Group’s review of human research in a variety of industries found central auditory effects associated with current and lifetime blood lead concentrations of approximately 28–57 µg/dl. Researchers publishing in Archives of Environmental Health: An International Journal investigated the effect of blood lead levels and noise exposures on hearing ability in two lead acid battery manufacturing facilities and found an average airborne lead concentration of 0.19 mg/m3, blood lead level of 56.9 µg/dL, and average noise exposure of 86 dBA were correlated with decreased hearing ability. An investigation published in Environmental Health Perspectives examined associations between blood cadmium and blood lead levels with hearing loss in the general U.S. population via the National Health and Nutrition Examination Survey. Personnel with cadmium blood concentrations of at least 8.5 µg/dL had a 13.8 percent decrease in hearing while people with blood lead levels of at least 54 µg/dL had an 18.6 percent decrease at 500–4,000 Hz compared to a reference group.  Solvents The Nordic Expert Group’s review of occupational studies for styrene reported that exposures among workers exhibiting significant hearing loss when compared to non-exposed controls ranged from 3.5 to 22 ppm and involved noise exposures less than 85 dBA. Long-term exposure of 30–50 ppm for at least 10 years has been shown to lead to auditory effects.  A 2008 paper in Critical Reviews in Toxicology summarized the literature regarding styrene concentrations leading to adverse audiological outcomes. A study at a plastic button and fiber-reinforced plastic bath factory revealed mean styrene concentrations of 8 ppm combined with mean exposures of toluene at 7.3 ppm, methanol at 14.5 ppm, and acetone at 5.7 ppm were correlated with decreases in hearing from 500 to 8,000 Hz. A study at a yacht yard and plastic factory revealed that mean styrene concentrations up to 46.5 ppm (14.5 ppm averaged over a working lifetime), combined with toluene and noise in excess of 85 dBA, led to over 78 percent of the population having abnormal audiograms. 
ACGIH: “Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices” (2019). American Journal of Industrial Medicine: “Effects of Combined Exposure to Metals, Solvents, and Noise on Permanent Threshold Shifts” (March 2017). Archives of Environmental Health: An International Journal: “Effects of Lead and Noise Exposures on Hearing Ability” (March 2000). Critical Reviews in Toxicology: “Ototoxicity of Toluene and Styrene: State of Current Knowledge” (2008). Department of the Army: “Army Hearing Program” (PDF, 2015). Environmental Health Perspectives: “Environmental Cadmium and Lead Exposures and Hearing Loss in US Adults: The National Health and Nutrition Examination Survey, 1999 to 2004” (November 2012). European Agency for Safety and Health at Work: “Combined Exposure to Noise and Ototoxic Substances” (2009). Institut de recherche Robert-Sauvé en santé et en sécurité du travail: “Effect of Chemical Substances on Hearing—Interactions with Noise” (2012). International Journal of Occupational Medicine and Environmental Health: “Exposure to Organic Solvent Mixture and Hearing Loss: Literature Overview” (2007). Journal of Occupational and Environmental Medicine: “Peripheral and Central Auditory Dysfunction Induced by Occupational Exposure to Organic Solvents” (October 2009). The Laryngoscope: “Lead and the Deafness of Ludwig van Beethoven” (November 2013). NIOSH: “National Occupational Research Agenda for Hearing Loss Prevention” (2019). NIOSH: “Preventing Hearing Loss Caused by Chemical (Ototoxicity) and Noise Exposure” (March 2018). NIOSH: “Preventing Occupational Hearing Loss—A Practical Guide” (1996). The Nordic Expert Group for Criteria Documentation of Health Risks from Chemicals: “Occupational Exposure to Chemicals and Hearing Impairment” (2010). Occupational and Environmental Medicine: “Organic Solvent Exposure and Hearing Loss in a Cohort of Aluminum Workers” (April 2008). OSHA: Occupational Safety and Health Standards, Toxic and Hazardous Substances, Medical Surveillance Guidelines. OSHA: OSHA Technical Manual, Section III: Chapter 5, “Appendix D—Combined Exposure to Noise and Ototoxic Substances” (2013). Safe Work Australia: “Model Code of Practice: Managing Noise and Preventing Hearing Loss at Work” (2018). Scandinavian Journal of Work, Environment & Health: “Effects of Occupational Exposure to Organic Solvents and Noise on Hearing” (August 1993). Science of the Total Environment: “The Association between Low Levels of Lead in Blood and Occupational Noise-induced Hearing Loss in Steel Workers” (December 2009).
