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Computational Methodologies for the Risk Assessment of Pesticides in the European Union Juan José Villaverde,* Beatriz Sevilla-Morán, Carmen López-Goti, José Luis Alonso-Prados, and Pilar Sandín-España Plant Protection Products Unit, DTEVPF, INIA, Ctra. de La Coruña, Km. 7.5, 28040 Madrid, Spain regulation encourages the use and development of nonexperimental tests to anticipate the possible health and environmental risks of pesticides. Given that these tools can potentially result in significant cost savings during the pesticide safety assessment process, they will provide a great economic impact for the agrochemical sector. The reduction in the necessary laboratory or field evaluations will decrease time and cost, leading to faster commercialization of formulations and thus promoting the productivity and competitiveness of European agriculture. In silico tools are especially important when experimental studies are not adequate because of ethical reasons (e.g., testing with animals would be reduced) or because experimental studies are either too complex or not viable (e.g., studies of the fate of pesticides in the atmosphere, including the long-range transportation of pesticides and/or their degradation products). In this regard, scientists are focusing on the development of theoretical tools to reduce animal testing and trial time through estimation of rticle 4 of the European Parliament and Council physicochemical properties, reaction mechanisms, degradation Regulation (EC) No. 1107/2009 concerning the placing pathways, and structure−activity/toxicity correlations.1−3 In of pesticides on the market establishes that pesticides used fact, the highly increased accuracy achieved in recent years according to good agricultural practices cannot have adverse suggests that computational studies could reach sufficient effects on human or animal health or unacceptable effects on reliability and predictive capacity to greatly contribute to the the environment. Meeting this regulation involves performing elimination of some in vivo and experimental tests and to risk assessments of the use of the pesticide for the environment compensate for the lack of knowledge in certain risk assessment and for human health. Therefore, it is necessary to define the areas. pesticide toxicological and ecotoxicological characteristics and QSARs studies are currently the most frequent approach the exposure pattern in the different environmental compartused by pesticide manufacturers (and to some extent accepted ments through a large number of experimental studies, in many by the European authorities) to estimate the physicochemical cases implying a high cost and delay in bringing the pesticide to and biological properties and the environmental fate of market. pesticides and their transformation products.4 QSAR models Risk assessment is done using information from experimental generally use experimental descriptors (e.g., molecular weight, substituent induced chemical shifts) and empirical descriptors studies and generic models and scenarios. A larger amount of (e.g., Verloop’s steric parameters, hydrophobic parameter) but available information makes this process more complex, but, on are also beginning to benefit from great advances in quantum the other hand, reduces the uncertainty. Prediction tools that chemistry. For example, quantum chemical descriptors encode allow for an improved focus on the type of studies that must be valuable information that can be used to develop QSAR models performed for generating the information that must be included for the toxicological assessment of substances. However, to the in the models and scenarios used for the risk assessment may be best of our knowledge, most research employing quantum highly useful. Computational methods have the potential to chemical descriptors has been performed in the field of accelerate advances in environmental and toxicological underpharmaceutical drugs, not in the field of pesticides.3 standing because they support the experimental data with Furthermore, quantum chemistry using density functional additional in silico studies and results. These methodologies are theory (DFT) calculations can be applied to obtain a deeper beginning to appear in the literature (including in the Journal of understanding of the behavior of pesticides in the atmosphere. Agricultural and Food Chemistry) with an increase in the papers Photolysis is one of the main processes that govern the fate of related to quantitative structure−activity relationships (QSARs) 1−3 pesticides in the atmosphere.5 The high-energy radiation and theoretical studies. According to Articles 4 and 29 of Regulation (EC) No. 1107/2009, authorization of pesticides shall be performed in Received: February 3, 2017 Published: March 2, 2017 the light of current scientific and technical knowledge. This
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© 2017 American Chemical Society
2017
DOI: 10.1021/acs.jafc.7b00516 J. Agric. Food Chem. 2017, 65, 2017−2018
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Journal of Agricultural and Food Chemistry together with hydroxyl radical reactions (the main troposphereoxidizing agent resulting from ozone photolysis) control pesticide dissipation and the degradation products formed in the atmosphere. Detailed knowledge of the kinetics of photochemical reactions and the stability of the possible products is necessary to establish the impact of pesticides and/ or their degradation products on the environment. To summarize, the development of adequate methodologies for the suitable use of computational tools together with field data (crop areas, soil properties, climate, vulnerability of specific areas) is of great interest for performing the risk assessment that enables the use of pesticides under good agricultural practices. These methodologies will be of interest for evaluating agencies (i.e., the European Food Safety Authority, EFSA) and regulatory decision-making bodies (i.e., the European Commission).
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AUTHOR INFORMATION
Corresponding Author
*(J.J.V.) Phone: +34 91 347 8767. Fax: +34 91 347 1479. Email:
[email protected]. ORCID
Juan José Villaverde: 0000-0002-5911-792X Beatriz Sevilla-Morán: 0000-0001-7663-2846 Carmen López-Goti: 0000-0001-7947-7052 José Luis Alonso-Prados: 0000-0001-8704-947X Pilar Sandín-España: 0000-0003-0776-222X Notes
The authors declare no competing financial interest.
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REFERENCES
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2018
DOI: 10.1021/acs.jafc.7b00516 J. Agric. Food Chem. 2017, 65, 2017−2018
