Sources of noise in the work environment are as vast as the width of the frequency range of the human ear. The most commonly identified sources of work-related noise include powered tools, machinery, flow-through pipes, vibrating equipment, and moving parts. Therefore, it is understandable that hearing conservation programs focus on assessing and controlling harmful sound pressure levels that cause damage to the hair cells of the inner ear. Yet noise is not the only etiology of hearing loss. Enter ototoxicants—chemical substances that cause hearing loss once they are introduced to the body through the traditional routes of exposure (inhalation, absorption, and ingestion). The issue of ototoxic chemicals in the workplace is not new. Studies on the ototoxic effects of solvents were published as early as the 1970s. In the 1980s, other types of chemicals were added to the list of potential ototoxic materials, and scientists began to evaluate the synergistic effects of exposure to both ototoxicants and noise in the same work environment. Today, according to the Nordic Expert Group, workers can claim compensation for hearing loss associated with occupational exposures to ototoxicants in two countries: Australia and Brazil. The ototoxic side effects of certain medications for treatment of cancer, high blood pressure, and other conditions have been well documented in the pharma-scientific literature. Numerous published studies aim at understanding how a chemical agent taken in by the body causes a negative impact on the ear—specifically, how it targets hair cells or other parts of the inner and middle ear.
When exposure to noise exceeds occupational exposure limits, the effects will start to manifest through the sudden or gradual loss of hearing, among other maladies such as tinnitus, heart disease, and high cholesterol. Hearing loss can result from damage to hair cells or from biochemical or metabolic processes. The gradual damage to hair cells, which most people associate with occupational hearing loss, is akin to the erosion of a grass path from the constant steps of passers-by. The steps represent the sound pressure waves pounding and breaking away the hair cells, which, unlike grass, can’t regrow. 
Threshold Limit Values for Chemical Substances and Physical Agents & Biological Exposure Indices
Archives of Industrial Hygiene and Toxicology
: “Ototoxic Substances at the Workplace” (2012).
Critical Reviews in Toxicology
: “Ototoxicity of Toluene and Styrene: State of Current Knowledge” (2008).
: “Chemical Exposure and Hearing Loss” (April 2013).
Ear and Hearing
: “The Role of Oxidative Stress in Noise-Induced Hearing Loss” (February 2006). European Agency for Safety and Health at Work:
Combined Exposures to Noise and Ototoxic Substances
Hearing Research
: “Increase in Cochlear Microphonic Potential after Toluene Administration” (2007). 
Hearing Research
: “Mechanisms of Cisplatin-Induced Ototoxicity and Prevention” (April 2007).
Hearing Research
: “Mechanisms of Noise-Induced Hearing Loss Indicate Multiple Methods of Prevention” (April 2007).
Institut de recherche Robert-Sauvé en santé et en sécurité du travail (IRSST):
Effect of Chemical Substances on Hearing: Interactions with Noise
Journal of the Acoustical Society of America
: “Use of the Kurtosis Statistic in an Evaluation of the Effects of Noise and Solvent Exposures on the Hearing Thresholds of Workers: An Exploratory Study” (March 2018). OSHA: OSHA Technical Manual, Section III, Chapter 5 – Noise,
Appendix D: Combined Exposure to Noise and Ototoxic Substances
. OSHA: OSHA Technical Manual, Section III, Chapter 5 – Noise,
Section G: Noise and Solvent Interaction
. OSHA/NIOSH: Preventing Hearing Loss Caused by Chemical (Ototoxicity) and Noise Exposure (
, March 2018).
Proceedings of ACOUSTICS 2016
: “Exposure to Ototoxic Agents and Noise in Workplace – A Literature Review” (
, November 2016). Safe Work Australia:
Managing Noise and Preventing Hearing Loss at Work: Code of Practice, Appendix A – Other Causes of Hearing loss in the Workplace
(September 2015). 
Seminars in Hearing
: “Mechanisms Involved in Ototoxicity” (2011). The Nordic Expert Group for Criteria Documentation of Health Risks from Chemicals: “142. Occupational Exposure to Chemicals and Hearing Impairment” (
, 2010).
