Biology subjects

Voelker, J.

Publications and source records attributed to Voelker, J..

4 recordsLinked to original sources

bioRxiv2024

Migration of endocrine and metabolism disrupting chemicals from plastic food packaging

Plastics constitute a vast array of substances, with over 16 000 known plastic chemicals, including intentionally and non-intentionally added substances. Toxicity and thousands of chemicals are extractable from plastics; however, the extent to which toxicity and chemicals migrate from everyday plastic products remains poorly understood. This study aims to characterize the endocrine and metabolism disrupting activity, as well as chemical composition of migrates from plastic food contact articles (FCAs) from four countries as significant sources of human exposure. Additionally, strategies for prioritization of chemicals were explored. Fourteen plastic FCAs covering seven polymer types with high global market shares were migrated into water and a water-ethanol mixture as food simulants according to European regulations. The migrates were analyzed using reporter gene assays for nuclear receptors relevant to human health and non-target chemical analysis to characterize the chemical composition of the migrates. All FCA migrates interfered with at least two nuclear receptors, predominantly targeting pregnane X receptor. Moreover, peroxisome proliferator receptor gamma was broadly activated by the migrates, though mostly with lower potencies, while estrogenic and antiandrogenic activities were more selectively induced by specific FCAs. Fewer chemicals and less toxicity migrated into water compared to the water-ethanol mixture. The latter exhibited similar toxicity and number of chemicals as methanol extracts of the same FCAs. Novel strategies were employed to address the chemical complexity of FCAs and narrow down the list of potential active chemicals. By comparing the composition of multiple leachates of one sample and using stepwise partial least squares regressions, we successfully reduced the chemical complexity, pinpointed potential endocrine disruptors such as triphenyl phosphate and prioritized chemicals for further identification efforts. This study demonstrates the migration of endocrine and metabolism disrupting chemicals from plastic FCAs into food simulants, rendering a migration of these compounds into food and beverages probable. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/588263v4_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@32490dorg.highwire.dtl.DTLVardef@15a1047org.highwire.dtl.DTLVardef@1e2b565org.highwire.dtl.DTLVardef@f323e2_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2023

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

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=84 SRC="FIGDIR/small/560665v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@e3b5edorg.highwire.dtl.DTLVardef@1bcf3aeorg.highwire.dtl.DTLVardef@224012org.highwire.dtl.DTLVardef@9c61ea_HPS_FORMAT_FIGEXP M_FIG C_FIG 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 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.

pharmacology and toxicology↗

bioRxiv2023

Plastic food packaging from five countries contains endocrine and metabolism disrupting chemicals

Plastics are complex chemical mixtures of polymers and various intentionally and non-intentionally added substances. Despite the well-established links between certain plastic chemicals (bisphenols, phthalates) and adverse health effects, the composition and toxicity of real-world mixtures of plastic chemicals is not well understood. To assess both, we analyzed the chemicals from 36 plastic food contact articles from five countries using nontarget high-resolution mass spectrometry and reporter gene assays for four nuclear receptors that represent key components of the endocrine and metabolic system. We found that chemicals activating the pregnane X receptor (PXR), peroxisome proliferator receptor gamma (PPAR{gamma}), estrogen receptor alpha (ER) and inhibiting the androgen receptor (AR) are prevalent in plastic packaging. We detected up to 9936 chemical features in a single product but found that each product has a rather unique chemical fingerprint. To tackle this chemical complexity, we used stepwise partial least squares regressions and prioritized and tentatively identified the chemical features associated with receptor activity. Our findings demonstrate that most plastic food packaging contains endocrine and metabolism disrupting chemicals. This shows that plastics are a relevant source of exposure to toxic chemicals and further supports the notion that plastic products designed for food contact cannot be considered safe. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/559713v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@44be3borg.highwire.dtl.DTLVardef@1252a31org.highwire.dtl.DTLVardef@f522a2org.highwire.dtl.DTLVardef@1b4f8be_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2021

Adipogenic activity of chemicals used in plastic consumer products

Bisphenols and phthalates, chemicals frequently used in plastic products, promote obesity in cell and animal models. However, these well-known metabolism disrupting chemicals (MDCs) represent only a minute fraction of all compounds found in plastics. To gain a comprehensive understanding of plastics as a source of exposure to MDCs, we characterized all chemicals present in 34 everyday products using nontarget high-resolution mass spectrometry and analyzed their joint adipogenic activities by high-content imaging. We detected 55,300 chemical features and tentatively identified 629 unique compounds, including 11 known MDCs. Importantly, chemicals that induced proliferation, growth, and triglyceride accumulation in 3T3-L1 adipocytes were found in one third of the products. Since the majority did not target peroxisome proliferator-activated receptor {gamma}, the effects are likely to be caused by unknown MDCs. Our study demonstrates that daily-use plastics contain potent mixtures of MDCs and can, therefore, be a relevant yet underestimated environmental factor contributing to obesity. TeaserPlastics contain a potent mixture of chemicals promoting adipogenesis, a key process in developing obesity.

pharmacology and toxicology↗