Response to comments received on the consultation for Proposed Maximum Residue Limits for Bromoxynil, (PMRL2024-11)

Health Canada – Pest Management Regulatory Agency
6 June 2025

Comments

Several comments were received from a non-governmental organization on the proposed maximum residue limit consultation document PMRL2024-11.

While these comments did not result in changes to the new MRLs proposed in this consultation document, it did highlight the importance of providing further explanation on MRLs and understanding acceptable risk.

The comments pertained primarily to the European Union's non-renewal of the approval of the active substance bromoxynil in September 2020, in particular the areas of reproductive and endocrine toxicity and exposure to children. Concerns were raised regarding the effectiveness of MRLs to ensure safety and the cumulative risks from pesticide mixtures. Comments were also received regarding public access to the studies used in PMRA's evaluation and increased transparency. Comments received on the above topics are addressed below. Only comments that are relevant and within the scope of the information presented in PMRL2024-11 were considered.

Health Canada responses

Health Canada's responsibility in pesticide regulation

Health Canada's primary objective is to protect the health and safety of Canadians, the environment and the food supply. This includes setting the conditions for each specific pesticide use in Canada, including the levels of pesticide residues that may be present in food commodities grown in Canada or that may be imported into the country. These conditions are set based on Health Canada's independent review of scientific data. With regards to food safety, the role of Health Canada's Pest Management Regulatory Agency (PMRA) is to set the amount of residues that may be present in or on food commodities grown in Canada and imported into Canada that do not pose a human health concern to any segment of the Canadian population including infants and toddlers, pregnant and nursing mothers, and the elderly.

International differences in pesticide regulations

Health Canada works collaboratively with international regulatory authorities such as the United States Environmental Protection Agency (USEPA) and European Food Safety Authority (EFSA) and monitors the regulatory status of pesticides in other Organisation for Economic Co-operation and Development (OECD) member countries. While each regulatory authority considers all the available scientific information, each country conducts independent risk assessments, taking into consideration country-specific legislation, policies and conditions of use. For these reasons, regulatory decisions may differ from country to country.

Health Canada continues to monitor for new information related to bromoxynil, including regulatory actions from other governments and international data, and will take appropriate action if risks of concern to human health or the environment are identified.

Maximum residue limit

A pesticide maximum residue limit (MRL) is the highest amount of a specific pesticide residue that may remain on or in a particular food commodity when the pesticide is used according to label directions. Health Canada is responsible for establishing science-based MRLs on food commodities grown domestically or imported into Canada to help ensure the food Canadians eat is safe. The MRL for each pesticide-crop combination is set at levels well below the amount that could pose a health concern. An MRL can be set on individual crops or on crop groups. For more details, refer to the Canada.ca webpage (Maximum residue limits, human health, and food safety - Canada.ca).

An MRL is not a measure of the toxicity of a pesticide. It is a scientifically-based calculation that estimates the maximum potential concentration of residues on food commodities. Once Health Canada determines that dietary risk from consuming the food commodity, that may be containing residues as observed in field trials where the pesticide was used according to approved label directions, is not a health concern, these field trial data are used to calculate the MRL. Health Canada establishes MRLs only when there are no health risks of concern to consumers.

Understanding acceptable risk

Before approving the registration of a pest control product for a specific use, Health Canada thoroughly assesses the risks to human health to make sure that the level of human exposure, when used according to the label directions, is well below the level that would be of health concern. The Pest Control Products Act (10(3)) requires that health risks are evaluated when specifying MRLs. Only pesticides for which health risks are shown to be acceptable are approved.

To do this assessment, Health Canada combines scientific information on pesticide toxicity with information on the degree and duration of dietary exposure to the pesticide residue from food. The risk assessment process involves four distinct steps:

1. Identifying the toxicology hazards of a pesticide
2. Determining the "acceptable dietary level" for Canadians (including all vulnerable populations, such as children, pregnant people and seniors) that is protective of adverse health effects, by setting the acceptable level at least 100-fold below the level where no effects are observed in animal studies;
3. Estimating how much of a pesticide people may be exposed to in their diet from all possible sources (domestic and imported commodities), based on how much residue remains in or on the food and the amount of treated food an individual may consume; and
4. Characterizing health risk by comparing the estimated dietary exposure to the acceptable dietary level set in Step 2.

Aggregate risk assessment also incorporates exposure from drinking water in the dietary exposure assessment (Step 3). If estimated human exposure from Step 3 is less than, or equal to the acceptable level (developed in Step 2), Health Canada concludes that consuming residues resulting from use according to approved label directions is not a health concern. The residue data from these studies are then used to calculate an MRL which is then subject to consultation to legally specify it as an MRL. If risks to human health from the consumption of treated crops are not shown to be acceptable, the pesticide product will not be permitted for sale or use in Canada, and an MRL (or import MRL) will not be established.

