Sf CDA United States JtWk Environmental Protection Agency June 2017 Office of Chemical Safety and Pollution Prevention Strategy for Conducting Literature Searches for N- Methylpyrrolidone (NMP): Supplemental Document to the TSCA Scope Document CASRN: 872-50-4 June 2017 ------- TABLE OF CONTENTS TABLE OF CONTENTS 2 1 OVERALL APPROACH 5 2 STEP 1: DEFINE SPECIFIC OBJECTIVES FOR THE SEARCHES 6 3 STEP 2: DEVELOP SEARCH STRATEGIES 8 3.1 Search Strategies for Physical/Chemical Properties 9 3.2 Search Strategies for Conditions of Use 9 3.3 Search Strategies for Fate, Engineering/Occupational Exposure, Exposure, and Human Health Hazard 10 3.3.1 Use of Existing Assessments 10 3.3.2 Peer-Reviewed Literature Database Search Strategies 10 3.3.3 Gray Literature Search Strategies 11 3.3.4 Initial Lifecycle/Conceptual Model Targeted Search 12 3.4 Search Strategies for Environmental hazard 12 4 STEP 3 AND 4: DEVELOP INCLUSION/EXCLUSION CRITERIA AND TAGS TO CATEGORIZE SEARCH RESULTS 12 4.1 Inclusion/Exclusion Criteria for Physical/Chemical Properties 12 4.2 Inclusion/Exclusion Criteria for Conditions of Use 13 4.3 Inclusion/Exclusion Criteria and Tags for Fate, Engineering/Occupational Exposure, Exposure, and Human Health Hazard 13 4.4 Inclusion/Exclusion Criteria for Fate, Engineering/Occupational Exposure, Exposure, and Human Health Hazard Gray Literature 14 4.5 Inclusion/Exclusion Criteria and Tags for Environmental hazard 15 5 STEP 5: SCREEN SEARCH RESULTS 15 5.1 Screening and Tagging for Physical/Chemical Properties 15 5.2 Screening and Tagging for Conditions of Use 15 5.3 Screening and Tagging for Fate, Engineering/Occupational Exposure, Exposure, and Human Health Hazard 16 5.3.1 Peer-Reviewed Literature Database Search Results 16 5.3.2 Gray Literature Search Results 16 5.4 Screening and Tagging for Environmental hazard 17 6 STEP 6. QUALITY ASSESSMENT PROCEDURE FOR SCREENING AND TAGGING 17 APPENDICES 18 A. LITERATURE SEARCH INFORMATION NEEDS FOR N-METHYLPYRROLIDONE (NMP) 18 A-l Fate Information Needs 18 A-2 Engineering/Occupational Exposure Information Needs 18 A-3 Exposure Information Needs 19 A-4 Human Health Information Needs 20 B. DATABASE (PEER-REVIEWED) LITERATURE SEARCHES FOR FATE, ENGINEERING/OCCUPATIONAL EXPOSURE, EXPOSURE, AND HUMAN HEALTH HAZARD 21 B-l N-methylpyrrolidone (NMP) Synonyms 21 B-2 Literature Search Strategies for Database Literature Searches for Fate, Engineering/Occupational Exposure, and Exposure 22 B-3 Literature Search Strategies for Database Literature Searches for Human Health 24 Page 2 of 83 ------- C. GRAY LITERATURE SEARCHES FOR FATE, ENGINEERING/OCCUPATIONAL EXPOSURE, EXPOSURE, AND HUMAN HEALTH HAZARD 29 D. LITERATURE SEARCHES FOR ENVIRONMENTAL HAZARD 61 E. DEVELOPMENT OF TAGS WITH INCLUSION/EXCLUSION CRITERIA 70 E-l Inclusion/Exclusion Criteria and Tags for the Fate Literature 70 E-2 Inclusion/Exclusion Criteria and Tags for the Engineering/Occupational Exposure Literature 73 E-3 Inclusion/Exclusion Criteria and Tags for the Exposure Literature 75 E-4 Inclusion/Exclusion Criteria and Tags for the Human Health Hazard Literature 78 E-5 Inclusion/Exclusion Criteria for the Environmental hazard Literature 81 LIST OF TABLES Table 2-1. Overview of Literature Search for N-Methylpyrrolidone (NMP) across All Topic Areas 7 Table 3-1. Overview of Search Strategies for N-Methylpyrrolidone (NMP) by Topic Area and Source Type 8 Table_Apx A-l. Fate Information Needs for N-Methylpyrrolidone (NMP) 18 Table_Apx A-2. Engineering/Occupational Exposure Information Needs for N-Methylpyrrolidone (NMP) 18 Table_Apx A-3. Exposure Information Needs for N-Methylpyrrolidone (NMP) 19 Table_Apx A-4. Human Health Information Needs for N-Methylpyrrolidone (NMP) 20 Table_Apx B-l. NMP Fate, Engineering/Occupational Exposure, and Exposure Search Strategy for Web of Science 22 Table_Apx B-2. N-Methylpyrrolidone (NMP) Human Health Hazard Peer-Reviewed Literature Search Strategy 24 Table_Apx C-l. Overview of Search Strategy for Gray Literature for Fate, Engineering/Occupational Exposure, Exposure, and Human Health Hazard Topic Areas 30 Table_Apx C-2. Sources Used For Gray Literature Search for Fate, Engineering/Occupational Exposure, Exposure, and Human Health Hazard Topic Areas with Source-Specific Inclusion/Exclusion Criteria .... 