Evaluating the potential impact of ototoxicant exposure on worker health

Abstract Occupational exposure to ototoxicants, substances that can cause hearing loss alone or exacerbate hearing loss when exposure occurs in combination with noise, is a workplace hazard that is poorly understood. A review of existing research indicates that some solvents and heavy metals may be ototoxic, but few studies have attempted to estimate the impact of ototoxicant exposure on the United States worker population. Researchers examined trends in workplace exposure to ototoxicants among workers in the United States by comparing exposure data collected by the Occupational Safety and Health Administration against worker hearing loss data provided by the Bureau of Labor Statistics (BLS) for 2012–2019. The study found that the noise exposure data was strongly correlated to the hearing loss data using Pearson’s correlation (p < .001), confirming that the exposure data collected by OSHA is predictive of the risk of occupational illness as reported by BLS. Chi-square analysis indicates that reported hearing loss was more common among industry subsectors with exposure to ototoxicants than those without exposure to ototoxicants. These findings suggest that workers with coexposure to ototoxicants and noise may be at a higher risk of experiencing hearing loss than those exposed to noise alone, and action should be taken to minimize this risk.


Introduction
Hearing loss continues to be a significant burden on worker health in the United States.In 2019 alone, 16,900 work-related hearing loss cases were reported in the United States, representing approximately 10% of all work-related illnesses (BLS 2020a).Occupational hearing loss (OHL) is believed to be a substantial source of hearing loss in the United States.Researchers suggested in a 2008 study that OHL is responsible for nearly 24% of hearing loss in the United States, which currently affects approximately 11.4% of the public (Tak and Calvert 2008).The potential adverse effects of hearing loss are numerous, including difficulty communicating with coworkers and family members and increased potential for injury resulting from an inability to hear alarms or equipment noises in the workplace.Extended impacts of hearing loss include reduced job performance in completing complex tasks, decreased quality of life, and lower income and higher medical costs (Themann and Masterson 2019).Workplace exposure to excessive noise is generally considered to be the primary cause of OHL, and it is estimated that up to 18% of workers exposed to excessive noise in the United States will develop hearing loss at some point in their careers (Tak et al. 2009;Masterson et al. 2013).
The Occupational Safety and Health Administration (OSHA) has established requirements for general industry to identify hazardous noise and control hearing loss in the workplace, found in 29 CFR 1910.95Occupational noise exposure.Initially established in 1971, the standard was formally amended to include the requirement for a hearing conservation program in 1981, which was finalized in 1983 (OSHA 1983;Middendorf 2004).Under the rule, if any employees are exposed to hazardous levels of noise in the workplace (defined as the equivalent of 85 dBA or higher for 8hr), the employer must establish a baseline audiogram to monitor the employee's hearing annually so that changes in the employee's hearing thresholds over time can be compared to baseline and monitored for early identification of hearing loss.OSHA's noise standard also requires employers to record cases of work-related hearing loss as recordable illnesses on the OSHA 300 Log, to provide training and protective equipment to employees included in the hearing conservation program, to monitor the workplace for hazardous noise regularly, and to maintain records collected under these requirements (OSHA 1983).However, the OSHA noise standard does not consider other workplace exposures that could contribute to occupational hearing loss, including exposure to ototoxic substances (Themann and Masterson 2019).Research has also noted that the definition of a Standard Threshold Shift (STSthe standard's indicator of OHL, which is defined as a hearing threshold change of 10 dB or more at 2,000, 3,000, and 4,000 hertz in one or both ears) may not fully capture hearing loss that occurs due to exposure to ototoxic substances, as the STS focuses only on specific frequencies and identifies 28-36% fewer cases of occupational hearing loss than more recent definitions proposed by the National Institute of Occupational Safety and Health (NIOSH 1998;Masterson et al. 2014;Blair et al. 2022).