An MRL applies to the identified raw agricultural food commodity as well as to any processed food product that contains that commodity. On occasion, and depending on the characteristics of a given pesticide, a different MRL may be specified for a processed product made from that raw agricultural commodity (for example, corn versus corn oil).

As noted above, Health Canada establishes MRLs only when there are no health risks of concern to consumers; in other words, the risks are shown to be acceptable. This approach is consistent with the international approach to health risk assessment and is considered protective, as exposure to pesticide residues in the diet must be below levels that could pose a health concern.

Reproductive and endocrine toxicity

Bromoxynil was recently examined by Health Canada under Proposed Special Review PSRD2019-01. Available toxicology data from submitted studies as well as published reviews from international regulatory bodies were taken into consideration during that review. In this case, the studies assessed by the European Commission resulting in the classification of bromoxynil as a category 1B reproductive toxicant were reviewed by Health Canada. Health Canada does not designate, categorize, or classify pesticide active ingredients as endocrine disruptors or reproductive toxicants. Rather, observed effects are specifically identified (for example, decreased thyroid hormone or delayed ossification of ribs), and toxicology reference values are then selected for the most sensitive toxic effects of the pesticide appropriate to the potential exposure scenario. Identified toxicology reference values are typically from a study in which animal exposure is representative of the route, frequency and duration of human exposure. Health Canada's recent special review assessment of bromoxynil included consideration of the effects on the thyroid and uterus noted in the European publication. During the exposure assessment, anticipated human exposures to bromoxynil were below the established reference values and therefore are protective of the identified effects.

Health Canada agrees with the European Commission that human exposure levels of bromoxynil are not negligible. However, as noted above, all human health risk assessments performed by Health Canada are conducted by comparing predicted exposure to the acceptable dietary level and product registrations are only granted when predicted exposures are below levels of concern.

Residential exposure and risk

There are no registered domestic-class products containing bromoxynil; therefore, domestic handler exposure is not anticipated. Further, commercial-class products are not registered for use in residential areas. As such, dermal and inhalation exposure to individuals from handling bromoxynil or entering a treated area at home are not expected. Nonetheless, there is a potential for bystander inhalation exposure to spray drift that results from agricultural applications of bromoxynil. Current bromoxynil labels have statements to mitigate spray drift to residential areas, and potential bystander exposure to spray drift is considered to be significantly lower than the inhalation exposure of an applicator, for whom the potential inhalation risks are considered to be acceptable under current conditions of use. On this basis, the PMRA has concluded that the potential residential risk is considered to be acceptable for all populations, including children, under the current conditions of use (PSRD2019-01).

Cumulative risk

The Pest Control Products Act requires that Health Canada consider available information on cumulative human health effects from pesticides that have a common mechanism of toxicity (i.e., cause a common toxic effect(s) by the same, or essentially the same, sequence of major biochemical events).

As reported in the Cumulative Health Risk Assessment Framework (SPN2018-02), exposure to more than one chemical at a time is required for there to be a cumulative effect. When combined, chemicals can act jointly, resulting in three distinct types of action: independent, as an interaction or in an additive manner. Chemicals that act independently typically do so through different modes of action and are referred to as complex mixtures. Independently-acting chemicals, by definition, are not addressed by cumulative assessment as mandated under current pesticide legislation.

Chemicals that exhibit common mechanisms of toxicity, referred to as simple mixtures when combined, can be characterized as behaving in an additive manner. The concept of dose or concentration addition assumes no chemical interactions, but acknowledges that the combination of effects will be greater than that of each individual chemical. For the purpose of cumulative assessment, an additive action is the default assumption used by most regulatory authorities (USEPA, 2002; EFSA, 2008) including Health Canada.

Consideration of mixtures and the use of new technologies to investigate potential effects of pesticides that may result in cumulative effects through disparate mechanisms of toxicity is an area that continues to be developed within the international regulatory community that includes Health Canada participation.

One of the studies submitted by the objector to support their comments was a dietary exposure of multiple pesticides tested at TDI (tolerable daily intake) levels as set by European regulations. These levels were chosen as plausibly relevant to real life human exposures as most previous testing used much higher dose levels. The study observed higher body weight gain and metabolic disruption following long-term exposure to the pesticide mixture in diet. Notably, bromoxynil was not one of the compounds tested in this study. Furthermore, long-term, daily exposure to multiple pesticides at their respective maximum residue levels (MRLs) is highly unlikely, due to various factors, including diverse dietary habits and degradation processes (such as environmental degradation through rain and sunlight, as well as physical degradation through washing, peeling, and cooking). Real-world data show that most foods contain pesticide residues, including bromoxynil, at levels well below the MRLs. Hence, the likelihood of Canadians receiving long-term exposures to a collection of pesticides, all at maximum exposure levels for an extended period, is extremely rare.

