Ototoxic Agents Research Articles

Strengthening cancer care through the inclusion of audiological services

Aim Commonly used cancer treatments that treat the priority cancers are ototoxic. Ototoxicity can add to the already severe morbidity experienced by cancer survivors. It affects the quality of life and consequently has dire psycho-socio-emotional, cognitive, occupational, and scholastic effects. This article aims to highlight that the inclusion of audiological services, such as ototoxicity monitoring and management, can strengthen cancer care by reducing the morbidity and effects of ototoxicity. It explores the current practices of ototoxicity monitoring and management for cancer patients in South Africa and offers practical and innovative evidence-based solutions on how the practice can be improved. The paper also discusses how the National Care Strategic Framework (NCSF) (2017-2022) can be expanded to support the inclusion of audiological services by including ototoxicity monitoring and management in cancer care. Methods A review of literature was conducted utilising a narrative approach to explore audiological service provision for cancer care in South Africa. Peer-reviewed publications and clinical guidelines related to audiological and/or vestibular ototoxicity caused by cancer treatments were reviewed. Findings Despite the inroads that have been made in South Africa, resource and logistical limitations hinder the effectiveness of ototoxicity monitoring and management programmes. In addition, a lack of awareness of the ototoxic effects of some cancer treatments by oncology nurses, as well as ambiguity regarding the roles and responsibilities of the multidisciplinary cancer team in terms of ototoxicity monitoring, management, and patient counselling, further exacerbate the problem. Conclusions The effectiveness of ototoxicity monitoring and management could be enhanced by having a national and standardised protocol and programme incorporating tele-audiology and task-shifting. In addition, collaborative work among the cancer multidisciplinary team will foster holistic practice and integration of audiological services. Future versions of the NCSF should encompass considerations to reduce the associated burdens of cancer treatment, and audiological services, through ototoxicity monitoring, and ought to be included when providing cancer care to patients being treated with ototoxic agents.

The Impact of Monoclonal Antibody Usage on Hearing Outcomes: A Systematic Review.

To ascertain trends in ototoxicity observed with monoclonal antibodies (mABs) and understand the impact they may have on hearing function. PubMed, Embase, Scopus. A systematic review was performed following PRISMA guidelines. Data were reviewed for demographics, utilized mABs with respective indication and dosing, audiometric outcomes, and treatment for otologic effects. Of 757 studies reviewed, a total of 44 were included, encompassing 18,046 patients treated with mABs. Mean age of the sample was 57.8 years old. The search yielded 18 agents of ototoxicity, with reported symptoms of ototoxicity such as hearing loss, tinnitus, and/or aural fullness occurring in 1079 of total patients. Main agents causing ototoxicity were teprotumumab (n = 17/44 studies), nivolumab (n = 10/44), ipilimumab (n = 9/44), pembrolizumab (n = 5/44), and rituximab (n = 4/44). Thirty-one of 44 studies encompassing eight agents reported audiometric data for ototoxic agents, showing sensorineural hearing loss primarily in the high-frequency range. Only two articles performed ultrahigh-frequency audiograms. Monoclonal antibody usage is expanding, but the vast majority of studies lack substantial audiometric data. Where reported, study design and inclusion criteria vary greatly. Future studies would benefit from rigid inclusion of audiometric data, prospective study design, and consideration of formal ototoxicity screening. Otolaryngologists should be aware of the cochlear immune response and potential impact of this expanding medication class on hearing function. Laryngoscope, 2024.

Roadmap to a Global Template for Implementation of Ototoxicity Management for Cancer Treatment.

