Challenges and opportunities for overcoming dog use in agrochemical evaluation and registration

Main Article Content

Patricia L. Bishop, Susy Brescia, Rachel Brunner, Warren Casey, Kathleen Conlee-Griffin, Richard A. Currie, Jeanne Domoradzki, Michelle Embry, Maria Ines Harris, Thomas Hartung , Gina M. Hilton, Barry Hooberman, Brandall Ingle, Kyung-Jin Jang, Lewis Kinter, Caroline Krall, Joseph Leedale, Anna Lowit, Jyotigna Mehta, Elizabeth Mendez, Bob Mingoia, Eliana Munarriz, Lynea Murphy, Angela Myer, Antoniana Ottoni, Martina Panzarea, Monique Perron, Juan Pina, Deborah Ramsingh, Fiona Sewell, Jennifer Swanson, Yu-Mei Tan, Andrea Terron, Maria A. Trainer, Marize Campos Valadares, Steven Webb, Elizabeth Webb, Catherine Willett, Douglas C. Wolf
[show affiliations]


Progress in developing new tools, assays, and approaches to assess human hazard and health risk provides an opportunity to re-evaluate the necessity of dog studies for the safety evaluation of agrochemicals. A workshop was held where partic­ipants discussed the strengths and limitations of past use of dogs for pesticide evaluations and registrations. Opportunities were identified to support alternative approaches to answer human safety questions without performing the required 90-day dog study. Development of a decision tree for determining when the dog study might not be necessary to inform pesticide safety and risk assessment was proposed. Such a process will require global regulatory authority participation to lead to its acceptance. The identification of unique effects in dogs that are not identified in rodents will need further evaluation and determination of their relevance to humans. The establishment of in vitro and in silico approaches that can provide critical data on relative species sensitivity and human relevance will be an important tool to advance the decision process. Promising novel tools including in vitro comparative metabolism studies, in silico models, and high-throughput assays able to identify metabolites and mechanisms of action leading to development of adverse outcome pathways will need further development. To replace or eliminate the 90-day dog study, a collaborative, multidisciplinary, international effort that transcends organi­zations and regulatory agencies will be needed in order to develop guidance on when the study would not be necessary for human safety and risk assessment.

Article Details

How to Cite
Bishop, P. L. (2023) “Challenges and opportunities for overcoming dog use in agrochemical evaluation and registration”, ALTEX - Alternatives to animal experimentation, 40(3), pp. 534–540. doi: 10.14573/altex.2302151.
Meeting Reports

Baudy, A. R., Otieno, M. A., Hewitt, P. et al. (2020). Liver microphysiological systems development guidelines for safety risk assessment in the pharmaceutical industry. Lab Chip 20, 215-225. doi:10.1039/c9lc00768g

Bokkers, B. and Slob, W. (2007). Deriving a data-based interspecies assessment factor using the NOAEL and benchmark dose approach. Crit Rev Toxicol 37, 355-373. doi:10.1080/10408440701249224

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. Reg Tox Pharm 108, 104481. doi:10.1016/j.yrtph.2019.104481

Dellarco, V. L., Rowland, J. and May, B. (2010). A retrospective analysis of toxicity studies in dogs and impact on the chronic reference dose for conventional pesticide chemicals. Crit Rev Toxicol 40, 16-23. doi:10.3109/10408440903401529

EC – European Commission (2013). Commission Regulation (EU) No 283/2013 of 1 March 2013: Setting out the data requirements for active substances, in accordance with Regulation (EC) No 1107/2009 of the European Parliament and of the Council concerning the placing of plant protection products on the market.

Harrer, S., Pratik, S., Bhavna, A. et al. (2019). Artificial intelligence for clinical trial design. Trends Pharm Sci 40, 577-591. doi:10.1016/

Hasiwa, N., Bailey, J., Clausing, P. et al. (2011). Critical evaluation of the use of dogs in biomedical research and testing in Europe. ALTEX 28, 326-340. doi:10.14573/altex.2011.4.326

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. Reg Tox Pharm 131, 105160. doi:10.1016/j.yrtph.2022.105160

Jang, K., Otieno, M. A., Ronxhi, J. et al. (2019). Reproducing human and cross-species drug toxicities using a liver-chip. Sci Transl Med 11, eaax5516. doi:10.1126/scitranslmed.aax5516

Kleiber, M (1932). Body size and metabolism. Hilgardia 6, 315-353. doi:10.3733/hilg.v06n11p315

Kleiber, M. (1947). Body size and metabolic rate. Physiol Rev 27, 511-541. doi:10.1152/physrev.1947.27.4.511

Kleiber, M. (1961). The Fire of Life: An Introduction to Animal Energetics. New York, USA: John Wiley and Sons, Inc.