Ototoxicants in the workplace
Ototoxic substances, or "ototoxicants," are chemical substances that may damage the auditory and vestibular systems.The list of known or suspected ototoxicants is diverse, spanning certain pharmaceuticals (including some antibiotics, antineoplastics, and diuretics), solvents, asphyxiants, nitriles, and heavy metals (Campo et al. 2009).Among ototoxicants, solvents and heavy metals appear to be those most relevant in an occupational setting (Campo et al. 2013;Rosati and Jamesdaniel 2020).Workers are most likely to be exposed to ototoxicants in manufacturing sectors (including manufacturing of furniture, chemicals, oil/gas, paint, plastics, and machinery), as well as the mining, agriculture, maritime, and construction sectors (which are typically not governed by the OSHA general industry standards) (OSHA 2018).However, managing occupational exposure to ototoxicants is difficult because the level of exposure at which hearing loss begins is largely unknown.It is also suspected that coexposure to multiple ototoxicants and to ototoxicants and noise together may further increase the potential for hearing loss (Campo et al. 2009).Existing research on ototoxicants consists almost entirely of cross-sectional studies, which may identify ototoxic effects but cannot establish a dose-response relationship, and epidemiological studies using animal data, which can identify an unsafe exposure level but may not accurately reflect the combination of factors present in an occupational setting that could augment the effects of ototoxicant exposure (Campo et al. 2013;Clerc and Pouyatos 2022).
While dose-response relationships have not been established for most individual ototoxicants, several studies have attempted to classify chemicals as ototoxicants based on existing research.A report by the European Agency for Safety and Health at Work (2009) and a study by Vyskocil et al. (2012) have applied a Weight of Evidence methodology, which considers the relative strength of evidence (such as animal studies vs. human studies) to determine whether certain substances show evidence of ototoxicity.Beginning in 2019, the American Conference of Governmental Industrial Hygienists (ACGIH V R ), which also uses a Weight of Evidence methodology in developing threshold limit values (TLVs V R ), which are occupational exposure limits (OELs) for exposure to chemical substances, identified certain ototoxicants using the "OTO" designation (ACGIH 2020).A selection of ototoxicants identified by EU-OSHA, Vyskocil et al. (2012), and ACGIH ( 2023) is provided in Table 1.OSHA has published OELs called Permissible Exposure Limits (PELs) for most substances identified in Table 1, but these OELs were not established based on the potential for ototoxicity and, therefore, may not prevent hearing loss (Masterson et al. 2013).
Solvent use is a common source of workplace exposure to ototoxicants.In a 2019 study of Australian workers, researchers found that an estimated 41.9% of the workforce was exposed to ototoxicants, the most common of which were toluene, xylene, ethylbenzene, n-hexane, and styrene (Lewkowski et al. 2019).Solvents appear to target cochlear hair cells in the inner ear, the loss of which is irreversible, and may also cause damage to the auditory nervous system (Campo et al. 2009).While several solvents appear to be ototoxic on their own, including toluene, styrene, and ethylbenzene, most research has focused on exposure to solvent mixtures as workers are most commonly exposed to several solvents at once (Vyskocil et al. 2012;Choi and Kim 2014;Pleban et al. 2017;Fernandes da Silva et al. 2018).A 2017 meta-analysis of studies related to occupational exposure to ototoxicants found that workers exposed to a mixture of solvents were twice as likely to develop hearing loss as those exposed to noise alone and that the risk of hearing loss increased as the length of exposure, a weighted dose of exposure, and the number of solvents in a mixture increased (Hormozi et al. 2017).It has also been suggested that exposure to ototoxicants at levels below the OELs may nonetheless result in an increased risk of hearing loss (Hormozi et al. 2017;Pleban et al. 2017).
Other workplace ototoxicants include certain heavy metals and asphyxiants.Heavy metals appear to cause hearing loss by damaging the nervous system, disrupting the brain's ability to receive and process auditory signals (Campo et al. 2009).Lead is the heavy metal with the most evidence of ototoxicity and is also present outside of the workplace (e.g., lead in drinking water from lead pipe contamination, lead-based paint) (Rosati and Jamesdaniel 2020).Other suspected ototoxicants include germanium dioxide, tin and organic tin compounds, and certain mercury compounds (Campo et al. 2009).Asphyxiants, such as carbon monoxide, may cause hearing loss in certain conditions due to the loss of oxygen to cochlear cells (Campo et al. 2009).
Coexposure to both ototoxicants and noise is of particular concern.Research has found that many ototoxicants interact with noise during coexposure, either increasing the impact of noise on the ear (potentiation) or causing damage to hearing greater than expected from each exposure individually (synergism).One meta-analysis of ototoxicant studies found that coexposure to solvent mixtures and noise raised the risk of experiencing hearing loss three-fold (Hormozi et al. 2017).Another study of Egyptian workers at several facilities found that workers co-exposed to ototoxicants and noise were more likely to develop hearing loss than workers exposed only to noise, even though the average duration of exposure was nearly eight years less for the co-exposed group than the noise-only group and the exposures were at or below the regulatory OELs (Metwally et al. 2012).The potential for coexposure to be synergistic or potentiative is especially concerning as it could result in adverse health effects (such as hearing loss) at exposures that otherwise appear to be acceptable.This is confirmed by several studies conducted on Department of Defense personnel, which noted that coexposure to metals and/or solvents with noise increased the likelihood that hearing loss would occur, even though the exposures were below the PELs (Schaal et al. 2017;Schaal et al. 2018).
Controlling occupational exposure to ototoxicants, especially in the presence of noise, is very difficult due to the complexity of workplace exposure and the lack of knowledge of "ototoxic thresholds," or concentrations at which exposure to a substance begins to cause hearing loss.As described in the EU-OSHA report by Campo et al. (2009), it is difficult to draw conclusions on the dose-response relationship between ototoxicants and hearing loss due to the variation of study conditions and possible exposures in different workplaces.However, there is evidence that the risk of hearing loss can be mitigated by minimizing ototoxicant exposure.Sch€ aper et al. (2008) found no difference between exposure to noise only and coexposure to toluene and noise, concluding that toluene was controlled to a low enough level to prevent ototoxicity as the average toluene exposure was below 50 ppm and the average noise exposure was approximately 82 dBA.Ju arez-P erez et al. (2014) found that, while hearing loss was present in the studied population, the prevalence was much lower than in similar studies, which was likely because both noise and solvent exposures, on the whole, were below regulatory OELs for all workers monitored.Indeed, for those substances that ACGIH has designated as ototoxicants, the TLVs are generally five to 10 times lower than the respective PELs regulated by OSHA.While research continues, ototoxic threshold concentrations for exposure to individual substances may be unknown, especially for employees who are also exposed to noise.These examples suggest that lowering exposure to ototoxicants to the greatest extent possible may be the best defense against hearing loss.There is also evidence that controlling exposure to ototoxicants is most important at noise exposures near or below 90 dBA.
As noise exposures increase, noise becomes the predominant cause of hearing loss, even in the presence of ototoxicants (Schaal et al. 2017).

