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1.
Inhal Toxicol ; 36(3): 158-173, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38583132

ABSTRACT

OBJECTIVE: Erionite is a naturally occurring fibrous mineral found in soils in some geographical regions. Known for its potency for causing mesothelioma in the Cappadocia region of Turkey, the erionite fiber has attracted interest in the United States due to its presence in a band of rock that extends from Mexico to Montana. There are few toxicology studies of erionite, but all show it to have unusually high chronic toxicity. Despite its high potency compared to asbestos fibers, erionite has no occupational or environmental exposure limits. This paper takes what has been learned about the chemical and physical characteristics of the various forms of asbestos (chrysotile, amosite, anthophyllite, and crocidolite) and predicts the potency of North American erionite fibers. MATERIALS AND METHODS: Based on the fiber potency model in Korchevskiy et al. (2019) and the available published information on erionite, the estimated mesothelioma potency factors (the proportion of mesothelioma mortality per unit cumulative exposure (f/cc-year)) for erionites in the western United States were determined. RESULTS AND DISCUSSION: The model predicted potency factors ranged from 0.19 to 11.25 (average ∼3.5), depending on the region. For reference, crocidolite (the most potent commercial form of asbestos) is assigned a potency factor ∼0.5. CONCLUSION: The model predicted mesothelioma potency of Turkish erionite (4.53) falls in this same range of potencies as erionite found in North America. Although it can vary by region, a reasonable ratio of average mesothelioma potency based on this model is 3,000:500:100:1 comparing North American erionite, crocidolite, amosite, and chrysotile (from most potent to least potent).


Subject(s)
Asbestos , Lung Neoplasms , Mesothelioma, Malignant , Mesothelioma , Zeolites , Humans , Asbestos, Crocidolite/toxicity , Asbestos, Serpentine/toxicity , Asbestos, Amosite/toxicity , Mesothelioma/chemically induced , Mesothelioma/epidemiology , Mesothelioma, Malignant/complications , Asbestos/toxicity , Montana , Lung Neoplasms/epidemiology
2.
J Occup Environ Hyg ; : 1-11, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38608274

ABSTRACT

The American Iron and Steel Institute (AISI) gathered data between 1989 and 1997 to build an "objective database" to further understand the occupational exposures generated by the few asbestos-containing materials remaining at various steelmaking companies at this time. This paper analyzed the 520 samples from this campaign which occurred at five different steel manufacturers: Georgetown Steel Company, Inland Steel Company, Ling-Temco-Vought (LTV) Corporation, United States Steel Corporation, and Weirton Steel Corporation. This database is believed to have never previously been systematically organized. Samples were grouped based on sampling times to determine whether they should most appropriately be compared to the OSHA short-term excursion limit (EL) or the 8-hr time-weighted average (TWA) permissible exposure limit (PEL). Sampling times of 30 min or less were considered short-term samples, and samples of 180 min or greater were considered representative workday samples. Samples that did not fit into either category, with sampling times between 31 and 179 min, were considered task samples. Overall, the data indicated that the airborne concentrations were quite low in 1989 and they continued to be low through the study period which ended in 1997. Only seven out of 286 (approximately 2.5%) short-term or representative workday samples were in exceedance of the current OSHA OELs that were implemented in 1994 (short-term samples being compared to the 1 f/cc EL and representative workday samples being compared to the 0.1 f/cc 8-hr TWA PEL). Consistent with prior data, analysis of this dataset supports the view that materials containing asbestos were not used in many applications in the steel industry, and measured airborne concentrations of asbestos were almost always below the occupational exposure limits (OELs) in the post-OSHA era (1972-2000).

