Proposed Re-evaluation Decision: Trichlorfon

18 April 2008
ISBN: 978-0-662-48483-7 (978-0-662-48484-4)
Cat. No.: H113-27/2008-14E (H113-27/2008-14E-PDF)
(PRVD2008-14)

Foreword

Proposed Re-evaluation Decision for Trichlorfon

Health Canada'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. In 1999, Health Canada's Pest Management Regulatory Agency (PMRA) announced in Re-evaluation Note REV99-01, Re-evaluation of Organophosphate Pesticides, that 27 organophosphate active ingredients, including trichlorfon, would be re-evaluated in Canada.

Health Canada's Pest Management Regulatory Agency (PMRA) has finalized the risk and value assessments for the active ingredient trichlorfon and its end-uses on food and non-food areas. This proposal affects all end-use products containing trichlorfon registered in Canada. Once the final re-evaluation decision is made, registrant will be instructed on how to address mitigation measures and data requirements.

On 17 May 2007, Re-evaluation Note REV2007-05, Preliminary Risk Assessment of Trichlorfon, was published for consultation. This preliminary assessment indicated a level of concern for workers and the environment for some uses. No additional information to refine the assessments and/or mitigate risks was received during the consultation period. Furthermore, no additional information with respect to the value of trichlorfon was provided in response to the preliminary assessment. Therefore the PMRA, under the authority of the Pest Control Products Act, is proposing continued registration of some trichlorfon uses in Canada and phase-out of the uses with risk concerns. An evaluation of available scientific information found the following.

• Under the revised conditions of use, certain uses of products containing trichlorfon that do not involve a level of concern to human health or the environment have value in the food and crop industry. These uses include ground application on Balsam fir and spruce trees in farm woodlots, rights-of way and Christmas tree plantations as well as uses on beef and non-lactating dairy cattle. As a condition of the continued registration for these particular uses, new risk-reduction measures are proposed the labels of products containing trichlorfon. In addition, registrant must submit additional scientific information.
• Residential uses of trichlorfon are proposed for phase-out because the human health risks do not meet current standards.
• The postapplication worker risk for use on outdoor ornamentals is of concern based on the length of time required for residues to decrease to an acceptable level. The restricted-entry intervals required to meet the targets are expected to be impractical. The estimated exposures are considered to represent conservative assessments and are based on the best available data. The PMRA is proposing the phase-out of the uses on outdoor ornamentals unless additional data to refine the occupational exposure assessment are received.
• The buffer zones calculated for aerial applications of trichlorfon are believed to be unfeasible. Therefore, PMRA is proposing to phase out the aerial application of trichlorfon unless additional information is received to refine the assessment and/or mitigate environmental risks.

This Proposed Re-evaluation Decision is a consultation document¹ that summarizes the science evaluation for trichlorfon 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 trichlorfon.

Table of Contents

• Overview
  • Proposed Re-evaluation Decision for Trichlorfon
  • What Does Health Canada Consider When Making a Re-evaluation Decision?
  • What Is Trichlorfon?
  • Health Considerations
  • Environmental Considerations
  • Value Considerations
  • Measures to Minimize Risk
  • What Additional Scientific Information is Being Requested?
  • Next Steps
  • Other Information
    
    
• 1.0 Introduction
  
  
• 2.0 The Active Substance, Its Properties and Uses
  • 2.1 Identity of the Active Substance
  • 2.2 Physical and Chemical Properties of the Active Substance
  • 2.3 Methods of Analysis
    • 2.3.1 Methods for Analysis of the Active Substance as Manufactured
      
      
  • 2.4 Description of Registered Trichlorfon Uses
    
    
• 3.0 Impact on Human and Animal Health
  • 3.1 Toxicology Summary
  • 3.2 Occupational and Non-Occupational Risk Assessment
    • 3.2.1 Occupational Exposure and Risk Assessment
    • 3.2.2 Non-Occupational (residential) Exposure and Risk Assessment
      
      
  • 3.3 Dietary Exposure and Risk Assessment
    • 3.3.1 Acute Dietary Exposure and Risk Assessment
    • 3.3.2 Chronic Dietary Exposure and Risk Assessment
      
      
  • 3.4 Exposure From Drinking Water
    • 3.4.1 Concentrations in Drinking Water
    • 3.4.2 Drinking Water Exposure and Risk Assessment
      
      
  • 3.5 Aggregate Exposure and Risk Assessment
• 4.0 Impact on the Environment
  • 4.1 Environmental Fate
  • 4.2 Environmental Toxicology
    • 4.2.1 Terrestrial Risk Assessment
    • 4.2.2 Aquatic Risk Assessment
      
      
  • 4.3 Environmental Assessment Conclusions
    
    
• 5.0 Value
  • 5.1 Commercial and/or Restricted Class Products
    • 5.1.1 Alternatives to Trichlorfon
      
      
• 6.0 Toxic Substances Management Policy Considerations
  • 6.1 Toxic Substances Management Policy
    
    
• 7.0 Summary
  • 7.1 Human Health and Safety
    • 7.1.1 Occupational Risk
    • 7.1.2 Dietary Risk From Food
    • 7.1.3 Dietary Risk From Drinking Water
    • 7.1.4 Residential Risk
    • 7.1.5 Aggregate Risk
      
      
  • 7.2 Environmental Risk
    
    
• 8.0 Proposed Regulatory Decision
  • 8.1 Proposed Regulatory Actions
    • 8.1.1 Proposed Regulatory Action Related to Human Health
    • 8.1.2 Proposed Regulatory Action Related to Environment
      
      
  • 8.2 Additional Data Requirements
    • 8.2.1 Data Requirements Related to Occupational Exposure Assessment
    • 8.2.2 Data Requirements Related to Food Residue Chemistry
      
      
• List of Abbreviations

Overview

Proposed Re-evaluation Decision for Trichlorfon

On 17 May 2007, Health Canada's Pest Management Regulatory Agency published Re-evaluation Note REV2007-05, Preliminary Risk Assessment of Trichlorfon, for consultation. That assessment indicated there is a level of concern for workers and the environment for some uses. No additional information to refine the assessments and/or mitigate risks was received during the consultation period. Furthermore, no additional information with respect to the value of trichlorfon was provided in response to the preliminary assessment. Therefore, the PMRA, under the authority of the Pest Control Products Act and Regulations, is proposing continued registration of some trichlorfon uses in Canada and phase-out of the uses with risk concerns.

Following the re-evaluation announcement for trichlorfon, Bayer CropScience Inc., the registrant of the technical grade active ingredient, indicated that it intended to discontinue all uses except for those on Balsam fir and spruce trees in farm woodlots, rights-of way, Christmas tree plantations and municipal parks, on beef and non-lactating dairy cattle and on ornamentals. Only uses the registrant supported were considered in the health and environmental risk assessments of trichlorfon.

An evaluation of available scientific information found that under the revised conditions of use, certain uses of products containing trichlorfon that do not involve a level of concern to human health or the environment have value in the food and crop industry. As a condition of the continued registration for these particular uses, the PMRA is proposing to include new risk-reduction measures on product labels.

Certain uses of trichlorfon are proposed for phase-out because of the human health risks and/or risks to the environment. These uses include in municipal parks, on outdoor ornamentals as well as applying trichlorfon by air. In addition, registrants must submit additional scientific information.

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 registration². 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 populations in humans (e.g. children) and organisms in the environment (e.g. 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 visit the PMRA's website at www.pmra-arla.gc.ca. Before making a re-evaluation decision on trichlorfon, the PMRA will consider all comments received from the public in response to this consultation document⁴. The PMRA will then publish a Re-evaluation Decision⁵ on trichlorfon, 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 overview, please refer to the Science Evaluation section of this consultation document.

What Is Trichlorfon?

Trichlorfon is a broad spectrum, Resistance Management Group 1B (organophosphate) insecticide that inhibits the enzyme acetylcholinesterase and interrupts the transmission of nerve impulses. It works by contact and ingestion action. Products containing trichlorfon are registered under the following use-site categories: Forest and Woodlots, Livestock for Food, Terrestrial Food Crops, Terrestrial Feed Crops, Ornamentals Outdoors, Greenhouse Food Crops, Industrial Oil Seed and Fibre Crops, Structural, and Human Habitat and Recreational Areas.

Health Considerations

Can Approved Uses of Trichlorfon Affect Human Health?

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

Exposure to trichlorfon may occur through diet (food and water), by mixing, loading or applying the pesticide, or when entering a treated site. The PMRA considers two key factors when assessing health risks: the dose levels at which 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 (e.g. 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.

Trichlorfon is highly to moderately toxic via the oral route and of low toxicity via the dermal and inhalation routes of exposure. Trichlorfon is moderately irritating to eyes, non-irritating to skin and is considered a skin sensitizer.

Following oral exposure, trichlorfon is readily absorbed and rapidly eliminated with little accumulation in the tissues. Exposure to trichlorfon in adult animals produced inhibition of acetylcholinesterase, progressing to clinical signs at higher doses. Effects on pup development, including transient behavioural changes and brain-weight effects, have been observed at doses resulting in maternal toxicity. Several studies from the published literature have also raised concerns regarding the neurotoxic effects of trichlorfon on prenatal brain development in guinea pigs and pigs.

In the environment, trichlorfon degrades to dichlorvos, which is also an organophosphate. Dichlorvos is also a mammalian metabolite and is a more potent acetylcholinesterase inhibitor than trichlorfon. Thus, the risk assessment took dichlorvos into consideration. Acetylcholinesterase is an enzyme responsible for the proper functioning of the nervous system and is inhibited following an overexposure via oral, dermal or inhalation routes. Symptoms including tremors, salivation, diarrhea and shortness of breath may occur in animals and humans.

The human data on trichlorfon indicate that acute exposure to high doses of trichlorfon results in those effects typically associated with acute organophosphate intoxication. Trichlorfon has been shown to cause neuropathology in hens and humans directly exposed. The occurrence of neuropathy in humans with low-level exposure heightens the concern for this compound, particularly because the neuropathy is of a persistent enough nature to render severe consequences in a subpopulation of aged individuals.

As some concerns were noted with the current use patterns for trichlorfon, the PMRA is proposing to phase out treatment in municipal parks and to add further protective measures--product use changes, protective equipment and improved work practices--to product labels to further reduce the level of human exposure to trichlorfon. In addition, specific toxicity information regarding symptoms of overexposure are required in the Toxicological Information section of the product labels. The key additional protective measures and improvements required for the Toxicological Information section of product labels can be found under the heading Measures to Minimize Risk.

Risks in Residential and Other Non-Occupational Environments

Residential risks are of concern. Therefore, residential uses are proposed for phase-out.

Exposure may occur after trichlorfon is used in outdoor residential and recreational areas. Given trichlorfon degrades to dichlorvos, adults and children can be exposed to both when entering a treated site. Adults and children could experience short-term exposure when or immediately after is used, for example hikers walking in treated municipal parks. There are insufficient data to estimate residues of trichlorfon and dichlorvos in municipal parks. It was assumed that exposure to hikers would be similar to scouters entering a treated forest.

Based on this activity, the risk estimates associated with the residential uses do not meet current standards. Postapplication exposure to toddlers is expected to be even greater because postapplication activities associated with toddlers is considered more intensive. Toddlers are expected to experience more exposure than adults. As well, these estimates do not include potential inhalation exposure to dichlorvos. Currently, no data are available to estimate the concentration of dichlorvos in the air after trichlorfon is applied on to spruce and fir trees in municipal parks.

