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Chicago Ridge, IL, United States

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. Source

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. Source

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. Source

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. Source

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. Source

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