[Show abstract][Hide abstract] ABSTRACT: Context:
Industrial hygiene assessments often focus on activity-based airborne asbestos concentration measurements, but few empirical data exist regarding the fiber removal rate from air after activities cease.
Grade 7T chrysotile indoor fiber settling (FS) rates were characterized using air sampling (NIOSH Method 7402).
Materials and methods:
Six replicate events were conducted in a 58 m(3) study chamber (ventilation 3.5 ACH), in which chrysotile-contaminated work clothing was manipulated for 15 min followed by 30 min of no activity. The fiber concentration decay constant and removal rate were characterized using an exponential decay model based on the measurements.
Breathing zone airborne chrysotile concentrations decreased by 86% within 15-30 min after fiber disturbance, compared to concentrations during active disturbance (p < 0.05). Estimated mean time required for 99% of the phase contrast microscopy-equivalent (PCME) fibers to be removed from air was approximately 30 min (95% CI: 22-57 min). The observed effective FS velocity was 0.0034 m/s. This settling velocity was between 4.5-fold and 180-fold faster than predicted by two different particulate gravitational settling models. Additionally, PCME concentrations decreased approximately 2.5-fold faster than predicted due to air exchange alone (32 versus 79 min to 99% decrease in concentration).
Other measurement studies have reported similar airborne fiber removal rates, supporting the finding that factors other than gravitational settling and dilution ventilation contribute measurably to PCM fiber removal from air (e.g. impaction, agglomeration).
Overall, the scientific weight of evidence indicates that the time necessary for removal of 99% of fibers greater than 5 μm in length (with aspect ratios greater than 3:1) is approximately 20-80 min.
No preview · Article · Dec 2015 · Inhalation Toxicology
[Show abstract][Hide abstract] ABSTRACT: 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 A total of 17 published and unpublished studies and datasets were identified that reported the results of 2058 samples collected from the 1960s through the 2000s across the US.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.
No preview · Article · Dec 2015 · Inhalation Toxicology
[Show abstract][Hide abstract] ABSTRACT: 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.
Preview · Article · Oct 2015 · Critical Reviews in Toxicology
[Show abstract][Hide abstract] ABSTRACT: Inductively coupled plasma with mass spectrometric detection (ICP-MS) has been used for clinical analysis of cobalt (Co) due to its sensitivity and specificity; however, media-specific validation studies are lacking. This study provides data on performance variables affecting differences between selected analytical platforms (Perkin Elmer and Agilent), tissue sample preparation, storage, and interferences affecting measurements in whole blood, serum, and synovial fluid. The limits of detection (LOD) range from 0.2–0.5 µg/L in serum and synovial fluid, and 0.6–1.7 µg Co/L in whole blood. The Agilent platform with collision reaction cell is more sensitive, while the Perkin Elmer platform with dynamic reaction cell demonstrates more polyatomic interferences near the LOD for serum and whole blood. Split sample analysis showed good accuracy, precision, and reproducibility between serum Co measurements using acid digestion or detergent dilution preparations for persons with metal hip implants or following supplement intake. The results demonstrated reliability of the ICP-MS methodology across the two analytical platforms and between two commercial laboratories for Co concentrations above 5 µg Co/L, but digestion procedures and polyatomic interferences may affect measurements in some media at lower concentrations. These studies validate the described ICP-MS methodology for clinical purposes with precautions at low cobalt concentrations (<5 µg Co/L).
