The presence of erionite in North American geologies and the estimated mesothelioma potency by region.

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).

Occupational exposures to asbestos in the steel industry: An analysis of the AISI sampling campaign (1989-1997).

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).

Occupational exposure to asbestos in the steel industry (1972-2006).

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.

Radiological risk assessment of the Hunters Point Naval Shipyard (HPNS).

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.

An analysis of workplace exposures to asbestos at three steel mills located in the United States (1972-1982).

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.

Shanghai Health Study (2001-2009): What was learned about benzene health effects?

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.

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.

History of knowledge and evolution of occupational health and regulatory aspects of asbestos exposure science: 1900-1975.

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.

Anthophyllite asbestos: state of the science review.

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.

Evaluation of take-home exposure to asbestos from handling asbestos-contaminated worker clothing following the abrasive sawing of cement pipe.

Although industrial uses of asbestos have declined since the 1970s, in recent years there has been a renewed interest in para-occupational ("take-home") exposure to these fibers. The aim of this study was to quantify the release of asbestos fibers, if any, during the shaking out of crocidolite- and chrysotile-contaminated clothing in a simulated at-home setting. An exposure study was conducted in which personal and area air samples were collected during the handling (i.e. shake-out) of work clothing (shirt and pants) previously worn by an operator who had cut asbestos-containing cement pipe. During eight "loading" events, the operator cut a historically representative asbestos-containing cement pipe (10% crocidolite and 25% chrysotile) using a powered abrasive saw. Subsequently, 30-minute air samples were collected during four "shake-out" events, each of which consisted of the handling of two complete sets of contaminated work clothes. Samples were analyzed in accordance with NIOSH methods 7400 and 7402. The mean phase contrast microscopy equivalent (PCME) airborne concentrations were 0.52 f/cc (SD = 0.34 f/cc) for total asbestos fibers, 0.36 f/cc (SD = 0.26 f/cc) for chrysotile and 0.17 f/cc (SD = 0.096 f/cc) for crocidolite. Based on likely estimates of the frequency of laundering activities, and assuming that the dusty clothing (1) is not blown off in the occupational setting using compressed air and (2) is not shaken out before entering the home, a family member handling the clothing could potentially have a lifetime cumulative exposure to chrysotile and crocidolite of approximately 0.20 f/cc-year and 0.096 f/cc-year, respectively.

Risks associated with arsenic exposure resulting from the consumption of California wines sold in the United States.

Concerns have recently been raised about the presence of arsenic (As) in wine. In this analysis, 101 different California wines were evaluated for organic and inorganic As concentration. The average concentrations of total inorganic As in red, blush and white wines were 6.12µg/L (range: 0.40-20.5µg/L), 21.6µg/L (range: 0.92-41.2µg/L) and 9.5µg/L (0.57-30.4µg/L). The average concentrations of total organic As in red, blush and white wines were 0.64µg/L (0.10-2.74µg/L), 0.99µg/L (0.50-2.28µg/L), and 0.51µg/L (0.10-1.78µg/L). A screening level risk assessment was conducted to assess the potential non-carcinogenic risk resulting from wine consumption. The hazard quotient (HQ) for the inorganic As RfD and the As content of red, blush and white wines was each less than one; indicating that the non-cancer health risk was insignificant. Results indicate that ingestion of California wine does not pose a hazard due to inorganic As content.

Airborne asbestos take-home exposures during handling of chrysotile-contaminated clothing following simulated full shift workplace exposures.

The potential for para-occupational, domestic, or take-home exposures from asbestos-contaminated work clothing has been acknowledged for decades, but historically has not been quantitatively well characterized. A simulation study was performed to measure airborne chrysotile concentrations associated with laundering of contaminated clothing worn during a full shift work day. Work clothing fitted onto mannequins was exposed for 6.5 h to an airborne concentration of 11.4 f/cc (PCME) of chrysotile asbestos, and was subsequently handled and shaken. Mean 5-min and 15-min concentrations during active clothes handling and shake-out were 3.2 f/cc and 2.9 f/cc, respectively (PCME). Mean airborne PCME concentrations decreased by 55% 15 min after clothes handling ceased, and by 85% after 30 min. PCM concentrations during clothes handling were 11-47% greater than PCME concentrations. Consistent with previously published data, daily mean 8-h TWA airborne concentrations for clothes-handling activity were approximately 1.0% of workplace concentrations. Similarly, weekly 40-h TWAs for clothes handling were approximately 0.20% of workplace concentrations. Estimated take-home cumulative exposure estimates for weekly clothes handling over 25-year working durations were below 1 f/cc-year for handling work clothes contaminated in an occupational environment with full shift airborne chrysotile concentrations of up to 9 f/cc (8-h TWA).