31 Table_Apx C-3. List of State Websites Included in the "States" Search for Fate, Engineering/Occupational Exposure, Exposure, and Human Health Hazard Topic Areas 50 Table_Apx C-4. List of Gray Literature Sources Removed from Search During Curation for Fate, Engineering/Occupational Exposure, Exposure, and Human Health Hazard Topic Areas 57 Table_Apx D-l. Sources Used For Gray Literature Search for the Ecotoxicity Topic Area 62 Table_Apx D-2. Chemical(s) located for N-Methylpyrrolidone (NMP) 65 Table_Apx E-l. Tags and Inclusion/Exclusion Criteria for N-Methylpyrrolidone (NMP) for the Fate Topic Area 70 Table_Apx E-2. Tags and Inclusion/Exclusion Criteria for N-Methylpyrrolidone (NMP) for the Engineering/Occupational Exposure Topic Area 73 Page 3 of 83 ------- Table_Apx E-3. Exposure Inclusion/Exclusion Criteria N-Methylpyrrolidone (NMP) and Tags 75 Table_Apx E-4. Human Health Hazard Inclusion/Exclusion Criteria and Tags 78 Table_Apx E-5. ECOTOX Codes Denoting Exclusion Criteria 82 Page 4 of 83 ------- 1 Overall Approach This appendix describes EPA/OPPT's initial methods, approaches and procedures for identifying, compiling, and screening publicly available information supporting TSCA risk evaluation for N- methylpyrrolidone (NMP). The literature searches were conducted by EPA1 and contractor2 staff for the following seven broad topic areas: 1. Physical/chemical properties (hereafter "pchem properties"), 2. Conditions of use of NMP, including known, intended, and reasonably foreseen industrial, commercial, and consumer uses, 3. Fate and transport in the environment (hereafter "fate"), 4. Chemical engineering, occupational exposure and environmental releases (hereafter "engineering"), 5. General population, consumer, and ecological exposure (hereafter "exposure"), 6. Human health hazard identification and dose-response (hereafter "human health hazard"), and 7. Environmental hazard identification and concentration-response (hereafter "environmental hazard") The following steps were generally conducted, with the exception of topic areas #1, 2 and 7: 1. Define the specific objectives of the literature search as part of the overall systematic review 2. Develop specific search strategies and execute search 3. Develop inclusion/exclusion criteria to determine which search results are "on-topic" versus "off-topic" 4. Develop topic-specific categories (or tags) to further categorize the search results 5. Screen literature search results 6. Validate the search strategy and tagging procedure (ongoing) EPA1 and contractors2 worked simultaneously to conduct the literature searches and leveraged existing information, wherever possible, to facilitate the data gathering effort supporting the risk evaluation. The current process included the following: EPA/OPPT chemists conducted the literature searches for pchem properties (topic area #1, Section Error! Reference source not found.) using an approach similar to the one used in the TSCA New Chemicals Program, but not the steps described above. When applicable, the chemists relied on literature already gathered in previous EPA/OPPT assessments to support the characterization of pchem properties. 1 EPA staff supported the literature searches for topic areas 1 and 2. 2ICF supported the literature searches for topic areas 3 to 6. ERG supported supplemental searches under topic area #4 to develop the life cycle diagrams. CSRA supported the literature search for ecological data under topic area #7. Page 5 of 83 ------- EPA/OPPT staff consulted a variety of sources to identify conditions of use (topic area #2) and to develop the Preliminary Information on Manufacturing, Processing, Distribution, Use and Disposal for N-Methylpyrrolidone (NMP) (hereafter "public use documents")3. Though the strategy did not include all the steps described above, EPA/OPPT included information reported to EPA, literature searches, trade publications, and reports developed for prior EPA and international assessments. These public use documents were used to elicit public feedback on conditions of use of the priority chemicals during and following a public meeting on February 14, 2017. Relevant public input was incorporated into this chemical's scope document. Searches for the fate, exposure, engineering and human health literature (topic areas #3 to 6) were conducted to (1) support the development of the initial life cycle and conceptual model diagrams, and (2) broadly capture information that would be necessary for preparing the environmental