Information Note – Animal testing and use of new approach methods in pesticide assessments

Health Canada's Pest Management Regulatory Agency
30 July 2025

Table of contents

• Introduction
• Background: Use of animal testing in current pesticide assessments
• Efforts to reduce reliance on vertebrate animal testing under Canadian Environmental Protection Act
• Challenges and future considerations
• For applicants and registrants
• For more information

The purpose of this Information Note is to describe the current role that toxicity studies in laboratory animals play in the regulation of pesticides in Canada, to summarize efforts underway to advance and expand the use of alternatives to animal testing, and to outline Pest Management Regulatory Agency (PMRA)'s vision pertaining to the incorporation of new approach methods (NAMs) into the pesticide regulatory framework.

Introduction

In Canada, the regulation of pesticides is shared among all levels of government. Federally, pesticides are regulated under the Pest Control Products Act, which is administered by Health Canada's Pest Management Regulatory Agency (PMRA). Our number one priority is to protect the health and safety of people in Canada and the environment.

Before a pesticide is allowed to be used or sold in Canada, it must undergo a rigorous scientific assessment process that provides reasonable certainty that no harm to human health and the environment will occur, and that products have value, when pesticides are used according to label directions. This assessment also takes into consideration populations who may be disproportionately impacted, such as pregnant and nursing people, infants, children and seniors. Health Canada also regularly re-evaluates pesticides that are on the market to determine whether they continue to meet the Department's health and environmental standards and hence whether they should continue to be permitted for use in Canada. The traditional approach to chemical risk assessment relies on toxicity testing in animals to evaluate a range of possible adverse effects. During the human health and environmental risk assessment process, toxicity tests covering a broad range of organisms, exposure routes and durations, parameters and endpoints are considered, where available or required.

Background: Use of animal testing in current pesticide assessments

Depending on the type of pesticide being evaluated, results from numerous scientific studies (in some cases hundreds of studies) are reviewed to determine whether the pesticide would have any negative effect on people or the environment. The PMRA also regularly re-evaluates pesticides that are on the market to determine whether they continue to meet the Agency's health and environmental standards and hence whether they should continue to be permitted for use in Canada. A special review of a registered pesticide may also be initiated under certain circumstances, such as when there are reasonable grounds to believe that the health or environmental risks are unacceptable.

As part of these rigorous scientific assessments, the PMRA requires information on the potential toxic effects of pesticides to determine any potential hazards to human health and the environment resulting from pesticide exposure. Toxicity information typically includes, in part, animal testing data generated by pesticide manufacturers that investigate effects that may result from various durations of exposure (acute, short-term, and chronic exposure), as well as various routes of exposure (including ingestion, deposition on skin, inhalation, and waterborne exposures) in various organisms (for example, mammalian vertebrates, birds, fish, and plants). These animal studies include examination of possible effects on reproduction and development, the endocrine, nervous and immune systems, or any other toxic effects such as cancer. There are many established tests that use a variety of techniques to assess the potential effects of chemicals on human health and the environment. No single test provides information on all potential hazards an exposure to a chemical may pose and thus multiple types of tests are considered when conducting a pesticide assessment. For ethical reasons, studies with human participants that assess systemic toxicity of a pesticide are not used by the PMRA in its assessments.

In the human health assessment, animal toxicity studies are designed to assess a pesticide's potential to cause adverse health effects, including, but not limited to, target organ toxicity (such as damage to the liver or kidneys), effects on the developing fetus through exposure via the maternal animal, impairment in the animal's ability to reproduce, and cancer. Results from these animal toxicity studies are used to extrapolate potential human health risks by identifying the dose level at which no adverse effects are observed in animal studies. This is then compared to levels at which humans are normally exposed when pesticide products are used according to label directions. For a pesticide to be considered acceptable for registration, a sufficient margin of safety (typically at least 100-fold) must exist between the dose levels at which there are no adverse health effects noted in animals and the estimated human exposure under approved conditions of use.

In the environmental assessment, effects from measurable holistic endpoints (for example, survival, reproduction, growth/development) are also evaluated to assess the potential risk to individual organisms, populations, or ecological systems at environmentally relevant concentrations. The environmental risk characterization integrates the effects and exposure information using an iterative process with a tiered approach, as per Health Canada's Approach to Environmental Risk Assessment for Pest Control Products.