Purpose
This study aims to examine if industries with exposure to ototoxicants have an increased risk of hearing loss compared to industries without exposure to ototoxicants, using chemical exposure data provided by OSHA and hearing loss data provided by the Bureau of Labor Statistics.

Sources of data
The data used in this analysis was sourced from the United States federal government.Data were sorted according to the North American Industry Classification System (NAICS) number throughout the study.NAICS is an economic classification system that indicates the industry subsector (ranging from 2-6 digits, based on the desired specificity) where the exposure occurred.Three-digit NAICS codes were selected for this analysis, corresponding to the industry subsector level.Basic employment information (the number of employees and establishments in 2019) was collected from the Bureau of Labor Statistics (BLS) website and is provided in Table 2.
Occupational noise and chemical exposure data, as collected by OSHA during workplace inspections between 2012 and 2020, were provided by OSHA via a Freedom of Information Act request (FOIA request no. 2021-F-08919, filed on May 13, 2021;OSHA 2021).This data included the sampling date, analyte, sample number, exposure concentration (measured as ppm for solvents or mg/m 3 for lead), exposure type, and sample duration.Other information reported for each sample included the establishment name and NAICS code, any emphasis campaigns (focused efforts at the federal or state level to collect samples of specific exposures, industries, or job functions) that may be connected to the sample, relevant OEL, and job title.The years 2012-2019 were selected due to limitations in the availability of OSHA chemical and noise exposure data related to the transition from the Integrated Management Information System (IMIS) to the OSHA Information System (OIS) in 2011.Data from 2020 were excluded to avoid bias introduced by changes in working or OSHA inspections and data collection due to the COVID-19 pandemic.
Data related to work-related cases and incidence of hearing loss were obtained from the annual Survey of Occupational Injuries and Illnesses Data published by BLS (BLS 2013(BLS , 2014(BLS , 2015(BLS , 2016(BLS , 2017(BLS , 2018(BLS , 2019b(BLS , 2020b)).These reports are published annually, based on data reported to OSHA on occupational injuries and illnesses from the previous year.The supplemental news release Table SNR08 provides rates of hearing loss (meeting the OSHA definition of a Standard Threshold Shift) and other occupational illnesses per 10,000 workers categorized by the NAICS code for each year from 2012-2019.Each year of data was used individually for this analysis, and the average rates of hearing loss over this period are provided in Table 3.

Selection of ototoxicants
The substances shown in Table 1 were selected for review in this research-based, in part, on a review of the literature (Campo et al. 2009;Vyskocil et al. 2012 which both used a weight of evidence methodology; ACGIH 2023) and based on substances for which exposure monitoring was available from OSHA.Campo et al. (2009) and Vyskocil et al. (2012) reviewed existing animal and human research and classified substances as an ototoxicant, suspected ototoxicant, or not an ototoxicant based on the number and type of studies (animal vs., human) and the relative strength of the findings.Substances that did not have strong evidence in any reviewed study to be designated as an ototoxicant (or as a suspected ototoxicant) were not considered in this research effort.Of the 18 substances reviewed, 13 were formally designated as ototoxic by at least one source.Five of the remaining substances (carbon disulfide, germanium dioxide, mercury compounds, n-propylbenzene, and trimethyl tin) did not have available exposure monitoring from OSHA and were eliminated from the review.Carbon monoxide was also eliminated because the majority of the available exposure monitoring were instantaneous data rather than data from a timeweighted average (TWA) assessment.The remaining ototoxicants selected for this study (as indicated in Table 1) are: ethylbenzene, n-hexane, lead, styrene, toluene, trichloroethylene, and xylenes.

Data preparation
While the BLS data collected did not need to be prepared for this analysis, the OSHA noise and chemical exposure data contained some data that was incomplete (indicated as "draft" or otherwise not final), erroneous (e.g., blank exposure results), reported in incorrect units (such as percent dose, when the units should be ppm or mg/m 3 ), or not applicable to this study.Other studies using OSHA noise exposure data, namely Middendorf (2004) and Sayler et al. (2019), also excluded or transformed some data.This study followed a similar approach.All data was maintained and analyzed using Microsoft Excel for Microsoft 365 MSO (Version 2202 Build 16.0.14931.20128).

