Developing prototypes of a modernized approach to assess crop protection chemical safety
Article Sidebar
Main Article Content
Abstract
In 2019, the US EPA Administrator issued a directive directing the agency away from reliance on vertebrate tests by 2035, whilst maintaining high quality human health and environmental risk assessments. There is no accepted approach to achieve this. The decade long duration of the crop protection (CP) chemical R&D process therefore requires both the invention, and application, of a modernized approach to those CP chemical projects entering corporate research portfolios by the mid-2020s. Consequently, we conducted problem formulation discussions with regulatory agency scientists which created the problem statement: “Develop, demonstrate, and implement a modern scientifically sound and robust strategy that applies appropriate and flexible exposure and effects characterization without chemical specific vertebrate tests to reliably address risk, uncertainties, and deficiencies in data and its interpretation with equivalent confidence as do the currently accepted test guidelines and meet the regulatory needs of the agencies”. The solution must provide the knowledge needed to confidently conclude human health and environmental protective risk assessments. Exploring this led to a conceptual model involving the creation, and parallel submission of a new approach without reliance on chemical specific vertebrate tests. Assessment in parallel to a traditional package will determine whether it supports some, or all, of the necessary risk management actions. Analysis of any deficiencies will provide valuable feedback to focus development of tools or approaches for subsequent iterations. When found to provide sufficient information, it will form the technical foundation of stakeholder engagement to explore acceptance of a new approach to CP chemical risk assessment.
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
Articles are distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is appropriately cited (CC-BY). Copyright on any article in ALTEX is retained by the author(s).
Alexander-White, C., Bury, D., Cronin, M., et al. (2022). A 10-step framework for use of read-across (RAX) in next generation risk assessment (NGRA) for cosmetics safety assessment. Regul Toxicol Pharmacol 129, 105094. doi:10.1016/j.yrtph.2021.105094
Belanger, S.E., Sanderson, H., Embry, M.R. et al. (2015). It is time to develop ecological thresholds of toxicological concern to assist environmental hazard assessment. Environ Toxicol Chem 34, 2864-9. doi:10.1002/etc.3132
Bhuller, Y., Ramsingh, D., Beal, M. et al. (2021). Canadian Regulatory Perspective on Next Generation Risk Assessments for Pest Control Products and Industrial Chemicals, Front Toxicol 3, 748406. doi:10.3389/ftox.2021.748406
Chen, D., Huang, H., Huang, Y. et al. (2023). Toxicity Tests for Chemical Pesticide Registration: Requirement Differences among the United States, the European Union, Japan, and China? J Agric Food Chem 71, 7192–7200. doi:10.1021/acs.jafc.3c00410
Connors, K.A., Beasley, A., Barron, M.G. et al. (2019). Creation of a Curated Aquatic Toxicology Database: EnviroTox. Environ Toxicol Chem 38, 1062-1073. doi:10.1002/etc.4382
Craig, E., Lowe, K., Akerman, G. et al. (2019). Reducing the need for animal testing while increasing efficiency in a pesticide regulatory setting: Lessons from the EPA Office of Pesticide Programs’ Hazard and Science Policy Council. Regul Toxicol Pharmacol 108, 104481. doi:10.1016/j.yrtph.2019.104481
Dent, M.P., Vaillancourt, E., Thomas, R.S. et al. (2021). Paving the way for application of next generation risk assessment to safety decision-making for cosmetic ingredients. Regul Toxicol Pharmacol 125, 105026. doi:10.1016/j.yrtph.2021.105026
Dreier, D.A., Connors, K.A., and Brooks, B.W. (2015). Comparative endpoint sensitivity of in vitro estrogen agonist assays. Regul Toxicol Pharmacol 72, 185-93. doi:10.1016/j.yrtph.2015.04.009
Dreier, D.A., Rodney, S.I., Moore, D.R.J. et al. (2021). Integrating Exposure and Effect Distributions with the Ecotoxicity Risk Calculator: Case Studies with Crop Protection Products. Integr Environ Assess Manag 17, 321-330. doi:10.1002/ieam.4344.
Embry, M.R., Bachman, A.N., Bell, D.R. et al. (2014). Risk assessment in the 21st century: roadmap and matrix. Crit Rev Toxicol 44 Suppl 3, 6-16. doi:10.3109/10408444.2014.931924
Escher, S.E., Partosch, F., Konzok, S. et al. (2022) Development of a Roadmap for Action on New Approach Methodologies in Risk Assessment. EFSA J 19, 7341E doi:10.2903/sp.efsa.2022.EN-7341
Hilton, G.M., Adcock, C., Akerman, G., et al. (2022). Rethinking chronic toxicity and carcinogenicity assessment for agrochemicals project (ReCAAP): A reporting framework to support a weight of evidence safety assessment without long-term rodent bioassays. Regul Toxicol Pharmacol 131,105160. doi:10.1016/j.yrtph.2022.105160.
