Transcriptomic points of departure for 6PPD-Quinone derived from human Caco-2 and HepG2 cells.

N-(1,3-Dimethyl butyl)-N'-phenyl-phenylenediamine-quinone (6ppd-quinone) is of emerging concern due to its widespread presence and toxicity to aquatic species. The chemical has been detected in human biofluids though little is known about its effects on human tissues. The objective of this study was to increase understanding of 6ppd-quinone's potential human health effects by deriving transcriptomic points of departure (tPOD) values in two human cell lines using the TPD-seq workflow.

Integrative Modeling of Urinary Metabolomics and Metal Exposure Reveals Systemic Impacts of Electronic Waste in Exposed Populations.

: Informal electronic waste (e-waste) recycling practices release a complex mixture of pollutants, particularly heavy metals, into the environment. Chronic exposure to these contaminants has been linked to a range of health risks, but the molecular underpinnings remain poorly understood. In this study, we investigated the alterations in metabolic profiles due to e-waste exposure and linked these metabolites to systemic biological effects.

Dietary Intake Is Associated with Biomarkers of Lead, Arsenic, and Cadmium in a Cohort of Mexican Adolescents.

Background: Lifestyle changes during adolescence can impact dietary habits and, subsequently, exposure to heavy metals.

Objectives: We aimed to evaluate the associations between food group intakes and metal exposures in a cohort of adolescents.

Methods: This study included 416 adolescents from Mexico City aged 10-18.

Interaction of mercury exposure and DNA methylation with sustained attention in children in a novel analysis of epigenetic susceptibility.

The etiology of attention-deficit/hyperactivity disorder (ADHD) remains poorly understood, despite it being one of the most common neurodevelopmental disorders worldwide. Past research suggests methylmercury exposure and DNA methylation (DNAm) levels are each associated with ADHD in children, yet whether they interact to affect ADHD is unknown. Leveraging data from a longitudinal cohort of children in Mexico, this novel epigenetic-environment interaction study identified significant interactions between childhood mercury exposure (measured at 6-12 years of age) and adolescent blood leukocyte DNAm in their association with sustained attention [quantified via the Conners continuous performance test, 3rd edition (CPT3)] measured on average 5.

Transcriptomics Points-of-Departure (tPODs) to Support Hazard Assessment of Benzo[]pyrene in Early-Life-Stage Rainbow Trout.

New approach methods (NAMs) are urgently needed to address the significant ethical and economic concerns associated with live animal testing as well as the low throughput associated with current toxicity testing frameworks. NAMs such as rapid mechanistic early-life-stage fish assays are promising alternatives to current hazard assessment approaches, as they can be used to derive toxicity thresholds and guide decision-makers on identifying or prioritizing chemicals of concern. This study aimed to derive benchmark concentrations from RNaseq data (transcriptomic points-of-departure; tPOD) from a short-term exposure study with early life stages of rainbow trout (RBT; ) using benzo[]pyrene (B[]P) as the model compound.

Cytotoxic and Molecular Effects of Soil Extracts from the Agbogbloshie Electronic-Waste Site on Fish and Human Cell Lines.

Effect-based methods (EBM) are of growing interest in environmental monitoring programs. Few EBM have incorporated transcriptomics even though these provide a wealth of biological information and can be modeled to yield transcriptomic points of departure (tPODs). The study objectives were to: A) characterize cytotoxic effects of soil extracts on the rainbow trout RTgill-W1 and the human Caco-2 cell lines; B) measure gene expression changes and calculate tPODs; and C) compare in vitro responses to available measures of plastic-related compounds and metals.

Comparison of in vitro transcriptomic points of departure with fish acute and chronic toxicity values: a case study of rainbow trout cells exposed to pesticides.

There is growing interest in transcriptomic points of departure (tPOD) values from in vitro experiments as an alternative to animal test method. The study objective was to calculate tPODs in rainbow trout gill cells (RTgill-W1 following Organisation for Economic Co-operaon and Development [OECD] 249) exposed to pesticides, and to evaluate how these values compare to fish acute and chronic toxicity data. Cells were exposed to one fungicide (chlorothalonil), 10 herbicides (atrazine, glyphosate, imazethapyr, metolachlor, diquat, s-metolachlor, aminomethylphosphonic acid, dicamba, dimethenamid-P, metribuzin), eight insecticides (chlorpyrifos, diazinon, permethrin, carbaryl, clothianidin, imidacloprid, thiamethoxam, chlorantraniliprole), and OECD 249 positive control 3,4-dichloroaniline.