3.
Article in English | MEDLINE | ID: mdl-37495866

ABSTRACT

BACKGROUND: Historically, the use of asbestos in steelmaking has been limited to a few applications. Due to its physical and chemical properties, asbestos was not necessary or suitable for most purposes in a steel mill. The few applications where asbestos were used (i.e., certain gaskets, brakes, protective cloth, refractory materials, insulation materials, and hot top products) were replaced by alternative materials as they became available. OBJECTIVE: We discuss historical uses of asbestos in steel manufacturing and the associated airborne asbestos concentrations collected at sixteen U. S. Steel facilities between 1972 and 2006. METHODS: A total of 495 personal airborne asbestos samples from the U. S. Steel industrial hygiene records were analyzed across four time periods corresponding to changes in the OSHA permissible exposure limit (PEL) for asbestos. 68% of the samples (n = 337) were considered representative of an employee's workday. The remaining samples (n = 158) represented task samples. Samples were grouped by facility, department, and job category within the four time periods. RESULTS: The average fiber concentrations measured for each facility and department over time were below the contemporaneous OSHA PEL. The mean representative workday asbestos air concentration from 1972 and 1975 was 1.09 f/cc. The mean representative workday concentration decreased to 0.13 f/cc between 1976 and 1985, then decreased again to 0.02 f/cc between 1986 and 1993 and 0.03 f/cc between 1994 and 2006. For task samples, the mean air concentration from 1972 to 1975 was 3.29 f/cc. The mean task sample concentration decreased to 0.48 f/cc between 1976 and 1985, then decreased again to 0.01 f/cc between 1986 and 1993 and 0.03 f/cc between 1994 and 2006. Only eleven out of the 495 samples (2.2%), for both task and representative workday samples, were in exceedance of the contemporaneous PEL(as an 8-hour TWA), ten of which occurred prior to 1978. Eight of these eleven PEL exceeding samples were task samples. Of the remaining three representative workday samples, two had unknown sampling times. IMPACT: This paper presents an analysis of all the available personal sampling data for airborne asbestos across 16 facilities of the U. S. Steel Corporation between 1972 and 2006. This dataset has previously never been publicly shared or analyzed. It represents one of the more complete industrial hygiene datasets from a corporation to be presented in a scientific journal and, due to the similarities in the processes at each mill, it should reflect analogous exposures throughout the steelmaking industry in the United States. One of the benefits of presenting these data is that it also provides insight into where asbestos-containing materials (ACMs) were used in the steel making process. This is just one example of a large firm that released information that had previously remained in file cabinets for decades. We believe that another benefit of publishing this paper is that it may encourage the largest firms in industry to assemble and analyze their industrial hygiene data to benefit the occupational hygiene, medical, and epidemiology communities. This can support future epidemiology studies and improve the design of future industrial hygiene programs.

4.
Crit Rev Toxicol ; 52(7): 499-545, 2022 08.
Article in English | MEDLINE | ID: mdl-36281736

ABSTRACT

Hunters Point Naval Shipyard in San Francisco, California was deemed a Superfund site by the USEPA in 1989 due to chemical and radiological contamination resulting from U.S. Navy operations from 1939 to 1974. During characterization and remediation efforts, over 50,000 radiological soil samples and 19,000 air samples were collected. This risk assessment, conducted in accordance with federal guidelines, represents the first comprehensive evaluation of past, present, and future health risks associated with radionuclides present at the site. The assessment indicated that before site remediation, most radionuclide soil concentrations were at or near local background concentrations. Had such low remedial goals not been established, significant remediation of surface soils would not have been necessary to protect human health. The pre-remediation lifetime incremental cancer morbidity risks for on-site workers and theoretical on-site residents due to radionuclide contamination were found to be 1.3 × 10-6 and 3.2 × 10-6, respectively. The post-remediation risks to future on-site residents were found to be 6.3 × 10-8 (without durable cover) and 3.7 × 10-8 (with durable cover), while post-remediation risks to on-site workers were found to be 2.6 × 10-8 (without durable cover) and 1.6 × 10-8 (with durable cover). Risk estimates for all scenarios were found to be significantly below the acceptable risk of 3 × 10-4 approved by regulatory agencies. Upwind and downwind air samples collected during remediation indicate that remediation activities never posed a measurable risk to off-site residents. This risk assessment emphasizes the importance of establishing clear and scientifically rigorous soil remedial goals at sites as well as understanding local radionuclide background concentrations.


