Critical Membrane Concentration and Mass-Balance Model to Identify Baseline Cytotoxicity of Hydrophobic and Ionizable Organic Chemicals in Mammalian Cell Lines DOI
Jungeun Lee, Georg Braun, Luise Henneberger

и другие.

Chemical Research in Toxicology, Год журнала: 2021, Номер 34(9), С. 2100 - 2109

Опубликована: Авг. 6, 2021

All chemicals can interfere with cellular membranes and this leads to baseline toxicity, which is the minimal toxicity any chemical elicits. The critical membrane burden constant for all chemicals; that is, dosing concentrations trigger decrease increasing hydrophobicity of chemicals. Quantitative structure-activity relationships, based on chemicals, have been established predict nominal causing in human mammalian cell lines. However, their applicability limited hydrophilic neutral compounds. To develop a prediction model includes more hydrophobic charged organic mass balance was applied cells (AREc32, AhR-CALUX, PPARγ-BLA, SH-SY5Y) considering different bioassay conditions. converted into concentration 10% cytotoxicity by (IC10,baseline) using whose main input parameter liposome-water partition constants (Klip/w) or speciation-corrected Dlip/w(pH 7.4) ionizable plus bioassay-specific protein, lipid, water contents media. In these models, log(1/IC10,baseline) increased hydrophobicity, relationship started level off at log Dlip/w around 2. models were 392 covering broad range speciation. Comparing predicted IC10,baseline experimental IC10, known toxicants many additional identified as toxicants, while others classified specificity modes action four lines, confirming excess some fungicides, antibiotics, uncouplers. Given similarity we propose generalized baseline-model adherent lines: log[1/IC10,baseline (M)] = 1.23 + 4.97 × (1 - e-0.236 Dlip/w). derived may serve analysis reporter gene neurotoxicity assays well planning cell-based assays.

Язык: Английский

Tracking complex mixtures of chemicals in our changing environment DOI
Beate I. Escher, Heather M. Stapleton, Emma Schymanski

и другие.

Science, Год журнала: 2020, Номер 367(6476), С. 388 - 392

Опубликована: Янв. 24, 2020

Chemicals have improved our quality of life, but the resulting environmental pollution has potential to cause detrimental effects on humans and environment. People biota are chronically exposed thousands chemicals from various sources through multiple pathways. Environmental chemists toxicologists moved beyond detecting quantifying single characterizing complex mixtures in indoor outdoor environments biological matrices. We highlight analytical bioanalytical approaches isolating, characterizing, tracking groups concern Techniques that combine chemical analysis bioassays facilitate identification pose a combined risk.

Язык: Английский

Процитировано

586

Contributions of City-Specific Fine Particulate Matter (PM2.5) to Differential In Vitro Oxidative Stress and Toxicity Implications between Beijing and Guangzhou of China DOI
Ling Jin, Jiawen Xie, Chris K.C. Wong

и другие.

Environmental Science & Technology, Год журнала: 2019, Номер 53(5), С. 2881 - 2891

Опубликована: Фев. 7, 2019

Growing literature has documented varying toxic potencies of source- or site-specific fine particulate matter (PM2.5), as opposed to the practice that treats particle toxicities independent composition given incomplete understanding toxicity constituents. Quantifying component-specific contribution is key unlocking geographical disparities from a mixture perspective. In this study, we performed integrated mixture–toxicity experiments and modeling quantify metals polycyclic aromatic hydrocarbons (PAHs), two default culprit component groups PM2.5 toxicity, in vitro oxidative stress caused by wintertime Beijing Guangzhou, megacities China. exhibited greater at equal mass concentrations. The targeted chemical analysis revealed higher burden PAHs per unit Beijing. These chemicals together explained 38 24% on average PM2.5-induced reactive oxygen species respectively, while >60% effects remained be resolved terms contributing chemicals. contributed approximately twice share metals. Fe, Cu, Mn were dominant metals, constituting >80% metal-shared proportion effects. Dibenzo[a,l]pyrene alone >65% PAH-shared significant coal combustion vehicular emissions suggested major source toxicologically active between cities. Our study provided novel quantitative insights into role profiles shaping differential city-specific pollution.

Язык: Английский

Процитировано

153

Comprehensive characterization of tire and road wear particles in highway tunnel road dust by use of size and density fractionation DOI
Philipp Klöckner, Bettina Seiwert, Steffen Weyrauch

и другие.

