Over the last decade or so, the field of environmental toxicology has shifted to more ethical, more efficient, and more scientifically rigorous methods to assess whether chemicals are safe or not. Until now, this assessment has relied on testing with vertebrates, using animals such as fish, amphibians, and birds. While these tests have been indispensable for collection of needed toxicological data, they are expensive ethically, financially, and procedurally. Animal testing has also been shown to lack the mechanistic insight that is the driving force of current predictive toxicology models, and we can close that gap with New Approach Methodologies (NAMs).

In my work with this issue, I’m particularly interested in how NAMs can lower the need to use standard in vivo research to capture faster and better information about the environmental security of products. In the last two decades, NAMs have exploited breakthroughs in both scientific and technological areas to provide a multitude of readouts to animal testing, ranging from in silico methods, cell based assays, organs on a chips, high content imaging and transgenic zebrafish embryo larva for high throughput screening. Methods using multiple 'omics add one more layer of data, adding up the promise of even a more nuanced understanding of chemical impact. However, in spite of their promise and increasing use in investigative toxicology, NAMs are only slowly becoming part of regulatory framework, exemplified in few cases such as OECD TG 249 guideline.

The Unique Power of NAMs in Environmental Toxicology

What I like about NAMs is that they allow us to look more quickly and in more detail at how chemicals interact with biological systems. Whereas traditional animal studies simply identify adverse effects without explaining underlying causes, NAMs enable us to do a real time, detailed, mechanistic assessment of these mechanisms. QSAR models, AI enabled toxicity predictions, and in vitro assays allow for new insights to environmental protection, which in turn leads to examples: application of the previously mentioned QSAR models, AI enabled toxicity predictions and in vitro assays.

AI and machine learning based toxicity predictions can provide rapid evaluation of massive datasets and their associated predicted behaviors with chemicals, whereas QSAR models are useful in elucidating the relationship between chemical structures and their biological effects. Not only does this align with ethical and financial goals of minimizing animal testing, but these approaches have the potential to provide significantly better understanding of chemical hazards, and contribute to shaping the next generation of predictive toxicology models.

Hands On For NAMs in Regulatory and Non-Regulatory Decision Making

The field's greatest challenge and opportunity is the regulatory application of NAMs. A complex task to integrate NAMs into regulatory frameworks is to thoroughly validate as true these methods should be accurate, reproducible and reliable. While the scientific community is working to show that NAMs are relevant to ecological contexts of the real world, regulatory agencies can start to use NAM derived data to perform chemical safety evaluations.

For example, Adverse Outcome Pathway (AOP) informed testing strategies are particularly promising. AOPs combine molecular and cellular events to adverse health outcomes, rooted in a more predictive and data rich framework for chemical hazard assessment. In theory, AOPs based testing strategies could potentially provide robust alternatives to current in vivo testing protocols, especially in fish and other vertebrates, for assessing sub-lethal effects.

Case Studies and the Weight of Evidence Approach

Case studies comparing NAM derived hazard characterizations with those from traditional animal testing employing a Weight of Evidence (WoE) framework can be one way to help foster the acceptance of NAMs as regulatory setting. Such comparisons also illustrate the accuracy and reliability of the NAMs, and provide the information needed for assessing the validity and domain of applicability of the NAMs.

From my Vision of the Future of NAMs in Environmental Toxicology.

First, I’m interested in the use of NAMs to reform environmental toxicology so it will lead to safer, more sustainable chemical assessment approaches. I am excited to hear from experts across the globe in the coming SETAC session, and hopefully, we will all grow together to drive this adoption of NAMs for complex scenarios, specifically assessment of chemical mixtures as well as environmental safety to ecologically relevant contexts.

In the end, NAMs are the gateway to the future of toxicology — more ethical, more efficient — and it is using available technology and innovative methodology to make smarter, data driven decisions about environmental health.

About the Author: Syed Nadeem Gillani is a solution-driven professional passionate about sustainable development and scientific research. With hands-on experience in tackling environmental issues, his focus is on addressing air, water, soil, and food pollution. His research interests include assessing nanomaterial toxicity’s impact on the environment and human health, emphasizing risk assessment and natural solutions. Motivated by personal experiences, Syed aims to specialize in environmental toxicology and human health, contributing to advancements in environmental solutions through analytical thinking, teamwork, and leadership.