Surface-mediated spontaneous emulsification of the acylated peptide, semaglutide.

Acylated peptides composed of glucagon-like peptide-1 receptor agonists modified with a fatty acid side chain are an important class of therapeutics for type 2 diabetes and obesity but are susceptible to an unusual physical instability in the presence of hydrophobic surfaces, i.e., spontaneous emulsification, also known as ouzo formation in practice. In this work, light scattering, small-angle X-ray scattering, and circular dichroism measurements are used to characterize the physical properties of the semaglutide colloidal phase, including size distribution, shape, secondary structure, internal structure, and internal composition, as a function of solution physico-chemical conditions. The existence and size of the colloids formed are successfully predicted by a classical Rayleigh model, which identifies the parameters controlling their size and formation. Colloid formation is found to be catalyzed by hydrophobic surfaces, and formation rates are modeled as an autocatalytic reaction, enabling the formation of a master curve for various surfaces that elucidates the mechanism. Surfaces differ due to differences in surface wettability, which can be correlated with Hansen solubility parameters. This work provides insights into this unusual colloidal phenomenon and guides the peptide synthesis process and drug product formulation in the pharmaceutical industry.

Estimating the likelihood of epilepsy from clinically noncontributory electroencephalograms using computational analysis: A retrospective, multisite case-control study.

OBJECTIVE: This study was undertaken to validate a set of candidate biomarkers of seizure susceptibility in a retrospective, multisite case-control study, and to determine the robustness of these biomarkers derived from routinely collected electroencephalography (EEG) within a large cohort (both epilepsy and common alternative conditions such as nonepileptic attack disorder). METHODS: The database consisted of 814 EEG recordings from 648 subjects, collected from eight National Health Service sites across the UK. Clinically noncontributory EEG recordings were identified by an experienced clinical scientist (N = 281; 152 alternative conditions, 129 epilepsy). Eight computational markers (spectral [n = 2], network-based [n = 4], and model-based [n = 2]) were calculated within each recording. Ensemble-based classifiers were developed using a two-tier cross-validation approach. We used standard regression methods to assess whether potential confounding variables (e.g., age, gender, treatment status, comorbidity) impacted model performance. RESULTS: We found levels of balanced accuracy of 68% across the cohort with clinically noncontributory normal EEGs (sensitivity =61%, specificity =75%, positive predictive value =55%, negative predictive value =79%, diagnostic odds ratio =4.64, area under receiver operated characteristics curve =.72). Group level analysis found no evidence suggesting any of the potential confounding variables significantly impacted the overall performance. SIGNIFICANCE: These results provide evidence that the set of biomarkers could provide additional value to clinical decision-making, providing the foundation for a decision support tool that could reduce diagnostic delay and misdiagnosis rates. Future work should therefore assess the change in diagnostic yield and time to diagnosis when utilizing these biomarkers in carefully designed prospective studies.

Methods for Spatial Extrapolation of Methane Measurements in Constructing Regional Estimates from Sample Populations.

Methane emission estimates for oil and gas facilities are typically based on estimates at a subpopulation of facilities, and these emission estimates are then extrapolated to a larger region or basin. Basin-level emission estimates are then frequently compared with basin-level observations. Methane emissions from oil and gas systems are inherently variable and intermittent, which make it difficult to determine whether a sample population is sufficiently large to be representative of a larger region. This work develops a framework for extrapolation of emission estimates using the case study of an operator in the Green River Basin. This work also identifies a new metric, the capture ratio, which quantifies the extent to which sources are represented in the sample population, based on the skewness of emissions for each source. There is a strong correlation between the capture ratio and extrapolation error, which suggests that understanding source-level emissions distributions can mitigate error when sample populations are selected and extrapolating measurements. The framework and results from this work can inform the selection and extrapolation of site measurements when developing methane emission inventories and establishing uncertainty bounds to assess whether inventory estimates are consistent with independent large spatial-scale observations.