Noise exposure data
The noise exposure data obtained from OSHA was provided in Microsoft Excel in 2-year increments (2011-2012, 2013-2014, 2015-2016, 2017-2018, and 2019-2020).First, the years 2012 through 2019 were combined into one sheet, yielding 109,197 rows of data.Then, the noise exposure data were separated based on which measurement criteria were used during sample collection to interpret data presented as a dose percentage.The Action Level (AL) criteria, which determines whether a hearing conservation program must be established, uses a sound level threshold of 80 dBA and a 100% dose of 85 dBA during measurement.The PEL criteria, by contrast, determines whether an employee's exposure exceeds the regulatory OEL and uses a sound level threshold of 90 dBA and a 100% dose of 90 dBA during measurement.
The data set included the substance identification number (either "8110" for PEL measurements or "8111" for AL measurements), the Exposure Type ("Dose," "AL," or "PEL"), and the applicable OEL (as 85 dBA or 90 dBA); however, the data was not consistently coded.For example, some items coded as 8110 would have the exposure type noted as "Action Level" or were compared against an OEL of 85 dBA.The researchers could not discern which was the correctly noted field and which was incorrectly noted.For consistency, it was assumed that the substance selected (8110 for PEL and 8111 for Action Level measurements) was the correct identifier if the exposure type or OEL did not match the expected values.
This method is similar to that used by Sayler et al. (2019), which was built upon the method employed by Middendorf (2004) to filter out data that was incomplete or inconsistent with this analysis.This method removed any records that met any of the following criteria: no dose level provided; average sound pressure level below 60 dBA or above 120 dBA; sample duration below 6 h (360 min) or above 16 h (960 min); area samples and any other non-personal monitoring; measurement units blank or unrelated to noise (degree, parts per million, or milligrams per cubic meter); site NAICS code blank; or any substance other than noise.Records were also removed if the sampling sheet status was set as "Draft," "Invalid," or The data reported as a dose percentage were converted to a full-shift time-weighted average (TWA) dose using Equation 1.
An evaluation of the noise sampling dataset also found data that appeared to be duplicated.A review of the data found that the duplicate records appeared to be multiple instantaneous readings taken during the same dosimetry record, which resulted in duplicate exposure records when reported by OIS.However, because the number of instantaneous readings differed by exposure record, these duplicates could have misrepresented the dosimetry data collected and introduced bias into the analysis.To avoid this, duplicate records with the same exposure record number were eliminated.This reduced the number of PEL records from 42,346 to 8,319 (a reduction of 80.3%) and the number of AL records from 47,970 to 969 (a 98% reduction).

Chemical exposure data
The data relating to chemical exposure monitoring performed by OSHA was also reviewed to remove any data inconsistent with this analysis or incompletely entered.OSHA originally sent a total of 161,849 records.Records that met the following criteria were removed: monitoring type was not "personal"; sample sheet status was not "Final" or "Ready for Exposure Assessment and E.A. Completed"; sampling time of 0 or greater than 16 h; exposure concentration was blank; or the OEL was blank.This reduced the data set to 131,254 records, of which 12,545 were related to ototoxicant exposure.

Data analysis
Evaluating the Compatibility of OSHA and BLS data The first step in this analysis was to determine whether the data obtained from OSHA and BLS were comparable.This is necessary because the collection methods for these two data sets were different.The BLS dataset is a collection of injury and illness data that must be recorded annually by OSHA and therefore represents a population rather than a sample.The OSHA data, by contrast, are collected during OSHA inspections.As OSHA does not inspect each employer annually, this dataset represents a sample.
To determine whether the OSHA chemical exposure data can be compared to the hearing loss data from BLS, the OSHA noise exposure data was used as a proxy, as it shares the same sample collection strategy.According to the OSHA Field Operations Manual and the OSHA Technical Manual, both noise and chemical samples are selected by the compliance officer based on a review of illness and injury records, hazard assessments, and other documentation provided by the employer that indicates potential exposure to a chemical or noise hazard (OSHA 2019(OSHA , 2021)).It is also well-established that a causal relationship exists between exposure to noise and hearing loss.Therefore, if the OSHA noise exposure data and the BLS hearing loss data are correlated, then it can be inferred that the OSHA sample collection strategy-that is, allowing the compliance officer to make a professional judgment of potential exposure risk as described aboveis predictive of the risk of adverse health effects.By extension, the OSHA data for worker exposure to ototoxicants can then be reliably compared to BLS hearing loss data for this analysis.
First, the noise exposure data from OSHA and the hearing loss data from BLS were stratified according to the NAICS code corresponding to the inspected site.The PEL noise exposure measurements were selected due to the larger dataset size after data preparation and cleaning were performed.The manufacturing industry was chosen for this analysis because 82% of all noise samples and 75.8% of all reported hearing loss cases were from subsectors in the manufacturing industry, although the manufacturing industry subsectors are 21 out of 92 three-digit industry subsectors represented in the NAICS code.The average hearing loss rate (per 10,000 workers) from 2012 through 2019 was determined (as reported in Table 3), and the mean noise measurement over the same period for each subsector in the manufacturing industry was calculated.Subsectors with fewer than 24 total measurements (fewer than three taken each year, on average) were removed due to insufficient data.Next, the average hearing loss rate was plotted against the mean noise exposure measurement, and a Pearson correlation analysis was performed to determine whether the OSHA and BLS datasets were correlated.This analysis was repeated with the median noise measurement for each industry subsector to determine if the OSHA sampling method (which may target "worst case" exposures) was skewing the data by introducing outliers (Table 4).