and occupational exposure and risk assessments4. These searches followed the steps described above. EPA/OPPT searched and screened the ecological literature following well accepted methods, approaches and procedures established for the ECOTOX knowledge base and used in EPA's ecological risk assessments5 (topic area #7). In general, the process was similar to the one outlined above. Subsequent sections describe the steps undertaken for each of these topic areas, with additional detail provided in the Appendices. Since the strategies for topic areas 3, 4, 5 and 6 (i.e., fate, engineering, exposure, and human health hazard) are similar, their strategies are in the same section. The results of the initial search based on title and abstract screening can be found in the "N- Methylpyrrolidone (NMP)(CASRN: 872-50-4) Bibliography: Supplemental File for the TSCA Scope Document". EPA/OPPT is currently evaluating the performance of the search and screening strategy (step 6) prior to commencing full-text screening. The literature search strategy may be refined and updated as the assessment progresses. Also, EPA/OPPT anticipates refinements to the literature search and screening strategy across chemicals to optimize the process for future chemicals. 2 Step 1: Define Specific Objectives for the Searches The information needs for each topic area were developed to translate the broad regulatory mandate of TSCA into questions that could be clearly addressed with the literature search. Table 2-1 Table 2-1 provides a broad overview of the information needs for each topic area. A 3 Initial compilation of data and/or information reported in the Preliminary Information on Manufacturing, Processing, Distribution, Use and Disposal for N-Methylpyrrolidone (NMP) released as part of the background materials for the public meeting on risk evaluation scoping efforts under TSCA for 10 chemical substances (Februrary 14, 2017; https://www.epa.gov/assessing-and-managing-chemicals-under-tsca/public-meeting-risk- evaluation-scoping-efforts-under-O). 4 Topic areas #2 and #4 complement each other. 5 ECOTOX database: https://cfpub.epa.gov/ecotox/. EPA's Office of Pesticides (OPP) and the Office of Research and Development (ORD) frequently use ECOTOX for ecological risk assessments. Page 6 of 83 ------- full list of information needs is provided in Appendix A for most of the topic areas. Note that general information needs for pchem properties, information on conditions of use and environmental hazard are in Table 2-1, but not in Appendix A. The ECOTOX standard operating procedures (SOPs) provide details about the information needs driving the ecological literature searches6. Table 2-1. Overview of Literature Search for N-Methylpyrrolidone (NMP) across All Topic Areas Discipline Information needs Physical/Chemical Properties Collection of pchem properties to inform the fate, exposure and hazard assessments of the risk evaluation Conditions of Use 1 Known, intended, and reasonably foreseen conditions of use, including manufacturing, processing, distribution, industrial, commercial and consumer uses, and disposal Fate Environmental mobility Environmental degradation Bioaccumulation and environmental persistence Wastewater removal processes Engineering Lifecycle and process related information Environmental releases Occupational exposure Exposure Lifecycle information to inform general population and consumer exposures Media concentrations in the environment Biomonitoring data Information to identify potentially exposed and susceptible subpopulations Human Health Hazard Information about health hazards including critical health effects and corresponding points of departure, associated with exposure via all routes, durations, sources, and pathways Characterization of exposure for general and potentially exposed and susceptible subpopulations Toxicokinetics Mode of action (MOA) Information to identify potentially exposed and susceptible subpopulations2 Environmental hazard Information about environmental hazards associated with acute and chronic toxic effects on aquatic and terrestrial species Notes: 1. The initial literature search and compilation of data and/or information are in the Preliminary Information on Manufacturing, Processing, Distribution, Use and Disposal for N-Methylpyrrolidone (NMP) released to the public in February 2017 as part of the background materials for the public meeting on risk evaluation scoping efforts under TSCA for 10 chemical substances (February 14, 2017; Docket ID EPA-HQ-OPPT-2016-0735 at regulations.gov and also at https://www.epa.gov/assessing-and-managing-chemicals-under-tsca/public- meeting-risk-evaluation-scoping-efforts-under-O). Also, EPA's "Use and Market Profile for N- Methylpyrrolidone (NMP)" contains data and/or information on conditions of use in the scope document (EPA, 2017b). 