As restricted-entry intervals (REIs) calculated for adults are not considered feasible for municipal parks, a postapplication assessment for children was not pursued. Children's exposure is expected to be higher. Consequently, the PMRA is proposing the phase-out of uses in residential settings such as municipal parks.

Occupational Risks From Handling Trichlorfon

Exposure risks for mixers, loaders and applicators are not of concern provided additional risk-reduction measures are observed.

Workers can be exposed to trichlorfon when mixing, loading or applying the pesticide. Worker exposure estimates are based on the best available data at this time. The assessment may be refined with exposure data that are more representative of modern application equipment and engineering controls. Biological monitoring data could also further refine the assessment. No specific handler exposure data were submitted for trichlorfon Therefore, dermal and inhalation exposures were estimated using data from the Pesticide Handlers Exposure Database (PHED), Version 1.1.

The risk estimates associated with mixing, loading and applying activities for current label uses meet current standards and are not of concern, provided engineering controls and/or personal protective equipment are used.

Postapplication risks are of concern for workers performing high exposure activities.

As trichlorfon degrades to dichlorvos, workers can be exposed to both when entering a treated site to conduct activities such as handling treated ornamentals and Christmas trees, or when handling treated livestock. The postapplication occupational risk assessment considered exposures to workers entering treated sites, including forests, nurseries and Christmas tree plantations. It is expected that exposure of livestock handlers would be less than that of individuals applying product. Therefore, a quantitative postapplication exposure assessment was not conducted. However, mitigation measure are recommended to protect people handling treated animals.

Restricted-entry intervals (REIs) are calculated to determine the minimum length of time required before workers or others can safely enter a treated site. An REI is the amount of time that must elapse before residues on surfaces or in air decline to a level at which performing a specific activity results in acceptable exposures.

The length of time it takes for trichlorfon and dichlorvos residues to reach acceptable levels is not considered feasible for all uses. The PMRA is proposing the phase-out of the uses on outdoor ornamentals unless additional data is received to refine the occupational exposure assessment.

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.

Acute and chronic dietary exposure to trichlorfon was estimated using anticipated residue data from dermal application studies with livestock. The use on livestock is the only supported food use of trichlorfon. The acute potential daily intake of trichlorfon accounts for 1.3% (99.9th percentile) of the acute reference dose for the general population, and 2.1% of the acute reference dose for the highest exposed population group, children three to five years of age. The chronic dietary exposure as a percentage of the acceptable daily intake is 7% for the general population and 13% for the highest exposed population groups, children one to two and three to five years of age. Therefore, the acute and chronic dietary risk from trichlorfon is not considered to be of concern.

The supported uses of trichlorfon are not expected to result in any significant drinking water exposure. Therefore, drinking water risks are not of concern.

The Food and Drugs Act prohibits the sale of food containing a pesticide residue that exceeds the established maximum residue limit (MRL). Pesticide MRLs are established for Food and Drugs 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/on certain foods. Food containing a pesticide residue that does not exceed the established MRL does not pose an unacceptable health risk.

Division 15, Table II, of the Food and Drug Regulations currently provides no definition for the residue of concern for trichlorfon, and no MRLs are specified. The supported food uses of trichlorfon are on beef cattle and non-lactating dairy cattle. Where no specific MRL is established for a pest control product under the Food and Drug Regulations, subsection B.15.002(1) applies. This requires that residues do not exceed 0.1 ppm, which is considered a general MRL for enforcement purposes. However, changes to this general MRL may be implemented in the future, as indicated in Discussion Document DIS2006-01, Revocation of 0.1 ppm as a General Maximum Residue Limit for Food Pesticide Residues [Regulation B.15.002(1)]. If and when the general MRL is revoked, a transition strategy will be established to allow permanent MRLs to be promulgated.

The general MRL of 0.1 ppm will apply for enforcement purposes with respect to the residues of trichlorfon in food for all commodities, including beef cattle and milk. Parties interested in supporting an import MRL for residues of trichlorfon on other commodities should contact the PMRA during the comment period of this document to discuss the submission of appropriate data.

Environmental Considerations

What Happens When Trichlorfon is Introduced Into the Environment?

Trichlorfon poses a potential risk to certain terrestrial and aquatic organisms; therefore, additional risk-reduction measures must be observed.

Trichlorfon is not expected to persist in soil or aquatic environments. There is a high potential for mobility due to the very high solubility in water and weak adsorption to soil. Trichlorfon has a minimal potential for bioaccumulation. Dichlorvos is a major transformation product when trichlorfon decomposes in water.

The forestry use as well as the livestock and ornamental outdoor uses of trichlorfon are not expected to contaminate drinking water sources. In addition, the relatively short half-lives for dichlorvos and trichlorfon in surface water further decreases the potential for contamination of drinking water sources. Therefore, drinking water risks are not of concern.

Estimated environmental concentrations for water and land ecosystems were determined for the forestry and ornamental outdoor uses of trichlorfon based on the range of application rates and number of applications listed on the current labels of registered products. The uses on livestock were not expected to result in appreciable exposure to non-target organisms found on land and in the water; therefore an assessment was not conducted for this use-pattern.

Birds, small wild mammals, bees and aquatic organisms such as fish and aquatic invertebrates can be affected when trichlorfon is used. To reduce exposure of these organisms, it is important that additional risk-reduction measures be observed.

Aerial application in forestry is of particular concern because the risk to pollinators, birds and small wild mammals cannot be mitigated. The buffer zones calculated for aerial application are large and believed to be operationally unfeasible. Therefore, aerial applications of trichlorfon are proposed for phase-out.

Value Considerations

What is the Value of Trichlorfon?

No additional information with respect to the value of trichlorfon was provided in response to the preliminary assessment published in Re-evaluation Note REV2007-05.

The registered chemical alternatives for unsupported uses of trichlorfon or for the supported uses of trichlorfon that have risk concerns are listed in Appendix V. While the chemical control methods are registered, the PMRA has not commented on the availability and extent of use of these options.

Trichlorfon was the only registered chemical control method for a number of insect pests in narcissus, alfalfa, blueberries, collards, tobacco, lettuce and spinach when the alternative assessment was done in December 2004. The list of site-pest combinations without alternatives may have expanded in the meantime as chemical alternatives have been re-evaluated and their use patterns shifted. Narcissus is the only supported use without alternatives; the registrant does not support the other uses. The PMRA searched information available for specific site-pest combinations and found a number of non-chemical measures of pest control. The effectiveness and extent of use of these non-chemical control measures has not been verified.

Measures to Minimize Risk

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

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

Additional Key Risk-Reduction Measures

Human Health

• Label updates to the Toxicological Information section, which will provide information about symptoms and treatment for exposed individuals.
• Engineering controls, additional personal protective equipment, restricted-entry intervals and restrictions on number of applications to protect mixers/loaders/applicators and workers entering treated sites.
• Phase-out of residential use (municipal parks).

Environment

• Changes to label statements--including precautionary statements for bees, birds, small wild mammals and aquatic organisms as well as restrictions on field sprayer and airblast applications--to reduce release of trichlorfon into the environment.
• The observance of buffer zones to mitigate the entry of spray drift into aquatic systems.
• The phase-out of aerial applications of trichlorfon to protect aquatic habitats that may contain sensitive species.

What Additional Scientific Information is Being Requested?

The human health risks and/or risks to the environment for certain uses of trichlorfon were found to be acceptable and additional confirmatory scientific information is being requested from registrants as a result of this re-evaluation.

Next Steps

• Before making a re-evaluation decision on trichlorfon, all comments received from the public in response to this consultation document will be considered. The PMRA will then publish a Re-evaluation Decision document that 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.
• Registrant will be asked to submit the confirmatory information when the Re-evaluation Decision is published.

Other Information

When the PMRA makes its registration decision, it will publish an Evaluation Report on trichlorfon (based on the Science Evaluation section of this consultation document). 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).

Once all organophosphate pesticides have been re-evaluated, a cumulative risk assessment will be conducted. The assessment will consider potential exposure to all chemicals causing toxicity in the same manner. The results of the cumulative risk assessment may affect any previous re-evaluation decision.

1.0 Introduction

Trichlorfon is a broad spectrum, Resistance Management Group 1B (organophosphate) insecticide that inhibits the enzyme acetylcholinesterase and interrupts the transmission of nerve impulses. It works by contact and ingestion action.

Following the re-evaluation announcement for trichlorfon, Bayer Cropscience Inc., the registrant of the technical grade active ingredient, indicated that it intended to discontinue all uses except for those on Balsam fir and spruce trees in farm woodlots, rights-of way, Christmas tree plantations and municipal parks, on beef and non-lactating dairy cattle, and on ornamentals. Only uses the registrant supported were considered in the health and environmental risk assessments of trichlorfon.

2.0 The Active Substance, Its Properties and Uses

2.1 Identity of the Active Substance

Common name Trichlorfon

Function Insecticide

Chemical name Dimethyl (2,2,2-trichloro-1- hydroxyethyl)phosphonate

Chemical family Organophosphate

Chemical Abstracts Service registry number 52-68-6

Molecular formula C₄H₈Cl₃O₄P

Molecular mass 257.4

Structural formula

Purity of technical grade active ingredient 98% minimum

Registration number 22482

Basic manufacturer Bayer do Brazil S.A.

Identity of relevant impurities of toxicological, environmental and/or other significance
Based on the manufacturing process and on the starting materials used, the technical grade active ingredient is not known to contain impurities of toxicological concern as identified in Section 2.13.4 of Regulatory Directive DIR98-04 or Toxic Substances Management Policy (TSMP) Track 1 materials as identified in Appendix II of Regulatory Directive DIR99-03.

2.2 Physical and Chemical Properties of the Active Substance

Property Result

Colour and physical state Colourless crystals

Melting point/range 78.5°C

Boiling point/range Not applicable

Specific gravity 1.73 at 20°C

Vapour pressure 0.21 mPa at 20°C

Ultraviolet (UV)-visible spectrum Not expected to absorb UV at wavelength above 300 nm.

Solubility in water at 20°C 120 g/L (20°C)

Solubility (g/L) in organic solvents

n-Octanol-water partition coefficient Log K_ow = 0.43

Dissociation constant No dissociable functionality.

2.3 Methods of Analysis

2.3.1 Methods for Analysis of the Active Substance as Manufactured

The active ingredient and impurities were quantitated by gas chromatography and high performance liquid chromatography. The method used for the active ingredient was found to be specific and precise for the determination.

2.4 Description of Registered Trichlorfon Uses

Appendix I lists all trichlorfon products registered under the authority of the Pest Control Products Act. Appendix II lists all the uses for which trichlorfon is presently registered, with an indication of which uses the registrant will continue to support, will no longer support or will partially support. Only the uses the registrant supports were considered in the health and environmental risk assessments of trichlorfon.

