Evaluation Report ERC2011-10, Metrafenone

This content was archived on June 24, 2013.

Pest Management Regulatory Agency
21 November 2011
ISSN: 1911-8082
Catalogue number: H113-26/2011-10E-PDF

Summary

Table of Contents

• Registration Decision for Metrafenone
• What Does Health Canada Consider When Making a Registration Decision?
• What Is Metrafenone?
• Health Considerations
• Environmental Considerations
• Value Considerations
• Measures to Minimize Risk
• What Additional Scientific Information Is Being Requested?
• Other Information

Registration Decision for Metrafenone

Health Canada's Pest Management Regulatory Agency (PMRA), under the authority of the  Pest Control Products Act and  Regulations, has granted conditional registration for the sale and use of Metrafenone Technical Fungicide and Vivando, containing the technical grade active ingredient metrafenone, to control powdery mildew on grapes.

An evaluation of available scientific information found that, under the approved conditions of use, the product has value and does not present an unacceptable risk to human health or the environment.

Although the risks and value have been found acceptable when all risk reduction measures are followed, the applicant must submit additional scientific information as a condition of registration.

This summary describes the key points of the evaluation, while the Science Evaluation of Evaluation Report ERC2011-10, Metrafenone provides detailed technical information on the human health, environmental and value assessments of metrafenone and Vivando.

What Does Health Canada Consider When Making a Registration 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 proposed conditions of registration. The Act also requires that products have value 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 modern, rigorous risk-assessment methods and policies. These methods consider the unique characteristics of sensitive subpopulations in humans (for example, children) as well as 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 when predicting the impact of pesticides. For more information on how the PMRA regulates pesticides, the assessment process and risk reduction programs, please refer to the following:

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

What Is Metrafenone?

Metrafenone is a benzophenone fungicide with protectant and curative properties for the control of powdery mildew (Uncinula necator) on grapes.

Health Considerations

Can Approved Uses of Metrafenone Affect Human Health?

Metrafenone is unlikely to affect your health when used according to label directions.

Potential exposure to metrafenone may occur through the diet (food and water) or when handling and applying the product. When assessing health risks, two key factors are considered:

• the levels where no health effects occur and
• the 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 uses for which the exposure is well below levels that cause no effects in animal testing are considered acceptable for 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-times higher (and often much higher) than levels to which humans are normally exposed when metrafenone products are used according to label directions.

In laboratory animals, the technical grade active ingredient is of low acute oral, dermal and inhalation toxicity; is non-irritating to the skin, not a dermal sensitizer and minimally irritating to the eyes. The end-use product, Vivando, is of low acute oral, dermal and inhalation toxicity; is non-irritating to the skin and not a sensitizer. The end-use product is mildly irritating to the eyes. Consequently, the signal words "CAUTION - EYE IRRITANT" are required on the label of the end-use product.

Metrafenone was not genotoxic and not likely to pose a carcinogenic risk to humans. There was also no indication that metrafenone caused damage to the nervous system. Common effects of toxicity in animals given daily doses of metrafenone over longer periods of time were changes to the kidneys and liver, irritation to the ear and effects on the blood indicative of the regenerative anaemia and possible immunotoxicity.

When metrafenone was given to pregnant animals, effects on the developing fetus, such as decreased body weight compared to controls and an increase in early fetal loss, were only observed at doses that were toxic to the mother, indicating that the fetus is not more sensitive to metrafenone 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.

Aggregate dietary intake estimates (food plus water) revealed that the general population and children 1-2 years old, the subpopulation which would ingest the most metrafenone relative to body weight, are expected to be exposed to less than 5% of the acceptable daily intake. Based on these estimates, the chronic dietary risk from metrafenone is not of concern for all population sub-groups. Metrafenone is not carcinogenic, therefore, a chronic cancer dietary risk assessment is not required.

Animal studies revealed no acute health effects. Consequently, a single dose of metrafenone is not likely to cause acute health effects in the general population (including infants and children).

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. Food containing a pesticide residue that does not exceed the established MRL does not pose an unacceptable health risk.

Residue trials conducted throughout the United States using metrafenone on grapes were acceptable. The MRLs for this active ingredient can be found in the Science Evaluation of Evaluation Report ERC2011-10, Metrafenone.

Occupational Risks From Handling Vivando

Occupational risks are not of concern when Vivando is used according to the label directions, which include protective measures.

Farmers and pesticide applicators who mix, load or apply Vivando as well as field workers entering freshly treated fields can come in direct contact with Vivando residues on the skin or through inhalation of spray mists. Therefore, the label specifies that anyone mixing/loading and applying Vivando must wear long sleeved shirt, long pants, chemical resistant gloves, socks and footwear. The label also requires that workers do not enter treated fields for 4 days after application to perform girdling or cane turning and 12 hours for all other postapplication activities. Taking into consideration these label statements, the number of applications and the expectation of the exposure period, risks for farmers and applicators are not a concern.

For bystanders, exposure is expected to be much less than that of field workers and is considered negligible. Therefore, health risks to bystanders are not of concern.

Environmental Considerations

What Happens When Metrafenone Is Introduced Into the Environment?