Ototoxicity is among the adverse events related to cancer treatment that can have far-reaching consequences and negative impacts on quality-of-life for cancer patients and survivors of all ages. Ototoxicity management (OtoM) comprises the prevention, diagnosis, monitoring, and treatment, including rehabilitation and therapeutic intervention, of individuals who experience hearing loss, tinnitus, or balance/vestibular difficulties following exposures to ototoxic agents, including platinum chemotherapy (cisplatin, carboplatin) and cranial radiation. Despite the well-established physical, socioeconomic, and psychological consequences of hearing and balance dysfunction, there are no widely adopted standards for clinical management of cancer treatment-related ototoxicity. Consensus recommendations and a roadmap are needed to guide development of effective and feasible OtoM programs, direct research efforts, address the needs of caregivers and patients at all stages of cancer care and survivorship. Here we review current evidence and propose near-term to longer-term goals to advance OtoM in five strategic areas: (1) beneficiary awareness, empowerment, and engagement, (2) workforce enhancement, (3) program development, (4) policy, funding, and sustainability, and (5) research and evaluation. The goal is to identify needs and establish a roadmap to guide worldwide adoption of standardized OtoM for cancer treatment and improved outcomes for patients and survivors.

Audiological Outcomes of Weekly vs. Triweekly Cisplatin in Head and Neck Cancer with Cochlear-Sparing Intensity-Modulated Radiation Therapy.

Cisplatin, one of the most ototoxic anti-neoplastic agents, causes permanent hearing loss in up to 90% of patients. We assessed ototoxicity rates and prospectively collected audiologic outcomes of patients receiving low-dose or high-dose cisplatin with concurrent cochlear-sparing intensity-modulated radiation therapy (IMRT). Patients with head and neck squamous cell carcinoma (HNSCC) receiving definitive or adjuvant cisplatin-based chemoradiotherapy (CRT) were analyzed. Cisplatin was administered either in low doses weekly (40 mg/m2) for up to seven doses or in high doses triweekly (100 mg/m2) for up to three doses. Cochlear-sparing IMRT was delivered in all cases. Audiologic data were prospectively collected before, during, and after treatment completion. The primary endpoint was a hearing change grade of ≥3 after CRT completion. Of the 96 HNSCC patients evaluated, 69 received weekly cisplatin and 58 received definitive CRT. Of patients receiving weekly cisplatin, 13% developed ≥G3 ototoxicity vs. 56% of patients who received triweekly cisplatin (p < 0.001). In multivariable modeling, the cisplatin dose schedule remained significant (OR: 8.4, 95%CI: 2.8-27.8, p < 0.001) for risk of severe irreversible ototoxicity. Triweekly cisplatin CRT significantly increased the ≥G3 severe irreversible ototoxicity risk compared to low-dose weekly cisplatin, irrespective of the cumulative cisplatin dose, even with the use of cochlear-sparing IMRT. No significant difference in oncologic outcomes was observed between the two schedules.

Hair Cell Regeneration: From Animals to Humans.

Cochlear hair cells convert sound into electrical signals that are relayed via the spiral ganglion neurons to the central auditory pathway. Hair cells are vulnerable to damage caused by excessive noise, aging, and ototoxic agents. Non-mammals can regenerate lost hair cells by mitotic regeneration and direct transdifferentiation of surrounding supporting cells. However, in mature mammals, damaged hair cells are not replaced, resulting in permanent hearing loss. Recent studies have uncovered mechanisms by which sensory organs in non-mammals and the neonatal mammalian cochlea regenerate hair cells, and outlined possible mechanisms why this ability declines rapidly with age in mammals. Here, we review similarities and differences between avian, zebrafish, and mammalian hair cell regeneration. Moreover, we discuss advances and limitations of hair cell regeneration in the mature cochlea and their potential applications to human hearing loss.

What's New in Ototoxicity Management?

Purpose: Ototoxic medications and chemical agents in the workplace can put individuals' hearing and vestibular health at risk for permanent injury. Proactive ototoxicity management (OtoM) strategies aim to minimize exposure, avoid onset of symptoms, provide ongoing monitoring, and manage auditory and vestibular changes as the clinical needs of the patient evolve. During a 2021 American Speech-Language-Hearing Association Special Interest Groups Open House, members of the International Ototoxicity Management Group discussed how best to integrate OtoM into routine clinical practice, what tools to use, and what special considerations need to be understood to best support patients and their families. Here, we have summarized their viewpoints to encourage widespread adoption of improved OtoM services for at-risk individuals. Conclusions: The field of audiology needs to move to a place where we better understand the full extent of ototoxicity and can agree on expanding minimum guidelines that can be implemented more universally to mitigate, detect, and manage the damage from ototoxic exposures. Only recently has our field seen a therapeutic drug that can protect against ototoxicity; however, the population served is restricted only to children receiving treatment for nonmetastatic carcinoma. This is hopefully just the beginning of future therapeutic interventions to come, but, in the meantime, ototoxicity resulting from other medications in different patient populations and chemical agents persists.