Toxicological Sciences
: “Toluene Can Perturb the Neuronal Voltage-dependent Ca2+ Channels Involved in the Middle-ear Reflex” (2009).  U.S. Army: Occupational Ototoxins (Ear Poisons) and Hearing Loss (2003).
The complex biochemical processes that lead to hearing loss are still being examined. One such process involves an enzyme that is triggered by the generation of free radicals in the cochlea after an exposure to elevated noise levels. This enzyme is a potent vasoconstrictor that reduces the diameter of blood vessels and therefore the access of red blood cells to the inner ear. Over time, the ensuing lack of oxygen impairs the functioning of hair cells, reducing the exposed individual’s ability to hear. Oxidative stress, another biochemical mechanism triggered by noise exposure that exceeds OELs, causes hair cells to augment their metabolic activity due to their higher energy consumption. During this stage of increased excitement, excess superoxides and nitric oxides are generated within the hair cells’ mitochondria, the organelle responsible for respiration at the cellular level, and react with cellular lipids that produce free radicals known as Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS). The uncontrolled generation of these free radicals, especially ROS, contributes to bioenergetics failures that cause apoptosis, a sort of controlled cell death or cellular suicide. The over-development of ROS can be sudden and temporary, but there is also clinical evidence of their delayed formation, establishing a peak concentration seven to 10 days after noise exposure, with progressive hair cell loss for up to 14 days after exposure. From this information one can conclude that the hearing loss may continue to occur even after exposure to noise has ceased or if the worker dons personal protective equipment after a significant noise exposure.  Research suggests that hearing loss from ototoxicants occurs mainly by reduced blood flow and oxidative stress. Other etiologies include negative impact to muscles in the middle ear that minimizes their shock-absorbing role, a decrease in antioxidants that makes the inner ear more vulnerable to noise exposure, chemical poisoning of hair cells, neurotoxic effects that disrupt the transmission of signals from the auditory nerve and the auditory pathway to the brain, and others that depend greatly on the agent’s toxicology. As an example, research from the Nordic Expert Group has shown that outer hair cell length response to sound stimulation is dependent on calcium concentrations in the hair cells, so ototoxic agents that interfere with cellular calcium regulation may also affect hair cell length. Images taken with electron microscopes post-ototoxic exposure depict hair cell apoptosis in separate clusters of the “V” shaped outer hair cells. In contrast, images of hair cells affected by noise exposure typically show continuous lines of damage.
Ototoxicants commonly found in occupational environments can be found in three general classes of chemicals: solvents, (heavy) metals, and asphyxiants. Some studies include a limited number of nitriles and pesticides. Exactly which chemical substances under each category are considered ototoxic is a matter of debate and depends on the parameter used to define an “ototoxic” chemical as well as the robustness of the particular research being considered. Various entities around the world—including the European Agency for Safety and Health at Work (EU-OSHA), Safe Work Australia, Institut de recherche Robert-Sauvé en santé et en sécurité du travail (IRSST), the U.S. Army, and the Nordic Expert Group for Criteria Documentation of Health Risks from Chemicals—have provided different classification protocols, designating ototoxicants with qualifiers such as “confirmed,” “suspect,” “questionable,” “possible,” “non-conclusive,” “common,” “potential,” or simply “ototoxic.” The Nordic Expert Group used a three-tiered quantitative classification scheme based on the quality of the human and animal data available. Before adopting ototoxic classifications from any of these entities for use in your organization, discuss the research and decision logic with management and other stakeholders. Substances relevant to the occupational environment that are frequently listed as ototoxic solvents include carbon disulfide, ethylbenzene, styrene, toluene, trichloroethylene, and xylene. Commonly listed under the category of ototoxic metals are lead and mercury. The most common ototoxic asphyxiant listed is carbon monoxide. Many other substances are potentially ototoxic. Some organizations that classify chemicals as ototoxicants list only the chemicals that are specific to their operations.
