New approach methodologies (NAMs) are increasingly being used for regulatory decision making by agencies worldwide because of their potential to reliably and efficiently produce information that is fit for purpose while reducing animal use. This article summarizes the ability to use NAMs for the assessment of human health effects of industrial chemicals and pesticides within the United States, Canada, and European Union regulatory frameworks. While all regulations include some flexibility to allow for the use of NAMs, the implementation of this flexibility varies across product type and regulatory scheme. This article provides an overview of various agencies’ guidelines and strategic plans on the use of NAMs, and specific examples of the successful application of NAMs to meet regulatory requirements. It also summarizes intra- and inter-agency collaborations that strengthen scientific, regulatory, and public confidence in NAMs, thereby fostering their global use as reliable and relevant tools for toxicological evaluations. Ultimately, understanding the current regulatory landscape helps inform the scientific community on the steps needed to further advance timely uptake of approaches that best protect human health and the environment.

In 2012, the Council of Canadian Academies published the expert panel on integrated testing of pesticide’s report titled: Integrating emerging technologies into chemical safety assessment. This report was prepared for the Government of Canada in response to a request from the Minister of Health and on behalf of the Pest Management Regulatory Agency. It examined the scientific status of the use of integrated testing strategies for the regulatory health risk assessment of pesticides while noting the data-rich/poor dichotomy that exists when comparing pesticide formulations to most industrial chemicals. It also noted that the adoption of integrated approaches to testing and assessment (IATA) strategies may refine and streamline testing of chemicals, as well as improve results in the future. Moreover, the experts expected to see an increase in the use of integrated testing strategies over the next decade, resulting in improved evidence-based decision-making. Subsequent to this report, there has been great advancements in IATA strategies, which includes the incorporation of adverse outcome pathways (AOPs) and new approach methodologies (NAMs). This perspective provides the first Canadian regulatory update on how Health Canada is also advancing the incorporation of alternative, non-animal strategies, using a weight of evidence approach, for the evaluation of pest control products and industrial chemicals. It will include specific initiatives and describe how this work is leading to the creation of next generation risk assessments. It also reflects Health Canada’s commitment towards implementing the 3Rs of animal testing: reduce, refine and replace the need for animal studies, whenever possible.

The 1-year dog toxicity study is no longer required by certain pesticide regulatory jurisdictions, including the United States and the European Union. Health Canada's Pest Management Regulatory Agency (PMRA) examined its current requirement for this study to determine if it could be refined or eliminated. A retrospective analysis was conducted to examine the impact of the 1-year dog study on human health risk assessment. The Acceptable Daily Intake (ADI), a measure of the amount of a pesticide in food that can be ingested on a daily basis over a lifetime without an appreciable health risk, was the metric for this analysis. For 143 pesticides evaluated by the PMRA between 2008 and 2015, the supporting toxicology databases were examined to determine if other toxicology studies were protective of the findings in the 1-year dog study. When this criterion was not met, further investigation was undertaken to determine the potential impact of not having the 1-year dog study. For most of the pesticides, effect levels in the 1-year dog study were not substantially different from those in other toxicology studies, when considering factors such as dose-spacing and known experimental variability. The results of this analysis suggest that absence of the 1-year dog study would have minimal impact on the assessment of human health risk. Therefore, Health Canada's PMRA has removed the routine requirement for the 1-year dog study from its pesticide data requirements.

The present agrochemical safety evaluation paradigm is long‐standing and anchored in well‐established testing and evaluation procedures. However, it does not meet the present‐day challenges of rapidly growing populations, food insecurity, and pressures from climate change. To transform the current framework and apply modern evaluation strategies that better support sustainable agriculture, the Health and Environmental Sciences Institute (HESI) assembled a technical committee to reframe the safety evaluation of crop‐protection products. The committee is composed of international experts from regulatory agencies, academia, industry and nongovernmental organizations. Their mission is to establish a framework that supports the development of fit‐for‐purpose agrochemical safety evaluation that is applicable to changing global, as well as local needs and regulatory decisions, and incorporates relevant evolving science. This will be accomplished through the integration of state‐of‐the‐art scientific methods, technologies and data sources, to inform safety and risk decisions, and adapt them to evolving local and global needs. The project team will use a systems‐thinking approach to develop the tools that will implement a problem formulation and exposure driven approach to create sustainable, safe and effective crop protection products, and reduce, replace and refine animal studies with fit‐for‐purpose assays. A new approach necessarily will integrate the most modern tools and latest advances in chemical testing methods to guarantee the robust human and environmental safety and risk assessment of agrochemicals. This article summarizes the challenges associated with the modernization of agrochemical safety evaluation, proposes a potential roadmap, and seeks input and engagement from the broader community to advance this effort. © 2022 Health and Environmental Sciences Institute (HESI). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

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