Evaluation Report ERC2011-06, Difenoconazole

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Pest Management Regulatory Agency
12 October 2011
ISSN: 1911-8082 (PDF version)
Catalogue number: H113-26/2011-6E-PDF (PDF version)

Summary

Table of Contents

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

Registration Decision for Difenoconazole

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 Difenoconazole Technical Fungicide and Inspire™ Fungicide, containing the technical grade active ingredient difenoconazole, to control or suppress fungal diseases on a variety of fruit and vegetable crops.

Difenoconazole (Registration Number 25631) is currently registered in Canada as a seed treatment on wheat, and the detailed review for this use can be found in the Proposed Regulatory Decision Document PRDD99-01: Difenoconazole as well as in the Regulatory Decision Document RDD2001-04: Difenoconazole Fungicide.

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 ERC2011-06, Difenoconazole provides detailed technical information on the human health, environmental and value assessments of difenoconazole and Inspire™ 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 Difenoconazole?

Difenoconazole is a Group 3 fungicide active ingredient that inhibits mycelial growth, which slows or stops the growth of the fungus and effectively prevents further infection or invasion of host tissues.

Health Considerations

Can Approved Uses of Difenoconazole Affect Human Health?

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

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

In laboratory animals, the technical grade active ingredient difenoconazole was of slight acute toxicity by the oral route; consequently, the hazard signal words "CAUTION - POISON" are required on the Difenoconazole Technical Fungicide label. It was of low acute toxicity dermally and through inhalation exposure. Difenoconazole was mildly irritating to the eyes, minimally irritating to the skin and did not cause an allergic skin reaction. The hazard signal words "CAUTION - EYE IRRITANT" are required on the Difenoconazole Technical Fungicide label.

The acute toxicity of the end-use product, Inspire™ Fungicide, which contains difenoconazole, was low via the oral, dermal and inhalation routes of exposure. It was slightly irritating to the skin and did not cause an allergic skin reaction. Inspire™ Fungicide was moderately irritating to the eyes; consequently, the hazard signal words "WARNING - EYE IRRITANT" are required on the Inspire™ Fungicide label.

There was limited evidence that difenoconazole caused damage to the nervous system or immune system. Difenoconazole did not cause birth defects in animals and there were no effects on the ability to reproduce. There was no evidence to suggest that difenoconazole damaged genetic material. Health effects in animals given repeated doses of difenoconazole included effects on the liver, body weight and food consumption. Difenoconazole caused liver tumours in mice, but not in rats. These tumours were observed at very high doses that were considered excessive.

When difenoconazole was given to pregnant animals, effects of a serious nature were observed on the developing fetus at doses that were toxic to the mother. There was an increased incidence of fetal mortality in utero, while the mothers had severely depressed body weight gains. The risk assessment takes these effects into account in determining the allowable level of human exposure to difenoconazole.

The risk assessment protects against the effects of difenoconazole 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 difenoconazole relative to body weight, are expected to be exposed to less than 35% and 89% of the acceptable daily intake, respectively. Based on these estimates, the chronic dietary risk from difenoconazole is not of concern for all population sub-groups. A lifetime cancer assessment was not performed since there was no cancer risk identified for difenoconazole.

An acute aggregate (food and water) dietary intake estimate for the highest exposed population (children 1-2 years old) was less than 52% of the acute reference dose, which is below the level of concern. An acute aggregate (food and water) dietary intake estimate for females (aged 13-49 years) was less than 31% of the acute reference dose for this population, which is not a health 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. 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 difenoconazole on various crops were acceptable. The MRLs for this active ingredient can be found in the Science Evaluation section of this Evaluation Report.

Risks in Residential and Other Non-Occupational Environments 

Entry by the public into treated commercial areas is considered acceptable.

An aggregate risk assessment was performed for adults and children entering treated commercial areas for 'pick-your-own' harvest activities in pome fruit. No risks of concern were identified.

Occupational Risks From Handling Inspire™ Fungicide

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

Farmers and custom applicators who mix, load or apply Inspire™ Fungicide as well as field workers re-entering treated fields can come in direct contact with difenoconazole on the skin. Therefore, the label specifies that anyone mixing/loading and applying Inspire™ Fungicidemust wear chemical-resistant gloves, protective eyewear, long-sleeved shirt and long pants and socks and shoes. The label also requires that workers do not enter treated fields or other treated sites for 1-10 days after application for specific activities in some crops. For all other uses, a restricted re-entry interval of 12 hours is specified. 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 Inspire™ Fungicide is not of concern.