2. Literature search for identifying potentially exposed and susceptible subpopulations was designed to be broad to capture information about possible susceptible subpopulations such as infants, children, pregnant women, and elderly. 6 ECOTOX and related SOPs (https://cfpub.epa.gov/ecotox/help.cfm?helptabs=tab4) Page 7 of 83 ------- 3 Step 2: Develop Search Strategies EPA/OPPT considered different categories of data sources when developing the search strategies: 1. Existing problem formulations, draft or final assessments completed by U.S. government agencies (e.g., EPA IRIS assessments7), 2. Databases containing peer-reviewed literature (e.g., PubMed, Web of Science), 3. Gray literature, which is defined as the broad category of studies not found in standard, peer-reviewed literature databases (e.g., PubMed). Gray literature includes studies that are difficult to find in conventional bibliographic databases, such as white papers, conference proceedings, technical reports, reference books, dissertations, and information on various stakeholder websites. Table 3-1 provides an overview of the search strategies for NMP. Additional details, including full lists of search terms and sources, are provided in Appendix B (peer reviewed literature) and Appendix C (gray literature). Table 3-1. Overview of Search Strategies for N-Methylpyrrolidone (NMP) by Topic Area and Source Type Discipline Use of Existing Assessments1 Peer-Reviewed Literature Database Search Strategies Gray Literature Search Strategies Physical/ Chemical Properties EPA/OPPT Existing Chemical Assessment Databases: public databases that redirect to primary sources; see "Search Strategies for Physical/Chemical Properties" section Date limit: none Keywords: CAS Registry Number (CASRN), chemical name, and chemical structure Sources: public databases; see "Search Strategies for Physical/Chemical Properties" section Date limit: none Keywords: CAS Registry Number (CASRN), chemical name, and chemical structure Conditions of Use EPA/OPPT Existing Chemical Assessment Databases: see "Search Strategies for Conditions of Use" section Date limit: Safety Data Sheets: 2000; see "Search Strategies for Conditions of Use" section Keywords: CAS Registry Number (CASRN), chemical names, synonyms, trade names, and common misspellings Sources: list of resources; see "Search Strategies for Conditions of Use" section Date limit: none; "Search Strategies for Conditions of Use" section for more information Keywords: CAS Registry Number (CASRN), chemical names, synonyms, trade names, and common misspellings Fate, Engineering, and Exposure EPA/OPPT Existing Chemical Assessment Databases: Web of Science Date limit: none; search conducted February 28, 2017 Key Words: See Appendix A Sources: Curated list of resources; see Appendix B Date limit: none; search conducted February 7-28, 2017 7 Integrated Risk Information System (IRIS), https://www.epa.gov/iris Page 8 of 83 ------- Human Health Hazard EPA/OPPT Existing Chemical Assessment Databases: PubMed, Web of Science, and Toxline Date limit none; search January 1, 2016- February 14, 2017 Key Words: See Appendix A Key words: Varies by source; see Appendix B Environment al hazard EPA/OPPT Existing Chemical Assessment Databases: Science Direct, Agricola, Toxline, Scifinder, Proquest. Refer to ECOTOX SOP2 Date limit: none; search conducted January 13, 2017 Key Words: See Appendix D Sources: Curated list of resources, see Appendix D. Date limit: none; search conducted January 13, 2017 Key words: Varies by source; see Appendix D Notes: 1 In general, EPA/OPPT existing chemical assessments, EPA's IRIS assessments and ATSDR Toxicological Profiles were used if available. EPA/OPPT assessments may include draft or final TSCA Work Plan risk assessments and final problem formulations. When available, the EPA/OPPT assessments were used to identify pertinent references supporting pchem properties, use, fate, exposure and