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Pure Appl. Chem., 2003, Vol. 75, No. 7, pp. 937-973


Significance of impurities in the safety evaluation of crop protection products (IUPAC Technical Report)

Á. Ambrus*, D. J. Hamilton, H. A. Kuiper and K. D. Racke

Abstract: There may be substantial differences in the chemical composition of technical-grade products of the same active ingredient manufactured under different conditions, from different raw materials, or by different routes of synthesis. Resulting differences in impurity content may significantly affect the toxicological properties of pesticide products. Relevant impurities are those that may exhibit pronounced toxic effects compared to the active ingredient, affect phytotoxicity or physical properties of formulations, result in undesirable residues in food,or cause environmental contamination. The first safety assessment of an active ingredient by a regulatory body considers toxicological data developed on a representative batch of technical products, with the assumption that the material produced commercially by the original or generic manufacturers has an equal or higher content of active ingredient and contains the same or fewer impurities at equal or lower concentrations as the fully characterized technical product used in the toxicological tests. Three steps are essential for ensuring the safety of commercial technical- grade pesticide products, whether produced by the original manufacturer or by generic manufacturers. First, the identity and chemical structure of the impurities must be elucidated.This should include positive identification of major (=1 %) and all toxicologically or environmentally relevant impurities, and characterization of minor impurities (>0.1 %). Second, in addition to recognition of a minimum active ingredient content, official specifications should also list relevant impurities and their maximum permissible concentrations.Implementation of these specifications should be aided by a decision-making scheme for establishing similarity of subsequently evaluated technical products. Third, appropriate analytical methods for the detection and quantification of impurity levels should be developed and employed in a quality-monitoring program associated with the manufacturing and formulation process.