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Response to comments received on the PMRL consultation for proposed new and revised maximum residue limits for sulfoxaflor (PMRL2021-25)

Health Canada's Pest Management Regulatory Agency
31 May 2024

Table of contents

Background

Applications were submitted by the Pest Management Centre (PMC) of Agriculture and Agri-Food Canada (AAFC) under several submissions pertaining to sulfoxaflor to add caneberries (crop subgroup 13-07A), bushberries (crop subgroup 13-07B), quinoa, asparagus, and globe artichokes to the product label of Closer Insecticide (PCP# 30826), for the control or suppression of aphids, leafhoppers, and/or Lygus bugs (including tarnished plant bugs) on these crops. These uses were requested in support of minor use projects identified by the Canadian minor use grower communities to register domestic uses on these crops. These uses will provide a new mode of action which may aid in resistance management for these pests (see the Value section of this document). Revised maximum residue limits (MRLs) for sulfoxaflor were proposed in PMRL2021-25, Sulfoxaflor as a result of these applications to accommodate domestic uses on lingonberries and lowbush blueberries. The MRLs currently specified on these commodities are import MRLs on the low growing berries subgroup (see the section on Amending maximum residue limits).

Approximately 1000 comments were received from the general public, growers/users, health professionals, academia, the pesticide industry, and non-governmental organizations on the proposed maximum residue limit consultation document PMRL2021-25 for the requested sulfoxaflor uses.

Many comments opposed the presence and/or increase of any pesticide residues in food and questioned the definition of acceptable risk and the use of the precautionary principle. There were also questions as to why MRLs differed for the same commodity in different countries, as well as why pesticide regulatory systems differed between various countries and jurisdictions, such as that of the European Union and the United States (U.S.). Comments were also received regarding the use of industry generated data and public access to these studies, transparency of the consultation process, cumulative risks, the toxic effects including the carcinogenic potential of sulfoxaflor and risks to vulnerable populations. Comments received on the above topics are addressed in this document.

The environmental risks of sulfoxaflor on bushberries, globe artichoke, and caneberries were assessed under several submissions pertaining to sulfoxaflor, and were determined to be acceptable and consistent with those previously evaluated under PRD2015-08, Sulfoxaflor with amended label language pertaining to bees. Comments, including any scientific information, related to the environment are not addressed in this document but, as relevant, will be considered following finalization of the new Proposed Policy on Continuous Oversight of Pesticides, PRO2024-01 from Health Canada's Pest Management Regulatory Agency (PMRA).

While these comments do not result in changes to the MRLs proposed in this consultation document, they do highlight the importance of providing further explanation on Canada's pesticide regulatory system, how MRLs are determined and the purpose of setting them.

Health Canada's responsibility in pesticide regulation

Health Canada's priority is to protect the health and safety of Canadians, the environment and the food supply. This includes setting the conditions for approval of 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. The role of Health Canada's PMRA is to help make sure that the amount of residues that may be present in or on food commodities grown in Canada and imported into Canada does not pose a human health concern to any segment of the Canadian population including infants and toddlers, pregnant and nursing people, and the elderly.

While Health Canada has the authority to register pesticides, municipalities and provinces/territories have the authority to further impose restrictions on the use of pesticides that have been approved at the federal level by the PMRA.

For more information on the activities of Health Canada's PMRA, you are invited to refer to the PMRA's Annual Report.

Health Canada's comprehensive regulatory framework for pesticides

Because of the toxic nature of pesticides, 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 assessment and regulation of pesticides in Canada, including the requirement that regulatory decisions about pesticides must be based on science.

There are nearly 400 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 purpose of these risk assessments is to put in place the conditions of use for each pesticide product so that the levels at which Canadians are exposed do not cause any harmful effects and also meet protection goals for the environment. Only products that can be used safely are approved for use in Canada.

Regulatory decisions 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. 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 in the environment, and what effect it has on non-target organisms. 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. Scientists compare various studies available for each pesticide looking for consistencies and inconsistencies between results and conclusions. They also compare available information on a pesticide with others 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 studies of poor quality claiming something is either safe or causes harm, especially when high-quality science contradicts those findings.

Value

The proposed sulfoxaflor applications for Canadian use on bushberries, caneberries, globe artichokes, and asparagus were joint reviews with the United States Environmental Protection Agency (USEPA). Residue trials were conducted cooperatively between the Interregional Research Project No. 4 (IR-4) and the PMC of Agriculture and Agri-Food Canada to support these minor use projects identified by the minor use grower communities in both countries as pest solution priorities.

Sulfoxaflor represents a new mode of action for aphids, leafhopper and Lygus bugs (including tarnished plant bug) on bushberries (crop subgroup 13-07B) and for aphids and Lygus bugs (including tarnished plant bug) on globe artichoke and for aphids on asparagus. For Lygus bugs (including tarnished plant bug) on caneberries (crop subgroup 13-07A) and globe artichoke, sulfoxaflor is the first active ingredient registered for these pest-crop combinations. Closer Insecticide has value in resistance management as it represents a new mode of action for these uses. The submitted value information demonstrates the control of aphids, Lygus bugs (including tarnished plant bug) and suppression of leafhopper and on bushberries (crop subgroup 13-07B), control of aphids and Lygus bugs (including tarnished plant bug) on globe artichoke, suppression of Asparagus aphids on asparagus and control of Lygus bugs (including tarnished plant bug) on caneberries (crop subgroup 13-07A) at the rates proposed. These User Requested Minor Use Label Expansions (URMULEs) would provide a new mode of action for these uses which may aid in resistance management for these pests. There are also no pesticide product alternatives for the use of sulfoxaflor on quinoa for the control of Lygus bugs.

Maximum residue limit

A pesticide MRL is the highest amount of pesticide residue that may remain on or in food when a 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 Maximum residue limits, human health, and food safety page on Canada.ca.

