Abstract
Comparative chemical hazard assessment, which compares hazards for several endpoints across several chemicals, can be used for a variety of purposes including alternatives assessment and the prioritization of chemicals for further assessment. A new framework was developed to compile and integrate chemical hazard data for several human health and ecotoxicity endpoints from public online sources including hazardous chemical lists, Globally Harmonized System hazard codes (H-codes) or hazard categories from government health agencies, experimental quantitative toxicity values, and predicted values using Quantitative Structure–Activity Relationship (QSAR) models. QSAR model predictions were obtained using EPA’s Toxicity Estimation Software Tool. Java programming was used to download hazard data, convert data from each source into a consistent score record format, and store the data in a database. Scoring criteria based on the EPA’s Design for the Environment Program Alternatives Assessment Criteria for Hazard Evaluation were used to determine ordinal hazard scores (i.e., low, medium, high, or very high) for each score record. Different methodologies were assessed for integrating data from multiple sources into one score for each hazard endpoint for each chemical. The chemical hazard assessment (CHA) Database developed in this study currently contains more than 990,000 score records for more than 85,000 chemicals. The CHA Database and the methods used in its development may contribute to several cheminformatics, public health, and environmental activities.
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References
Allaj E (2018) Two simple measures of variability for categorical data. J Appl Stat 45:1497–1516. https://doi.org/10.1080/02664763.2017.1380787
Arena VC, Sussman NB, Mazumdar S, Yu S, Macina OT (2004) The utility of structure–activity relationship (SAR) models for prediction and covariate selection in developmental toxicity: comparative analysis of logistic regression and decision tree models. SAR QSAR Environ Res 15:1–18. https://doi.org/10.1080/1062936032000169633
Barrett WM, Takkellapati S, Tadele K, Martin TM, Gonzalez MA (2019) Linking molecular structure via functional group to chemical literature for establishing a reaction lineage for application to alternatives assessment. ACS Sustain Chem Eng 7:7630–7641. https://doi.org/10.1021/acssuschemeng.8b05983
California (2018) The proposition 65 list. https://oehha.ca.gov/proposition-65/proposition-65-list. Accessed 2 Oct 2018
Chemhat.org (2018) Chemical hazards and alternatives Toolbox. http://www.chemhat.org/en. Accessed 24 Sep 2018
Chemsec (2018) Substitute it now (SIN) list. http://sinlist.chemsec.org/search/searchall. Accessed 4 Oct 2018
Clean Production Action (2018a) GreenScreen for safer chemicals hazard assessment guidance; Version 1.4, January 2018
Clean Production Action (2018b) Greenscreen list translator™. https://www.greenscreenchemicals.org/learn/greenscreen-list-translator. Accessed 24 Sep 2018
CNESST (2015) WHMIS 2015 classification. http://www.csst.qc.ca/en/prevention/reptox/Pages/list-whmis-2015-a.aspx Accessed 2 Oct 2018
Department of Occupational Safety and Health Ministry of Human Resources Malaysia (2014) Industry code of practice on chemicals classification and hazard communication. http://www.dosh.gov.my/index.php/en/list-of-documents/osh-info/chemical-management-1/2217-industry-code-of-practice-on-chemicals-classification-and-hazard-communication-2014-pdf/file. Accessed 3 Oct 2018
ECHA (2018a) Classification labeling and packaging (CLP) Annex VI. https://echa.europa.eu/information-on-chemicals/annex-vi-to-clp. Accessed 2 Oct 2018
ECHA (2018b) Registration, evaluation, authorization and restriction of chemicals (REACH) candidate list of substances of very high concern for authorization. https://echa.europa.eu/candidate-list-table. Accessed 4 Oct 2018
ECHA and OECD (2018) International uniform chemical information database (IUCLID). https://iuclid6.echa.europa.eu/. Accessed 16 Oct 2018
Environment and Climate Change Canada (2006) Domestic substance list (DSL) categorizations. Document available upon request from: eccc.substances.eccc@canada.ca