Historical ambient airborne asbestos concentrations in the United States - an analysis of published and unpublished literature (1960s-2000s).

Outdoor concentrations of airborne asbestos have been measured throughout the US over time. However, a thorough review and analysis of these data has not been conducted. The purpose of this study is to characterize asbestos concentrations in ambient air by environment type (urban, rural) and by decade, using measurements collected in the absence of known asbestos emission sources. A total of 17 published and unpublished studies and datasets were identified that reported the results of 2058 samples collected from the 1960s through the 2000s across the US. Most studies did not report asbestos fiber type, and data based on different analytical methods (e.g. Phase Contrast Microscopy, Transmission Electron Microscopy, etc.) were combined in the dataset; however, only fibers ≥5 µm in length were considered. For a small subset of the measurements (n = 186, 9.0%), a conversion factor was used to convert mass-based data (e.g. ng/m(3)) to count-based values (i.e. f/cc ≥5 µm). The estimated overall mean and median ambient asbestos concentrations for the 1960s through 2000s were 0.00093 f/cc and 0.00022 f/cc, respectively. Concentrations generally increased from the 1960s through the early 1980s, after which they declined considerably. While asbestos use decreased throughout the 1970s, these results indicate that ambient concentrations peaked during the early 1980s, which suggests the possible contribution of abatement or demolition activities. Lastly, ambient asbestos concentrations were higher in urban than rural settings, which is consistent with the greater use of asbestos-containing materials in more densely populated areas.

The toxicity of crude 4-methylcyclohexanemethanol (MCHM): review of experimental data and results of predictive models for its constituents and a putative metabolite.

Crude 4-methylcyclohexanemethanol (MCHM) is an industrial solvent used to clean coal. Approximately 10 000 gallons of a liquid mixture containing crude MCHM were accidently released into the Elk River in West Virginia in January 2014. Because of the proximity to a water treatment facility, the contaminated water was distributed to approximately 300 000 residents. In this review, experimental data and computational predictions for the toxicity for crude MCHM, distilled MCHM, its other components and its putative metabolites are presented. Crude MCHM, its other constituents and its metabolites have low to moderate acute and subchronic oral toxicity. Crude MCHM has been shown not to be a skin sensitizer below certain doses, indicating that at plausible human exposures it does not cause an allergic response. Crude MCHM and its constituents cause slight to moderate skin and eye irritation in rodents at high concentrations. These chemicals are not mutagenic and are not predicted to be carcinogenic. Several of the constituents were predicted through modeling to be possible developmental toxicants; however, 1,4-cyclohexanedimethanol, 1,4-cyclohexanedicarboxylic acid and dimethyl 1,4-cyclohexanedicarboxylate did not demonstrate developmental toxicity in rat studies. Following the spill, the Centers for Disease Control and Prevention recommended a short-term health advisory level of 1 ppm for drinking water that it determined was unlikely to be associated with adverse health effects. Crude MCHM has an odor threshold lower than 10 ppb, indicating that it could be detected at concentrations at least 100-fold less than this risk criterion. Collectively, the findings and predictions indicate that crude MCHM poses no apparent toxicological risk to humans at 1 ppm in household water.

Toxicology-based cancer causation analysis of CoCr-containing hip implants: a quantitative assessment of genotoxicity and tumorigenicity studies.

In this paper, quantitative methods were used to evaluate the weight of evidence regarding a causative relationship between cobalt-chromium (CoCr)-containing hip implants and increased cancer risk. We reviewed approximately 80 published papers and identified no-observed-adverse-effect level (NOAEL) and/or lowest-observed-adverse-effect level (LOAEL) values for specific endpoints of interest: genotoxic effects from in vitro studies with human cell lines as well as genotoxicity and tumor formation in animal bioassays. Test articles included Co particles and ions, Cr particles and ions, and CoCr alloy particles as well as CoCr alloy implants. The NOAEL/LOAEL values were compared with body burdens of Co/Cr particles and ions we calculated to exist in systemic tissues of hip implant patients under normal and excessive wear conditions. We found that approximately 40 tumor bioassays have been conducted with CoCr alloy implants or Co/Cr particles and ions at levels hundreds to thousands of times higher than those present in hip implant patients, and none reported a statistically significant increased incidence of systemic tumors. Results from in vitro and in vivo genotoxicity assays, which are relatively less informative owing to false positives and other factors, also indicated that DNA effects would be highly unlikely to occur as a result of wear debris from a CoCr implant. Hence, the toxicological weight of evidence suggests that CoCr-containing hip implants are unlikely to be associated with an increased risk of systemic cancers, which is consistent with published and ongoing cancer epidemiology studies involving patients with CoCr hip implants.

