Abundance and distribution of tire and road wear particles in the Seine River, France.

Tire and road wear particles (TRWP) are formed at the frictional interface between tires and the road surface. Tire tread and road pavement materials are denser than water but can be washed from the road surface into receiving water bodies, ultimately depositing into sediment, soil, or other media depending on the receiving environment. However, the paucity of mass-based measurements has limited the knowledge on the nature and extent of environmental concentrations necessary for environmental risk assessment of TRWP. Surface water and sediment samples were collected from the Seine River, France to characterize TRWP concentration. Sample locations were established upstream, within, and downstream of a major metropolitan area (Paris); downstream of smaller urban areas; adjacent to undeveloped land; and near the confluence of the estuary. Surface water and sediment were collected from the left and right banks at each of the eight locations, including two duplicates, for a total of 18 samples. Additionally, three sediment traps were deployed near the mouth of the river to quantify the flux of TRWP to sediment. Retained solids and sediment samples were analyzed using a modified pyrolysis gas chromatography/mass spectrometry (Py-GC/MS) method that minimized the matrix interferences in the samples thus improving the current ISO Technical Specification ISO/TS 21396 : 2017 for TRWP mass concentration by Py-GC/MS. TRWP concentration was alternatively estimated by separating the sediment into the <1.9 g cm-3 fraction and analyzing for tread-derived zinc content. TRWP concentrations estimated by zinc method were significantly higher than results from the modified Py-GC/MS method. TRWP and total zinc concentrations show a decreasing trend from available historical data.

Refinement of a microfurnace pyrolysis-GC-MS method for quantification of tire and road wear particles (TRWP) in sediment and solid matrices.

Tire and road wear particles (TRWP) are produced by abrasion at the interface of the pavement and tread surface and contain tread rubber with road mineral encrustations. Quantitative thermoanalytical methods capable of estimating TRWP concentrations are needed to assess the prevalence and environmental fate of these particles. However, the presence of complex organic constituents in sediment and other environmental samples presents a challenge to the reliable determination of TRWP concentrations using current pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS) methodologies. We are unaware of a published study evaluating pretreatment and other method refinements for microfurnace Py-GC-MS analysis of the elastomeric polymers in TRWP including polymer-specific deuterated internal standards as specified in ISO Technical Specification (ISO/TS) 20593:2017 and ISO/TS 21396:2017. Thus, potential method refinements were evaluated for microfurnace Py-GC-MS, including chromatography parameter modification, chemical pretreatment, and thermal desorption for cryogenically-milled tire tread (CMTT) samples in an artificial sediment matrix and a sediment field sample. The tire tread dimer markers used for quantification were 4-vinylcyclohexene (4-VCH), a marker for styrene-butadiene rubber (SBR) and butadiene rubber (BR), 4-phenylcyclohexene (4-PCH), a marker for SBR, and dipentene (DP), a marker for natural rubber (NR) or isoprene. The resultant modifications included optimization of GC temperature and mass analyzer settings, along with sample pretreatment with potassium hydroxide (KOH) and thermal desorption. Peak resolution was improved while minimizing matrix interferences with overall accuracy and precision consistent with those typically observed in environmental sample analysis. The initial method detection limit for an artificial sediment matrix was approximately 180 mg/kg for a 10 mg sediment sample. A sediment and a retained suspended solids sample were also analyzed to illustrate the applicability of microfurnace Py-GC-MS towards complex environmental sample analysis. These refinements should help encourage the adoption of pyrolysis techniques for mass-based measurements of TRWP in environmental samples both near and distant from roadways.

Can oral toxicity data for PFAS inform on toxicity via inhalation?