European Union (2006) Regulation (EC) No. 1907/2006 of the european parliament and of the council concerning the registration, evaluation, authorisation and restriction of chemicals (REACH) and establishing a european chemicals agency
Faludi J, Hoang T, Gorman P, Mulvihill M (2016) Aiding alternatives assessment with an uncertainty-tolerant hazard scoring method. J. Environ Manag 182:111–125. https://doi.org/10.1016/j.jenvman.2016.07.028
GAO (2005) Chemical regulation: options exist to improve EPA’s ability to assess health risks and manage its chemical review program GAO-05-458
Germany MAK Commission (2017) List of MAK and BAT values 2017: permanent senate commission for the investigation of health hazards of chemical compounds in the work area; Report 53
Government of Canada (1995) Canadian environmental protection act: priority substances list. https://www.canada.ca/en/environment-climate-change/services/canadian-environmental-protection-act-registry/substances-list/priority-list.html. Accessed 11 Oct 2018
Hansen K, Mika S, Schroeter T, Sutter A, ter Laak A, Steger-Hartmann T, Heinrich N, Müller KR (2009) Benchmark data set for in silico prediction of Ames mutagenicity. J Chem Inf Model 49:2077–2081. https://doi.org/10.1021/ci900161g
Healthy Building Network (2018) Pharos chemical and material library (CML) full system description, June 2018. https://www.pharosproject.net/uploads/files/library/Pharos_CML_System_Description.pdf. Accessed 9 Sep 2019
Healthy Building Network (2019) Pharos. https://pharosproject.net. Accessed 9 Sept 2019
Hertwich EG, McKone TE, Pease WS (1999) Parameter uncertainty and variability in evaluative fate and exposure models. Risk Anal 19:1193–1204. https://doi.org/10.1111/j.1539-6924.1999.tb01138.x
Jacobs MM, Malloy TF, Tickner JA, Edwards S (2016) Alternatives assessment frameworks: research needs for the informed substitution of hazardous chemicals. Environ Health Perspect 124:265–280. https://doi.org/10.1289/ehp.1409581
Kavlock R, Chandler K, Houck K, Hunter S, Judson R, Kleinstreuer N, Knudsen T, Martin M, Padilla S, Reif D, Richard A, Rotroff D, Sipes N, Dix D (2012) Update on EPA’s ToxCast program: providing high throughput decision support tools for chemical risk management. Chem Res Toxicol 25:1287–1302. https://doi.org/10.1021/tx3000939
Knudsen TB, Martin MT, Kavlock RJ, Judson RS, Dix DJ, Singh AV (2009) Profiling the activity of environmental chemicals in prenatal developmental toxicity studies using the U.S. EPA’s ToxRefDB. Reprod Toxicol 28:209–219. https://doi.org/10.1016/j.reprotox.2009.03.016
Martin MT, Mendez E, Corum DG, Judson RS, Kavlock RJ, Rotroff DM, Dix DJ (2009) Profiling the reproductive toxicity of chemicals from multigeneration studies in the toxicity reference database. Toxicol Sci 110:181–190. https://doi.org/10.1093/toxsci/kfp080
Martin TM (2016) User’s guide for T.E.S.T. (version 4.2) (Toxicity Estimation Software Tool). https://www.epa.gov/sites/production/files/2016-05/documents/600r16058.pdf
Martin TM (2019) Github Repository: GHS data gathering. https://github.com/tmarti02/ghs-data-gathering. Accessed 18 Nov 2019
Ministry of Environment and Food of Denmark (2010) Advisory list for self-classification of dangerous substances. https://eng.mst.dk/chemicals/chemicals-in-products/assessment-of-chemicals/the-advisory-list-for-self-classification-of-hazardous-substances/. Accessed 9 Aug 2019
National Toxicology Program (2016) 14th Report on carcinogens. https://ntp.niehs.nih.gov/pubhealth/roc/index-1.html. Accessed 4 Oct 2018
New Zealand Environmental Protection Authority (2018) Chemical classification and information database (CCID). https://www.epa.govt.nz/database-search/chemical-classification-and-information-database-ccid/. Accessed 4 Oct 2018
NIOSH (2012) Occupational cancer carcinogen list. https://www.cdc.gov/niosh/topics/cancer/npotocca.html. Accessed 4 Oct 2018
NITE of Japan (2018) GHS classification results. http://www.safe.nite.go.jp/english/ghs/all_fy_e.html. Accessed 3 Oct 2018
NRC (1984) NRC (1984) Toxicity testing: strategies to determine needs and priorities.The National Academies Press, Washington, D.C. https://doi.org/10.17226/317