Hearing and Diet (Narrative Review).

It seems that food factors and the type of nutrition have an effect on the function of the auditory system. Hearing is one of the most important senses for social communication and high cognitive behaviors. Sensorineural hearing loss leaves adverse and permanent consequences in all aspects of personal and social life of affected patients. Hence, this narrative review study was designed to determine the relationship between sensorineural hearing loss and type of diet. Based on the inclusion criteria, the full text of 62 articles published between 2005 and 2023 were extracted from Scopus, Medline [PubMed], Web of Science, and Google Scholar websites and constituted the sources of this research. The results of the studies showed that by limiting the consumption of foods rich in cholesterol, sugar, carbohydrates, and protein, hearing is protected against the factors that cause sensorineural hearing loss. Also, increasing the consumption of vegetables, fruits, omega-3, antioxidants in the form of vitamins A, C, E reduce hearing susceptibility due to noise exposure, presbycusis, ototoxic agents, and etc. Healthy diet includes eating all the nutrients the body needs in a balanced way. Healthy lifestyle factors including continuous physical activity, good sleep quality, quitting smoking, stay away from stressful factors or relaxation, and avoiding exposure to environmental noise. By following healthy eating and lifestyle patterns, the conditions for hearing, physical and mental health are provided.

Progress on mechanisms of age-related hearing loss.

Age-related hearing loss, or presbycusis, is a common cause of hearing loss in elderly people worldwide. It typically presents as progressive, irreversible, and usually affects the high frequencies of hearing, with a tremendous impact on the quality of life. Presbycusis is a complex multidimensional disorder, in addition to aging, multiple factors including exposure to noise, or ototoxic agents, genetic susceptibility, metabolic diseases and lifestyle can influence the onset and severity of presbycusis. With the aging of the body, its ability to clean up deleterious substances produced in the metabolic process is weakened, and the self-protection and repair function of the body is reduced, which in turn leads to irreversible damage to the cochlear tissue, resulting in the occurrence of presbycusis. Presently, oxidative stress (OS), mitochondrial DNA damage, low-grade inflammation, decreased immune function and stem cell depletion have been demonstrated to play a critical role in developing presbycusis. The purpose of this review is to illuminate the various mechanisms underlying this age-related hearing loss, with the goal of advancing our understanding, prevention, and treatment of presbycusis.

From Bench to Booth: Examining Hair-Cell Regeneration Through an Audiologist's Scope.

Damage to auditory hair cells is a key feature of sensorineural hearing loss due to aging, noise exposure, or ototoxic drugs. Though hair-cell loss is permanent in humans, research in bird species led to the discovery that analogous hair cells of the avian basilar papilla are able to regenerate after being damaged by ototoxic agents. Regeneration appears to occur through a combination of the mitotic expansion of a precursor population of supporting cells and direct transdifferentiation of supporting cells into functioning hair cells. This review will synthesize the relevant anatomy and pathophysiology of sensorineural hearing loss, the historical observations that led to the genesis of the hair-cell regeneration field, and perspectives on initial human hair-cell regeneration trials.

