Expanded Systematic Evidence Map for Hundreds of Per- and Polyfluoroalkyl Substances (PFAS) and Comprehensive PFAS Human Health Dashboard.

Background: Per- and polyfluoroalkyl substances (PFAS) encompass a class of chemically and structurally diverse compounds that are extensively used in industry and detected in the environment. The US Environmental Protection Agency (US EPA) 2021 PFAS Strategic Roadmap describes national research plans to address the challenge of PFAS.

Objectives: Systematic Evidence Map (SEM) methods were used to survey and summarize available epidemiological and mammalian bioassay evidence that could inform human health hazard identification for a set of 345 PFAS that were identified by the US EPA's Center for Computational Toxicology and Exposure (CCTE) for toxicity and toxicokinetic assay testing and through interagency discussions on PFAS of interest.

Integrating climate model projections into environmental risk assessment: A probabilistic modeling approach.

The Society of Environmental Toxicology and Chemistry (SETAC) convened a Pellston workshop in 2022 to examine how information on climate change could be better incorporated into the ecological risk assessment (ERA) process for chemicals as well as other environmental stressors. A major impetus for this workshop is that climate change can affect components of ecological risks in multiple direct and indirect ways, including the use patterns and environmental exposure pathways of chemical stressors such as pesticides, the toxicity of chemicals in receiving environments, and the vulnerability of species of concern related to habitat quality and use. This article explores a modeling approach for integrating climate model projections into the assessment of near- and long-term ecological risks, developed in collaboration with climate scientists.

Phenol and Phthalate Effects on Thyroid Hormone Levels during Pregnancy: Relying on Assays and Adverse Outcome Pathways to Inform an Epidemiological Analysis.

Background: Studies characterizing associations between phenols, phthalates and thyroid hormones during pregnancy produce inconsistent results. This divergence may be partly attributable to false positives due to multiple comparison testing of large numbers of chemicals, and measurement error as studies rely on small numbers of biospecimens despite high intra-individual variability in urinary chemical metabolite concentrations.

Objectives: This study employs chemical filtering and expanded urinary biomonitoring to evaluate associations between phenol/phthalate exposures and serum thyroid hormones assessed during pregnancy.

Systematic Evidence Map for Over One Hundred and Fifty Per- and Polyfluoroalkyl Substances (PFAS).

Background: Per- and polyfluoroalkyl substances (PFAS) are a large class of synthetic (man-made) chemicals widely used in consumer products and industrial processes. Thousands of distinct PFAS exist in commerce. The 2019 U.

Application of evidence-based methods to construct mechanism-driven chemical assessment frameworks.

The workshop titled “Application of evidence-based methods to construct mechanism-driven chemical assessment frameworks” was co-organized by the Evidence-based Toxicology Collaboration and the European Food Safety Authority (EFSA) and hosted by EFSA at its headquarters in Parma, Italy on October 2 and 3, 2019. The goal was to explore integration of systematic review with mechanistic evidence evaluation. Participants were invited to work on concrete products to advance the exploration of how evidence-based approaches can support the development and application of adverse outcome pathways (AOP) in chemical risk assessment.

Evaluating Chemicals for Thyroid Disruption: Opportunities and Challenges with in Vitro Testing and Adverse Outcome Pathway Approaches.

Background: Extensive clinical and experimental research documents the potential for chemical disruption of thyroid hormone (TH) signaling through multiple molecular targets. Perturbation of TH signaling can lead to abnormal brain development, cognitive impairments, and other adverse outcomes in humans and wildlife. To increase chemical safety screening efficiency and reduce vertebrate animal testing, in vitro assays that identify chemical interactions with molecular targets of the thyroid system have been developed and implemented.

A Chemical Category-Based Prioritization Approach for Selecting 75 Per- and Polyfluoroalkyl Substances (PFAS) for Tiered Toxicity and Toxicokinetic Testing.

Per- and polyfluoroalkyl substances (PFASs) are a group of fluorinated substances of interest to researchers, regulators, and the public due to their widespread presence in the environment. A few PFASs have comparatively extensive amounts of human epidemiological, exposure, and experimental animal toxicity data (e.g.