Subject(s)
Environmental Restoration and Remediation , High Pressure Neurological Syndrome , Humans , Risk Assessment , Soil
5.
J Occup Environ Hyg ; 17(10): 464-479, 2020 10.
Article in English | MEDLINE | ID: mdl-32809925

ABSTRACT

In this pilot-scale study, a wide range of potential emissions were evaluated for four types of additive manufacturing (AM) machines. These included material extrusion (using acrylonitrile-butadiene-styrene [ABS]); material jetting (using liquid photopolymer); powder bed fusion (using nylon); and vat photopolymerization (using liquid photopolymer) in an industrial laboratory setting. During isolated operation of AM machines, adjacent area samples were collected for compounds of potential concern (COPCs), including total and individual volatile organic compounds (VOCs), nano- and micron-sized particulate matter, and inorganic gases. A total of 61 compounds were also sampled using a canister followed by gas chromatography and mass spectrometry analysis. Most COPCs were not detected or were measured at concentrations far below relevant occupational exposure limits (OELs) during AM machine operations. Submicron particles, predominantly nanoparticles, were produced during material extrusion printing using ABS at approximately 12,000 particles per cubic centimeter (p cm-3) above background. After subtracting the mean background concentration, the mean concentration for material extrusion printing operations correlated with a calculated emission rate of 2.8 × 1010 p min-1 under the conditions tested. During processing of parts produced using material jetting or powder bed fusion, emissions were generally negligible, although concentrations above background of respirable and total dust were measured during processing of powder bed fusion parts. Results of this pilot-scale study indicate that airborne emissions associated with AM operations are variable, depending on printing and parts handling processes, raw materials, and ventilation characteristics. Although personal samples were not collected in this pilot-scale study, the results can be used to inform future exposure assessments. Based on the results of this evaluation, measurement of submicron particles emitted during material extrusion printing operations and dust associated with handling parts manufactured using powder bed fusion processes should be included in exposure assessments.


Subject(s)
Air Pollution, Indoor/analysis , Particulate Matter/analysis , Printing, Three-Dimensional , Volatile Organic Compounds/analysis , Gases/analysis , Nanoparticles/analysis , Particle Size , Pilot Projects
6.
Toxicol Ind Health ; 35(11-12): 726-737, 2019.
Article in English | MEDLINE | ID: mdl-31818240

ABSTRACT

The objective is to present historical asbestos airborne concentrations associated with activities involving presumably asbestos-containing materials in steel mills. A total of 138 historical industrial hygiene air samples collected in three US steel mills from 1972 to 1982 were analyzed. The majority of samples were collected during relining of open hearth furnaces, stoves, and blast furnaces by steel mill bricklayers and bricklayer helpers. Over 75% of the samples (n = 106) were collected for 50 min or less, four samples were collected for 227 to 306 min, and sample durations were not reported for the remaining 28 samples. Average airborne fiber concentrations measured during relining activities of open hearth furnaces, stoves, and blast furnaces were 0.21 f/cc, 0.72 f/cc and 0.13 f/cc phase-contrast microscopy (PCM), respectively. Measured airborne fiber concentrations of four time-weighted average (TWA) samples (>227 min) averaged 0.045 f/cc. Estimated 8-h TWAs concentrations averaged 0.34 f/cc for bricklayers and 0.2 f/cc bricklayer helpers. While 8-h TWA concentration estimates for monitored tasks/jobs may often have exceeded current Occupational Safety and Health Administration (OSHA) Permissible Exposure Limits (PELs), they did not exceed relevant contemporaneous occupational exposure standards. This analysis provides a better understanding of historical airborne asbestos exposures that bricklayers and other tradesmen experienced during furnace and stove work in the US steel mills.


