Search Results - "Clewell, Rebecca"

Adaptive Posttranslational Control in Cellular Stress Response Pathways and Its Relationship to Toxicity Testing and Safety Assessment by Zhang, Qiang, Bhattacharya, Sudin, Pi, Jingbo, Clewell, Rebecca A, Carmichael, Paul L, Andersen, Melvin E

“…Although transcriptional induction of stress genes constitutes a major cellular defense program against a variety of stressors, posttranslational control…”
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Dose-dependence of chemical carcinogenicity: Biological mechanisms for thresholds and implications for risk assessment by Clewell, Rebecca A., Thompson, Chad M., Clewell, Harvey J.

“…Current regulatory practices for chemical carcinogens were established when scientific understanding of the molecular mechanisms of chemical carcinogenesis was…”
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Estimating provisional margins of exposure for data-poor chemicals using high-throughput computational methods by Nicolas, Chantel I., Linakis, Matthew W., Minto, Melyssa S., Mansouri, Kamel, Clewell, Rebecca A., Yoon, Miyoung, Wambaugh, John F., Patlewicz, Grace, McMullen, Patrick D., Andersen, Melvin E., Clewell III, Harvey J.

“…Current computational technologies hold promise for prioritizing the testing of the thousands of chemicals in commerce. Here, a case study is presented…”
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Time-dependent genomic response in primary human uroepithelial cells exposed to arsenite for up to 60 days by Efremenko, Alina, Balbuena, Pergentino, Clewell, Rebecca A., Black, Michael, Pluta, Linda, Andersen, Melvin E., Gentry, P. Robinan, Yager, Janice W., Clewell, Harvey J.

“…Evidence from both in vivo and in vitro studies suggests that gene expression changes from long-term exposure to arsenite evolve markedly over time, including…”
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Approaches for characterizing threshold dose-response relationships for DNA-damage pathways involved in carcinogenicity in vivo and micronuclei formation in vitro by Clewell, Rebecca A, Andersen, Melvin E

“…Assessing the shape of dose-response curves for DNA-damage in cellular systems and for the consequences of DNA damage in intact animals remains a controversial…”
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Multiple receptors shape the estrogen response pathway and are critical considerations for the future of in vitro-based risk assessment efforts by Miller, Michelle M., McMullen, Patrick D., Andersen, Melvin E., Clewell, Rebecca A.

“…Current in life toxicity testing paradigms are being challenged as the future of risk assessment moves towards more comprehensive mode of action/adverse…”
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An in vitro approach for prioritization and evaluation of chemical effects on glucocorticoid receptor mediated adipogenesis by Hartman, Jessica K., Beames, Tyler, Parks, Bethany, Doheny, Daniel, Song, Gina, Efremenko, Alina, Yoon, Miyoung, Foley, Briana, Deisenroth, Chad, McMullen, Patrick D., Clewell, Rebecca A.

“…Rising obesity rates worldwide have socio-economic ramifications. While genetics, diet, and lack of exercise are major contributors to obesity, environmental…”
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Contribution of ATM and ATR kinase pathways to p53‐mediated response in etoposide and methyl methanesulfonate induced DNA damage by Sun, Bin, Ross, Susan M., Rowley, Sean, Adeleye, Yeyejide, Clewell, Rebecca A.

“…p53 is a key integrator of cellular response to DNA damage, supporting post‐translational repair and driving transcription‐mediated responses including cell…”
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A map of the PPARα transcription regulatory network for primary human hepatocytes by McMullen, Patrick D., Bhattacharya, Sudin, Woods, Courtney G., Sun, Bin, Yarborough, Kathy, Ross, Susan M., Miller, Manda E., McBride, Mary T., LeCluyse, Edward L., Clewell, Rebecca A., Andersen, Melvin E.

“…•We characterize gene expression and DNA-binding of PPARα in human hepatocytes.•Only half of regulated genes show PPARα binding.•Directly bound genes include…”
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The role of fit-for-purpose assays within tiered testing approaches: A case study evaluating prioritized estrogen-active compounds in an in vitro human uterotrophic assay by Beames, Tyler, Moreau, Marjory, Roberts, L. Avery, Mansouri, Kamel, Haider, Saad, Smeltz, Marci, Nicolas, Chantel I., Doheny, Daniel, Phillips, Martin B., Yoon, Miyoung, Becker, Richard A., McMullen, Patrick D., Andersen, Melvin E., Clewell, Rebecca A., Hartman, Jessica K.

“…Chemical risk assessment relies on toxicity tests that require significant numbers of animals, time and costs. For the >30,000 chemicals in commerce, the…”
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Identifying qualitative differences in PPARα signaling networks in human and rat hepatocytes and their significance for next generation chemical risk assessment methods by McMullen, Patrick D., Bhattacharya, Sudin, Woods, Courtney G., Pendse, Salil N., McBride, Mary T., Soldatow, Valerie Y., Deisenroth, Chad, LeCluyse, Edward L., Clewell, Rebecca A., Andersen, Melvin E.