To be acceptable, studies are typically conducted according to international testing protocols published by the Organisation for Economic Co-operation and Development (OECD) or the United States Environmental Protection Agency (USEPA), and must adhere to international and Canadian requirements to ensure protection of the welfare of laboratory animals. Additionally, the PMRA makes every effort to make the best use of available animal studies and toxicity information in assessing the hazards of a particular pesticide, and does not endorse testing if not necessary for the protection of human health or the environment. This is consistent with the OECD Mutual Acceptance of Data (MAD) System, which ensures that test data generated in one country is accepted in other jurisdiction thus preventing unnecessary duplication of testing, as well as the Comprehensive Economic and Trade Agreement (CETA) between Canada and the European Union, which also discourages duplicative animal testing and encourages sharing of animal studies among applicants.

The approach used within the PMRA for assessing the hazards of pesticides and potential risks is consistent with approaches taken by other reputed pesticide regulatory systems, including the USEPA, in that it ensures that a protective margin exists between anticipated exposure levels and those levels at which toxic effects have been observed through animal toxicity testing.

Efforts to reduce reliance on animal testing under the Pest Control Products Act

Animal testing continues to be used as an indicator of the risk to human health and the environment from exposure to pesticides because such testing has historically been considered reliable in the assessment of whole-system toxicity. Nevertheless, studies on experimental animals may have limitations in terms of biological relevance, time required for tests, low throughput, and expense. The drive to modernize toxicity testing as well as ethical and scientific considerations are driving the search for non-vertebrate approaches to toxicity evaluation.

In line with many international regulators in various sectors, the PMRA supports the reduction of unnecessary animal testing where scientifically justified and remains committed to applying the international principles on the judicious use of animals in toxicity testing through the replacement, reduction, and refinement of animals studies, known as the 3R, wherever possible as previously communicated in the 2021 article Canadian Regulatory Perspective on Next Generation Risk Assessments for Pest Control Products and Industrial Chemicals.

NAMs present a desirable alternative to traditional vertebrate animal-based methods for toxicity testing of chemicals. NAMs are broadly defined as any technology, methodology, approach, or combination thereof that can be used to replace, reduce, or refine animal toxicity testing and allow for more rapid or effective screening, prioritization and/or assessment of chemicals. These methods may include the use of computer-based (computational) models, modernized whole-organism assays, or assays with biological molecules, cells, tissues or organs, as well as exposure prediction approaches.

The Pest Control Products Act currently provides flexibility for the PMRA to take into consideration alternatives to animal testing in the assessment of pest control products, including NAMs. For instance, the PMRA considers requests from pesticide manufacturers to waive requirements for animal studies or to consider non-animal alternatives to meet the hazard assessment requirements when feasible and scientifically demonstrated. In addition, the PMRA issued guidance for industry on the waiving of mammalian acute toxicity studies in 2013 and revised the data requirements for pesticides to remove the routine requirement for the 1-year dog study in 2016 and the acute dermal toxicity study in 2018. The PMRA also started accepting the use of in vitro data alone for estimating dermal absorption in 2021. The PMRA has made progress in this area and continues to seek opportunities to apply non-animal approaches in the fulfillment of data requirements and information gaps.

Efforts to reduce reliance on vertebrate animal testing under Canadian Environmental Protection Act

While not specific to pesticides, the Government of Canada introduced amendments to the Canadian Environmental Protection Act, 1999 (CEPA) under Bill S-5 (Strengthening Environmental Protection for a Healthier Canada Act) in 2024 that recognize the need to replace, reduce, or refine the use of vertebrate animal testing when assessing the risks that substances may pose to human health and the environment.

Health Canada and Environment and Climate Change Canada are developing a strategy as part of the Plan of Priorities to guide their path to replace, reduce or refine the use of vertebrate animals for toxicity testing and assessment under CEPA. As pest control products are regulated under the Pest Control Products Act, which is separate legislation, the recent amendments to CEPA do not apply directly to the regulation of pesticides. However, the strategy currently being developed under CEPA could be applicable, where relevant and possible, to other Government of Canada regulatory programs, including pesticides.

