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

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.

Automated summary

Toxicology has transformed from observational to predictive science with the development of new approaches, such as in vitro assays and in silico models. In vitro to in vivo extrapolation (IVIVE) is gaining acceptance for risk assessment, and there has been a surge of IVIVE publications in the past decade. This review proposes operational definitions for IVIVE, explores its implications in decision-making processes, and highlights the challenges and future needs for its continued development.