“…In this paper, we evaluate the PPARα signaling network in rats, examining transcriptional responses in primary hepatocytes exposed to a PPARα specific ligand,…”
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Application of a combined aggregate exposure pathway and adverse outcome pathway (AEP-AOP) approach to inform a cumulative risk assessment: A case study with phthalates by Clewell, Rebecca A., Leonard, Jeremy A., Nicolas, Chantel I., Campbell, Jerry L., Yoon, Miyoung, Efremenko, Alina Y., McMullen, Patrick D., Andersen, Melvin E., Clewell, Harvey J., Phillips, Katherine A., Tan, Yu-Mei

“…Advancements in measurement and modeling capabilities are providing unprecedented access to estimates of chemical exposure and bioactivity. With this influx of…”
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Mechanism-based testing strategy using in vitro approaches for identification of thyroid hormone disrupting chemicals by Murk, AlberTinka J., Rijntjes, Eddy, Blaauboer, Bas J., Clewell, Rebecca, Crofton, Kevin M., Dingemans, Milou M.L., David Furlow, J., Kavlock, Robert, Köhrle, Josef, Opitz, Robert, Traas, Theo, Visser, Theo J., Xia, Menghang, Gutleb, Arno C.

“…The thyroid hormone (TH) system is involved in several important physiological processes, including regulation of energy metabolism, growth and…”
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Addressing systematic inconsistencies between in vitro and in vivo transcriptomic mode of action signatures by McMullen, Patrick D., Pendse, Salil N., Black, Michael B., Mansouri, Kamel, Haider, Saad, Andersen, Melvin E., Clewell, Rebecca A.

“…Because of their broad biological coverage and increasing affordability transcriptomic technologies have increased our ability to evaluate cellular response to…”
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Profiling dose-dependent activation of p53-mediated signaling pathways by chemicals with distinct mechanisms of DNA damage by Clewell, Rebecca A, Sun, Bin, Adeleye, Yeyejide, Carmichael, Paul, Efremenko, Alina, McMullen, Patrick D, Pendse, Salil, Trask, O J, White, Andy, Andersen, Melvin E

“…As part of a larger effort to provide proof-of-concept in vitro-only risk assessments, we have developed a suite of high-throughput assays for key readouts in…”
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An in vitro approach to determine the human relevance of anti-spermatogenic effects of 4-methylmorpholine 4-oxide, monohydrate (NMMO) in rat reproductive toxicity studies by Clewell, Rebecca A., Clewell, Harvey J., Linakis, Matthew W., Easley, Charles A., Langmo, Jacqueline N., Salley, Joshua, Gentry, Robinan, Rücker, Thomas

“…Reduced sperm counts have been observed in male rats in an extended one generation reproductive toxicity study (EOGRTS, OECD 443) following repeated…”
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Dose-response modeling of etoposide-induced DNA damage response by Li, Zhenhong, Sun, Bin, Clewell, Rebecca A, Adeleye, Yeyejide, Andersen, Melvin E, Zhang, Qiang

“…The 2007 National Research Council Report "Toxicity Testing in the 21st Century: A Vision and A Strategy" recommended an integrated, toxicity pathway-oriented…”
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In vitro metabolism of di(2-ethylhexyl) phthalate (DEHP) by various tissues and cytochrome P450s of human and rat by Choi, Kyoungju, Joo, Hyun, Campbell, Jerry L., Clewell, Rebecca A., Andersen, Melvin E., Clewell, Harvey J.

“…► The hydrolysis of DEHP to MEHP by microsomal and/or cytosolic esterases in organs. ► MEHP was metabolized by CYP-dependent oxidation and dealkylation in…”
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Developing context appropriate toxicity testing approaches using new alternative methods (NAMs) by Andersen, Melvin E, McMullen, Patrick D, Phillips, Martin B, Yoon, Miyoung, Pendse, Salil N, Clewell, Harvey J, Hartman, Jessica K, Moreau, Marjory, Becker, Richard A, Clewell, Rebecca A

“…In the past 10 years, the public, private, and non-profit sectors have found agreement that hazard identification and risk assessment should capitalize on the…”
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An evaluation of the USEPA Proposed Approaches for applying a biologically based dose-response model in a risk assessment for perchlorate in drinking water by Clewell, Harvey J., Gentry, P. Robinan, Hack, C. Eric, Greene, Tracy, Clewell, Rebecca A.

“…The United States Environmental Protection Agency's (USEPA) 2017 report, “Draft Report: Proposed Approaches to Inform the Derivation of a Maximum Contaminant…”
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