Use of human predictive patch test (HPPT) data for the classification of skin sensitization hazard and potency.

Since the 1940s, patch tests in healthy volunteers (Human Predictive Patch Tests, HPPTs) have been used to identify chemicals that cause skin sensitization in humans. Recently, we reported the results of a major curation effort to support the development of OECD Guideline 497 on Defined Approaches (DAs) for skin sensitization (OECD in Guideline No. 497: Defined Approaches on Skin Sensitisation, 2021a. https://doi.org/10.1787/b92879a4-en ). In the course of this work, we compiled and published a database of 2277 HPPT results for 1366 unique test substances (Strickland et al. in Arch Toxicol 97:2825-2837, 2023. https://doi.org/10.1007/s00204-023-03530-3 ). Here we report a detailed analysis of the value of HPPT data for classification of chemicals as skin sensitizers under the United Nations' Globally Harmonized System of Classification and Labelling of Chemicals (GHS). As a result, we propose the dose per skin area (DSA) used for classification by the GHS to be replaced by or complemented with a dose descriptor that may better reflect sensitization incidence [e.g., the DSA causing induction of sensitization in one individual (DSA1+) or the DSA leading to an incidence of induction in 5% of the tested individuals (DSA05)]. We also propose standardized concepts and workflows for assessing individual HPPT results, for integrating multiple HPPT results and for using them in concert with Local Lymph Node Assay (LLNA) data in a weight of evidence (WoE) assessment. Overall, our findings show that HPPT results are often not sufficient for deriving unambiguous classifications on their own. However, where they are, the resulting classifications are reliable and reproducible and can be integrated well with those from other skin sensitization data, such as the LLNA.

Differences in the anatomy and physiology of the human and rat respiratory tracts and impact on toxicological assessments.

Inhalation is a critical route through which substances can exert adverse effects in humans; therefore, it is important to characterize the potential effects that inhaled substances may have on the human respiratory tract by using fit for purpose, reliable, and human relevant testing tools. In regulatory toxicology testing, rats have primarily been used to assess the effects of inhaled substances as they-being mammals-share similarities in structure and function of the respiratory tract with humans. However, questions about inter-species differences impacting the predictability of human effects have surfaced. Disparities in macroscopic anatomy, microscopic anatomy, or physiology, such as breathing mode (e.g., nose-only versus oronasal breathing), airway structure (e.g., complexity of the nasal turbinates), cell types and location within the respiratory tract, and local metabolism may impact inhalation toxicity testing results. This review shows that these key differences describe uncertainty in the use of rat data to predict human effects and supports an opportunity to harness modern toxicology tools and a detailed understanding of the human respiratory tract to develop testing approaches grounded in human biology. Ultimately, as the regulatory purpose is protecting human health, there is a need for testing approaches based on human biology and mechanisms of toxicity.

Evaluation of in silico model predictions for mammalian acute oral toxicity and regulatory application in pesticide hazard and risk assessment.

The United States Environmental Protection Agency (USEPA) uses the lethal dose 50% (LD50) value from in vivo rat acute oral toxicity studies for pesticide product label precautionary statements and environmental risk assessment (RA). The Collaborative Acute Toxicity Modeling Suite (CATMoS) is a quantitative structure-activity relationship (QSAR)-based in silico approach to predict rat acute oral toxicity that has the potential to reduce animal use when registering a new pesticide technical grade active ingredient (TGAI). This analysis compared LD50 values predicted by CATMoS to empirical values from in vivo studies for the TGAIs of 177 conventional pesticides. The accuracy and reliability of the model predictions were assessed relative to the empirical data in terms of USEPA acute oral toxicity categories and discrete LD50 values for each chemical. CATMoS was most reliable at placing pesticide TGAIs in acute toxicity categories III (>500-5000 mg/kg) and IV (>5000 mg/kg), with 88% categorical concordance for 165 chemicals with empirical in vivo LD50 values ≥ 500 mg/kg. When considering an LD50 for RA, CATMoS predictions of 2000 mg/kg and higher were found to agree with empirical values from limit tests (i.e., single, high-dose tests) or definitive results over 2000 mg/kg with few exceptions.