Comparing ototoxicant exposure and hearing loss data
The second step of the analysis was to compare the OSHA data on ototoxicant exposure to the BLS hearing loss data.First, the data were stratified by the NAICS code to determine the number of exposure samples collected in each industry subsector from 2012 through 2019 and to exclude industry subsectors without adequate data from further analysis.Industry subsectors were excluded if fewer than 39 samples, the equivalent of three average inspections (see Table 5), were collected over the 8 years.After eliminating industry subsectors with inadequate data, 59 remained, representing more than 100 million workers or approximately 81% of the private industry workforce (see Table 2).The data was then filtered to identify the 12,545 samples collected for ototoxicant exposure (see Table 5 for a summary).
Next, the samples were stratified by year, and the number of total samples, samples over 0, and samples over the PEL for each selected ototoxicant were counted and summed for each year.Along with the BLS hearing loss data for each industry subsector each year, the ototoxicant data was used to determine whether each industry subsector identified ototoxicant exposure and hearing loss for each year of the analysis.Hearing loss was straightforward-if the hearing loss rate was greater than 0 for the industry subsector, it was marked as "Yes" for that year; otherwise, it was marked as "No."An industry subsector was considered to have ototoxicant exposure (i.e., marked as "Yes" for that year) if any samples were over the PEL or if at least 20% of the samples had measurable exposure (i.e., a result greater than the limit of detection, LOD).This criterion was selected because existing research suggests that coexposure to noise and ototoxicants below the PEL or TLV may nevertheless result in hearing loss.Samples that did not meet these criteria, including industry subsectors with only 1 sample (lack of samples), were marked as "No" for ototoxicant exposure in the given year.
Finally, industry subsectors were subdivided into the following categories: those that had ototoxicant exposure and reported hearing loss; those that had ototoxic exposure and did not report hearing loss; those that did not have ototoxicant exposure but did report hearing loss; and those that did not have ototoxicant exposure and did not report hearing loss.The sum of industry subsectors in each category was counted for each year and arranged in a matrix for Chi-square analysis to be performed.For the analysis, the null hypothesis was that, for each given year, there was no association in hearing loss between the industry subsectors with ototoxicant exposure and those without.A p-value of .05 was selected for the analysis.
To ensure that no single ototoxicant was skewing the results, based on the fact that lead comprised nearly 60% of the ototoxicant samples collected by OSHA, the Chi-square analysis described above was also performed based on exposure results to each selected ototoxicant individually.As before, the null hypothesis was that, for each given year, there was no association in hearing loss between the industry subsectors with exposure to the selected ototoxicant and those without.A p-value of .1 was chosen for this analysis because the size of each dataset was smaller.

Qualifying ototoxicant exposure risk by industry
The final step of the analysis was to determine the risk of ototoxicant exposure by industry qualitatively.An exposure risk ranking was calculated for each subsector based on three factors calculated from the OSHA chemical exposure data and the 2019 employment data provided by BLS: the number of workers represented per sample of the selected ototoxicants, the percentage of samples for the selected ototoxicants which were greater than the limit of detection, and the percentage of samples for the selected ototoxicants which were greater than the PEL.Each industry was ranked in each category from 1 to 59, with 1 representing the smallest number of employees per sample or the greatest percentage, respectively.Then, the collective exposure risk ranking was determined by calculating the geometric mean of each risk rank and ranking the geometric mean values for each industry from 1 to 59, with 1 being the smallest mean rank and 59 being the greatest.
Each category was selected to represent one facet of exposure risk.The number of workers represented by each sample collected was chosen to represent the relative risk from the use of the selected ototoxicants qualified by the relative size of the industry-a smaller ratio means that more samples were collected, indicating a higher risk of exposure (given OSHA's sample collection strategy).The percentage of exposures greater than the LOD represents the risk of overall exposure to the selected ototoxicants, as a larger percentage indicates many of the samples collected identified exposure.The percentage of exposures greater than the PEL likewise represents the risk of higher exposures to the selected ototoxicants.The geometric mean was selected due to the potential variation between the rank scores of each category.

Evaluating the Compatibility of OSHA and BLS data
A chart plotting the average rate of hearing loss against the mean noise exposure reading is provided in  1).The same analysis performed using median noise exposure revealed a strong positive correlation with the average rate of hearing loss, r(14) ¼ .8203,p ¼ .0001(see Figure 2).
Comparing ototoxicant exposure to hearing loss data Table 5 provides a summary of the chemical exposure data provided by OSHA.After applying exclusion criteria, a total of 131,254 samples remained, of which 93,033 (70.9%) were coded under a National Emphasis Program (NEP) and 12,545 (9.6%) were samples of the ototoxicants selected for analysis in this study.Most of the ototoxicant samples collected were lead (7,482, or 59.6% of the ototoxicant samples).The next most common sample was toluene, totaling 2,175 samples.The most sampled industries included fabricated metal product manufacturing (31,165 samples collected), primary metal manufacturing (21,603), transportation equipment manufacturing (12,216), and machinery manufacturing (10,286).Industries with the broadest ototoxicant sampling included: printing (24% of all samples were for ototoxicants), plastics/rubber manufacturing (23%), furniture manufacturing (21%), and amusement, gambling, and recreation industries (22%).
For each year, the ratio of industry subsectors with reported hearing loss to those without reported hearing loss was greater for the group of subsectors with ototoxicant exposure than the group without ototoxicant exposure.A summary of the Chi-square analyses for each year of the analysis is provided in Table 6.The Chi-square analyses for 2014 through 2019 showed that hearing loss was more common among industries with exposure to ototoxicants than industries without exposure and were significant at the p < .05level.The analyses performed for 2012 and 2013 showed a similar trend to the remaining years, but the   trend was not statistically significant.The Chi-square analysis performed for the selected individual ototoxicants is also provided in Table 6.When analyzed individually, ethylbenzene, lead, styrene, toluene, and xylene show a statistically significant difference between hearing loss among exposed and non-exposed industries.Trichloroethylene and n-hexane did not yield statistically significant results.

