03 March 2010
HC Pub.: 100098
ISBN: 978-1-100-15007-9 (print version)
ISBN: 978-1-100-15008-6 (PDF version)
Catalogue number: H113-27/2010-2E (print version)
Catalogue number: H113-27/2010-2E-PDF (PDF version)

Summary

Table of Contents

• Proposed Re-evaluation Decision for Imazethapyr
• What Does Health Canada Consider When Making a Re-evaluation Decision?
• What Is Imazethapyr?
• Health Considerations
• Environmental Considerations
• Value Considerations
• Proposed Measures to Minimize Risk
• Next Steps
• Other Information

Proposed Re-evaluation Decision for Imazethapyr

After a re-evaluation of the herbicide imazethapyr, Health Canada's Pest Management Regulatory Agency (PMRA), under the authority of the Pest Control Products Act and Regulations, is proposing continued registration of products containing imazethapyr for sale and use in Canada.

An evaluation of available scientific information found that, under the proposed conditions of use, products containing imazethapyr have value and do not present unacceptable risks to human health or the environment. As a condition of the continued registration of imazethapyr, further risk-reduction measures are proposed for the labels of all products. No additional data are being requested at this time.

The PMRA's pesticide re-evaluation program considers potential risks as well as the value of pesticide products to ensure they meet modern standards established to protect human health and the environment. Regulatory Directive , PMRA Re-evaluation Program, presents the details of the re-evaluation activities and program structure. Re-evaluation draws on data from registrants, published scientific reports, information from other regulatory agencies and any other relevant information available.

This proposal affects all end-use products containing imazethapyr registered in Canada. Once the final re-evaluation decision is made, registrants will be instructed on how to address any new requirements.

Proposed Re-evaluation Decision PRVD2010-02, Imazethapyr, is a consultation document¹ that summarizes the science evaluation for imazethapyr and presents the reasons for the proposed re-evaluation decision. It also proposes additional risk-reduction measures to further protect human health and the environment.

The information is presented in two parts. The Overview describes the regulatory process and key points of the evaluation, while the Science Evaluation provides detailed technical information on the human health, environmental and value assessment of imazethapyr.

The PMRA will accept written comments on this proposal up to 60 days from the date of publication of Proposed Re-evaluation Decision PRVD2010-02, Imazethapyr. Please forward all comments to Publications.

What Does Health Canada Consider When Making a Re-evaluation Decision?

The key objective of the Pest Control Products Act is to prevent unacceptable risks to people and the environment from the use of pest control products. Health or environmental risk is considered acceptable if there is reasonable certainty that no harm to human health, future generations or the environment will result from use or exposure to the product under its conditions or proposed conditions of registration.² The Act also requires that products have value³ when used according to the label directions. Conditions of registration may include special precautionary measures on the product label to further reduce risk.

To reach its decisions, the PMRA applies hazard and risk assessment methods as well as policies that are rigorous and modern. These methods consider the unique characteristics of sensitive subpopulations in both humans (for example, children) and organisms in the environment (for example, those most sensitive to environmental contaminants). These methods and policies also consider the nature of the effects observed and the uncertainties present when predicting the impact of pesticides. For more information, please refer to the following:

• Protecting Your Health and the Environment
• Pesticide Registration Process
• Pesticide Risk Reduction Program

Before making a re-evaluation decision on imazethapyr, the PMRA will consider all comments received from the public in response to Proposed Re-evaluation Decision PRVD2010-02, Imazethapyr.⁴ The PMRA will then publish a Re-evaluation Decision⁵ on imazethapyr, which will include the decision, the reasons for it, a summary of comments received on the proposed registration decision and the PMRA's response to these comments.

For more details on the information presented in this summary, please refer to the Science Evaluation section of Proposed Re-evaluation Decision PRVD2010-02, Imazethapyr.

What Is Imazethapyr?

Imazethapyr is a selective systemic herbicide. It is registered for preplant, pre-emergence or postemergence use on terrestrial food and/or feed crops. Imazethapyr may be used alone or in co-formulation with imazamox or pendimethalin to control a broad spectrum of broadleaf and grassy weeds. It is applied once per year at a rate of 10 to 100 g a.e./ha by ground equipment only.

Health Considerations

Can Approved Uses of Imazethapyr Affect Human Health?