Per- and poly-fluoroalkyl substances (PFAS) are ubiquitous in the environment and are detected in wildlife and humans. With respect to human exposure, studies have shown that ingestion is the primary route of exposure; however, in certain settings, exposure via inhalation could also be a significant source of exposure. While many studies examined toxicity of PFAS via ingestion, limited information is available for PFAS toxicity via the inhalation route, translating into a lack of exposure guidelines. Consequently, this article examined whether route-to-route extrapolation to derive guidelines for inhalation exposure is appropriate for PFAS. Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) were used as exemplary PFAS given the abundance of toxicity data for these two compounds. Our evaluation determined that available toxicity and toxicokinetic data support route-to-route extrapolation for PFAS in order to derive inhalation-based standards. Results from this analysis suggest that an air concentration of 7.0 × 10-5  mg/m3 (or 0.07 µg/m3 ) would be an appropriate RfC for PFOA and PFOS assuming the 2016 EPA RfD of 0.00002 mg/kg-day, whereas use of the interim RfDs proposed in 2022 of 1.5 × 10-9 and 7.9 × 10-9  mg/kg would yield much lower RfCs of 5.25 × 10-9 and 2.77 × 10-8  mg/m3 (or 5.25 × 10-6 and 2.77 × 10-5 µg/m3 ) for PFOA and PFOS, respectively.

Assessment of ethanol exposure from hand sanitizer use and potential for developmental toxicity in nursing infants.

Ingestion of ethanol during pregnancy is known to have detrimental effects on the fetus. Although the potential developmental effects of maternal ethanol intake during lactation are less well characterized, public health guidelines recommend avoidance of alcohol or, if alcohol is consumed, to allow for 1-2 h to pass before nursing. A proposal to classify ethanol as potentially harmful to breast-fed children warrants an investigation of the potential adverse neurodevelopmental effects of low-dose ethanol exposure during lactation. There currently are no studies that have examined neurodevelopmental outcomes from lactational exposure to ethanol from the use of topical products that contain ethanol, such as alcohol-based hand sanitizers (ABHS). Furthermore, the epidemiological literature of lactational ethanol exposures from maternal alcohol consumption is limited in design, provides equivocal evidence of neurological effects in infants, and is insufficient to characterize a dose-response relationship for developmental effects. Toxicological studies that observed neurodevelopmental effects in pups from ethanol via lactation did so at exceedingly high doses that also caused maternal toxicity. In this investigation, blood ethanol concentrations (BECs) of breastfeeding women following typical-to-intense ABHS use were computationally predicted and compared to health benchmarks to quantify the risk for developmental outcomes. Margins of 2.2 to 1000 exist between BECs associated with ABHS use compared to BECs associated with neurotoxicity adverse effect levels in the toxicology literature or oral ethanol intake per public health guidelines. Neurodevelopmental effects are not likely to occur in infants due to ABHS use by breastfeeding women, even when ABHSs are used at intense frequencies.

An integrated benefit-risk assessment of cobalt-containing alloys used in medical devices: Implications for regulatory requirements in the European Union.

In 2017, the European Union (EU) Committee for Risk Assessment (RAC) recommended the classification of metallic cobalt (Co) as Category 1B with respect to its carcinogenic and reproductive hazard potential and Category 2 for mutagenicity but did not evaluate the relevance of these classifications for patients exposed to Co-containing alloys (CoCA) used in medical devices. CoCA are inherently different materials from Co metal from a toxicological perspective and thus require a separate assessment. CoCA are biocompatible materials with a unique combination of properties including strength, durability, and a long history of safe use that make them uniquely suited for use in a wide-range of medical devices. Assessments were performed on relevant preclinical and clinical carcinogenicity and reproductive toxicity data for Co and CoCA to meet the requirements under the EU Medical Device Regulation triggered by the ECHA re-classification (adopted in October 2019 under the 14th Adaptation to Technical Progress to CLP) and to address their relevance to patient safety. The objective of this review is to present an integrated overview of these assessments, a benefit-risk assessment and an examination of potential alternative materials. The data support the conclusion that the exposure to CoCA in medical devices via clinically relevant routes does not represent a hazard for carcinogenicity or reproductive toxicity. Additionally, the risk for the adverse effects that are known to occur with elevated Co concentrations (e.g., cardiomyopathy) are very low for CoCA implant devices (infrequent reports often reflecting a unique catastrophic failure event out of millions of patients) and negligible for CoCA non-implant devices (not measurable/no case reports). In conclusion, the favorable benefit-risk profile also in relation to possible alternatives presented herein strongly support continued use of CoCA in medical devices.

A hazard evaluation of the reproductive/developmental toxicity of cobalt in medical devices.