Subject(s)
Air Pollutants, Occupational/analysis , Air Pollutants, Occupational/toxicity , Asbestos/toxicity , Occupational Exposure/analysis , Environmental Monitoring , History, 20th Century , Humans , Inhalation Exposure , Occupational Health , Steel , United States
7.
Dermatitis ; 30(2): 116-128, 2019.
Article in English | MEDLINE | ID: mdl-30829810

ABSTRACT

BACKGROUND: An essential step in ensuring the toxicological safety of cosmetic or personal care products is the evaluation of the skin sensitizing potential of product ingredients. OBJECTIVE: We used a standardized protocol from cosmetic trade industry and consumer safety groups to evaluate the sensitization potential of ingredients in 3 commercially available cleansing conditioners. METHODS: A total of 33 ingredients were evaluated. Each ingredient underwent (1) dermatological evaluation, (2) in silico analysis for irritation and sensitization potential, and (3) a literature evaluation to determine risk of sensitization. Consumer exposure level was compared with the weight-of-evidence no-expected sensitization induction level for the constituent. If a no-expected sensitization induction level for a specific ingredient was not available, the dermal sensitization threshold approach was used. A margin of safety was calculated for each constituent. RESULTS: The margins of safety for all evaluated ingredients in the cleansing conditioners were greater than 1. CONCLUSIONS: This analysis indicates that exposure to the individual ingredients present in these cleansing conditioners would not be expected to induce dermal sensitization in a consumer under the examined exposure scenario.


Subject(s)
Dermatitis, Allergic Contact/etiology , Hair Preparations/adverse effects , Scalp Dermatoses/chemically induced , Skin Care/adverse effects , Adult , Clinical Protocols , Computer Simulation , Consumer Product Safety/standards , Female , Hair Preparations/toxicity , Humans , Risk Assessment , Scalp Dermatoses/etiology , Skin Care/methods
8.
Cutan Ocul Toxicol ; 38(1): 44-47, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30124079

ABSTRACT

Purpose/Aim: The U.S. Food and Drug Administration (FDA) does not require specific testing to demonstrate the safety of personal care and cosmetic products or their ingredients. Recently, there have been reports of skin irritation associated with the use of commercially available cleansing conditioners. The goal of this study was to implement a tier-based safety assessment to evaluate the skin irritation potential of six commercially available cleansing conditioners and their ingredients. MATERIALS AND METHODS: The first tier of testing utilized the Organization for Economic Co-operation and Development (OECD) QSAR Toolbox to perform an in silico evaluation of the skin irritation potential of the product ingredients, and the second tier of testing utilized an OECD in vitro guideline test to evaluate the skin irritation potential of each product. RESULTS: Thirty-two ingredients were evaluated using the OECD QSAR Toolbox profiler for the tier one analysis; nine ingredients received a structural alert for skin irritation/corrosion. In the tier two in vitro analysis, the evaluated cleansing conditioner products were all classified as non-irritants. CONCLUSIONS: These results provide evidence that use of the evaluated commercially available cleansing conditioners would not be expected to cause skin irritation among consumers. Additionally, this study demonstrates that the presence of structural alerts does not always accurately predict the safety of a product, as focused tier-based testing is necessary to comprehensively evaluate a product. This study illustrates a tier-based safety assessment approach, applicable to a wide variety of health endpoints, which efficiently and adequately evaluates the safety of personal care and cosmetic products and their ingredients.