In 2009, the Journal of Occupational and Environmental Medicine published a paper that found toluene concentrations as low as 4.8 ppm combined with noise exposures ranging from 74 to 84 dBA in a coating factory were sufficient to cause hearing loss nearly 12 dB greater than in a reference group from 3,000 to 6,000 Hz. These exposures also elicited worse central auditory processing as measured with a dichotic digits test. This study indicated not only that solvent exposure may induce both peripheral and central auditory dysfunction but that other audiological tests in addition to audiometry may be suitable methods of detecting adverse hearing effects.  In a review of literature, IRSST, a Quebec-based research organization, reported that simultaneous exposure to toluene ranging from 100 to 365 ppm and noise ranging from 88 to 98 dBA significantly predicted the probability of developing hearing loss compared to a reference group with only noise exposures among plant workers. Hearing impairment was identified due to simultaneous exposure to toluene ranging from 33 to 165 ppm and 85 dB noise in workers at an adhesives manufacturing plant. However, no hearing impairment was observed in a printing industry study where workers were simultaneously exposed to toluene up to 45 ppm and noise at 82 dB, which suggests the threshold for developing hearing loss due to toluene could be greater than 50 ppm. 
Mixtures A 2017 paper in the American Journal of Industrial Medicine investigated inhalation exposures to lead, cadmium, arsenic, toluene, and xylene in combination with noise exposures in a shipyard environment. Concentrations beginning at 0.03 mg/m3 for lead, 0.0025 mg/m3 for cadmium, 0.005 mg/m3 for arsenic, 25 ppm for toluene, 3 ppm for xylene, and 85 dBA for noise were enough to result in a greater probability of hearing loss compared to a reference group and nearly equal probability of hearing loss than workers with only noise exposures greater than 85 dBA.  A review of literature in the International Journal of Occupational Medicine and Environmental Health found that lifetime exposures of xylene up to 25 ppm and toluene up to 24.7 ppm, combined with noise exposures greater than 85 dBA, had an increased risk of hearing loss in the paint and lacquer industry. An exposure range of 1 to 4 years was not enough to elicit hearing loss.  An investigation published in 1993 in the Scandinavian Journal of Work, Environment & Health found printing and paint manufacturing workers had a significantly greater relative risk (an RR of 11) of hearing loss with noise exposures greater than 85 dBA and toluene concentrations ranging from 10 to 70 ppm. Exposure to only a solvent mixture of xylene from 12 to 40 ppm, benzene from 0 to 2 ppm, MEK from 0 to 32 ppm, MIBK from 0 to 20 ppm, and ethanol from 0 to 16 ppm also resulted in a higher relative risk (an RR of 5) for hearing loss.  A study of a cohort of aluminum workers published in Occupational and Environmental Medicine found that five-year mean time-weighted average exposures to toluene at 4 ppm, MEK at 21.4 ppm, xylene at 7.6 ppm, and a solvent summation index of 0.26 were associated with hearing loss at 3,000-6,000 Hz while controlling for demographic risk factors and noise exposure. The solvent summation index was the sum of the mean toluene, MEK, and xylene time-weighted average exposures divided by the ACGIH TLV of each solvent. TAKEAWAYS The summary of studies in this article does not constitute an exhaustive review of the literature, but it does provide examples of the concentrations of certain ototoxicants found to adversely affect certain audiological functions. Taken together, these studies provide three main takeaways: 1. It is not possible to make conclusions regarding dose- response relationships, nor is it wise to speculate about “safe” levels of ototoxicant exposures to prevent adverse audiological outcomes. However, it appears that adverse outcomes begin, for most chemicals, at concentrations below currently established OELs.  2. Combinations of ototoxicant exposures are more important in describing adverse audiological effects than single ototoxicants or, in some cases, an ototoxicant and noise together. Specifically, adverse effects appear to begin at lower concentrations for chemical mixtures than for individual chemicals. 