Cobalt (Co) is an essential element with human exposure occurring from the diet, supplement ingestion, occupational sources, and medical devices. The European Chemical Agency (ECHA) recently voted to classify Co metal as a Reproductive Hazard Category 1B; presumed human reproductive toxicant due to adverse testicular effects in male rodents. A weight of evidence evaluation of the preclinical reproductive and developmental toxicity studies and available clinical data was performed to critically evaluate the relevance of this proposed classification for Co in medical devices. Reproductive responses to Co are limited to the male testes and sperm function following high systemic exposure in rodents, only at Co concentrations/doses that result in overt toxicity (i.e., above the maximum tolerable dose (MTD)). The potential mechanisms of Co reproductive/developmental toxicity, including its indirect mode of action in the testes and relevance to humans, are discussed. The available preclinical and clincial evidence suggests that it would be more appropriate to classify Co as a Reproductive Hazard Category 2 compound: suspected human reproductive toxicant and, in the case of Co-containing medical devices, it should not be considered a reproductive hazard.

Carcinogenic hazard assessment of cobalt-containing alloys in medical devices: Review of in vivo studies.

Cobalt (Co) alloys have been used for over seven decades in a wide range of medical devices, including, but not limited to, hip and knee implants, surgical tools, and vascular stents, due to their favorable biocompatibility, durability, and mechanical properties. A recent regulatory hazard classification review by the European Chemicals Agency (ECHA) resulted in the classification of metallic Co as a Class 1B Carcinogen (presumed to have carcinogenic potential for humans), primarily based on inhalation rodent carcinogenicity studies with pure metallic Co. The ECHA review did not specifically consider the carcinogenicity hazard potential of forms or routes of Co that are relevant for medical devices. The purpose of this review is to present a comprehensive assessment of the available in vivo preclinical data on the carcinogenic hazard potential of exposure to Co-containing alloys (CoCA) in medical devices by relevant routes. In vivo data were reviewed from 33 preclinical studies that examined the impact of Co exposure on local and systemic tumor incidence in rats, mice, guinea pigs, and hamsters. Across these studies, there was no significant increase of local or systemic tumors in studies relevant for medical devices. Taken together, the relevant in vivo data led to the conclusion that CoCA in medical devices are not a carcinogenic hazard in available in vivo models. While specific patient and implant factors cannot be fully replicated using in vivo models, the available in vivo preclinical data support that CoCA in medical devices are unlikely a carcinogenic hazard to patients.

A comprehensive weight of evidence assessment of published acetaminophen genotoxicity data: Implications for its carcinogenic hazard potential.

In 2019, the California Office of Environmental Health Hazard Assessment initiated a review of the carcinogenic hazard potential of acetaminophen, including an assessment of its genotoxicity. The objective of this analysis was to inform this review process with a weight-of-evidence assessment of more than 65 acetaminophen genetic toxicology studies that are of widely varying quality and conformance to accepted standards and relevance to humans. In these studies, acetaminophen showed no evidence of induction of point or gene mutations in bacterial and mammalian cell systems or in in vivo studies. In reliable, well-controlled test systems, clastogenic effects were only observed in unstable, p53-deficient cell systems or at toxic and/or excessively high concentrations that adversely affect cellular processes (e.g., mitochondrial respiration) and cause cytotoxicity. Across the studies, there was no clear evidence that acetaminophen causes DNA damage in the absence of toxicity. In well-controlled clinical studies, there was no meaningful evidence of chromosomal damage. Based on this weight-of-evidence assessment, acetaminophen overwhelmingly produces negative results (i.e., is not a genotoxic hazard) in reliable, robust high-weight studies. Its mode of action produces cytotoxic effects before it can induce the stable, genetic damage that would be indicative of a genotoxic or carcinogenic hazard.

Chemical mapping of tire and road wear particles for single particle analysis.