Imazethapyr is unlikely to affect your health when used according to the revised label directions.

Potential exposure to imazethapyr may occur through consuming food and water, working as a mixer/loader/applicator or by entering treated sites. The PMRA considers two key factors when assessing health risks:

• the dose levels where no health effects occur; and
• the dose levels to which people may be exposed.

The dose levels used to assess risks are established to protect the most sensitive human population (for example, children and nursing mothers). Only those uses where exposure is well below levels that cause no effects in animal testing are considered acceptable for continued registration.

Toxicology studies in laboratory animals describe potential health effects from varying levels of exposure to a chemical and identify the dose where no effects are observed. The health effects noted in animals occur at doses more than 100-fold higher (and often much higher) than levels to which humans are normally exposed when using imazethapyr products according to label directions.

Imazethapyr belongs to the imidazolinone family of herbicides which demonstrate a very low toxicity profile in mammals due to a plant-specific mode of action. While acute overexposures to imazethapyr resulted in low toxicity by the oral, dermal and inhalation routes, results showed that contact with the eye may cause mild eye irritation. To prevent overexposure, label directions must be followed.

Additional findings in repeat-dose animal studies, including those in pregnant animals, consisted of decreases in some blood parameters, body weight, body-weight gain and food consumption. Overall, there was no concern with respect to carcinogenicity, genotoxicity, neurotoxicity or reproductive toxicity.

When imazethapyr was given to pregnant animals, effects on the developing fetus were only observed at doses that were toxic to the mother, indicating that the fetus is not more sensitive to imazethapyr than the adult animal.

The risk assessment protects against these effects by ensuring that the level of human exposure is well below the lowest dose at which these effects occurred in animal tests.

Residues in Water and Food

Dietary risks from food and water are not of concern.

Reference doses define levels to which an individual can be exposed over a single day (acute) or lifetime (chronic) and expect no adverse health effects. Generally, dietary exposure from food and water is acceptable if it is less than 100% of the acute reference dose or chronic reference dose (acceptable daily intake). An acceptable daily intake is an estimate of the level of daily exposure to a pesticide residue that, over a lifetime, is believed to have no significant harmful effects.

Human exposure to imazethapyr from residues in treated crops and drinking water, including the most sensitive subpopulation (children 1 to 2 years old) was estimated. Only long-term (chronic) exposure estimates were determined for different subpopulations representing different ages, genders and reproductive status. Acute and cancer dietary assessments were not required.

Aggregate chronic exposure (that is, imazethapyr from food and drinking water) represents 8.9% and 43.4% of the chronic reference dose for the general population and children 1 to 2 years old, respectively, when using drinking water modelling. As a result, chronic risks were below the PMRA's level of concern.

The Food and Drugs Act prohibits the sale of adulterated food, that is, food containing a pesticide residue that exceeds the established maximum residue limit (MRL). Pesticide MRLs are established for Food and Drugs Act purposes through the evaluation of scientific data under the Pest Control Products Act. Each MRL value defines the maximum concentration in parts per million (ppm) of a pesticide allowed in or on certain foods. Food containing a pesticide residue that does not exceed the established MRL does not pose an unacceptable health risk.

Based on metabolism data, the current residue definition in all commodities is the parent compound, imazethapyr (CL 263499 or BAS 685 H) (±)-2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-5-ethyl-3-pyridinecarboxylic acid, expressed as ammonium salt.

For this residue definition, MRLs for imazethapyr are currently specified for kidney beans, lima beans, navy beans, pinto beans, runner beans, snap beans, soybeans, tepary beans, wax beans, which have a value of 0.1 ppm, and fenugreek and canola at a value of 0.05 ppm. Where no specific MRL has been established, a default MRL of 0.1 ppm applies, which means that pesticide residues in a food commodity must not exceed 0.1 ppm.

Risks in Residential and Other Non-Occupational Environments

Residential and other non-occupational risks are not of concern.

Imazethapyr is not registered for use in any residential areas. Therefore, a non-occupational risk assessment was not required. Basic statements to reduce drift to residential areas were recommended.

Occupational Risks from Handling Imazethapyr

Occupational risks are not of concern when used according to the label directions.

Based on the precautions and directions for use on the current label and considering the use of appropriate protective equipment, the risk estimates associated with mixing, loading and applying activities meet current standards for all use scenarios and are not of concern. Additional personal protective equipment is not required beyond what is currently specified on the label.

