Madl A.K.,Cardno ChemRisk |
Liong M.,Cardno ChemRisk |
Kovochich M.,Cardno ChemRisk |
Finley B.L.,Cardno ChemRisk |
And 2 more authors.
Nanomedicine: Nanotechnology, Biology, and Medicine | Year: 2015
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 (<1mm3 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 100mm3 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 suitable for a 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. From the Clinical Editor: Metallic implants are very common in the field of orthopedics. Nonetheless, concerns have been raised about the implications of nano-sized particles generated from the wear of these implants. In this two-part review, the authors first attempted to identify and critically evaluate the relevant physicochemical characteristics of CoCr wear particles from hip implant patients and simulator systems. Then they evaluated in vitro and animal toxicology studies with respect to the physicochemistry and dose-relevance to metal-on-metal implant patients. © 2015 Elsevier Inc.
Gross S.A.,Cardno ChemRisk |
Fedak K.M.,Colorado State University
BioMed Research International | Year: 2015
Information on polymorphisms, mutations, and epigenetic events has become increasingly important in our understanding of molecular mechanisms associated with exposures-disease outcomes. Molecular landscapes can be developed to illustrate the molecular characteristics for environmental carcinogens as well as associated disease outcomes, although comparison of these molecular landscapes can often be difficult to navigate. We developed a method to organize these molecular data that uses a weight-of-evidence approach to rank overlapping molecular events by relative importance for susceptibility to an exposure-disease paradigm. To illustrate the usefulness of this approach, we discuss the example of benzene as an environmental carcinogen and myelodysplastic syndrome (MDS) as a causative disease endpoint. Using this weight-of-evidence method, we found overlapping polymorphisms in the genes for the metabolic enzymes GST and NQO1, both of which may infer risk of benzene-induced MDS. Polymorphisms in the tumor suppressor gene, TP53, and the inflammatory cytokine gene, TNF-, were also noted, albeit inferring opposing outcomes. The alleles identified in the DNA repair gene RAD51 indicated an increased risk for MDS in MDS patients and low blood cell counts in benzene-exposed workers. We propose the weight-of-evidence approach as a tool to assist in organizing the sea of emerging molecular data in exposure-disease paradigms. © 2015 Sherilyn A. Gross and Kristen M. Fedak.
Fedak K.M.,Colorado State University |
Bernal A.,Cardno ChemRisk |
Capshaw Z.A.,Cardno ChemRisk |
Gross S.,Cardno ChemRisk
Emerging Themes in Epidemiology | Year: 2015
In 1965, Sir Austin Bradford Hill published nine "viewpoints" to help determine if observed epidemiologic associations are causal. Since then, the "Bradford Hill Criteria" have become the most frequently cited framework for causal inference in epidemiologic studies. However, when Hill published his causal guidelines - just 12 years after the double-helix model for DNA was first suggested and 25 years before the Human Genome Project began - disease causation was understood on a more elementary level than it is today. Advancements in genetics, molecular biology, toxicology, exposure science, and statistics have increased our analytical capabilities for exploring potential cause-and-effect relationships, and have resulted in a greater understanding of the complexity behind human disease onset and progression. These additional tools for causal inference necessitate a re-evaluation of how each Bradford Hill criterion should be interpreted when considering a variety of data types beyond classic epidemiology studies. Herein, we explore the implications of data integration on the interpretation and application of the criteria. Using examples of recently discovered exposure-response associations in human disease, we discuss novel ways by which researchers can apply and interpret the Bradford Hill criteria when considering data gathered using modern molecular techniques, such as epigenetics, biomarkers, mechanistic toxicology, and genotoxicology. © 2015 Fedak et al.
