The Future of Developmental Toxicity Testing

June 28, 2017
An important aspect of the safety profile for medicines, chemicals, and physical agents is the protection of developing offspring from the potential adverse effects of in utero exposures. To this end, the standard safety test design for this type of endpoint was developed in the mid-1960’s and has changed little in the ensuing half-century. Dr. John M. DeSesso recently authored an opinion that explores the future of developmental toxicity testing and how this will impact safety testing. The full article can be accessed here.

While embryo-fetal development studies have done a good job of protecting pregnant women and their babies, the tests are labor intensive, time-consuming, and use a large number of test animals. The advent and exploitation of the technology revolution has changed much of what we know about biology and has the potential to streamline the decision-making process for the identification of substances that may be teratogenic hazards. These welcome changes will save animals and expenses in addition to shortening the time to some decisions about whether or not to develop a new medicine or how to protect workers from potential occupational exposures. Data from informatics and computational approaches already inform hypothesis-driven studies to incisively address safety issues and will continue to do so and to a greater extent in the future. However, despite the impressive advances already available in the world of virtual biology, the anatomic, physiologic, and pharmacologic complexities of the entwined maternal-placental-fetal unit as well as the varied potential mechanisms for compensation in reaction to challenges are not yet able to be sufficiently modeled to enable conclusions to be made regarding safety. As a result, for at least the next few decades, the pregnant mammal will remain the final linchpin in teratology testing.

How Exponent Can Help

Exponent toxicologists have extensive experience in planning, conducting and coordinating regulatory guideline-based toxicity studies and investigative mechanistic studies to address potential developmental and reproductive issues. This includes interpreting study data relative to children’s health and developmental and reproductive toxicity for standard-setting and risk/safety assessment, screening assays for endocrine disruptors, quantitative benchmark dose analysis and risk assessment, and designing and interpreting mechanistic studies to address potential susceptibility in human fetuses and infants.