Citation: Chang, X.; Tan, Y.-M.; Allen, D.G.; Bell, S.; Brown, P.C.; Browning, L.; Ceger, P.; Gearhart, J.; Hakkinen, P.J.; Kabadi, S.V.; et al. IVIVE: Facilitating the Use of In Vitro Toxicity Data in Risk Assessment and Decision Making. Toxics 2022, 10, 232. https://doi.org/10.3390/toxics10050232 Academic Editors: Sunmi Kim and Eduardo Rocha Received: 25 March 2022 Accepted: 24 April 2022 Published: 1 May 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). toxics Review IVIVE: Facilitating the Use of In Vitro Toxicity Data in Risk Assessment and Decision Making Xiaoqing Chang 1,† , Yu-Mei Tan 2,† , David G. Allen 1 , Shannon Bell 1 , Paul C. Brown 3 , Lauren Browning 1,‡ , Patricia Ceger 1 , Jeffery Gearhart 4,§ , Pertti J. Hakkinen 5,§ , Shruti V. Kabadi 6 , Nicole C. Kleinstreuer 7 , Annie Lumen 8, ‖ , Joanna Matheson 9 , Alicia Paini 10,¶ , Heather A. Pangburn 11 , Elijah J. Petersen 12 , Emily N. Reinke 13 , Alexandre J. S. Ribeiro 3,** , Nisha Sipes 14 , Lisa M. Sweeney 15 , John F. Wambaugh 14 , Ronald Wange 3 , Barbara A. Wetmore 14 and Moiz Mumtaz 16, * 1 Inotiv-RTP, 601 Keystone Park Drive, Suite 200, Morrisville, NC 27560, USA; xiaoqing.chang@inotivco.com (X.C.); dave.allen@inotivco.com (D.G.A.); shannon.bell@inotivco.com (S.B.); lauren.browning@icf.com (L.B.); patricia.ceger@inotivco.com (P.C.) 2 U.S. Environmental Protection Agency, Office of Pesticide Programs, 109 T.W. Alexander Drive, Durham, NC 27709, USA; tan.cecilia@epa.gov 3 U.S. Food and Drug Administration, Center for Drug Evaluation and Research, 10903 New Hampshire Avenue, Silver Spring, MD 20903, USA; paul.brown@fda.hhs.gov (P.C.B.); axribeiro@hovione.com (A.J.S.R.); ronald.wange@fda.hhs.gov (R.W.) 4 The Henry M. Jackson Foundation, Air Force Research Laboratory, 711 Human Performance Wing, Wright-Patterson Air Force Base, OH 45433, USA; jgearhart@hjfresearch.org 5 National Library of Medicine, National Center for Biotechnology Information, 8600 Rockville Pike, Bethesda, MD 20894, USA; pertti.hakkinen@nih.gov 6 U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Food Additive Safety, 5001 Campus Drive, HFS-275, College Park, MD 20740, USA; shruti.kabadi@fda.hhs.gov 7 National Institute of Environmental Health Sciences, National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, P.O. Box 12233, Research Triangle Park, NC 27709, USA; nicole.kleinstreuer@nih.gov 8 U.S. Food and Drug Administration, National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, USA; alumen@amgen.com 9 U.S. Consumer Product Safety Commission, Division of Toxicology and Risk Assessment, 5 Research Place, Rockville, MD 20850, USA; jmatheson@cpsc.gov 10 European Commission, Joint Research Centre (JRC), 21027 Ispra, Italy; alicia.paini@esqlabs.com 11 Air Force Research Laboratory, 711 Human Performance Wing, 2729 R Street, Area B, Building 837, Wright-Patterson Air Force Base, OH 45433, USA; heather.pangburn.1@us.af.mil 12 U.S. Department of Commerce, National Institute of Standards and Technology, 100 Bureau Drive, Gaithersburg, MD 20899, USA; elijah.petersen@nist.gov 13 U.S. Army Public Health Center, 8252 Blackhawk Rd., Aberdeen Proving Ground, MD 21010, USA; emily.n.reinke.civ@mail.mil 14 U.S. Environmental Protection Agency, Center for Computational Toxicology and Exposure, 109 TW Alexander Dr., Research Triangle Park, NC 27711, USA; sipes.nisha@epa.gov (N.S.); wambaugh.john@epa.gov (J.F.W.); wetmore.barbara@epa.gov (B.A.W.) 15 UES, Inc., 4401 Dayton-Xenia Road, Beavercreek, OH 45432, Assigned to Air Force Research Laboratory, 711 Human Performance Wing, Wright-Patterson Air Force Base, OH 45433, USA; lisa.sweeney.3.ctr@us.af.mil 16 Agency for Toxic Substances and Disease Registry, Office of the Associate Director for Science, 1600 Clifton Road, S102-2, Atlanta, GA 30333, USA * Correspondence: mgm4@cdc.gov † These authors contributed equally to this work. ‡ Current address: ICF, 2635 Meridian Pkwy Suite 200, Durham, NC 27713, USA. § Retired. ‖ Current address: Clinical Pharmacology Modeling and Simulations, Amgen, South San Francisco, CA 94080, USA. ¶ Current address: esqLABS GmbH, Hambierich 34, 26683 Saterland, Germany. ** Current address: R&D Analytical Development, Hovione Farmaciência S.A., 1649-038 Lisboa, Portugal. Abstract: During the past few decades, the science of toxicology has been undergoing a transfor- mation from observational to predictive science. New approach methodologies (NAMs), including in vitro assays, in silico models, read-across, and in vitro to in vivo extrapolation (IVIVE), are being Toxics 2022, 10, 232. https://doi.org/10.3390/toxics10050232 https://www.mdpi.com/journal/toxics