J Toxicol Env Heal A
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J Toxicol Env Heal A · Jan 2019
Model qualification of the PK-Sim® pediatric module for pediatric exposure assessment of CYP450 metabolized compounds.
Pediatric physiologically based pharmacokinetic (PBPK) models facilitate the estimation of pharmacokinetic (PK) parameters in children under specific exposure conditions. In human health risk assessment, PBPK modeling has been used to determine a chemical-specific human kinetic adjustment factor (HKAF). Due to increased demands in regulatory assessment, model evaluation and qualification have gained growing attention. ⋯ The sensitivity analysis revealed that fraction unbound in plasma, parameters related to CYP enzyme-mediated metabolism and liver volumewere most important in the estimation of pediatric exposure. A comparison of variabilities in weight, height and liver volume in virtual children showed reliable agreement with observed data. The presented results of predictive performance and properties of virtual populations provide confidence in the use of PK-Sim for pediatric PBPK modeling in toxicological applications including PBPK-based-HKAF derivation.
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J Toxicol Env Heal A · Jan 2018
Involvement of nerve growth factor in mouse hippocampal neuronal cell line (HT22) differentiation and underlying role of DNA methyltransferases.
DNA methylation is an epigenetic event involved in regulation of gene transcription during cell differentiation. DNA methyltransferases (DNMT) play a role in differentiation of neural stem cells into neurons. The aim of this study was to determine whether nerve growth factor (NGF) was involved in differentiation of mouse hippocampal neuronal cell line (HT22) as assessed by IncuCyte. ⋯ Compared to undifferentiating cells, the percentage of differentiating cells at S phase increased significantly when incubated with NGF. In undifferentiated cells, NGF failed to induce gene and protein expressions and activity of DNMTs. Data demonstrate that differentiation of HT22 cells by exposure to NGF involve the activation of DNMTs pathway.
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J Toxicol Env Heal A · Jan 2015
The Biomarkers of Exposure and Effect in Agriculture (BEEA) Study: Rationale, Design, Methods, and Participant Characteristics.
Agricultural exposures including pesticides, endotoxin, and allergens have been associated with risk of various cancers and other chronic diseases, although the biological mechanisms underlying these associations are generally unclear. To facilitate future molecular epidemiologic investigations, in 2010 the study of Biomarkers of Exposure and Effect in Agriculture (BEEA) was initiated within the Agricultural Health Study, a large prospective cohort in Iowa and North Carolina. Here the design and methodology of BEEA are described and preliminary frequencies for participant characteristics and current agricultural exposures are reported. ⋯ Among those still farming, the most commonly reported crops were corn (81%) and soybeans (74%), and the most frequently noted animals were beef cattle (35%) and hogs (13%). There were 861 (70%) participants who reported occupational pesticide use in the 12 months prior to interview; among these participants, the most frequently noted herbicides were glyphosate (83%) and 2,4-D (72%), and most commonly reported insecticides were malathion (21%), cyfluthrin (13%), and permethrin (12%). Molecular epidemiologic investigations within BEEA have the potential to yield important new insights into the biological mechanisms through which these or other agricultural exposures influence disease risk.
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J Toxicol Env Heal A · Jan 2015
Short-term effects of fine particulate air pollution on hospital admissions for cardiovascular diseases: a case-crossover study in a tropical city.
This study was undertaken to determine whether there was an association between fine particles (PM2.5) levels and hospital admissions for cardiovascular diseases (CVD) in Kaohsiung, Taiwan. Hospital admissions for CVD (including ischemic heart disease [IHD], stroke, congestive heart failure [CHF], and arrhythmias) and ambient air pollution data for Kaohsiung were obtained for the period from 2006-2010. The relative risk of hospital admissions for CVD was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. ⋯ No significant associations between PM2.5 and hospital admissions for CVD were observed on warm days. In the two-pollutant models, PM2.5 levels remained significant even controlling for sulfur dioxide, nitrogen dioxide, carbon monoxide, or ozone on cool days. This study provides evidence that higher levels of PM2.5 enhance the risk of hospital admissions for CVD in Kaohsiung, Taiwan.
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J Toxicol Env Heal A · Jan 2015
Effect of Providing Information on Students' Knowledge and Concerns about Hydraulic Fracking.
Governmental agencies, regulators, health professionals, and the public are faced with understanding and responding to new development practices and conditions in their local and regional environment. While hydraulic fracking (fracking) for shale gas has been practiced for over 50 years in some states, it is a relatively recent event in the northeastern United States. Providing environmental health information to the public about fracking requires understanding both the knowledge base and the perceptions of the public. ⋯ There was no change in support for further development of natural gas, but support for solar, wind, and wave energy decreased. Data suggest that students' knowledge and perceptions change with exposure to information, but many of these changes were due to students using the Internet to look up information immediately after the initial survey and lecture. Class discussions indicated a general lack of trust for several information sources available on the Web.