Subject(s)
Hair Preparations/toxicity , Computer Simulation , Consumer Product Safety , Hair Preparations/chemistry , Hair Preparations/classification , Humans , Quantitative Structure-Activity Relationship , Risk Assessment , Skin/drug effects , Skin Irritancy Tests
9.
Dermatitis ; 29(6): 324-331, 2018.
Article in English | MEDLINE | ID: mdl-30422886

ABSTRACT

BACKGROUND: Many chemicals used for fragrance purposes in a diversity of products have allergenic potential. Based on such concerns, industry groups developed concentration limits for use of fragrance chemicals in personal care and cosmetic products. OBJECTIVE: The aim of this study was to use a quantitative risk assessment to evaluate the potential for skin sensitization induction resulting from daily exposure to fragrance chemicals present in personal care and cosmetic products. METHODS: Product-specific dermal consumer exposure levels were calculated based on product use data in US adult females and benchmarked against acceptable exposure levels based on reported no expected sensitization induction levels to determine a margin of safety for each fragrance under evaluation. CONCLUSIONS: The results demonstrate an increased risk of skin sensitization induction for several leave-on products (lipstick, solid antiperspirant, eye shadow, face cream) for most of the evaluated fragrance chemicals, particularly under high-use exposure scenarios. In contrast, rinse-off products (shampoo, conditioner, facial cleanser) were not associated with risk of skin sensitization induction. Because the approach was based on maximum use limits for fragrance chemicals with skin sensitization concerns, the results suggest these limits may not be protective, particularly in the United States.


Subject(s)
Cosmetics/adverse effects , Dermatitis, Allergic Contact/etiology , Perfume/adverse effects , Antiperspirants/adverse effects , Body Surface Area , Consumer Product Safety , Cosmetics/administration & dosage , Female , Hair Preparations/administration & dosage , Hair Preparations/adverse effects , Humans , Mathematical Concepts , Perfume/administration & dosage , Risk Assessment , Skin/drug effects , Skin Cream/administration & dosage , Skin Cream/adverse effects
10.
Dermatitis ; 29(3): 132-138, 2018.
Article in English | MEDLINE | ID: mdl-29570489

ABSTRACT

BACKGROUND: Kathon CG is a commonly used cosmetic-grade preservative that contains active ingredients methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI). OBJECTIVE: The aim of the study was to perform a skin sensitization induction risk assessment of daily exposure to Kathon CG after use of various personal care and cosmetic products. METHODS: We calculated an estimated daily consumer exposure level for rinse-off and leave-on products using the amount of product applied per application, number of applications per day, a retention factor, the MCI/MI concentration, and body surface area values. We assumed that the products contained the maximum recommended safe concentration of MCI/MI: 15 ppm in rinse-off products and 7.5 ppm in leave-on products. We compared estimated consumer exposure levels with the no expected sensitization induction level for MCI/MI and applied sensitization assessment factors to calculate product-specific margins of safety (MOSs). CONCLUSIONS: The MOSs for rinse-off products ranged from 5 to 63, whereas the MOSs for leave-on products ranged from 0.03 to 1.49. Overall, our results provide evidence that some leave-on products containing the maximum recommended safe concentration of Kathon CG may increase the risk of sensitization induction due to exposure to MCI/MI. In contrast, rinse-off products were not associated with a potential increased risk of skin sensitization induction.


Subject(s)
Dermatitis, Allergic Contact/diagnosis , Preservatives, Pharmaceutical/adverse effects , Thiazoles/adverse effects , Cosmetics/adverse effects , Cosmetics/analysis , Cosmetics/pharmacology , Dermatitis, Allergic Contact/etiology , Female , Humans , Preservatives, Pharmaceutical/analysis , Preservatives, Pharmaceutical/pharmacology , Risk Assessment , Skin/drug effects , Thiazoles/analysis , Thiazoles/pharmacology
11.
Sci Rep ; 8(1): 2384, 2018 02 05.
Article in English | MEDLINE | ID: mdl-29402892

ABSTRACT

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.


Subject(s)
Endotoxins/analysis , Hip Prosthesis , Lubricants/radiation effects , Sterilization/methods , Chemical Phenomena/radiation effects , Lubricants/chemistry , Metals
12.
Crit Rev Toxicol ; 48(10): 853-901, 2018 11.
Article in English | MEDLINE | ID: mdl-30912993

ABSTRACT

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.