3.0 Impact on Human and Animal Health

3.1 Toxicology Summary

The toxicology database supporting trichlorfon is based on studies from the registrant as well as numerous citations from the literature. In acute studies using laboratory animals, trichlorfon was highly to moderately toxic via the oral route and of low toxicity via the dermal and inhalation routes. Trichlorfon was moderately irritating to eyes, non-irritating to skin and was found to be a skin sensitizer. Acute toxic signs induced by trichlorfon are consistent with signs of cholinesterase intoxication and include tremors, salivation, diarrhea, decreased motor activity, respiratory distress and death. With oral exposure, trichlorfon was readily absorbed and rapidly eliminated with little tissue retention. Excretion occurred primarily via the urine and, to a lesser degree, in the feces and expired air. The identified urinary metabolites were demethyl trichlorfon, demethyl dichlorvos, dimethyl hydrogen phosphate, methyl hydrogen phosphate and phosphoric acid. Thus, the main degradation routes of trichlorfon are demethylation, phosphate-carbon cleavage and ester hydrolysis via dichlorvos. Trichlorfon rearranges via dehydrochlorination to form dichlorvos (a more potent cholinesterase inhibitor) under physiological conditions. The influence of gender on pharmacokinetics could not be ascertained from the available database.

Following single and repeated dosing, one of the most sensitive indicators of toxicity was the inhibition of acetylcholinesterase, an enzyme necessary for the proper functioning of the nervous system, progressing to clinical signs at higher doses. When tested in study animals (mouse, rat, rabbit, dog and monkey), acetylcholinesterase was affected by oral, dermal and inhalation routes, with no appreciable gender differences. The monkey appeared to be the most sensitive species to the cholinesterase inhibition, whereas the mouse was the least sensitive. Repeat-dose oral data suggest that increased duration of dosing results in a slight increase in toxicity with chronic exposure. At higher doses, trichlorfon affected the liver, kidney, lungs, spleen, gastrointestinal tract and hematological components.

In an acute oral study in chickens, no evidence of delayed neurotoxicity was evident; however, this study was considered supplemental due to study limitations. In a subchronic oral study in chickens, there were no clinical or behavioural signs of neurotoxicity, but slight axonal degeneration was noted at the highest dose tested. Neurotoxic esterase activity was not measured in this study. In the subchronic neurotoxicity study in the rat, minimal myelin degeneration of the spinal nerve roots was demonstrated at levels producing cholinesterase depression, clinical signs and neurobehavioural alterations.

A developmental neurotoxicity study conducted recently in rats showed functional changes in offspring (albeit transient) as well as effects on brain weight and size. These changes occurred at levels that also caused cholinesterase inhibition in the offspring as well as toxicity in the maternal animals. No convincing evidence was provided to demonstrate lactational transfer of trichlorfon; hence, there is residual uncertainty over the level of exposure received by the pups during the entire peak brain growth spurt period. While the study indicates that fetuses are unlikely to be more sensitive than maternal animals, the study may not adequately predict the potential effects associated with direct exposure of infants to trichlorfon.

Trichlorfon presented limited evidence of potential for carcinogenicity in the available database. Trichlorfon was evaluated for carcinogenicity in mice, rats and monkeys. In female mice, there was an increased incidence of mammary tumours at the high dose only; however, this dose was considered excessive based on increased mortality. In rats, increased incidences of alveolar/bronchiolar adenomas in males, alveolar/bronchiolar carcinomas in females and renal tubular adenomas in males were noted at the high dose; however, this dose exceeded the maximum tolerated dose. There was no significant pathology, including tumorigenicity, and no preneoplastic lesions in monkeys exposed to daily doses of trichlorfon for 10 years. Trichlorfon has also tested positive in various in vitro assays of cell damage and negative in an in vivo assay for clastogenicity.

Reproductive effects observed at the highest dose in the two-generation reproduction study included a reduction in live birth index. At this dose level, adults had toxicologically significant reductions in erythrocyte and brain cholinesterase as well as renal and pulmonary pathology, but no clinical signs of cholinergic poisoning. Adults also showed cholinesterase inhibition at the low and mid-dose level. Effects observed in the high-dose offspring included reduced viability, brain cholinesterase and increased incidence of dilated renal pelvises. Based on the results of this study, there is no evidence of increased sensitivity of the offspring compared to the adults due to treatment with trichlorfon. Similar effects (e.g. a decrease in the live birth index and the viability index) were also observed at comparable dose levels in the developmental neurotoxicity study. The only effect indicative of endocrine toxicity is the decreased spermatogenesis observed in dogs treated for one year with trichlorfon.

All rat developmental studies conducted by gavage were considered supplemental due to various study limitations. In two supplemental gavage studies and one supplemental dietary study, maternal toxicity was evident as clinical signs, cholinesterase inhibition, mortality or decreased food intake at doses at or below those causing developmental toxicity. In a third gavage study using high-dose levels, fetal death and malformations were observed in the absence of effects on maternal weight gain or food intake. In an acceptable dietary study, delayed ossification and rib abnormalities were noted in fetuses at a level resulting in maternal toxicity (i.e. cholinesterase inhibition and decreased weight gain and food intake). In the rabbit developmental study, no treatment-related terata were observed; however, increases in resorptions as well as decreases in ossification and fetal weights were identified at a dose causing maternal toxicity (clinical signs, abortions and cholinesterase inhibition). In a published study, administration of trichlorfon to pregnant mice and hamsters resulted in an increase in malformations, but only at doses that were maternally toxic. The study in mice showed an effect on fetal weight in the absence of maternal toxicity; however, maternal animals were monitored for weight gain and food intake only.

Several studies from the published literature raise concerns regarding the effects of trichlorfon on prenatal brain development in guinea pigs and pigs.

In general, organophosphate intoxication in humans is manifested by symptoms that appear in three stages. For those who survive the acute effects of organophosphate intoxication (characterized by peripheral muscarinic effects such as nausea, vomiting, anorexia, abdominal cramps, diarrhea and bradycardia), an intermediate syndrome can develop, which involves nicotinic effects such as muscle weakness, fatigability, twitching and paralysis affecting the neck flexors, proximal limb muscles, cranial nerve-innervated muscles and respiratory muscles. Symptoms develop 24 to 96 hours after the acute cholinergic phase and can last 2 to 3 weeks. A delayed syndrome can subsequently be observed, which worsens over several days to weeks and comprises central nervous system effects such as confusion, ataxia, slurred speech and central respiratory paralysis and a sensorimotor axonal polyneuropathy that is most severe distally. Death due to organophosphorus intoxication generally arises due to respiratory failure that is multifactorial in etiology and may involve pulmonary edema.

The human data available on trichlorfon are abundant with respect to poisoning cases, case studies following therapeutic administration for parasitic infestations and clinical trials for treatment of Alzheimer's disease. These data substantiate that acute exposure to high doses of trichlorfon results in those effects typically associated with acute organophosphate intoxication. The data also support the premise that individuals who survive an acute poisoning episode could suffer from the delayed syndrome manifested as distal neuropathy. Of greater concern, however, are those individuals who have been exposed to non life-threatening doses that appear to develop the intermediate syndrome. The proximal muscle weakness associated with this intermediate syndrome can itself be life-threatening and recovery from this effect cannot be assured. This syndrome has been observed in humans at doses equal to or close to 0.65 mg/kg bw/day.

3.2 Occupational and Non-Occupational Risk Assessment

Occupational and residential risk is estimated by comparing potential exposures with the most relevant endpoint from toxicology studies to calculate a margin of exposure (MOE). This is compared to a target MOE incorporating safety factors protective of the most sensitive subpopulation. If the calculated MOE is less than the target MOE, it does not necessarily mean that exposure will result in adverse effects. However, MOEs less than the target MOE require measures to reduce risk. For trichlorfon, the adverse toxicological endpoint of cholinesterase inhibition is the same regardless of exposure route; thus, it is appropriate to combine the route-specific exposures to generate a single risk estimate. Where the target MOEs for exposure routes are the same, a "combined-route MOE" may be generated.

Trichlorfon has been shown to cause central nervous system malformations following prenatal exposure, to affect brain weight in offspring (which does not appear to be related solely to general growth retardation) and to cause persistent functional changes as well as neuropathology in the offspring of pigs and guinea pigs. The developmental neurotoxicity study showed functional changes in offspring (albeit transient) as well as effects on brain weight and size. Trichlorfon has been shown to cause neuropathology in hens and humans that were directly exposed to this organophosphate. In addition, human data indicate that exposure to sublethal doses may subsequently lead to later development of an intermediate syndrome that includes proximal muscle weakness as well as a myriad of other possible neurological manifestions. On this basis, an additional safety factor of threefold was considered appropriate to address neurotoxicity concerns.

For short- and intermediate-term dermal risk assessment in adults, the dermal no observed adverse effect level (NOAEL) of 100 mg/kg bw/day from a 21-day rabbit dermal study was selected. Inhibition of erythrocyte cholinesterase was observed at the lowest observed adverse effect level (LOAEL) of 300 mg/kg bw/day in this study. The target MOE selected when using this study is 300, accounting for standard uncertainty factors of 10-fold for interspecies extrapolation, 10-fold for intraspecies variability as well as an additional 3-fold safety factor for neurotoxicity concerns. This NOAEL and MOE is considered to be protective of all populations including pregnant women and their unborn children.

For assessment of short- and intermediate-term inhalation risk assessment in adults, the inhalation NOAEL of 3.5 mg/kg bw/day from a 21-day rat inhalation study was selected. Inhibition of plasma, erythrocyte and brain cholinesterase was observed at the LOAEL of 9.5 mg/kg bw/day in this study. The target MOE selected when using this study is 300, accounting for standard uncertainty factors of 10-fold for interspecies extrapolation, 10-fold for intraspecies variability as well as an additional 3-fold safety factor for neurotoxicity concerns. The selection of this study and MOE is considered to be protective of all populations including pregnant women and their unborn children.

3.2.1 Occupational Exposure and Risk Assessment

Workers can be exposed to trichlorfon when mixing, loading or applying the pesticide. As trichlorfon degrades to dichlorvos, workers can be exposed to both when entering a treated site to conduct activities such as handling treated ornamentals and Christmas trees or when handling treated livestock.

3.2.1.1 Mixer/Loader/Applicator Exposure and Risk Assessment

There is a potential for exposures in mixers, loaders, applicators and other handlers. Based on typical use patterns, The major scenario identified for the solution formulation is a pour-on formulation (graduated applicator). The major scenarios identified for the soluble-powder formulation include the following:

• mixing/loading/applying by low-pressure handwand, high-pressure handwand and backpack;
• mixing/loading for aerial application;
• ultra-low volume (ULV) aerial application;
• mixing/loading/applying by right-of-way sprayer;
• mixing/loading/applying by airblast; and
• mixing/loading/applying by groundboom.

Based on the number of applications, workers applying trichlorfon would generally have a shortto intermediate-term duration of exposure (< 30 days to 1-3 months, respectively). The PMRA estimated handler exposure based on different levels of personal protection.

• Engineering Controls: Closed mixed/loading. Engineering controls cannot be used with handheld application methods because no known devices can be used routinely to lower the exposures for these methods.
• Baseline personal protective equipment (PPE): long-sleeved shirt and long pants, chemical-resistant gloves, with and without respirator and open or closed mixing.
• Mid-level PPE: cotton coveralls over long-sleeved shirt and long pants, chemicalresistant gloves, with and without respirator and open or closed mixing.
• Maximum PPE: chemical-resistant coveralls over long-sleeved shirt and long pants, chemical-resistant gloves, with respirator and open or closed mixing.

Mixer/loader/applicator exposure estimates are based on the best available data at this time. The assessment might be refined with exposure data more representative of modern application equipment and engineering controls. Biological monitoring data could also refine the assessment further.