hazard information. In this case, EPA/OPPT considered, when pertinent, the data and/or information reported in the TSCA Work Plan Risk Assessment for NMP (https://www.epa.gov/assessing-and-managing-chemicals-under-tsca/assessments- tsca-work-plan-chemicals). No ATSDR Toxicological Profile has been developed for NMP. No IRIS assessment has been developed for NMP. 2 ECOTOX Literature Searches, Citation Identification and Skimming" (https://cfpub.epa.eov/ecotox/blackbox/help/ECOTOXLiteratureSearchesCitationldentificationandSkimmine.pdf) 3.1 Search Strategies for Physical/Chemical Properties Most of the physical/chemical (pchem) property searches were already conducted when EPA/OPPT was preparing the TSCA Work Plan risk assessment for NMP. The physical/chemical information pchem properties cited in this document was retained for the scope document unless the chemist found newer studies through supplemental searches between December 2016 and March 2017. The general approach for determining pchem properties is to first search for the specific substance in question (using CAS Registry Number (CASRN), chemical name, or the chemical structure) by following an organized path of literature and database sources, starting with public databases such as STN and REAXYS online, which links directly to the primary references. Additional searches may be conducted using resources such as ChemSpider, which provides both measured and predicted values, with limited primary references. If the exact substance cannot be found, then close structural analogs may be located and their property values extrapolated to the substance in question, or by computer estimation programs. All estimated values as well as measured ones are critically reviewed and deemed reasonable based on professional judgement. Values that are sought, as a minimum, for any physical/chemical pchem property search include: the physical state of the substance at ambient temperature (gaseous, liquid, or solid), melting point (MP) for solids, normal boiling point (BP) at 760 mmHg for liquids, vapor pressure (ideally at 25 ฐC), solubility in water (ideally at 25 ฐC) and octanol/water partition coefficient (log Kow). 3.2 Search Strategies for Conditions of Use EPA/OPPT conducted internet searches between December 2016 and January 2017 to identify the conditions of use of NMP, using CAS numbers, chemical names, synonyms, trade names, and common misspellings. Various sources were searched including, but not limited to, Page 9 of 83 ------- information reported to EPA (e.g., Chemical Data Reporting8 and the Toxics Release Inventory9), trade publications, reports in the open literature, or citations in EPA and international assessments10. To identify formulated products, EPA searched for safety data sheets (SDS) using internet searches, EPA's Chemical and Product Categories (CPCat) data, the National Institute for Health's (NIH) Household Product Database, and other resources in which a SDS could be found. Each SDS was then cross-checked with company websites to make sure that each product SDS was current. The list of products was crosschecked with public data, publicly available literature, and trade publications to find known uses of NMP. SDS dated prior to 2000 were excluded if additional sources supporting their accuracy could not be located. The full list of data sources for conditions of use information can be found in the public use document for NMP released as background material for the public meeting on February 14, 2017 (https://www.regulations.gov/docket?D=EPA-HQ-QPPT-2016-0743). EPA/OPPT also communicated with companies and industry groups to make sure the list of uses was correct, complete, and up-to-date. EPA/OPPT integrated into the scope document for this chemical relevant public input submitted to the docket for the public meeting (EPA-HQ-OPPT-2017-0002) and for this chemical, (EPA-HQ-OPPT-2016-0743), as well as information from other engagements with stakeholders. Summaries of the public engagement are in this chemical's docket (EPA-HQ-OPPT-2016-0743). 3.3 Search Strategies for Fate, Engineering/Occupational Exposure, Exposure, and Human Health Hazard A broad search and a targeted search were conducted. The fate, engineering, exposure, and human health hazard topic areas were searched broadly to capture data and/or information that would be necessary for preparing the environmental and occupational exposure assessments- For the scope documents, a second targeted search was conducted to locate information needed to create the lifecycle diagrams and conceptual models. The first three sections below discuss the broad search, while the fourth describes the targeted lifecycle/conceptual model search. 