NRC (2007) Toxicity testing in the 21st Century: a vision and a strategy. The National Academies Press, Washington, D.C. https://doi.org/10.17226/11970
NRC (2014) A framework to guide selection of chemical alternatives. The National Academies Press, Washington, D.C. https://doi.org/10.17226/18872
OECD (2013) Current landscape of alternatives assessment practice: a meta-review. http://www.oecd.org/officialdocuments/publicdisplaydocumentpdf/?cote=ENV/JM/MONO%282013%2924&docLanguage=En. Accessed 22 Nov 2019
OECD (2018) The global portal to information on chemical substances (eChemPortal). https://www.echemportal.org/echemportal/index.action. Accessed 16 Oct 2018
Panko J, Hitchcock K, Fung M, Spencer P, Kingsbury T, Mason A (2017) A comparative evaluation of five hazard screening tools. Integr Environ Assess Manag 13:139–154. https://doi.org/10.1002/ieam.1757
Public Law 114-182; 15 USC 2601 Frank R. Lautenberg Chemical Safety for the 21st Century Act (2016)
Richard A, Judson RS, Houck KA, Grulke CM, Volarath P, Thillainadarajah I, Yang C, Rathman J, Martin MT, Wambaugh JF, Knudsen TB, Kancherla J, Mansouri K, Patlewicz G, Williams AJ, Little SB, Crofton KM, Thomas RS (2016) ToxCast chemical landscape: paving the road to 21st century toxicology. Chem Res Toxicol 29:1225–1251. https://doi.org/10.1021/acs.chemrestox.6b00135
Safe Work Australia (2018) Hazardous chemical information system (HCIS). http://hcis.safeworkaustralia.gov.au/HazardousChemical. Accessed 2 Oct 2018
SQLite Consortium and Hipp Wyrick & Company Inc. (2018) SQLite. https://www.sqlite.org/index.html. Accessed 14 Nov 2018
TEDX (2018) The TEDX List of potential endocrine disruptors. https://endocrinedisruption.org/interactive-tools/tedx-list-of-potential-endocrine-disruptors/search-the-tedx-list. Accessed 4 Oct 2018
Tong W, Fang H, Hong H, Xie Q, Perkins R, Sheehan DM (2004) Receptor-mediated toxicity: QSARs for estrogen receptor binding and priority setting of potential estrogenic endocrine disruptors. In: Cronin MT, Livingstone DJ (eds) Predicting chemical toxicity and fate. CRC Press, Boca Raton
Toxnot PBC (2018). https://toxnot.com/. Accessed 24 Sept 2018
UN (2017) Globally harmonized system of classification and labelling of chemicals (GHS). Rev. 7
University of Maryland (2018) List of Acute Toxins, Teratogens, Carcinogens, or Mutagens (via ACToR). https://actor.epa.gov/actor/assay.xhtml?assayId=2198. Accessed 4 Oct 2018
US EPA (2006a) ACToR link to Health Canada Priority Substance Lists (2006) (Carcinogenicity). https://actor.epa.gov/actor/assay.xhtml?assayId=1558. Accessed 20 Nov 2019
US EPA (2006b) ACToR link to Health Canada Priority Substance Lists (2006) (Reproductive Toxicity). https://actor.epa.gov/actor/assay.xhtml?assayId=1561. Accessed 20 Nov 2019
US EPA (2008) DSSTox EPA integrated risk information system structure-index locator file: SDF file and documentation. https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=186904&Lab=NCCT. Accessed 10 Dec 2019
US EPA (2011a) Comments on the design for the environment (DfE) program alternatives assessment criteria for hazard evaluation. https://www.epa.gov/sites/production/files/2014-01/documents/aa_criteria_comments.pdf
US EPA (2011b) Design for the environment program alternatives assessment criteria for hazard evaluation Version 2.0. https://www.epa.gov/sites/production/files/2014-01/documents/aa_criteria_v2.pdf. Accessed 20 Nov 2019
US EPA (2012) Estimation program interface suite (EPI Suite) Version 4.11. syracuse research corporation. https://www.epa.gov/tsca-screening-tools/epi-suitetm-estimation-program-interface. Accessed 16 Oct 2018
US EPA (2014) TSCA Work plan for chemical assessments: 2014 update. https://www.epa.gov/assessing-and-managing-chemicals-under-tsca/tsca-work-plan-chemical-assessments-2014-update. Accessed 4 Oct 2018
US EPA (2016a) ECOTOX Knowledgebase. https://cfpub.epa.gov/ecotox/. Accessed 22 July 2016
US EPA (2016b) T.E.S.T. Version 4.2. http://www2.epa.gov/chemical-research/toxicity-estimation-software-tool-test. Accessed 20 Nov 2019
US EPA (2018a) ACToR link to Chemical substances that meet the university of maryland definition of an acute toxin, teratogen, carcinogen, or mutagen. https://actor.epa.gov/actor/collection.xhtml?dataCollectionId=2111. Accessed 18 Dec 2018