Tire and road wear particles (TRWP), which are comprised of polymer-containing tread with pavement encrustations, are generated from friction between the tire and the road. Similar to environmentally dispersed microplastic particles (MP), the fate of TRWP depends on both the mass concentration as well as individual particle characteristics, such as particle diameter and density. The identification of an individual TRWP in environmental samples has been limited by inherent characteristics of black particles, which interfere with the spectroscopic techniques most often used in MP research. The purpose of this research was to apply suitable analytical techniques, including scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM/EDX) mapping and time-of-flight secondary ion mass spectrometry (ToF-SIMS) mapping, to characterize the specific physical and chemical properties of individual TRWP. Detailed elemental and organic surface maps were generated for numerous samples including bulk tread material, cryogenically milled tire tread particles, and TRWP generated from two separate road simulator methods. Key physical and chemical characteristics of TRWP for single particle identification included (1) elongated/round shape with variable amounts of mineral encrustation, (2) elemental surface characteristics including co-localization of (S + Zn/Na) ± (Si, K, Mg, Ca, and Al), and (3) co-localization of organic surface markers, such as C6H5+ and C7H7+. Comparisons of TRWP with other polymeric (polystyrene) and non-polymeric (carbon black) particle types demonstrated that a combination of physical and chemical markers is necessary to identify TRWP. Addition of a density separation step to the single particle analysis techniques allowed for the determination of average primary TRWP particle size (34 µm by number distribution and 49 µm by volume distribution) and aspect ratio (65% of TRWP with an aspect ratio > 1.5). The use of chemical mapping techniques, such as SEM/EDX and/or ToF-SIMS mapping as demonstrated herein, can support future research efforts that aim to identify complex MP.

Assessing and managing the risks of COVID-19 in the workplace: Applying industrial hygiene (IH)/occupational and environmental health and safety (OEHS) frameworks.

As businesses attempt to reopen to varying degrees amid the current coronavirus disease (COVID-19) pandemic, industrial hygiene (IH) and occupational and environmental health and safety (OEHS) professionals have been challenged with assessing and managing the risks of COVID-19 in the workplace. In general, the available IH/OEHS tools were designed to control hazards originating in the workplace; however, attempts to tailor them specifically to the control of infectious disease outbreaks have been limited. This analysis evaluated the IH decision-making framework (Anticipate, Recognize, Evaluate, Control, and Confirm ("ARECC")) as it relates to biological hazards, in general, and to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), specifically. Available IH/OEHS risk assessment and risk management tools (e.g. control banding and the hierarchy of controls) are important components of the ARECC framework. These conceptual models, however, were primarily developed for controlling chemical hazards and must be adapted to the unique characteristics of highly infectious and virulent pathogens, such as SARS-CoV-2. This assessment provides an overview of the key considerations for developing occupational infection control plans, selecting the best available controls, and applying other emerging tools (e.g. quantitative microbial risk assessment), with the ultimate goal of facilitating risk management decisions during the current global pandemic.

A critical review of the acetaminophen preclinical carcinogenicity and tumor promotion data and their implications for its carcinogenic hazard potential.

In 2019 the California Office of Environmental Health Hazard Assessment (OEHHA) initiated a review of the carcinogenic hazard potential of acetaminophen, including an assessment of the long-term rodent carcinogenicity and tumor initiation/promotion studies. The objective of the analysis herein was to inform this review process with a weight-of-evidence assessment of these studies and an assessment of the relevance of these models to humans. In most of the 14 studies, there were no increases in the incidences of tumors in any organ system. In the few studies in which an increase in tumor incidence was observed, there were factors such as absence of a dose response and a rodent-specific tumor supporting that these findings are not relevant to human hazard identification. In addition, we performed qualitative analysis and quantitative simulations of the exposures to acetaminophen and its metabolites and its toxicity profile; the data support that the rodent models are toxicologically relevant to humans. The preclinical carcinogenicity results are consistent with the broader weight of evidence assessment and evaluations of multiple international health authorities supporting that acetaminophen is not a carcinogenic hazard.

Cobalt-containing dust exposures: Prediction of whole blood and tissue concentrations using a biokinetic model.