Pesticide residues in or on food commodities

Pesticides are used on food commodities grown using conventional and organic practices to maintain food quality or prevent damage caused by pests, including insects, weeds, and fungal diseases. This helps ensure Canada has a secure supply of healthy food.

Pesticide residues are small amounts of conventional or organic pesticides that may stay in or on food. Residues are measured in parts per million (or ppm). One part per million is equal to a single granule of sugar in 273 cubes of sugar (or 1 granule in one million granules). Therefore, 1 or even 50 ppm of residue on a food commodity from a pesticide is exceedingly small.

Pesticide residues can get in or on our food when:

Pesticide residues also break down over time, so by the time the food reaches the market there can be very small amounts of pesticide residues left in or on food. Typically, the amount of pesticide residue in or on a food or crop is lower than the MRL set for that specific combination of pesticide and food or crop. The Canadian Food Inspection Agency (CFIA), which is responsible for monitoring MRLs for chemical residues on food, has consistently reported a high degree of overall compliance of about 97% in their annual reports. Nevertheless, Health Canada must be satisfied that the amount of residue that could be present in or on a food commodity, once a crop has been treated with a pesticide according to label instructions, is not a health concern.

Calculating a maximum residue limit

Health Canada calculates an MRL using the Organisation for Economic Co-operation and Development (OECD) MRL Calculator, a statistical method that is used internationally. The MRL represents the highest residue that could remain on a particular crop at harvest when the pesticide is used according to the approved label directions. An MRL is not a measure of the toxicity of a pesticide. It is a scientifically-based calculation that estimates the maximum potential amount of residue on food commodities. Studies called field trials are used for this purpose. These studies are conducted according to how a particular pesticide is proposed to be used for a specific crop or commodity. If Health Canada determines that residue from consuming the food commodity is not a health concern, these field trial data are then used to calculate the MRL. Health Canada establishes MRLs only when there are no health risks of concern to consumers.

MRLs can be established on crop groups as well as on individual crops. A crop group includes crops that have similar features (physical characteristics of the crop), growth habits, and have the same part of the crop that is edible. Crop groupings allow for residue data on a "representative crop" to be used as a surrogate (or proxy) for other crops within the same crop group when the label directions are the same for all crops.

Often, the residues that remain are much lower under typical use conditions. If the use directions change for a given pesticide, the MRL can also change. However, before any change to an MRL is proposed, the risks must meet Health Canada's requirements for the protection of human health.

MRLs are an important aspect of food safety, but exceedances do not automatically mean a food safety concern. This is because an MRL reflects the maximum residue that may be found on a crop based on how a pesticide is applied to that crop; MRLs are not the maximum safe limit. If a pesticide is used differently, the residue may be higher and therefore the MRL may increase, but the health risk can still be acceptable.

Anyone can request a maximum residue limit

As per the Pest Control Products Act (Section 10(2)), any person may submit an application to Health Canada to set an MRL. For the pesticides that will be used in Canada, Health Canada's PMRA requires that the use of the pesticide product on that food commodity is supported by the manufacturer.

For example, an application can come from:

Applicants must submit a full data package including scientific studies that fulfill each of the data requirements to address health risks in support of an MRL application.

Amending maximum residue limits

Section 7(1) of the Pest Control Products Act requires that an application be made to the Minister to amend a product's registration, including changing the conditions related to its label. Section 9 of the Pest Control Products Act states that when making a decision regarding the registration of a pest control product, the Minister shall, if necessary, specify any maximum residue limits for the product or for its components or derivatives that the Minister considers appropriate in the circumstances. Accordingly, an application was received from the PMC of Agriculture and Agri-Food Canada, in support of the minor use grower communities, to register sulfoxaflor for domestic use on lingonberries and lowbush berries as members of the bushberries subgroup (crop subgroup 13-07B). The MRLs previously established for residues of sulfoxaflor in or on lingonberries and lowbush berries were import MRLs as part of crop subgroup 13-07G, the low growing berries subgroup (PMRL2015-10).

Amending an existing, approved use of a pesticide may, at times, require amending an existing MRL for that particular use as well. MRLs are routinely amended as agricultural practices change in Canada and internationally. If an MRL increases, it does not mean that human health protection decreases. As previously noted, MRLs are a function of how a pesticide is used and not a measurement of pesticide toxicity or safety. Also, if an import MRL increases, it does not mean that a Canadian grower can use more pesticide on their crops, as the use directions and conditions of use indicated on the Canadian registered label must be adhered to at all times and is a legal requirement.

Situations that could lead to an application to amend the established MRL include:

Maximum residue limit differences between countries

To the extent possible, and only when there are no health concerns, Health Canada will align MRLs with those of other countries as part of Canada's international treaty obligations to facilitate trade. MRLs may vary from one country to another for a number of reasons, including differences in how the pesticide is used on a particular crop in various countries and the geographical locations of the crop field trials that are used to analyse and measure residue data on these crops.

The MRLs for sulfoxaflor proposed under PMRL2021-25 are aligned with the corresponding U.S. tolerances and Codex MRLs, where established.

Enforcing maximum residue limits

MRLs are legal limits that are specified under the Pest Control Products Act and enforced by the CFIA. The latest National Chemical Residue Monitoring Program and Chemistry Food Safety report that uses MRLs to determine compliance rates can be requested on the Food safety testing reports and journal articles page on Canada.ca.

Every year, the CFIA tests over 15,000 domestically-produced and imported food samples for pesticide residues. Each sample can include monitoring for more than 450 different pesticides, including sulfoxaflor, generating more than 6 million pesticide residue monitoring results.

The most recent testing (2020-21 CFIA annual report) shows that 93.8% of imported foods and 99.2% of domestically-produced foods meet the established MRL. If the CFIA finds a food with residues greater than the MRL (or the default level of 0.1 ppm when no specific MRL is established), appropriate regulatory action is taken (see the section MRL exceedance does not mean there is a human health risk).

