Significance of impurities in the safety evaluation of crop protection products - (IUPAC technical report)

A. Ambrus, D.J. Hamilton, H.A. Kuiper, K.D. Racke

    Research output: Contribution to journalArticleAcademicpeer-review

    28 Citations (Scopus)

    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
    Original languageEnglish
    Pages (from-to)937-973
    JournalPure and Applied Chemistry
    Volume75
    Issue number7
    DOIs
    Publication statusPublished - 2003

    Fingerprint

    Crops
    Impurities
    Pesticides
    Specifications
    Poisons
    Raw materials
    Contamination
    Physical properties
    Decision making
    Monitoring
    Chemical analysis

    Keywords

    • o,o,s-trimethyl phosphorothioate
    • toxicological properties
    • o,s,s-trimethyl phosphorodithioate
    • liquid-chromatography
    • breakdown products
    • white mouse
    • formulations
    • 3,3',4,4'-tetrachloroazobenzene
    • malathion
    • toxicity

    Cite this

    Ambrus, A. ; Hamilton, D.J. ; Kuiper, H.A. ; Racke, K.D. / Significance of impurities in the safety evaluation of crop protection products - (IUPAC technical report). In: Pure and Applied Chemistry. 2003 ; Vol. 75, No. 7. pp. 937-973.
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    Significance of impurities in the safety evaluation of crop protection products - (IUPAC technical report). / Ambrus, A.; Hamilton, D.J.; Kuiper, H.A.; Racke, K.D.

    In: Pure and Applied Chemistry, Vol. 75, No. 7, 2003, p. 937-973.

    Research output: Contribution to journalArticleAcademicpeer-review

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    AB - 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

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    KW - liquid-chromatography

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    KW - white mouse

    KW - formulations

    KW - 3,3',4,4'-tetrachloroazobenzene

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