Consultation Summary: Consultation on Proposed Guidance for Residual Solvents in Technical Grade Active Ingredients

Health Canada's Pest Management Regulatory Agency 
30 October 2023

Table of contents

• The consultation
• Summary of comments received
• Conclusion

In Health Canada’s Guidance for developing datasets for conventional pest control product applications (updated February 2021), registrants and applicants are informed of the need to minimize the presence of impurities of toxicological concern (IOCs) in the manufacture of pest control products (DACO 2.13.4) in order to protect the health of Canadians and the environment.

To provide clarity to registrants and applicants on the data requirements, Health Canada's Pest Management Regulatory Agency (PMRA) has established generally acceptable limits for certain residual solvents of concern in technical grade active ingredient (TGAI) products.

The consultation

On 29 March 2023, the PMRA initiated a 30-day consultation on a proposal to publish guidance on residual solvents in TGAIs. The proposal outlined PMRA's intent to identify these residual solvents of concern, their general limits in TGAIs, and the required analytical limits of quantitation (LOQs).
In total, eight comments were received, seven from industry stakeholders and one from a non-governmental organization (NGO).

Summary of comments received

1. Comments from industry stakeholders generally confirmed support for PMRA’s proposal.

   Overall, there is strong support for this PMRA initiative to provide additional guidance to TGAI applicants and registrants regarding allowable levels of residual solvents. Such guidance is in line with PMRA’s transparency objectives and will facilitate the production of improved-quality product chemistry submissions. As the primary audience is pesticide applicants, the guidance will be available through the Registrants and Applicants webpage.

   PMRA response:

   As the new guidance is intended to clarify product chemistry data requirements for applicants/registrants, the text describing its background has been updated. This guidance, which is applicable to all TGAIs, addresses acceptable limits for solvents commonly used in the manufacture of technical-grade pesticide active ingredients (as well as in various other industries) that may unintentionally remain at trace levels and are considered by PMRA to be of concern. As such, these are distinct from intentionally added formulants that appear in PMRA’s List of Formulants where no limits are specified, and are therefore handled differently under PMRA’s assessment framework.

   It should be noted that residual solvents have already been identified as impurities of concern in PMRA’s Guidance for Developing Datasets for Conventional Pest Control Product Applications (updated 2021), a document that includes all product chemistry guidance and supersedes the earlier directives on chemistry data requirements, Dir98-03 and Dir98-04.

2. Some stakeholders questioned the scientific basis for establishing the list of solvents of concern and their acceptable levels. It was noted that the list appears to represent a hazard- rather than risk-based approach, and that the consequences of a TGAI not meeting the specified limits were not laid out.

   PMRA response:

   The list of solvents and their limits was established based on a weight-of-evidence approach relying on several sources of information, including other jurisdictions and guidelines, but is specific to the Canadian pesticide context. This is a tiered approach that takes into consideration current Canadian pesticide use patterns and registrations while protecting consumers, applicators, workers and bystanders as well as the environment. It is intended to provide broadly applicable guidance on solvents that are commonly used in pesticide manufacturing. If a limit is exceeded, consultation with the PMRA will be needed and further data may be requested.

3. Some stakeholders requested clarification of the term “to be avoided”.

   PMRA Response:

   A solvent identified in the list as “to be avoided” has no broadly acceptable limit. If it is present at detectable levels in a TGAI using the specified LOQ, consultation with PMRA will be needed to determine acceptability. However, as none of the solvents on the list are Track 1 substances, PMRA would not take the virtual elimination approach under the Toxic Substances Management Policy (TSMP).

4. Some industry stakeholders requested that the identity of the specific compounds in the list be clarified.

   PMRA Response:

   The table has been amended to include CAS Registry numbers for unambiguous identification of the solvents, as well as footnotes clarifying those solvents that exist as multiple chemical isomers.

5. Some industry stakeholders questioned whether the guidance would be applied retroactively to existing registrations, and how the list might be amended in future.

   PMRA Response:

   This guidance on residual solvents will not be applied retroactively to registered products, but is to be applied whenever such solvents are expected to be present in a TGAI source under review in an open submission or during re-evaluation. If a solvent not listed in the guidance is used in the manufacturing of a TGAI and may pose a concern, it is recommended that PMRA be consulted to establish any corresponding data requirements. Consistent with its overall regulatory approach, PMRA anticipates updating the guidance as the underlying science evolves.

6. One industry stakeholder requested that similar maximum limits and LOQs be provided for the other impurities listed under DACO 2.13.4 in Guidance for Developing Datasets for Conventional Pest Control Product Applications.

   PMRA Response:

   The Agency’s goal is to provide as much applicant guidance as possible with respect to impurities of concern, while also protecting confidential business information (CBI) from disclosure. To that end, further guidance is planned in future.

Conclusion

Following consideration of the comments received from stakeholders, as of 30 October 2023, the PMRA will be publishing its established limits for residual solvents in TGAIs via the Registrants and Applicants webpage, and will be updating it regularly.