No chemical-specific handler exposure data were submitted for trichlorfon. Consequently, dermal and inhalation exposures were estimated using data from the Pesticide Handlers Exposure Database (PHED), Version 1.1. The PHED is a compilation of generic mixer/loader applicator passive dosimetry data with associated software that facilitates the generation of scenario-specific exposure estimates based on formulation type, application equipment, mixing/loading systems and level of PPE. In most cases, the PHED did not contain appropriate data sets to estimate exposure to workers wearing chemical-resistant coveralls or a respirator. This was estimated by incorporating a 90% clothing protection factor for chemical-resistant coveralls and a 90% protection factor for a respirator into the unit exposure data.

PHED data for high and low-pressure handwand scenarios are representative of application to low and mid level shrubs, and may underestimate exposures to the head and upper body for application to trees. Additionally, there are no reliable PHED data for soluble powder with water-soluble packaging (closed mixing/loading) for these scenarios or for backpack application scenarios. Mixing/loading/application data for liquid high- and low-pressure handwand and backpack were used to represent closed mixing/loading and open application; they are not believed to underestimate exposure.

Calculated MOEs (summarized in Appendix IV) exceed target MOEs for application, mixing and loading for current label uses, provided engineering controls and/or personal protective equipment are used.

3.2.1.2 Occupational Postapplication Exposure and Risk Assessment

Forestry, Ornamentals and Christmas Tree Plantations

Based on the trichlorfon use pattern, there is potential for short-term (< 30 days) postapplication exposure to trichlorfon and dichlorvos. The postapplication occupational risk assessment considered exposures to workers entering treated sites, including forests, nurseries and Christmas tree plantations.

Given that trichlorfon degrades to dichlorvos, dislodgeable foliar residues (DFRs) of dichlorvos were also estimated. No relevant studies were available for estimating the DFRs of dichlorvos after application of trichlorfon on ornamentals. However, Murphy, Cooper and Clark (1996) measured turf transferable residues (TTR) of dichlorvos after application of trichlorfon; this was examined to estimate a degradation value (percentage of trichlorfon residues that break down to dichlorvos residues). The highest TTR value reported in the study was 27%, which represents the percentage of total TTRs that was dichlorvos at 3 hours after application. This value was used to support an estimate of 50% (as opposed to 27%) because the study examined application on turf (not representative of ornamentals) as well as had a number of limitations.

Other data considered for the estimate of the amount of trichlorfon that degrades to dichlorvos were hydrolysis laboratory studies in which, at pHs levels between 7 and 9, dichlorvos made up 25.5 to 52% of the applied radioactivity. Based on a weight-of-evidence approach, a conservative value of 50% was estimated for the amount of trichlorfon that degrades to dichlorvos on the foliage.

The default dissipation rate of 10% per day was increased to 50% per day based on the volatility of dichlorvos (vapour pressure = 1.2 × 10^-2 to 3.2 × 10^-2 mm Hg) and its dissipation rate from a number of turf studies dichlorvos. Three proprietary TTR studies conducted in Ontario, California and Florida showed dissipation rates between 66% and 73% for dichlorvos applied on turf.

Inhalation exposure to trichlorfon is not considered to be a significant route of exposure for people entering treated forests, nurseries or Christmas tree plantations compared to the dermal routes. In addition, trichlorfon has low volatility based on a vapour pressure of 7.8 × 10^-6 mm Hg at 20°C. Thus, a postapplication inhalation exposure assessment was not conducted.

However, dichlorvos--a breakdown product of trichlorfon--has a high vapour pressure, 1.2 × 10^-2 mm Hg, under field conditions. No relevant studies were available to determine the air concentrations of dichlorvos after trichlorfon is applied on ornamentals. However, Murphy, Cooper and Clark's study in which trichlorfon was applied to irrigated and non-irrigated turf plots with a groundboom sprayer summarized air concentrations of dichlorvos on days one and two after application. Based on these air concentrations (0.23 µg a.i./m³ on day 1 and 0.12 µg a.i./m³ on day 2 corrected for the lower application rate in Canada for ornamentals and forestry), inhalation exposure is not expected to be of concern (see Table 3.2.1.2.1 below). Additional data would be needed to confirm air concentrations of dichlorvos are similar after application of trichlorfon on ornamentals, forestry and narcissus.

Table 3.2.1.2.1 Concentrations of Dichlorvos After Application With Trichlorfon on Turf

Day After Application on Turf	Air Concentration (mg/m3)a	Respiratory Exposure (mg/kg bw/day)b	MOEc
2	0.0003528	0.0000403	1240
3	0.0001764	0.0000202	2480

a Maximum air concentration sampled 70 cm above centre of treated plot; corrected for application rate (from 9.2 to 1.8 kg a.i./ha).
b Where inhalation exposure = [concentration (mg a.i./m³) × respiratory volume m³/hour × 8 hours/day] / 70 kg. Respiratory volume is based on the Draft International Harmonisation Position Paper on Methodology Issues values for light activity 1.0 m³/hour.
c Based on a short-term oral NOAEL of 0.05 mg/kg/day for dichlorvos established by the PMRA in 2004 assuming 100% absorption (target MOE of 1000).

Restricted-entry intervals (REIs) are calculated to determine the minimum length of time required before workers or others can safely re-enter a treated site. An REI is the duration of time that must elapse before residues on surfaces or in air decline to a level where performance of a specific activity results in exposures above the target MOE (i.e. > 300 for trichlorfon and > 1000 for dichlorvos for short-term exposure scenarios). REIs and postapplication exposure calculations for each use site are summarized in Appendix IV.

In the forestry and Christmas tree scenarios, calculated MOEs exceed target MOEs for postapplication exposure to trichlorfon at day 0, assuming 2 applications, 7 days apart, with the exception of hand-line irrigation (REI of 7 days). For postapplication exposure to dichlorvos, target MOEs were not met until day 7 (grading and tagging) to 11 (hand-line irrigation).

For ornamentals and narcissus, target MOEs for trichlorfon residues were not met until 28 days after application for ornamentals (assuming 2 applications, 7 days apart) and 33 days for narcissus. For dichlorvos residues, target MOEs were not met until day 14 for ornamentals and day 15 for narcissus.

The length of time that it takes for trichlorfon and dichlorvos residues to reach acceptable levels (i.e. when the target MOE is met) is not considered feasible for all crops (see Table 3.2.1.2.2). Postapplication exposure estimates are based on the best available data. The calculated REIs may be further refined with DFR studies that characterize the residues of both.

Table 3.2.1.2.2 Restricted-Entry Interval for Commercial Postapplication Activities

Crop	Activity	Transfer Coefficienta	Trichlorfon Proposed REIb	Dichlorvos Proposed REIc	Feasible REId
Christmas trees	Hand-line irrigation	1100	7	11	7
Christmas trees	Hand pruning, scouting, pinching, tying, training, shaping	500	0	10	7
Christmas trees	Hand weeding, propping, grading/tagging Christmas trees	100	0	7	7
Forestry	Scouting, tying, training,	500	0	10	7
Forestry	Grading/tagging	100	0	7	7
Ornamentals (cut flowers)	Hand harvesting, hand pruning, thinning, pinching	7000	25	14	1
Ornamentals (cut flowers)	Irrigation, scouting	4000	19	13	1
Ornamentals (cut flowers)	Irrigation, scouting, thinning, hand weeding	2500	15	12	1
Outdoor ornamentals (shrubs)	Transplant ball/burlap	10000	28	14	7
Outdoor ornamentals (shrubs)	Irrigate	4000	19	13	1 to 7
Outdoor ornamentals (shrubs)	Sort/pack	2500	15	12	7
Narcissus	Irrigation, scouting	4000	33	15	14

a Based on transfer coefficients as set out in Transfer Coefficients for Orchard Tree Crops and Christmas, Science Advisory Council for Exposure Agricultural Transfer Coefficient and Science Advisory Council for Exposure Agricultural Default Transfer Coefficient.
b Based on worker short-term dermal NOAEL of 100 mg/kg bw/day with a target MOE of 300 for trichlorfon and 2 applications, 7 days apart (except for narcissus where one application was assumed).
c Based on worker short-term oral NOAEL of 0.05 mg/kg bw/day with a target MOE of 1000 for dichlorvos and a dermal absorption of 30% where 50% of trichlorfon breaks down to dichlorvos with 50% dissipation per day.
d Feasible REIs based on crop-specific information.

Livestock Use Pattern

It is expected that postapplication exposure for livestock handlers would be less than that for individuals applying product. Therefore, a quantitative postapplication exposure assessment was not conducted.

3.2.2 Non-Occupational (residential) Exposure and Risk Assessment

Residential risk assessment is concerned with estimating risks to the general population, including children, during or after pesticide application. Postapplication exposure may occur when trichlorfon is used in outdoor residential and recreational areas. Although the registrant does not support trichlorfon use on ornamentals in residential areas, the registrant does support ground and aerial application of trichlorfon in municipal parks for controlling spruce budworm larvae.

There is potential for short-term exposure to adults and children during or immediately following application of trichlorfon (e.g. hikers entering treated municipal parks). There is insufficient data to estimate deposition rates or DFR values of trichlorfon (and dichlorvos) from aerial ULV or ground application in municipal parks. It was assumed that exposure of hikers would be similar to scouters entering a treated forest. Based on this re-entry activity, the calculated MOEs were 1315 for trichlorfon and 6 for dichlorvos, based on 2 hours of activity in a municipal park on day 0 (see Table 3.2.2.1).

Postapplication exposure in toddlers is expected to be greater than that of a hiker because postapplication activities associated with toddlers are considered more intensive (incidental non-dietary oral exposure resulting from hand-to-mouth transfer and direct ingestion of soil or turf). As well, these estimates do not include potential inhalation exposure to dichlorvos. Currently, no data are available to estimate air concentrations of dichlorvos following application of trichlorfon (day 0) on spruce and fir trees in municipal parks via ULV aerial or ground application equipment.

Table 3.2.2.1 Residential Postapplication Exposure for Adults in Municipal Parks^a

Activity	Day After Application	Transfer Coefficientb (cm2/hour)	DFRc (µg/cm2)		Duration (hours per day)	Dermal Exposure (µg/kg bw/day)		MOE
			TRI	DVP		TRId	DVPe	TRId	DVPe
Scouting/ hiker (adult)	0	500	5.3	1.8	2	76.03	7.77	1315	6
	7	500	2.5	0	2	36.36	0.06	2750	823
	8	500	2.3	0	2	32.73	0.03	3056	1646

* Shaded cells indicate MOE < target MOE.
a Estimates do not include potential inhalation exposure.
b Transfer coefficients for orchard tree crops and Christmas trees.
c Based on 2 applications, 7 days apart and a default of 20% of the maximum application rate with 10% dissipation per day for trichlorfon; based on the assumption that 50% of trichlorfon breaks down to dichlorvos with 50% dissipation per day.
d Based on a short-term dermal NOAEL of 100 mg/kg bw/day with a target MOE of 300.
e Based on a short-term oral NOAEL of 0.05 mg/kg bw/day with a target MOE of 1000 and a dermal absorption of 30%.

As the REIs summarized above for adults are not considered feasible for municipal parks, a postapplication assessment for children was not pursued. In addition, children's exposure is expected to be higher.

