Evaluation Report ERC2011-02, Metconazole

This content was archived on June 24, 2013.

Pest Management Regulatory Agency
5 July 2011
ISSN: 1911-8082 (PDF version)
Catalogue number: H113-26/2011-2E-PDF (PDF version)

Summary

Table of Contents

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

Registration Decision for Metconazole

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 Metconazole Fungicide Technical and Caramba Fungicide, containing the technical grade active ingredient metconazole, to control a variety of fungal diseases on barley, oats, rye, wheat, soybeans and sugar beets.

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 registrant 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 ERC2011-02, Metconazole provides detailed technical information on the human health, environmental and value assessments of metconazole and Caramba Fungicide.

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 Metconazole?

Metconazole is a triazole fungicide (DMI; demethylation inhibiting fungicide) that inhibits sterol biosynthesis. The end-use product, Caramba Fungicide, is a chemical fungicide that contains 90 g/L metconazole formulated as an emusulfiable concentrate for use on barley, oats, rye, wheat, soybeans and sugar beets to control or to suppress certain foliar fungal diseases.

Health Considerations

Can Approved Uses of Metconazole Affect Human Health?

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

Potential exposure to metconazole 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 metconazole products are used according to label directions.

The technical grade active ingredient metconazole was moderately toxic to rats and highly toxic to mice when given as a single oral dose. It was of low dermal and inhalation toxicity. It was slightly irritating to the eyes of rabbits and a potential skin sensitizer to guinea pigs. The signal words, "DANGER - POISON", "EYE IRRITANT" and "POTENTIAL SKIN SENSITIZER" have been included on the label in light of these findings. The end-use product, Caramba Fungicide, was found to be of low oral, dermal and inhalation toxicity in rats. It was an eye irritant in rabbits, was not dermally irritating to rabbits and not a dermal sensitizer in guinea pigs. The signal words, "WARNING - EYE IRRITANT" were required.

Although metconazole was not genotoxic, it did cause cancer in mice, but not in rats. A cancer risk assessment was conducted based on the skin tumours found in the mouse.

The first signs of toxicity in animals given daily doses of metconazole over longer periods of time were decreased body weights, effects in blood (regenerative anaemia) and microscopic changes to the liver, spleen and adrenal glands. 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.

When metconazole was administered to pregnant animals, an increase in cranio-facial malformations was observed. These effects were observed at doses that were not toxic to the mother, indicating that the foetus is more sensitive to metconazole than the adult animal. Due to the serious nature of these endpoints, extra protective factors were applied during the risk assessment to further reduce the allowable level of human exposure to metconazole.

Residues in Water and Food

Dietary risks from food and water are not of concern.

Refined aggregate dietary intake estimates (food plus water) revealed that the general population and children, the subpopulation that would ingest the most metconazole relative to body weight, are expected to be exposed to less than 33.9% of the acceptable daily intake. Based on these estimates, the chronic dietary risk from metconazole is not of concern for all population sub groups. The lifetime cancer risk from the use of metconazole on all supported food uses is considered acceptable.

A single dose of metconazole is not likely to cause acute health effects. Aggregate (food and water) dietary intake for females 13-49 years old was 50.1% of the acute reference dose, which is not a health concern.

The  Food and Drugs Act prohibits the sale of adulterated food, namely, 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.

The majority of the residue trials were conducted in the United States using metconazole on barley, oats, rye, wheat, soybeans and sugar beets. The MRLs for this active ingredient can be found in the Science Evaluation section of this Evaluation Document.

Occupational Risks From Handling Caramba Fungicide

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

Farmers and custom applicators who mix, load or apply Caramba Fungicide as well as field workers re-entering freshly treated fields can come in direct contact with metconazole residues on the skin. Mixers, loaders and applicators may also be exposed by breathing sprays and mists. Therefore, the label specifies that anyone mixing, loading or applying Caramba Fungicide or performing clean-up or repair activities must wear coveralls over long-sleeved shirt, long pants, chemical-resistant gloves, socks and footwear, except for aerial applicators who must wear long sleeved shirts, long pants, socks and footwear. Closed cabs are required for all groundboom applications. Closed mixing/loading systems are required when handling more than 164 L of Caramba Fungicide per day. The label also requires that workers do not enter treated fields for 4 to 9 days after application depending on the crop treated. Taking into consideration these label statements, the number of applications and the expectation of the exposure period for handlers and workers, the risk to workers handling Caramba Fungicide is not of concern.

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

Environmental Considerations

What Happens When Metconazole Is Introduced Into the Environment?

Metconazole is toxic to non-target terrestrial plants and aquatic organisms. It is persistent in soil and aquatic sediment; however, it is not persistent in water. Metconazole is a potential leacher and may reach groundwater. Label instructions, including spray buffer zones, are required.

Metconazole enters the environment when used as a fungicide on agricultural crops including barley, oats, rye, wheat, soybeans and sugar beets. Metconazole is moderately persistent to persistent in the terrestrial environment. It is relatively stable to hydrolysis and phototransformation, undergoing minor biotransformation in both soil and water. Despite its high soil absorption, metconazole has the potential to leach into groundwater due to its solubility in water, persistence in sediment, low volatility and stability (however, residues in groundwater were not above the level of concern for human health). Based on its low volatility (low vapour pressure and Henry's law constant), metconazole residues are not expected in the air, nor is long range aerial transport expected. Specific instructions to prevent carryover, groundwater contamination and runoff into aquatic habitats are provided on the end-use product label.