Retrospective evaluation of the eye irritation potential of agrochemical formulations.

Multiple in vitro eye irritation methods have been developed and adopted as OECD health effects test guidelines. However, for predicting the ocular irritation/damage potential of agrochemical formulations there is an applicability domain knowledge gap for most of the methods. To overcome this gap, a retrospective evaluation of 192 agrochemical formulations with in vivo (OECD TG 405) and in vitro (OECD TG 437, 438, and/or 492) data was conducted to determine if the in vitro methods could accurately assign United Nations Globally Harmonized System for Classification and Labelling of Chemicals (GHS) eye irritation hazard classifications. In addition, for each formulation the eye irritation classification was derived from the classification of the contained hazardous ingredients and their respective concentration in the product using the GHS concentration threshold (CT) approach. The results herein suggest that the three in vitro methods and the GHS CT approach were highly predictive of formulations that would not require GHS classification for eye irritation. Given most agrochemical formulations fall into this category, methods that accurately identify non-classified agrochemical formulations could significantly reduce the use of animals for this endpoint.

The impact of the pandemic on the presentation and treatment of head and neck squamous cell carcinoma at a county hospital.

INTRODUCTION: In March 2020, the World Health Organization declared COVID-19 a pandemic, initiating stay-at-home orders which delayed cancer care and screening. The impact on head and neck cancer care in populations at risk has yet to be elucidated. The objective of this investigation is to evaluate how the presentation, diagnosis, and treatment of head and neck squamous cell carcinoma cancer patients at a county hospital were affected by the pandemic. METHODS: A retrospective review of patients with head and neck squamous cell carcinoma that were diagnosed at a county hospital 365 days before and after stay-at-home orders were initiated. The primary outcomes were duration between diagnosis from imaging and initiation of treatment. Secondary outcomes included mortality, stage, nodal status, and distant metastasis at presentation. RESULTS: There was a total of 105 diagnoses. Sixty-five (62 %) head and neck squamous cell carcinoma diagnoses were diagnosed before the stay-at-home orders were initiated, and 40 (38 %) after. Eighty percent (32/40) of diagnoses presenting after had stage IV disease compared to 58 % (38/65) in those before (p < 0.05). A higher percentage of patients who presented later had a >30-day delay to biopsy (43 % v. 20 %, OR: 3.0, p < 0.05). This difference was exacerbated by those with laryngeal, oral cavity, or oropharyngeal cancer (45 % v. 15 %, OR: 4.5, p < 0.05). There was a larger delay from diagnosis to treatment after the orders were initiated (68 v. 53, p < 0.05) however there was no difference in one-year mortality (25 % v. 23 %, p > 0.05). This investigation found a 14 % loss to follow-up. CONCLUSIONS AND RELEVANCE: In this cohort of head and neck squamous cell carcinoma diagnoses at a county hospital, those diagnosed after the stay-at-home orders were initiated presented with more advanced disease. They also had more delays in diagnosis and initiation of treatment. There was no difference in one-year mortality rates between the two groups however there was a significant loss to follow-up, limiting prognostication. These findings serve to better prepare healthcare providers to implement optimized care during future shutdowns related to public health crises. LEVEL OF EVIDENCE: III.

Long-term Outcomes of Revision Total Hip Arthroplasty Using a Modular Fluted Conical Femoral Stem.

