A vision for safer food contact materials: Public health concerns as drivers for improved testing

Muncke, Jane; Andersson, Anna-Maria; Backhaus, Thomas; Belcher, Scott M.; Boucher, Justin M.; Carney Almroth, Bethanie; Collins, Terrence J.; Geueke, Birgit; Groh, Ksenia J.; Heindel, Jerrold J.; von Hippel, Frank A.; Legler, Juliette; Maffini, Maricel V.; Martin, Olwenn V.; Peterson Myers, John; Nadal, Angel; Nerin, Cristina; Soto, Ana M.; Trasande, Leonardo; Vandenberg, Laura N.; Wagner, Martin; Zimmermann, Lisa; Thomas Zoeller, R.; Scheringer, Martin

doi:10.1016/j.envint.2023.108161

Cited by 13 publications

(8 citation statements)

References 273 publications

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“…Assessing toxicity of the overall mixture of compounds released by plastics encompasses all exposurerelevant chemicals and is key to understanding their joint impacts and hazards. 22 In contrast to the dedicated research on plastic chemicals mediating their toxicity via nuclear receptors, an interrogation of such chemicals across human GPCRs has not yet been undertaken. Given that there are ∼400 non-olfactory GPCRs that may, in principle, be targeted by plastic chemicals, highthroughput screening of many GPCRs represents an ideal approach.…”

Section: Introductionmentioning

confidence: 99%

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Beyond the Nucleus: Plastic Chemicals Activate G Protein-Coupled Receptors

McPartland,

Stevens,

Bartosova

et al. 2024

Environ. Sci. Technol.

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G protein-coupled receptors (GPCRs) are central mediators of cell signaling and physiological function. Despite their biological significance, GPCRs have not been widely studied in the field of toxicology. Herein, we investigated these receptors as novel targets of plastic chemicals using a high-throughput drug screening assay with 126 human non-olfactory GPCRs. In a first-pass screen, we tested the activity of triphenol phosphate, bisphenol A, and diethyl phthalate, as well as three real-world mixtures of chemicals extracted from plastic food packaging covering all major polymer types. We found 11 GPCR-chemical interactions, of which the chemical mixtures exhibited the most robust activity at adenosine receptor 1 (ADORA1) and melatonin receptor 1 (MTNR1A). We further confirm that polyvinyl chloride and polyurethane products contain ADORA1 or MTNRA1 agonists using a confirmatory secondary screen and pharmacological knockdown experiments. Finally, an analysis of the associated gene ontology terms suggests that ADORA1 and MTNR1A activation may be linked to downstream effects on circadian and metabolic processes. This work highlights that signaling disruption caused by plastic chemicals is broader than that previously believed and demonstrates the relevance of nongenomic pathways, which have, thus far, remained unexplored.

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Section: Introductionmentioning

confidence: 99%

“…Thus, realistic exposure scenarios must consider complex mixtures of plastic chemicals. Assessing toxicity of the overall mixture of compounds released by plastics encompasses all exposure-relevant chemicals and is key to understanding their joint impacts and hazards …”

Section: Introductionmentioning

confidence: 99%

Beyond the Nucleus: Plastic Chemicals Activate G Protein-Coupled Receptors

McPartland,

Stevens,

Bartosova

et al. 2024

Environ. Sci. Technol.

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“…Assessing toxicity of the overall mixture of compounds released by plastics encompasses all exposurerelevant chemicals and is key to understand their joint impacts and hazard. 21 In contrast to the dedicated research on plastic chemical mediating their toxicity via nuclear receptors, an interrogation of such chemicals across human GPCRs has not yet been undertaken. Given there are ~400 non-olfactory GPCRs that may, in principle, be targeted by plastic chemicals, a high-throughput screening of many GPCRs represents an ideal approach.…”

Section: Introductionmentioning

confidence: 99%

“…Assessing toxicity of the overall mixture of compounds released by plastics encompasses all exposure-relevant chemicals and is key to understand their joint impacts and hazard. 21…”

Section: Introductionmentioning

confidence: 99%

Beyond the nucleus: Plastic chemicals activate G protein-coupled receptors

McPartland,

Stevens,

Bartosova

et al. 2023

Preprint

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FigureG protein-coupled receptors (GPCRs) are central mediators of cell signaling and physiological function. Despite their biological significance, GPCRs have not been widely studied in the field of toxicology. Herein, we investigated these receptors are novel targets of plastic chemicals using a high-throughput drug screening assay with 126 human non-olfactory GPCRs. In a first-pass screen, we tested the activity of triphenol phosphate, bisphenol A, and diethyl phthalate as well as three real-world mixtures of chemicals extracted from plastic food packaging covering all major polymer types. We found 11 GPCR-chemical interactions, of which the chemical mixtures exhibited the most robust activity at Adenosine receptor 1 (ADORA1) and Melatonin receptor 1 (MTNR1A) in a confirmatory secondary screen. We further confirmed that polyvinyl chloride and polyurethane products contain ADORA1 or MTNRA1 agonists using pharmacological knockdown experiments. Finally, an analysis of the associated gene ontology terms suggests that ADORA1 and MTNR1A activation may be linked to downstream effects on circadian and metabolic processes. Our findings exemplify the diversity of endpoints plastic chemicals can target and demonstrate the relevance of non-genomic pathways which have thus far remained unexplored.

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“…Plastics production doubled between 2000 and 2019, with 460 million tonnes produced in 2019 alone (OECD, 2022). With cumulative production reaching 10,000 million tonnes in 2020, we have a growing body of evidence about the harmful impacts of plastics on human and environmental health and climate (Cabernard et al, 2022;Muncke et al, 2023;Trasande et al, 2024). The evidence base shows that due to the persistent and cumulative nature of plastic pollution (Geyer et al, 2017), plastic removal and recycling technologies cannot keep pace with the scale of the global plastic pollution crisis (e.g., Borrelle et al, 2020;Lau et al, 2020;OECD, 2022).…”

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confidence: 99%

Primary plastic polymers: Urgently needed upstream reduction

Baztan,

Jorgensen,

Carney Almroth

et al. 2024

Camb. prisms Plast.

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The fourth session of the United Nations Environmental Program (UNEP) Intergovernmental Negotiating Committee (INC-4) to develop a legally binding global Plastics Treaty takes place in Ottawa, Canada, at the end of April 2024. As Inger Andersen (UNEP Executive Director) reminded us in her opening plenary remarks at INC-3: the resolution called for an instrument that is, and I quote: "Based on a comprehensive approach that addresses the full life cycle of plastic." Not a plastic instrument that deals with plastic pollution from recycling or waste management alone, the full life cycle and this means rethinking everything along the chain from polymer to production, from product to packaging. We need to use fewer virgin materials, less plastic and no harmful chemicals. We need to ensure that we use and reuse, and recycle resources more efficiently. And dispose safely of what is left over. This is how we protect human and ecosystem health… Cambridge Prisms: Plastics www.cambridge.org/plc

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A vision for safer food contact materials: Public health concerns as drivers for improved testing

Cited by 13 publications

References 273 publications

Beyond the Nucleus: Plastic Chemicals Activate G Protein-Coupled Receptors

Beyond the Nucleus: Plastic Chemicals Activate G Protein-Coupled Receptors

Beyond the nucleus: Plastic chemicals activate G protein-coupled receptors

Primary plastic polymers: Urgently needed upstream reduction

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