No preview · Article · Oct 2015 · Toxicological and Environmental Chemistry
[Show abstract][Hide abstract] ABSTRACT: Cobalt (Co) can stimulate erythropoietin production in individuals at doses exceeding 25 mg CoCl2/day. Co has also been shown to exert effects on the thyroid gland, heart and nervous system at sufficient doses. The biological activity of Co is dictated by the concentration of free (unbound) ionic Co(2+). Blood concentrations, as well as, urinary excretion rates of Co are reliable biomarkers for systemic Co exposure. A recent series of human volunteer Co-supplement studies simultaneously measured Co blood and urine concentrations, as well as, Co speciation in serum, and a number of biochemical and clinical parameters. It was found in these studies that peak Co whole blood concentration as high as 117 μg/L were not associated with changes in hematological parameters such as increased red blood cell (RBC) count, hemoglobin (Hgb) or hematocrit (Hct) levels, nor with changes in cardiac, neurological or, thyroid function. Using a Co biokinetic model, the estimated Co systemic tissue concentrations (e.g., liver, kidney, and heart) following 90-days of Co-dietary supplementation with ∼1 mg Co/day were found to be similar to estimated tissue concentrations in implant patients after 10 years of exposure at continuous steady state Co blood concentration of ∼10 μg/L. This study is the first to present modeled Co tissue concentrations at various doses following sub-chronic and chronic exposure. The modeled steady state tissue Co concentrations in combination with the data on adverse health effects in humans should help in the characterization of potential hazards associated with increased blood Co concentrations due to exposure to dietary supplements or cobalt-chromium (Co-Cr) containing implants.
Full-text · Article · Jan 2015 · Critical Reviews in Toxicology
[Show abstract][Hide abstract] ABSTRACT: Chromium (Cr) (III) is a trace metal essential to human health and exposure typically occurs via the diet on a daily basis. Some groups of individuals, such as those consuming Cr(III) supplements or patients with Cr-containing implants, may have elevated blood Cr(III) concentrations. Although blood Cr(III) levels are thought to be an accurate metric of exposure, little is known about the relationship between these concentrations and possible adverse health risks. This study evaluated the various effects reported in animal and human epidemiological studies of Cr(III) exposure in an attempt to correlate them with blood Cr(III) concentrations. The target endpoints identified in this analysis included the hematological, hepatic, and renal systems. Animal and human physiological-based pharmacokinetic (PBPK) models were used to estimate steady state blood Cr(III) concentrations from a variety of dosing regimens. Based on the animal studies, our results suggest that blood Cr(III) concentrations as high as 480–580 μg/L are not associated with any responses. For each of the three health endpoints considered in this analysis (hematological, hepatic, and renal) no adverse effects were observed below 3,700 μg/L. Some hematological responses were observed at 3,700 μg/L, and adverse effects clearly occurred at 7,500 μg/L. These findings can be used to assess potential health risks to individuals with elevated blood Cr(III) concentrations.
No preview · Article · Jul 2014 · Critical Reviews in Toxicology
[Show abstract][Hide abstract] ABSTRACT: An updated biokinetic model for human exposures to cobalt (Co) was developed based on a comprehensive set of human pharmacokinetics data collected from five male and five female volunteers who ingested ∼1.0 mg Co/day of a Co supplement for three months. Three key experimental observations from the human dosing studies were incorporated into the model: 1) an increase in the measured fraction of large molecular serum protein bound Co from 95% during dosing to 99% after dosing; 2) a linear decrease in Co red blood cell concentration after dosing; and 3) Co renal clearance consistent with estimated glomerular filtration rates and free Co(2+) concentration. The model was refined by adding compartments accounting for 1) albumin bound Co in intravascular fluid (serum); 2) albumin bound Co in extravascular fluid with physiologic exchange rates of albumin bound Co between extravascular and intravascular fluid; and 3) a novel sequential cascade of compartments representing red blood cell ages between 1 and 120 days. Reasonable agreement between the modeled and measured urine, serum, and whole blood concentrations were observed (r>0.84, slope= 0.79 - 1.0) with gastrointestinal absorption rates between 9% and 66%. In addition, model predictions agreed well with data from several external studies representing healthy human volunteers, dialysis patients, anephric patients, a Co-poisoning incident and whole body retention studies. Our revised model considerably improves the state of knowledge on human Co kinetics, and should be helpful for evaluating elevated blood Co concentrations in currently exposed populations, such as metal-on-metal (MoM) hip implant patients.
