Established limits for residual solvents in technical grade active ingredients

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.

Solvents are commonly used in the manufacturing of products for various industries including pesticides. Although most are removed through purification during the manufacturing process, residual levels of solvents may remain in products and some are considered by the Pest Management Regulatory Agency (PMRA) to be of concern. To provide clarity to registrants and applicants on the data requirements, the PMRA has established generally acceptable limits for certain residual solvents of concern in technical grade active ingredient (TGAI) products. 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 international guidelines, but is specific to the Canadian pesticide context. If a solvent is present in a TGAI below the specified limit, it will be considered acceptable without further data. If a particular limit is exceeded, consultation with the PMRA will be needed to determine whether further data are required. For example, higher solvent levels for a new source of TGAI could be supported with toxicological data or a well-developed scientific rationale that considers all relevant routes of exposure.

As described in the Guidance for developing datasets for conventional pest control product applications, the use of several of these solvents is to be avoided completely where possible, while others are to be limited. 

PMRA established limits for residual solvents in TGAIs
Residual solvent CAS Registry Number Maximum PMRA general limit (ppm) Required limit of quantitation (LOQ) (ppm)
carbon tetrachloride 56-23-5 --- (to be avoided) 1
1,2-dichloroethane 107-06-2 --- (to be avoided) 1
benzene 71-43-2 --- (to be avoided) 1
1,4-dioxane 123-91-1 4 1
chloroform 67-66-3 10 1
tetrahydrofuran 109-99-9 100 10
pyridine 110-86-1 200 100
hexaneFootnote 1 110-54-3 290 100
dichloromethane 75-09-2 300 100
acetonitrile75-05-8 410 100
N,N-dimethylformamide68-12-2 500 100
N-methyl-2-pyrrolidone872-50-4 530 100
chlorobenzene 108-90-7 600 100
cyclohexane 110-82-7 710 100
methylcyclohexane 108-87-2 1000 500
N,N-dimethylacetamide127-19-5 1090 500
xylenesFootnote 2 1330-20-7 2170 1000
methanol67-56-1 3000 1000
toluene108-88-3 15000 1000

These limits are to be applied in the analytical determination of these solvents whenever they are expected to be present in a TGAI source under review in an open submission or during re-evaluation. If a solvent not listed here is used in the manufacturing of a TGAI and may pose a concern, it is recommended that the PMRA be consulted to establish any corresponding data requirements. Health Canada anticipates updating this list as needed.

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