Metconazole presents a negligible risk to terrestrial invertebrates including earthworms and honeybees, terrestrial vertebrates including small wild mammals and birds, freshwater invertebrates including daphnids, marine invertebrates including mysid shrimps and molluscs, juvenile stages of freshwater fish, freshwater algae, marine fish and marine algae. However, it may adversely affect non-target terrestrial plants, amphibians, early life stages of freshwater fish and freshwater aquatic vascular plants. Therefore, toxicity statements for non-target terrestrial plants and aquatic organisms are specified on the product label. Spray buffer zones are also required to protect terrestrial, freshwater and estuarine/marine habitats adjacent to areas treated with metconazole fungicide.

Value Considerations

What Is the Value of Caramba Fungicide?

Caramba Fungicide suppresses Fusarium head blight (Fusarium graminearum) on wheat, barley, rye and oats, and controls Septoria leaf blotch (Septoria tritici), leaf rust (Puccinia recondita) and tan spot (Pyrenophora tritici repentis) on wheat, Asian soybean rust (Phakospora pachyrhizi) on soybeans and Cercospora leaf spot (Cercospora beticola) on sugarbeets.

Caramba Fungicide is an additional product for Canadian growers, in particular the cereal, soybean and sugar beet industries. The active ingredient of Caramba Fungicide, metconazole, belongs to the triazole group (Group 3) and has been classified as having a moderate risk for resistance development. Moreover, Caramba Fungicide can be an important tool when used in an IPM program in conjunction with other elements such as resistant varieties, cultural controls and predictive models.

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 Caramba Fungicide to address the potential risks identified in this assessment are as follows.

Key Risk-Reduction Measures

Human Health

A Plant Back Interval of 35 days is required for all crops not listed on the label.

As there is a concern with users coming into direct contact with Caramba Fungicide on the skin, anyone mixing, loading and applying Caramba Fungicide must wear coveralls over a long sleeved shirt, long pants, chemical-resistant gloves, socks and footwear, except for aerial applicators who must wear long-sleeved shirts, long pants, socks and footwear. Closed cabs are required for all groundboom applications. Closed mixing/loading systems are required when handling more than 164 L of Caramba Fungicide per day. The label also requires that workers do not enter treated fields for 4 to 9 days after application depending on the crop treated. In addition, standard label statements to protect against drift during application were added to the label.

What Additional Scientific Information Is Being Requested?

Although the risks and value have been found acceptable when all risk-reduction measures are followed, the registrant must submit additional scientific information as a condition of registration. More details are presented in the Science Evaluation of Evaluation Report ERC2011-02, Metconazole or in the section 12 Notice associated with these conditional registrations. The registrant must submit the following information within the time frames indicated.

Human Health

• The registrant is required to submit a modified plant analytical method for D0508 that reflects the recommendation of the ILV laboratory and is reviewed by the registrant's quality assurance unit. Additionally, the registrant must provide a confirmatory method either by modifying the method to provide information on a second MS/MS ion transition or an alternate chromatographic system.
• The registrant is required to submit a validated animal enforcement method.
• Metconazole must be tested through a valid and appropriate multiresidue method.
• Rotational crop studies are considered conditionally acceptable pending the submission of acceptable freezer storage stability data for M11 in wheat forage stored frozen for up to 21 months, as well as for cis- and trans-metconazole in wheat grain and straw stored frozen for up to 18 months, in wheat forage and radish tops stored frozen for up to 21 months, and in lettuce stored frozen for up to 19 months.
• Confirmatory crop field trials for barley, oats, rye and wheat conducted at the Canadian rate of 90 g a.i./ha in Canadian representative growing regions are required. For barley, 5 field trials conducted in NAFTA Region 14 are required. For oats, 4 field trials conducted in NAFTA Region 14 are required. For rye, 1 field trial conducted in NAFTA Region 7, and 2 field trials conducted in NAFTA Region 14 are required. For wheat, 2 field trials conducted in NAFTA Region 7, 1 field trial conducted in NAFTA Region 7A, and 3 field trials conducted in NAFTA Region 14 are required.

Environment

• Non-target freshwater invertebrate study: Acute and chronic ecotoxicity study exposing chironomids to metconazole.
• Fish life cycle toxicity test: Chronic ecotoxicity study exposing all life stages of fish to metconazole

Value

To support aerial application, at least three confirmatory trials are required comparing efficacy of Caramba Fungicide when applied with high water volume (a minimum of 100 L of water per ha) versus low water volume (50 L of water per ha) on one of the crop/pest combinations listed on the Caramba Fungicide label (namely, barley/fusarium head blight, wheat/fusarium head blight, sugar beets/Cercospora leaf spot, etc.). Data should be submitted within 2 years after registration.

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 ERC2011-02, Metconazole (namely, 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.