Interpreting cobalt blood concentrations in hip implant patients.

INTRODUCTION. There has been some recent concern regarding possible systemic health effects resulting from elevated blood cobalt concentrations in patients with cobalt containing hip implants. To date there are no blood cobalt criteria to help guide physicians when evaluating an individual hip implant patient's risk of developing systemic health effects because historically there was little or no concern about systemic cobalt toxicity in implant patients. OBJECTIVE. Our purpose is to describe recently completed research regarding the relationship between blood cobalt concentrations and clinical health effects. We discuss the possibility of systemic health effects in patients with metal containing implants and propose various blood cobalt concentrations that are not associated with an increased risk of developing certain adverse effects. METHODOLOGY. The primary literature search was conducted using PubMed and Web of Science using the following search terms: cobalt AND (toxicity OR health effects OR cardiotoxicity OR hematological OR endocrine OR immunological OR reproductive OR testicular effects OR neurological OR case report OR cohort OR Roncovite). The searches identified 6786 papers of which 122 were considered relevant. The Agency for Toxic Substances and Disease Registry toxicological profile for cobalt and the U.S. Environmental Protection Agency Office of Research and Development's National Center for Environmental Assessment's documentation on the provisional peer-reviewed toxicity value for cobalt were also utilized to identify secondary literature sources. RESULTS. Our review of the toxicology and medical literature indicates that highly elevated blood cobalt concentrations can result in certain endocrine, hematological, cardiovascular, and neurological effects in animals and/or humans. These studies, in addition to historical clinical findings involving the therapeutic use of cobalt, indicate that significant systemic effects of cobalt will not occur below blood cobalt concentrations of 300 µg/L in most persons. Some individuals with specific risk factors for increased susceptibility (e.g., severe and sustained hypoalbuminemia) may exhibit systemic effects at lower cobalt blood concentrations. This review also describes several cobalt dosing studies performed with human volunteers that consumed cobalt for 15, 30, or 90 days. Overall, the results of these dosing studies indicate that sustained blood cobalt concentrations averaging 10-70 µg/L for up to 90 days cause no significant clinical effects (maximum concentrations approached 120 µg/L). Some proposed blood criteria for assessing implant wear and local tissue damage have been suggested by several medical groups. For example, the UK Medicines and Healthcare Products Regulatory Agency has proposed a blood cobalt guidance value of 7 µg/L, and the Mayo Clinic has suggested serum cobalt concentrations greater than 10 µg/L, but both of these values are primarily intended to address implant wear and to alert physicians to the possibility of an increased incidence of local effects. There is a clear lack of consensus regarding how to identify a specific numerical blood concentration of concern and whether whole blood or serum is a better matrix to assess total cobalt concentration. CONCLUSIONS. Based on currently available data, only under very unusual circumstances should a clinician expect that biologically important systemic adverse effects might occur in implant patients with blood cobalt concentrations less than 300 µg/L. Patients with metal-containing hip implants who exhibit signs or symptoms potentially related to polycythemia, hypothyroidism, neurological, or cardiac dysfunction should be clinically evaluated for these conditions. Polycythemia appears to be the most sensitive endpoint.

Evaluation of the California Safer Consumer Products Regulation and the impact on consumers and product manufacturers.

Chemistry enables more than 95% of products in the marketplace. Over the past 20 years, various entities began to generate inventories of chemicals ("chemical watch lists") potentially associated with human or environmental health risks. Some lists included thousands of chemicals, while others listed only a few chemistries with limited properties or toxicological endpoints (e.g., neurotoxicants). Enacted on October 1, 2013, the California Safer Consumer Products Regulation (SCP) utilized data from chemical inventory lists to create one master list. This paper aims to discuss the background and requirements of this regulation. Additionally, we wanted to understand the universe of Candidate Chemicals identified by the Regulation. Data from all 23 chemical lists identified in the SCP Regulation were entered into a database. The most prevalent chemicals among the ∼2900 chemicals are identified, including the most prevalent chemical, lead, appearing on 65% of lists, followed by DEHP (52%), perchloroethylene (48%), and benzene (48%). Our results indicated that the most prevalent Candidate Chemicals were either persistent, bioaccumulative, carcinogenic, or reprotoxic. This regulation will have wide-ranging impact in California and throughout the global supply chain, which is highlighted through selected examples and case studies.

The role of genotoxicity in asbestos-induced mesothelioma: an explanation for the differences in carcinogenic potential among fiber types.