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

Environmental Considerations

What Happens When Difenoconazole Is Introduced Into the Environment?

Difenoconazole will be persistent in terrestrial and aquatic environments and may affect beneficial arthropods and aquatic life. The effects of difenoconazole can be mitigated with the observance of precautionary measures including spray drift buffer zones for protection of aquatic life.

When difenoconazole is used to control diseases on a variety of crops, any difenoconazole deposited on the ground will remain in soil for a considerable period of time as it is broken down very slowly. With repeated yearly applications, difenoconazole will accumulate in soil and could eventually move to lower soil depths. Difenoconazole is not volatile and is not expected to bioaccumulate.

Amphibians would be at the highest risk through exposure from off-target spray drift entering aquatic systems resulting from the application of difenoconazole. There is also a risk to freshwater and marine/estuarine invertebrates and fish, and beneficial terrestrial arthropods. 

Value Considerations

What Is the Value of Inspire™ Fungicide?

Difenoconazole, the active ingredient in Inspire™ Fungicide, controls or suppresses a range of economically important pathogens on fruit and vegetable crops.

Inspire™ Fungicide is a product formulated as a foliar treatment against various fungal diseases on fruit and vegetable crops. Inspire™ Fungicide is a broad spectrum fungicide with systemic and curative properties, offers a new fungicide chemistry to Canadian growers and may be applied as a foliar spray in alternating spray programs. Inspire™ Fungicide may also be applied in tank mixes with other crop protection products for pest resistance management, or to increase the disease spectrum on crops that are registered on both product labels.

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

Key Risk-Reduction Measures

Human Health

As there is a concern with users coming into direct contact with Inspire™ Fungicide on the skin, anyone mixing, loading and applying Inspire™ Fungicide must wear a long-sleeved shirt, long pants, chemical-resistant gloves and protective eyewear. The label also requires restricted-entry intervals (REIs) of ten (10) days for cane-turning and vine girdling in grape, four (4) days for hand thinning in pome fruit, three (3) days for hand harvesting and irrigation in brassica vegetables, two (2) days for all other postapplication activities in grape, and one (1) day for scouting in brassica vegetables. A 12 hour REI is required for all other re-entry activities. In addition, standard label statements to protect against drift during application appear on the Inspire™ Fungicide label.

Environment

Label statements to mitigate the risk of spray drift to aquatic organisms

• Label statements to mitigate contamination of irrigation or drinking water supplies and aquatic habitats
• Buffer zones to mitigate the risk of spray drift to aquatic organisms
• Label statements to mitigate the risk of surface runoff from treated fields
• Label statements to mitigate accumulation in soil from repeated seasonal applications
• Label statements to mitigate the risk to beneficial arthropods

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 ERC2011-06, Difenoconazole 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

As the nature of the residue in rotational crops has not been adequately demonstrated, an additional confined crop rotational study reflecting the maximum potential seasonal application rate in rotated crops (512 g a.i./ha) using phenyl-labelled difenoconazole is required.

Environment

Quantitative data on non-target terrestrial plants pertaining to seedling emergence and vegetative growth is required. Validated analytical methods for the determination of difenoconazole and its transformation products in water and biota (fish) are required.

Value

The following small-scale field or greenhouse trialsare required for the disease claims with conditional registration:

• Three trials on alternaria blight of brassica (Cole) leafy vegetables;
• Three trials on powdery mildew of broccoli and cabbage;
• Three trials on purple blotch of garlic and/or leek;
• Three trials on powdery mildew of cucumber and/or melon;
• Three trials on gummy stem blight of cucumber and/or melon;
• Two trials on powdery mildew of grape;
• Three trials on anthracnose of tomato and/or pepper;
• Two trials on powdery mildew of apple;
• Two trials on scab of apple and/or pear. 

All required data must be submitted by September 1, 2014.

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 the Science Evaluation of Evaluation Report ERC2011-06, Difenoconazole (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.