Biokinetic models estimating cobalt (Co) tissue burden can help assess the potential for systemic effects. Such models, however, have not been used to estimate remote tissue concentrations associated with inhalation exposure to Co-containing dust in general environments, work spaces, or animal toxicity tests. We have therefore updated a Co biokinetic model previously developed for oral dosing to include the inhalation pathway by incorporating the International Commission on Radiological Protection (ICRP) Human Respiratory Tract Model. Further, data from animal studies allowed for characterization of testes Co tissue concentration supplementing previous predictions for the liver, heart and blood. Reasonable agreement (within a factor of two) was found between modeled and measured blood, liver, testes and tissue concentrations when animal doses were modeled using human equivalent concentrations to account for species differences in regional lung deposition. We applied the updated model to occupational inhalation exposure scenarios, and found that upper-bound plausible human systemic body burden associated with Co ingestion is much higher than the burden associated with Co inhalation. Chronic ingestion of Co at a previously proposed oral reference dose (RfD) of 0.03 mg/kg-day resulted in predicted tissue levels of 22-54 µg/L (blood), 0.05-0.1 µg/g (heart), 0.01-0.02 µg/g (testes), and 0.2-0.5 µg/g (liver), which were at least 5-fold more than the systemic burden associated with various Co inhalation occupational exposure limits (OELs) of 0.1 mg/m3 or less (for 8 h/d and 5 d/w). Overall, our analysis indicated that Co-metal or dust induced systemic health effects, including myocardial damage, are unlikely for the inhalation pathway when personal exposures levels are below concentrations associated with local respiratory effects such as pulmonary fibrosis.

Evaluation of Personal Exposure to Surgical Smoke Generated from Electrocautery Instruments: A Pilot Study.

Hospital technician surgical smoke exposures during several types of electrocautery-based procedures were evaluated. Personal and area air sampling was performed for 106 individual analytes including ultrafine particulate matter (UFP), volatile organic compounds, polycyclic aromatic hydrocarbons, phenol, aldehydes, carbon monoxide, hydrogen sulfide, and hydrogen cyanide. Acetone, d-limonene, ethanol, ethyl acetate, and fluorene were measured in surgical suites at concentrations 1.1- to 3.7-fold higher than those observed in background. Benzene, α-pinene, methylene chloride, and n-hexane were measured in the absence of a detectable background concentration. All analytes were measured at concentrations that were <1% of the corresponding US federal and state 8-h permissible exposure limits (PELs), if PELs existed. Full-shift average UFP concentrations ranged from 773 to 2257 particles/cm3, approximately one order of magnitude higher than surgical suite background concentrations. A comparison of two breast reduction procedures suggested that the use of smoke evacuators reduced UFP exposure by 6-fold. We concluded that selection and evaluation of key hazards, particularly UFP, under a variety of experimental conditions would be beneficial to elucidate potential health effects and causes osf employee complaints. Recommendations for successful sampling campaigns in future surgical smoke occupational exposure studies are provided. We also recommend the continued use of engineering controls, local exhaust ventilation, and surgical N95 respirators to reduce personal exposures to UFP in surgical smoke.

Potential Airborne Asbestos Exposure and Risk Associated with the Historical Use of Cosmetic Talcum Powder Products.

Over time, concerns have been raised regarding the potential for human exposure and risk from asbestos in cosmetic-talc-containing consumer products. In 1985, the U.S. Food and Drug Administration (FDA) conducted a risk assessment evaluating the potential inhalation asbestos exposure associated with the cosmetic talc consumer use scenario of powdering an infant during diapering, and found that risks were below levels associated with background asbestos exposures and risk. However, given the scope and age of the FDA's assessment, it was unknown whether the agency's conclusions remained relevant to current risk assessment practices, talc application scenarios, and exposure data. This analysis updates the previous FDA assessment by incorporating the current published exposure literature associated with consumer use of talcum powder and using the current U.S. Environmental Protection Agency's (EPA) nonoccupational asbestos risk assessment approach to estimate potential cumulative asbestos exposure and risk for four use scenarios: (1) infant exposure during diapering; (2) adult exposure from infant diapering; (3) adult exposure from face powdering; and (4) adult exposure from body powdering. The estimated range of cumulative asbestos exposure potential for all scenarios (assuming an asbestos content of 0.1%) ranged from 0.0000021 to 0.0096 f/cc-yr and resulted in risk estimates that were within or below EPA's acceptable target risk levels. Consistent with the original FDA findings, exposure and corresponding health risk in this range were orders of magnitude below upper-bound estimates of cumulative asbestos exposure and risk at ambient levels, which have not been associated with increased incidence of asbestos-related disease.