3.3 Dietary Exposure and Risk Assessment

In a dietary exposure assessment, the PMRA determines how much of a pesticide residue, including residues in milk and meat, may be ingested with the daily diet. These dietary assessments are age-specific and incorporate the different eating habits of the population at various stages of life. For example, the assessments take into account differences in children's eating patterns, such as food preferences and the greater consumption of food relative to their body weight when compared to adults. Dietary risk is then determined by the combination of the exposure and the toxicity assessments. High toxicity may not indicate high risk if the exposure is low. Similarly, there may be risk from a pesticide with low toxicity if the exposure is high.

The PMRA considers limiting use of a pesticide when risk exceeds 100% of the reference dose. The PMRA's Science Policy Note SPN2003-03, Assessing Exposure from Pesticides, A User's Guide, presents detailed acute and chronic risk assessment procedures.

Acute and chronic dietary exposure and risk estimates were generated using Dietary Exposure Evaluation Model (DEEM^®) software and updated consumption data from the United Sates Department of Agriculture's Continuing Survey of Food Intakes by Individuals 1994-1998.

3.3.1 Acute Dietary Exposure and Risk Assessment

Acute dietary risk is calculated considering food consumption and food residue values. A probabilistic statistical analysis allows all possible combinations of consumption and residue levels to be combined to estimate a distribution of the amount of trichlorfon residue that might be eaten in a day. A value representing the high end (99.9th percentile) of this distribution is compared to the acute reference dose, which is the dose at which an individual could be exposed on any given day and expect no adverse health effects. When the expected intake from residues is less than the acute reference dose, the expected intake is not considered to be of concern.

To estimate acute dietary risk (1 day), the NOAEL of 10 mg/kg bw/day from the acute neurotoxicity study in rats was selected for risk assessment based on clinical signs, alteration in functional observational battery, decreased motor activity, and significant erythrocyte and brain cholinesterase inhibition at 50 mg/kg bw/day. Standard uncertainty factors were used for an uncertainty factor of 100 (10-fold for interspecies extrapolation and 10-fold for intraspecies variability). An additional uncertainty/safety factor of 3-fold, as discussed in Section 3.2, was also applied, resulting in a total uncertainty factor of 300. The acute reference dose was calculated to be 0.03 mg/kg bw. It is the opinion of PMRA that uncertainty associated with the direct exposure of non-nursing infants is accommodated within the additional threefold safety factor for neurotoxicity concerns.

This reference dose provides a margin of safety of 3400 to the lowest developmental NOAEL of 102 mg/kg bw/day from a rat dietary study and ~1200 to the lowest developmental NOAEL of 35 mg/kg bw/day from the rabbit gavage study. This reference dose also provides a margin of safety of ~1700 to the NOAEL of 50 mg/kg bw/day for increased stillbirths in the reproduction and developmental neurotoxicity studies. Thus, this value is considered protective of all populations including pregnant females and their unborn children. In supplemental human studies, a single oral dose of 5 mg/kg bw of trichlorfon has been shown to inhibit erythrocyte cholinesterase inhibition by > 20%, yielding a margin of exposure of ~170 to the acute reference dose.

The acute dietary exposure was assessed in a mixed tier probabilistic assessment using anticipated residue data from dermal application studies with livestock. This represents the only supported food use of trichlorfon. The acute potential daily intake accounts for 1.3% (99.9th percentile) of the acute reference dose for the general population and 2.1% of the acute reference dose for children three to five years of age. Therefore, the acute dietary risk from trichlorfon is not considered to be of concern.

3.3.2 Chronic Dietary Exposure and Risk Assessment

The chronic dietary risk was calculated by using the average consumption of different foods, and the average residue values on those foods, over a 70-year lifetime. This expected intake of residues was compared to the acceptable daily intake, which is the dose at which an individual could be exposed over the course of a lifetime and expect no adverse health effects. When the expected intake from residues is less than the acceptable daily intake, the expected intake is not considered to be of concern.

The 10-year chronic toxicity/oncogenicity Rhesus monkey study was selected to estimate dietary risk from repeat exposure. A LOAEL was established at 0.2 mg/kg bw/day based on decreased erythrocyte and brain cholinesterase activity in the males. It is worth noting that in two clinical trials, similar maintenance doses of 0.2-0.25 mg/kg bw/day produced significant erythrocyte cholinesterase inhibition in humans.

For all populations, standard uncertainty factors were used (10-fold for interspecies extrapolation and 10-fold for intraspecies variability) as well as an additional factor of 10-fold. The additional factor accounted for the use of a LOAEL instead of a NOAEL and for the neurotoxicity concerns (see Section 3.2) resulting in an overall factor of 1000 and an acceptable daily intake of 0.0002 mg/kg bw/day. It is the opinion of the PMRA that uncertainty associated with the direct exposure of non-nursing infants is accommodated within the additional 10-fold safety factor.

This reference dose provides a margin of exposure of > 3000 to the dose at which the intermediate syndrome of organophosphate intoxication has been observed in humans.

The chronic dietary exposure was assessed using anticipated residue data from livestock dermal application studies, which represents the only supported food use of trichlorfon. Chronic dietary exposure as a percentage of the acceptable daily intake is 7% for the general population and 13% for the most affected subpopulations--children one to two years of age and children three to five years of age. Therefore, the chronic dietary risk from trichlorfon is not considered to be of concern.

3.4 Exposure From Drinking Water

3.4.1 Concentrations in Drinking Water

The forestry use of trichlorfon is not expected to result in significant contamination of drinking water sources. Forestry applications are usually carried out in remote locations and away from human habitations. The spray programs are infrequent and may be required only once every few years depending on the pest pressure. The amount of pesticide that would reach the soil would be much less than in an agricultural field because of the heavy canopy in a forest. The forest floor usually has an organic layer formed from dead leaves and pine needles, which covers the soil beneath. This organic layer would be expected to decrease any potential runoff. In addition, the relatively short half-lives for dichlorvos and trichlorfon in surface water further decrease the potential for contamination of drinking water sources.

The livestock and ornamental outdoor uses of trichlorfon are also not expected to result in significant contamination of drinking water. Both uses would only be spot treatments and would result in minimal exposure to soil; hence, these uses would result in limited potential for contamination of drinking water sources.

3.4.2 Drinking Water Exposure and Risk Assessment

The supported uses of trichlorfon are not expected to result in any significant drinking water exposure. Therefore, drinking water risks are not of concern. Nonetheless, drinking water levels of comparison (DWLOC) were determined for all subpopulations. The DWLOCs can only be calculated if other relevant exposures are not of concern to the PMRA as they simply express the difference between the reference dose and the non-drinking water exposure. The DWLOC values were compared to model estimates of potential water exposure. The acute DWLOC values ranged from 294 µg/L for children three to five years of age, to 1037 µg/L for the general population. The chronic DWLOCs ranged from 1.7 µg/L for the most affected subpopulations--children from 1 to 2 years of age and children 3 to 5 years of age--to 6.5 µg/L for the general population.

3.5 Aggregate Exposure and Risk Assessment

The dietary exposure estimates encompass all potential non-occupational exposures from trichlorfon. There are no residential uses of trichlorfon and there is no expectation of exposure through drinking water. The use in municipal parks is of concern based on health risks, and the PMRA is proposing to phase out this use (see sections 7.0 and 8.0). Given that dietary exposure is acceptable for all populations and durations (see Section 3.3), aggregate risk is not of concern.

4.0 Impact on the Environment

In assessing the environmental risk of trichlorfon, a deterministic assessment was conducted. In this assessment, risk was characterized by the quotient method, calculated as the ratio of the estimated environmental concentration to the effects endpoints of concern. Quotient values less than one are considered to indicate a low risk to non-target organisms, whereas values greater than one are considered to indicate that some degree of risk exists for non-target organisms.

Estimated environmental concentrations for aquatic and terrestrial ecosystems were determined for the forestry and ornamental outdoor uses of trichlorfon based on the range of application rates and number of applications listed on the current registered labels. The livestock uses were not expected to result in appreciable exposure to non-target terrestrial and aquatic organisms; therefore, an assessment was not conducted for this use pattern. Effects toxicity endpoints (acute and chronic) were chosen for the most sensitive species tested and used as surrogates for the wide range of species that could be exposed following treatment with trichlorfon.

4.1 Environmental Fate

In terrestrial environments, trichlorfon is expected to be non-persistent in soil, with aerobic biotransformation being an important route of dissipation and hydrolysis contributing in neutral to acidic environments. There is a high potential for mobility due to the very high solubility in water and weak adsorption to soil. In aquatic environments, trichlorfon is also expected to be non-persistent. Trichlorfon has a minimal potential for bioaccumulation in biota.

Table 4.1.1 Summary of the Physicochemical Properties, Transformation and Fate of Trichlorfon

Property/Process	Result	Interpretation
Solubility in water at 20°C	120 000 mg/L (20°C)	Very soluble.
Vapour pressure	1.58 × 10-6 mm Hg at 20°C	Relatively nonvolatile under field conditions.
Henry's law constant	4.46 × 10-12 atm m3/mol-1 at 20°C	Not likely to volatilize from water or moist soil.
1/H	5.0 × 109
n-Octanol-water partition coefficient	Log Kow = 0.43	Minimal potential for bioaccumulation.
Hydrolysis half-life	pH 5 - 104 days pH 7 - 1.4 days pH 9 - 31 minutes	Stable at pH levels below 5, rapidly transformed at pH levels > 7. Dichlorvos major transformation product.
Aerobic soil biotransformation	DT50 1 to 27 days	Important route of transformation. Hydrolysis may have contributed.
Anaerobic soil biotransformation	DT50 1.8 days	Observed transformation probably due to hydrolysis. Dichlorvos major transformation product.
Aerobic aquatic biotransformation	DT50 8 hours	Observed transformation may have been due to hydrolysis.
Soil adsorption	Koc values 19-38	Does not adsorb strongly to soil and sediment.
Canadian field dissipation	Not detected in soil 2 weeks following aerial application.	Non-persistent in soil.

Dichlorvos is the major transformation product resulting from the hydrolysis of trichlorfon. Pest control products with dichlorvos as the active ingredient are registered for the control of a number of insect pests in Canada.

Table 4.1.2 Summary of the Physicochemical Properties, Transformation and Fate of Dichlorvos

Property/Process	Result	Interpretation
Solubility in water	15 000 mg/L at 25°C	Very soluble.
Vapour pressure	1.2 × 10-2 mm Hg at 20°C (1.6 Pa)	Intermediate to high volatility under field conditions.
Henry's law constant	2.32 × 10-7 atm·m3/mol	Slightly volatile from water or moist soil.
1/H	9.63 × 104
n-Octanol-water partition coefficient	1.47	Low potential for bioaccumulation.
UV-visible absorption spectrum	Does not absorb UV light above 240 nm	Photolysis not expected to be important route of transformation.
Hydrolysis half-life	pH 5 - 12 days pH 7 - 5 days pH 9 - 0.88 days	Hydrolysis is pH dependant and an important route of transformation at alkaline pH levels.
Aerobic soil biotransformation	DT50 1 hour to 19 days	Important route of transformation.
Anaerobic soil biotransformation	DT50 6.3 days	Important route of transformation.
Aerobic aquatic biotransformation	DT50 ≤ 1 day	Important route of transformation.
Soil adsorption	Koc values 0-150	Potential for very high mobility.

4.2 Environmental Toxicology

Trichlorfon

The lethal dose 50% (LD₅₀) to the honeybee (Apis mellifera) is 3.6 µg a.i./bee. No data are available to characterize toxicity to earthworms.

