New Approach Methodologies for the Endocrine Activity Toolbox: Environmental Assessments for Fish and Amphibians
Jen Lynch and Tamar Schlekat, SETAC
A new critical review by Mitchell et al., published in Environmental Toxicology and Chemistry, examines the potential for expanding the use of New Approach Methodologies (NAMs) in endocrine activity testing and assessment. In the paper, “New Approach Methodologies for the Endocrine Activity Toolbox: Environmental Assessments for Fish and Amphibians,” the authors discuss the challenges of using NAMs for endocrine activity assessments for fish and amphibians and what is needed to reduce the uncertainties with such approaches. The authors recognize that the multiple in vivo test guidelines focusing on endocrine activity assessments have been validated, but work is needed on the use of NAMs for such assessments to support replacement, reduction and refinement of animal use. The authors also discuss the current and potential role for the use of NAMs for ecotoxicology testing, and in paradigms like adverse outcome pathways (AOPs) and integrated approaches to testing and assessments (IATAs). While the paper focuses on endocrine pathways, many of the points can apply to other endpoints in ecotoxicology.
In the paper, NAMs are defined as “all ecotoxicological tools other than traditional in vivo toxicity tests,” and the authors acknowledge that the lack of complexity of NAMs limits confidence in the ability to use them broadly. However, the paper does acknowledge that NAMs can increase the efficiency of screening to inform regulatory decisions while reducing the need for resource intensive studies reliant on large numbers of animals.
Mitchell and co-authors outline some known issues with NAMs and make suggestions to overcome them. They note that NAMs often have high false negatives or false positive outcomes – though, they also note that this is not unique to NAMs. They suggest the use of multiple NAMs to cover a variety of pathways, could help cover “gaps” and provide multiple lines of evidence to determine hazard potential. They also go into some detail about the challenge around validating NAMs. NAMs are often validated with reference substances that illicit strong positive or negative results; however, test substances, which the authors call “real world” chemicals, do not illicit clear positive or negative effects. To remedy that issue, they recommend that a range of reference chemicals are included in validation studies to cover the spectrum of effect magnitudes.
The paper comprehensively examines computational NAMs, which are often high speed and throughput, low cost, and can assess many molecules with relative ease. Yet, reliance on these tools is often limited by data quality. Streamlined data packages and harmonized data templates that satisfy multiple global chemical assessment regulatory requirements will ensure that collected data can be broadly utilized for chemical management. On that note, Mitchell et al. review the databases from which some of the tools, such as SeqAPASS and ToxCast, extrapolate their screening data.
The authors round out the article with several short- and longer-term priorities to help facilitate the regulatory use of NAMs. They underscore the importance of engaging regulatory authorities early on in defining data needs, to create consistent dialog across the scientific and regulatory communities. They re-emphasize the need to curate high-quality in vivo data in standardized formats, and they look to a future where case studies for chemicals and chemical classes using NAMs and in vivo data can support risk or hazard assessment, not just screening or prioritization. In the longer-term, the authors call for continued funding and resource allocation to NAMs and the development of new technologies and approaches.
In conclusion, the authors note that work moving forward to advance the use of NAMs in regulatory context is possible by gaining confidence in methodologies and using multiple assays in a battery to be protective of environmental health.
Author’s contact: [email protected]