Maximum residue limit exceedance does not mean there is a human health risk

MRLs are used for monitoring purposes to help ensure the safety of Canada's food supply. When Good Agricultural Practices are followed, including the use of pesticides according to the approved label directions/conditions, residues in foods should comply with MRLs. However, an exceedance of an MRL, does not automatically mean there is a health risk of concern. That said, when a pesticide residue level exceeds the MRL, follow-up actions for non-compliant products are initiated by CFIA in a manner that reflects the magnitude of the potential health concern. Actions may include further analysis, notification to the producer or importer, follow-up inspections, additional directed sampling, a health risk assessment of MRL exceedances by Health Canada, and recall of products.

Understanding acceptable risk

Before approving the registration of a pesticide for a specific use or allowing the importation of a pesticide-treated food, 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. 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:

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. This quantity of residue is then subject to consultation to legally specify it as an MRL. If risks to human health from the consumption of treated food 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).

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.

Understanding toxicity testing of pesticides

Health Canada scientists use the four-step scientific risk assessment process (described in the section Understanding acceptable risk) to protect human health. The process is accepted by scientists and organizations across the world. The first step is referred to as hazard identification and is described on the Pesticide assessments in Canada: Human health risk page, as well as in more detail in this section. The goal of this process is to understand the toxicity of a pesticide, and the extent of human exposure based on how the product will be used, so that Health Canada can specify the conditions for safe use for the product label so that human exposure is well below the level that could cause harm.

The registration of a new pesticide is a multi-year process that involves evaluation of the results from a robust dataset of laboratory studies that include in vitro and in vivo toxicology studies. These studies assess the potential of the pesticide to cause effects following exposure to various doses, via multiple routes (in other words, oral, dermal and inhalation, where relevant) and for different periods of time. The suite of toxicology studies that are provided to Health Canada for evaluation includes studies that are designed to assess the potential for a pesticide to cause specific health effects, such as effects on reproduction and development over one or more generations, cancer, and effects on the nervous and endocrine systems, among other effects. Studies on how pesticides are broken down or act in the body are also examined. The results of all of these studies are taken into consideration when determining the safe use of a pesticide.

The dose levels used in these laboratory studies are much higher than the levels to which humans would be exposed when pesticide products are used according to label directions. These higher dose levels help scientists understand when and how effects may occur, and also identify levels when no effects occur, in order to set acceptable levels for pesticide exposure, called reference values. In addition, when setting these reference values, a 100-fold uncertainty factor is applied to a dose that has no effects, to account for observations in laboratory animals being extended to humans as well as variability between humans. An additional margin is included through retention of another factor (called the Pest Control Products Act (PCPA) factor) if there are any concerns for potential sensitivity of the young. The application of these uncertainty factors in setting reference values helps ensure there is a protective margin between the dose levels that elicit toxicity in laboratory animal studies and the anticipated human exposure. For more information, please refer to Science Policy Note SPN2008-01, The Application of Uncertainty Factors and the Pest Control Products Act Factor in the Human Health Risk Assessment of Pesticides.

In animal studies assessing the long-term effects of a pesticide, including the potential to cause cancer, the animals are exposed to the pesticide at high dose levels over their entire lifetime and potential effects on all tissues and organ systems are investigated. Endpoints evaluated in these studies include clinical signs of toxicity, effects on body weight, organ weights and pathology, effects on hematology and clinical chemistry parameters, and the potential to cause gene mutations and tumour formation. Human epidemiology studies are also taken into consideration, when available and relevant. When there is evidence from these studies that a pesticide has the potential to cause cancer, consideration is given to whether or not the type of cancer would be relevant to humans and all the ways that humans may be exposed to the pesticide over a lifetime (for example, through the ingestion of food and water, exposure to pesticides in the workplace, and in and around the home). The probability that an individual will develop cancer if exposed to the pesticide for a lifetime is calculated mathematically, and only pesticides that are predicted not to increase the lifetime risk for developing cancer by one in one million are registered for use in Canada.

The studies provided to Health Canada also include those that are specifically designed to assess the potential neurological effects of a pesticide. These studies pay particular attention on potential effects of the pesticide on nervous system tissues, such as pathology of the brain and nerves, and also include a battery of tests conducted on the animals, called a Functional Observational Battery, which is designed to detect gross functional deficits in the animals. Endpoints examined in these tests include things such as (but not limited to) any unusual behaviours, the presence of convulsions and tremors, unusual respiration, pupil dilation or constriction, increased levels of salivation, vocalization, sensory function (vision, auditory capability, pain perception), and grip strength in the animals. In addition, these studies are designed to evaluate effects on motor activity (for example, increases or decreases in activity) and learning and memory in the animals. These endpoints are assessed through observation of the animals' behaviour under various situations, such as in an open area and using tests involving specialized chambers and mazes.

The potential of a pesticide to cause effects on the endocrine system is also assessed in various scientific studies with laboratory animals that are provided to Health Canada. Gross and microscopic examinations of endocrine tissues such as the ovaries, testes, adrenals, thyroid, pituitary and thymus, are conducted in these studies, as well as measurement of hormone levels (for example, thyroid hormones) in relevant studies. In addition, the potential for the pesticide to have an effect on growth, reproduction and development is evaluated in studies specifically designed for this purpose.

In studies that assess effects on reproduction, both male and female parental animals (usually rodents) are given high levels of the pesticide via an appropriate route (usually orally in the diet) before and during mating, and then the females continue to receive the pesticide throughout gestation, and then throughout birth, lactation, and weaning of their young. Once they are weaned, the young animals also begin receiving the pesticide at the same dose levels as the maternal animals, and this continues until they themselves are considered adults and are able to be mated to produce a second generation of offspring, if required. In this way, the effect of the pesticide on the ability of the animals to successfully mate, become pregnant, and produce viable offspring is examined throughout the lifecycle, an in some cases, over multiple generations.