Comprehensive Blood Metabolome and Exposome Analysis, Annotation, and Interpretation in E-Waste Workers.

Electronic and electrical waste (e-waste) production has emerged to be of global environmental public health concern. E-waste workers, who are frequently exposed to hazardous chemicals through occupational activities, face considerable health risks. To investigate the metabolic and exposomic changes in these workers, we analyzed whole blood samples from 100 male e-waste workers and 49 controls from the GEOHealth II project (2017-2018 in Accra, Ghana) using LC-MS/MS.

TPD-seq: A high throughput RNA-seq method to derive transcriptomic points of departure from cell lines.

There is growing scientific and regulatory interest in transcriptomic points of departure (tPOD) values from high-throughput in vitro experiments. To further help democratize tPOD research, here we outline 'TPD-seq' which links microplate-based exposure methods involving cell lines for human (Caco-2, Hep G2) and environmental (rainbow trout RTgill-W1) health, with a commercially available RNA-seq kit, with a cloud-based bioinformatics tool (ExpressAnalyst.ca).

Inconsistent transcriptomic responses to hexabromocyclododecane in Japanese quail: a comparative analysis of results from four different study designs.

Efforts to use transcriptomics for toxicity testing have classically relied on the assumption that chemicals consistently produce characteristic transcriptomic signatures that are reflective of their mechanism of action. However, the degree to which transcriptomic responses are conserved across different test methodologies has seldom been explored. With increasing regulatory demand for New Approach Methods (NAMs) that use alternatives to animal models and high-content approaches such as transcriptomics, this type of comparative analysis is needed.

Screening 800 putative endocrine disrupting chemicals in a representative mammal, bird, and fish using a neurochemical cell-free testing platform.

There is global demand for novel ecotoxicity testing tools that are based on alternative to animal models, have high throughput potential, and may be applicable to a wide diversity of taxa. Here we scaled up a microplate-based cell-free neurochemical testing platform to screen 800 putative endocrine disrupting chemicals from the U.S.

MetaboAnalystR 4.0: a unified LC-MS workflow for global metabolomics.

The wide applications of liquid chromatography - mass spectrometry (LC-MS) in untargeted metabolomics demand an easy-to-use, comprehensive computational workflow to support efficient and reproducible data analysis. However, current tools were primarily developed to perform specific tasks in LC-MS based metabolomics data analysis. Here we introduce MetaboAnalystR 4.

Exploring practices, challenges, and priorities for human health and ecological risk assessments in Indigenous communities in Canada.

Indigenous peoples in Canada are disproportionately exposed to environmental contaminants and may face elevated health risks related to their unique cultural, spiritual, and economic relationships with the land, including the use of traditional food systems. However, to date, institutionalized approaches to assess risks to human and ecological health from contaminants have not been well developed or implemented with Indigenous community contexts in mind. There is regulatory interest in developing new approach methods for risk assessment, and thus an opportunity to increase their relevance to Indigenous communities in which they will be ultimately applied.

Tibial Plateau Fracture With Use of Tibia Strut and Bone Filler in a 37-Year-Old Male: A Case Report.

Tibial plateau fractures (TPFs) are orthopedic challenges with multiple injury modalities and clinical presentations. TPFs are often classified using the Schatzker classification system, which can dictate management. In our case, a 37-year-old male presented at an orthopedic specialty hospital with right knee pain after a fall from a truck ramp.

Simultaneous targeted and non-targeted analysis of plastic-related contaminants in e-waste impacted soil in Agbogbloshie, Ghana.

An LC-MS based analytical method was developed and validated for the simultaneous targeted analysis and suspect screening of plastic-related contaminants in e-waste impacted soils. Satisfactory recoveries (97 ± 13 %) were achieved using ultrasound-assisted extraction for 14/15 of the targeted analytes (7 bisphenols and 8 plasticizers) in a range of agricultural and non-agricultural soils. The method was applied to 53 soil samples collected in May 2015 in the region of Agbogbloshie (Ghana) at e-waste facilities (incl.