Chemosphere, Год журнала: 2021, Номер 279, С. 130530 - 130530

Опубликована: Апрель 8, 2021

Язык: Английский

Процитировано

136

Neurotoxic Effects of Mixtures of Perfluoroalkyl Substances (PFAS) at Environmental and Human Blood Concentrations DOI Creative Commons

Karla M. Ríos-Bonilla,

Diana S. Aga, Jungeun Lee

и другие.

Environmental Science & Technology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 11, 2024

Per- and polyfluoroalkyl substances (PFAS) may cause various deleterious health effects. Epidemiological studies have demonstrated associations between PFAS exposure adverse neurodevelopmental outcomes. The cytotoxicity, neurotoxicity, mitochondrial toxicity of up to 12 including perfluoroalkyl carboxylates, sulfonates, 6:2 fluorotelomer sulfonic acid (6:2 FTSA), hexafluoropropylene oxide-dimer (HPFO-DA) were tested at concentrations typically observed in the environment (e.g., wastewater, biosolids) human blood using high-throughput

Язык: Английский

Процитировано

21

Systematic Review of Toxicity Removal by Advanced Wastewater Treatment Technologies via Ozonation and Activated Carbon DOI Creative Commons
Johannes Völker,

Michael Stapf,

Ulf Miehe

и другие.

Environmental Science & Technology, Год журнала: 2019, Номер 53(13), С. 7215 - 7233

Опубликована: Май 23, 2019

Upgrading wastewater treatment plants (WWTPs) with advanced technologies is one key strategy to reduce micropollutant emissions. Given the complex chemical composition of wastewater, toxicity removal an integral parameter assess performance WWTPs. Thus, goal this systematic review evaluate how effectively ozonation and activated carbon remove in vitro vivo toxicity. Out 2464 publications, we extracted 46 relevant studies conducted at 22 pilot or full-scale We performed a quantitative qualitative evaluation (100 assays) data (20 species), respectively. Data more abundant on (573 points) than (162 points), certain end points (especially estrogenicity) models (e.g., daphnids) dominate. The literature shows that while conventional reduces toxicity, residual effects effluents may represent risk receiving ecosystem basis effect-based trigger values. In general, upgrade will significantly increase similar performance. Nevertheless, generates toxic transformation products can be removed by post-treatment. By assessing growing body studies, identify sensitive underrepresented species provide guidance for future research.

Язык: Английский

Процитировано

147

Effects of Leachates from UV-Weathered Microplastic in Cell-Based Bioassays DOI Creative Commons
Christoph Rummel, Beate I. Escher,

Oskar Sandblom

и другие.

Environmental Science & Technology, Год журнала: 2019, Номер 53(15), С. 9214 - 9223

Опубликована: Июнь 30, 2019

Standard ecotoxicological testing of microplastic does not provide insight into the influence that environmental weathering by, e.g., UV light has on related effects. In this study, we leached chemicals from plastic artificial seawater during simulated UV-induced weathering. We tested largely additive-free preproduction polyethylene, polyethylene terephthalate, polypropylene, and polystyrene two types obtained electronic equipment as positive controls. Leachates were concentrated by solid-phase extraction dosed cell-based bioassays cover (i) cytotoxicity; (ii) activation metabolic enzymes via binding to arylhydrocarbon receptor (AhR) peroxisome proliferator-activated (PPARγ); (iii) specific, receptor-mediated effects (estrogenicity, ERα); (iv) adaptive response oxidative stress (AREc32). LC-HRMS analysis was used identify possible chain-scission products polymer degradation, which then in AREc32 PPARγ. Explicit all assays controls provided proof-of-concept experimental setup demonstrate liberated All leachates activated response, most cases with increased induction UV-treated samples compared dark For PPARγ, polyethylene-specific partially explained detected dicarboxylic acids. Since showed low often range blanks future studies should investigate implications end consumer containing additives.

Язык: Английский

Процитировано

118

Maternal paraben exposure triggers childhood overweight development DOI Creative Commons
Beate Leppert,

Sandra Strunz,

Bettina Seiwert

и другие.