BACKGROUND: This study presents minimum 6-year follow-up data on the survival and satisfaction of an uncemented modular revision femoral system, following on from our previously published earlier results. METHODS: We retrospectively reviewed all revision hip arthroplasties performed at our institution between January 2005 and October 2012, using a single modular femoral revision system. Patient-reported outcomes were collected (satisfaction score and Oxford Hip Score). Preoperative and postoperative radiographs were reviewed for stem subsidence, and Kaplan-Meier analysis was performed for survival. A total of 115 femoral revisions were performed in 106 patients. RESULTS: All-cause survival was 82% (95% confidence interval 74 to 91%) at 10.8 years, and 96% (95% confidence interval 90 to 100%) excluding septic failure. Of the 19 cases requiring reoperation, 16 were for infection, 2 for aseptic loosening, and 1 for mechanical failure. At final follow-up, 88.5% of patients were "satisfied" or "very satisfied". CONCLUSIONS: This study showed excellent clinical results of a commonly used revision hip stem with at least 10 years follow-up. Satisfaction rates were high, with few aseptic failures. Stem subsidence was more common in revisions for infection, but did not correlate with lower satisfaction scores.

Defined approaches to classify agrochemical formulations into EPA hazard categories developed using EpiOcularTM reconstructed human corneal epithelium and bovine corneal opacity and permeability assays.

Many sectors have seen complete replacement of the in vivo rabbit eye test with reproducible and relevant in vitro and ex vivo methods to assess the eye corrosion/irritation potential of chemicals. However, the in vivo rabbit eye test remains the standard test used for agrochemical formulations in some countries. Therefore, two defined approaches (DAs) for assessing conventional agrochemical formulations were developed, using the EpiOcularTM Eye Irritation Test (EIT) [Organisation for Economic Co-operation and Development (OECD) test guideline (TG) 492] and the Bovine Corneal Opacity and Permeability (OECD TG 437; BCOP) test with histopathology. Presented here are the results from testing 29 agrochemical formulations, which were evaluated against the United States Environmental Protection Agency's (EPA) pesticide classification system, and assessed using orthogonal validation, rather than direct concordance analysis with the historical in vivo rabbit eye data. Scientific confidence was established by evaluating the methods and testing results using an established framework that considers fitness for purpose, human biological relevance, technical characterisation, data integrity and transparency, and independent review. The in vitro and ex vivo methods used in the DAs were demonstrated to be as or more fit for purpose, reliable and relevant than the in vivo rabbit eye test. Overall, there is high scientific confidence in the use of these DAs for assessing the eye corrosion/irritation potential of agrochemical formulations.

Quantifying the impact of urban road traffic on air quality: activity pre-pandemic and during partial and full lockdowns.

The impact of partial and full COVID lockdowns in 2020 on vehicle miles traveled (VMT) in Kuwait was estimated using data extracted from the Directions API of Google Maps and a Python script running as a cronjob. This approach was validated by comparing the predictions based on the app to measuring traffic flows for 1 week across four road segments considered in this study. VMT during lockdown periods were compared to VMT for the same calendar weeks before the pandemic. NOx emissions were estimated based on VMT and were used to simulate the spatial patterns of NOx concentrations using an air quality model (AERMOD). Compared to pre-pandemic periods, VMT was reduced by up to 25.5% and 42.6% during the 2-week partial and full lockdown episodes, respectively. The largest reduction in the traffic flow rate occurred during the middle of these 2-week periods, when the traffic flow rate decreased by 35% and 49% during the partial and full lockdown periods, respectively. The AERMOD simulation results predicted a reduction in the average maximum concentration of emissions directly related to VMT across the region by up to 38%, with the maximum concentration shifting to less populous residential areas as a result of the lockdown.

Absence of Dystrophin Disrupts Skeletal Muscle Signaling: Roles of Ca2+, Reactive Oxygen Species, and Nitric Oxide in the Development of Muscular Dystrophy.