Janowska-Sejda, E., Adeleye, Y., and Currie, R.A. (2022). Exploration of the DARTable Genome- a Resource Enabling Data-Driven NAMs for Developmental and Reproductive Toxicity Prediction. Front Toxicol 3, 806311 doi:10.3389/ftox.2021.806311
Johnson, K.J., Auerbach, S.S., Stevens, T. et al. (2022) A Transformative Vision for an Omics-Based Regulatory Chemical Testing Paradigm. Toxicol Sci 190,127-132. doi:10.1093/toxsci/kfac097
Judson, R.S., Magpantay, F.M., Chickarmane, V. et al. (2015). Integrated model of chemical perturbations of a biological pathway using 18 in vitro high-throughput screening assays for the estrogen receptor. Toxicol Sci 148,137–154, doi: 10.1093/toxsci/kfv168
Judson, R.S., Paul Friedman, K., Houck, K. et al. (2018). New approach methods for testing chemicals for endocrine disruption potential. Curr Opin Toxicol 9, 40–47, 10.1016/j.cotox.2018.10.002.
Kavlock, R.J., Ankley, G.T., Blancato, J.N. et al. (2003). A Framework for a Computational Toxicology Research Program In ORD. U.S. Environmental Protection Agency, Washington, DC, EPA 600/R-03/065 (NTIS PB2005-105438) Hammerstromm, K., Swartout, J., Tilson, H.A., Toth, G.P., Veith, G.D., Weber, E.J., Wolf, D.C. https://nepis.epa.gov/Exe/ZyPURL.cgi?Dockey=100046MA.txt
Kavlock, R.J., Bahadori, T., Barton-Maclaren, T.S. et al. (2018) Accelerating the Pace of Chemical Risk Assessment. Chem. Res. Toxicol. 31(5): 287-290. doi:10.1021/acs/chemrestox.7b00339
Kleinstreuer, N.C., Ceger, P., Watt, E.D. et al. (2017.) Development and validation of a computational model for androgen receptor activity. Chem Res Toxicol 30, 946–964, doi: 10.1021/acs.chemrestox.6b00347
Kroes, R., and Kozianowski, G. (2002). Threshold of toxicological concern (TTC) in food safety assessment. Toxicol Lett 127, 43-6. doi:10.1016/s0378-4274(01)00481-7
Kroes, R., Renwick, A.G., Feron, V. et al. (2007). Application of the threshold of toxicological concern (TTC) to the safety evaluation of cosmetic ingredients. Food Chem Toxicol 45, 2533-62. doi:10.1016/j.fct.2007.06.021.
Lanzoni, A., Castoldi, A.F., Kass, G.E. et al. (2019). Advancing human health risk assessment. EFSA J 17(Suppl 1), e170712. doi:10.2903/j.efsa.2019.e170712
Lehman, A.J., Laug, E.P., Woodard, G. et al. (1949). Procedures for the appraisal of the toxicity of Chemicals in Foods. Food Drug Cosmet Law Q 4,412–434. https://www.jstor.org/stable/26651773 .
Middleton, A.M., Reynolds, J., Cable, S. et al. (2022) Are Non-animal Systemic Safety Assessments Protective? A Toolbox and Workflow. Toxicol Sci 189, 124-147. doi:10.1093/toxsci/kfac068
NRC – National Research Council (US) Committee on Improving Risk Analysis Approaches Used by the U.S. EPA. Science and Decisions: Advancing Risk Assessment. National Academies Press (US), 2009. doi:10.17226/12209
Nitsche, K.S., Müller, I., Malcomber, S. et al. (2022). Implementing organ-on-chip in a next-generation risk assessment of chemicals: a review. Arch Toxicol 96, 711–741. doi:10.1007/s00204-022-03234-0
OECD (2020). Overview of Concepts and Available Guidance related to Integrated Approaches to Testing and Assessment (IATA). Series on Testing and Assessment No 329. https://www.oecd.org/chemicalsafety/risk-assessment/concepts-and-available-guidance-related-to-integrated-approaches-to-testing-and-assessment.pdf
OECD (2022). Case Study on the use of an Integrated Approach for Testing and Assessment (IATA) for New Approach Methodology (NAM) for Refining Inhalation Risk Assessment from Point of Contact Toxicity of the Pesticide, Chlorothalonil. Series on Testing and Assessment. No. 367 http://www.oecd.org/officialdocuments/displaydocument/?cote=env/cbc/mono(2022)31&doclanguage=en
OECD Test Guidelines for Chemicals (2023a). Last accessed April 06, 2023. https://www.oecd.org/chemicalsafety/testing/oecdguidelinesforthetestingofchemicals.htm
OECD (2023b). Guideline No. 497: Defined Approaches on Skin Sensitisation, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris, doi:10.1787/b92879a4-en .