Qualifying ototoxicant exposure risk
The upper quartile of industries with higher ototoxicant exposure risk is provided in Table 7, representing 13.7 million workers.The majority of the upper quartile were manufacturing industries, eight out of the fourteen industries.The three manufacturing sectors with the highest exposure risk were 335 (Electrical Equipment, Appliance, and Component Manufacturing), 331 (Primary Metal Manufacturing), and 337 (Furniture and Related Product Manufacturing).The three non-manufacturing sectors with the highest exposure risk were 237 (Heavy and Civil Engineering Construction), 713 (Amusement, Gambling, and Recreation Industries), and 238 (Specialty Trade Contractors [General Industry]).

Discussion
This paper assessed data related to hearing loss, noise exposure, and exposure to ototoxicants among U.S. workers across various industries, resulting in several findings.First, the noise exposure samples collected during OSHA inspections were correlated with cases of hearing loss reported to the Bureau of Labor Statistics.This confirms the relationship between noise exposure and hearing loss.In addition, it also suggests that the methods used by OSHA to identify individual exposure assessments (i.e., to select tasks/personnel for evaluation based on a hazard analysis) is predictive of the risk of adverse health effects (in this case, noise, and hearing loss, respectively).This finding is significant, because the same collection method is used for chemical exposure assessments by OSHA, and the comparison of OSHA inspection data to BLS injury and illness data is an understudied area.These findings may allow other sources of occupational injury and illness to be studied to identify trends in worker exposure and control methods.
OSHA chemical exposure data confirms that many industries have measurable ototoxicant exposure.Unsurprisingly, the largest number of samples were collected in subsectors representing larger numbers of establishments and employees.However, when factoring in the ratio of ototoxicant samples out of all samples collected, and the proportions of those samples over the LOD or PEL, the risk of exposure was evident.Many of the manufacturing subsectors mentioned in OSHA's 2018 Technical Bulletin regarding ototoxicants were confirmed to have a higher risk of ototoxicant exposure, including the manufacture of electrical equipment and components, metal products, furniture, leather, plastics and rubber products, chemicals, and paper.In addition, some non-manufacturing industries were shown to have a high risk of ototoxicant exposure, including amusement, gambling, and recreation, heavy construction, specialty trade contractors, and sporting goods and hobby stores.Ototoxicants are ubiquitous and exposure to ototoxicants extends well beyond the manufacturing industries.While the OSHA Technical Bulletin mainly focuses on exposure in a manufacturing setting, this analysis shows that exposure can also occur in many non-manufacturing workplaces.
In addition, OSHA inspection data showed that industry subsectors with exposure to ototoxicants were more likely to exhibit cases of hearing loss than those without exposure to ototoxicants.This trend was observed across ototoxicant data assessed in combination and individually.It was not immediately evident to the researchers why the analyses for the years 2012 and 2013 were not statistically significant, though the ratio of hearing loss among exposed industries was greater than that among unexposed industries, as observed in the remaining years.These findings confirm the general consensus among the existing body of research that ototoxicants play a role in occupational hearing loss.In addition, the results suggest that ototoxicant exposure represents a potential workplace hazard in the U.S. that warrants further research.
When examined individually, many of the selected ototoxicants showed a similar trend: industries with exposure to the selected ototoxicant tended to exhibit hearing loss more commonly than industries without exposure to the selected ototoxicant, even though the number of samples for each ototoxicant varied.Lead, the most frequently sampled ototoxicant by OSHA with 60% of the total samples, showed statistically significant results for 4 of the 8 years.Ethylbenzene, toluene, and xylene provided statistically significant results for 5, 6, and 7 years, respectively.Trichloroethylene and n-hexane did not yield similar results, likely due to the much smaller number of samples.While Campo et al. (2009) and Vyskocil et al. (2012) considered these chemicals to be ototoxic, ACGIH has not formally designated either n-hexane or trichloroethylene as ototoxic but states that these are "under investigation for ototoxic effects" (2023,133).
Of the research in this field, Clerc and Pouyatos (2022) is the most analogous to this study.Clerc and Pouyatos attempted to use several public databases of occupational exposures and disease among the French workforce to identify whether trends in hearing loss could be observed in workers exposed to ototoxicants and noise.Ultimately, Clerc and Pouyatos (2022) were unable to produce a predictive model and theorized the results were due to underreporting of occupational hearing loss and the fact that hearing loss is only considered work-related due to exposure to noise and not ototoxicants.This analysis faced similar limitations, with slightly different analyses, demonstrating that public databases may produce limited but viable results.Choi and Kim (2014) reviewed audiometric reports and chemical exposure data for 30,000 Korean workers across various industries and identified increased hearing loss in individuals co-exposed to selected heavy metals and organic solvents than unexposed individuals.Though Choi and Kim's analysis differed in scope (Choi and Kim analyzed each individual's records and later aggregated at the industry level whereas this analysis was performed at the industry level only), their findings are consistent with this study's.This study confirms the findings of Vyskocil et al. (2012), which suggested that several chemicals exhibit ototoxicity at concentrations found in occupational settings.
One of the reviewed studies, Sch€ aper et al. ( 2008), conflicts with the results of this study, finding that there was no significant difference in hearing loss between individuals exposed to both toluene and noise and those who were exposed to noise alone.Sch€ aper et al. suggested that one possible reason for this discrepancy was that the exposure concentration to toluene was too low to elicit ototoxic effects.By including all exposures greater than the LOD, this analysis may be erroneously counting some exposures that are at or below ototoxic threshold concentrations, and therefore not likely to result in hearing loss.However, Metwally et al. (2012) reported differently, finding that hearing loss occurred earlier in co-exposed individuals than those with exposure to noise alone, even at exposure levels similar to those in Sch€ aper et al. 's (2008) study.Schaal et al. (2017) and ( 2018) also identified hearing loss in populations exposed to concentrations well below the applicable exposure limits.
This study yielded two additional unexpected findings.First, an examination of the noise data provided by OSHA revealed that the vast majority of noise exposures appeared to be "repeat measurements" due to the reporting of instantaneous readings taken during a single dosimetry measurement as multiple lines of data.Neither Middendorf (2004) nor Sayler et al. (2019) noted this in their analysis of data from IMIS, the sample management system previously used by OSHA to store exposure monitoring data.Future researchers should use care when using noise dosimetry data collected by OSHA to avoid skewed findings resulting from duplicate samples.Second, a review of available literature found that several substances were suspected or likely to be ototoxic but were not identified as such by ACGIH, even though several studies (Campo et al. 2009;Vyskocil et al. 2012) used a Weight-of-Evidence model similar to that employed by ACGIH.The Audible Sound section of the ACGIH TLV book does mention additional substances in an endnote that may exacerbate hearing loss or are under investigation for ototoxicity, but there is no respective note or designation within the TLV table where other target organ toxicities are mentioned, including designated ototoxicants (ACGIH 2023, 133).

