4.5 Article

Per- and polyfluoroalkyl substances (PFAS) in mixtures show additive effects on transcriptomic points of departure in human liver spheroids

Related references

Note: Only part of the references are listed.
Review Public, Environmental & Occupational Health

Historical and current usage of per- and polyfluoroalkyl substances (PFAS): A literature review

Linda G. T. Gaines

Summary: This study extensively researched publicly available sources to summarize the wide range of applications of PFAS, providing more details to understand which industries and occupations may lead to potential exposure for workers and the environment.

AMERICAN JOURNAL OF INDUSTRIAL MEDICINE (2023)

Article Toxicology

In vitro transcriptomic analyses reveal pathway perturbations, estrogenic activities, and potencies of data-poor BPA alternative chemicals

Geronimo Matteo et al.

Summary: Since 2010, BPA has been replaced by alternative chemicals in Canada. However, many of these chemicals lack sufficient data for toxicological risk assessment. In this study, high-throughput transcriptomics was used to assess the hazards of BPA and 15 alternative chemicals in breast cancer cells. The results indicate that several BPA alternative chemicals may cause similar hazards at similar concentrations to BPA, highlighting the importance of transcriptomic profiling for risk assessment of data-poor chemicals.

TOXICOLOGICAL SCIENCES (2023)

Article Pharmacology & Pharmacy

Targeted Per- and Polyfluoroalkyl substances (PFAS) assessments for high throughput screening: Analytical and testing considerations to inform a PFAS stock quality evaluation framework

Marci G. Smeltz et al.

Summary: To accelerate the evaluation of PFAS, a high-throughput framework was developed to assess the quality of screening stocks for 205 selected PFAS. A quality scoring system was created using mass spectrometry coupled with chromatography, providing a pass or fail notation based on observations during mass spectral examination. Results showed that 148 PFAS passed the quality assessment and could proceed to in vitro testing, while 57 PFAS scored failing primarily due to detection issues or confounding effects of the diluent (DMSO).

TOXICOLOGY AND APPLIED PHARMACOLOGY (2023)

Article Environmental Sciences

A proposed approach to defining per- and polyfluoroalkyl substances (PFAS) based on molecular structure and formula

Linda G. T. Gaines et al.

Summary: This study proposes a new definition for addressing per- and polyfluoroalkyl substances (PFAS), aiming to address the issues arising from the various previous definitions. The new definition is based on fractional fluorination, combining both structure-based and fraction-based definitions for a more inclusive and concise definition.

INTEGRATED ENVIRONMENTAL ASSESSMENT AND MANAGEMENT (2023)

Article Environmental Sciences

A proposed approach to defining per- and polyfluoroalkyl substances (PFAS) based on molecular structure and formula

Linda G. T. Gaines et al.

Summary: This work proposes a narrow and simple definition of PFAS to facilitate communication among different groups and prioritize substances that pose real environmental concerns. The new definition is based on four substructures and any structures where the molecular formula contains 30% fluorine by atom count.

INTEGRATED ENVIRONMENTAL ASSESSMENT AND MANAGEMENT (2023)

Article Engineering, Environmental

Combined effects of mixed per- and polyfluoroalkyl substances on the Nrf2-ARE pathway in ARE reporter-HepG2 cells

Atinuke F. Ojo et al.

Summary: This study investigated the effects of PFAS mixtures on the Nrf2-ARE pathway, revealing that PFAS mixtures can induce the Nrf2-ARE pathway in ARE reporter-HepG2 cells, with synergistic effects observed with co-exposure to PFOS and additive effects with PFOA co-exposure. The concentration addition (CA) model may underestimate the mixture toxicity of PFAS with PFOS co-exposures, potentially impacting health risk assessments.

JOURNAL OF HAZARDOUS MATERIALS (2022)

Article Gastroenterology & Hepatology

Exposure to environmental contaminants is associated with altered hepatic lipid metabolism in non-alcoholic fatty liver disease

Partho Sen et al.

Summary: This study reveals that exposure to specific environmental contaminants like PFAS affects metabolic processes associated with NAFLD, and females may be more susceptible to the harmful impacts of PFAS.

