G. Patlewicz , R.S. Judson , A.J. Williams , T. Butler , S. Barone Jr. , K.E. Carstens , J. Cowden , J.L. Dawson , S.J. Degitz , K. Fay , T.R. Henry , A. Lowit , S. Padilla , K. Paul Friedman , M.B. Phillips , D. Turk , J.F. Wambaugh , B.A. Wetmore , R.S. Thomas
{"title":"制定全氟烷基和多氟烷基物质(PFAS)的化学类别,并采用概念验证方法确定可能的候选物质,以便进行分级毒理学测试和人类健康评估","authors":"G. Patlewicz , R.S. Judson , A.J. Williams , T. Butler , S. Barone Jr. , K.E. Carstens , J. Cowden , J.L. Dawson , S.J. Degitz , K. Fay , T.R. Henry , A. Lowit , S. Padilla , K. Paul Friedman , M.B. Phillips , D. Turk , J.F. Wambaugh , B.A. Wetmore , R.S. Thomas","doi":"10.1016/j.comtox.2024.100327","DOIUrl":null,"url":null,"abstract":"<div><p>Per- and Polyfluoroalkyl substances (PFAS) are a class of manufactured chemicals that are in widespread use and many present concerns for persistence, bioaccumulation and toxicity. Whilst a handful of PFAS have been characterized for their hazard profiles, the vast majority have not been extensively studied. Herein, a chemical category approach was developed and applied to PFAS that could be readily characterized by a chemical structure. The PFAS definition as described in the Toxic Substances Control Act (TSCA) section 8(a)(7) rule was applied to the Distributed Structure-Searchable Toxicity (DSSTox) database to retrieve an initial list of 13,054 PFAS. Plausible degradation products from the 563 PFAS on the non-confidential TSCA Inventory were simulated using the Catalogic expert system, and the unique predicted PFAS degradants (2484) that conformed to the same PFAS definition were added to the list resulting in a set of 15,538 PFAS. Each PFAS was then assigned into a primary category using Organisation for Economic Co-operation and Development (OECD) structure-based classifications. The primary categories were subdivided into secondary categories based on a chain length threshold (>=7 vs < 7). Secondary categories were subcategorized using chemical fingerprints to achieve a balance between total number of structural categories vs.<!--> <!-->level of structural similarity within a category based on the Jaccard index. A set of 128 terminal structural categories were derived from which a subset of representative candidates could be proposed for potential data collection, considering the sparsity of relevant toxicity data within each category, presence on environmental monitoring lists, and the ability to identify plausible manufacturers/importers. Refinements to the approach taking into consideration ways in which the categories could be updated by mechanistic data and physicochemical property information are also described. This categorization approach may be used to form the basis of identifying candidates for data collection with related applications in QSAR development, read-across and hazard assessment.</p></div>","PeriodicalId":37651,"journal":{"name":"Computational Toxicology","volume":"31 ","pages":"Article 100327"},"PeriodicalIF":3.1000,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S246811132400029X/pdfft?md5=a51ea72ab10d67bffbfe8c69cb4c6b5b&pid=1-s2.0-S246811132400029X-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Development of chemical categories for per- and polyfluoroalkyl substances (PFAS) and the proof-of-concept approach to the identification of potential candidates for tiered toxicological testing and human health assessment\",\"authors\":\"G. Patlewicz , R.S. Judson , A.J. Williams , T. Butler , S. Barone Jr. , K.E. Carstens , J. Cowden , J.L. Dawson , S.J. Degitz , K. Fay , T.R. Henry , A. Lowit , S. Padilla , K. Paul Friedman , M.B. Phillips , D. Turk , J.F. Wambaugh , B.A. Wetmore , R.S. Thomas\",\"doi\":\"10.1016/j.comtox.2024.100327\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Per- and Polyfluoroalkyl substances (PFAS) are a class of manufactured chemicals that are in widespread use and many present concerns for persistence, bioaccumulation and toxicity. Whilst a handful of PFAS have been characterized for their hazard profiles, the vast majority have not been extensively studied. Herein, a chemical category approach was developed and applied to PFAS that could be readily characterized by a chemical structure. The PFAS definition as described in the Toxic Substances Control Act (TSCA) section 8(a)(7) rule was applied to the Distributed Structure-Searchable Toxicity (DSSTox) database to retrieve an initial list of 13,054 PFAS. Plausible degradation products from the 563 PFAS on the non-confidential TSCA Inventory were simulated using the Catalogic expert system, and the unique predicted PFAS degradants (2484) that conformed to the same PFAS definition were added to the list resulting in a set of 15,538 PFAS. Each PFAS was then assigned into a primary category using Organisation for Economic Co-operation and Development (OECD) structure-based classifications. The primary categories were subdivided into secondary categories based on a chain length threshold (>=7 vs < 7). Secondary categories were subcategorized using chemical fingerprints to achieve a balance between total number of structural categories vs.