Other specialized studies, called developmental toxicity studies, are designed to examine the effect of the pesticide on developing young (in other words, in utero) when their mothers are given high doses of the pesticide throughout the critical time in pregnancy. Studies in two different species are required (usually rats and rabbits). In these studies, fetuses are subjected to detailed external and internal examinations for any effects on development. Assessment of the fetuses includes examination of the morphology of internal organs as well examination of the skeletal system for any observed alterations in bone growth and development.

In summary, toxicology studies are designed to identify a variety of potential health effects from varying levels of exposure to a pesticide and also identify the dose level at which no effects are observed.

When assessing health risks from exposure to pesticides, only uses for which the exposure is well below levels that cause no effects in laboratory testing are considered acceptable for registration. In fact, the health effects noted in laboratory tests occur at dose levels more than 100-times higher (and often much higher) than levels to which humans are normally exposed when pesticide products are used according to label directions, which is protective.

Understanding the toxic effects of sulfoxaflor, including the potential for neurodevelopmental and neurotoxic effects, and cancer

A detailed summary of Health Canada's toxicology assessment for sulfoxaflor can be found in PRD2015-08. A complete toxicology database was available for sulfoxaflor, consisting of the full array of toxicity studies currently required for hazard assessment purposes. These studies assessed potential hazards from short- to long-term (lifetime) exposure, including neurotoxicity, chronic toxicity, cancer, reproductive and developmental toxicity, and various other effects. Results of toxicology data summarized by other regulatory authorities subsequent to the 2015 assessment were considered, which did not impact the previous assessment.

Based on Health Canada's assessment, evidence of neurotoxicity was observed in the acute neurotoxicity and developmental neurotoxicity studies in rats. Health Canada considered these findings to be relevant to the human health risk assessment. The reference values for human health risk assessment were selected to ensure that levels of sulfoxaflor to which humans may be exposed when sulfoxaflor-containing products are used according to label directions are at least 100-times lower than dose levels causing any toxic effect, including neurotoxicity, in animals.

A pesticide fact sheet for sulfoxaflor prepared by Le Centre de the Québec Reference Centre for Agriculture and Agri-food (CRAAQ) was cited by some commenters (Fiche Matière active - SAgE pesticides; available in French only). It is noted that the information contained in the pesticide fact sheet prepared by CRAAQ is largely based on an assessment conducted by the USEPA in 2012, and is not based on Health Canada's 2015 assessment of sulfoxaflor. One of the conclusions in this fact sheet is that neurodevelopmental effects have been observed in rats without confirmation of the relevance, or otherwise, of these effects in humans. It is noted that the USEPA did conclude that the neurotoxic effects in rats were relevant to humans. Health Canada also considered the observed neurotoxic effects in rats dosed with sulfoxaflor to be relevant to the human health risk assessment and set reference values to protect against these and other effects

In Health Canada's assessment of the available toxicology database for sulfoxaflor (PRD2015-08), it was concluded that tumour findings in rats were either not relevant to humans or of low concern. The reference values selected for human health risk assessment are protective of any residual concerns regarding the cancer potential of sulfoxaflor. As indicated in Health Canada's registration decisions for sulfoxaflor (RD2015-09, RD2016-12, as well as proposed decision PRD2016-02), an evaluation of available scientific information found that, under the approved conditions of use, products containing sulfoxaflor have value and do not present an unacceptable risk to human health or the environment. It is noted that reference values established by other regulatory authorities for the human health risk assessment of sulfoxaflor are equivalent to, or higher (less protective) than, those selected by Health Canada.

Protecting sensitive sub-populations / vulnerable populations

Health Canada conducts a rigorous assessment of scientific data when determining the conditions for safe use of a pesticide product prior to registration. The human health risk assessment characterizes both the hazard profile of the pesticide as well as the potential for exposure. The potential hazards are investigated through evaluation of a large number of in vitro and in vivo toxicology studies as outlined in the section Understanding toxicity testing of pesticides. Variability in the human population is addressed in the risk assessments performed by Health Canada by setting reference values based on these toxicity studies that incorporate additional uncertainty factors. A 10-fold uncertainty factor for intraspecies variability is applied in addition to a 10-fold uncertainty factor to account for differences between humans and animals (interspecies variability), as observations in laboratory animals are extended to humans. An additional margin is included through retention of another factor (the PCPA factor) if there are any residual concerns for potential sensitivity of the young. The application of these uncertainty factors in setting reference values helps to ensure that there is a protective margin between the dose levels that elicit toxicity in laboratory animal studies and the anticipated human exposure. For more information, please refer to SPN2008-01, The Application of Uncertainty Factors and the Pest Control Products Act Factor in the Human Health Risk Assessment of Pesticides. In the case of sulfoxaflor, the 10-fold PCPA factor was retained when assessing risk to females of reproductive age, thus providing additional protection to the unborn child.

Health Canada also receives studies that assess potential dietary and non-dietary exposure to the pesticide product when it is used according to label directions. Using this information, Health Canada conducts specific risk assessments for sensitive groups, including children and pregnant people, taking their unique physiological characteristics into account. The behaviours and play-habits of children, such as their body weight and hand-to-mouth contact while playing near treated areas are considered when determining their potential exposure, and the highest potential exposure scenarios are taken into account when determining acceptable application rates for a product, in order to be protective.

The health of workers exposed to pesticides is also considered by Health Canada. Label directions provide workers with information for safe use, including proper handling information and directions on required personal protective equipment. In addition, provinces and territories are responsible for training and licensing professional pesticide users.

Thus, Health Canada's risk assessments are designed to protect all population subgroups including the most vulnerable.