Noise is prevalent in many industries, and it isn’t hard to find ototoxicants in work environments where noise is also an agent of concern, creating an additional risk. Animal research and human epidemiological studies suggest that the combined effects of dual exposure to noise and ototoxicants can be either additive, potentiate, or synergistic. It is important to note that in cases of dual exposure, noise levels may not need to be above exposure limits for the combined effects to manifest themselves, and that impulse noise may be more harmful than continuous noise in the presence of some solvents, according to a paper in the March 2018
Journal of the Acoustical Society of America
. In general terms, the effect of exposure to noise and ototoxic solvents is found to be additive at best, and synergistic at worst (as with toluene); exposure to carbon monoxide may potentiate noise-induced hearing loss. Research suggests that exposure to other chemicals and metals (such as lead) may interact with physical noise exposure, but the association has not been confirmed. Another consideration is that many workers are exposed to both occupational and non-occupational noise, as well as a variety of chemicals both inside and outside the work environment. This can make it difficult for researchers to isolate the effects of a single chemical on hearing loss or distinguish the impact of occupational exposure from environmental exposure. 
It is also worth noting that occupational exposure limits are established to address a few critical effects, yet hearing loss due to ototoxicants or combined exposure is hardly ever included under these adverse health effects for the purposes of OEL development. Experts are calling for more research in these areas. In the meantime, the safety and hygiene community can help mitigate the risk presented by ototoxicants and co-exposures with noise by adding ototoxicants to risk assessment matrices, educating stakeholders about the risks associated with occupational ototoxicants, and adhering to the hierarchy of controls when addressing ototoxicants and noise in the workplace. The U.S. Army, Safe Work Australia, EU-OSHA, and ACGIH have published recommendations for addressing ototoxic exposure. These recommendations include:
  • requiring periodic audiograms for personnel exposed to 50 percent of the occupational exposure limit regardless of the presence of noise in the work environment and inclusion of these personnel in hearing conservation programs
  • requiring periodic audiograms for employees where dermal exposure to an ototoxic is uncontrolled
  • creating an employer awareness program regarding medical and non-occupational ototoxicants, especially where noise and ototoxicants are an issue within the work force
  • using a notation for ototoxicants similar to the Skin notation (“S”) used for chemicals with an important dermal absorption concern (ACGIH is considering adopting this change for its threshold limit values) 
  • evaluating inclusion in hearing conservation or medical surveillance programs for chemicals identified with an ototoxicant notation, even when noise exposures are below occupational limits (see “OTO” notation in the 2018 ACGIH Notice of Intended Change and as originally recommended by the Belgian toxicologists Hoet and Lison in 2008)
Where dual exposure to noise and ototoxicants exists, published recommendations from EU-OSHA and Safe Work Australia include:
  • reducing the 8-hour occupational exposure limit for noise to 80 decibels (A-weighted)
  • reducing the occupational exposure limit for the ototoxicant of concern
  • requiring use of hearing protection

Some of these recommendations are required by the health and safety regulations of certain countries (mostly in Europe).  The prevalence of noise as a physical agent in many workplaces and its potential for illness is unquestioned. Industrial hygienists are compelled to familiarize ourselves with information regarding ototoxicants and include these agents in hearing conservation programs and guidelines. Further research is necessary to advance our understanding of the concentrations of specific chemicals that elicit adverse auditory effects, identify all potential ototoxicants, and determine which chemicals are ototoxic alone and which are ototoxic only when combined with noise. But sufficient peer-reviewed evidence is available to make informed decisions for the benefit and better health of workers.   
is the head of Occupational Health and Safety for Latin America at Ericsson, based in Panama. He can be reached via
Acknowledgement: The Synergist
thanks LCDR N. Cody Schaal, PhD, CIH, CSP, and Jeremy M. Slagley, PhD, CIH, CSP, for reviewing this article. Schaal is an assistant professor in the Department of Preventive Medicine and Biostatistics at Uniformed Services University in Bethesda, Md. Slagley is an assistant professor in the Department of Systems Engineering and Management at the Air Force Institute of Technology. Send feedback to The Synergist.

Getty Images/evryka23, Getty Images/9nong

OELs are established to address a few critical effects, yet hearing loss due to ototoxicants or combined exposure is hardly ever included for the purposes of OEL development.
An Introduction to Ototoxicants

The Ear Poisons