Subject(s)
Hip Prosthesis/adverse effects , Metal-on-Metal Joint Prostheses/adverse effects , Metals/toxicity , Prosthesis Design , Prosthesis Failure , Arthroplasty, Replacement, Hip , Humans , Metals/blood , Risk Factors , Surface Properties
13.
Arch Environ Occup Health ; 73(5): 292-301, 2018.
Article in English | MEDLINE | ID: mdl-28692341

ABSTRACT

Approximately 10,000 gallons of crude 4-methylcyclohexanemethanol and propylene glycol phenyl ether were accidentally released into the Elk River upstream from a water treatment facility in West Virginia. The objective of this study was to use logistic and Poisson regression analyses to determine the effect potential exposures had on adverse birth outcomes (birth weight, small for gestational age, and abnormal Apgar score). We adjusted for confounding factors and assessed prevalence of adverse birth outcomes by residential location and timing of the pregnancy. There were no statistically significant interactions between residential location and timing of the pregnancy (range of p values: .157-.806). Changes in the prevalence of birth outcomes were consistent before and after the spill regardless of residential location. There was no evidence of an association between adverse birth outcomes and potential exposure to the released chemicals.


Subject(s)
Apgar Score , Birth Weight/drug effects , Cyclohexanes/analysis , Infant, Small for Gestational Age , Prenatal Exposure Delayed Effects/epidemiology , Water Pollutants, Chemical/analysis , Adult , Female , Humans , Infant, Newborn , Male , Pregnancy , Prenatal Exposure Delayed Effects/chemically induced , Prevalence , Residence Characteristics , Seasons , West Virginia/epidemiology , Young Adult
14.
Cardiovasc Toxicol ; 18(3): 206-220, 2018 06.
Article in English | MEDLINE | ID: mdl-29188590

ABSTRACT

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.


Subject(s)
Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Hip/instrumentation , Cardiomyopathies/chemically induced , Chromium Alloys/adverse effects , Cobalt/adverse effects , Hip Prosthesis/adverse effects , Metal-on-Metal Joint Prostheses/adverse effects , Aged , Biomarkers/blood , Cardiomyopathies/blood , Cardiomyopathies/diagnosis , Chromium Alloys/metabolism , Cobalt/blood , Female , Humans , Male , Middle Aged , Prosthesis Design , Risk Assessment , Risk Factors , Treatment Outcome
15.
J Biomed Mater Res B Appl Biomater ; 106(3): 986-996, 2018 04.
Article in English | MEDLINE | ID: mdl-28480531

ABSTRACT

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.


Subject(s)
Hip Prosthesis , Metal-on-Metal Joint Prostheses , Prosthesis Design/methods , Chromium , Chromium Alloys , Humans , Particle Size , Particulate Matter , Prosthesis Failure
16.
Crit Rev Toxicol ; 48(3): 217-251, 2018 03.
Article in English | MEDLINE | ID: mdl-29243948

ABSTRACT

The Shanghai Health Study (SHS) was a large epidemiology study conducted as a joint effort between the University of Colorado and Fudan University in Shanghai, China. The study was funded by members of the American Petroleum Institute between 2001 and 2009 and was designed to evaluate the human health effects associated with benzene exposure. Two arms of the SHS included: an occupational-based molecular epidemiology study and several hospital-based case control studies. Consistent with historical literature, following sufficient exposure to relatively high airborne concentrations and years of exposure, the SHS concluded that exposure to benzene resulted in an increased risk of various blood and bone marrow abnormalities such as benzene poisoning, aplastic anemia (AA), myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML). Non-Hodgkin lymphoma (NHL) was not significantly increased for the exposures examined in this study. Perhaps the most important contribution of the SHS was furthering our understanding of the mechanism of benzene-induced bone marrow toxicity and the importance of identifying the proper subset of MDS relevant to benzene. Investigators found that benzene-exposed workers exhibited bone marrow morphology consistent with an immune-mediated inflammatory response. Contrary to historic reports, no consistent pattern of cytogenetic abnormalities was identified in these workers. Taken together, findings from SHS provided evidence that the mechanism for benzene-induced bone marrow damage was not initiated by chromosome abnormalities. Instead, chronic inflammation, followed by an immune-mediated response, is likely to play a more significant role in benzene-induced disease initiation and progression than previously thought.