Occupational postapplication risks are not of concern when used according to the revised label directions.

Occupational postapplication risk assessments consider exposures to workers entering treated agricultural sites. Based on the precautions and directions for use on the original product labels reviewed for this re-evaluation, postapplication risk to workers meets current standards and is not of concern. To meet current standards, a minimum 12-hour restricted-entry interval is proposed for all uses.

Environmental Considerations

What Happens When Imazethapyr Is Introduced Into the Environment?

Imazethapyr is mobile and persistent and poses a potential risk to terrestrial and aquatic vascular plants; therefore, additional risk reduction measures need to be observed.

When imazethapyr is applied for control of weeds in crops, some of it finds its way into soil and water. The chemical is persistent in soil, sediment and water and could carry over. Imazethapyr is mobile and has the potential to leach to groundwater. However, field evidence indicates that imazethapyr remains within the top 15 cm of the soil after application. Water monitoring of ponds and rivers have revealed residues from runoff, but at concentration below levels of concern for aquatic life. Two major transformation products are formed from the breakdown of imazethapyr in soil and aquatic systems, but their fate in the environment, especially of CL 290395, has not been fully characterized.

When imazethapyr is used for weed control in crops, there is a potential that sensitive plant species on land and in water may be exposed to the chemical as a result of the spray drift and runoff. Some of these species are sensitive to the chemical and would be adversely affected. In order to mitigate effects in non-target areas, spray buffer zones between the agricultural field and the non-target terrestrial or aquatic areas are required. The width of these buffer zones will be specified on the product label. Imazethapyr presents negligible risk to wild birds, mammals, bees, earthworms, fish, amphibians, aquatic invertebrates and algae because concentrations in the environments are expected to be at levels that are not harmful.

Value Considerations

What Is the Value of Imazethapyr?

Imazethapyr continues to contribute to weed management in a variety of crops when used in accordance with the label directions.

Several major crops including canola, corn and lentils have been modified through mutagenesis followed by conventional breeding and selection to acquire imazethapyr tolerant traits (CLEARFIELD^® traits). Imazethapyr has also been widely used in soybeans, field peas and processing peas. It is the only herbicide registered for the control of broadleaf weeds in chickling vetch and fenugreek. Moreover, imazethapyr is the only alternative for the control of grassy weeds in chickling vetch and fenugreek. Imazethapyr controls both grassy and broadleaf weeds in adzuki beans, lima beans, snap common beans and dry common beans while alternatives only control either grassy or broadleaf weeds. Although imazethapyr plays a role in mitigating resistance development in weeds to other herbicide groups, consideration has to be given to resistance management as more weed species are reported to be resistant to herbicides that inhibit acetolactate synthase (such as imazethapyr) than to herbicides having other modes of action.

Proposed Measures to Minimize Risk

The labels of registered pesticide products include specific instructions for use. Directions include risk-reduction measures to protect human and environmental health. These directions must be followed by law.

Further risk-reduction measures are being proposed to address potential risks identified in this assessment. These measures, in addition to those already identified on existing imazethapyr product labels, are designed to further protect human health and the environment.

Additional Key Risk-Reduction Measures

Human Health

• To protect workers entering treated fields, a 12-hour restricted-entry interval is being proposed for all formulations.
• Precautionary statements are being proposed to avoid drift to areas of human habitation or areas of human activity.

Environment

• Updated precautionary statements and terrestrial and minimal aquatic buffer zones (1 m) are being proposed for the protection of terrestrial and aquatic habitats that may contain sensitive plant species.

Next Steps

Before making a re-evaluation decision on imazethapyr, the PMRA will consider all comments received from the public in response to Proposed Re-evaluation Decision PRVD2010-02, Imazethapyr. The PMRA will then publish a Re-evaluation Decision, which will include the decision, the reasons for it, a summary of comments received on the proposed decision and the PMRA's response to these comments.

Other Information

At the time that the re-evaluation decision is made, the PMRA will publish an Evaluation Report on imazethapyr in the context of this re-evaluation decision (based on the Science Evaluation section of Proposed Re-evaluation Decision PRVD2010-02, Imazethapyr. In addition, the test data on which the decision is based will also be available for public inspection, upon application, in the PMRA's Reading Room (located in Ottawa).