Description of Solvent-Extractable Chemicals in Thermal Receipts and Toxicological Assessment of Bisphenol S and Diphenyl Sulfone.

Research on thermal receipts has previously focused on the toxic effects of dermal exposure from the most publicized developers (e.g., bisphenol A (BPA) and bisphenol S (BPS)), while no studies have reported on the other solvent-extractable compounds therein. Diphenyl sulfone (DPS) is a sensitizer added to thermal receipts, but little is known about DPS concentrations in receipts or potential toxicity. Here, we quantified BPA, BPS, and DPS concentrations and tentatively identified the solvent-extractable compounds of thermal receipts collected from three South Dakota (USA) cities during 2016-2017. An immortalized chicken hepatic cell line, cultured as 3D spheroids, was used to screen effects of DPS, BPS, and 17ß estradiol (E2; 0.1-1000 µM) on cell viability and gene expression changes. These chemicals elicited limited cytotoxicity with LC50 values ranging from 113 to 143 µM, and induced dysregulation in genes associated with lipid and bile acid homeostasis. Taken together, this study generated novel information on solvent-extractable chemicals from thermal receipts and toxicity data for DPS.

Development and Initial Testing of EcoToxChip, a Novel Toxicogenomics Tool for Environmental Management and Chemical Risk Assessment.

New approach methods (NAMs) are increasingly important to help accelerate the pace of ecological risk assessment and offer more ethical, affordable, and efficient alternatives to traditional toxicity tests. In the present study, we describe the development, technical characterization, and initial testing of a toxicogenomics tool, EcoToxChip (384-well quantitative polymerase chain reaction [qPCR] array), to support chemical management and environmental monitoring for three laboratory model species-fathead minnow (Pimephales promelas), African clawed frog (Xenopus laevis), and Japanese quail (Coturnix japonica). Chip design, including gene selection, was informed by a diverse end-user group and quality control metrics (e.g., primer assay, reverse transcription, and PCR efficiency) performed well based on a priori established criteria. Correlation with RNA sequencing (seq) data provided additional confidence in this novel toxicogenomics tool. Although the present study represents an initial testing of only 24 EcoToxChips for each of the model species, the results provide increased confidence in the robustness/reproducibility of EcoToxChips for evaluating perturbations in gene expression associated with chemical exposure and thus, this NAM, combined with early-life stage toxicity testing, could augment current efforts for chemical prioritization and environmental management. Environ Toxicol Chem 2023;42:1763-1771. © 2023 SETAC.

Drivers of and Obstacles to the Adoption of Toxicogenomics for Chemical Risk Assessment: Insights from Social Science Perspectives.

BACKGROUND: Some 20 y ago, scientific and regulatory communities identified the potential of omics sciences (genomics, transcriptomics, proteomics, metabolomics) to improve chemical risk assessment through development of toxicogenomics. Recognizing that regulators adopt new scientific methods cautiously given accountability to diverse stakeholders, the scope and pace of adoption of toxicogenomics tools and data have nonetheless not met the ambitious, early expectations of omics proponents. OBJECTIVE: Our objective was, therefore, to inventory, investigate, and derive insights into drivers of and obstacles to adoption of toxicogenomics in chemical risk assessment. By invoking established social science frameworks conceptualizing innovation adoption, we also aimed to develop recommendations for proponents of toxicogenomics and other new approach methodologies (NAMs). METHODS: We report findings from an analysis of 56 scientific and regulatory publications from 1998 through 2017 that address the adoption of toxicogenomics for chemical risk assessment. From this purposeful sample of toxicogenomics discourse, we identified major categories of drivers of and obstacles to adoption of toxicogenomics tools and data sets. We then mapped these categories onto social science frameworks for conceptualizing innovation adoption to generate actionable insights for proponents of toxicogenomics. DISCUSSION: We identify the most salient drivers and obstacles. From 1998 through 2017, adoption of toxicogenomics was understood to be helped by drivers such as those we labeled Superior scientific understanding, New applications, and Reduced cost & increased efficiency but hindered by obstacles such as those we labeled Insufficient validation, Complexity of interpretation, and Lack of standardization. Leveraging social science frameworks, we find that arguments for adoption that draw on the most salient drivers, which emphasize superior and novel functionality of omics as rationales, overlook potential adopters' key concerns: simplicity of use and compatibility with existing practices. We also identify two perspectives-innovation-centric and adopter-centric-on omics adoption and explain how overreliance on the former may be undermining efforts to promote toxicogenomics. https://doi.org/10.1289/EHP6500.

Toxicogenomic Assessment of Complex Chemical Signatures in Double-Crested Cormorant Embryos from Variably Contaminated Great Lakes Sites.

Using omics approaches to monitor complex environmental mixtures is challenging. Previously, we evaluated in vitro transcriptomic effects of complex organic extracts derived from avian eggs. However, there is a lack of studies using wild species that are naturally exposed to contaminant mixtures. Here, we examined polychlorinated biphenyl (PCB) and polybrominated diphenyl ether (PBDE) residues and gene expression in embryonic liver tissue of double-crested cormorants (Phalacrocorax auritus) collected from six variably contaminated colonies. Colonies near industrialized areas were distinguished from less contaminated sites based on their PCB and PBDE concentrations. The most variably expressed genes between sites were involved in pathways including, xenobiotic metabolism (e.g., Cyp1a4), lipid/bile acid homeostasis (e.g., Lbfabp), and oxidative stress (e.g., Mt4). Hierarchical clustering, based on relative gene expression, revealed a grouping pattern similar to chemical residue concentrations. Further, partial least squares regression analysis was used to estimate chemical concentrations from transcriptomics data. PCB 155 and BDE 47 showed the highest slopes (0.77 and 0.69, respectively) fitted by linear regression of measured and estimated chemical concentrations. The application of transcriptomics to a wild avian species, naturally exposed to complex chemical mixtures and other stressors, represents a promising means to distinguish and prioritize variably contaminated sites.

Fluorescent RNA arbitrarily primed polymerase chain reaction. A new differential display approach to detect contaminant-induced alterations of gene expression in wildlife species.

Differential display polymerase chain reaction (PCR) can facilitate the identification of novel molecular end points related to contaminant exposure in a wide range of species. To date, various differential display methodologies have been described in detail. Herein, we describe a modification of the RNA arbitrarily primed PCR (RAP-PCR) method that involves the fluorescent labeling of cDNA transcripts via 5' rhodamine-labeled 18-mer arbitrary primers. These arbitrary primers typically bind to the coding regions of cDNA, which simplifies the downstream identification of contaminant-responsive genes. The technique has been aptly named fluorescent RNA arbitrarily primed PCR, FRAP-PCR, and has been successfully utilized with several avian species and RNA sources (e.g., cultured cells, tissue). This straightforward, safe, and cost-effective approach represents a useful alternative to the radiometric-based RAP-PCR method.