Subject(s)
Benzene/toxicity , Occupational Diseases/chemically induced , Occupational Exposure/adverse effects , Case-Control Studies , China/epidemiology , Environmental Exposure , Humans , Leukemia, Myeloid, Acute/chemically induced , Leukemia, Myeloid, Acute/epidemiology , Myeloproliferative Disorders/chemically induced , Myeloproliferative Disorders/epidemiology , Occupational Diseases/epidemiology , Occupational Diseases/genetics , Polymorphism, Genetic
17.
Cutan Ocul Toxicol ; 36(4): 351-355, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28277879

ABSTRACT

Crude 4-methylcyclohexanemethanol (MCHM) is an industrial chemical used to wash and clean coal. On January 9th, 2014 approximately 10,000 gallons of a mixture containing crude MCHM were released into the Elk River near Charleston, West Virginia, contaminating the local water supply. Following the spill, residents reported numerous health complaints, and sought medical attention for ailments including rashes and itching. The relationship between the complaints and the spill were unknown, as such symptoms are reported frequently in the background. In this study, the primary irritation potential of crude MCHM was evaluated in 206 individuals who underwent 48 hour semi-occluded patch testing. MCHM concentrations assessed in this study were 1, 5, 15, and 100 ppm. No appreciable skin reactions were observed in individuals at any concentration. Three of the five concentrations evaluated were above the highest measured concentration of MCHM in the tap water of residents in West Virginia (3.7 ppm). The results of this study suggest that crude MCHM would not be a dermal irritant for the vast majority, if not all, potentially exposed persons at the concentrations in the water reported after the spill.


Subject(s)
Cyclohexanes/toxicity , Skin/drug effects , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Patch Tests , Young Adult
18.
Crit Rev Toxicol ; 47(4): 286-316, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28328293

ABSTRACT

The understanding by industrial hygienists of the hazards of asbestos and appropriate ways to characterize and control exposure has evolved over the years. Here, a detailed analysis of the evolution of industrial hygiene practices regarding asbestos and its health risks, from the early 1900s until the advent of the national occupational health and safety regulatory structure currently in place in the US (early-to-mid 1970s) is presented. While industrial hygienists recognized in the early 1900s that chronic and high-level exposures to airborne concentrations of asbestos could pose a serious health hazard, it was not until the mid-1950s that the carcinogenic nature of asbestos began to be characterized and widespread concern followed. With the introduction of the membrane filter sampling method in the late 1960s and early 1970s, asbestos sampling and exposure assessment capabilities advanced to a degree which allowed industrial hygienists to more precisely characterize the exposure-response relationship. The ability of industrial hygienists, analytical chemists, toxicologists, and physicians to more accurately define this relationship was instrumental to the scientific community's ability to establish Occupational Exposure Levels (OELs) for asbestos. These early developments set the stage for decades of additional study on asbestos exposure potential and risk of disease. This was followed by the application of engineering controls and improved respiratory protection which, over the years, saved thousands of lives. This paper represents a state-of-the-art review of the knowledge of asbestos within the industrial hygiene community from about 1900 to 1975.