Acute oral toxicity values for birds range from 22.4 mg a.i./kg bw for the bobwhite quail (Colinus virginianus) to 123 mg a.i./kg bw for the rock dove (Columbia livia). Acute dietary toxicity values for birds range from 720 mg a.i./kg diet for the bobwhite quail (Colinus virginianus) to > 5000 mg a.i./kg diet for the mallard duck (Anas platyrhnchos). Avian reproduction studies indicate that trichlorfon can affect reproduction at levels as low as 30 mg a.i./kg diet with a reported no observed effect concentration (NOEC) of 9 mg a.i./kg diet.

Trichlorfon acute oral toxicity to mammals ranges from 136 to 800 mg a.i./kg bw in rats and mice. Acute dietary data indicates a NOAEL of 50 mg a.i./kg bw in rats based on cholinesterase inhibition. A 2-generation reproduction study with rats indicates a reproductive NOAEL of 175 mg a.i./kg bw in rats.

Trichlorfon acute lethal concentration 50% (LC₅₀) values to freshwater crustaceans and insects ranges from 0.18 µg a.i./L (Daphnia spp.) to 150 µg a.i./L (dragonfly). Snails and crayfish were less sensitive, with LC₅₀ values ranging from 1800 µg a.i./L to 25 000 µg a.i./L, respectively. A chronic study on Daphnia magna indicates a NOEC of 0.0056 µg a.i./L. A wide range of acute toxicity values with both end-use products and technical grade trichlorfon are observed for freshwater fish species, with LC₅₀ values ranging from 230 µg a.i./L to 110 000 µg a.i./L.

An early life-stage study on rainbow trout using technical trichlorfon reported a NOEC of 110 µg a.i./L . For marine invertebrates and fish, LC₅₀ values ranged from 0.36 µg a.i./L for pink shrimp up to 1110 µg a.i./L for cherry salmon. No data are available to address toxicity to algae, vascular plants and amphibians.

Dichlorvos

The 14-day LC₅₀ of dichlorvos (purity 99.8%) to the earthworm Eisenia foetida was 80.9 mg a.i./kg dry soil, with a NOEC of < 12.3 mg a.i./kg dry soil. Laboratory tests show toxicity to honeybees (Apis mellifera), with topical application or oral dosing giving LD₅₀ values ranging from 0.052 mg a.i./bee to approximately 0.9 mg a.i./bee.

LD₅₀s from a single acute oral dose of dichlorvos to a wide range of bird species range from 2.5 mg a.i./kg bw for canaries to 42.1 mg a.i./kg bw for starlings. Acute/subacute avian dietary toxicity studies indicate LC₅₀s in the diet ranging from 298 to > 5000 mg a.i./kg. Chronic early life/reproductive toxicity studies with dichlorvos indicated a NOEC of 30 mg a.i./kg diet to bobwhite quail (Colinus virginianus), a NOEC of 20 mg a.i./kg diet to Japanese quail (Coturnix japonica) and NOECs of < 2 and < 12 mg a.i./kg diet to the mallard duck (Anas platyrhynchos) in two separate studies.

LC₅₀ values for aquatic invertebrates from studies with a range of freshwater and estuarine/marine crustacea, molluscs and aquatic insects are from 0.066 mg a.i./L to 881 mg a.i./L for exposure periods of 24-96 hours.

Available data on the chronic or reproductive toxicity of dichlorvos to aquatic invertebrates include a 14-day study with the water flea (Daphnia magna), where the NOEC for adult immobilisation was the highest concentration tested, 0.00256 mg a.i./L. However, where there was a significant delaying effect of dichlorvos on the length of time for the appearance of the first brood (NOEC = 0.00016 mg a.i./L, lowest observed effect concentration [LOEC] = 0.00064 mg a.i./L, effect concentration 50% [EC₅₀] > 0.00256 mg a.i./L). Thus, dichlorvos may have subtle effects on aquatic invertebrate populations at concentrations well below lethal levels.

Studies with the common lobster (Homarus gammarus) indicates a 23-day LC₅₀ of 1.25 mg a.i./L and 23-day NOEC of 0.63 mg a.i./L.

The range in acute toxicity (LC₅₀) of dichlorvos (as the technical grade active ingredient or various formulations) to a wide variety of freshwater and estuarine/marine species of fish from various studies is ~200 µg a.i./L to > 40 000 µg a.i./L. African catfish exposed to sublethal concentrations of dichlorvos for 30 days have a NOEC of 30 mg a.i./L. A 61-day LOEC of 10.1 µg a.i./L is observed for rainbow trout.

The reported EC₅₀ of 52 800 µg a.i./L based on 96-hour biomass production for the algae (Scenedesmus subspicatus) is consistent with values (48-hour EC₅₀ = 14 000-100 000 µg a.i./L for four algal/diatom species) listed by the United States Environmental Protection Agency. No studies with dichlorvos and aquatic plants are available.

The 48-hour LC₅₀ for an EC formulation of dichlorvos to tadpoles of the toad Bufo bufo japonicus is reported as 76 000 µg a.i./L. The United States Environmental Protection Agency's Aquatic Information Retrieval (AQUIRE) database lists 48-hour LC₅₀ values to tadpoles of the frog species Rana hexadactyla and Rana limnocharis of 9700 and 10 000 µg a.i./L, respectively.

4.2.1 Terrestrial Risk Assessment

It was not possible to determine the risk of trichlorfon to earthworms because no acceptable toxicity data were available. Honeybees may be at risk during sprays using the higher rates of trichlorfon.

Standard exposure scenarios on vegetation and other food sources based on correlations in Hoerger and Kenaga (1972) and Kenaga (1973) and modified according to Fletcher et al. (1994) were used to determine the risk to birds and small mammals due to the consumption of contaminated food items.

Single or multiple applications of trichlorfon at 1800 g a.i./ha to control insect pests in forests and woodlots as well as single or multiple applications of trichlorfon at 1200 g a.i./ha or 1800 g a.i./ha to control insect pests on ornamentals could present a risk from acute exposure to bird species such as bobwhite quail from the consumption of contaminated food. It would only take 1.2 hours of continuous feeding to reach the NOEL. Larger species such as the mallard duck would not be at risk due to acute exposure.

Acute dietary risk quotients (RQs) for birds such as the bobwhite quail ranged from 2.9 to 5.9 for single and multiple forestry applications of 1800 g a.i./ha and all applications used on ornamentals indicating they would be at moderate risk. The percentage of contaminated diet required to result in risk ranged from 17 to 35%; this indicates that they would only need to consume a portion of their diet contaminated with trichlorfon to be at risk. It is expected that smaller species of birds such as songbirds would be at even greater risk than species with a body weight similar to the bobwhite quail due to the consumption of contaminated food items following trichlorfon applications.

Dermal exposure may be a very important route of exposure for birds frequenting the forest canopy following forestry aerial applications. Mineau (2002) used data from avian field studies to model the probability that bird mortality may occur after treatment with a pesticide. A forestry model incorporating oral and dermal toxicity was used to estimate the likelihood of avian mortality in trichlorfon treated forests. The model results indicated avian mortality may occur in 83-93% of forests treated at the application rates used to control forest insect pests on conifers (1.155-1.8 kg a.i./ha), indicating use of trichlorfon will result in high bird mortality.

Based on the RQs, species of birds such as bobwhite quail are at moderate risk (RQ = 5.5-7.4) due to chronic exposure from applications of 283.5 g a.i./ha to control insect pests in forestry as well as at high risk (RQ = 35-47) due to chronic exposure from forestry applications of 1800 g a.i./ha and all applications used on ornamentals (RQ = 23.3-53.0). Larger bird species such as mallard ducks are at low risk (RQ = 0.36-0.48) due to chronic exposure from applications of 283.5 g a.i./ha to control insect pests in forestry as well as at moderate risk (RQ = 2.3-3.0) due to chronic exposure from forestry applications of 1800 g a.i./ha and all applications used on ornamentals (RQ = 1.5-3.4). There is uncertainty, however, concerning risk from chronic exposure to birds following trichlorfon applications because trichlorfon is not persistent on vegetation (half-lives ranging from 1.6 to 4.6 days). Therefore, birds will not be chronically exposed to trichlorfon residues in contaminated food following most uses. Of possible concern would be using high rates with four applications for outdoor ornamentals; a month of continuous exposure could pose a risk due to reproductive effects for smaller bird species.

Single and multiple applications of 1800 g a.i./ha trichlorfon in forestry and all applications on outdoor ornamentals could result in risk from acute exposure to small wild mammals feeding on contaminated vegetation because it would only take approximately one hour of continuous feeding to reach the NOEL.

Acute dietary RQs for small wild mammals ranged from 11.1-22.3 for single and multiple forestry applications of 1800 g a.i./ha and all applications used on ornamentals, indicating ornamentals would be at high risk. The percentage of contaminated diet required to result in risk ranged from 5% to 9% indicating that they would only need to consume a small portion of their diet contaminated with trichlorfon to be at risk.

Applications of 283.5 g a.i./ha in forestry are expected to result in a low risk (RQ = 0.82-0.97) from chronic exposure to small mammals. Single and multiple applications of 1800 g a.i./ha in forestry and all applications on outdoor ornamentals are expected to result in a moderate risk (RQ = 3.2-6.4) from chronic exposure to small mammals feeding on contaminated vegetation. Similar to birds, there is uncertainty concerning the risk due to chronic exposure for small wild mammals because they would not be exposed chronically to trichlorfon because of the short half-life observed on plants (1.6-4.6 days). Of possible concern would be using high rates with four applications for outdoor ornamentals; a month of continuous exposure could pose a chronic risk to small mammals feeding on contaminated vegetation.

4.2.2 Aquatic Risk Assessment

Trichlorfon is rapidly transformed in water under aerobic conditions (DT₅₀ = 8 hours); therefore, any toxicity and resulting risks to aquatic organisms is due to both trichlorfon and its transformation products including dichlorvos.

In this initial deterministic assessment for aquatic organisms, RQs were calculated for aquatic invertebrates, fish and algae. Estimated environmental concentrations in water were calculated for the different rates and numbers of applications for a screening level scenario assuming a direct application to a body of water 15 cm deep for the forestry uses and 80 cm deep for the outdoor ornamental uses. The effects endpoint used was the NOEC of the most sensitive species tested.

The acute RQs for aquatic invertebrates ranged from 10 600 to 66 700 for the forestry uses and from 22 200 to 34 400 for the outdoor ornamental uses. Freshwater aquatic invertebrates are, therefore, at an extremely high risk from acute exposure to trichlorfon, even at the lowest rates of application for use in forestry and outdoor ornamentals based on this assessment.

The chronic RQs for aquatic invertebrates ranged from 33 900 to 214 000 for the forestry uses and from 71 400 to 111 000 for the outdoor ornamentals uses. Based on these RQs, freshwater aquatic invertebrates are at an extremely high risk from chronic exposure to trichlorfon, even at the lowest rates of application for use in forestry and outdoor ornamentals. It should be noted that trichlorfon is rapidly hydrolysed at pH levels above 7 (half-life 1.4 days); therefore, chronic exposure may not occur under these conditions. Chronic exposure could occur in acidic waters where the half-life of trichlorfon is 104 days at pH level 5.

Freshwater fish are at moderate risk (RQ = 8.3) due to acute exposure from applications of 283.5 g a.i./ha trichlorfon to control insect pests in forests as well as at high risk (RQ = 17.4-52.2) due to acute exposure from applications of 1800 g a.i./ha in forestry and for all applications to control insect pests on ornamentals.