Characterization of airborne BTEX exposures during use of lawnmowers and trimmers.

Few studies have evaluated airborne exposures to benzene, toluene, ethylbenzene, and xylenes (BTEX) during operation of two-stroke and four-stroke small engines, such as those in lawn maintenance equipment. Full-shift, 8-hour personal samples were collected during a simulation study to characterize yard maintenance activities including mowing, trimming, and fueling. Short-term, 15-minute personal samples were collected to separately evaluate mowing and trimming exposures. Mean 8-hour time weighted average (TWA) BTEX concentrations were 2.3, 5.8, 0.91, and 4.6 ppb, respectively (n = 2). Mean 15-minute TWA BTEX concentrations were 1.6, 1.8, 0.22, and 1.3 ppb, respectively, during mowing and 1.2, 3.6, 0.68, and 3.3 ppb, respectively, during trimming (n = 3 per task). Measured BTEX concentrations during fueling were 20-110, 61-310, 8-41, and 40-203 ppb, respectively (n = 2, duration 2-3 minutes). These exposure concentrations were well below applicable US occupational exposure limits.

Methods for Sterilizing Clinically Relevant Wear Particles Isolated from Metal-on-Metal Hip Implants.

Engineered or incidental particles may contain endotoxin from contaminated environments associated with generation, production, or handling activities. Endotoxins are ubiquitous contaminants that may yield false positive responses in immunological assays if present. The purpose of this study was to develop a sterilization method for removal of endotoxin from clinically relevant wear particles isolated from metal-on-metal (MoM) hip implant lubricant. In this case, the goal of particle sterilization was to sufficiently reduce endotoxin levels to acceptable levels for sensitive biological assays while retaining the physical and chemical characteristics of the original particles. Optimization of treatment with 0.05 NaOH in 50% ethanol successfully achieved a 5-log (>99.999%) reduction of endotoxin content while retaining the size and chemistry of MoM hip implant wear particles. Using the optimized method, the concentration of endotoxin was reduced from 161,000 to 1.19 EU/mL. As particle types can vary, sterilization strategies will also differ to optimize endotoxin removal while retaining key particle characteristics. To our knowledge, this study represents the first published sterilization method for clinically relevant MoM hip implant wear particles isolated from serum-rich lubricant.

Understanding outcomes and toxicological aspects of second generation metal-on-metal hip implants: a state-of-the-art review.

Hip implants have improved the mobility and quality of life in millions of individuals. This review presents the evolution of scientific knowledge regarding the history and understanding of systemic and local metal toxicological concerns of hip implants designs utilizing metal-on-metal (MoM) bearing surfaces used in hip resurfacing arthroplasty (HRA) and total hip arthroplasty (THA). This analysis addresses: (1) the history of the development of MoM hip implants; (2) the clinical and toxicological rationale for introducing second-generation MoM implants in the early 2000s as an alternative to metal-on-polyethylene bearings; (3) the subsequent history regarding success and failure of second-generation MoM devices; (4) a detailed review of the history of MoM toxicology, including carcinogenic potential, metal blood levels, hypersensitivity, and release of wear particles; and (5) a review of local tissue effects and MoM patient management. We have included an analysis of MoM THA and HRA survivorship trends aggregated from over 200 studies. By around 2008, HRA continued to be a challenging procedure with variable success rates, and concurrently, some THA devices began to experience higher than expected revision rates based on annual registry reports. The unexpected THA outcomes and continued challenges with HRA devices prompted many surgeons to question the role of toxicological effects in device performance. Regarding hypersensitivity, while conversion to metal sensitized status in some MoM patients occurs based on the skin patch or lymphocyte transformation testing, there is no evidence of a causal relationship between positive test results and device failure. The weight of evidence indicates that nanoparticles released from MoM implants are cleared from the local synovial space under normal wear conditions. The available data indicate that there are no discernible increases in local or systemic tumors following CoCr alloy implantation. Systemic health effects are rarely reported in MoM implant patients and are unlikely when blood concentrations are below 300 µg/L except when patients have specific risk factors. Over time, patient management evolved to include assays aimed at predicting implant function (blood monitoring) and soft tissue reactions (MRI and ultrasound imaging). Validation of these biomarkers as a diagnostic tool for implant function, patient pain, and, ultimately, implant survival, remains lacking. After the introduction of these biomarkers, differences in implant revision decisions emerged based on imaging abnormalities, increased serum metal ion levels, and overall clinical presentation. Discrepancies in patient management algorithms and the lack of consensus in local biological effects terminology have contributed to variability in reporting incidence, etiology, and dose effects on local tissue responses in MoM implants. This variability has contributed to a debate regarding the benefit or risk of revising asymptomatic patients. Therefore, while toxicological assessments of normal functioning MoM implants indicate that MoM implants are relatively safe because of low wear and clearance of metal, more analysis of revision data is needed in order to best inform patient management decisions, particularly for asymptomatic patients, as well as patients with minor symptoms under consideration for conservative pain management treatments.

