The overall objective of this project is to assist industry, contract research organizations (CROs) and regulators in determining an acceptable and practicable approach for generating the data relevant to human health risk assessment required for the registration of nano-enabled pesticide formulations.
Broadly speaking, a nano-enabled pesticide represents a product where nanotechnology is employed (e.g. delivery via a nano-carrier) to enhance efficacy, reduce environmental footprint or enhance usability of a pesticide active ingredient.
The previous IUPAC Nanopesticides projects (e.g. project 2012-020-3-600, 2016-016-2-600) have developed risk assessment frameworks and key criteria that could help risk assessment process for nano-enabled pesticides (especially for ecological risk assessment), as published by Kookana et al. 2014 (J. Ag Food Chem 62: 4227-4240; https://dx.doi.org/10.1021/jf500232f) and Walker et al. 2017 (J. Ag Food Chem (in press); https://doi.org/10.1021/acs.jafc.7b02373).
While the approach elucidated in above IUPAC projects is now being considered by regulatory agencies internationally (e.g. USEPA, Environment Canada, APVMA Australia, EFSA Europe), there is a need to expand the thinking and provide more practical information to answer some key questions, such as those listed below:
1. When a new product is presented to the regulators, what are the key questions that they would like to ask? This essentially defines the problem formulation step in the health risk assessment framework.
2. What are the key characterization and analytical requirements for the specific product that may be necessary to answer the question posed at 1 for a specific product type?
3. What are the specific methods or approaches for human health effects that are readily available and appropriate to answer the questions for the specific product under consideration?
4. What are the current knowledge gaps and uncertainties that the regulators and industry need to consider for a pragmatic approach to decision making?
This project would consist of three phases.
Phase I – Bring together a core group of task members to define the scope of the project, identify specific active ingredients and product types, and undertake problem formulation from the risk assessment perspective.
Phase II – Organize a workshop bringing together expertise from industry, regulatory bodies and researchers on human health effects and the risk assessment of nano-enabled pesticides as well as characterization of nanomaterials that have been identified in phase I.
Phase III – Recommend a sound methodological approach for generating data that is likely to be needed by the regulators. Identify research priorities where current knowledge or methodology are found to be inadequate.
Project announcement published in CI Apr 2018, pp. 38-39 <https://doi.org/10.1515/ci-2018-0218>
Recent ref of relevance: Melanie Kah, et al. ‘A critical evaluation of nanopesticides and nanofertilizers against their conventional analogues’, Nature Nanotechnology, 2018, published online 7 May 2018, https://doi.org/10.1038/s41565-018-0131-1
May 2019 update: the project got an excellent start in June 2018 with a project workshop in Boston to coincide with the Gordon Research Conference on Nanoscale Science and Engineering for Agriculture and Food Systems. The objective of the workshop was to identify questions that are specific to nano-enabled pesticides that must be addressed in addition to the questions normally asked for conventional pesticides.
The workshop brought together a range of expertise from regulators, industry, researchers and academia. Regulatory agencies namely, US Environment Protection Agency (EPA), US Food and Drug Administration (FDA), Health Canada, Australian Pesticides and Veterinary Medicines Authority (APVMA), each provided an overview of their approach for regulating nano-enabled pesticides/nanomaterials. Vive Crop Protection provided an overview of products likely to enter the market as well as an industry perspective on how these products are likely to be different than conventional AIs. In breakout sessions, the group then discussed different routes of exposure (e.g. dermal, inhalation, ingestion) as well as stages of exposure (e.g. during mixing-loading, during application, workers, bystanders, residents). These were considered in relation to two case studies where (i) a nanocarrier system is used for a slow release of a pesticide AI (e.g. an insecticide molecule) and (ii) a pure AI nanoparticle is used for modifying the inherent chemical properties of the AI (e.g. to increase the “apparent solubility”, retention on leaves or uptake in target organisms).
The workshop raised more questions than answers and identified several issues that need to be addressed while considering nano-enabled pesticides implications for human health, for example:
• Different jurisdictions have slightly different criteria for defining nano-enabled pesticides at the moment, similar to the current situation with defining nanomaterials by regulatory agencies. The boundaries are not yet clearly defined.
• The vast majority of nano-enabled pesticides are based on existing and already authorised AIs. The AI is the bioactive component, which is primarily tested for efficacy and potential undesirable effects, similarly to pharmaceuticals. In many cases, the other components of the formulations (inerts/excipients) also have to be considered.
• Pesticide AIs are always formulated, e.g. with surfactants, solvents, and/or inerts. Many formulations currently contain relatively large amounts of inerts, including non-nano forms of TiO2 or silica. Can data related to existing excipients be used or should these inerts/excipients be treated differently in nanoformulations?
• The persistence of a nanocarrier may be assessed as part of the inert assessment on individual components. However, the persistence of the full formulated nanocarrier (with all ingredients, including the AI) may not be known. Does this raise issues?
• Considering the variability in excipients and formulations, what is the correct reference material? AI alone is currently used for toxicity studies, not the formulations.
• Nano AI may be stabilised with e.g. surfactants: Does the fact that they are, or are associated with, a nanoparticle, make them different from a toxicological perspective?
• For a nanocarrier composed of ingredients that are already considered safe: are there ways to design bridging studies and potentially use existing toxicity data? How should the dose be compared? What data is needed for bridging? How does one determine dose? What tests/end points are needed?
Considering the above and many more questions that were raised at the Boston workshop, a 2nd workshop is being organised directly following the IUPAC General Assembly in July 2019, and will be held in at the Middlesex University (The Burroughs) London 15-16 July 2019. We hope to develop well-considered views on some of the above challenges. The project will bring together Task Group members and invited experts.
Project update published in Chem Int Oct 2019, p. 41
Page last updated 31 October 2019