Study limitations and assumptions
There were several limitations to this study.First, NAICS codes, used to stratify the data in this study, are economic classifications.The risk to all workers in the same industry subsector is not equal and may vary from company to company or from occupational setting to occupational setting within the industry subsector.Additional research should be performed along other stratifications, such as setting or specific work environment, to reduce any potential impact of other variables not considered in this study.
There are several limitations inherent to the data provided by OSHA.Primarily, because the noise and chemical exposure data are anonymized, it is impossible to tie exposure to an individual.As a result, the analysis cannot directly control for noise, determine whether coexposure to both ototoxicants and noise is present for an individual sample, or to tie a specific exposure assessment to an incidence of disease.Instead, this analysis examined exposure results as an aggregate at the industry level, in which the assessed exposure results are assumed to be representative of the industry as a whole.The exposure data collected by OSHA may not represent average worker exposure (as it is based on a hazard assessment performed by the compliance officer) and does not include other information about the exposure risk, such as the personal protective equipment worn by the assessed worker.When worn correctly (alongside additional exposure controls an employer may choose to implement), PPE reduces the exposure and potentially mitigates the adverse effects of exposure to ototoxicants and noise.This study attempts to ameliorate these limitations by considering the OSHA data to represent "worst-case" exposure.This matches the approach taken by Sayler et al. (2019), who nevertheless considered "worst-case" evaluations to be crucial to minimizing adverse health effects because workers exposed to "worst-case" levels are those most at risk for occupational illness.
The data provided by BLS also introduces several limitations.First, the rates of hearing loss reported by BLS may underrepresent the actual rates of OHL.NIOSH and others have recognized the OSHA definition of a standard threshold shift may undercount hearing loss by up to 28-36% (Masterson et al. 2014).In addition, other factors may encourage employers to underreport cases of hearing loss, such as a desire to avoid regulatory inspections or fines (Masterson et al. 2015).Blair et al. (2022) noted that the OSHA definition of a standard threshold shift may not capture ototoxicant-related hearing loss.A case of occupational hearing loss occurs only when an employee is included in a hearing conservation program (HCP) which includes annual surveillance.Under the OSHA standard, an employee is only required to be entered into an HCP when exposed to high noise levels.This would, by definition, exclude employees exposed to ototoxicants if workers are not already entered into an HCP, or to both ototoxicants and noise at a level too low to trigger inclusion in an HCP.The employee may experience undetected hearing loss as a result.BLS data also does not indicate why an employer was monitoring hearingthe employer may be monitoring the hearing of employees exposed to lower noise levels, or those exposed to ototoxicants as recommended by the 2018 OSHA Technical Bulletin.The monitoring may also occur at the employee's request.However, because the data is reported in the aggregate, it is impossible to differentiate these cases from hearing loss reported by companies strictly following the OSHA standard.To conduct this analysis, it was assumed that hearing loss was recorded per the OSHA standard.
The final limitation of this analysis is the presence of confounding variables.One confounder present in this analysis is that of noise.As previously noted, because the chemical and noise exposure data provided by OSHA is anonymized and the hearing loss data provided by BLS is aggregated at the industry level, the relationships shown in the current analysis may be present due to noise exposure alone.However, the researchers believe these findings nevertheless support further mitigation of factors contributing to workplace hearing loss.It is widely agreed that ototoxicants increase the risk of hearing loss during co-exposure with noise, and this study confirmed that ototoxicants are present in many workplaces in the U.S.This study also showed statistically significant results that industries with exposures to the selected ototoxicants, both alone and as a group, were more likely to exhibit hearing loss than industries without such exposures.If nothing else, this strongly suggests that ototoxicants may present an under-controlled hazard in the workplace and that further research to address these confounders is warranted.

