Canada – Organophosphate Pesticides – Cumulative Health Risk Scoping Assessment, Problem Formulation and Planned Approach of Analysis, Re-evaluation Note (REV2024-02)
Pest Management Regulatory Agency
24 July 2024
ISSN: 1925-0649 (PDF version)
Catalogue number: H113-5/2024-2E-PDF (PDF version)
Summary
Organophosphate pesticides – Cumulative health risk scoping assessment, problem formulation and planned approach of analysis
In Canada, the cumulative health risk assessment of active ingredients belonging to the organophosphate (OP) class of pesticides, as described in SPN2018-02, Cumulative Health Risk Assessment Framework , was initiated in May 2022.
Under the authority of section 16 of the Pest Control Products Act , the Canadian registrants of 11 OP pesticides were notified of the initiation of the cumulative risk assessment (CRA) of this class of compounds. Following notification, the registrants indicated support for all uses included on the labels of the end-use products for 10 of the 11 OP pesticides registered in Canada at the time of initiation. Registrants of one OP pesticide chose to discontinue registration. This CRA includes 10 OP pesticides that are registered in Canada: acephate, azamethiphos, bensulide, dichlorvos, dimethoate, malathion, naled, phorate, phosmet and tetrachlorvinphos.
As outlined in SPN2018-02, cumulative risk assessments are aimed at evaluating human health risks associated with co-exposure to two or more pesticides that have a common mechanism of toxicity, based on available information. It may consist of a quantitative or qualitative cumulative risk assessment or result in a determination that a cumulative risk assessment is not required, for example, in situations that do not involve co-exposures.
Metabolites/Transformation Products: For the OP pesticides, the common mechanism of toxicity relates to their shared ability to irreversibly bind to and phosphorylate the acetylcholinesterase (AChE) enzyme in mammalian central and peripheral nervous systems. Some transformation products of the OP pesticides also inhibit AChE and will thus be considered in the cumulative risk assessment if there is potential for exposure to these chemicals. For example, when formed, oxon metabolites of OP pesticides are known to inhibit AChE. Some of these oxon metabolites were previously determined to be relevant in the individual Health Canada assessments for several OP pesticides and will be considered in the OP CRA (as outlined in Appendix I, Tables 1 and 2, of the full version of REV2024-02). Methamidophos, an OP pesticide registered in other countries, is also a metabolite of acephate, and will be considered in the CRA. The relevance of other transformation products of OP pesticides in the CRA will be further considered during the full review.
A quantitative approach will be used in this CRA to assess risk from major exposure pathways, routes, and uses of OP pesticides. This will include deterministic and/or probabilistic assessments, as required. The results of this complex analysis must be interpreted with a full understanding of the assumptions made and the uncertainties introduced as a result of these assumptions. Qualitative assessments will also be used to assess risk from minor exposure pathways, routes, and uses of OP pesticides.
The process Health Canada’s Pest Management Regulatory Agency (PMRA) undertook to identify available evidence relating to a common mechanism of toxicity for the OP pesticides, their co-exposure and their potential to result in a material contribution to non-occupational (dietary and residential) exposure, in order to define the cumulative assessment group (CAG), is outlined in the appendices.
A scoping assessment is included in Appendix I of REV2024-02. A decision tree is included in Appendix II, while the planned approach for analysis of the OP CRA is included in Appendix III of REV2024-02.
Scoping Assessment: The anticipated exposure scenarios resulting from the uses of each of the 10 OP pesticides registered in Canada are provided in Appendix I, Table 1 of REV2024-02. Additional OP pesticides that belong to the OP common mechanism group are listed in Appendix I, Table 2, of REV2024-02. Although these OP pesticides are not registered in Canada, the active ingredients could be present on imported food commodities, and accordingly, are included in the scoping assessment. The decision tree used by Health Canada to determine which active ingredients would be included (quantitatively or qualitatively), or excluded, from the dietary exposure cumulative assessment group (CAG) is presented in Appendix II of REV2024-02. This 5-step process was used to categorize the 42 OP pesticides that are listed in Appendix I, Table 2 into the three categories described below:
OP pesticides not registered in Canada that will be quantitatively included in the cumulative assessment group,
OP pesticides not registered in Canada and determined to be minor contributors to overall cumulative exposure to OP pesticides and will be considered qualitatively in the cumulative assessment group, and
OP pesticides not registered in Canada that will be excluded from the cumulative assessment group as their food residues are not relevant to dietary exposure based on the available Canadian food supply.
Problem Formulation and CRA Analysis: The planned approach for analyzing the OP CRA is presented in Appendix III, Table I of REV2024-02 to clearly identify and describe the problem formulation elements that will be considered in the OP CRA, and to summarize the key information that will be used to support Health Canada’s assessment.