JOURNAL OF HEPATOLOGY (2022)

Review Environmental Sciences

Exposure to per- and Polyfluoroalkyl Substances and Markers of Liver Injury: A Systematic Review and Meta-Analysis

Elizabeth Costello et al.

Summary: This study conducted a systematic review and meta-analysis to evaluate the evidence of liver injury related to PFAS exposure. The results showed that PFAS exposure in rodents consistently resulted in higher ALT levels and steatosis, while in human studies, PFAS exposure was associated with elevated ALT levels.

ENVIRONMENTAL HEALTH PERSPECTIVES (2022)

Article Medicine, Legal

R-ODAF: Omics data analysis framework for regulatory application

Marcha C. T. Verheijen et al.

Summary: Despite the widespread use of transcriptomics technologies in toxicology research, the acceptance of the data for regulatory purposes is limited due to the lack of reproducibility and differences in data processing. To address this issue and enhance the credibility of the data, we propose a user-friendly pipeline called R-ODAF for analyzing raw transcriptomics data and also provide additional statistical steps to remove false positives.

REGULATORY TOXICOLOGY AND PHARMACOLOGY (2022)

Article Engineering, Environmental

Characterizing Variability and Uncertainty Associated with Transcriptomic Dose-Response Modeling

Jessica D. Ewald et al.

Summary: Transcriptomics dose-response analysis (TDRA) is a promising approach for integrating toxicogenomics data into risk assessment. This study evaluated the variability and uncertainty associated with experimental design in TDRA. The results showed that the selection of dose range and spacing is more important than the number of replicates, and tPOD values should be interpreted as order-of-magnitude estimates.

ENVIRONMENTAL SCIENCE & TECHNOLOGY (2022)

Article Toxicology

A Transformative Vision for an Omics-Based Regulatory Chemical Testing Paradigm

Kamin J. Johnson et al.

Summary: This paper proposes a logic framework for using transcriptomic methods to refine and replace current toxicity testing paradigms. Four foundational principles are outlined and discussed. If substantiated, these principles will significantly reduce animal use while protecting human health, and have general applicability in the assessment of industrial chemicals and agrochemicals.

TOXICOLOGICAL SCIENCES (2022)

Article Environmental Sciences

Cumulative maternal and neonatal effects of combined exposure to a mixture of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) during pregnancy in the Sprague-Dawley rat

Justin M. Conley et al.

Summary: The study demonstrates cumulative effects from combined exposure to PFOA and PFOS on shared endpoints, and dose addition approaches accurately predict mixture effects.

ENVIRONMENT INTERNATIONAL (2022)

Review Environmental Sciences

Per- and Polyfluoroalkyl Substance Toxicity and Human Health Review: Current State of Knowledge and Strategies for Informing Future Research

Suzanne E. Fenton et al.

Summary: Reports on the impacts of per- and polyfluoroalkyl substances (PFAS) on the environment and human health have increased substantially in peer-reviewed literature. Epidemiological studies have shown associations between exposure to specific PFAS and various health effects, and further research is needed to understand differences in responses between sexes, species, and life stages. More contemporary approaches such as read-across, molecular dynamics, and protein modeling are proposed to accelerate the development of toxicity information on PFAS, as well as the need for precaution to protect human health given the known effects of certain PFAS compounds.

ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY (2021)

Review Environmental Sciences

Ten years of research on synergisms and antagonisms in chemical mixtures: A systematic review and quantitative reappraisal of mixture studies

Olwenn Martin et al.

Summary: This study conducted a systematic review and quantitative reassessment of experimental mixture studies over the past 10 years, finding that approximately one quarter of studies claimed synergistic or antagonistic effects, while another quarter arrived at different evaluations. Although the majority of studies did not exceed acceptable between-study variability, and observed mixture doses were usually within two-fold higher or lower than predicted additive doses, there were still relatively few cases of synergistic or antagonistic effects that stood up to scrutiny.