Transcriptomic and phenotypic profiling in developing zebrafish exposed to thyroid hormone receptor agonists.

There continues to be a need to develop in vivo high-throughput screening (HTS) and computational methods to screen chemicals for interaction with the estrogen, androgen, and thyroid pathways and as complements to in vitro HTS assays. This study explored the utility of an embryonic zebrafish HTS approach to identify and classify endocrine bioactivity using phenotypically-anchored transcriptome profiling. Transcriptome analysis was conducted on zebrafish embryos exposed to 25 estrogen-, androgen-, or thyroid-active chemicals at concentrations that elicited adverse malformations or mortality at 120 h post-fertilization in 80% of animals exposed.

Application of Adverse Outcome Pathways to U.S. EPA's Endocrine Disruptor Screening Program.

Background: The U.S. EPA's Endocrine Disruptor Screening Program (EDSP) screens and tests environmental chemicals for potential effects in estrogen, androgen, and thyroid hormone pathways, and it is one of the only regulatory programs designed around chemical mode of action.

ZEBRAFISH AS AN IN VIVO MODEL FOR SUSTAINABLE CHEMICAL DESIGN.

Heightened public awareness about the many thousands of chemicals in use and present as persistent contaminants in the environment has increased the demand for safer chemicals and more rigorous toxicity testing. There is a growing recognition that the use of traditional test models and empirical approaches is impractical for screening for toxicity the many thousands of chemicals in the environment and the hundreds of new chemistries introduced each year. These realities coupled with the green chemistry movement have prompted efforts to implement more predictive-based approaches to evaluate chemical toxicity early in product development.

Phenotypically anchored transcriptome profiling of developmental exposure to the antimicrobial agent, triclosan, reveals hepatotoxicity in embryonic zebrafish.

Triclosan (TCS) is an antimicrobial agent commonly found in a variety of personal care products and cosmetics. TCS readily enters the environment through wastewater and is detected in human plasma, urine, and breast milk due to its widespread use. Studies have implicated TCS as a disruptor of thyroid and estrogen signaling; therefore, research examining the developmental effects of TCS is warranted.

Advancements in zebrafish applications for 21st century toxicology.

The zebrafish model is the only available high-throughput vertebrate assessment system, and it is uniquely suited for studies of in vivo cell biology. A sequenced and annotated genome has revealed a large degree of evolutionary conservation in comparison to the human genome. Due to our shared evolutionary history, the anatomical and physiological features of fish are highly homologous to humans, which facilitates studies relevant to human health.

Advanced morphological - behavioral test platform reveals neurodevelopmental defects in embryonic zebrafish exposed to comprehensive suite of halogenated and organophosphate flame retardants.

The increased use of flammable plastics and electronic devices along with stricter fire safety standards has led to the heavy use of flame retardant chemicals in many consumer, commercial, and industrial products. Although flame retardant use has increased, a great deal of uncertainty surrounds their safety with some evidence showing toxicity and risk to human and environmental health. Recent efforts have focused on designing high-throughput biological platforms with nonmammalian models to evaluate and prioritize chemicals with limited hazard information.

Rapid method for the measurement of circulating thyroid hormones in low volumes of teleost fish plasma by LC-ESI/MS/MS.

Thyroid hormones are critical regulators of normal development and physiological functioning in all vertebrates. Radioimmunoassay (RIA) approaches have been the method of choice for measuring circulating levels of thyroid hormones in vertebrates. While sensitive, RIA-based approaches only allow for a single analyte measurement per assay, can lack concordance across platforms and laboratories, and can be prone to analytical interferences especially when used with fish plasma.

Tissue distribution and thyroid hormone effects on mRNA abundance for membrane transporters Mct8, Mct10, and organic anion-transporting polypeptides (Oatps) in a teleost fish.

