Investigation of Peroxisome Proliferator-Activated Receptor Genes as Requirements for Visual Startle Response Hyperactivity in Larval Zebrafish Exposed to Structurally Similar Per- and Polyfluoroalkyl Substances (PFAS)

Gutsfeld, Sebastian; Wehmas, Leah; Omoyeni, Ifeoluwa; Schweiger, Nicole; Leuthold, David; Michaelis, Paul; Howey, Xia Meng; Gaballah, Shaza; Herold, Nadia; Vogs, Carolina; Wood, Carmen; Bertotto, Luísa; Wu, Gi-Mick; Klüver, Nils; Busch, Wibke; Scholz, Stefan; Schor, Jana; Tal, Tamara

doi:10.1289/ehp13667

Cited by 3 publications

References 108 publications

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Effects of organic and inorganic contaminants and their mixtures on metabolic health and gene expression in developmentally exposed zebrafish

Bérubé,

LeFauve,

Khalaf

et al. 2024

Preprint

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Organic and inorganic chemicals co-occur in household dust, and these chemicals have been determined to have endocrine and metabolic disrupting effects. While there is increasing study of chemical mixtures, the effects of complex mixtures mimicking household dust and other environmental matrices have not been well studied and their potential metabolism disrupting effects are thus poorly understood. Previous research has demonstrated high potency adipogenic effects of residential household dust extracts using in vitro adipogenesis assays. More recent research simplified this to a mixture relevant to household dust and comprised of common co-occurring organic and inorganic contaminants, finding that these complex combinations often exhibited additive or even synergistic effects in cell models. This study aimed to translate our previous in vitro observation to an in vivo model, the developing zebrafish, to evaluate the metabolic effects of early exposure to organic and inorganic chemicals, individually and in mixtures. Zebrafish embryos were exposed from 1 day post fertilization (dpf) to 6 dpf, then metabolic energy expenditure, swimming behavior and gene expression were measured. Globally, we observed that most mixtures did not reflect the effects of individual chemicals; the BFR mixture produced a less potent effect when compared to the individual chemicals, while the PFAS and the inorganic mixtures seemed to have a more potent effect than the individual chemicals. Finally, the environmental mixture, mimicking household dust proportions, was less potent than the inorganic chemical mix alone. Additional work is necessary to better understand the mixture effect of inorganic and organic chemicals combined.

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Effects of organic and inorganic contaminants and their mixtures on metabolic health and gene expression in developmentally exposed zebrafish

Bérubé,

LeFauve,

Khalaf

et al. 2024

Preprint

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A 2024 inventory of test methods relevant to thyroid hormone system disruption for human health and environmental regulatory hazard assessment

Vergauwen,

Bajard,

Tait

et al. 2024

Open Res Europe

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Thyroid hormone system disruption (THSD) is a growing concern in chemical hazard assessment due to its impact on human and environmental health and the scarce methods available for assessing the THSD potential of chemicals. In particular, the general lack of validated in silico and in vitro methods for assessing THS activity is of high concern. This manuscript provides an inventory of test methods relevant to THSD. Building on the Organisation for Economic Co-operation and Development (OECD) Guidance Document 150 and recent international developments, we highlight progress in in silico and in vitro methods, as well as in vivo assays. The provided inventory categorizes available methods according to the levels of the OECD Conceptual Framework, with an assessment of the validation status of each method. At Level 1, 12 in silico models that have been statistically validated and are directly related to THSD have been identified. At Level 2, 67 in vitro methods have been listed including those assessed in key initiatives such as the European Union Network of Laboratories for the Validation of Alternative Methods (EU-NETVAL) validation study to identify potential thyroid disruptors. At Levels 3-5, THSD-sensitive endpoints are being included in existing fish-based OECD Test Guidelines to complement amphibian assays. In total, the inventory counts 108 entries comprising established methods (e.g., OECD Test Guidelines) as well as citable methods that are under further development and in some cases are ready for validation or in the initial stages of validation. This work aims to support the ongoing development of strategies for regulatory hazard assessment, such as integrated approaches to testing and assessment (IATAs), for endocrine disruptors, addressing critical gaps in the current testing landscape for THSD in both human and environmental health contexts.

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Neurotox Screen? Zebrafish Study Points to PFOS Early-Life Exposure Effects

Seltenrich

2024

Environ Health Perspect

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Investigation of Peroxisome Proliferator-Activated Receptor Genes as Requirements for Visual Startle Response Hyperactivity in Larval Zebrafish Exposed to Structurally Similar Per- and Polyfluoroalkyl Substances (PFAS)

Cited by 3 publications

References 108 publications

Effects of organic and inorganic contaminants and their mixtures on metabolic health and gene expression in developmentally exposed zebrafish

Effects of organic and inorganic contaminants and their mixtures on metabolic health and gene expression in developmentally exposed zebrafish

A 2024 inventory of test methods relevant to thyroid hormone system disruption for human health and environmental regulatory hazard assessment

Neurotox Screen? Zebrafish Study Points to PFOS Early-Life Exposure Effects

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