Estimated prevalence and characteristics of bilateral vestibulopathy diagnosed in Japan: A nationwide survey

ObjectiveTo assess the prevalence and annual incidence of bilateral vestibulopathy (BV) diagnosed in the Japanese adult population. MethodsWe conducted a mail-based survey targeting otolaryngologic clinics and hospitals across Japan to estimate the annual number of patients who were diagnosed as having bilateral vestibulopathy after vestibular function tests during a 12-month period ending March 2019. Using a stratified sampling method, we selected 1,106 departments and asked them to report the number of patients with BV and their demographics. The total number of patients was estimated by multiplying the reported numbers by the reciprocal of the sampling rate and response rate. ResultsThe overall survey response rate was 51.4% (568 departments). The estimated number of patients diagnoses with BV in 2018 was 1,063 (95% confidential interval [CI], 127-1,998) which included 407 patients (95% CI: 134-680) newly-diagnosed with BV. The prevalence and annual incidence of BV in Japan were 0.84 and 0.32, respectively per 100,000 population in Japan. The male-to-female ratio of BV patients was 1.29, and the mean age was 63.7 ± 16.4 years (range 18-84 years). The most frequent etiologies of BV were Meniere's disease (11.4%), meningitis (3.4%), and ototoxic agents (3%). ConclusionsPatients who were diagnosed as having BV were extremely rare in Japan.

Experimental animal models of drug-induced sensorineural hearing loss: a narrative review.

ObjectiveThis narrative review describes experimental animal models of sensorineural hearing loss (SNHL) caused by ototoxic agents.BackgroundSNHL primarily results from damage to the sensory organ within the inner ear or the vestibulocochlear nerve (cranial nerve VIII). The main etiology of SNHL includes genetic diseases, presbycusis, ototoxic agents, infection, and noise exposure. Animal models with functional and anatomic damage to the sensory organ within the inner ear or the vestibulocochlear nerve mimicking the damage seen in humans are employed to explore the mechanism and potential treatment of SNHL. These animal models of SNHL are commonly established using ototoxic agents.MethodsA literature search of PubMed, Embase, and Web of Science was performed for research articles on hearing loss and ototoxic agents in animal models of hearing loss.ConclusionsCommon ototoxic medications such as aminoglycoside antibiotics (AABs) and platinum antitumor drugs are extensively used to induce SNHL in experimental animals. The effect of ototoxic agents in vivo is influenced by the chemical mechanisms of the ototoxic agents, the species of animal, routes of administration of the ototoxic agents, and the dosage of ototoxic agents. Animal models of drug-induced SNHL contribute to understanding the hearing mechanism and reveal the function of different parts of the auditory system in humans.

Analysis of Pharmacokinetics in the Cochlea of the Inner Ear.

Hearing loss affects >5% of the global population and therefore, has a great social and clinical impact. Sensorineural hearing loss, which can be caused by different factors, such as acoustic trauma, aging, and administration of certain classes of drugs, stems primarily from a dysfunction of the cochlea in the inner ear. Few therapeutic strategies against sensorineural hearing loss are available. To develop effective treatments for this disease, it is crucial to precisely determine the behavior of ototoxic and therapeutic agents in the microenvironment of the cochlea in live animals. Since the 1980s, a number of studies have addressed this issue by different methodologies. However, there is much less information on pharmacokinetics in the cochlea than that in other organs; the delay in ontological pharmacology is likely due to technical difficulties with accessing the cochlea, a tiny organ that is encased with a bony wall and has a fine and complicated internal structure. In this review, we not only summarize the observations and insights obtained in classic and recent studies on pharmacokinetics in the cochlea but also describe relevant analytical techniques, with their strengths, limitations, and prospects.

Protective Effects of Deferoxamine on Vestibulotoxicity in Gentamicin-Induced Bilateral Vestibulopathy Rat Model.

