Dennis J Paustenbach

Cardno ChemRisk, San Francisco, California, United States

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Publications (279)699.91 Total impact

  • Dennis J Paustenbach · Bethany Winans · Rachel M Novick · Steven M Green ·
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    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.
    Critical Reviews in Toxicology 10/2015; 45(sup2):1-55. DOI:10.3109/10408444.2015.1076376 · 5.10 Impact Factor
  • Brent D. Kerger · Russell Gerads · Hakan Gurleyuk · Ania Urban · Dennis J. Paustenbach ·

    Toxicological and Environmental Chemistry 10/2015; 97(9):1145-1163. DOI:10.1080/02772248.2015.1092735 · 0.83 Impact Factor
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    ABSTRACT: 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).Journal of Exposure Science and Environmental Epidemiology advance online publication, 29 April 2015; doi:10.1038/jes.2015.15.
    Journal of Exposure Science and Environmental Epidemiology 04/2015; DOI:10.1038/jes.2015.15. · 3.19 Impact Factor
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    ABSTRACT: The objective of Part I of this analysis was to identify the relevant physicochemical characteristics of wear particles from cobalt-chromium alloy (CoCr) metal-on-metal (MoM) hip implant patients and simulator systems. For well-functioning MoM hip implants, the volumetric wear rate is low (<1mm(3) per million cycles or per year) and the majority of the wear debris is composed of oxidized Cr nanoparticles (<100nm) with minimal or no Co content. For implants with surgical malpositioning, the volumetric wear rate is as high as 100mm(3) per million cycles or per year and the size distribution of wear debris can be skewed to larger sizes (up to 1000nm) and contain higher concentrations of Co. In order to obtain data for risk assessment of wear debris in MoM hip implant patients, future studies need to focus on particle characteristics relevant to those generated in patients or in properly conducted simulator studies. Copyright © 2015. Published by Elsevier Inc.
    Nanomedicine Nanotechnology Biology and Medicine 03/2015; 11(5). DOI:10.1016/j.nano.2014.12.005 · 6.16 Impact Factor
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    ABSTRACT: The objective of Part II analysis was to evaluate animal and in vitro toxicology studies of CoCr particles with respect to their physicochemistry and dose relevance to metal-on-metal (MoM) implant patients as derived from Part I. Physicochemical characteristics were infrequently considered and administered doses were orders of magnitude higher than what occurs in patients. Despite this, distinct observations emerge from these studies. Co was consistently shown to rapidly release from CoCr particles for distribution and elimination from the body. CoCr micron sized particles appear more biopersistent in vivo resulting in inflammatory responses that are not seen with similar mass concentrations of nanoparticles. We conclude, that in an attempt to obtain data for complete risk assessment, future studies need to focus on physicochemical characteristics of nano and micron sized particles and on doses and dose metrics relevant to those generated in patients or in properly conducted hip simulator studies. Copyright © 2015. Published by Elsevier Inc.
    Nanomedicine Nanotechnology Biology and Medicine 02/2015; 11(5). DOI:10.1016/j.nano.2015.02.006 · 6.16 Impact Factor
  • Brooke E Tvermoes · Dennis J Paustenbach · Brent D Kerger · Brent L Finley · Kenneth M Unice ·
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    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.
    Critical Reviews in Toxicology 01/2015; 45(5):1-21. DOI:10.3109/10408444.2014.985818 · 5.10 Impact Factor
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    ABSTRACT: 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. Copyright © 2014 John Wiley & Sons, Ltd.
    Journal of Applied Toxicology 09/2014; 34(9):939-967. DOI:10.1002/jat.3039 · 2.98 Impact Factor
  • Andrew D. Monnot · Whitney V. Christian · Dennis J. Paustenbach · Brent L. Finley ·
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    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.
    Critical Reviews in Toxicology 07/2014; 44(7). DOI:10.3109/10408444.2014.926472 · 5.10 Impact Factor
  • Dennis Paustenbach · David Galbraith · Brent Finley ·

