IVIVE: Facilitating the Use of <i>In Vitro</i> Toxicity Data in Risk Assessment and Decision Making
Xiaoqing Chang,
Yu-Mei Tan,
David G. Allen,
Shannon Bell,
Paul C. Brown,
Lauren Browning,
Patricia Ceger,
Jeffery Gearhart,
Pertti J. Hakkinen,
Shruti V. Kabadi,
Nicole C. Kleinstreuer,
Annie Lumen,
Joanna Matheson,
Alicia Paini,
Heather A. Pangburn,
Elijah J. Petersen,
Emily N. Reinke,
Alexandre J. S. Ribeiro,
Nisha Sipes,
Lisa M. Sweeney,
John F. Wambaugh,
Ronald Wange,
Barbara A. Wetmore,
Moiz Mumtaz
Affiliations
Xiaoqing Chang
Inotiv-RTP, 601 Keystone Park Drive, Suite 200, Morrisville, NC 27560, USA
Yu-Mei Tan
U.S. Environmental Protection Agency, Office of Pesticide Programs, 109 T.W. Alexander Drive, Durham, NC 27709, USA
David G. Allen
Inotiv-RTP, 601 Keystone Park Drive, Suite 200, Morrisville, NC 27560, USA
Shannon Bell
Inotiv-RTP, 601 Keystone Park Drive, Suite 200, Morrisville, NC 27560, USA
Paul C. Brown
U.S. Food and Drug Administration, Center for Drug Evaluation and Research, 10903 New Hampshire Avenue, Silver Spring, MD 20903, USA
Lauren Browning
Inotiv-RTP, 601 Keystone Park Drive, Suite 200, Morrisville, NC 27560, USA
Patricia Ceger
Inotiv-RTP, 601 Keystone Park Drive, Suite 200, Morrisville, NC 27560, USA
Jeffery Gearhart
The Henry M. Jackson Foundation, Air Force Research Laboratory, 711 Human Performance Wing, Wright-Patterson Air Force Base, OH 45433, USA
Pertti J. Hakkinen
National Library of Medicine, National Center for Biotechnology Information, 8600 Rockville Pike, Bethesda, MD 20894, USA
Shruti V. Kabadi
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
Nicole C. Kleinstreuer
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
Annie Lumen
U.S. Food and Drug Administration, National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, USA
Joanna Matheson
U.S. Consumer Product Safety Commission, Division of Toxicology and Risk Assessment, 5 Research Place, Rockville, MD 20850, USA
Alicia Paini
European Commission, Joint Research Centre (JRC), 21027 Ispra, Italy
Heather A. Pangburn
Air Force Research Laboratory, 711 Human Performance Wing, 2729 R Street, Area B, Building 837, Wright-Patterson Air Force Base, OH 45433, USA
Elijah J. Petersen
U.S. Department of Commerce, National Institute of Standards and Technology, 100 Bureau Drive, Gaithersburg, MD 20899, USA
Emily N. Reinke
U.S. Army Public Health Center, 8252 Blackhawk Rd., Aberdeen Proving Ground, MD 21010, USA
Alexandre J. S. Ribeiro
U.S. Food and Drug Administration, Center for Drug Evaluation and Research, 10903 New Hampshire Avenue, Silver Spring, MD 20903, USA
Nisha Sipes
U.S. Environmental Protection Agency, Center for Computational Toxicology and Exposure, 109 TW Alexander Dr., Research Triangle Park, NC 27711, USA
Lisa M. Sweeney
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
John F. Wambaugh
U.S. Environmental Protection Agency, Center for Computational Toxicology and Exposure, 109 TW Alexander Dr., Research Triangle Park, NC 27711, USA
Ronald Wange
U.S. Food and Drug Administration, Center for Drug Evaluation and Research, 10903 New Hampshire Avenue, Silver Spring, MD 20903, USA
Barbara A. Wetmore
U.S. Environmental Protection Agency, Center for Computational Toxicology and Exposure, 109 TW Alexander Dr., Research Triangle Park, NC 27711, USA
Moiz Mumtaz
Agency for Toxic Substances and Disease Registry, Office of the Associate Director for Science, 1600 Clifton Road, S102-2, Atlanta, GA 30333, USA
During the past few decades, the science of toxicology has been undergoing a transformation 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 developed to reduce, refine, or replace whole animal testing, encouraging the judicious use of time and resources. Some of these methods have advanced past the exploratory research stage and are beginning to gain acceptance for the risk assessment of chemicals. A review of the recent literature reveals a burst of IVIVE publications over the past decade. In this review, we propose operational definitions for IVIVE, present literature examples for several common toxicity endpoints, and highlight their implications in decision-making processes across various federal agencies, as well as international organizations, including those in the European Union (EU). The current challenges and future needs are also summarized for IVIVE. In addition to refining and reducing the number of animals in traditional toxicity testing protocols and being used for prioritizing chemical testing, the goal to use IVIVE to facilitate the replacement of animal models can be achieved through their continued evolution and development, including a strategic plan to qualify IVIVE methods for regulatory acceptance.
