Use of pesticides is a key factor in control agricultural and food pests and to pest vector control, especially in epidemics. However, poor-quality pesticides do not reach their purpose and at the same time, they may be phytotoxic to treated crops and harmful to humans and the environment. Thus, it seems clear the need for good-quality pesticide products and in this regard, specifications are crucial in improving pesticides quality.
Chemical pesticide registration requires the inclusion of administrative information and technical documentation such as chemical composition, physicochemical properties, analytical methods, toxicological and ecotoxicological information and maximum residue limits. For physicochemical and toxicological studies, assays made under international guidelines (OECD, EPA, etc.) and under Good Laboratory Practices statement are generally considered valid.
In relation with impurities appearing in pesticides, they are usually formed from starting materials or side-reactions within the synthesis and also during final product storage. These impurities generally exhibit similar physical and/or chemical characteristics to the active ingredient, but the toxicological or ecotoxicological hazards may differ. When they cannot be removed they should be kept to a minimum. It is noteworthy that manufacturing processes cannot be optimized for control of all impurities, so they could vary along produced batches.
Any impurity capable of creating an adverse effect, above or beyond that of the active ingredient, is potentially relevant and may therefore have to be controlled by the specification. The adverse effects may reflect toxic or non-toxic hazards. Interestingly, a potentially relevant impurity may be designated as non-relevant if evidence indicates no significant likelihood of its hazards being manifested in practice. Thus, the limits adopted are the result of case-by-case scientific judgement.
According to the Joint FAO/WHO Meeting on Pesticide Residues, a concentration of 1 g / kg is considered as a limit for the irritating impurities of the skin and the eyes, while for sensitizing, mutagenic, carcinogenic and toxic substances reproduction the limit is lower (0.1 g / kg). For chemicals with a well-defined target organ, the limit will be defined when possible as 10% of the maximum acceptable concentration (based on toxicological values such as LD50, LOAEL, NOAEL, BMD, BMDL, ADI). These FAO and WHO specifications provide standards for products and also internal reference point. In addition, they define the chemical and physical properties linked to the efficacy and safe use of a product.
The exhaustive toxicological evaluation through bibliographic reviews, preclinical studies or QSAR models (structure quantitative activity relationship), will allow to determine whether a relevant impurity presents a hazardous toxicity profile or on the contrary it is aligned with the active compound, which will lead ultimately to the establishment of the corresponding security limits.
At Azierta we are able to evaluate impurities in pesticides. Our toxicology team have a broad experience on QSAR analysis of impurities with the support of our consultant partner Ledscope for statistical QSAR assessments.
If you want to learn more details, visit https://www.azierta.com/en/pharma/toxicology and contact us.