Dystrophin is a long rod-shaped protein that connects the subsarcolemmal cytoskeleton to a complex of proteins in the surface membrane (dystrophin protein complex, DPC), with further connections via laminin to other extracellular matrix proteins. Initially considered a structural complex that protected the sarcolemma from mechanical damage, the DPC is now known to serve as a scaffold for numerous signaling proteins. Absence or reduced expression of dystrophin or many of the DPC components cause the muscular dystrophies, a group of inherited diseases in which repeated bouts of muscle damage lead to atrophy and fibrosis, and eventually muscle degeneration. The normal function of dystrophin is poorly defined. In its absence a complex series of changes occur with multiple muscle proteins showing reduced or increased expression or being modified in various ways. In this review, we will consider the various proteins whose expression and function is changed in muscular dystrophies, focusing on Ca(2+)-permeable channels, nitric oxide synthase, NADPH oxidase, and caveolins. Excessive Ca(2+) entry, increased membrane permeability, disordered caveolar function, and increased levels of reactive oxygen species are early changes in the disease, and the hypotheses for these phenomena will be critically considered. The aim of the review is to define the early damage pathways in muscular dystrophy which might be appropriate targets for therapy designed to minimize the muscle degeneration and slow the progression of the disease.

International regulatory uses of acute systemic toxicity data and integration of new approach methodologies.

Chemical regulatory authorities around the world require systemic toxicity data from acute exposures via the oral, dermal, and inhalation routes for human health risk assessment. To identify opportunities for regulatory uses of non-animal replacements for these tests, we reviewed acute systemic toxicity testing requirements for jurisdictions that participate in the International Cooperation on Alternative Test Methods (ICATM): Brazil, Canada, China, the European Union, Japan, South Korea, Taiwan, and the USA. The chemical sectors included in our review of each jurisdiction were cosmetics, consumer products, industrial chemicals, pharmaceuticals, medical devices, and pesticides. We found acute systemic toxicity data were most often required for hazard assessment, classification, and labeling, and to a lesser extent quantitative risk assessment. Where animal methods were required, animal reduction methods were typically recommended. For many jurisdictions and chemical sectors, non-animal alternatives are not accepted, but several jurisdictions provide guidance to support the use of test waivers to reduce animal use for specific applications. An understanding of international regulatory requirements for acute systemic toxicity testing will inform ICATM's strategy for the development, acceptance, and implementation of non-animal alternatives to assess the health hazards and risks associated with acute toxicity.

Assessing Detection Efficiencies for Continuous Methane Emission Monitoring Systems at Oil and Gas Production Sites.

Continuous monitoring systems, consisting of multiple fixed sensors, are increasingly being deployed at oil and gas production sites to detect methane emissions. While these monitoring systems operate continuously, their efficiency in detecting emissions will depend on meteorological conditions, sensor detection limits, the number of sensors deployed, and sensor placement strategies. This work demonstrates an approach to assess the effectiveness of continuous sensor networks in detecting infinite-duration and fixed-duration emission events. The case studies examine a single idealized source and a group of nine different sources at varying heights and locations on a single pad. Using site-specific meteorological data and dispersion modeling, the emission detection performance is characterized. For these case studies, infinite-duration emission events are detected within 1 h to multiple days, depending on the number of sensors deployed. The percentage of fixed-duration emission events that are detected ranged from less than 10% to more than 90%, depending on the number of sources, emission release height, emission event duration, and the number of sensors deployed. While these results are specific to these case studies, the analysis framework described in this work can be broadly applied in the evaluation of continuous emission monitoring network designs.

High Chlorine Concentrations in an Unconventional Oil and Gas Development Region and Impacts on Atmospheric Chemistry.

Growth in unconventional oil and gas development (UOGD) in the United States has increased airborne emissions, raising environmental and human health concerns. To assess the potential impacts on air quality, we deployed instrumentation in Karnes City, Texas, a rural area in the middle of the Eagle Ford Shale. We measured several episodes of elevated Cl2 levels, reaching maximum hourly averages of 800 ppt, the highest inland Cl2 concentration reported to date. Concentrations peak during the day, suggesting a strong local source (given the short photolysis lifetime of Cl2) and/or a photoinitiated production mechanism. Well preproduction activity near the measurement site is a plausible source of these high Cl2 levels via direct emission and photoactive chemistry. ClNO2 is also observed, but it peaks overnight, consistent with well-known nocturnal formation processes. Observations of organochlorines in the gas and particle phases reflect the contribution of chlorine chemistry to the formation of secondary pollutants in the area. Box modeling results suggest that the formation of ozone at this location is influenced by chlorine chemistry. These results suggest that UOGD can be an important source of reactive chlorine in the atmosphere, impacting radical budgets and the formation of secondary pollutants in these regions.