Metrafenone enters the environment when used as a fungicide on grape crops. Metrafenone is toxic to some non-target aquatic organisms. It is persistent in aerobic soil and is expected to carryover. Metrafenone is not persistent in anaerobic soil or in water, and it does not form any transformation products of environmental concern. Metrafenone is not expected to reach groundwater. Label instructions including spray buffer zones are required during pesticide application and handling.

Metrafenone is persistent in the terrestrial environment and displays low soil mobility. Based on field studies, approximately 40-45% carryover into the next growing season may be expected in soil. Metrafenone is sparingly soluble in water and is stable to hydrolysis. Despite these characteristics, it is not persistent in the aquatic environment. Many minor transformation products are formed, however, they do not pose an environmental concern because they are transient in nature and their concentrations are low. Due to low volatility (volatile organic compounds were not detected in the volatility traps used in laboratory incubation studies), metrafenone residues are not expected in the air, nor is long-range aerial transport expected. Leaching to groundwater is not a concern for metrafenone. It is not expected to bioaccumulate. Specific instructions to prevent soil carryover into the next growing season and runoff into aquatic habitats are provided on the end-use product label.

Metrafenone poses a negligible risk to the non-target terrestrial invertebrates tested including earthworms, honeybees, and beneficial arthropods. It also poses a negligible risk to the terrestrial vertebrates tested, including birds and small mammals. Although it displays low toxicity to terrestrial plants, there is some uncertainty regarding risk to plants owing to low application test rates. For freshwater organisms inhabiting waters close to 1 m in depth (80 cm deep or greater), metrafenone poses a negligible risk to all species tested. These include daphnids, chironomids, cold water fish (juvenile and early life stages), warm water fish (juvenile life stages), green algae, blue green algae, diatoms and aquatic vascular plants. However, metrafenone may pose an acute and chronic risk to amphibians inhabiting shallow waters (15 cm or less in depth). On an acute basis, metrafenone poses a negligible risk to estuarine/marine species including mysid shrimp, eastern oyster, and marine algae (represented by diatoms). It may pose a risk to marine fish (represented by sheepshead minnow) on an acute basis. On a chronic basis, it may pose a risk to mysid shrimp. Although the level of concern was exceeded for amphibians (acute and chronic), sheepshead minnow (acute), and mysid shrimp (chronic), proposed precautionary measures including label statements and spray buffer zones (1-2 m in size) are expected to adequately mitigate risk resulting from drift of metrafenone into the habitats of these sensitive organisms.

Value Considerations

What Is the Value of Vivando?

Vivando is a broad spectrum fungicide with strong activity against powdery mildew.

Vivando is to be used to control powdery mildew on grapes. There are several alternative modes of action registered for control of this disease, three of which are strobilurin fungicides, with high risk of development of pest resistance. Metrafenone has a different mode of action which will aid in resistance management when used in combination with other currently registered labelled products.

Measures to Minimize Risk

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.

The key risk-reduction measures being proposed on the label of Vivando to address the potential risks identified in this assessment are as follows.

Key Risk-Reduction Measures

Human Health

Because there is a concern with users coming into direct contact with Vivando on the skin, anyone mixing, loading and applying Vivando must wear a long sleeved shirt, long pants, chemical resistant gloves, socks and footwear during mixing/loading, application, clean-up and repair.

In addition, standard label statements to protect against drift during application were added to the label.

Environment

• A hazard statement to inform the user that this product is toxic to non-target terrestrial plants and aquatic organisms;
• Guidance to reduce runoff from treated areas into aquatic areas;
• A precautionary statement to avoid groundwater contamination, especially in areas with sandy soils;
• Spray buffer zones 1-2 m in size are required for airblast application on grapes for the protection of sensitive terrestrial and aquatic habitats.

What Additional Scientific Information Is Being Requested?

Although the risks and value have been found acceptable when all risk-reduction measures are followed, the applicant must submit additional scientific information as a condition of registration. More details are presented in the Science Evaluation of Evaluation Report ERC2011-10, Metrafenone or in the section 12 Notice associated with these conditional registrations. The applicant must submit the following information within the time frames indicated.

Human Health

• Additional method validation data for the proposed enforcement Method FAMS 105-01 in grapes.
• Radiovalidation data for Methods FAMS 105-01 and BASF Method 535/0 to demonstrate the extraction efficiencies for bioincurred residues.
• An immunotoxicity study.

Environment

Clarification is being requested for the results in the aerobic/anaerobic aquatic biotransformation study (PMRA 6120223).

All data is to be submitted to the PMRA by September 30, 2011.

Other Information

As these conditional registrations relate to a decision on which the public must be consulted, the PMRA will publish a consultation document when there is a proposed decision on applications to convert the conditional registrations to full registrations or on applications to renew the conditional registrations, whichever occurs first.

The test data cited in Evaluation Report ERC2011-10, Metrafenone (i.e. the test data relevant in supporting the registration decision) will be made available for public inspection when the decision is made to convert the conditional registrations to full registrations or to renew the conditional registrations (following public consultation). If more information is required, please contact the PMRA's Pest Management Information Service.