Simultaneous toxicokinetic studies of aristolochic acid I and II and aristolactam I and II using a newly-developed microdialysis liquid chromatography-tandem mass spectrometry.

Aristolochic acids (AAs) are naturally occurring genotoxic carcinogens linked to Balkan endemic nephropathy and aristolochic acid nephropathy. Aristolochic acid I and II (AA-I and AA-II) are the most abundant AAs, and AA-I has been reported to be more genotoxic and nephrotoxic than AA-II. This study aimed to explore metabolic differences underlying the differential toxicity.

Unseen Risk: Mapping Contamination Hazards to Enhance Risk Perception in Galena Park, Texas.

As extreme weather events have become more frequently observed in recent decades, concerns about exposure to potential flood risk have increased, especially in underserved and socially vulnerable communities. Galena Park, Texas, is a socially vulnerable community that also confronts escalated physical vulnerabilities due to existing flood risks from Buffalo Bayou and the Houston Ship Channel as well as proximity to industrial facilities that emit chemical pollution. To better understand the underlying risks that Galena Park is facing, this research assesses and visualizes the existing contamination hazards associated with the chemical facilities within Galena Park.

Quantitative Characterization of Population-Wide Tissue- and Metabolite-Specific Variability in Perchloroethylene Toxicokinetics in Male Mice.

Quantification of interindividual variability is a continuing challenge in risk assessment, particularly for compounds with complex metabolism and multi-organ toxicity. Toxicokinetic variability for perchloroethylene (perc) was previously characterized across 3 mouse strains and in 1 mouse strain with various degrees of liver steatosis. To further characterize the role of genetic variability in toxicokinetics of perc, we applied Bayesian population physiologically based pharmacokinetic (PBPK) modeling to the data on perc and metabolites in blood/plasma and tissues of male mice from 45 inbred strains from the Collaborative Cross (CC) mouse population.

PBPK modeling of impact of nonalcoholic fatty liver disease on toxicokinetics of perchloroethylene in mice.

Background: Nonalcoholic fatty liver disease (NAFLD), a major cause of chronic liver disease in the Western countries with increasing prevalence worldwide, may substantially affect chemical toxicokinetics and thereby modulate chemical toxicity.

Objectives: This study aims to use physiologically-based pharmacokinetic (PBPK) modeling to characterize the impact of NAFLD on toxicokinetics of perchloroethylene (perc).

Methods: Quantitative measures of physiological and biochemical changes associated with the presence of NAFLD induced by high-fat or methionine/choline-deficient diets in C57B1/6 J mice are incorporated into a previously developed PBPK model for perc and its oxidative and conjugative metabolites.

Predicting tubular reabsorption with a human kidney proximal tubule tissue-on-a-chip and physiologically-based modeling.

Kidney is a major route of xenobiotic excretion, but the accuracy of preclinical data for predicting in vivo clearance is limited by species differences and non-physiologic 2D culture conditions. Microphysiological systems can potentially increase predictive accuracy due to their more realistic 3D environment and incorporation of dynamic flow. We used a renal proximal tubule microphysiological device to predict renal reabsorption of five compounds: creatinine (negative control), perfluorooctanoic acid (positive control), cisplatin, gentamicin, and cadmium.

Montmorillonites Can Tightly Bind Glyphosate and Paraquat Reducing Toxin Exposures and Toxicity.

Among the numerous contaminants of soil, glyphosate and paraquat are two of the most widely used herbicides that are commonly detected in the environment. Soil and sediment contaminated with glyphosate, paraquat, and other environmental toxins can be mobilized and redistributed to lawns, vegetable gardens, parks, and water supplies in vulnerable communities at the site of disasters such as hurricanes and flooding. Glyphosate and paraquat bind strongly to soils containing clays, making their bioavailability (bioaccessibility) from these types of soil very low.

Thorough QT/QTc in a Dish: An In Vitro Human Model That Accurately Predicts Clinical Concentration-QTc Relationships.

"Thorough QT/corrected QT (QTc)" (TQT) studies are cornerstones of clinical cardiovascular safety assessment. However, TQT studies are resource intensive, and preclinical models predictive of the threshold of regulatory concern are lacking. We hypothesized that an in vitro model using induced pluripotent stem cell (iPSC)-derived cardiomyocytes from a diverse sample of human subjects can serve as a "TQT study in a dish.

A human population-based organotypic in vitro model for cardiotoxicity screening.

Assessing inter-individual variability in responses to xenobiotics remains a substantial challenge, both in drug development with respect to pharmaceuticals and in public health with respect to environmental chemicals. Although approaches exist to characterize pharmacokinetic variability, there are no methods to routinely address pharmacodynamic variability. In this study, we aimed to demonstrate the feasibility of characterizing inter-individual variability in a human in vitro model.

Beyond the RfD: Broad Application of a Probabilistic Approach to Improve Chemical Dose-Response Assessments for Noncancer Effects.

Background: The National Academies recommended risk assessments redefine the traditional noncancer Reference Dose (RfD) as a probabilistically derived risk-specific dose, a framework for which was recently developed by the World Health Organization (WHO).

Objectives: Our aim was to assess the feasibility and implications of replacing traditional RfDs with probabilistic estimates of the human dose associated with an effect magnitude M and population incidence I (HDI).

Methods: We created a comprehensive, curated database of RfDs derived from animal data and developed a standardized, automated, web-accessible probabilistic dose-response workflow implementing the WHO framework.

Incorporation of the glutathione conjugation pathway in an updated physiologically-based pharmacokinetic model for perchloroethylene in mice.

Background: Perchloroethylene (perc) induced target organ toxicity has been associated with tissue-specific metabolic pathways. Previous physiologically-based pharmacokinetic (PBPK) modeling of perc accurately predicted oxidative metabolites but suggested the need to better characterize glutathione (GSH) conjugation as well as toxicokinetic uncertainty and variability.

Objectives: We updated the previously published "harmonized" perc PBPK model in mice to better characterize GSH conjugation metabolism as well as the uncertainty and variability of perc toxicokinetics.

Probabilistic risk assessment of exposure to leucomalachite green residues from fish products.

To assess the potential risk of human exposure to carcinogenic leucomalachite green (LMG) due to fish consumption, the probabilistic risk assessment was conducted for adolescent, adult and senior adult consumers in Taiwan. The residues of LMG with the mean concentration of 13.378±20.

River water contaminated with perfluorinated compounds potentially posing the greatest risk to young children.

Although, humans are exposed to perflourinated compounds (PFCs) from various media, water consumption could be an important source for the residents living near to contaminated areas. Since comprehensive multimedia exposure model has not been developed for PFCs, assessment of the potential risk due to exposure to PFCs through direct water consumption could be a conservative estimate. The human health risks derived from the exposure to PFCs through water consumption were assessed for different age groups of general population in Taiwan using probabilistic approach.

Poverty and household food insecurity in Mongolia.

This study was designed to review the food security of the country and to study the household food insecurity of poor households in relation to the poverty level. Cross-sectional survey design was used to assess the perceptions of socio-economic changes, food insecurity in national and household levels, and their health impact. A total of 731 poor households were involved in our study.

A study of the quality and hygienic conditions of spring water in Mongolia.

Unlabelled: An assessment on quality and hygienic conditions of spring water was undertaken in Mongolia in 2004 with financial and technical support from the World Health Organization through AGFUND.

Methodology: A total of 127 springs, 99 from rural areas and 28 from Ulaanbaatar city were included in the study. The study included hygienic conditions, physical, microbiological and chemical parameters of springs.