Proposed Re-evaluation Decision PRVD2013-05, Clofentezine

Pest Management Regulatory Agency
3 December 2013
ISSN: 1925-0967 (PDF version)
Catalogue number: H113-27/2013-5E-PDF (PDF version)

Summary

Table of Contents

• Proposed Re-evaluation Decision for Clofentezine
• What Does Health Canada Consider When Making a Re-evaluation Decision?
• What is Clofentezine?
• Health Considerations
• Environmental Considerations
• Value Considerations
• Measures to Minimize Risk
• What Additional Information is Being Requested?
• Next Steps
• Other Information

Proposed Re-evaluation Decision for Clofentezine

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

An evaluation of available scientific information found that, under the proposed conditions of use:

• clofentezine has value in the food and crop industry and does not pose unacceptable risks to human health or the environment. As a condition of the continued registration for clofentezine uses, new risk-reduction measures must be included on the labels of clofentezine products. No additional data are required.
• The application rate of 600 mL product/hectare (300 g a.i./ha) used on apples and pears is no longer supported by the registrant and will be removed. The lower rate of 300 mL product/hectare (150 g a.i./ha) will be maintained on product labels.

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.

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

The regulatory approach and project plan regarding the re-evaluation of clofentezine was published in Re-evaluation Note REV2012-06, Re-evaluaton Update: Clofentezine on 26 September 2012.

Proposed Re-evaluation Decision PRVD2013-05, Clofentezine is a consultation document that summarizes the science evaluation for clofentezine 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.

Proposed Re-evaluation Decision PRVD2013-05, Clofentezine 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 clofentezine.

The PMRA will accept written comments on Proposed Re-evaluation Decision PRVD2013-05, Clofentezine up to 60 days from the date of publication of this document. 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. 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 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 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

Before making a re-evaluation decision on clofentezine, the PMRA will consider all comments received from the public in response to Proposed Re-evaluation Decision PRVD2013-05, Clofentezine. The PMRA will then publish a Re-evaluation Decision document on clofentezine, 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 of Proposed Re-evaluation Decision PRVD2013-05, Clofentezine.

What is Clofentezine?

Clofentezine is an acaricide that controls specific mite species in the egg stage and early larval stages. Clofentezine is registered to control European red mite, two-spotted spider mite and McDaniel spider mite on apples and pears, European red mite and two-spotted spider mite on peaches and nectarine and two-spotted spider mite on raspberries, strawberries and outdoor deciduous nursery stock. It is applied using ground application equipment by farmers and farm workers.

Health Considerations

Can Approved Uses of Clofentezine Affect Human Health?

Additional risk-reduction measures are required on clofentezine labels. Clofentezine is unlikely to affect your health when used according to the revised label directions.

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

• the levels where no health effects occur in animal testing 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 pesticide products are used according to label directions.

Clofentezine is of low acute oral toxicity, and low or slight dermal toxicity. Clofentezine is minimally irritating to the eyes, and slightly irritating to the skin. Exposure to clofentezine is not expected to cause skin sensitization.

Target organs of toxicity resulting from repeated oral exposure to clofentezine were the liver and thyroid. Clofentezine administration in repeat-dose oral studies resulted in stimulation of the thyroid gland in rats (but not mice, rabbits or dogs) leading to thyroid tumors in male rats. Clofentezine was not genotoxic.

Clofentezine may induce thyroid follicular cell tumours in rats by a non genotoxic pathway which is mediated by disruption of the pituitary thyroid feedback mechanism. However, data are insufficient to confidently assess the mode of action for carcinogenesis of clofentezine in male rats. Since a threshold mode of action was not established, a quantitative cancer risk assessment was conducted.

When administered to pregnant rabbits, there was no evidence that clofentezine causes malformations, and no evidence of increased sensitivity of the young exposed to this substance.

The risk assessment protects against the above noted 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.

Due to the low acute toxicity of clofentezine, an acute exposure assessment was not required. An aggregate (for example, food + water) chronic dietary exposure assessment was conducted, using residues of clofentezine per se in treated crops and drinking water as well as the sum of residues of clofentezine and the 4-hydroxyclofentezine metabolite in animal commodities. The assessment was conducted for different subpopulations representing different ages, genders and reproductive status. The cancer risk was assessed for the general population.

The aggregate chronic exposure estimates do not exceed 1.2% of the chronic reference dose for the general population and all population subgroups when using drinking water concentrations generated from water modelling and are, therefore, not of concern. The aggregate cancer exposure estimate is at about 7 × 10-7, which is below the PMRA's level of concern for the general population (for example <1 × 10-6).

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 is at or below the established MRL does not pose an unacceptable health risk.

MRLs for clofentezine are currently established on registered domestic and import agricultural uses and published in Health Canada's List of MRLs Regulated under the Pest Control Products Act on the Maximum Residue Limits for Pesticides webpage. No amendment to the current MRLs is being proposed as a result of this re-evaluation. However, as no preharvest interval (PHI) was specified on the label for use on apples, a 21-day PHI is being proposed to support the current MRL of 0.5 ppm in/on apples.

Risks in Residential and Other Non-Occupational Environments

Residential risks from the use of clofentezine on fruit trees in residential areas are not of concern.

Even though there are no domestic class registrations for clofentezine, it is possible that commercial applicators could apply clofentezine to fruit trees in residential areas. Estimates of exposure exceed the target Margin of Exposure (MOE) for adults and youth, and are therefore, not of concern. Cancer risk was also not of concern (for example below 1 × 10-6).

Aggregate risk from exposure incurred as a patron of a "Pick Your Own" orchard or berry facility is not of concern.