Kobel, W., Fegert, I., Billington, R. et al. (2010). A 1-year toxicity study in dogs is no longer a scientifically justifiable core data requirement for the safety assessment of pesticides. Crit Rev Toxicol 40, 1-15. doi:10.3109/10408440903300098

Kobel, W., Fegert, I., Billington, R. et al. (2014). Relevance of the 1-year dog study in assessing human health risks for registration of pesticides. An update to include pesticides registered in Japan. Crit Rev Toxicol 44, 842-848. doi:10.3109/10408444.2014.936550

Linke, B., Mohr, S., Ramsingh, D. et al. (2017). A retrospective analysis of the added value of 1-year dog studies in pesticide human health risk assessments. Crit Rev Toxicol 47, 581-591. doi:10.1080/10408444.2017.1290044

Luijten, M., Corvi, R., Mehta, J. et al. (2020). A comprehensive view on mechanistic approaches for cancer risk assessment of non-genotoxic agrochemicals. Reg Tox Pharm 118, 104789. doi:10.1016/j.yrtph.2020.104789

Monticello, T. M., Jones, T. W., Dambach, D. M. et al. (2017). Current nonclinical testing paradigm enables safe entry to first-in-human clinical trials: The IQ consortium nonclinical to clinical translational database. Tox Appl Pharm 334, 100-109. doi:10.1016/j.taap.2017.09.006

NASEM – National Academies of Sciences, Engineering, and Medicine (2020). Necessity, Use, and Care of Laboratory Dogs at the U.S. Department of Veterans Affairs. Washington, DC, USA: The National Academies Press. doi:10.17226/25772

Sauve-Ciencewicki, K. P. D., McDonald, J., Ramanarayanan, T. et al. (2019). A simple problem formulation framework to create the right solution to the right problem. Reg Tox Pharm 101, 187-193. doi:10.1016/j.yrtph.2018.11.015

Spielmann, H. and Gerbracht, U. (2001). The use of dogs as second species in regulatory testing of pesticides. Part II. Subacute, subchronic and chronic studies in the dog. Arch Toxicol 75, 1-21. doi:10.1007/s002040000195

Turner, M. (2011). Call to curb lab tests on dogs. Nature 474, 551. doi:10.1038/474551a

USEPA – U. S. Environmental Protection Agency (2013). Guiding Principles for Data Requirements. Office of Pesticide Programs, USEPA, Washington, DC.

USEPA (2016). Guidance for waiving acute dermal toxicity tests for pesticide formulations & supporting retrospective analysis. Office of Pesticide Programs, USEPA, Washington, DC.

USEPA (2018). Animal Toxicity Studies: Effects and Endpoints.

USEPA (2020a). Guidance for waiving acute dermal toxicity tests for pesticide technical chemicals and supporting retrospective analysis. Office of Pesticide Programs, USEPA, Washington, DC.

USEPA (2020b). Final guidance for waiving sub-acute avian dietary tests for pesticide registration and supporting retrospective analysis. Office of Pesticide Programs, USEPA, Washington, DC.

USEPA (2021). New approach methods workplan. Office of Research Development, USEPA, Washington, DC.

US FDA – U. S. Food and Drug Administration (2010). M3(R2) Nonclinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals.

US Federal Register (2022). Code of Federal Regulations. Title 40, Part 158 – Data requirements for pesticides.

Zurdo, J. (2013). Developability assessment as an early de-risking tool for biopharmaceutical development. Pharm Bioprocessing 1, 29-50.

Zurlo, J., Bayne, K. A., Brown, D. C. et al. (2011). Critical evaluation of the use of dogs in biomedical research and testing. ALTEX 28, 355-359. doi:10.14573/altex.2011.4.355

Most read articles by the same author(s)

<< < 9 10 11 12 13 14 15 16 17 > >>