The mechanism(s) underlying asbestos toxicity associated with the pathogenesis of mesothelioma has been a challenge to unravel for more than 60 years. A significant amount of research has focused on the characteristics of different fiber types and their potential to induce mesothelioma. These mechanistic studies of fiber toxicity have proceeded along two lines: those demonstrating biochemical mechanisms by which fibers induce disease and those investigating human susceptibility. Most recent studies focused on in vitro genotoxic effects induced by asbestos as the mechanism responsible for asbestos-induced disease. Although asbestos exerts a genotoxic effect at certain concentrations in vitro, a positive response in these tests does not indicate that the chemical is likely to produce an increased risk of carcinogenesis in exposed human populations. Thus far, findings from studies on the effects of fiber type in mesothelial cells are seriously flawed by a lack of a dose response relationship. The common limitation of these in vitro experiments is the lack of attention paid to the complexities of the human anatomy, biochemistry and physiology, which make the observed effects in these experimental systems difficult to extrapolate to persons in the workplace. Mechanistic differences between carcinogenic and genotoxic processes indicate why tests for genotoxicity do not provide much insight regarding the ability to predict carcinogenic potential in workers exposed to asbestos doses in the post-Occupational Safety and Health Administration era. This review discusses the existing literature on asbestos-induced genotoxicity and explains why these studies may or may not likely help characterize the dose-response curve at low dose.

A review of the health hazards posed by cobalt.

Cobalt (Co) is an essential element with ubiquitous dietary exposure and possible incremental exposure due to dietary supplements, occupation and medical devices. Adverse health effects, such as cardiomyopathy and vision or hearing impairment, were reported at peak blood Co concentrations typically over 700 µg/L (8-40 weeks), while reversible hypothyroidism and polycythemia were reported in humans at ~300 µg/L and higher (≥2 weeks). Lung cancer risks associated with certain inhalation exposures have not been observed following Co ingestion and Co alloy implants. The mode of action for systemic toxicity relates directly to free Co(II) ion interactions with various receptors, ion channels and biomolecules resulting in generally reversible effects. Certain dose-response anomalies for Co toxicity likely relate to rare disease states known to reduce systemic Co(II)-ion binding to blood proteins. Based on the available information, most people with clearly elevated serum Co, like supplement users and hip implant patients, have >90% of Co as albumin-bound, with considerable excess binding capacity to sequester Co(II) ions. This paper reviews the scientific literature regarding the chemistry, pharmacokinetics and systemic toxicology of Co, and the likely role of free Co(II) ions to explain dose-response relationships. Based on currently available data, it might be useful to monitor implant patients for signs of hypothyroidism and polycythemia starting at blood or serum Co concentrations above 100 µg/L. This concentration is derived by applying an uncertainty factor of 3 to the 300 µg/L point of departure and this should adequately account for the fact that persons in the various studies were exposed for less than one year. A higher uncertainty factor could be warranted but Co has a relatively fast elimination, and many of the populations studied were of children and those with kidney problems. Closer follow-up of patients who also exhibit chronic disease states leading to clinically important hypoalbuminemia and/or severe ischemia modified albumin (IMA) elevations should be considered.

An analysis of historical exposures of pressmen to airborne benzene (1938-2006).

Benzene is an aromatic hydrocarbon that, with sufficient cumulative lifetime doses, can cause acute myelogenous leukemia. Because of its volatility and solvent properties, it was used in the printing industry in inks, ink solvents, and cleaning agents from the 1930s to the 1970s. This analysis represents the first known attempt to gather and synthesize the available data on historical airborne benzene concentrations in printing facilities and exposures to pressmen. The sources of fugitive benzene vapors from printing operations have been identified as evaporation from ink fountains, exposed sections of the printing cylinder, the paper web, the paper post exit, and spilled ink. In addition, specific activities that could lead to benzene exposure, such as filling the fountains, using solvents to clean the press, and using solvents as personal cleaning agents, potentially occurred multiple times per work period. Eighteen studies were identified that reported workplace airborne concentrations in printing facilities between 1938 and 2006. Typical benzene air concentrations, considering both personal and area samples of various durations, were as high as 200 p.p.m. in the 1930s through the 1950s, 3-35 p.p.m. in the 1960s, 1.3-16 p.p.m. in the 1970s, 0.013-1 in the 1980s, and far less than 1 p.p.m. in the 1990s and 2000s. The decrease in benzene air concentrations by the late 1970s was likely to be linked to the decreased benzene content of printing materials, increased engineering controls, and to more stringent occupational exposure limits.