IVIVE: Facilitating the Use of In Vitro Toxicity Data in Risk Assessment and Decision Making

• Published in: Toxics (Basel) Vol. 10; no. 5; p. 232
• Main Authors: Chang, Xiaoqing, Tan, Yu-Mei, Allen, David G, Bell, Shannon, Brown, Paul C, Browning, Lauren, Ceger, Patricia, Gearhart, Jeffery, Hakkinen, Pertti J, Kabadi, Shruti V, Kleinstreuer, Nicole C, Lumen, Annie, Matheson, Joanna, Paini, Alicia, Pangburn, Heather A, Petersen, Elijah J, Reinke, Emily N, Ribeiro, Alexandre J S, Sipes, Nisha, Sweeney, Lisa M, Wambaugh, John F, Wange, Ronald, Wetmore, Barbara A, Mumtaz, Moiz
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.05.2022; MDPI
• Subjects: absorption; Acceptance tests; Animal models; Biocompatibility; Biological activity; Chemicals; Decision making; distribution; Dosimetry; Drug dosages; Environmental health; Environmental protection; excretion (ADME); Government agencies; Hazardous materials; Health risk assessment; Health risks; In vitro methods and tests; in vitro to in vivo extrapolation (IVIVE); In vivo methods and tests; International organizations; Literature reviews; Metabolism; Metabolites; Pharmacokinetics; Plasma; Public health; Review; Risk acceptance; Risk assessment; Test procedures; Toxicity; Toxicity testing; Toxicology; United States > US; new approach methodologies (NAMs); risk assessment; dosimetry; in vitro to in vivo extrapolation (IVIVE); absorption; physiologically based pharmacokinetic (PBPK) model; excretion (ADME); metabolism; toxicity tests; distribution; Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM)
• ISSN: 2305-6304; 2305-6304
• DOI: 10.3390/toxics10050232

During the past few decades, the science of toxicology has been undergoing a transformation from observational to predictive science. New approach methodologies (NAMs), including assays, models, read-across, and to 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.