Cytotoxicity of 19 pesticides in rainbow trout gill, liver, and intestinal cell lines.

The rainbow trout gill cell line (RTgill-W1), via test guideline 249 of the Organisation for Economic Co-operation and Development, has been established as a promising New Approach Methodology, although to advance confidence in the method more case studies are needed that: 1) expand our understanding of applicability domains (chemicals with diverse properties); 2) increase methodological throughput (96-well format); and 3) demonstrate biological relevance (in vitro to in vivo comparisons; gill vs. other cells). Accordingly, the objective of our study was to characterize the cytotoxicity of 19 pesticides against RTgill-W1 cells, and also liver (RTL-W1) and gut epithelial (RTgutGC) cell lines, and then to compare the in vitro and in vivo data.

Hepatic Transcriptomic Responses to Ethinylestradiol in Embryonic Japanese Quail and Double-Crested Cormorant.

Understanding species differences in sensitivity to toxicants is a critical issue in ecotoxicology. We recently established that double-crested cormorant (DCCO) embryos are more sensitive than Japanese quail (JQ) to the developmental effects of ethinylestradiol (EE2). We explored how this difference in sensitivity between species is reflected at a transcriptomic level.

Comparing transcriptomic responses to chemicals across six species using the EcoToxChip RNASeq database.

The EcoToxChip project includes RNA-sequencing data from experiments involving model (Japanese quail, fathead minnow, African clawed frog) and ecological (double-crested cormorant, rainbow trout, northern leopard frog) species at multiple life stages (whole embryo and adult) exposed to eight chemicals of environmental concern known to perturb a wide range of biological systems (ethinyl estradiol, hexabromocyclododecane, lead, selenomethionine, 17β trenbolone, chlorpyrifos, fluoxetine, and benzo[a]pyrene). The objectives of this short communication were to (1) present and make available this RNA-sequencing database (i.e.

Contaminated sites and Indigenous peoples in Canada and the United States: A scoping review.

Indigenous communities are disproportionately exposed to contaminated sites, and this poses unique challenges as many Indigenous peoples consider land as an integral part of their culture and economy. This scoping review aimed to identify and map information on contaminated sites and Indigenous peoples in Canada and the United States, namely (1) the relationship between contaminated sites and Indigenous peoples and their land and food systems; (2) strategies, challenges, and successes for contaminated sites assessment and management on Indigenous land; and (3) Indigenous leadership and inclusion in contaminated site assessment and management. We followed a PRISMA-ScR (Transparent Reporting of Systematic Reviews and Meta-Analyses-Extension for Scoping Reviews) checklist to collect data that could be categorized into these three objectives.

Factors influencing mercury exposure in Arctic-breeding shorebirds.

Mercury (Hg) pollution remains a concern to Arctic ecosystems, due to long-range transport from southern industrial regions and melting permafrost and glaciers. The objective of this study was to identify intrinsic, extrinsic, and temporal factors influencing Hg concentrations in Arctic-breeding shorebirds and highlight regions and species at greatest risk of Hg exposure. We analyzed 1094 blood and 1384 feather samples from 12 shorebird species breeding at nine sites across the North American Arctic during 2012 and 2013.

Association between heavy metal uptake and growth and reproduction in the anecic earthworm, Alma nilotica (Grube 1855).

Elevated heavy metal concentrations in soils are a cause for concern as they are hazardous to soil organisms including earthworms which are considered as ecosystem engineers. Current ecotoxicity tests predominantly use temperate earthworm species, and thus there is the need to include a broader genera of native species to improve ecological risk assessment. Alma nilotica, is a tropical anecic earthworm species that survives well under laboratory conditions and has potential for use in ecotoxicology testing but lacks published toxicity data for important pollutants.

Mercury accumulation, biomagnification, and relationships to δC, δN and δS of fishes and marine mammals in a coastal Arctic marine food web.

Combining mercury and stable isotope data sets of consumers facilitates the quantification of whether contaminant variation in predators is due to diet, habitat use and/or environmental factors. We investigated inter-species variation in total Hg (THg) concentrations, trophic magnification slope between δN and THg, and relationships of THg with δC and δS in 15 fish and four marine mammal species (249 individuals in total) in coastal Arctic waters. Median THg concentration in muscle varied between species ranging from 0.