Bleach Emissions Interact Substantially with Surgical and KN95 Mask Surfaces.

Mask wearing and bleach disinfectants became commonplace during the COVID-19 pandemic. Bleach generates toxic species including hypochlorous acid (HOCl), chlorine (Cl2), and chloramines. Their reaction with organic species can generate additional toxic compounds. To understand interactions between masks and bleach disinfection, bleach was injected into a ventilated chamber containing a manikin with a breathing system and wearing a surgical or KN95 mask. Concentrations inside the chamber and behind the mask were measured by a chemical ionization mass spectrometer (CIMS) and a Vocus proton transfer reaction mass spectrometer (Vocus PTRMS). HOCl, Cl2, and chloramines were observed during disinfection and concentrations inside the chamber are 2-20 times greater than those behind the mask, driven by losses to the mask surface. After bleach injection, many species decay more slowly behind the mask by a factor of 0.5-0.7 as they desorb or form on the mask. Mass transfer modeling confirms the transition of the mask from a sink during disinfection to a source persisting >4 h after disinfection. Humidifying the mask increases reactive formation of chloramines, likely related to uptake of ammonia and HOCl. These experiments indicate that masks are a source of chemical exposure after cleaning events occur.

A database of human predictive patch test data for skin sensitization.

Critical to the evaluation of non-animal tests are reference data with which to assess their relevance. Animal data are typically used because they are generally standardized and available. However, when regulatory agencies aim to protect human health, human reference data provide the benefit of not having to account for possible interspecies variability. To support the evaluation of non-animal approaches for skin sensitization assessment, we collected data from 2277 human predictive patch tests (HPPTs), i.e., human repeat insult patch tests and human maximization tests, for skin sensitization from 1555 publications. We recorded protocol elements and positive or negative outcomes, developed a scoring system to evaluate each test for reliability, and calculated traditional and non-traditional dose metrics. We also traced each test result back to its original report to remove duplicates. The resulting database, which contains information for 1366 unique substances, was characterized for physicochemical properties, chemical structure categories, and protein binding mechanisms. This database is publicly available on the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods website and in the Integrated Chemical Environment to serve as a resource for additional evaluation of alternative methods and development of new approach methodologies for skin sensitization assessments.

Evaluation of the fish acute toxicity test for pesticide registration.

The U.S. Environmental Protection Agency (USEPA) uses the in vivo fish acute toxicity test to assess potential risk of substances to non-target aquatic vertebrates. The test is typically conducted on a cold and a warm freshwater species and a saltwater species for a conventional pesticide registration, potentially requiring upwards of 200 or more fish. A retrospective data evaluation was conducted to explore the potential for using fewer fish species to support conventional pesticide risk assessments. Lethal concentration 50% (LC50) values and experimental details were extracted and curated from 718 studies on fish acute toxicity submitted to USEPA. The LC50 data were analysed to determine, when possible, the relative sensitivity of the tested species to each pesticide. One of the tested freshwater species was most sensitive in 85% of those cases. The tested cold freshwater species was the most sensitive overall among cases with established relative sensitivity and was within 3X of the LC50 value of the most sensitive species tested in 98% of those cases. The results support potentially using fewer than three fish species to conduct ecological risk assessments for the registration of conventional pesticides.

Evaluation of cost data associated with pediatric cochlear implantation (CI) throughout 2016-2021.