Concerns over food allergies and intolerances to foods due to pesticides

The hazard assessment of pesticides includes evaluations of studies that assess the potential for pesticides to cause allergic skin reactions and effects on the immune system. There are many potential causes of food allergies and intolerance to food in general, including genetics. Additional information related to food allergies and food intolerances can be found at the following resources: Food allergies – Canada.ca; Food Allergies and Intolerances – Canada.ca; Food Allergy Canada. Currently, there is no compelling evidence demonstrating a link between pesticide exposure and food allergies or food intolerances. However, Health Canada will take into consideration any emerging science that may indicate such a concern and ensure that the risk assessment is protective of these potential effects.

Dietary risks are calculated using consumption data from the Dietary Exposure Evaluation Model - Food Commodity Intake Database™

Health Canada's dietary exposures assessments for new active ingredients, re-evaluations, and new uses to registered active ingredients, such as for sulfoxaflor, rely upon the "Dietary Exposure Evaluation Model - Food Commodity Intake Database™ (DEEM-FCID™), and uses the most recent version available at the time of the assessment.

In support of the proposed MRLs in PMRL2021-25, DEEM-FCID™ Version 4.02, 05-10-c, was used to update the dietary risk assessment. This version of the software incorporates food consumption data from the National Health and Nutritional Examination Survey, What We Eat in America (NHANES/ WWEIA) conducted in the United States from 2005 to 2010. The update to the dietary risk assessment included the proposed new and revised MRLs.

While Canadian dietary consumption data is available from the Canadian Community Health Survey (CCHS) a comparison of the Canadian data and American consumption data from NHANES/WWEIA showed no significant differences between the two surveys. In addition, the NHANES/WWEIA data is a larger sample size relative to the Canadian data, and it collects data for infants less than 1 year old (often the most sensitive age subgroup for dietary risk assessment) while the CCHS does not. NHANES/WWEIA is also a continuous survey that covers multiple years and captures consumption patterns over a longer period of time than CCHS, thus providing robust data that is regularly updated (SPN2014-01, General Exposure Factor Inputs for Dietary, Occupational, and Residential Exposure Assessments).

It is also important to note that the residue input in DEEM obtained from field trial studies on crops treated with sulfoxaflor according to Good Agricultural Practice (GAP) is determined based on the analysis of the entire unwashed sample of each crop (for example, whole berries are harvested in the field and the entire sample is analyzed so that the results represent residues both on the surface and interior of the fruit). So even though sulfoxaflor is a systemic pesticide, residues both on and inside the crop are taken into account in the dietary exposure assessment. In addition, the use of samples from unwashed produce is an additional protective measure when considering potential residues present, which is not necessarily the case for data from the CCHS survey, given it is a nutrition survey of foods as eaten.

Dietary risk assessment results for sulfoxaflor

Before an MRL can be set, scientists from Health Canada make sure the amount of pesticide residue on or in food commodities is low enough that there would be no effects on human health. Scientists evaluate the relevant scientific information on the toxicity and dietary exposure of the pesticide. This process is called a dietary risk assessment, which is also described under the heading Understanding acceptable risk, with additional detail provided here.

The dietary risk assessment process involves four distinct steps:

If the PDI is lower than the ADI and the ARfD, the scientists at Health Canada conclude that all food commodities that could be treated with this pesticide based on the label directions are safe to eat.

The reference values for sulfoxaflor for use in the dietary risk assessments can be found in PRD2015-08. The parent sulfoxaflor is not expected to be present in drinking water. The metabolite/transformation product X11719474 is used to assess presence in drinking water (98% conversion from parent). The ARfD of 0.25 mg/kg bw and the ADI of 0.01 mg/kg bw/day for sulfoxaflor are also appropriate for assessing the risk to all populations (including females 13 to 49 years old) from exposure to X11719474 in drinking water (as per PRD2015-08).

Table 1 Summary of toxicology information for sulfoxaflor for use in the dietary risk assessment
Exposure scenario Toxicology reference value used in risk assessment Study Toxicology endpoint
Acute Dietar
General population		 NOAELTable 1 footnote 1 = 25 mg/kg bw
CAFTable 1 footnote 1 = 100
ARfDTable 1 footnote 1 = 0.25 mg/kg bw		 Acute oral neurotoxicity study in rats

LOAELTable 1 footnote 1 = 75 mg/kg bw

Based on reduced motor activity
Acute dietary
Females 13-49 years old		 NOAEL = 1.9 mg/kg bw
CAF = 300
ARfD = 0.006 mg/kg bw		 Develop-mental neurotoxicity study in rats

LOAEL= 7.4 mg/kg bw

Based on decreased neonatal survival
Chronic Dietary
General population		 NOAEL = 1.04 mg/kg bw/day
CAF = 100
ADI = 0.01 mg/kg bw/day		 Two-year chronic dietary study in rats

LOAEL= 4.24 mg/kg bw/day

Based on decreased food consumption, increased liver and testes weights, decreased epididymidal weight, bilateral atrophy of the seminiferous tubule, decreased spermatic elements
Chronic dietary
Females 13-49 years old		 NOAEL = 1.9 mg/kg bw/day
CAF = 300
ADI = 0.006 mg/kg bw/day		 Develop-mental neurotoxicity study in rats

LOAEL= 7.4 mg/kg bw/day

Based on decreased neonatal survival
Table 1 footnote 1

ARfD = Acute Reference Dose; NOAEL = No Observed Adverse Effect Level; LOAEL = Lowest Observed Adverse Effect Level; CAF = Composite Assessment Factor; ADI = Acceptable Daily Intake; bw = body weight; Reference values and endpoints cited in PRD2015-08 and finalized via decision document RD2015-09.

Return to table 1 footnote 1 referrer

The acute dietary risk assessment for sulfoxaflor was updated for these applications, and therefore included uses and proposed uses since the publication of PRD2015-08 and RD2015-09. The results of the acute dietary risk assessment are shown in Table 2.

Acute dietary (food plus drinking water) intake estimates indicated that the general population and all population subgroups (excluding females 13- 49 years old) are exposed to less than 19% of the acute reference value (ARfD), which is not of human health concern.

