Article
Environmental Sciences
Zhiquan Liu, Huikang Lin, Yueyue Zheng, Yixuan Feng, Chaoli Shi, Ruoxin Zhu, Xingyao Shen, Yu Han, Hangjun Zhang, Yuchi Zhong
Summary: This study found that exposure to environmentally relevant concentrations of PFOA and PFOS had negative impacts on the immune system of black-spotted frogs. PFOS had a stronger effect on immune indicators compared to PFOA, and both chemicals activated the NF-Kappa B pathway, leading to immunotoxicity.
Article
Environmental Sciences
Jae-Hoon Hwang, Yuen Yee Li Sip, Keug Tae Kim, Gaehee Han, Kelsey L. Rodriguez, David W. Fox, Sajia Afrin, Alex Burnstine-Townley, Lei Zhai, Woo Hyoung Lee
Summary: The study showed that embedding nanoparticles on hydrogel fibers significantly improved the electrochemical oxidation of perfluoroalkyl substances, leading to higher charge transport rates and removal efficiencies.
Article
Biochemical Research Methods
Dong-Gyu Heo, Dong-Cheol Lee, Ye-Min Kwon, Mi-Ji Seol, Jun Sung Moon, Seung Min Chung, Ju-Hyun Kim
Summary: A high-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous analysis of PFOA and linear PFOS in human serum. Surrogate analytes C-13(8)-PFOA and C-13(8)-PFOS were used for quantification. A sensitive and selective sample preparation method combining solid-phase extraction and protein precipitation was developed and optimized. After validation, the method was successfully applied to evaluate the exposure levels of PFOA and linear PFOS in the Korean population.
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2022)
Article
Food Science & Technology
Geun-Hyoung Choi, Deuk-Yeong Lee, A-Reum Song, Bo-Yeon Moon, Jin-Hyo Kim
Summary: Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) are persistent organic pollutants that are prohibited from being produced and used. However, they can still be found in the agricultural environment and transferred to crops. A study was conducted to assess the residues of PFOA and PFOS in upland soil and cultivated root crops, as well as their potential risks to human health. The results showed low concentrations of PFOA and PFOS residues in the soil and crops, indicating low exposure and risk to humans.
APPLIED BIOLOGICAL CHEMISTRY
(2022)
Article
Environmental Sciences
Celine Breton, Kaitlyn Kessel, Ariel Robinson, Kainat Altaf, Eric S. Luth
Summary: This study investigated the effects of PFOA on development and reproduction using the roundworm Caenorhabditis elegans and compared it to PFOS exposure. The results showed that PFAS exposure did not significantly affect egg hatching but delayed population growth by slowing down larval development and reaching reproductive maturity.
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES
(2023)
Article
Environmental Sciences
Jacqueline Bangma, James McCord, Nathan Giffard, Kate Buckman, Jonathan Petali, Celia Chen, Daniel Amparo, Barbara Turpin, Glenn Morrison, Mark Strynar
Summary: While high-resolution MS is suitable for novel PFAS identification and quantification, low-resolution MS/MS is the more commonly used and affordable approach for routine PFAS monitoring. However, the interference of chemical compounds in the quantitative ion channel hinders the verification of PFPeA and PFBA on low-resolution instrumentation. Adjustments to analytical methods, such as altering LC conditions and using matched internal standards, are recommended to investigate and confirm PFBA and PFPeA detections in both biological and environmental samples.
Article
Toxicology
Fabrice A. Muller, Marianna Stamou, Felix H. Englert, Ole Frenzel, Sabine Diedrich, Laura Suter-Dick, John F. Wambaugh, Shana J. Sturla
Summary: In this study, a combination of in vitro and in silico models were used to identify chemicals that may induce lipid accumulation and hepatotoxicity. High-content imaging was used to quantify cellular markers in chemically exposed human liver cells, and extrapolation of human oral equivalent doses was performed using computational models. Known steatosis-inducing chemicals as well as food-related chemicals were characterized, and orotic acid was confirmed to induce hepatotoxicity.