ENVIRONMENT INTERNATIONAL (2021)

Article Toxicology

High-Throughput Transcriptomics Platform for Screening Environmental Chemicals

Joshua A. Harrill et al.

Summary: This study evaluated the TempO-Seq assay for HTTr concentration-response screening of chemicals in the human-derived MCF7 cell model. A robust bioinformatics pipeline was developed using open-source tools, along with a novel gene expression signature-based concentration-response modeling approach. Analysis showed highly reproducible differential gene expression signatures, along with in vitro transcriptional biological pathway altering concentrations closely aligned with previous high-throughput screening assays.

TOXICOLOGICAL SCIENCES (2021)

Review Toxicology

Systemic PFOS and PFOA exposure and disturbed lipid homeostasis in humans: what do we know and what not?

Styliani S. Fragki et al.

Summary: The association between PFOS/PFOA and increased blood lipids in humans has been observed, while rodent studies show opposite effects, likely due to different exposure levels. Mechanistic research suggests that PFOS/PFOA activate the PPAR alpha pathway in human liver cells, but the involvement of other nuclear receptors is less clear. Future studies focusing on human-relevant test systems are needed to better understand the implications of PFOS/PFOA exposure on lipid homeostasis and human health.

CRITICAL REVIEWS IN TOXICOLOGY (2021)

Article Toxicology

High-Throughput Transcriptomic Analysis of Human Primary Hepatocyte Spheroids Exposed to Per- and Polyfluoroalkyl Substances as a Platform for Relative Potency Characterization

Andrea Rowan-Carroll et al.

Summary: This study focused on four model PFAS and found that they may have common molecular targets and toxicities, with PFOS and PFDS being the most similar. The data from the study provide baseline toxicity levels for comparison with other known PFAS.

TOXICOLOGICAL SCIENCES (2021)

Article Toxicology

Potency Ranking of Per- and Polyfluoroalkyl Substances Using High-Throughput Transcriptomic Analysis of Human Liver Spheroids

Anthony J. F. Reardon et al.

Summary: This study aimed to compare the potencies of different PFAS in human liver microtissues, with findings suggesting that longer-chain PFAS are more likely to induce gene expression changes and have lower transcriptional BMCs. The high-throughput transcriptomic and bioinformatic analyses support the efficiency of NAMs in assessing the effects of PFAS. These findings improve understanding of PFAS health effects and will aid in human health risk assessment read-across.

TOXICOLOGICAL SCIENCES (2021)

Article Public, Environmental & Occupational Health

A Modern Genotoxicity Testing Paradigm: Integration of the High-Throughput CometChip® and the TGx-DDI Transcriptomic Biomarker in Human HepaRG™ Cell Cultures

Julie K. Buick et al.

Summary: In this study, a combination of high-throughput alkaline DNA damage-sensing CometChip(R) assay and TGx-DDI transcriptomic biomarker was used to evaluate genotoxicity of chemicals in HepaRG (TM) cell cultures. The results demonstrated that these two assays can be integrated for efficient identification and potency ranking of DNA damaging agents. The BMCs for the CometChip(R) assay and the TGx-DDI biomarker were highly concordant and resulted in identical potency rankings, showcasing the accuracy and efficacy of this integrated approach.

FRONTIERS IN PUBLIC HEALTH (2021)

Article Toxicology

Activation of human nuclear receptors by perfluoroalkylated substances (PFAS)

Anne-Cathrin Behr et al.

TOXICOLOGY IN VITRO (2020)

Article Environmental Sciences

Risk Assessment of Per- and Polyfluoroalkyl Substance Mixtures: A Relative Potency Factor Approach

Wieneke Bil et al.

ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY (2020)

Article Biochemical Research Methods

BMDExpress 2: enhanced transcriptomic dose-response analysis workflow

Jason R. Phillips et al.

BIOINFORMATICS (2019)

Article Public, Environmental & Occupational Health

Selective Associations of Recent Low Concentrations of Perfluoroalkyl Substances With Liver Function Biomarkers NHANES 2011 to 2014 Data on US Adults Aged >= 20 Years

Ram B. Jain et al.

JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE (2019)

Article Chemistry, Medicinal

Accelerating the Pace of Chemical Risk Assessment

Robert J. Kavlock et al.

CHEMICAL RESEARCH IN TOXICOLOGY (2018)

Article Environmental Sciences

Changes in markers of liver function in relation to changes in perfluoroalkyl substances - A longitudinal study

Samira Salihovic et al.

ENVIRONMENT INTERNATIONAL (2018)

Editorial Material Multidisciplinary Sciences

Regulate to reduce chemical mixture risk

Andreas Kortenkamp et al.

SCIENCE (2018)

Article Food Science & Technology

Toxic effects of perfluorinated compounds at human cellular level and on a model vertebrate

Sandra Rainieri et al.

FOOD AND CHEMICAL TOXICOLOGY (2017)

Article Environmental Sciences

The association between PFOA, PFOS and serum lipid levels in adolescents

Sarah Dee Geiger et al.

CHEMOSPHERE (2014)

Article Biotechnology & Applied Microbiology

Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

Michael I. Love et al.

GENOME BIOLOGY (2014)

Article Environmental Sciences

Combined Effects of PFOS and PFOA on Zebrafish (Danio rerio) Embryos

Guanghui Ding et al.

ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY (2013)

Article Environmental Sciences

Perfluorinated compounds affect the function of sex hormone receptors

Lisbeth Stigaard Kjeldsen et al.

ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH (2013)

Article Pharmacology & Pharmacy

Testing for departures from additivity in mixtures of perfluoroalkyl acids (PFAAs)

Caroline K. Carr et al.

TOXICOLOGY (2013)

Article Environmental Sciences

Dietary exposure to perfluoroalkyl acids for the Swedish population in 1999, 2005 and 2010

Robin Vestergren et al.

ENVIRONMENT INTERNATIONAL (2012)

Article Engineering, Environmental

Indoor Sources of Poly- and Perfluorinated Compounds (PFCS) in Vancouver, Canada: Implications for Human Exposure

Mahiba Shoeib et al.

ENVIRONMENTAL SCIENCE & TECHNOLOGY (2011)

Article Public, Environmental & Occupational Health

Association of Perfluorooctanoic Acid and Perfluorooctane Sulfonate With Serum Lipids Among Adults Living Near a Chemical Plant

Kyle Steenland et al.

AMERICAN JOURNAL OF EPIDEMIOLOGY (2009)

Article Engineering, Environmental

Exposure of an adult population to perfluorinated substances using duplicate diet portions and biomonitoring data

Hermann Fromme et al.

ENVIRONMENTAL SCIENCE & TECHNOLOGY (2007)

Article Biotechnology & Applied Microbiology

BMDExpress: a software tool for the benchmark dose analyses of genomic data

Longlong Yang et al.

BMC GENOMICS (2007)

Article Engineering, Environmental

A global mass balance analysis of the source of perfluorocarboxylic acids in the Arctic ocean

Frank Wania

ENVIRONMENTAL SCIENCE & TECHNOLOGY (2007)

Article Environmental Sciences

How Well Can We Predict the Toxicity of Pesticide Mixtures to Aquatic Life?

Jason B. Belden et al.

INTEGRATED ENVIRONMENTAL ASSESSMENT AND MANAGEMENT (2007)

Article Engineering, Environmental

Global distribution of perfluorooctane sulfonate in wildlife

JP Giesy et al.

ENVIRONMENTAL SCIENCE & TECHNOLOGY (2001)

Article Engineering, Environmental

Compound-specific, quantitative characterization of organic: Fluorochemicals in biological matrices

KJ Hansen et al.

ENVIRONMENTAL SCIENCE & TECHNOLOGY (2001)

Article Environmental Sciences

Predictability of the toxicity of a multiple mixture of dissimilarly acting chemicals to Vibrio fischeri

T Backhaus et al.

ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY (2000)

Article Environmental Sciences

Predictability of the toxicity of multiple chemical mixtures to Vibrio fischeri:: Mixtures composed of similarly acting chemicals

R Altenburger et al.

ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY (2000)