INTRODUCTION: Cochlear Implants (CI) are a mainstay in the treatment of severe sensorineural hearing loss with proven cost-effectiveness and improved quality of life. However, costs associated with CI are variable. During the Covid-19 pandemic, elective surgeries decreased. The investigation into how the pandemic affected CI procedures, costs, and demographic utilization has not been elucidated. METHODS: A retrospective cohort study using the Pediatric Health Information System® (PHIS) database, which consists of 50 children's hospitals, was performed. Regions were defined according to PHIS guidelines. We evaluated number of CIs, total charges and costs, Charge to Cost Ratios (CCR), demographic information, and subgrouped this analysis by region throughout 2016-2021. Charges were adjusted by CMS wage index for hospital location. RESULTS: During the years of 2016-2021, there was a rising number of CIs every year except for 2020 which had a decrease, largely driven by the southern and midwestern regions. The median number of cases did not differ between the years. The median adjusted charges increased every year, but not significantly ($103,883-$125,394). The median CCR also did not differ throughout the years (2.7-3.1). Still, there was a larger interquartile range in 2021 (2.3-4.4) for the median CCR compared to all other years (2.1-3.8), particularly in the South. The percentage of white, non-Hispanic/Latino patients who underwent CI was larger in 2020-2021 (78-79.8 %) compared to 2016-2019 (73.3-77.5 %). CONCLUSIONS: The number of CIs in 2020 was lower than in 2019 or 2021. The median CCR for CI procedures increased from 2016 to 2021 but not significantly. The range of CCR was larger in 2021 compared to the years prior, suggestive of cost shifting by some hospitals to offset the loss in revenue. There was a small but significant increase in white, non-Hispanic patients receiving CI in 2020 and 2021, suggestive of a socio-economic shift in care post pandemic.

Noise exposure in pediatric otolaryngology clinic: A sound survey of a single-institution tertiary care facility.

BACKGROUND: The Occupational Safety and Health Administration (OSHA) considers acoustic exposure of 90 decibels (dB) an occupational risk for noise-induced hearing loss. Pediatric healthcare clinicians are exposed to considerable noise especially during invasive procedures, predisposing them to noise-induced hearing loss, increased work-related stress, and increased complications associated with intense noise exposure. While there has been extensive research in noise exposure in dentistry, to date there has been no research on noise exposure in the pediatric otolaryngology clinic setting. The objective of this study is to quantify the degree of noise exposure that pediatric otolaryngologists encounter in the clinical setting. METHODS: A sound survey was performed of 420 pediatric otolaryngology clinic visits within a single-institution tertiary care facility from January 2022 to March 2022, with a total of 409 visits included. At each visit, noise was measured using a calibrated National Institute for Occupational Safety and Health (NIOSH) Sound Meter application, an iPad, and a microphone. The Equivalent Continuous Sound Pressure Level (LAeq), peak sound pressure level (SPL), C-weighted peak noise level (LCpeak), and the 8-hour time-weighted average (TWA) sound level were recorded. RESULTS: The average LAeq was 61.1 dB, the median LAeq was 60.3 dB, and the average peak SPL was 80.5 dB. Only 0.5 % of visits reached an LAeq above 80 dB, however, 51 % were above 60 dB and 99 % were above 45 dB. No clinicians were exposed to noise exceeding established limits of safety. Patients younger than ten years old (p < 0.001) and those who underwent procedures such as cerumen removal (p < 0.001) elicited higher ranges of elevated noise. Multivariate analysis confirmed that increased age decreased acoustic exposure while procedures increased acoustic exposure. CONCLUSIONS: The results of this study suggest that pediatric otolaryngology clinicians do not exceed hazardous noise limit exposure. However, they are exposed to levels above those which have been linked to stress, poor productivity, and stress-related disorders. This analysis also reports that patients who are younger and those that undergo procedures, specifically cerumen removal, tend to expose their providers to the highest levels of noise. This is the first study examining noise exposure in pediatric otolaryngology, and further research should evaluate the risks of noise exposure in this environment.