Many variables can contribute to employee hearing loss even if measured noise exposures are below the OELs. One of those variables is a group of chemicals known as ototoxicants that can contribute to hearing loss. As suggested in the Synergist articles “The Ear Poisons: An Introduction to Ototoxicants” and “Ototoxicants and Hearing Impairment,” ototoxicants may be the reason for this “unexplainable” hearing loss. I view them as the potential missing link between noise and chemical overexposures.

There are three types of ototoxicants: neurotoxicants, cochleotoxicants, and vestibulotoxicants. Neurotoxicants alter normal nervous system activity. This can eventually disrupt or kill neurons, which are key cells that transmit and process signals in the brain and other parts of the nervous system. Cochleotoxicants can affect the different cochlear structures including the hair cells, which are the hearing sensory receptors. Vestibulotoxicants affect balance sensors in the ear and result in imbalance that may be accompanied by dizziness and vertigo.

The History The word “ototoxic” derives from the Greek oto for ear and toxic for poisonous. Ototoxicants were recognized in the 11th century by Avicenna, a Persian philosopher and medical scholar, who is considered the first person to describe the harmful effect of a chemical substance on ear function. In the 19th century, the medical industry discovered that some drugs such as anti-inflammatory salicylates are inducers of temporary ear impairments. In the mid-20th century, according to a publication of the European Agency for Safety and Health at Work, pharmacologists and toxicologists carried out deeper research to identify the types of medications that can affect the inner ear and the associated signal transmission pathways in the nervous system. European researchers have performed studies related to ototoxic substances since the 1970s.

In 2018, OSHA and NIOSH developed a safety and health information bulletin on ototoxicity and noise exposure. The bulletin called attention to research studies that demonstrated exposure to certain chemicals that may cause hearing loss or balance problems, regardless of noise exposure. The risk of hearing loss increased when workers were exposed to ototoxicants while working around elevated noise levels.

Dose-Response The relationship between the physical agent (noise) and the chemical agent (ototoxicants) is a newer perspective on hearing loss. While several research papers identify some medications as ototoxicants, information on the dose-response relationship is still limited. This makes assessing hearing loss in cases where noise exposures are below the OELs a unique puzzle for the OEHS profession. According to N. Cody Schaal in “Ototoxicants and Hearing Impairment,” exposure limits have not focused on the dose-response relationship with hearing loss as the effect, so identifying specific concentrations where adverse audiological effects begin is a challenge. Reporting air concentrations that lead to ototoxic effects is complex and requires consideration of other exposure routes such as dermal and ingestion. Biological monitoring can be helpful in determining the internal dose of a contaminant; however, using these results to detect adverse audiological outcomes requires invasive testing.

Like Other Chemicals, Yet Different Ototoxicants are much like any other chemical, physical, or biological agent. They have the same routes of exposure (ingestion, inhalation, and dermal), and their health effects are based on the frequency, intensity, and duration of exposure, as well as workplace conditions. However, as explained in AIHA’s Noise Manual, ototoxicants are different in that they interact with noise through synergistic, additive, and potentiation effects: • Styrene, toluene, and trichloroethylene are chemicals that enhance the loss, through synergistic effect, of the outer hair cells, which increases hearing loss. • Ethylbenzene and lead enter the bloodstream and are circulated to the ear, where they damage the sensory cells of the inner ear used in hearing and balance. Noise elevates the blood flow in the inner ear, which in turn adds a vehicle for chemicals to enter it (additive effect). • Carbon monoxide, hydrogen cyanide, and acrylonitrile are examples of systemic asphyxiants that interfere with oxygen transport, which impedes the cells from repairing noise-induced damage and causes an increase in hearing loss (potentiation effect).

Ototoxicants can be found in machinery, painting, medical, petroleum, pesticides, and many other industries. Solvents such as toluene, p-xylene, and carbon disulfide; asphyxiants such as carbon monoxide, hydrogen cyanide, and tobacco smoke; and heavy metals such as mercury and lead are considered ototoxicants. Many pharmaceuticals including antibiotics, diuretics, analgesics, and antipyretics are also considered ototoxicants. The potential exposures are not only in the production of the pharmaceuticals but also in their consumption. This is another challenging facet to assessing ototoxicant exposures because health privacy regulations, at least in the United States, prohibit asking employees about the medications they are taking. Tobacco smoke is also considered an ototoxicant that affects the central nervous system, neurotransmitters, and blood pressure. According to research published in the International Journal of Pediatric Otorhinolaryngology, the data on hearing loss and the use of electronic cigarettes, while minimal, suggest that e-cigarettes may have the same hearing loss effect as tobacco cigarettes because of their flavoring agents and other components.

Tools for OEHS Professionals While most existing ototoxicant chemicals have OELs, these limits are based on toxicology studies on inhalation or dermal exposures, not necessarily on ototoxicity. But there are tools that can help the OEHS professional identify an ototoxicant in the workplace. Section 11 of safety data sheets includes toxicological information and may mention whether a chemical is an ototoxicant. If the term is not used directly, look for the keywords “neurotoxicant” and “central nervous system,” which may suggest ototoxicity. In addition, the ACGIH Threshold Limit Values (TLVs) use the designation “OTO” for contaminants that have been identified as ototoxicants and chemicals that can cause hearing impairment alone or in combination with noise, even below 85 dBA.

As OEHS professionals, we can apply the main concepts of occupational hygiene—anticipation, recognition, evaluation, and control—to assess ototoxicants: • anticipation: identify the industries that handle ototoxicants • recognition: determine if the chemicals in the workplace are considered ototoxicants or if they have any designation that may allude to ototoxicity • evaluation: perform air monitoring and noise surveys preferably in the same timeframe to evaluate potential exposures (evaluating both at the same time is very useful; ACGIH suggests yearly audiograms for workers whose exposure are at 20 percent or more of the TLV) • control: implement NIOSH’s hierarchy of controls (elimination, substitution, engineering controls, administrative controls, and personal protective equipment) as applicable

Hearing Conservation Programs and Ototoxicants When dealing with ototoxicants, the biggest question is, “Should an employee who is exposed to ototoxicants be included in the hearing conservation program even though noise exposures are below the OELs?” The OSHA noise standard (29 CFR 1910.95) provides no direction on this issue. However, ACGIH recommends that affected employees may need to be enrolled in the hearing conservation and medical surveillance programs to closely monitor auditory capacity even when the exposures are below the applicable limits. ACGIH also recommends periodic audiograms in settings with combined exposures to noise, carbon monoxide, hydrogen cyanide, lead, and solvent mixtures, and when ethylbenzene, styrene, toluene, or xylene exposures occur in the absence of noise.

Putting a Name to the Missing Link While ototoxicants may be challenging, at least OEHS professionals are able to put a name to that missing link between noise and chemical overexposures. As OEHS professionals, we need to be cognizant of the variables that contribute to employee hearing loss, especially ototoxicants. Future investigation is needed to identify the dose-response relationship between noise and chemical exposures to better characterize ototoxicants, establish more quantitative standards to minimize potential exposures, and, most importantly, protect employee hearing in the workplace.