    Clinical Toxicology 04/2014; 52(5). DOI:10.3109/15563650.2014.908473 · 3.67 Impact Factor
  • Kenneth M Unice · Brent D Kerger · Dennis J Paustenbach · Brent L Finley · Brooke E Tvermoes ·
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    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.
    Chemico-biological interactions 04/2014; 216(1). DOI:10.1016/j.cbi.2014.04.001 · 2.58 Impact Factor
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    Luda M. Kopelovich · Kerry A. Thuett · Pamela S. Chapman · Dennis J. Paustenbach ·
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    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.
    Regulatory Toxicology and Pharmacology 04/2014; 68(3). DOI:10.1016/j.yrtph.2014.01.015 · 2.03 Impact Factor
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    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).
    Risk Analysis 02/2014; 34(8). DOI:10.1111/risa.12174 · 2.50 Impact Factor
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    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 as NCT01990794.
    American Journal of Clinical Nutrition 02/2014; 99(3). DOI:10.3945/ajcn.113.071449 · 6.77 Impact Factor
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    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.
    International Journal of Vehicle Safety 01/2014; 7(3/4):409 - 424. DOI:10.1504/IJVS.2014.063251
  • Dennis J Paustenbach · Matthew H Le ·

    Health physics 12/2013; 105(6):486-7. DOI:10.1097/HP.0b013e3182a8e16c · 1.27 Impact Factor
  • Dennis J Paustenbach · David A Galbraith · Brent L Finley ·
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    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.
    Clinical Toxicology 11/2013; 52(2). DOI:10.3109/15563650.2013.857024 · 3.67 Impact Factor
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    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.
    Regulatory Toxicology and Pharmacology 11/2013; 68(1). DOI:10.1016/j.yrtph.2013.11.001 · 2.03 Impact Factor
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    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.
    Journal of Toxicology and Environmental Health Part A 11/2013; 76(21):1210-1224. DOI:10.1080/15287394.2013.848391 · 2.35 Impact Factor
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    ABSTRACT: Abstract 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.
    Inhalation Toxicology 08/2013; 25(9):553-67. DOI:10.3109/08958378.2013.807321 · 2.26 Impact Factor
  • J Sahmel · K Devlin · A Burns · T Ferracini · M Ground · D Paustenbach ·
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    ABSTRACT: Benzene, a known carcinogen, can be generated as a by-product during the use of petroleum-based raw materials in chemical manufacturing. The aim of this study was to analyze a large data set of benzene air concentration measurements collected over nearly 40 years during routine employee exposure monitoring at a petrochemical manufacturing facility. The facility used ethane, propane, and natural gas as raw materials in the production of common commercial materials such as polyethylene, polypropylene, waxes, adhesives, alcohols, and aldehydes. In total, 3607 benzene air samples were collected at the facility from 1962 to 1999. Of these, in total 2359 long-term (>1 h) personal exposure samples for benzene were collected during routine operations at the facility between 1974 and 1999. These samples were analyzed by division, department, and job title to establish employee benzene exposures in different areas of the facility over time. Sampling data were also analyzed by key events over time, including changes in the occupational exposure limits (OELs) for benzene and key equipment process changes at the facility. Although mean benzene concentrations varied according to operation, in nearly all cases measured benzene quantities were below the OEL in place at the time for benzene (10 ppm for 1974-1986 and 1 ppm for 1987-1999). Decreases in mean benzene air concentrations were also found when data were evaluated according to 7- to 10-yr periods following key equipment process changes. Further, an evaluation of mortality rates for a retrospective employee cohort (n = 3938) demonstrated that the average personal benzene exposures at this facility (0.89 ppm for the period 1974-1986 and 0.125 ppm for the period 1987-1999) did not result in increased standardized mortality ratio (SMRs) for diseases or malignancies of the lymphatic system. The robust nature of this data set provides comprehensive exposure information that may be useful for assessing human benzene exposures at similar facilities. The data also provide a basis for comparable measured exposure levels and the potential for adverse health effects. These data may also prove beneficial for comparing relative exposure potential for production versus nonproduction operations and the relationship between area and personal breathing zone samples.
    Journal of Toxicology and Environmental Health Part A 06/2013; 76(12):723-46. DOI:10.1080/15287394.2013.821393 · 2.35 Impact Factor

Publication Stats

5k Citations
699.91 Total Impact Points


  • 1990-2015
    • Cardno ChemRisk
      San Francisco, California, United States
    • University of Wisconsin–Madison
      Madison, Wisconsin, United States
    • Maryland Department Of Agriculture
      Annapolis, Maryland, United States
  • 2010-2013
    • The Harvard Drug Group
      Ливония, Michigan, United States
  • 2004-2013
    • University of California, San Francisco
      San Francisco, California, United States
  • 2012
    • University of Michigan
      Ann Arbor, Michigan, United States
    • Fudan University
      • Institutes of Biomedical Sciences
      Shanghai, Shanghai Shi, China
  • 2000-2003
    • Exponent
      San Mateo, California, United States
  • 1994
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States
  • 1992
    • College of Alameda
      Аламеда, California, United States
  • 1983-1986
    • Purdue University
      • School of Health Sciences
      West Lafayette, Indiana, United States