Conclusions
This study compared occupational ototoxicant exposure data collected by OSHA during workplace inspections to work-related cases of hearing loss reported to BLS to determine whether exposure to ototoxicants increased the risk of OHL.It was determined that the exposure assessments performed by OSHA compliance officers are predictive of the risk of hearing loss as reported by the Bureau of Labor Statistics.A review of the chemical exposure data also identified specific industries with a higher risk of exposure to ototoxicants, which confirmed a 2018 OSHA Technical Bulletin for manufacturing sectors but also identified non-manufacturing sectors that may be at risk.A chi-square analysis of data from 2012 through 2019 found that industry subsectors with exposure to selected ototoxicants individually and as an aggregate were more likely to have reported hearing loss than those without exposure to ototoxicants for six years out of the eight years.The individual ototoxicants that showed a similar trend were ethylbenzene, lead, toluene, styrene, and xylene.While individual worker exposures will vary across the selected industry subsectors, these findings provide evidence that workers co-exposed to ototoxicants and noise may be at increased risk of experiencing hearing loss and that further assessment is needed to better understand the impact on the workforce.

Recommendations
This study supports several recommendations.First, employers should consider limiting employee exposure to ototoxicants for any employees exposed to noise over the OSHA Action Level (85 dBA).As ototoxic threshold concentrations have not been identified for these substances, employers should consider using As Low As Reasonably Practicable (ALARP) principles to control ototoxicant exposure in these workplaces.Employers should also consider including employees who may be exposed to ototoxicants and noise in a hearing conservation program, as recommended by ACGIH.To further support these efforts, ACGIH should adapt its "OTO" determination to include a "potential ototoxicant" designation, as many of the substances identified as a potential ototoxicant in this study were not formally designated by ACGIH.Other studies applying a weight of evidence model have utilized a "potential" designation, and ACGIH itself has identified some substances as "under investigation for ototoxicity" in the TLV/BEI handbook.The potential ototoxicity hazard should be identified in the main TLV table alongside the other hazard definitions to identify the potential risks of exposure more prominently.
It may also be beneficial to consider other applications of the analysis method used in this study.To the authors' knowledge, no other study has compared OSHA inspection data against BLS injury and illness data to identify trends.Other researchers (including NIOSH and other governmental research bodies) should review available data to determine other trends that could further minimize worker injury and illness.Future research should also review different stratifications, such as occupation, job title, exposure frequency, and exposure quantification or concentration triggers (e.g., above/below PEL, AL, TLV).
Finally, OSHA should consider updating the Technical Bulletin (2018) to further emphasize that ototoxicants exist in many workplaces and that the research is still evolving.The technical bulletin briefly mentions hearing conservation programs, but this should be expanded based on these findings and others that have reviewed the applicability of puretone audiometry for ototoxicant-driven hearing loss (OSHA 2018).OSHA should also consider implementing a National Emphasis Program (NEP) regarding occupational exposure to ototoxicants.NEPs can be particularly successful at driving sample collection during inspections, and additional data would create a further understanding of this emerging occupational health concern.

Figure 1 .
Sixteen manufacturing industry subsectors are shown in the chart.The mean noise exposure ranged from 85.4 in the Printing and Related Support Activities subsector (NAICS code 323) to 97.7 in the Primary Metal Manufacturing subsector (NAICS code 331).The rates of hearing loss per 10,000 workers ranged from 1.0 in the Computer and Electronic Product Manufacturing subsector (NAICS code 334) to 21.7 in the Wood Product Manufacturing subsector.The Pearson correlation test indicated a moderate positive correlation between the mean noise exposure and the average rate of hearing loss, r(14) ¼ 0.5959, p ¼ .0149(see Figure

Figure 1 .
Figure 1.Comparing average noise exposure (OSHA data) and average hearing loss for selected industries (BLS data).

Figure 2 .
Figure 2. Comparing median noise exposure (OSHA data) and average hearing loss for selected industries (BLS data).

Table 1 .
Weight-of-evidence summaries for potentially ototoxic substances and respective exposure limits.

Table 3 .
Comparison of BLS hearing loss data against OSHA noise exposure data (2012-2019, manufacturing industry subsectors)."Readyforlab."Sayloret al. (2019)did not mention the sampling sheet status in the data cleaning method.

Table 4 .
Summary of BLS hearing loss data.

Table 5 .
OSHA Chemical exposure data summary.

Table 6 .
Chi-Square analysis results.a

Table 7 .
Top quartile industries with ototoxicant exposure risk.