In another cited study, bromoxynil was assessed alongside other pesticides registered in Canada. This in vitro cell culture study showed that bromoxynil can induce gene expression. Additionally, gene expression is further amplified when multiple compounds are present simultaneously. Not only does the concentration of bromoxynil tested in this study far exceed the maximum allowable levels in diet and the environment, but exposing cells directly to a specific concentration greatly exaggerates the true concentration that would be encountered by those same cells when pesticide residues were orally ingested by a person. These in-vitro studies provide information about underlying mechanisms of toxicity and guidance for further areas of research. However, no direct correlations can be drawn on the apical adverse effects likely to be observed in humans. Nonetheless, Health Canada continues to monitor the public literature for data relevant to human health risk assessments, and will incorporate relevant studies in its risk assessment when available.

Health Canada's comprehensive regulatory framework

The federal government has a comprehensive regulatory framework in place to prevent unacceptable risks to the health of Canadians and the environment from the use of pesticides. The Pest Control Products Act sets out very clear requirements for the safety assessment, establishment of MRLs and regulation of pesticides in Canada, including the fact that regulatory decisions about pesticides must be based on science.

There are over 300 scientists at Health Canada's PMRA conducting health and environmental risk assessments. These scientists are Canadians with families and children, who expect the same level of protection from harm as every person in Canada.

The regulatory decisions on pesticides are based on the review of hundreds, sometimes thousands, of scientific studies that have been conducted according to internationally-approved study protocols and Good Laboratory Practices (GLP). The studies required to complete a registration application include those that describe possible short- and long-term effects, how a pesticide can be absorbed and broken down in the body, what happens to it after it is applied to a crop and in the environment, and what effect it has on non-target organisms. The scientific data requirements to register a single pesticide costs many millions of dollars and take many years to generate. Thus, the onus is on industry to fund these studies, given they are the developers and owners of the products. Health Canada scientists examine and critically review the study methodology and raw data for all available studies to assess the validity of the study conclusions. Health Canada scientists compare the various studies available for each pesticide looking for consistencies and inconsistencies between results and conclusions. Health Canada scientists also review published literature to assure safety of all registered pesticides. They also compare this available information to other substances that are similar or belong to the same class of pesticides and examine peer-reviewed academic research available in the public domain. If a study does not meet the requirements, it is not considered acceptable for risk assessment purposes. Health Canada scientists do not accept findings of studies of poor quality claiming something is either safe or causes harm, especially when high-quality science contradicts those findings.

Access to scientific data

Scientific data and information considered during Health Canada's pre- and post-market scientific evaluations may come from a variety of sources, such as from applicants/registrants, federal and provincial governments, academia and the research community, other internationally recognized regulatory agencies, as well as a large body of published independent scientific studies.

The notice of intent for the proposed amendments to the Pest Control Products Regulations to facilitate access to confidential test data (CTD) was published for consultation in June 2023. Currently, members of the public may inspect confidential test data either in-person in the Reading Room, located at the Health Canada PMRA National Head Office in Ottawa, Ontario, or remotely, and initiatives are underway to allow for greater accessibility of this information. Refer to NOI2023-01, Strengthening the regulation of pest control products in Canada (20 June 2023) for further details.

Increased transparency

Health Canada's PMRA has made substantial improvements to the transparency and clarity of its published proposals and decisions, with more initiatives underway.

Health Canada's PMRA has also developed and consulted on a Notice of Intent on the proposed amendments to the Pest Control Products Regulations. This includes the intent to publish notifications to increase transparency of MRL applications for pesticide residues on imported food products.

To further increase transparency as well as to further promote science literacy and help people in Canada better understand the complicated aspects of pesticide science, including about MRLs, Health Canada's PMRA has published an Infographic on MRLs in Canada to explain what MRLs are and how they are set; it has posted a blog Collaborating for safer food and stronger agriculture (science.gc.ca), written in collaboration with the CFIA that explains the roles of CFIA and the PMRA in pesticide regulation and cooperation in keeping Canada's food safe; and has also issued a podcast on MRLs in conjunction with AAFC.

Conclusion

Dietary risks from the consumption of bromoxynil residues in or on the food commodities noted in the PMRL consultation document (PMRL2024-11) were shown to be acceptable when bromoxynil is used according to the approved label directions. Findings of the submitted studies with the comments would not change this conclusion. Therefore, the foods containing these residues are safe to eat, and the MRLs will be specified in the MRL Database as proposed (PMRL2024-11).