Based on the RQs, freshwater fish are at moderate risk (RQ = 1.7) due to chronic exposure from applications of 283.5 g a.i./ha trichlorfon to control insect pests in forests, at high risk (RQ = 10.9) due to chronic exposure from applications of 1800 g a.i./ha in forestry and at moderate risk (RQ = 3.6-5.6) due to chronic exposure for all applications to control insect pests on ornamentals. Chronic exposure would only be a concern in acidic waters, however, as DT₅₀ values of trichlorfon increase substantially in water of pH level 7 and lower.

4.3 Environmental Assessment Conclusions

Pollinators are at risk following applications of trichlorfon at the higher rates to control insect pests in forestry and on ornamentals.

Single or multiple applications of trichlorfon at 1800 g a.i./ha to control insect pests in forests and woodlots present a high risk to smaller bird species from acute exposure from the consumption of contaminated food. Single or multiple applications of trichlorfon at 1200 g a.i./ha or 1800 g a.i./ha to control insect pests on ornamentals present a high risk to smaller bird species due to acute exposure from the consumption of food contaminated with trichlorfon. Dermal exposure may be a very important route of exposure for birds frequenting the forest canopy following forestry aerial applications. A forestry model incorporating oral and dermal toxicity indicated avian mortality may occur in 83-93% of forests treated at the application rates used to control forest insect pests on conifers (1.155-1.8 kg a.i./ha), indicating a potentially high frequency of bird mortality following these applications.

All applications of trichlorfon in forestry and on outdoor ornamentals could result in risk from acute exposure to small wild mammals feeding on contaminated vegetation.

Freshwater aquatic invertebrates are at an extremely high risk from acute and chronic exposure to trichlorfon, even at the lowest rates of application for use in forestry and outdoor ornamentals. It should be noted that trichlorfon is rapidly hydrolysed to dichlorvos at pH levels above 7 (half-life 1.4 days); therefore, chronic exposure will not occur under these conditions. Chronic exposure could occur in acidic waters where the half-life of trichlorfon was observed to be 104 days at pH level 5.

Freshwater fish are at moderate risk due to acute exposure from applications of 283.5 g a.i./ha trichlorfon to control insect pests in forests as well as at high risk due to acute exposure from applications of 1800 g a.i./ha in forestry and for all applications to control insect pests on ornamentals. Freshwater fish are at moderate risk due to chronic exposure from applications of 283.5 g a.i./ha trichlorfon to control insect pests in forests, at high risk due to chronic exposure from applications of 1800 g a.i./ha in forestry and at moderate risk from chronic exposure for all applications to control insect pests on ornamentals. Chronic exposure would only be a concern in acidic waters, however, as DT₅₀ values of trichlorfon increase substantially in water of pH level 7 and lower.

The aquatic risk assessment is conservative particularly for aerial applications in forestry because estimated environmental concentrations in water were calculated for the different rates and numbers of applications assuming a direct application to a body of water 15 cm deep. However, even if 50% forest canopy interception is assumed, the calculated RQs still indicate risk from acute exposure to aquatic organisms.

The aerial application in forestry is of particular concern because the risk to pollinators, birds and small wild mammals cannot be mitigated. It is also difficult to mitigate the risk to aquatic organisms using buffer zones because the high toxicity of trichlorfon and the transformation product dichlorvos result in large buffer zones that are operationally unfeasible (see Table 4.3.1). Buffer zones were capped at 800 m, which only mitigates 7% and 13% of the risk to aquatic invertebrates inhabiting shallow waterbodies (< 1 metre) for applications by fixed-wing and rotary-wing aircraft, respectively. Dermal exposure would probably be the main route of exposure to birds following aerial application in forestry and a model incorporating this route of exposure indicated a potentially high frequency of bird mortality following these applications.

Table 4.3.1 Buffer Zones Required for the Protection of Aquatic Habitat Following Applications of Trichlorfon

The buffer zones are required between the point of direct application and the closest downwind edge of sensitive freshwater habitats (such as lakes, rivers, sloughs, ponds, prairie potholes, creeks, marshes, streams, reservoirs, and wetlands) and estuarine/marine habitats.
Method of Application	Crop	Buffer Zones (metres) Required for the Protection of
		Freshwater Habitat of Depths		Estuarine/Marine Habitats of Depths
		Less than 1 m	Greater than 1 m	Less than 1 m	Greater than 1 m
Field sprayer*	Ornamentals	20	10	20	10
Airblast (early growth stage)	Forests, woodlots, ornamentals	50	40	50	40
Airblast (late growth stage)	Forests, woodlots, ornamentals	40	30	40	30
Aerial (fixed-wing)	Forests, woodlots	800**	800**	800**	800**
Aerial (rotary-wing)	Forests, woodlots	800**	800**	800**	800**

* For field sprayer application, buffer zones can be reduced with the use of drift reducing spray shields. When using a spray boom fitted with a full shield (shroud, curtain) that extends to the crop canopy or ground, the labelled buffer zone can be reduced by 70%. When using a spray boom where individual nozzles are fitted with cone-shaped shields that are no more than 30 cm above the crop canopy or ground, the labelled buffer zone can be reduced by 30%.
** Buffer zones were capped at 800 m (limit of AGDISP prediction).

Trichlorfon can enter aquatic ecosystems through spray drift and surface runoff. Observing buffer zones can effectively mitigate the entry of spray drift into aquatic systems. Pesticide spray drift from aerial application of trichlorfon in forestry is the most important source of exposure to aquatic habitats and was predicted using the AGDISP Model version 8.08. The data of Wolfe and Caldwell (2001) were utilized for predicting the spray drift from ground boom sprayers. The data of Ganzelmeier et al. (1995) were used to estimate spray drift from airblast sprayers used in orchards and vineyards. Based on these model predictions and the hazardous concentration above which 95% of aquatic invertebrate species are protected (HC₅) of 0.49 µg/L, buffer zones were calculated for mitigating the entry of spray drift into aquatic systems. In addition, the buffer zone estimation was based on the maximum application rate, the number of applications per season and the interval between applications.

5.0 Value

5.1 Commercial and/or Restricted Class Products

5.1.1 Alternatives to Trichlorfon

The registered chemical alternatives for unsupported uses of trichlorfon or for the supported uses of trichlorfon that have risk concerns are listed in Appendix V. While these chemical control methods are registered, the PMRA has not commented on the availability and extent of use of these options.

Most sources of non-chemical alternatives are focussed on general cultural practices (including weed control, crop rotation, resistant varieties, appropriate soil cultivation and natural enemies). The PMRA searched the information available for specific site-pest combinations and found a number of non-chemical measures of pest control. The effectiveness and extent of use of these non-chemical control measures are not verified. These measures are as follows:

• using sprinkler irrigation to discourage the development of diamondback larvae on Brussels sprouts, cabbage, cauliflower, rutabaga and turnip;
• removing horse nettle to decrease populations of pepper maggot on peppers;
• harvesting alfalfa early to decrease crop loss due to alfalfa webworm, alfalfa caterpillar and other pests;
• planting beans away from alfalfa to decrease lygus bug populations;
• pruning out caterpillar tents on blueberries in the fall to decrease caterpillar populations;
• providing float row covers to prevent diamondback moths from laying eggs in small cabbage and cauliflower fields;
• using physical barriers or ditches filled with water to stop migrating caterpillars in lettuce and kale fields; and
• intercropping corn and soybean to decrease European corn borer populations.

6.0 Toxic Substances Management Policy Considerations

6.1 Toxic Substances Management Policy

The management of toxic substances is guided by the federal government's Toxic Substances Management Policy, which puts forward a preventive and precautionary approach to deal with substances that enter the environment and could harm the environment or human health. The policy provides decision makers with direction and sets out a science-based management framework to ensure that federal programs are consistent with its objectives. One of the key management objectives is virtual elimination from the environment of toxic substances that result predominantly from human activity and that are persistent and bioaccumulative. These substances are referred to in the policy as Track 1 substances.

Trichlorfon does not meet the TSMP Track 1 criteria because the reported half-life values in soil and water are below the TSMP Track 1 cut-off criteria for persistence. No data were provided for the persistence of trichlorfon in air. The reported log K_ow for trichlorfon also falls below the TSMP Track 1 cut-off criterion for bioaccumulation. It has also been determined that dichlorvos does not meet the TSMP Track 1 criteria because the reported log K_ow for dichlorvos (1.47) falls below the TSMP Track 1 cut-off criterion for bioaccumulation. The reported half-life values in soil (19.3 days) and water (1 day) are also below the TSMP Track 1 cut-off criteria for persistence.

Products containing trichlorfon are subject to all the requirements in Regulatory Directive DIR2006-02, Formulants Policy and Implementation Guidance Document, published on 31 May 2006.

7.0 Summary

7.1 Human Health and Safety

7.1.1 Occupational Risk

Occupational risk estimates associated with applying, mixing and loading activities are not of concern, when the proposed risk-reduction measures are followed. Postapplication worker risk for use on outdoor ornamentals is of concern based on the length of time required for residues to decrease to an acceptable level. For some uses, the REIs required to meet the target MOEs are unfeasible. Occupational risk estimates associated with applying, mixing and loading activities are not of concern, when the proposed risk-reduction measures are followed. Postapplication worker risk for use on outdoor ornamentals is of concern based on the length of time required for residues to decrease to an acceptable level. For some uses, the REIs required to meet the target MOEs are unfeasible.

7.1.2 Dietary Risk From Food

Acute and chronic dietary risk assessments demonstrate that there are no dietary concerns for any population subgroup in Canada, including infants, children, teenagers, adults and seniors.

7.1.3 Dietary Risk From Drinking Water

The potential for the contamination of drinking water with trichlorfon is expected to be minimal. Therefore, drinking-water risks are not of concern.

7.1.4 Residential Risk

The use in municipal parks is of concern based on the health risks.

7.1.5 Aggregate Risk

Aggregate exposure from all relevant sources is not considered a health concern, assuming the use of trichlorfon in residential areas is phased out.

7.2 Environmental Risk

Trichlorfon is expected to be non-persistent in soil and aquatic environments. However, trichlorfon and its major transformation product, dichlorvos, pose a concern to the following terrestrial organisms: birds, small wild mammals, bees. These products also pose a concern to aquatic organisms such as fish and aquatic invertebrates.

8.0 Proposed Regulatory Decision

The PMRA has determined that certain trichlorfon uses are acceptable for continued registration in Canada. These uses have value in the food and crop industry and do not involve a level of concern to human health or the environment. These uses are ground application on Balsam fir and spruce trees in farm woodlots, rights-of way and Christmas tree plantations as well as the uses on beef and non-lactating dairy cattle. As a condition of the continued registration of these uses, new risk-reduction measures must be included on the labels of trichlorfon products. In addition, the registrant must submit additional confirmatory scientific information.

The remaining uses of trichlorfon are proposed for phase-out as registrant do not support continued registration or because of the human health risks and/or risks to the environment. The risk assessment conducted with the information available to the PMRA indicates a level of concern for workers and the environment for some uses of trichlorfon the registrant supports. As such, the uses on outdoor ornamentals and in municipal parks are proposed for phase-out unless further data are received to refine the assessment and/or mitigate exposure risks. The buffer zones calculated for aerial applications of trichlorfon are large and believed to be operationally unfeasible. Therefore, aerial applications of trichlorfon are also proposed for phase-out unless additional data are received to refine the assessment and/or mitigate environmental risks.