Introduction: Administration of aminoglycoside (AG) antibiotics is one of the most common causes of ototoxicity. This study aimed to determine the protective effects of deferoxamine, an iron-chelating agent, on vestibulotoxicity using an intratympanic gentamicin injection (ITGM)-induced bilateral vestibulopathy rat model.Methods: Fifteen Sprague-Dawley rats were randomly assigned to the ITGM only (n = 5), the ITGM combined with intramuscular deferoxamine (DFO) injection (ITGM+DFO, n = 5), or the intratympanic normal saline (control, n = 5) group. The rats in the ITGM+DFO group received intramuscular injection of 150 mg/kg of deferoxamine at 30, 90, and 150 min after the ITGM. The vestibular function was evaluated using the rotarod and open field test every 3 days after the injection until Day 16 when the rats were subjected to histological changes.Results: The rats in the ITGM only group began to show significantly impaired vestibular function 2 days after ITGM into both ears. In contrast, the vestibular function was maintained in the control and ITGM+DFO groups without a difference throughout the experiments. The rats in the ITGM only group showed a near-complete loss of the type I and II hair cells and a collapse of the sensory epithelium in both the saccule and utricle. In contrast, the rats in the ITGM+DFO and control groups showed a relatively well-preserved sensory epithelium including the hair cells, cilia, and otolith layer.Conclusion: This study provides experimental evidence for preventive effects of iron-chelating agents on AG-induced vestibulotoxicity. Simultaneous administration of iron-chelating agents may be considered when using ototoxic agents, especially in those considered to be vulnerable to toxic damage of the inner ear.

Assessment of cochlear toxicity in response to chronic 3,3\u2032-iminodipropionitrile in mice reveals early and reversible functional loss that precedes overt histopathology

The peripheral auditory and vestibular systems rely on sensorineural structures that are vulnerable to ototoxic agents that cause hearing loss and/or equilibrium deficits. Although attention has focused on hair cell loss as the primary pathology underlying ototoxicity, evidence from the peripheral vestibular system indicates that hair cell loss during chronic exposure is preceded by synaptic uncoupling from the neurons and is potentially reversible. To determine if synaptic pathology also occurs in the peripheral auditory system, we examined the extent, time course, and reversibility of functional and morphological alterations in cochleae from mice exposed to 3,3′-iminodipropionitrile (IDPN) in drinking water for 2, 4 or 6 weeks. Functionally, IDPN exposure caused progressive high- to low-frequency hearing loss assessed by measurement of auditory brainstem response wave I absolute thresholds and amplitudes. The extent of hearing loss scaled with the magnitude of vestibular dysfunction assessed behaviorally. Morphologically, IDPN exposure caused progressive loss of outer hair cells (OHCs) and synapses between the inner hair cells (IHCs) and primary auditory neurons. In contrast, IHCs were spared from ototoxic damage. Importantly, hearing loss consistent with cochlear synaptopathy preceded loss of OHCs and synapses and, moreover, recovered if IDPN exposure was stopped before morphological pathology occurred. Our observations suggest that synaptic uncoupling, perhaps as an early phase of cochlear synaptopathy, also occurs in the peripheral auditory system in response to IDPN exposure. These findings identify novel mechanisms that contribute to the earliest stages of hearing loss in response to ototoxic agents and possibly other forms of acquired hearing loss.

Monitoring Ototoxicity through Otoacoustic Emissions. Present, COVID-19, and Future Related Insights

The administration of certain drugs is directly related to inner ear damage. Due to the potential of these elements and their usage, more extensive monitoring of adverse effects should be implemented. That is why, baseline evaluation for ototoxicity must be adequately extensive and should embrace conventional PTA thresholds, HFA, immittance measurements, speech audiometry in quiet and in noise, and assessment of OAEs. Health care specialists have reasonably quested other test modalities for ototoxic monitoring, in their effort to eliminate behavioral – subjective testing and even more establishing further improvements in test efficacy. To iterate, drug induced ototoxicities typically are initially presented as OHC dysfunction, and the exact correlation between present OAEs and functional OHCs is fairly well demonstrated. This study provides recent evidence regarding OAEs’ strategic advantages as a part of an ototoxicity monitoring program, as they can detect earlier ototoxic induced thresholds shifts, do not need patient’s own cooperation and are substantially easy to perform and quick. This fact is particularly crucial during present COVID-19 pandemic where ototoxic agents such as chloroquine and hydroxychloroquine are routinely administered in many patients who may be too sick and haggard to perform adequately enough in conventional PTA or similar, behavioral based exams.

