August 2021
Research at Texas A&M University Superfund Research Center is paving the way for the use of in vitro and in silico methods in regulatory decision-making. Studies into replacement of animal tests with alternative methods has been ongoing for decades, but a recent shift in how regulatory agencies in the United States, Europe and the rest of the world approach regulatory science creates a renewed emphasis on actionable new methods that can be relied upon when deciding on human and environmental health hazards. The focus on development and application of the so-called “New Approach Methodologies (NAMs)”, technologies and approaches that can potentially provide relevant hazard and risk assessment information without the use of animal testing, is creating opportunities for the researchers and regulators to join forces to further establish scientific confidence in these approaches.
Development and application of NAMs is especially important for rapid hazard and risk assessment in cases of environmental and anthropogenic emergencies that may lead to redistribution of chemical contaminants of unknown type and quantities. In these situations, traditional approaches are often too slow or incomplete to provide timely information to decision-makers. To evaluate the complexities of hazardous chemical exposures, potential adverse health impacts, and potential hazards of exposures to complex mixtures, the Center’s multi-disciplinary teams collaborate on a number of projects that advance the field of NAMs in regulatory toxicology.
Just in the past 2 years, scientists in the Center published more than a dozen peer-reviewed articles (see below) that demonstrate the opportunities of applying human cell-based in vitro, tissue chip and computational methods to test for potential human health hazards of chemicals, complex substances and mixtures. These projects involve collaborations between research teams and Center’s Decision Science and Data Science support cores. In addition, almost all of these studies have been driven by Center’s trainees who gain valuable experience in fundamental research and the regulatory applications of the new science.
| 1. | Cardiotoxicity Hazard and Risk Characterization of ToxCast Chemicals Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes from Multiple Donors. Burnett SD, Blanchette AD, Chiu WA, Rusyn I. Chem Res Toxicol. 2021 Aug 27. doi: 10.1021/acs.chemrestox.1c00203. Online ahead of print. PMID: 34448577 |
| 2. | A new approach method for characterizing inter-species toxicodynamic variability. Burnett SD, Karmakar M, Murphy WJ, Chiu WA, Rusyn I. J Toxicol Environ Health A. 2021 Aug 24:1-20. doi: 10.1080/15287394.2021.1966861. Online ahead of print. PMID: 34427174 |
| 3. | Heart Muscle Microphysiological System for Cardiac Liability Prediction of Repurposed COVID-19 Therapeutics. Charrez B, Charwat V, Siemons BA, Goswami I, Sakolish C, Luo YS, Finsberg H, Edwards AG, Miller EW, Rusyn I, Healy KE. Front Pharmacol. 2021 Aug 4;12:684252. doi: 10.3389/fphar.2021.684252. PMID: 34421592 |
| 4. | Molecular mechanisms of environmental toxin cadmium at the feto-maternal interface investigated using an organ-on-chip (FMi-OOC) model. Kim S, Richardson L, Radnaa E, Chen Z, Rusyn I, Menon R, Han A. J Hazard Mater. 2021 Aug 2;422:126759. doi: 10.1016/j.jhazmat.2021.126759. PMID: 34391970 |