No preview · Article · Apr 2014 · Chemico-biological interactions
[Show abstract][Hide abstract] ABSTRACT: There have been claims over the years that asbestos-containing product manufacturers did not sufficiently warn end users early enough regarding the potential health hazards associated with their products (1930s-1990s). To address this issue, we compared the content of the warnings associated with asbestos-containing friction products (brakes, clutches, and gaskets) manufactured by the US automotive industries to what was expected by regulatory agencies during the time period in which an understanding of asbestos health hazards was being developed. We ended our evaluation around 1990, since asbestos-containing manufacturer supplied automotive products were functionally removed from commerce by 1985 in the United States. We assessed the warnings issued in users’ manuals, technical service bulletins, product packaging materials, and labels placed on products themselves. Based on our evaluation, regulatory agencies had no guidelines regarding specific warning language for finished friction products, particularly when a product contained encapsulated asbestos fibers (i.e., modified by a bonding agent). Even today, federal regulations do not require labeling on encapsulated products when, based on professional judgment or sampling, user exposure is not expected to exceed the OSHA PEL. We concluded that, despite limited regulatory guidance, the US automotive industry provided adequate warnings with regards to its friction products.
[Show abstract][Hide abstract] ABSTRACT: The potential for para-occupational (or take-home) exposures from contaminated clothing has been recognized for the past 60 years. To better characterize the take-home asbestos exposure pathway, a study was performed to measure the relationship between airborne chrysotile concentrations in the workplace, the contamination of work clothing, and take-home exposures and risks. The study included air sampling during two activities: (1) contamination of work clothing by airborne chrysotile (i.e., loading the clothing), and (2) handling and shaking out of the clothes. The clothes were contaminated at three different target airborne chrysotile concentrations (0-0.1 fibers per cubic centimeter [f/cc], 1-2 f/cc, and 2-4 f/cc; two events each for 31-43 minutes; six events total). Arithmetic mean concentrations for the three target loading levels were 0.01 f/cc, 1.65 f/cc, and 2.84 f/cc (National Institute of Occupational Health and Safety [NIOSH] 7402). Following the loading events, six matched 30-minute clothes-handling and shake-out events were conducted, each including 15 minutes of active handling (15-minute means; 0.014-0.097 f/cc) and 15 additional minutes of no handling (30-minute means; 0.006-0.063 f/cc). Percentages of personal clothes-handling TWAs relative to clothes-loading TWAs were calculated for event pairs to characterize exposure potential during daily versus weekly clothes-handling activity. Airborne concentrations for the clothes handler were 0.2-1.4% (eight-hour TWA or daily ratio) and 0.03-0.27% (40-hour TWA or weekly ratio) of loading TWAs. Cumulative chrysotile doses for clothes handling at airborne concentrations tested were estimated to be consistent with lifetime cumulative chrysotile doses associated with ambient air exposure (range for take-home or ambient doses: 0.00044-0.105 f/cc year).
[Show abstract][Hide abstract] ABSTRACT: Over-the-counter cobalt supplements are available for sale in the United States, but little is known regarding their clinical effects and biokinetic distribution with long-term use.
We assessed blood kinetics, biochemical responses, and clinical effects in 5 adult men and 5 adult women who voluntarily ingested ∼1.0 mg Co/d (0.080-0.19 mg Co ⋅ kg(-1) ⋅ d(-1)) of a commercially available cobalt supplement over a 3-mo period.
Volunteers were instructed to take the cobalt dietary supplement in the morning according to the manufacturer's label. Blood samples were collected and analyzed for a number of biochemical variables before, during, and after dosing. Hearing, vision, cardiac, and neurologic functions were also assessed in volunteers before, during, and after dosing.
