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Environmental triggers is part of five focus areas of the Challenges in IBD research document, which also includes preclinical human IBD mechanisms, novel technologies, precision medicine and pragmatic clinical research. The Challenges in IBD research document provides a comprehensive overview of current gaps in inflammatory bowel diseases (IBD) research and delivers actionable approaches to address them. It is the result of a multidisciplinary input from scientists, clinicians, patients, and funders, and represents a valuable resource for patient centric research prioritization. In particular, the environmental triggers section is focused on the main research gaps in elucidating causality of environmental factors in IBD. Research gaps were identified in: 1) epidemiology of exposures; 2) identification of signatures of biological response to exposures; and 3) mechanisms of how environmental exposures drive IBD. To address these gaps, the implementation of longitudinal prospective studies to determine disease evolution and identify sub-clinical changes in response to exposures is proposed. This can help define critical windows of vulnerability and risk prediction. In addition, systems biology analysis and in silico modeling were proposed as approaches to integrate the IBD exposome for the identification of biological signatures of response to exposures, and to develop prediction models of the effects of environmental factors in driving disease activity and response to therapy. This research could lead to identification of biomarkers of exposures and new modalities for therapeutic intervention. Finally, hypothesis-driven mechanistic studies to understand gene-environment interactions and to validate causality of priority factors should be performed to determine how environment influences clinical outcomes.

Background: Bisphenol A (BPA) is known to be biologically active in experimental models even at low levels of exposure. However, its impact on endometrial cancer remains unclear. Objectives: This study aimed to investigate whether lifelong exposure to different doses of BPA induced uterine abnormalities and molecular changes in a rat model. Methods: Sprague-Dawley rats were exposed to 5 doses of BPA [0, 25, 250, 2,500, or 25,000 [micro]g/kg body weight (BW)/d] or 2 doses of 17[alpha]--ethynylestradiol (EE2) (0.05 and 0.5 [micro]g/kg BW/d) starting from gestational day 6 up to 1 y old according to the CLARITY-BPA consortium protocol. The BW, uterus weight, and histopathology end points of the uteri were analyzed at postnatal (PND) day 21, 90, and 365. Estrous cycling status was evaluated in PND90 and PND365 rats. Transcriptomic analyses of estrus stage uteri were conducted on PND365 rats. Results: Based on the analysis of the combined effects of all testing outcomes (including immunohistological, morphological, and estrous cycle data) in a semiblinded fashion, using statistical models, 25 [micro]g/kg BW/d BPA [BPA(25)], or 250 [micro]g/kg BW/d BPA [BPA(250)] exerted effects similar to that of EE2 at 0.5 [micro]g/kg BW/d in 1-y-old rats. Transcriptome analyses of estrus stage uteri revealed a set of 710 genes shared only between the BPA(25) and BPA(250) groups, with 115 of them predicted to be regulated by estradiol and 57 associated with female cancers. An interesting finding is that the expression of 476 human orthologous genes in this rat BPA signature robustly predicted the overall survival (p =1.68x[10.sup.-5], hazard ratio = 2.62) of endometrial cancer patients. Discussion: Lifelong exposure of rats to low-dose BPA at 25 and 250 [micro]g/kg BW/d altered the estrous cycle and uterine pathology with similarity to EE2. The exposure also disrupted a unique low-dose BPA-gene signature with predictive value for survival outcomes in patients with endometrial cancer. https://doi.org/10.1289/EHP6875, Introduction Bisphenol A (BPA) is used extensively in the manufacturing of plastic consumer products. It is a key building block of polycarbonate-based plastics and vinyl ester resin (Lorber et al. [...]

Electronic waste (e-waste) generation is increasing worldwide, and its management becomes a significant challenge because of the many toxicants present in electronic devices. The U.S. is a major producer of e-waste, although its management practice and policy regulation are not sufficient to meet the challenge. We reviewed e-waste generation, current management practices and trends, policy challenges, potential health impact, and toxicant exposure prevention in the U.S. A large amount of toxic metals, flame retardants, and other persistent organic pollutants exist in e-waste or can be released from the disposal of e-waste (e.g., landfill, incineration, recycling). Landfill is still a major method used to dispose of obsolete electronic devices, and only about half of the states have initiated a landfill ban for e-waste. Recycling of e-waste is an increasing trend in the past few years. There is potential, however, for workers to be exposed to a mixture of toxicants in e-waste and these exposures should be curtailed. Perspectives and recommendations are provided regarding managing e-waste in the U.S. to protect public health, including enacting federal legislation, discontinuing landfill disposal, protecting workers in recycling facilities from toxicant exposure, reducing toxicant release into the environment, and raising awareness of this growing environmental health issue among the public., Introduction Electronic waste, or e-waste, refers to obsolete electronic devices for disposal, including TVs, desktop and laptop computers, mobile computers (notebooks, netbooks, tablets, e-book readers), cellular phones, printers, copiers, video [...]