Further measures may be necessary/proposed pending the outcome of the cumulative risk assessment for all organophosphates, which share a common mechanism of toxicity.

8.1 Proposed Regulatory Actions

The PMRA has determined that the following uses are acceptable, provided that the mitigation measures listed in this section are implemented: ground application on Balsam fir and spruce trees in farm woodlots, rights-of way and Christmas tree plantations, as well as the uses on beef and non-lactating dairy cattle.

8.1.1 Proposed Regulatory Action Related to Human Health

8.1.1.1 Toxicological Information

Labels of pesticide products must carry statements regarding symptoms of poisoning and treatment, which are especially important for those who may be overexposed when working with the product in a commercial or industrial setting, e.g. mixers/loaders who handle more concentrated forms. Based on the toxicological assessments, the label text of products containing trichlorfon should be expanded and/or standardized, as follows.

Toxicological Information

Trichlorfon is an organophosphate that is a cholinesterase inhibitor. Typical symptoms of overexposure to cholinesterase inhibitors include headache, nausea, dizziness, sweating, salivation, runny nose and eyes. This may progress to muscle twitching, weakness, tremor, incoordination, vomiting, abdominal cramps and diarrhea in more serious poisonings. A life-threatening poisoning is signified by loss of consciousness, incontinence, convulsions and respiratory depression with a secondary cardiovascular component. Treat symptomatically. If exposed, plasma and red blood cell cholinesterase tests may indicate degree of exposure (baseline data are useful). Atropine, only by injection, is the preferable antidote. Oximes, such as pralidoxime chloride, may be therapeutic if used early; however, use only in conjunction with atropine. In cases of severe acute poisoning, use antidotes immediately after establishing an open airway and respiration. With oral exposure, the decision of whether to induce vomiting or not should be made by an attending physician.

For products that contain greater than 10% petroleum distillates, the following text should also be added to the Toxicological Information section (placed at the end of the paragraph presented above), as an additional aid to the attending physician.

Note: Product contains a petroleum distillate solvent.

8.1.1.2 Proposals Pertaining to Mixer/Loader/Applicator and Postapplication Exposure

For the uses deemed acceptable for continued registration, the following mitigation measures and label statements are proposed.

Engineering Controls

• The use of water-soluble packets for soluble powder formulations to reduce exposure when mixing or loading the product.

Label Statements

General (all)

Not to be used in conjunction with products containing naled or dichlorvos.

Neguvon Pour-On Cattle Insecticide

Wear long, chemical-resistant gloves or gauntlets during use.

Wear chemical-resistant gloves when handling treated cattle.

8.1.1.3 Residue Definition for Risk Assessment and Enforcement

Division 15, Table II, of the Food and Drug Regulations currently provides no definition for the residue of concern. It is proposed that the residue of concern be defined as the parent compound, trichlorfon (dimethyl (2,2,2-trichloro-1-hydroxyethyl) phosphate). However, this definition cannot be finalized until nature of the residue in livestock is fully delineated.

8.1.1.4 Maximum Residue Limits for Trichlorfon in Food

In general, when the re-evaluation of a pesticide has been completed, the PMRA intends to update Canadian maximum residue limits (MRLs) and to remove MRLs that are no longer supported. The Agency recognizes, however, that interested parties may want to retain an MRL in the absence of a Canadian registration to allow legal importation of treated commodities into Canada. The PMRA requires similar chemistry and toxicology data for such import MRLs as those required to support Canadian food use registrations. In addition, the PMRA requires residue data that are representative of use conditions in exporting countries, in the same manner that representative residue data are required to support domestic use of the pesticide. These requirements are necessary so that the Agency may determine whether the requested MRLs are needed, and to ensure they would not result in unacceptable health risks.

The Food and Drugs Act prohibits the sale of adulterated food, that is, food containing a pesticide residue that exceeds the established 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/on certain foods. Food containing a pesticide residue that does not exceed the established MRL does not pose an unacceptable health risk.

Division 15, Table II, of the Food and Drug Regulations currently provides no definition for the residue of concern for trichlorfon, and no MRLs are specified. The supported food uses of trichlorfon are on beef cattle and non-lactating dairy cattle. Where no specific MRL is established for a pest control product under the Food and Drug Regulations, subsection B.15.002(1) applies. This requires that residues do not exceed 0.1 ppm, which is considered a general MRL for enforcement purposes. However, changes to this general MRL may be implemented in the future, as indicated in Discussion Document DIS2006-01, Revocation of 0.1 ppm as a General Maximum Residue Limit for Food Pesticide Residues [Regulation B.15.002(1)]. If and when the general MRL is revoked, a transition strategy will be established to allow permanent MRLs to be promulgated.

The general MRL of 0.1 ppm will apply for enforcement purposes with respect to the residues of trichlorfon in food for all commodities, including beef cattle and milk. Parties interested in supporting an import MRL for residues of trichlorfon on other commodities should contact the PMRA during the comment period of this document to discuss submitting appropriate data.

8.1.2 Proposed Regulatory Action Related to Environment

For the uses deemed acceptable for continued registration, the following changes to statements on the registered labels are proposed to mitigate the risk to non-target organisms.

Environmental Hazards

Toxic to aquatic organisms, birds, and small wild mammals.

Toxic to bees exposed to direct treatment, drift or residues on flowering crops or weeds. Do not apply this product to flowering crops or weeds if bees are visiting the treatment area. Minimize spray drift to reduce harmful effects on bees in habitats close to the application site.

Directions for use

Field sprayer application: Do not apply during periods of dead calm. Avoid application of this product when winds are gusty. Do not apply with spray droplets smaller than the American Society of Agricultural Engineers (ASAE) fine/medium/coarse classification. Boom height must be 60 cm or less above the crop or ground.

Airblast application: Do not apply during periods of dead calm. Avoid application of this product when winds are gusty. Do not direct spray above plants to be treated. Turn off outward pointing nozzles at row ends and outer rows. Do not apply when wind speed is greater than 16 km/h at the application site as measured outside of the treatment area on the upwind side.

Do not apply by air.

Buffer zones

The buffer zones specified in the table below are required between the point of direct application and the closest downwind edge of sensitive freshwater habitats (such as lakes, rivers, sloughs, ponds, prairie potholes, creeks, marshes, streams, reservoirs and wetlands) and estuarine/marine habitats.

Buffer Zones Required for the Protection of Aquatic Habitat Following Applications of Trichlorfon

Method of application	Crop	Freshwater Habitat of Depths:
		Freshwater Habitat of Depths:		Estuarine/Marine Habitats of Depths:
		Less than 1 m	Greater than 1 m	Less than 1 m	Greater than 1 m
Airblast (early growth stage)	Forests, woodlots	50	40	50	40
Airblast (late growth stage)	Forests, woodlots	40	30	40	30

* For field sprayer application, buffer zones can be reduced with the use of drift reducing spray shields. When using a spray boom fitted with a full shield (shroud, curtain) that extends to the crop canopy, the labelled buffer zone can be reduced by 70%. When using a spray boom where individual nozzles are fitted with cone-shaped shields that are no more than 30 cm above the crop canopy, the labelled buffer zone can be reduced by 30%.

8.2 Additional Data Requirements

8.2.1 Data Requirements Related to Occupational Exposure Assessment

The following data could refine the occupational risk assessment, possibly reducing or removing some restrictions and/or personal protective equipment requirements.

Mixer/Loader/Applicator Exposure

DACO 5.4 and/or 5.5
Exposure data representative of modern application equipment and engineering controls (e.g. passive dosimetry, biological monitoring).

DACO 5.4 and/or 5.5
Exposure data for all handheld equipment including rights-of-way, aerial application, mix and load with water-soluble packets, high-pressure handwand, low-pressure handwand and backpack (e.g. passive dosimetry, biological monitoring) including equipment cleaning and maintenance activities.

Postapplication Exposure

DACO 5.6, 5.7, 5.9 and 5.10
Transfer coefficients, air concentrations and dislodgeable foliar residues (for trichlorfon and for dichlorvos) for application to Balsam fir and spruce trees in farm woodlots, rights-of-way, Christmas tree plantations, municipal parks and ornamentals.

DACO 5.6, 5.7, 5.9 and 5.10
Additional data to refine/confirm calculated REIs.

8.2.2 Data Requirements Related to Food Residue Chemistry

The following confirmatory data are required to support the continued registration of trichlorfon.

DACO 6.2

The nature of the residue in livestock is not understood. Complete identification of metabolites is required to fully depict the metabolism in livestock.

DACO 7.6

1. The registrant is required to explain the difference between the concentration of trichlorfon found in magnitude of residue study and that which was found in the nature of the residue study.
   
   
2. The registrant is required to provide all available studies related to the magnitude of residues that may be incurred in milk.

List of Abbreviations

µg

microgram(s)

°C

degree(s) Celsius

a.i.

active ingredient

AGDISP

AGricultural DISPersal

atm

atmospheres

bw

body weight

cm

centimetre(s)

DACO

data code

DEEM^®

Dietary Exposure Evaluation Model

DFR

dislodgeable foliar residue

DT₅₀

dissipation time to 50% (the dose required to observe a 50% decline in the test population)

DVP

dichlorvos

DWLOC

drinking water level of comparison

EC₅₀

effect concentration 50%

g

gram(s)

ha

hectare(s)

HC₅

hazardous concentration above which 95% of aquatic invertebrate species are protected

Hg

mercury

kg

kilogram(s)

K_oc

organic carbon partition coefficient

K_ow

octanol-water partition coefficient

LC₅₀

lethal concentration to 50% (a concentration causing 50% mortality in the test population)

LD₅₀

lethal dose to 50% (a dose causing 50% mortality in the test population)

L

litre(s)

LOAEL

lowest observed adverse effect level

LOEC

lowest observed effect concentration

m

metre(s)

m³

metre(s) cubed

mg

milligram(s)

M/L

mixer/loader

M/L/A

mixer/loader/applicator

mm

millimetre(s)

MOE

margin of exposure

mol

mole

MRL

maximum residue limit

N/A

not applicable

NOAEL

no observed adverse effect level

NOEC

no observed effect concentration

Pa

Pascal

pH

-log10 hydrogen ion concentration

PHED

Pesticide Handlers Exposure Database

PMRA

Pest Management Regulatory Agency

PPE

personal protective equipment

ppm

parts per million

REI

restricted-entry interval

RQ

risk quotient

SF

safety factor

TSMP

Toxic Substances Management Policy

TRI

trichlorfon

TTR

turf transferable residue

UF

uncertainty factor

ULV

ultra-low volume

USEPA

United States Environmental Protection Agency

UV

ultraviolet

WSP

water-soluble packaging

¹ "Consultation statement" as required by subsection 28(2) of the Pest Control Products Act.

² "Acceptable risks" as defined by subsection 2(2) of the Pest Control Products Act.

³ "Value" as defined by subsection 2(1) of the Pest Control Products Act: "the product's actual or potential contribution to pest management, taking into account its conditions or proposed conditions of registration, and includes the product's (a) efficacy; (b) effect on host organisms in connection with which it is intended to be used; and (c) health, safety and environmental benefits and social and economic impact".

⁴ "Consultation statement" as required by subsection 28(2) of the Pest Control Products Act.

⁵ "Decision statement" as required by subsection 28(5) of the Pest Control Products Act.