3. Research suggests that OELs may need to be lower to adequately protect workers from hearing loss when both noise and ototoxicants are present in the workplace. Exposure Assessment Challenges Most human studies have not focused on dose-response relationships, so identifying specific concentrations where adverse audiological effects begin is a challenge. Also, reporting air concentrations that lead to ototoxic effects is complex and requires consideration of other exposure routes such as dermal and ingestion. While biological monitoring is helpful in determining the internal dose of a contaminant, use of these results to detect adverse audiological outcomes requires invasive testing. Other challenges in both occupational and non-occupational environments include exposures to stressors that last longer than eight hours, ototoxicant and noise exposure occurring outside the workplace (including ototoxicant medication), and impulse noise in addition to continuous noise.  Future Study Additional investigation is needed, particularly in determining what chemical concentrations are “safe” to the auditory system. NIOSH’s National Occupational Research Agenda for Hearing Loss Prevention identifies a need to assess OELs for mixtures of noise and other ototoxicants because many OELs have been developed to prevent adverse effects from outcomes such as upper respiratory tract irritation and central nervous system impairment, among others, rather than an adverse auditory outcome.  There may be numerous workers with unmet hearing conservation needs. When considering adverse auditory outcomes, workplace interventions should target exposure reduction of multiple ototoxicant stressors rather than just noise.    N. CODY SCHAAL, PhD, CIH, CSP, LCDR, MSC, USN, is a member of the Naval Medical Research Unit-Dayton at Wright Patterson Air Force Base in Ohio. He is also an assistant professor in the Department of Preventive Medicine & Biostatistics, F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda, Md. Disclaimer: The views expressed in this article are those of the author and do not necessarily reflect the official policy or position of the Department of the Navy, the Department of Defense, or the U.S. government. Send feedback to The Synergist.
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Research suggests that OELs may need to be lower to adequately protect workers from hearing loss when both noise and ototoxicants are present in the workplace.
The Challenge for Occupational Hygiene
Ototoxicants and Hearing Impairment
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Disadvantages of being unacclimatized:
  • Readily show signs of heat stress when exposed to hot environments.
  • Difficulty replacing all of the water lost in sweat.
  • Failure to replace the water lost will slow or prevent acclimatization.
Benefits of acclimatization:
  • Increased sweating efficiency (earlier onset of sweating, greater sweat production, and reduced electrolyte loss in sweat).
  • Stabilization of the circulation.
  • Work is performed with lower core temperature and heart rate.
  • Increased skin blood flow at a given core temperature.
Acclimatization plan:
  • Gradually increase exposure time in hot environmental conditions over a period of 7 to 14 days.
  • For new workers, the schedule should be no more than 20% of the usual duration of work in the hot environment on day 1 and a no more than 20% increase on each additional day.
  • For workers who have had previous experience with the job, the acclimatization regimen should be no more than 50% of the usual duration of work in the hot environment on day 1, 60% on day 2, 80% on day 3, and 100% on day 4.
  • The time required for non–physically fit individuals to develop acclimatization is about 50% greater than for the physically fit.
Level of acclimatization:
  • Relative to the initial level of physical fitness and the total heat stress experienced by the individual.
Maintaining acclimatization:
  • Can be maintained for a few days of non-heat exposure.
  • Absence from work in the heat for a week or more results in a significant loss in the beneficial adaptations leading to an increase likelihood of acute dehydration, illness, or fatigue.
  • Can be regained in 2 to 3 days upon return to a hot job.
  • Appears to be better maintained by those who are physically fit.
  • Seasonal shifts in temperatures may result in difficulties.
  • Working in hot, humid environments provides adaptive benefits that also apply in hot, desert environments, and vice versa.
  • Air conditioning will not affect acclimatization.
Acclimatization in Workers