Kerger B.D.,Exponent, Inc. |
Bernal A.,Cardno ChemRisk |
Paustenbach D.J.,Cardno ChemRisk |
Huntley-Fenner G.,5319 University Drive and 137
BMC Public Health | Year: 2016
Background: Negative news media reports regarding potential health hazards of implanted medical devices and pharmaceuticals can lead to a 'negative halo effect,' a phenomenon whereby judgments about a product or product type can be unconsciously altered even though the scientific support is tenuous. To determine how a 'negative halo effect' may impact the rates of use and/or explantation of medical products, we analyzed the occurrence of such an effect on three implanted medical devices and one drug: 1) intrauterine contraceptive devices (IUDs); 2) silicone gel-filled breast implants (SGBI); 3) metal-on-metal hip implants (MoM); and 4) the drug Tysabri. Methods: Data on IUD use from 1965 to 2008 were gathered from the Department of Health and Human Services Vital and Health Statistics and peer-reviewed publications. Data regarding SGBI implant and explantation rates from 1989 to 2012 were obtained from the Institute of Medicine and the American Society of Plastic Surgeons. MoM implant and explantation data were extracted from the England and Wales National Joint Registry and peer-reviewed publications. Tysabri patient data were reported by Elan Corporation or Biogen Idec Inc. Data trends for all products were compared with historical recall or withdrawal events and discussed in the context of public perceptions following such events. Results: We found that common factors altered public risk perceptions and patterns of continued use. First, a negative halo effect may be driven by continuing patient anxiety despite positive clinical outcomes. Second, negative reports about one product can spill over to affect the use of dissimilar products in the same category. Third, a negative halo effect on an entire category of medical devices can be sustained regardless of the scientific findings pertaining to safety. Fourth, recovery of a product's safety reputation and prevalent use may take decades in the U.S., even while these products may exhibit widespread use and good safety records in other countries. Conclusions: We conclude that the 'negative halo effect' associated with a stigma, rather than an objective risk-benefit assessment of medical products can increase negative health outcomes for patients due to reduced or inappropriate product usage. © 2016 The Author(s).
Scott P.K.,Cardno ChemRisk |
Abelmann A.,Cardno ChemRisk |
Hoyt S.,Environmental Analytical Services Inc. |
Kerger B.D.,Exponent, Inc.
Toxicological and Environmental Chemistry | Year: 2015
Laboratory studies were conducted to evaluate airborne release of diacetyl from selected mixtures simulating butter flavorings added to foods. The test materials included diacetyl (97% purity); 0.015%, 0.15%, 1.5%, and 3.0% diacetyl in a water/propylene glycol mixture; 1.5% diacetyl in deionized water or soybean oil; and 3% or 6% diacetyl in a commercial steam distillate from milk fermentation known as “butter starter distillate.” Diacetyl was quantified by gas chromatography with flame ionization detection. Expected concentration-dependent emission patterns based on liquid diacetyl content were demonstrated, but were significantly altered by mixture composition. Soybean oil and deionized water more readily released diacetyl when compared with starter distillate, propylene glycol solutions, and pure diacetyl. Measured diacetyl concentrations under static headspace and dynamic flow-chamber conditions were compared to estimated concentrations utilizing Raoult's law with published and fitted activity coefficient corrections for each mixture, indicating that published coefficients often understated the measured concentrations. It is concluded that headspace (static) and small-chamber (dynamic) measurements of airborne diacetyl provide data to assist in validating model-estimated airborne diacetyl concentrations by using mixture-specific activity coefficients. Implications of these empirical data for validating exposure estimates for diacetyl based on near-field/far-field modeling in workplace settings are discussed. © 2015 Taylor & Francis.
Cyrs W.D.,Cardno ChemRisk |
Avens H.J.,Cardno ChemRisk |
Capshaw Z.A.,Cardno ChemRisk |
Kingsbury R.A.,Cardno ChemRisk |
And 2 more authors.