Challenges and future considerations

The primary limitation in adoption of alternative testing methods in the pesticide regulatory regime is a lack of validation of such new approaches for use in hazard and risk assessment that demonstrate equivalent robustness and proof of safety or toxicity compared to the current standard of animal testing. Validation and scientific confidence play important roles in the regulatory acceptance of alternative and new approach methods, as does ensuring the same level or better protection of human health and the environment. Alternatives to animal testing are considered in a weight-of-evidence assessment and would generally carry more weight if these requirements have been demonstrated.

While there have been some key advancements in the development and implementation of non-animal testing methods, science has not yet progressed to the point where alternative methods can completely replace animal testing by providing equivalent or better protection to human health or the environment. Validated, non-animal alternatives exist for certain types of tests (for example, in vitro tests for irritation and dermal sensitization); however, there are several complex health endpoints that lack validated alternative methods to animal testing. Complex endpoints, such as systemic toxicity, developmental or reproductive toxicity, or carcinogenicity require further research to establish approaches that are protective of the multitude of possible effects using NAMs. For example, in human health, a key factor for assessing any type of systemic toxicity includes an evaluation of the process by which compounds are absorbed, metabolized, distributed throughout the body and excreted, and these processes can be difficult to fully capture with cell-based NAMs. Moreover, currently available cell-based NAMs may lack sufficient biological coverage (that is, to be representative of all tissues) of the target species. Accordingly, it is expected that for most applications, a battery of NAMs will need to be integrated to provide adequate coverage of toxicokinetic processes and protection of humans and non-target organisms against the toxicological effects of pesticides.

It is also important to note that some NAMs may still make use of animals (for example, short-term studies intended to collect information on effects on gene and protein activity, or toxicogenomic data), but the methods are typically refined to maximize the information generated and provide critical information, such as mechanistic knowledge, that may lead to the replacement of other animal tests. This is an important step towards reducing the total number of animals used in chemical risk assessment until the necessary NAMs become available to replace animal toxicity testing altogether.

As NAMs develop further, harmonization among regulatory partners to the extent possible will be key to the effective adoption of NAMs across various jurisdictions. This is of particular significance when it comes to harmonization of testing data under the OECD Mutual Acceptance of Data (MAD) System, which facilitates the sharing of data across multiple countries. Efforts to align with regulatory partners may present broader challenges and delays in the availability of validated or accepted alternative testing data for use in regulatory decision-making.

The PMRA is an active participant in various international activities and several multi-stakeholder initiatives that are exploring alternative approaches to animal testing and aim to reduce animal testing while ensuring the protection of human health and the environment. Examples of such collaborations include the Health and Environmental Sciences Institute Transforming the Evaluation of Agrochemicals Committee and the project organized by the International Union of Pure and Applied Chemistry: A Global Framework Using Weight of Evidence Incorporating New Approach Methods for Risk Assessment of Crop Protection Chemicals. The insight gained from these initiatives will help with the identification of NAMs, where available, that may serve as alternatives to animal testing while maintaining scientific rigor to ensure that regulatory decisions will continue to protect people living in Canada and the environment from potential risks posed by pesticides. The development and assessment of case studies exploring the use of NAMs in pesticide assessments will be critical to building regulator confidence going forward. This iterative process of collaboration and experimentation will ensure that decisions made by the PMRA remain supported by the best available science.

The PMRA is open to further collaboration with stakeholders and welcomes the opportunity to share progress, successes and challenges in incorporating NAMs into hazard assessments. In particular, the PMRA may gain insight from the experiences of pesticide manufacturers in using NAMs during the development phase of a pesticide toxicology database and from the knowledge of academics and other innovators involved in the development of NAMs. The PMRA would also benefit from the receipt of any studies conducted using NAMs that are generated in parallel with traditional in vivo studies from pesticide applicants as part of the pre-submission or regular submission process. This will help to broaden the regulatory experience with evaluating NAMs and how they may be able to meet the PMRA's regulatory requirements. Finally, the PMRA welcomes further collaboration with stakeholders on the advancement of case studies in order to explore interpretation and practical application of NAMs in pesticide assessments.

For applicants and registrants

The PMRA offers a free pre-submission consultation service that provides regulatory guidance to applicants prior to the submission of an application. To request a pre-submission consultation or to obtain additional information on submitting an application that includes a NAM-based approach, contact the PMRA at pmra.presubs-prealables@hc-sc.gc.ca.

For more information

Pest Management Information Service