Nature Communications, Год журнала: 2020, Номер 11(1)

Опубликована: Фев. 11, 2020

Abstract Parabens are preservatives widely used in consumer products including cosmetics and food. Whether low-dose paraben exposure may cause adverse health effects has been discussed controversially recent years. Here we investigate the effect of prenatal on childhood overweight by combining epidemiological data from a mother–child cohort with experimental approaches. Mothers reporting use paraben-containing cosmetic have elevated urinary concentrations. For butyl (BuP) positive association is observed to within first eight years life stronger trend girls. Consistently, maternal BuP mice induces higher food intake weight gain female offspring. The accompanied an epigenetic modification neuronal Pro-opiomelanocortin (POMC) enhancer 1 leading reduced hypothalamic POMC expression. report that contribute development altered POMC-mediated appetite regulation.

Язык: Английский

Процитировано

115

Assessing the Mixture Effects in In Vitro Bioassays of Chemicals Occurring in Small Agricultural Streams during Rain Events DOI
Peta A. Neale, Georg Braun, Werner Brack

и другие.

Environmental Science & Technology, Год журнала: 2020, Номер 54(13), С. 8280 - 8290

Опубликована: Июнь 5, 2020

Rain events may impact the chemical pollution burden in rivers. Forty-four small streams Germany were profiled during several rain for presence of 395 chemicals and five types mixture effects vitro bioassays (cytotoxicity; activation estrogen, aryl hydrocarbon, peroxisome proliferator-activated receptors; oxidative stress response). While these selected to cover a wide range agricultural impacts, addition expected pesticides, wastewater-derived typical street runoff detected. The unexpectedly high estrogenic many samples indicated by wastewater or overflow combined sewer systems. 128 water exhibited diversity effect patterns, even different at same site. detected 290 explained only fraction (<8%) measured effects. experimental designed mixtures that dominate consistent with predictions concentration within factor two 94% mixtures. Overall, was much higher than previously surface dry weather, often exceeding proposed effect-based trigger values.

Язык: Английский

Процитировано

90

Cytotoxicity Burst? Differentiating Specific from Nonspecific Effects in Tox21 in Vitro Reporter Gene Assays DOI Creative Commons
Beate I. Escher, Luise Henneberger, Maria König

и другие.

Environmental Health Perspectives, Год журнала: 2020, Номер 128(7)

Опубликована: Июль 1, 2020

High-throughput screening of chemicals with in vitro reporter gene assays Tox21 has produced a large database on cytotoxicity and specific modes action. However, the validity some reported activities is questionable due to "cytotoxicity burst," which refers supposition that many stress responses are activated nonspecific way at concentrations close cell death.We propose pragmatic method identify whether activation or cytotoxicity-triggered by comparing measured effects baseline toxicity.Baseline toxicity, also termed narcosis, minimal toxicity any chemical causes. Quantitative structure-activity relationships (QSARs) developed for mammalian lines served as anchors define chemical-specific threshold burst evaluate degree specificity activation. Measured 10% effect were related QSAR-predicted yielding ratios (SR). We applied this approach our own experimental data ∼8,000 tested six high-throughput assays.Confirmed toxicants activity around cytotoxic triggered burst. In assays, 37%-87% active hits presumably caused (SR<1) only 2%-14% SR≥10 against but 75%-97% toxicity. This difference was fraction showing excess cytotoxicity.The analysis identified had likely occurred. The SR-analysis not prevented false positives, it may serve measure relative potency can be used quantitative vitro-in vivo extrapolation risk assessment chemicals. https://doi.org/10.1289/EHP6664.

Язык: Английский

Процитировано

85

Introduction to the Use of Linear and Nonlinear Regression Analysis in Quantitative Biological Assays DOI Creative Commons

Stephen Jarantow,

Eileen D. Pisors,

Mark L. Chiu

и другие.

Current Protocols, Год журнала: 2023, Номер 3(6)

Опубликована: Июнь 1, 2023

Abstract Biological assays are essential tools in biomedical and pharmaceutical research. In simplest terms, such an assay is analytical method used to measure or predict a response biological system the presence of given stimulus (e.g., drug). The inherent complexity involved evaluating requires use rigorous appropriate for data analysis. Linear nonlinear regression models represent critically important statistical analyses define relationships between variables interest systems. Recent challenges relating reproducibility published suggest absence standardized routine statistics support experimental results across wide range scientific disciplines. current situation warrants introductory review basic concepts using current, practical examples, along with references in‐depth resources. goal provide necessary information help standardize analysis academic research drug discovery development, elevating their utility increasing transparency reproducibility. © 2023 Authors. Current Protocols by Wiley Periodicals LLC.

Язык: Английский

Процитировано

38