Plastic Food Packaging from Five Countries Contains Endocrine- and Metabolism-Disrupting Chemicals.

Plastics are complex chemical mixtures of polymers and various intentionally and nonintentionally added substances. Despite the well-established links between certain plastic chemicals (bisphenols and phthalates) and adverse health effects, the composition and toxicity of real-world mixtures of plastic chemicals are 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 γ (PPARγ), estrogen receptor α (ERα), and inhibiting the androgen receptor (AR) are prevalent in plastic packaging. We detected up to 9936 chemical features in a single product and found that each product had 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. Since samples with fewer chemical features induce less toxicity, chemical simplification is key to producing safer plastic packaging.

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

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.

Expression of DNA repair genes in arctic char (Salvelinus alpinus) from Bjørnøya in the Norwegian Arctic.

High levels of organochlorines (OCs) have been measured in arctic char (Salvelinus alpinus) from Lake Ellasjøen on Bjørnøya, Norway (74.30°N, 19.0°E). In a nearby lake, Laksvatn, the OC-levels in arctic char were low. A previous study has shown that char from Ellasjøen had significantly higher levels of DNA double strand breaks (DSBs) than char from Lake Laksvatn. Even though there is increasing evidence of the genotoxic effects of OCs, little is known about the effects of OCs on the DNA repair system. The aim of the present study was to determine if the two main DNA DSB repair mechanisms, homologous recombination (HR) and non-homologous end-joining (NHEJ), are affected by the higher OC and DSB level in char from Ellasjøen. This was analysed by comparing the transcript level of 11 genes involved in DNA DSB repair in char liver samples from Ellasjøen (n = 9) with char from Laksvatn (n = 12). Six of the investigated genes were significantly upregulated in char from Ellasjøen. As the expression of DNA DSB repair genes was increased in the contaminant-exposed char, it is likely that the DNA DSB repair capacity is induced in these individuals. This induction was positively correlated with the DNA DSB and negatively correlated with one or several OCs for four of these genes. However, the strongest predictor variable for DNA repair genes was habitat, indicating genetic differences in repair capacity between populations. As char from Ellasjøen still had significantly higher levels of DSBs compared to char from Laksvatn, it is possible that chronic exposure to OCs and continued production of DSB has caused selective pressure within the population for fixation of adaptive alleles. It is also possible that DSB production was exceeding the repair capacity given the prevailing conditions, or that the OC or DSB level was above the threshold value of inhibition of the DNA repair system resulting in the rate of DNA damage exceeding the rate of repair.

Circulating trace elements: Comparison between early and late incubation in common eiders (Somateria mollissima) in the central Baltic Sea.

We analyzed body mass and a panel of 64 trace elements in blood from incubating common eiders (Somateria mollissima) in the central Baltic Sea during the breeding seasons of 2017 (n = 27) and 2018 (n = 23). Using a non-invasive approach, the same incubating eiders nesting on Christiansø, Denmark were sampled once on day 4 and day 24 of incubation to provide a comparison between the early and late stages of incubation. Blood concentrations of chemical elements were quantified using high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS). Cadmium and lead significantly increased over the course of the incubation period while body mass, barium, calcium, cerium, cesium, iron, magnesium, manganese, molybdenum, phosphorus, selenium, strontium, sulfur, uranium, and zinc all significantly decreased. Excluding lead, all trace elements were within expected ranges. Lead blood concentrations had a 4.7-fold increase from 2017 to 2018 indicating a potential health threat. However, internal interactions between trace elements must be considered when making comparisons to toxicological thresholds. Body mass and many essential elements showed significantly higher levels in 2017 than 2018, which could be an indication of limitations in preferred food availability or harsher fasting conditions. Additional sampling years are needed to further investigate if these results reflect yearly fluctuations or decreasing health within the Christiansø eider colony. There was little overlap in element blood concentrations and body mass between days of incubation, indicating these parameters are affected by the physiological processes of reproduction and incubation. We recommend continued biomonitoring and use of complete trace element analysis for the Christiansø eiders to further understand year-to-year variations within colonies. Further investigation into the spatial ecology of the colony is also needed to provide a more robust understanding of exposure and source identification of trace elements.

Lead isotopic signatures in blood from incubating common eiders (Somateria mollissima) in the central Baltic Sea.