Characteristics of Cobalt-Related Cardiomyopathy in Metal Hip Implant Patients: An Evaluation of 15 Published Reports.

Over 300,000 hip replacements occurred in the USA in 2010, and the frequency is likely increasing annually. Blood Cobalt (Co) concentrations in patients with well-functioning cobalt-chromium (Co-Cr) hip implants are usually elevated above background concentrations relative to the general population. Excessive Co exposure, in rare cases, can result in cardiomyopathy. The purpose of this review was to identify cases of cardiomyopathy in metal-containing hip implant patients and to evaluate the possible cause of each patient's cardiomyopathy. We evaluated 15 cases published between 2009 and 2016, and, based on a review of the preexisting risk factors, blood Co concentrations, and histopathological information published for each patient, they were stratified into one of four categories regarding the association between Co exposure and the development of cardiomyopathy: (1) Co was causal (five cases); (2) Co was contributory (two cases); (3) Co was possibly contributory (six cases); and (4) Co was non-causal (two cases). In all 15 cases, blood Co concentrations (14-6521 µg/L) were elevated beyond levels associated with the majority of metal-containing implant patients (0.1-10 µg/L), and, in many cases, there was evidence of a malfunctioning implant. The data indicate that individuals with well-functioning implants, even those with preexisting risk factors, are at no risk of developing cardiac effects. We conclude that blood Co measurements are informative, but should be interpreted with caution, and in context of other factors evaluated in this analysis. The mere presence of elevated Co is not sufficient to indicate causation for a patient's cardiomyopathy.

Characterization of wear debris from metal-on-metal hip implants during normal wear versus edge-loading conditions.

Advantages of second-generation metal-on-metal (MoM) hip implants include low volumetric wear rates and the release of nanosized wear particles that are chemically inert and readily cleared from local tissue. In some patients, edge loading conditions occur, which result in higher volumetric wear. The objective of this study was to characterize the size, morphology, and chemistry of wear particles released from MoM hip implants during normal (40° angle) and edge-loading (65° angle with microseparation) conditions. The mean primary particle size by volume under normal wear was 35 nm (range: 9-152 nm) compared with 95 nm (range: 6-573 nm) under edge-loading conditions. Hydrodynamic diameter analysis by volume showed that particles from normal wear were in the nano- (<100 nm) to submicron (<1000 nm) size range, whereas edge-loading conditions generated particles that ranged from <100 nm up to 3000-6000 nm in size. Particles isolated from normal wear were primarily chromium (98.5%) and round to oval in shape. Edge-loading conditions generated more elongated particles (4.5%) (aspect ratio ≥ 2.5) and more CoCr alloy particles (9.3%) compared with normal wear conditions (1.3% CoCr particles). By total mass, edge-loading particles contained approximately 640-fold more cobalt than normal wear particles. Our findings suggest that high wear conditions are a potential risk factor for adverse local tissue effects in MoM patients who experience edge loading. This study is the first to characterize both the physical and chemical characteristics of MoM wear particles collected under normal and edge-loading conditions. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 986-996, 2018.