After ∼90 d of dosing, mean cobalt blood concentrations were lower in men than in women. Mean cobalt whole blood and serum concentrations in men were 20 μg/L (range: 12-33 μg/L) and 25 μg/L (range: 15-46 μg/L), respectively. In women, mean cobalt whole blood and serum concentrations were 53 μg/L (range: 6-117 μg/L) and 71 μg/L (range: 9-149 μg/L), respectively. Estimated red blood cell (RBC) cobalt concentrations suggested that cobalt was sequestered in RBCs during their 120-d life span, which resulted in a slower whole blood clearance compared with serum. The renal clearance of cobalt increased with the serum concentration and was, on average, lower in women (3.5 ± 1.3 mL/min) than in men (5.5 ± 1.9 mL/min). Sex-specific differences were observed in cobalt absorption and excretion. There were no clinically significant changes in biochemical, hematologic, and clinical variables assessed in this study.
Peak cobalt whole blood concentrations ranging between 9.4 and 117 μg/L were not associated with clinically significant changes in basic hematologic and clinical variables. This study was registered at clinicaltrials.gov as NCT01990794.
No preview · Article · Feb 2014 · American Journal of Clinical Nutrition
[Show abstract][Hide abstract] ABSTRACT: Carbon monoxide (CO) is a well-known asphyxiant. As part of an incident investigation involving two fatalities, a study was conducted to determine key factors that influence CO concentrations inside motor homes/recreational vehicles. Test parameters examined included the condition of the on-board generator exhaust pipe (attached/detached), generator load (<1-20 amps), position of ventilation hatches (open/closed), parking location (adjacent/perpendicular to a masonry wall), and weather conditions (breezy/calm). A tracer gas test was also performed of the motor home undercarriage because of concerns for possible damage (no visible damage was observed). Results showed that all five parameters affected the CO concentrations detected within the motor home, but the generator exhaust tailpipe was found to have the greatest impact. Further, a specific combination of conditions, along with documented invisible undercarriage leaks, was necessary for CO concentrations to become high enough to produce acutely toxic and fatal conditions inside the motor home.
No preview · Article · Jan 2014 · International Journal of Vehicle Safety
[Show abstract][Hide abstract] ABSTRACT: 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.
No preview · Article · Nov 2013 · Clinical Toxicology
[Show abstract][Hide abstract] ABSTRACT: 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 aimed 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.
Full-text · Article · Nov 2013 · Regulatory Toxicology and Pharmacology
[Show abstract][Hide abstract] ABSTRACT: The United Kingdom Expert Group on Vitamins and Minerals concluded that ingesting cobalt (Co)-containing supplements up to 1400 μg Co/d is unlikely to produce adverse health effects. However, the associated blood Co concentrations and safety of Co-containing dietary supplements have not been fully characterized. Thus, blood Co kinetics and a toxicological assessment of hematological and biochemical parameters were evaluated following Co dietary supplementation in 5 male and 5 female volunteers who ingested approximately 1000 μg Co/d (10-19 μg Co/kg-d) as cobalt(II) chloride for a period of 31 d. Supplement intake was not associated with significant overt adverse events, alterations in clinical chemistries including blood counts and indicators of thyroid, cardiac, liver, or kidney functions, or metal sensitization. A non-clinically significant (<5%) increase in hemoglobin, hematocrit, and red blood cell (RBC) counts were observed in males but not females 1 wk after dose termination. Mean Co concentrations in whole blood/serum after 31 d of dosing were approximately two-fold higher in females (33/53 μg/L) than in males (16/21 μg/L). In general, steady-state concentrations of Co were achieved in whole blood and/or red blood cells (RBC) within 14-24 d. Temporal patterns of whole blood and serum Co concentrations indicated metal sequestration in RBC accompanied by slower whole blood clearance compared to serum. Data also indicated that peak whole blood Co concentrations up to 91.4 μg/L were not associated with clinically significant changes in clinical chemistries. In addition, Co blood concentrations and systemic uptake via ingestion were generally higher in females.
No preview · Article · Nov 2013 · Journal of Toxicology and Environmental Health Part A