ARCHIVES OF TOXICOLOGY
(2023)
Article
Chemistry, Medicinal
Marci Smeltz, John F. Wambaugh, Barbara A. Wetmore
Summary: New approaches using in vitro screening and in silico approaches, rely on in vitro toxicokinetic (TK) data to evaluate chemical substances. The evaluation of 71 PFAS compounds was conducted to understand their plasma protein binding (PPB) by ultracentrifugation with liquid chromatography-mass spectrometry analysis. Results showed that over half of the PFAS compounds had PPB exceeding 99.5%, and binding was lower for longer carbon chain length PFCAs. Bayesian modeling was used to provide uncertainty bounds for incorporation into TK modeling. This evaluation greatly expands our current knowledge and will aid in PFAS NAM development.
CHEMICAL RESEARCH IN TOXICOLOGY
(2023)
Article
Engineering, Environmental
Daniel L. Villeneuve, Brett R. Blackwell, Jenna E. Cavallin, Jacob Collins, John X. Hoang, Rachel N. Hofer, Keith A. Houck, Kathleen M. Jensen, Michael D. Kahl, Robin N. Kutsi, Anne S. Opseth, Kelvin J. Santana Rodriguez, Christopher Schaupp, Emma H. Stacy, Gerald T. Ankley
Summary: The effectiveness of previous in vitro screening for identifying PFAS capable of inducing estrogenic responses in fish exposed in vivo was evaluated. Exposure to different PFAS showed concentration-dependent increases in the expression of transcript coding for vitellogenin and estrogen receptor alpha, as well as reduced expression of insulin-like growth factor and apolipoprotein eb. The rank order of potency in vivo matched that determined in vitro, providing a benchmark for evaluating the potential estrogenic hazards of PFAS.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Zoe Li, Jie Liu, Fan Dong, Nancy Chang, Ruili Huang, Menghang Xia, Tucker A. Patterson, Huixiao Hong
Summary: The United States is facing a severe opioid crisis, with increasing numbers of deaths caused by both prescription and illegal opioids over the past two decades. Opioids are important for pain treatment but also highly addictive, making it difficult to combat this public health issue.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Toxicology
Drake W. Phelps, Anika I. Palekar, Haleigh E. Conley, Giuliano Ferrero, Jacob H. Driggers, Keith E. Linder, Seth W. Kullman, David M. Reif, M. Katie Sheats, Jamie C. DeWitt, Jeffrey A. Yoder
Summary: This report investigates the impact of nine environmentally-relevant PFASs on the respiratory burst, and finds that PFHxA and GenX can suppress the respiratory burst. The study demonstrates for the first time that these PFASs can suppress neutrophil function, and supports the use of zebrafish larvae and a human cell line as screening tools for identifying chemicals that may suppress human immune function.
JOURNAL OF IMMUNOTOXICOLOGY
(2023)
Article
Statistics & Probability
Bora Jin, David B. Dunson, Julia E. Rager, David M. Reif, Stephanie M. Engel, Amy H. Herring
Summary: We propose a Bayesian hierarchical framework to infer bioactivity of chemicals by assay endpoint combination, addressing the sparsity of toxicology data. Our approach borrows information across different chemicals and assay endpoints, allows out-of-sample prediction of activity, quantifies uncertainty of predicted activity, and adjusts for multiplicity in hypothesis testing. Furthermore, this study makes a novel attempt in toxicology to simultaneously model heteroscedastic errors and a nonparametric mean function, leading to a broader definition of activity suggested by toxicologists. Real application identifies chemicals most likely active for neurodevelopmental disorders and obesity.
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS
(2023)
Article
Toxicology
Krystal D. Taylor, Tracey L. Woodlief, Aya Ahmed, Qing Hu, Patrick C. Duncker, Jamie C. DeWitt
Summary: Perfluorooctanoic acid (PFOA) exposure affects B-cell subclasses and markers of their metabolism, hindering B-cell development and survival, but not activation of the remaining B cells.