Subject(s)
Air Pollutants, Occupational/analysis , Asbestos/analysis , Asbestosis/epidemiology , Occupational Exposure/statistics & numerical data , Occupational Health , Inhalation Exposure , Occupational Exposure/analysis
19.
J Appl Toxicol ; 37(1): 38-49, 2017 01.
Article in English | MEDLINE | ID: mdl-27397058

ABSTRACT

Anthophyllite is an amphibole form of asbestos historically used in only a limited number of products. No published resource currently exists that offers a complete overview of anthophyllite toxicity or of its effects on exposed human populations. We performed a review focusing on how anthophyllite toxicity was understood over time by conducting a comprehensive search of publicly available documents that discussed the use, mining, properties, toxicity, exposure and potential health effects of anthophyllite. Over 200 documents were identified; 114 contained relevant and useful information which we present chronologically in this assessment. Our analysis confirms that anthophyllite toxicity has not been well studied compared to other asbestos types. We found that toxicology studies in animals from the 1970s onward have indicated that, at sufficient doses, anthophyllite can cause asbestosis, lung cancer and mesothelioma. Studies of Finnish anthophyllite miners, conducted in the 1970s, found an increased incidence of asbestosis and lung cancer, but not mesothelioma. Not until the mid-1990s was an epidemiological link with mesothelioma in humans observed. Its presence in talc has been of recent significance in relation to potential asbestos exposure through the use of talc-containing products. Characterizing the health risks of anthophyllite is difficult, and distinguishing between its asbestiform and non-asbestiform mineral form is essential from both a toxicological and regulatory perspective. Anthophyllite toxicity has generally been assumed to be similar to other amphiboles from a regulatory standpoint, but some notable exceptions exist. In order to reach a more clear understanding of anthophyllite toxicity, significant additional study is needed. Copyright © 2016 John Wiley & Sons, Ltd.


Subject(s)
Asbestos, Amphibole/toxicity , Environmental Exposure/adverse effects , Environmental Pollutants/toxicity , Lung Neoplasms/chemically induced , Mesothelioma/chemically induced , Mining , Animals , Environmental Exposure/analysis , Humans , Lung Neoplasms/epidemiology , Mesothelioma/epidemiology
20.
Chemosphere ; 167: 541-550, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27769007

ABSTRACT

This study provides an exposure and risk assessment of diundecyl phthalate (DUP), a high molecular weight phthalate plasticizer present in automobile interiors. Total daily intake of DUP was calculated from DUP measured in wipe samples from vehicle seats from six automobiles. Four of the vehicles exhibited atypical visible surface residue on the seats. Two vehicles with no visible surface residue were sampled as a comparison. DUP was the predominant organic compound identified in each of the wipes from all seats. A risk assessment of DUP via oral, dermal, and inhalation routes resulting from contact with automobile seats was conducted. The mean, standard deviation, and maximum DUP concentrations on the seats with visible surface residue were 6983 ± 7823 µg/100 cm2 and 38300 µg/100 cm2, respectively. The mean and 95th percentile of the mean for daily cumulative dose of DUP for all exposure routes for the seats with no visible surface residue ranged from 7 × 10-4 to 4 × 10-3 mg/kg-day and from 8 × 10-4 to 5 × 10-3 mg/kg-day, respectively. For seats with visible surface residue, cumulative doses ranged from 2 × 10-3 to 2 × 10-2 mg/kg-day and from 4 × 10-3 to 2 × 10-2 mg/kg-day, respectively. The estimated daily intake (contact or absorbed dose) of DUP from automobile seats were far lower than the NOAELs reported in and derived from animal studies, and are well below the reported Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Derived No Effect Levels (DNELs) for the general population. Based on this analysis, using virtually any benchmark for evaluating safety, exposure to DUP via automobile seat covers did not pose a measureable increased health-risk in any population under any reasonably plausible exposure scenario.


Subject(s)
Air Pollutants/analysis , Air Pollution, Indoor/analysis , Automobiles/standards , Inhalation Exposure/analysis , Phthalic Acids/analysis , Plasticizers/analysis , Air Pollutants/chemistry , Animals , Humans , Molecular Weight , No-Observed-Adverse-Effect Level , Phthalic Acids/chemistry , Plasticizers/chemistry , Risk Assessment , Safety
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