Many of the actions of thyroid hormones (THs) occur via TH binding to intracellular receptors. Although it was long thought that THs diffused passively across plasma membranes, it is now recognized that cellular entry is mediated by a variety of membrane transporter proteins. In this study, we identified cDNAs encoding the TH transporters monocarboxylate transferases 8 (mct8) and 10 (mct10) as well as eight distinct organic anion-transporting polypeptide (oatp) proteins from fathead minnow (Pimephales promelas).

Low level exposure to the flame retardant BDE-209 reduces thyroid hormone levels and disrupts thyroid signaling in fathead minnows.

Polybrominated diphenyl ether (PBDE) flame retardants have been shown to disrupt thyroid hormone regulation, neurodevelopment, and reproduction in some animals. However, effects of the most heavily used PBDE, decabromodiphenyl ether (BDE-209), on thyroid functioning remain unclear. This study examined low-dose effects of BDE-209 on thyroid hormone levels and signaling in fathead minnows.

Interactions between chemical and climate stressors: a role for mechanistic toxicology in assessing climate change risks.

Incorporation of global climate change (GCC) effects into assessments of chemical risk and injury requires integrated examinations of chemical and nonchemical stressors. Environmental variables altered by GCC (temperature, precipitation, salinity, pH) can influence the toxicokinetics of chemical absorption, distribution, metabolism, and excretion as well as toxicodynamic interactions between chemicals and target molecules. In addition, GCC challenges processes critical for coping with the external environment (water balance, thermoregulation, nutrition, and the immune, endocrine, and neurological systems), leaving organisms sensitive to even slight perturbations by chemicals when pushed to the limits of their physiological tolerance range.

Accumulation and debromination of decabromodiphenyl ether (BDE-209) in juvenile fathead minnows (Pimephales promelas) induces thyroid disruption and liver alterations.

Polybrominated diphenyl ether (PBDE) flame retardants are known to affect thyroid hormone (TH) regulation. The TH-regulating deiodinases have been implicated in these impacts; however, PBDE effects on the fish thyroid system are largely unknown. Moreover, the liver as a potential target of PBDE toxicity has not been explored in young fish.

Species-specific differences and structure-activity relationships in the debromination of PBDE congeners in three fish species.

Previous studies have suggested that there may be species-specific differences in the metabolism of polybrominated diphenyl ethers (PBDEs) among different fish species. In this study, we investigated the in vitro hepatic metabolism of eleven individual PBDE congeners (tri- through decaBDEs) in three different fish species: rainbow trout (Oncorhynchus mykiss), common carp (Cyprinus carpio), and Chinook salmon (O. tschwatcha).

Characterizing the in vitro hepatic biotransformation of the flame retardant BDE 99 by common carp.

Polybrominated diphenyl ethers (PBDEs) are a class of flame retardant chemicals known to biomagnify in aquatic foodwebs. However, significant biotransformation of some congeners via reductive dehalogenation has been observed during in vivo and in vitro laboratory exposures, particularly in fish models. Little information is available on the enzyme systems responsible for catalyzing this metabolic pathway in fish.

The toxicology of climate change: environmental contaminants in a warming world.

Climate change induced by anthropogenic warming of the earth's atmosphere is a daunting problem. This review examines one of the consequences of climate change that has only recently attracted attention: namely, the effects of climate change on the environmental distribution and toxicity of chemical pollutants. A review was undertaken of the scientific literature (original research articles, reviews, government and intergovernmental reports) focusing on the interactions of toxicants with the environmental parameters, temperature, precipitation, and salinity, as altered by climate change.

CYP1B1 knockdown does not alter synergistic developmental toxicity of polycyclic aromatic hydrocarbons in zebrafish (Danio rerio).

Polycyclic aromatic hydrocarbons (PAHs) are contaminants increasing in the environment largely due to burning of fossil fuels. Our previous work identified a synergistic toxicity interaction in zebrafish embryos occurring when PAHs that are agonists for the aryl hydrocarbon receptor (AHR) co-occur with PAHs that are CYP1A inhibitors. This toxicity is mediated by the AHR2, and morpholino knockdown of CYP1A exacerbated toxicity.