For females 13-49 years old, acute dietary intake estimates for food alone indicated that this subpopulation is exposed to less than 102% of the ARfD, and drinking water exposure is less than 4% of the ARfD.

The acute dietary risk for each subpopulation is reported in Table 2.

Table 2. Summary of acute dietary risk for sulfoxaflor
Population subgroup ARfD
(mg/kg bw/day)		 Food
% ARfD		 Drinking waterTable 2 footnote 1
% ARfD		 Food + drinking water
% ARfD
All Infants Sulfoxaflor: 0.25
X11719474Table 2 footnote 1 : 0.25		 12.69 10.44 18.38
Children 1-2 years old 14.83 4.40 17.33
Children 3-5 years old 11.56 3.46 13.63
Children 6-12 years old 6.27 2.72 8.17
Youth 13-19 years old 3.82 2.54 5.20
Adults 20-49 years old 4.51 2.98 6.35
Adults 50+ years old 3.75 2.59 5.59
Females 13-49 years old Sulfoxaflor: 0.006
X11719474Table 2 footnote 1 : 0.25		 101.53 3.01 NATable 2 footnote 2
Table 2 footnote 1

The parent sulfoxaflor is not expected to be present in drinking water. The metabolite/transformation product X11719474 is used to assess presence in drinking water (98% conversion from parent). The ARfD of 0.25 mg/kg bw for sulfoxaflor is also appropriate for assessing the risk to all populations (including females 13-49 years old) from exposure to X11719474 in drinking water (as per PRD2015-08).

Return to table 2 footnote 1 referrer

Table 2 footnote 2

Exposure from food and drinking water for females 13-49 years old cannot be aggregated given that the reference values (ARfDs) were derived from different toxicity studies using different adverse effects.

Return to table 2 footnote 2 referrer

The chronic dietary risk assessment for sulfoxaflor was updated for these applications, and therefore included uses and proposed uses since the publication of PRD2015-08 and RD2015-09. The results of the chronic dietary risk assessment are shown in Table 3.

Chronic (non-cancer and cancer) dietary (food plus drinking water) intake estimates indicated that the general population and all population subgroups (excluding females 13 to 49 years old) are exposed to less than 101% of the acceptable daily intake (ADI).

For females 13 to 49 years old, chronic (non-cancer and cancer) dietary intake estimates for food alone indicated that this subpopulation is exposed to 28% of the ADI, and drinking water exposure is less than 4% of the ADI, which are not of human health concern.

The chronic (non-cancer and cancer) dietary risk for each subpopulation is reported in Table 3.

Table 3. Summary of chronic (non-cancer and cancer) dietary risk for sulfoxaflor
Population subgroup ADI (mg/kg) Food
% ADI		 Drinking waterTable 3 footnote 1
% ADI		 Food + drinking water
% ADI
All Infants Sulfoxaflor: 0.01
X117194741Table 3 footnote 1 :0.25		 62.1 74.7 100.8
Children 1-2 years old 86.1 27.4 88.7
Children 3-5 years old 57.5 22.3 59.4
Children 6-12 years old 31.9 16.6 36.3
Youth 13-19 years old 17.3 14.0 23.6
Adults 20-49 years old 21.5 19.8 29.1
Adults 50+ years old 15.8 19.2 28.1
Females 13-49 years old Sulfoxaflor: 0.006
X117194741Table 3 footnote 1 :0.25		 28.0 19.5 NATable 3 footnote 2
Table 3 footnote 1

The parent sulfoxaflor is not expected to be present in drinking water. The metabolite/transformation product X11719474 is used to assess presence in drinking water (98% conversion from parent). The ARfD of 0.25 mg/kg bw for sulfoxaflor is also appropriate for assessing the risk to all populations (including females 13-49 years old) from exposure to X11719474 in drinking water (as per PRD2015-08).

Return to table 3 footnote 1 referrer

Table 3 footnote 2

Exposure from food and drinking water for females 13-49 years old cannot be aggregated given that the reference values (ARfDs) were derived from different toxicity studies using different adverse effects.

Return to table 3 footnote 2 referrer

When the acute or chronic dietary risk assessments are lower than 100% of the ARfD or ADI, it means that there are no short -term or long-term human health concerns from eating foods treated with sulfoxaflor. Health Canada considers acute and chronic risk may be of concern when exposure is greater than 100% of the ARfD and ADI, respectively. Risks above 100% thus require further analysis of the risk considerations to confirm there are no potential short-term or long-term health concerns.

Factors that impact risk considerations include the level of conservatism used in the assessments, as well as the protectionary measures used. Protectionary measures include basing a toxicology reference value (such as an ADI or ARfD) on the dose at which no harmful effects were observed in animals (in other words, the NOAEL), rather than setting reference values on the lowest dose at which harmful effects were observed in animals (in other words, the LOAEL); and then setting the ADI or ARfD at least 100-fold less than the NOAEL. Examples of conservatisms used in the exposure assessment are that the risk assessment is based on the worst-case scenario of someone eating all foods that could possibly be treated with sulfoxaflor on the same day, every day; assuming the maximum pesticide application rate was used to treat each crop, assuming the maximum number of pesticide applications were used, and that the shortest preharvest interval was followed for each crop harvested. In the case of sulfoxaflor, although the acute dietary (food only) intake estimate for females 13 to 49 years old and the chronic dietary (food and drinking water) for all infants slightly exceed 100% of the reference values, these are not considered a human health concern due to the nature of the conservatisms and protectionary measures incorporated into these assessments.