<!--> <!-->level of structural similarity within a category based on the Jaccard index. A set of 128 terminal structural categories were derived from which a subset of representative candidates could be proposed for potential data collection, considering the sparsity of relevant toxicity data within each category, presence on environmental monitoring lists, and the ability to identify plausible manufacturers/importers. Refinements to the approach taking into consideration ways in which the categories could be updated by mechanistic data and physicochemical property information are also described. 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Development of chemical categories for per- and polyfluoroalkyl substances (PFAS) and the proof-of-concept approach to the identification of potential candidates for tiered toxicological testing and human health assessment
Per- and Polyfluoroalkyl substances (PFAS) are a class of manufactured chemicals that are in widespread use and many present concerns for persistence, bioaccumulation and toxicity. Whilst a handful of PFAS have been characterized for their hazard profiles, the vast majority have not been extensively studied. Herein, a chemical category approach was developed and applied to PFAS that could be readily characterized by a chemical structure. The PFAS definition as described in the Toxic Substances Control Act (TSCA) section 8(a)(7) rule was applied to the Distributed Structure-Searchable Toxicity (DSSTox) database to retrieve an initial list of 13,054 PFAS. Plausible degradation products from the 563 PFAS on the non-confidential TSCA Inventory were simulated using the Catalogic expert system, and the unique predicted PFAS degradants (2484) that conformed to the same PFAS definition were added to the list resulting in a set of 15,538 PFAS. Each PFAS was then assigned into a primary category using Organisation for Economic Co-operation and Development (OECD) structure-based classifications. The primary categories were subdivided into secondary categories based on a chain length threshold (>=7 vs < 7). Secondary categories were subcategorized using chemical fingerprints to achieve a balance between total number of structural categories vs. level of structural similarity within a category based on the Jaccard index. A set of 128 terminal structural categories were derived from which a subset of representative candidates could be proposed for potential data collection, considering the sparsity of relevant toxicity data within each category, presence on environmental monitoring lists, and the ability to identify plausible manufacturers/importers. Refinements to the approach taking into consideration ways in which the categories could be updated by mechanistic data and physicochemical property information are also described. This categorization approach may be used to form the basis of identifying candidates for data collection with related applications in QSAR development, read-across and hazard assessment.
期刊介绍:
Computational Toxicology is an international journal publishing computational approaches that assist in the toxicological evaluation of new and existing chemical substances assisting in their safety assessment. -All effects relating to human health and environmental toxicity and fate -Prediction of toxicity, metabolism, fate and physico-chemical properties -The development of models from read-across, (Q)SARs, PBPK, QIVIVE, Multi-Scale Models -Big Data in toxicology: integration, management, analysis -Implementation of models through AOPs, IATA, TTC -Regulatory acceptance of models: evaluation, verification and validation -From metals, to small organic molecules to nanoparticles -Pharmaceuticals, pesticides, foods, cosmetics, fine chemicals -Bringing together the views of industry, regulators, academia, NGOs