A5103115342- Effects and risks of endocrine disrupting chemicals
- Computational Drug Discovery Methods
- Carcinogens and Genotoxicity Assessment
- 3D Printing in Biomedical Research
- Pharmacogenetics and Drug Metabolism
- Animal testing and alternatives
- Toxic Organic Pollutants Impact
- Potato Plant Research
- Pancreatic function and diabetes
- Health, Environment, Cognitive Aging
- Liver physiology and pathology
- Polyamine Metabolism and Applications
- Pesticide Exposure and Toxicity
- Chemical Analysis and Environmental Impact
- Melamine detection and toxicity
- Immunotoxicology and immune responses
- Indoor Air Quality and Microbial Exposure
- Heavy Metal Exposure and Toxicity
- Plant tissue culture and regeneration
- Water Treatment and Disinfection
- Vitamin C and Antioxidants Research
- Drug-Induced Hepatotoxicity and Protection
- Alcohol Consumption and Health Effects
- Chemical Safety and Risk Management
- Cannabis and Cannabinoid Research
Triangle
2016-2018
Oak Ridge Institute for Science and Education
2015-2017
Oak Ridge Associated Universities
2015-2016
Minnesota Department of Health
2015
Environmental Protection Agency
2014
University of Minnesota
2009-2014
Developing physiologically-based pharmacokinetic (PBPK) models for chemicals can be resource-intensive, as neither chemical-specific parameters nor in vivo data are easily available model construction. Previously developed, well-parameterized, and thoroughly-vetted a great resource the construction of pertaining to new chemicals. A PBPK knowledgebase was compiled developed from existing PBPK-related articles used develop models. From 2,039 published between 1977 2013, 307 unique were...
Furan is a liver toxicant and carcinogen in rodents. On the basis of these observations large potential for human exposure, furan has been classified as possible carcinogen. The mechanism tumor induction by unknown. However, toxicity requires cytochrome P450-catalyzed oxidation furan. product this oxidation, cis-2-butene-1,4-dial (BDA), reacts readily with glutathione, amino acids, DNA bacterial mutagen Ames assay strain TA104. Characterization urinary metabolites expected to provide...
Metabolism of the hepatotoxicant furan leads to protein adduct formation in target organ. The initial bioactivation step involves cytochrome P450-catalyzed oxidation furan, generating cis-2-butene-1,4-dial (BDA). BDA reacts with lysine form pyrrolin-2-one adducts. Metabolic studies indicate that also glutathione (GSH) generate 2-(S-glutathionyl)butanedial (GSH-BDA), which then GSH-BDA-lysine cross-links. To explore relative reactivity these two reactive intermediates, c was reacted presence...
Furan is toxic and carcinogenic in rodents. Because of the large potential for human exposure, furan classified as a possible carcinogen. The detailed mechanism by which causes toxicity cancer not yet known. Since requires cytochrome P450-catalyzed oxidation furan, we have characterized urinary hepatocyte metabolites to gain insight into chemical nature reactive intermediate. Previous studies hepatocytes indicated that oxidized α,β-unsaturated dialdehyde, cis-2-butene-1,4-dial (BDA), reacts...
The use of human biomonitoring data to characterize exposure environmental contaminants in epidemiology studies has expanded greatly recent years. Substantial variability effect measures may arise when using different metrics for a given contaminant, and it is often not clear which metric the best surrogate 'causal' or 'true' exposure. Here we evaluated potential bias epidemiologic associations resulting from phthalate 2009–2010 National Health Nutrition Examination Survey (NHANES). We...
Adverse outcome pathways (AOPs) link adverse effects in individuals or populations to a molecular initiating event (MIE) that can be quantified using vitro methods. Practical application of AOPs chemical-specific risk assessment requires incorporation knowledge on exposure, along with absorption, distribution, metabolism, and excretion (ADME) properties chemicals.We developed conceptual workflow examine exposure ADME relation an MIE. The utility this was evaluated previously established AOP,...
A few different exposure prediction tools were evaluated for use in the new vitro-based safety assessment paradigm using di-2-ethylhexyl phthalate (DEHP) and dibutyl (DnBP) as case compounds. Daily intake of each was estimated both high-throughput (HT) models such HT Stochastic Human Exposure Dose Simulation model (SHEDS-HT) ExpoCast heuristic non-HT approaches based on chemical specific estimations environment conjunction with human factors. Reverse dosimetry performed a published...
Furan is a liver toxicant and carcinogen in rodents. Although humans are most likely exposed to furan through variety of sources, the effect exposure on human health still unknown. In rodents, requires metabolism exert its toxic effects. The initial product cytochrome P450 2E1-catalyzed oxidation reactive <i>α</i>,<i>β</i>-unsaturated dialdehyde, <i>cis</i>-2-butene-1,4-dial (BDA). BDA mutagenic consequently considered responsible for effects furan. urinary metabolites rats derived from...
Accurate prediction of metabolism is a significant outstanding challenge in toxicology. The best predictions are based on experimental data from vitro systems using primary hepatocytes. predictivity the hepatocyte-based culture systems, however, still limited due to well-known phenotypic instability and rapid decline metabolic competence within few hours. Dynamic flow bioreactors for three-dimensional cell cultures thought be better at recapitulating tissue microenvironments show potential...
Chemical risk assessment relies on toxicity tests that require significant numbers of animals, time and costs. For the >30,000 chemicals in commerce, current scale animal testing is insufficient to address chemical safety concerns as regulatory product stewardship considerations evolve more comprehensive understanding potential biological effects, conditions use, associated exposures. We demonstrate use a multi-level new approach methodology (NAMs) strategy for hazard- risk-based...
The Korean National Environmental Health Survey (KoNEHS 2009-2011) tracks levels of environmental pollutants in biological samples from the adult population (age 19-88). Recent survey results for blood mercury (Hg) suggest some exceedance above existing Hg reference levels. Because total represents both organic and inorganic forms, methylmercury (MeHg) has been specifically linked to several adverse health outcomes, a need exists quantify MeHg intake this population. Gender, age, frequency...
There are many types of biomarkers; the two common ones biomarkers exposure and effect. The utility a biomarker for estimating exposures or predicting risks depends on strength correlation between concentrations exposure/effects. In current study, combined physiologically-based pharmacokinetic/pharmacodynamic (PBPK/PD) model carbaryl was used to demonstrate use computational modeling providing insight into selection different purposes. Cumulative Aggregate Risk Evaluation System (CARES)...
Introduction: Application of in vitro-to-in vivo extrapolation to chemical safety assessment has gained significant attention the past few years. Accurate prediction hepatic metabolic clearance from vitro data is critical this regard as it determines compound pharmacokinetics and exposure at sites action. To estimate clearance, intrinsic (CLint) typically measured using systems such primary hepatocytes or subcellular fractions derived liver tissues. However, currently available used these...
Computational technologies hold promise for informing decisions on the use of thousands chemicals in commerce that have little or no toxicological data. Threshold Toxicological Concern (TTC) groups compounds based outcome an established analysis chemical structure. Characterizations hazard representative within these can be used various decision contexts to evaluate risk present trace amounts food, drugs, and consumer products. Here, we introduce TTC calculations a 45,000-compound universe...