The sulfoxaflor dietary risk assessments include Canadian MRLs/U.S. tolerances as well as crop field trial data for many commodities, which generally overestimate actual residue levels of pesticides in food. For example, while monitoring data were available for sulfoxaflor on some food commodities, it is not available for all commodities included in the risk assessment. When monitoring data were not available for food commodities, MRLs and/or crop field trial residue data were used in the risk assessment as conservative values. Where monitoring data for sulfoxaflor was available, the actual levels of sulfoxaflor residues detected in or on foods in the market were either several fold lower than the MRLs and/or crop field trial data, or were non detectable. Hence, the sulfoxaflor dietary risk assessment over represents exposure and this means that acute and chronic dietary exposure to sulfoxaflor will not affect your health.

For more information on how Health Canada assesses and manages risk from pesticides, refer to these documents, which can be found in Pesticides and Pest Management Reports and Publications on Canada.ca:

For more information on the MRL process, refer to Section 19 Maximum Residue Limits found within PMRA Guidance Document, Updated Residue Chemistry Guidelines.

Cumulative risk

The Pest Control Products Act requires Health Canada's PMRA to consider the cumulative effects of pest control products as per the Science Policy Note SPN2018-02, Cumulative Health Risk Assessment Framework. A cumulative risk assessment (CRA) evaluates the potential adverse health effects from being exposed to more than one pesticide at a time from the same pesticide "group". These groups are created based on a common toxic effect that occurs by the same or similar mechanism.

CRAs may consist of a qualitative or quantitative assessment, or result in a determination that a cumulative risk assessment is not required. For example, situations in which no common mechanism of toxicity exists or that do not involve co-exposures, would not require a cumulative risk assessment.

It is essential that toxicology and exposure assessments of individual pesticides are up-to-date prior to undertaking the complex task of assessing cumulative health effects. Consequently, cumulative assessments are performed when both toxicity and exposure assessments are available for all pesticides within a common mechanism group. This could occur following the review of new active ingredients or a major new use of a previously registered active ingredient, or following the completion of a re-evaluation.

In addition to identifying a common mechanism of toxicity, other important considerations must be explored as part of the process to determine the need to conduct a CRA. These considerations include defining and comparing the use patterns of the different chemicals belonging to a class of pesticides with a common mechanism of toxicity to determine if the same uses are registered, whether the uses are wide-ranging, if there are residential uses, the potential routes of exposure and the potential for co-occurrence of exposure to the different chemicals. In addition, monitoring data from the CFIA and/or the United States Department of Agriculture (USDA) Pesticide Data Program (PDP), as well as drinking water monitoring information, are important sources of real-world data for dietary exposure assessment, and are key in order to conduct realistic CRAs.

Sulfoxaflor is a member of the sulfoximine class of insecticides. Sulfoxaflor exerts its insecticidal activity as an agonist at the insect nicotinic acetylcholine receptor (nAChR), which plays a central role in the mediation of fast excitatory synaptic transmission in the insect central nervous system. Other competitive modulators of the nAChR include the neonicotinoids, butenolides, and mesoionics. Collectively, these nAChR modulators are sometimes referred to broadly as neonicotinoid insecticides. The broader group of neonicotinoid insecticides, despite displaying certain structural similarities that may result in shared modes of action and effects, do not possess uniform toxicity profiles. Currently, Health Canada's PMRA has not identified a common mechanism of toxicity or a common metabolite for the neonicotinoids. The PMRA is considering evidence that neonicotinoids are agonists (of varied affinity among different species) of the nicotinic acetylcholine receptor in the central nervous system and may disturb synaptic signal transmissions. As noted in PRVD2016-20, and reiterated in RVD2021-05, the cumulative effects assessment for neonicotinoids will be undertaken according to the process outlined in SPN2018-02 in the future, as evaluations of other neonicotinoids are required to be finished with up-to-date scientific data. In the meantime, the current human health risk assessment of sulfoxaflor is considered complete.

Worker and bystander exposure and risk

Worker and bystander assessments were conducted as part of the applications to add new crops to the label of the product Closer Insecticide, which contains the active ingredient sulfoxaflor. The use on crop subgroups 13-07A and 13-07B, globe artichokes, quinoa, and asparagus, as listed in PMRL2021-25, is not expected to result in risks of concern for chemical handlers, post-application workers, and bystanders, provided that the product is used according to the label directions. The label specifies the conditions for safe use for the product label so that human exposure is well below the level that could cause harm.

Precautionary principle

The concept of exercising precaution is applied by Health Canada's PMRA in its regulatory decision-making. The Act and Regulations specify that a scientifically-based approach is required as a basis for regulatory decisions. Therefore, a detailed rigorous risk assessment of scientific data is necessary before a pesticide can be registered in Canada. Uncertainty factors and the PCPA factor, as discussed in previous sections, are applied in the risk assessment, where appropriate. Conservative considerations are also applied to the assessment to be protective. A product will be registered or continue to be registered as a result of periodic re-evaluation, only if there is sufficient scientific evidence to show that health and environmental risks posed by a product under the approved conditions of use are acceptable, and that it serves a useful purpose. Conditions of registration are specified for every product, including detailed use instructions, and a product can only be used according to label directions. If the proposed use could pose an unacceptable risk, additional conditions or restrictions can be imposed so that the remaining risk becomes acceptable. If the risks remain unacceptable, a registration is denied or cancelled, and the product cannot be used. When uncertainty remains in risk assessment – for example, insufficient data to assure safety, a use will not be approved.

As indicated in the Pest Control Products Act, the Precautionary Principle may be applied where there are threats of serious or irreversible damage. In the case of sulfoxaflor, sufficient data were available to conduct a robust science based risk assessment. Health Canada determined that the pesticide can be used safely when used as directed for bushberries, caneberries, globe artichokes, quinoa, and asparagus.

Organic farming

Health Canada recognizes that to be healthy, we need to eat a variety of foods, especially fresh fruits and vegetables. Pesticides play an important role in making sure there is enough food for everyone, by protecting crops from pests like insects, weeds, and fungal diseases. Food safety is a priority of the Government of Canada, and while pesticides help protect our food supply, some people have concerns about small amounts of pesticide residue that may be on the food they eat.