Pastoor, T.P., Bachman, A.N., Bell, D.R. et al. (2014) A 21st century roadmap for human health risk assessment. Crit Rev Toxicol 44 Suppl 3,1-5. doi:10.3109/10408444.2014.931923.
Paul Friedman, K., Gagne, M., Lit Loo, L.H. et al. (2020). Utility of In Vitro Bioactivity as a Lower Bound Estimate of In Vivo Adverse Effect Levels and in Risk-Based Prioritization. Toxicol Sci 173, 202-225. doi:10.1093/toxsci/kfz201
Ramanarayanan, T., Szarka, A., Flack, S. et al. (2022). Application of a new approach method (NAM) for inhalation risk assessment. Regul Toxicol Pharmacol 133, 105216. doi:10.1016/j.yrtph.2022.105216
Rizzi, C., Villa, S., Cuzzeri, A.S., and Finizio, A. (2021). Use of the Species Sensitivity Distribution Approach to Derive Ecological Threshold of Toxicological Concern (eco-TTC) for Pesticides. Int J Environ Res Public Health 18, 12078. doi:10.3390/ijerph182212078
Sauve-Ciencewicki, A., Davis, K.P., McDonald, J. et al. (2019). Reg Toxicol Pharmacol 101, 187-193. doi:10.1016/j.yrtph.2018.11.015
Solomon, K., Giesy, J. and Jones, P. (2000). Probabilistic risk assessment of agrochemicals in the environment. Crop Protection 19, 649-655. doi:10.1016/S0261-2194(00)00086-7
Stucki, A.O., Barton-Maclaren, T.S., Bhuller, Y. et al. (2022). Use of new approach methodologies (NAMs) to meet regulatory requirements for the assessment of industrial chemicals and pesticides for effects on human health. Front Toxicol 4, 964553. doi:10.3389/ftox.2022.964553
Suter II, G.W. (2008). Ecological risk assessment in the USEPA: A historical overview. Integr Environ Assess Manag 4, 285–289. doi:10.1897/IEAM_2007-062
Thomas, R.S., Bahadori, T., Buckley, T.J. et al. (2019). The Next Generation Blueprint of Computational Toxicology at the U.S. Environmental Protection Agency. Toxicol Sci 169, 317-332. doi: doi:10.1093/toxsci/kfz058.
US EPA (1992), Framework for Ecological Risk Assessment. EPA/630/R-92/001, https://www.epa.gov/sites/default/files/2014-11/documents/framework_eco_assessment.pdf
US EPA (2013), GUIDING PRINCIPLES for DATA REQUIREMENTS. U.S. Environmental Protection Agency, Washington, DC 31 May 2013. https://www.epa.gov/sites/default/files/2016-01/documents/data-require-guide-principle.pdf
US EPA (2019), Directive to Prioritize Efforts to Reduce Animal Testing. Memorandum. U.S. Environmental Protection Agency, Washington, DC. 10 September 2019. https://www.epa.gov/newsreleases/administrator-wheeler-signs-memo-reduce-animal-testing-awards-425-million-advance
US EPA (2021), EPA New Approach Methods Work Plan. Office of Research and Development. Office of Chemical Safety and Pollution Prevention. U.S. Environmental Protection Agency, Washington, DC. December 2021. EPA 600/X-21/209 https://www.epa.gov/system/files/documents/2021-11/nams-work-plan_11_15_21_508-tagged.pdf
US EPA (2023a), Master List of Test Guidelines for Pesticides and Toxic Substances. Last accessed April, 2023. https://www.epa.gov/test-guidelines-pesticides-and-toxic-substances/master-list-test-guidelines-pesticides-and-toxic
US EPA (2023b), Models for Pesticide Risk Assessment. Last accessed May 2023. https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/models-pesticide-risk-assessment
Williams, E.S., Berninger, J.P., and Brooks, B.W. (2011). Application of chemical toxicity distributions to ecotoxicology data requirements under REACH. Environ Toxicol Chem 30, 1943-54. doi:10.1002/etc.583.
Wolf, D.C., Aggarwal, M., Battalora, M. et al. (2020). Implementing a globally harmonized risk assessment-based approach for regulatory decision-making of crop protection products. Pest Manag Sci 76, 3311-3315. doi:10.1002/ps.5793
Wolf, D.C., Bhuller, Y., Cope, R. et al. (2022). Transforming the evaluation of agrochemicals. Pest Manag Sci 78, 5049-5056. doi:10.1002/ps.7148.