| 5. | Curated Data In – Trustworthy In Silico Models Out: The Impact of Data Quality on the Reliability of Artificial Intelligence Models as Alternatives to Animal Testing. Alves VM, Auerbach SS, Kleinstreuer N, Rooney JP, Muratov EN, Rusyn I, Tropsha A, Schmitt C. Altern Lab Anim. 2021 Jul 7:2611929211029635. doi: 10.1177/02611929211029635. Online ahead of print. PMID: 34233495 |
| 6. | Quantitative in Vitro-to-in Vivo Extrapolation for Mixtures: A Case Study of Superfund Priority List Pesticides. Valdiviezo A, Luo YS, Chen Z, Chiu WA, Rusyn I. Toxicol Sci. 2021 Jun 17:kfab076. doi: 10.1093/toxsci/kfab076. Online ahead of print. PMID: 34142158 |
| 7. | Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes as an in vitro model in toxicology: strengths and weaknesses for hazard identification and risk characterization. Burnett SD, Blanchette AD, Chiu WA, Rusyn I. Expert Opin Drug Metab Toxicol. 2021 Aug;17(8):887-902. doi: 10.1080/17425255.2021.1894122. PMID: 33612039 |
| 8. | Risk Characterization and Probabilistic Concentration-Response Modeling of Complex Environmental Mixtures Using New Approach Methodologies (NAMs) Data from Organotypic in Vitro Human Stem Cell Assays. Hsieh NH, Chen Z, Rusyn I, Chiu WA. Environ Health Perspect. 2021 Jan;129(1):17004. doi: 10.1289/EHP7600. Epub 2021 Jan 4. PMID: 33395322 |
| 9. | Risk Characterization of Environmental Samples Using In Vitro Bioactivity and Polycyclic Aromatic Hydrocarbon Concentrations Data. Chen Z, Lloyd D, Zhou YH, Chiu WA, Wright FA, Rusyn I. Toxicol Sci. 2021 Jan 6;179(1):108-120. doi: 10.1093/toxsci/kfaa166. PMID: 33165562 |
| 10. | Testing the efficacy of broad-acting sorbents for environmental mixtures using isothermal analysis, mammalian cells, and H. vulgaris. Wang M, Chen Z, Rusyn I, Phillips TD. J Hazard Mater. 2021 Apr 15;408:124425. doi: 10.1016/j.jhazmat.2020.124425. PMID: 33162237 |
| 11. | Grouping of UVCB substances with new approach methodologies (NAMs) data. House JS, Grimm FA, Klaren WD, Dalzell A, Kuchi S, Zhang SD, Lenz K, Boogaard PJ, Ketelslegers HB, Gant TW, Wright FA, Rusyn I. ALTEX. 2021;38(1):123-137. doi: 10.14573/altex.2006262. PMID: 33086383 |
| 12. | A Bayesian Method for Population-wide Cardiotoxicity Hazard and Risk Characterization Using an In Vitro Human Model. Blanchette AD, Burnett SD, Grimm FA, Rusyn I, Chiu WA. Toxicol Sci. 2020 Dec 1;178(2):391-403. doi: 10.1093/toxsci/kfaa151. PMID: 33078833 |
| 13. | Cardiovascular Effects of Polychlorinated Biphenyls and Their Major Metabolites. Grimm FA, Klaren WD, Li X, Lehmler HJ, Karmakar M, Robertson LW, Chiu WA, Rusyn I. Environ Health Perspect. 2020 Jul;128(7):77008. doi: 10.1289/EHP7030. PMID: 32701041 |
| 14. | Rapid hazard characterization of environmental chemicals using a compendium of human cell lines from different organs. Chen Z, Liu Y, Wright FA, Chiu WA, Rusyn I. ALTEX. 2020 Jun 8;37(4):623-638. doi: 10.14573/altex.2002291. PMID: 32521033 |
| 15. | In Vitro Bioavailability of the Hydrocarbon Fractions of Dimethyl Sulfoxide Extracts of Petroleum Substances. Luo YS, Ferguson KC, Rusyn I, Chiu WA. Toxicol Sci. 2020 Apr 1;174(2):168-177. doi: 10.1093/toxsci/kfaa007. PMID: 32040194 |
| 16. | Predicting tubular reabsorption with a human kidney proximal tubule tissue-on-a-chip and physiologically-based modeling. Sakolish C, Chen Z, Dalaijamts C, Mitra K, Liu Y, Fulton T, Wade TL, Kelly EJ, Rusyn I, Chiu WA. Toxicol In Vitro. 2020 Mar;63:104752. doi: 10.1016/j.tiv.2019.104752. PMID: 31857146 |