Eating organic or conventionally grown produce is a personal choice. Health Canada regulates all products that make pesticidal claims, including products intended to repel pests and protect organic produce. To date, there is no evidence to show that there is a health risk from eating conventionally-grown produce that contain small amounts pesticide residues, or that organic foods are safer to consume than conventionally produced food.

Food safety in Canada is a shared responsibility and priority between growers, industry, provinces and federal organizations. Health Canada, the CFIA and the AAFC work together on a number of programs that help provide safe food for Canadians and encourage environmental protection. Food producers help keep food safe by using and improving upon good agricultural and pest management practices. One key practice, which is required by law, is to follow pesticide label directions, because labels give instructions for the safe and proper use of pesticides. This helps keep residues within the limits, thus helping to ensure a safe food supply. Food producers also participate in a variety of on-farm programs to help implement effective food safety procedures in their day-to-day operations.

Health Canada works in collaboration with AAFC to register pesticides that meet the criteria for certified organic food production. To this end, Health Canada registers many biopesticides as part of reduced risk and sustainable pest management, which is in line with the goals of the Pest Control Products Act. The PMRA annual report shows increasing numbers of biopesticide registrations over the years, relative to conventional pesticides. All growers use pesticides, whether from synthetic or natural sources, and both sources of pesticides present various levels of toxicity and risk. When growing food, it is always recommended to do so in a sustainable way and pesticides play a role in this practice. Furthermore, by adopting a sustainable approach, growers can produce more with less on the same area of land, in addition to using natural resources wisely. Pesticide use can reduce food losses, help with better harvesting and are one tool used by growers to produce safe, quality foods at affordable prices. Responsible use of pesticides as part of an integrated pest management (IPM) program, that may include cultural production practices such as reduced or conservation tillage, contributing to reduced soil erosion and improved soil health, also supports sustainable agricultural production systems.

Pesticides offer benefits other than controlling and destroying pests in agricultural crops. They help reduce labour, fuel and machinery required for crop protection activities, thus reducing impacts of these activities on the environment.

Finally, by controlling toxin-producing microorganisms in food and feed crops, pesticides also contribute to reduced exposure to harmful food contaminants.

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 (virtual Reading Room pilot project), 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

It is noted that since PMRL2021-25 was published for consultation in May 2021, Health Canada's PMRA has made substantial improvements to the transparency and clarity of its published proposals and decisions, with more initiatives underway.

As of 1 April 2023, the names of applicants and registrants have been released in the Pesticide Product Information Database. This new measure, as noted in the Consultation Summary: Notice of Intent Enhanced Transparency of the Pesticide Regulatory Process, NOI2022-01, supports the Government of Canada's initiatives towards Open Government as well as its commitment to enhanced transparency of the pesticide review process.

As noted in previous sections, MRLs were proposed under PMRL2021-25 for the pesticide sulfoxaflor, as part of applications for Canadian use on bushberries, globe artichokes, asparagus, caneberries, and quinoa, and were submitted by the PMC of Agriculture and Agri-Food Canada to support minor use grower communities, under various URMULE D.3.2 applications.

The addition of the applicant's or registrant's name will provide additional information about the application that has been filed to further support meaningful public participation in the regulatory process. Health Canada's PMRA recognizes that the transparency and openness of its work is critical in strengthening trust in the regulatory decisions. Disclosing the applicant's or registrant's name in the public registry is one step in revisiting the types of information and data that are made available.

Health Canada's PMRA has also developed and consulted on a Notice of Intent (NOI) on the proposed amendments to the PCPR. 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.

Health Canada's consultations

Health Canada's PMRA consults with the public on all proposed major registration decisions, including new registrations, major new uses of a pesticide, re-evaluations and special reviews. Consultations can be found on our Pesticides and pest management consultations page.

For each open consultation, you can learn more about the proposed decision, access a consultation statement that outlines the major findings of the evaluation and the proposed decision, and leave a comment that will be considered before the final decision is made. Final decisions are available on our decisions and updates page.

Health Canada's PMRA is undergoing a transformation process that will strengthen its oversight and its protection of human health and the environment. The Minister of Health's Mandate letter (2021) as well as the information regarding the Pest Management Regulatory Agency's transformation resulted in 4 pillars of action: improved transparency, increased use of real-world data and independent advice, strengthened human health and environmental protection through modernized pesticide business processes and a targeted review of the Pest Control Products Act.

Health Canada's PMRA has engaged and received positive feedback from non-governmental organizations (NGOs) and academic organizations on these proposed initiatives. In addition, the Science Advisory Committee on Pest Control Products (SAC-PCP), established in 2022, provides Health Canada with independent scientific advice on various evidence-based decisions for pesticides.

The transformation process is helping to make Health Canada's pesticide program more transparent to people in Canada. Over the course of 2022 and 2023, Health Canada's PMRA engaged in comprehensive stakeholder consultations on the Agency's transformation agenda, including on ways it could continue to improve transparency. To help improve overall transparency and science communication, we have established a Science Communication Team. This unit of trained science communicators develops communication products that describe how science is conducted at Health Canada's PMRA and how it informs decision-making. They work to communicate decisions clearly with the right information for the audience. Their improvements have included re-designed webpages with more plain language and easier navigation for users to find what they are looking for and documents written using language suited to an engaged public audience along with clearer explanations of the basis for proposed decisions. If you would like to learn more about the science on pest management, you can reach them at: scicomm.pmra-commsci.arla@hc-sc.gc.ca.

Conclusion

Dietary risks from the consumption of sulfoxaflor residues in or on the food commodities noted in the PMRL consultation document (PMRL2021-25) were shown to be acceptable when sulfoxaflor is used according to the approved label directions. Therefore, the foods containing these residues are safe to eat, and the MRLs will be specified in the MRL Database as proposed (PMRL2021-25).

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