TOXICOLOGICAL SCIENCES
(2023)
Review
Biochemical Research Methods
Jessie R. Chappel, Kaylie I. Kirkwood-Donelson, David M. Reif, Erin S. Baker
Summary: The goal of lipidomic studies is to provide a comprehensive characterization of cellular lipids and their changes in a specific sample. Recent research in lipidomics has revealed the diverse roles of lipids in cellular processes and their dynamic response to perturbations. However, the analysis of lipidomics data is challenging due to the size of the datasets and the correlated nature of lipid data. This review presents statistical approaches and bioinformatic tools commonly used to analyze lipidomic datasets, providing a framework for interpreting and contextualizing the results.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
Jessie R. Chappel, Mary E. King, Jonathon Fleming, Livia S. Eberlin, David M. Reif, Erin S. Baker
Summary: Mass spectrometry imaging (MSI) is popular for tissue-based diagnostics, but current statistical approaches often fail to visualize subtle molecular changes. To address this, researchers developed aggregated molecular phenotype (AMP) scores using ensemble machine learning. AMP scores can evaluate multiple features simultaneously and accurately distinguish phenotypes. When combined with spatial coordinates, AMP scores allow for visualization of tissue sections, highlighting their diagnostic utility.
ANALYTICAL CHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Liang Xu, Ru Chen, Jie Liu, Tucker A. Patterson, Huixiao Hong
Summary: The SARS-CoV-2 main protease plays a crucial role in viral replication and is a key target for COVID-19 drug development. A variety of inhibitors have been identified or designed to bind to the main protease. Analyzing over 550 3D structures of the main protease provides valuable insights into its role in polyprotein cleavage, alternative conformations during maturation, and ligand interactions. These structural features can facilitate the development of drugs targeting the SARS-CoV-2 main protease for COVID-19.
DRUG DISCOVERY TODAY
(2023)
Article
Environmental Sciences
Michael Cuffney, Adrien A. Wilkie, Nadine Kotlarz, Detlef Knappe, C. Suzanne Lea, David N. Collier, Jamie Dewitt, Jane A. Hoppin
Summary: The study found that drinking water is the primary source of serum PFAS concentrations among residents in New Hanover County. It also found that using home filters or other water sources for consuming municipal water is associated with lower PFAS concentrations compared to consuming untreated municipal water. Additionally, it observed higher levels of PFAS in males compared to females.
ENVIRONMENTAL RESEARCH
(2023)
Article
Engineering, Environmental
Dylan J. Wallis, Nadine Kotlarz, Detlef R. U. Knappe, David N. Collier, C. Suzanne Lea, David Reif, James McCord, Mark Strynar, Jamie C. DeWitt, Jane A. Hoppin
Summary: The GenX Exposure Study estimated the half-lives for novel fluoroethers and developed a model to predict PFAS half-lives based on structural properties. While certain properties can predict the half-lives of PFAS, further understanding is needed.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2023)
Article
Toxicology
Matthew Boyce, Kristin A. A. Favela, Jessica A. A. Bonzo, Alex Chao, Lucina E. E. Lizarraga, Laura R. R. Moody, Elizabeth O. O. Owens, Grace Patlewicz, Imran Shah, Jon R. R. Sobus, Russell S. S. Thomas, Antony J. J. Williams, Alice Yau, John F. F. Wambaugh
Summary: Understanding the metabolic fate of xenobiotic substances is important for assessing their health risks and identifying associated metabolites. Non-targeted analysis using high-resolution LCMS has become a popular method for characterizing metabolites of poorly studied or novel substances. In this study, suspect screening analysis using LCMS was evaluated for xenobiotic chemical metabolism. Thirty-three diverse chemicals were incubated with primary hepatocytes and analyzed using LCMS. Predictive tools were used to generate suspect screening lists of potential metabolites for each compound. The workflow was applied to several test chemicals, resulting in the identification of known and potential novel metabolites. This study demonstrates that suspect screening analysis can be a valuable tool for rapidly identifying and characterizing metabolites of xenobiotic chemicals.
FRONTIERS IN TOXICOLOGY
(2023)