Energy Policy | Year: 2014
Grid-connected solar photovoltaic (PV) power is currently one of the fastest growing power-generation technologies in the world. While PV technologies provide the environmental benefit of zero emissions during use, the use of heavy metals in thin-film PV cells raises important health and environmental concerns regarding the end-of-life disposal of PV panels. To date, there is no published quantitative assessment of the potential human health risk due to cadmium leaching from cadmium telluride (CdTe) PV panels disposed in a landfill. Thus, we used a screening-level risk assessment tool to estimate possible human health risk associated with disposal of CdTe panels into landfills. In addition, we conducted a literature review of potential cadmium release from the recycling process in order to contrast the potential health risks from PV panel disposal in landfills to those from PV panel recycling. Based on the results of our literature review, a meaningful risk comparison cannot be performed at this time. Based on the human health risk estimates generated for PV panel disposal, our assessment indicated that landfill disposal of CdTe panels does not pose a human health hazard at current production volumes, although our results pointed to the importance of CdTe PV panel end-of-life management. © 2014 Elsevier Ltd.
Pierce J.S.,Cardno ChemRisk |
Abelmann A.,Cardno ChemRisk |
Spicer L.J.,Cardno ChemRisk |
Adams R.E.,Cardno ChemRisk |
Finley B.L.,Cardno ChemRisk
Critical Reviews in Toxicology | Year: 2014
Diacetyl and 2,3-pentanedione inhalation have been suggested as causes of severe respiratory disease, including bronchiolitis obliterans, in food/flavoring manufacturing workers. Both compounds are present in many food items, tobacco, and other consumer products, but estimates of exposures associated with the use of these goods are scant. A study was conducted to characterize exposures to diacetyl and 2,3-pentanedione associated with cigarette smoking. The yields (μg/cigarette) of diacetyl and 2,3-pentanedione in mainstream (MS) cigarette smoke were evaluated for six tobacco products under three smoking regimens (ISO, Massachusetts Department of Public Health, and Health Canada Intense) using a standard smoking machine. Mean diacetyl concentrations in MS smoke ranged from 250 to 361 ppm for all tobacco products and smoking regimens, and mean cumulative exposures associated with 1 pack-year ranged from 1.1 to 1.9 ppm-years. Mean 2,3-pentanedione concentrations in MS smoke ranged from 32.2 to 50.1 ppm, and mean cumulative exposures associated with 1 pack-year ranged from 0.14 to 0.26 ppm-years. We found that diacetyl and 2,3-pentanedione exposures from cigarette smoking far exceed occupational exposures for most food/flavoring workers who smoke. This suggests that previous claims of a significant exposure-response relationship between diacetyl inhalation and respiratory disease in food/flavoring workers were confounded, because none of the investigations considered or quantified the non-occupational diacetyl exposure from cigarette smoke, yet all of the cohorts evaluated had considerable smoking histories. Further, because smoking has not been shown to be a risk factor for bronchiolitis obliterans, our findings are inconsistent with claims that diacetyl and/or 2,3-pentanedione exposure are risk factors for this disease. © 2014 Informa Healthcare USA, Inc.
Dahlen E.,Cardno ChemRisk
Journal of Environmental Hydrology | Year: 2013
While promising to make huge quantities of oil and gas available from already existing shale reservoirs, hydraulic fracturing produces very high volumes of saline water as a by-product. What questions should operators be asking to address economic risk caused by varying formation geochemistry, regulatory uncertainty, and the complexity of wastewater treatment options? © 2013 International Association for Environmental Hydrology.
Finley B.L.,Cardno ChemRisk |
Unice K.M.,Cardno ChemRisk |
Kerger B.D.,Cardno ChemRisk |
Otani J.M.,Cardno ChemRisk |
And 3 more authors.
Journal of Toxicology and Environmental Health - Part A: Current Issues | Year: 2013
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. © 2013 Cardno ChemRisk.
Sahmel J.,Cardno ChemRisk
Journal of Exposure Science and Environmental Epidemiology | Year: 2015
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. © 2015 Nature America, Inc.