US EPA (2018b) ACToR link to NIOSH list of potential occupational carcinogens. https://actor.epa.gov/actor/assay.xhtml?assayId=1936. Accessed 4 Oct 2018
US EPA (2018c) RapidTox Dashboard. https://www.epa.gov/chemical-research/rapidtox-dashboard. Accessed 19 Dec 2018
US EPA (2018d) Series 870 Health Effects Test Guidelines. https://www.epa.gov/test-guidelines-pesticides-and-toxic-substances/series-870-health-effects-test-guidelines
US EPA (2018e) TSCA Inventory Notification (Active-Inactive) Rule. https://www.epa.gov/tsca-inventory/tsca-inventory-notification-active-inactive-rule. Accessed 20 Nov 2019
US EPA (2018f) TSCA Inventory, active non-confidential portion. https://comptox.epa.gov/dashboard/chemical_lists/tscaactivenonconf. Accessed 7 Nov 2018
US EPA (2018g) WebTEST. https://comptox.epa.gov/dashboard/predictions/index
US EPA (2018h) A working approach for identifying potential candidate chemicals for prioritization. https://www.epa.gov/sites/production/files/2018-09/documents/preprioritization_white_paper_9272018.pdf. Accessed 10 Oct 2018
US EPA (2019a) CompTox chemicals dashboard. https://www.epa.gov/chemical-research/comptox-chemicals-dashboard. Accessed 3 Sep 2019
US EPA (2019b) Distributed structure-searchable toxicity (DSSTox) database. https://www.epa.gov/chemical-research/distributed-structure-searchable-toxicity-dsstox-database. Accessed 20 Nov 2019
US EPA (2019c) ACToR (Aggregated Computational Toxicology Resource). https://actor.epa.gov. Accessed 20 Nov 2019
US EPA (2019d) Integrated risk information system (IRIS). https://www.epa.gov/iris. Accessed 20 Nov 2019
US EPA mid-Atlantic Region (2018) Human health risk-based concentrations. https://actor.epa.gov/actor/assay.xhtml?assayId=1092. Accessed 2 Oct 2018
U.S. National Library of Medicine (2018) ChemIDplus. https://chem.nlm.nih.gov/chemidplus/. Accessed 2 Oct 2018
Wehage K, Chenhansa P, Schoenung JM (2017) An open framework for automated chemical hazard assessment based on GreenScreen for Safer Chemicals: a proof of concept. Integr Environ Assess Manag. https://doi.org/10.1002/ieam.1763
Whittaker MH (2015) Risk assessment and alternatives assessment: comparing two methodologies. Risk Anal 35:2129–2136. https://doi.org/10.1111/risa.12549
Whittaker MH, Heine LG (2013) Chemical alternatives assessment (CAA): tools for selecting less hazardous chemicals. In: Hester RE, Harrison R (eds) Chemical Alternatives Assessments. Issues in Environmental Science and Technology, Burlington, pp 1–43
WHO IARC (2018) IARC monographs on the evaluation of carcinogenic risks to humans. https://monographs.iarc.fr/list-of-classifications. Accessed 9 Aug 2019
Williams AJ, Grulke CM, Edwards J, McEachran AD, Mansouri K, Baker NC, Patlewicz G, Shah I, Wambaugh JF, Judson RS, Richard AM (2017) The CompTox Chemistry Dashboard: a community data resource for environmental chemistry. J. Cheminformatics. https://doi.org/10.1186/s13321-017-0247-6
Yang Y, Tao M, Suh S (2018) Geographic variability of agriculture requires sector-specific uncertainty characterization. Int J Life Cycle Assess 23:1581–1589. https://doi.org/10.1007/s11367-017-1388-6
Acknowledgements
The authors thank Valery Tkachenko and Jonathan Fox for their assistance with code development and data mining. The authors thank Michael Gonzalez, William Barrett, Richard Judson, and Maureen Gwinn for helpful feedback on earlier drafts of the manuscript, and Sudhakar Takkellapati, Kidus Tadele, Paul Harten, Jane Bare, Grace Patlewicz, and Antony Williams for helpful suggestions and insights on comparative chemical hazard assessment. Dr. Vegosen gratefully acknowledges support by an appointment to the Research Participation Program at the U.S. Environmental Protection Agency (EPA), administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy and EPA.
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Vegosen, L., Martin, T.M. An automated framework for compiling and integrating chemical hazard data. Clean Techn Environ Policy 22, 441–458 (2020). https://doi.org/10.1007/s10098-019-01795-w
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DOI: https://doi.org/10.1007/s10098-019-01795-w