"Pick Your Own" (PYO) facilities are considered commercial farming operations that allow public access for harvesting in large-scale fields or orchards treated with commercially labelled clofentezine products. A non-cancer aggregate PYO assessment was not required, as there were no acute toxicological endpoints identified. Estimates of cancer risk that aggregate the dermal exposure incurred during harvest and the dietary exposure from consuming fresh fruit were not of concern (for example below 1 × 10-6).

Occupational Risks from Handling Clofentezine

Occupational risks to mixers/loaders and applicators are not of concern, when used according to current label directions.

Occupational risk assessments consider exposure to workers who mix, load, and apply the pesticide. Occupational risks are not of concern for agricultural scenarios based on the current use pattern, and current label mitigation.

Occupational postapplication risks are not of concern based on proposed label directions.

Postapplication occupational risk assessments consider exposure to workers entering treated sites in agriculture. Occupational postapplication risks are not of concern if proposed protective measures are followed. When the proposed mitigation measures such as lengthened restricted-entry intervals are considered, the risk estimates for postapplication workers are not of concern to the Agency.

Environmental Considerations

What Happens When Clofentezine is Introduced Into the Environment?

Clofentezine poses a potential risk to bird and mammal reproduction and saltwater arthropods, and therefore, additional risk reduction measures need to be observed. 

Clofentezine, an acaricide, has very low solubility in water, a low vapour pressure and is not expected to volatilize under field conditions. 

Clofentezine is non-persistent to moderately persistent in aerobic and anaerobic aquatic systems where it breaks down in a few days by chemical reaction in water (especially hydrolysis) and by biotransformation. Major transformation products are hydrazide-hydrazone, oxadiazole, 2-chlorobenzonitrile and 2-chlorobenzoic acid. These also decline relatively quickly in terrestrial and aerobic aquatic environments.

Clofentezine and its transformation products are not mobile in soils and are not expected to leach to groundwater. Clofentezine was not detected in water monitoring data from Canada and the U.S.

The use of clofentezine poses a negligible risk to terrestrial invertebrates and vascular plants but poses a reproductive risk to birds and mammals feeding on treated fields. Airblast spray drift presents a chronic risk to marine invertebrates, but this can be mitigated with spray buffer zones. Clofentezine does not present an acute or chronic risk to freshwater organisms.

Clofentezine and its transformation products, hydrazide-hydrazone, oxadiazole, 2-chlorobenzonitrile and 2-chlorobenzoic acid, do not meet any of the criteria under the Toxic Substances Management Policy to be considered as Track 1 substances and are not expected to form any further transformation products that meet all Track 1 criteria.

Value Considerations

What is the Value of Clofentezine?

Clofentezine is an ovicidal acaricide.

In Canada, there are few registered acaricides that control specific mite species at the egg stage and early larval stages. When treatment thresholds for pest mite eggs are reached an ovicide may be required. Clofentezine's uniqueness as an ovicide makes it a valuable tool in mite control and resistance management because it can be rotated with the few other acaricides that are also effective against the egg stage. Also, an early application of an ovicide may keep pest mite populations below damaging levels and reduce the need for an additional application of an acaricide. Avoiding additional acaricide applications is an effective strategy for minimizing the potential for development of pesticide resistance.

Clofentezine contributes to pesticide resistance management.

Resistance by mites to acaricides is a serious concern in orchards, berry crops and ornamentals because plant-feeding mites can adversely affect crop yield or product. Clofentezine can be rotated with the few other registered acaricides so it can help extend the useful life of these acaricides.

In Canada, the limited number of available acaricides does not allow for sufficient rotation between products with differing modes of action to reduce the risk of development of resistance. Clofentezine offers a different mode of action to control specific mite species in the egg stage and early larval stages on apples, pears, peaches, nectarines, raspberries, strawberries and outdoor deciduous nursery stock.

Measures to Minimize Risk

Registered pesticide product labels include specific instructions for use. Directions include risk-reduction measures to protect human health and the environment. These directions are required by law to be followed.

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

Additional Key Risk-Reduction Measures

Human Health

To protect workers entering treated sites, restricted-entry intervals (REIs) are to be implemented:

• Apples, pears, peaches, nectarine - REI = 2 days (hand thinning), REI = 12 hours (all other activities);
• Raspberries - REI = 10 days (hand pruning, training, tying), REI = 12 hours (all other activities);
• Strawberries - REI = 12 hours;
• Outdoor deciduous nursery stock - REI = 12 hours.

To support the current MRL of 0.5 ppm in/on apples, a 21-day PHI is required to be added to label directions for use on apples.

To ensure no clofentezine residue uptake by secondary crops, a minimum rotational crop plant back interval (PBI) of 12 months must be observed for all crops other than those registered for use with clofentezine.

Environment

To reduce the exposure of terrestrial and aquatic habitats, additional advisory statements to protect non-target species and the use of spray buffer zones (1-5 metres) to protect aquatic life are required.

Value

The application rate of 600 mL product/hectare (300 g a.i./ha) used on apples and pears is no longer supported by the registrant and will be removed. The lower rate of 300 mL product/hectare (150 g a.i./ha) will be maintained on product labels.

What Additional Information is Being Requested?

The risks and value have been found to be acceptable when all risk-reduction measures are followed; therefore, no additional information is being requested as a result of this re-evaluation.

Next Steps

Before making a re-evaluation decision on clofentezine, the PMRA will consider all comments received from the public in response to Proposed Re-evaluation Decision PRVD2013-05, Clofentezine. The PMRA will then publish a Re-evaluation Decision Document, 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

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).