Occupational exposures to hazardous chemicals and agents among healthcare workers in Bhutan

Occupational exposures to hazardous chemicals among healthcare workers can result in long-term adverse health outcomes. Research on such exposures from low- and middle-income countries is limited. The aim of this study was to estimate the prevalence of exposures to a range of chemicals used in healthcare settings among Bhutanese healthcare workers. A cross-sectional study was conducted among healthcare workers (n = 370) working in three hospitals in the western region of Bhutan. Demographic and occupational information was collected, and exposures to asthmagens, carcinogens, ototoxic and other agents were assessed using a web-based tool. The prevalence of exposure to these chemicals was calculated and the circumstances resulting in such exposures were examined. The prevalence of exposure to one or more asthmagen, carcinogen, and ototoxic agent was 98.7%, 28.1%, and 7.6%, respectively; and was 6.2% for anesthetic gases and 2.2% for antineoplastic drugs. The most common exposures were to latex, and cleaning and disinfecting agents in the asthmagens group; formaldehyde in the carcinogens group; and p-xylene among ototoxic agents. The circumstances resulting in exposures were using latex gloves, using bleach and chlorhexidine for cleaning, using formaldehyde as a disinfectant and in the laboratory, and using p-xylene in the laboratory. The results indicate that a large proportion of Bhutanese healthcare workers are occupationally exposed to chemicals linked to chronic diseases, with exposure prevalence higher than in high-income countries. The study provides information that can be used to formulate policies and to implement control measures to protect healthcare workers.

STAT1 deficiency predisposes to spontaneous otitis media.

Signal transducer and activator of transcription 1 (STAT1) is known to be an important player in inflammatory responses. STAT1 as a transcription factor regulates the expression of multiple proinflammatory genes. Inflammatory response is one of the common effects of ototoxicity. Our group reported that hair cells of STAT1 knockout (STAT1-KO) mice are less sensitive to ototoxic agents in-vitro. The effect of inflammatory responses in STAT1-KO mice has primarily been studied challenging them with several pathogens and analyzing different organs of those mice. However, the effect of STAT1 ablation in the mouse inner ear has not been reported. Therefore, we evaluated the cochlear function of wild type and STAT1-KO mice via auditory brain stem response (ABR) and performed histopathologic analysis of their temporal bones. We found ABR responses were affected in STAT1-KO mice with cases of bilateral and unilateral hearing impairment. Histopathologic examination of the middle and inner ears showed bilateral and unilateral otitis media. Otitis media was characterized by effusion of middle and inner ear that varied between the mice in volume and inflammatory cell content. In addition, the thickness of the middle ear mucosae in STAT1-KO mice were more pronounced than those in wild type mice. The degree of middle and inner ear inflammation correlated with ABR threshold elevation in STAT1-KO mice. It appears that a number of mice with inflammation underwent spontaneous resolution. The ABR thresholds were variable and showed a tendency to increase in homozygous and heterozygous STAT1-KO mice. These findings suggest that STAT1 ablation confers an increased susceptibility to otitis media leading to hearing impairment. Thus, the study supports the new role of STAT1 as otitis media predisposition gene.

Chloroquine kills hair cells in zebrafish lateral line and murine cochlear cultures: Implications for ototoxicity

Hearing and balance deficits have been reported during and following treatment with the antimalarial drug chloroquine. However, experimental work examining the direct actions of chloroquine on mechanoreceptive hair cells in common experimental models is lacking. This study examines the effects of chloroquine on hair cells using two common experimental models: the zebrafish lateral line and neonatal mouse cochlear cultures. Zebrafish larvae were exposed to varying concentrations of chloroquine phosphate or hydroxychloroquine for 1 h or 24 h, and hair cells assessed by antibody staining. A significant, dose-dependent reduction in the number of surviving hair cells was seen across conditions for both exposure periods. Hydroxychloroquine showed similar toxicity. In mouse cochlear cultures, chloroquine damage was specific to outer hair cells in tissue from the cochlear basal turn, consistent with susceptibility to other ototoxic agents. These findings suggest a need for future studies employing hearing and balance monitoring during exposure to chloroquine and related compounds, particularly with interest in these compounds as therapeutics against viral infections including coronavirus.