The Christiansø colony of common eiders (Somateria mollissima) in the central Baltic Sea were exposed to high levels of Pb during the 2018 breeding season that were not present in 2017. Due to these high Pb blood levels, the present study investigated possible Pb sources and Pb dynamics within this vulnerable colony. We analyzed body mass and lead isotopic ratios (Pb-IRs) in blood taken from the same incubating eiders at the early (day 4) and late (day 24) stages of incubation during the 2018 breeding season (n = 23). Pb-IRs 208/207, 208/206, 206/207, and 207/206 were analyzed using high resolution inductively coupled mass spectrometry. We found largely similar Pb-IRs from the different stages of incubation indicating a predominantly constant endogenous source of Pb exposure. We suggest the increasing Pb levels come from pre-nesting and nesting foraging and from medullary bone release. The similar Pb-IRs also indicate continued metabolization of the medullary bone to meet the nutritional and energy demands of incubation. Comparisons to Pb-IR reports from the Baltic Sea showed multiple sources of pollution distinguished by a difference between Pb-IRs in individuals with Pb blood concentrations >500 µg/kg ww and <500 µg/kg ww. The most highly contaminated individuals in the present study had Pb-IRs similar to those of Pb ammunition indicating shot pellet uptake. This study further emphasizes the need for continued biomonitoring of the Christiansø colony, including fecal sampling and environmental field sampling to identify the origin and extent of dietary Pb exposure on Christiansø. As a representative unit of the Baltic Flyway population; the Christiansø colony provides an important opportunity for continued investigation into Pb contamination, population dynamics, and declines.

Lead concentrations in blood from incubating common eiders (Somateria mollissima) in the Baltic Sea.

Here we investigate if lead may be a contributing factor to the observed population decline in a Baltic colony of incubating eiders (Somateria mollissima). Body mass and blood samples were obtained from 50 incubating female eiders at the Baltic breeding colony on Christiansø during spring 2017 (n = 27) and 2018 (n = 23). All the females were sampled twice during early (day 4) and late (day 24) incubation. The full blood was analysed for lead to investigate if the concentrations exceeded toxic thresholds or changed over the incubation period due to remobilisation from bones and liver tissue. Body mass, hatch date and number of chicks were also analysed with respect to lead concentrations. The body mass (mean ± SD g) increased significantly in the order: day 24 in 2018 (1561 ± 154 g) < day 24 in 2017 (1618 ± 156 g) < day 4 in 2018 (2183 ± 140 g) < day 4 in 2017 (2359 ± 167 g) (all p < 0.001). The lead concentrations increased significantly in the opposite order i.e. day 4 in 2017 (41.7 ± 67.1 µg/L) < day 24 in 2017 (55.4 ± 66.8 µg/L) < day 4 in 2018 (177 ± 196 µg/L) < day 24 in 2018 (258 ± 243) (all p < 0.001). From day 4 to 24, the eider females had a 1.33-fold increase in blood lead concentrations in 2017 and a 1.46-fold increase in 2018. Three of the birds (13%) sampled in 2018 had lead concentrations that exceeded concentrations of clinical poisoning (500 µg/L) and eleven (48%) had concentrations that exceeded the threshold for subclinical poisoning (200 µg/L). In 2017, none of the birds exceeded the high toxic threshold of clinical poisoning while only one (4%) exceeded the lower threshold for subclinical poisoning. Three of the birds (6%) sampled in 2018 had lead concentrations that exceeded those of clinical poisoning while 12 birds (24%) resampled in both years exceeded the threshold for subclinical poisoning. In addition, lead concentrations and body mass on day 4 affected hatch date positively in 2018 (both p < 0.03) but not in 2017. These results show that bioavailable lead in bone and liver tissue pose a threat to the health of about 25% of the incubating eiders sampled. This is particularly critical because eiders are largely capital breeding which means that incubating eiders are in an energetically stressed state. The origin of lead in incubating eiders in the Christiansø colony is unknown and it remains an urgent priority to establish the source, prevalence and mechanism for uptake. The increase in lead from day 4 to day 24 is due to bone and liver remobilization; however, the additional lead source(s) on the breeding grounds needs to be identified. Continued investigations should determine the origin, uptake mechanisms and degree of exposure to lead for individual birds. Such research should include necropsies, x-ray, lead isotope and stable C and N isotope analyses to find the lead sources(s) in the course of the annual cycle and how it may affect the population dynamics of the Christiansø colony which reflects the ecology of the Baltic eiders being suitable for biomonitoring the overall flyway.