Citation:

Mitchell, C., N. Burden, M. Bonnell, M. Hecker, T. Hutchinson, M. Jagla, C. LaLone, L. Lagadic, S. Lynn, B. Shore, Y. Song, S. Vliet, J. Wheeler, AND M. Embry. New Approach Methodologies for the Endocrine Activity Toolbox: Environmental Assessment for Fish and Amphibians. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, 42(4):757-777, (2023). https://doi.org/10.1002/etc.5584

Impact/Purpose:

Scientific research suggests that environmental contaminants can disrupt the endocrine system by mimicking naturally produced hormones and binding to receptors in the body. This can lead to negative health outcomes in both humans and wildlife. Testing for these types of chemicals typically involves exposing animal models and recording adverse outcomes. However, these methods use a large number of animals and resources. New screening methods using cells and computer-based methods can help identify changes at the molecular, cellular, and tissue level that can be used to predict effects in individual or populations while reducing the number of animals used.

Description:

Multiple in vivo test guidelines focusing on the estrogen, androgen, thyroid, and steroidogenesis pathways have been developed and validated for mammals, amphibians, or fish. However, these tests are resource-intensive and often use a large number of laboratory animals. Developing alternatives for in vivo tests is consistent with the replacement, reduction, and refinement principles for animal welfare considerations, which are supported by increasing mandates to move toward an “animal-free” testing paradigm worldwide. New approach methodologies (NAMs) hold great promise to identify molecular, cellular, and tissue changes that can be used to predict effects reliably and more efficiently at the individual level (and potentially on populations) while reducing the number of animals used in (eco)toxicological testing for endocrine disruption. In a collaborative effort, experts from government, academia, and industry met in 2020 to discuss the current challenges of testing for endocrine activity assessment for fish and amphibians. Continuing this cross-sector initiative, our review focuses on the current state of the science regarding the use of NAMs to identify chemical-induced endocrine effects. The present study highlights the challenges of using NAMs for safety assessment and what work is needed to reduce their uncertainties and increase their acceptance in regulatory processes. We have reviewed the current NAMs available for endocrine activity assessment including in silico, in vitro, and eleutheroembryo models. New approach methodologies can be integrated as part of a weight-of-evidence approach for hazard or risk assessment using the adverse outcome pathway framework. The development and utilization of NAMs not only allows for replacement, reduction, and refinement of animal testing but can also provide robust and fit-for-purpose methods to identify chemicals acting via endocrine mechanisms. 

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