Correspondence/Rebuttal Cite This: Environ. Sci. Technol. XXXX, XXX, XXX-XXX
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Response to “Comment on ‘Mode of Action (MOA) Assignment Classifications for Ecotoxicology: An Evaluation of Approaches’”
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above; it is critical that the literature is reflective of new advances in the science and associated classification systems. We are quite confident that there is no confusion on these points, contrary to the points made by McCarty and Borgert1 in their concluding paragraph. We stand by our conclusion that “The existing MOA frameworks have great potential to improve risk assessment and strengthen the use of alternative methods. However, these frameworks lack harmonization and therefore often give contradictory results. Harmonizing and updating classification frameworks (built for a variety of purposes) with emerging knowledge on ecotoxicity and toxicological mode of action will significantly improve chemical risk assessment outcomes”. We hope that other scientists would agree with this conclusion. Our quantitative assessment of assignment outcomes is based on the available systems commonly applied in regulatory contexts, and represents an important and highly relevant step forward.
hile we appreciate the response of Drs. McCarty and Borgert,1 we respectfully disagree with many of their points regarding our recent publication2 on Mode of Action (MOA) classifications in ecotoxicology and believe that the main point of our publication was ignored in their letter. In our paper, we clearly acknowledge that MOA is operationally defined and in some situations “loosely defined” (see third paragraph of the Introduction). Regulators and some scientists use extant classification systems to make real-world regulatory decisions, and the purpose of our paper was to provide a quantitative evaluation of the most frequently used systems. We explicitly note that there is a hierarchy of specificity in the various systems and that, in some instances, this results in different outcomes depending on how they were built and for what purpose. McCarty and Borgert3 provide a theoretical view of various aspects of Mode and Mechanism of Action and clearly state that development of classification schemes for both are needed (see Recommendations section from their paper).3 However, this recognized need does not prevent legal regulatory systems from utilizing the currently available schemes, and our review2 provides a quantitative evaluation of the implications of using these approaches. Although a definitive solution is not given, our paper provides a comprehensive understanding of the scope and magnitude of the issues and needs. In addition, our quantitative review uses classification systems that were not available at the time the McCarty and Borgert3 article was published, including large additions to the OECD QSAR Toolbox and ToxTree, the associated KNIME workflow, and MOATox. While McCarty and Borgert1 may be unsatisfied with the current specificity of assignments (as are we), this does not imply any “confusion” of the concepts of MoA, MeA, or Adverse Outcome Pathways (AOPs). At no point in our article do we equate MoA or MeA with AOPs, as neither of the former conclude with a true adverse outcome postulated at the population or community level of biological organization. Several of the co-authors have been deeply involved in the AOP efforts for quite some time and are well-aware of the differences in terminology and application (see Volz et al.4 and Villeneuve et al.5). We stand by our statement that “MOA classification has never been standardized” as it has simply not occurred. In addition, it is true that a “...comprehensive comparison of approaches has never been reported2” in the sense that earlier assessments were nonquantitative in nature. Theoretical background is given in McCarty and Borgert,3 but a true side-by-side comparison of the approaches was not the intent of their article nor was it presented as such. The authors did cover a vast expanse of historical literature, much of it also including the use of MoA in human safety and in environmental mixture toxicity, which was the largest focus of the paper. Further, their review was neither quantitative nor did it include the most recent advances and classification system improvements cited © XXXX American Chemical Society
A. Kienzler† M. G. Barron‡ S. E. Belanger§ A. Beasley∥ M. R. Embry*,⊥
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† European Commission, Joint Research Centre, Directorate FHealth, Consumers and Reference Materials; F.3 Chemicals Safety & Alternative Methods, TP 126, Via E. Fermi, 2749, I-21027 Ispra, Italy ‡ United States Environmental Protection Agency, Gulf Ecology Division, 1 Sabine Island Drive, Gulf Breeze, Florida 32561, United States § The Procter & Gamble Company, Global Product Stewardship, Mason Business Center, 8700 Mason Montgomery Road, Cincinnati, Ohio 45050, United States ∥ The Dow Chemical Company, 1803 Building, Midland, Michigan 48640, United States ⊥ International Life Sciences Institute Health and Environmental Sciences Institute, 1156 15th Street, NW, Suite 200, Washington, D.C. 20005, United States
AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
M. R. Embry: 0000-0002-0376-2743 Notes
The authors declare no competing financial interest.
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REFERENCES
(1) McCarty, L.; Borgert, C. Comment on “Mode of Action (MOA) Assignment Classifications for Ecotoxicology: An Evaluation of
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DOI: 10.1021/acs.est.7b05413 Environ. Sci. Technol. XXXX, XXX, XXX−XXX
Environmental Science & Technology
Correspondence/Rebuttal
Approaches”. Environ. Sci. Technol. 2017, DOI: 10.1021/acs.est.7b04967. (2) Kienzler, A.; Barron, M. G.; Belanger, S. E.; Beasley, A.; Embry, M. R. Mode of Action (MOA) Assignment Classifications for Ecotoxicology: An Evaluation of Approaches. Environ. Sci. Technol. 2017, 51 (17), 10203−10211. (3) McCarty, L. S.; Borgert, C. J. Review of the toxicity of chemical mixtures: theory, policy, and regulatory practice. Regul. Toxicol. Pharmacol. 2006, 45, 119−143. (4) Volz, D. C.; Belanger, S. E.; Embry, M.; Padilla, S.; Sanderson, H.; Schirmer, K.; Scholz, S.; Villeneuve, D. Adverse Outcome Pathways during Early Fish Development: A Conceptual Framework for Identification of Chemical Screening and Prioritization Strategies. Toxicol. Sci. 2011, 123 (2), 349−358. (5) Villeneuve, D.; Volz, D. C.; Embry, M. R.; Ankley, G. T.; Belanger, S. E.; Leonard, M.; Schirmer, K.; Tanguay, R.; Truong, L.; Wehmas, L. Investigating Alternatives to the Fish Early Life-Stage Test: A Strategy for Discovering and Annotating Adverse Outcome Pathways for Early Fish Development. Environ. Toxicol. Chem. 2014, 33 (1), 158−169.
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DOI: 10.1021/acs.est.7b05413 Environ. Sci. Technol. XXXX, XXX, XXX−XXX