Agentes Químicos Ototóxicos (para além dos Solventes)

Introduction / framework / objectives Classically in Occupational Health Hypoacusis is associated to noise exposure; however, there are several chemical agents with this capability. Among these, the most frequently associated are solvents, although not always with irrefutable scientific evidence for some cases. Within other classes of chemical agents the data is even scarcer and less robust. The aim of this review was to summarize the most recent and pertinent publications on ototoxic agents (other than solvents). Methodology This is an Integrative Bibliographic Review, initiated at September 2019 on the databases “CINALH plus with full text, Medline with full text, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Cochrane Methodology Register, Nursing and Allied Health Collection: Comprehensive, MedicLatina, Academic Search Ultimate, Science Direct, Web of Science, SCOPUS and RCAAP”. Content The most commonly mentioned classes are solvents (there is already an article published in this journal related to the risk of hypoacusis), heavy metals, asphyxiants and pesticides. It is also described that some antibiotics, anticancer drugs and diuretics may be ototoxic directly. In turn, hydrogen cyanide and carbon monoxide can have a synergistic effect with noise, as well as some heavy metals, asphyxiants and pesticides. However, in contexts where there is noise and ototoxic chemical agents, it is difficult to understand the contribution of each, and synergism may occur. Moreover, the situation seems to be clearer in animals; In humans some researchers assume that further studies are needed and the levels at which injury arises are not known clearly. At higher concentrations, hypoacusis seems evident, but for smaller amounts, data are not always consensual. There is also no consensus on the lowest dose that will induce damage. In addition, in most occupational situations exposure includes several chemical agents and not one isolated. Animal is not equivalent to human metabolism, so generalizations of results should be made with reservations. At work level, there are fewer standards for chemical versus noise agents in the context of hearing loss. Global ototoxicity is believed to be related to oxidative stress; not only due to the formation of reactive oxygen species, but also through the attenuation of antioxidant defense mechanisms. Discussion, Limitations, and Conclusions Most of the published studies on this subject are not very robust, besides that they have heterogeneous conditions among themselves. Hence, the conclusions of these studies cannot be generalized directly to the population of workers exposed to ototoxic agents. Still, among the latter there are some that seem to associate more clearly with hearing loss. Whenever the association is proven and/ or suspected, the Occupational Health team should provide measures that mitigate exposure to provide the safest and healthiest working environment possible. It would be relevant to know more about the national reality and to have published data of professionals working in companies with these agents, comparing the effect of different concentrations/ products and/ or simultaneous exposure to noise (possibly at different intensities), depending on the existing production process.

The estimated prevalence of exposure to carcinogens, asthmagens, and ototoxic agents among healthcare workers in Australia.

Healthcare workers are occupationally exposed to various hazardous chemicals and agents that can potentially result in long-term adverse health effects. These exposures have not been comprehensively examined at a population level. The aim of this study was to examine occupational exposures to a wide range of asthmagens, carcinogens, and ototoxic agents among healthcare workers in Australia. Data were collected as part of the Australian Work Exposures Studies, which were computer-assisted telephone surveys conducted in 2011, 2014, and 2016 to assess the prevalence of occupational exposures to carcinogens, asthmagens, and ototoxic agents, respectively, among Australian workers. Using data on healthcare workers, the prevalence of exposures to these agents was calculated and associations of demographic variables and occupation groups with exposure status were examined. The prevalence of exposure to at least one asthmagen, carcinogen, and ototoxic agent was 92.3%, 50.7%, and 44.6%, respectively. The most common exposures were to (a) cleaning and sterilizing agents in the asthmagen group; (b) shift work in the carcinogen group; and (c) toluene and p-xylene among ototoxic agents. Exposure varied by occupation, with exposure to carcinogens and ototoxic agents highest among personal carers and exposure to carcinogens most likely among nursing professionals and health and welfare support workers. The results demonstrate that a substantial proportion of Australian healthcare workers are occupationally exposed to asthmagens, carcinogens, and ototoxic agents. These exposures are more common among certain occupational groups. The information provided by this study will be useful in prioritizing and implementing control strategies.