3.3.1 Use of Existing Assessments Where possible, EPA/OPPT used existing U.S. government assessments or summaries as a starting point for the literature searches when these assessments asked similar literature search questions to the current TSCA assessment. 3.3.2 Peer-Reviewed Literature Database Search Strategies A professional librarian developed the database search strategies for each topic area by: 1) Considering search terms and data sources identified EPA/OPPT's assessment team, 2) Considering strategies used for human health hazard in IRIS documents, 3) Incorporating known chemical synonyms for NMP (see Appendix B), and 8 Chemical Data Reporting (CDR) under TSCA: https://www.epa.gov/chemical-data-reporting 9 Toxics Release Inventory (TRI) Program: https://www.epa.gov/toxics-release-inventorv-tri-program 10 e.g., EPA/OPPT TSCA Work Plan assessments, https://www.epa.gov/assessing-and-managing-chemicals-under- tsca/assessments-tsca-work-plan-chemicals Page 10 of 83 ------- 4) Tailoring terms for each database to make use of any additional details or categories available in that database (e.g., MeSH terms for the PubMed search strategy and research areas for the Web of Science search). Relevant subject headings and text words were crafted into a search strategy that was designed to maximize the sensitivity and specificity of the search results (Appendix B). Because each database has its own search architecture, the resulting search strategy was tailored to account for each database's unique search functionality. The search strategies were executed, and EPA/OPPT is in the process of assessing their performance (see Section 6). Literature search results were imported into EndNoteฎ reference management software to automatically remove duplicates. Since EndNote may not remove all duplicates, additional duplicates were identified and removed manually by comparing fields (e.g., title, author, year). All of the unique references were then sent to Health & Environmental Research Online (HERO)11, where they were assigned a unique HERO ID linked to their citation information. 3.3.3 Gray Literature Search Strategies Automated searches were used to gather information from the gray literature using Google API (application program interface), with custom code to "scrape" (i.e., locate and download) all the targeted PDFs (e.g., NIOSH Health Hazard Evaluations). Some sites required manual searching, including databases and those with internal search functions (see Table Apx_C-2). The complete list of sites and search methods is in Appendix C. The following data sources were considered when generating the list of websites/sources to search: Lists of sources identified by EPA/OPPT's assessment team, U.S. and International Government and Non-Government Organizations (NGOs) websites, Chemical/production dictionaries/encyclopedias, References used for the searches for conditions of use identified in EPA/OPPT's public use documents, State government websites covering environmental quality/management, environmental health/human health, and occupational health and safety, Trade Associations websites of member organizations from the National Association of Manufacturers (http://www.nam.org/Alliances/CMA/CMA-Member-Organizations/) and additional trade groups identified by the assessment team (Appendix C). Each trade group website was reviewed to identify data and/or information related to the potential uses of NMP based on the information reported in the public use document. If the industrial sector was likely to engage in use activity identified in the public use document, the sector was included in the list of trade associations. In general, different search terms were required for the different sources depending on the content structure of the website; all sources and search terms are documented in Appendix C. EPA/OPPT reviewed the list of sources; sites that were initially considered but removed during 11 EPA/OPPT plans to use the HERO database for the draft risk evaluation, https://hero.epa.gov/hero/ Page 11 of 83 ------- the search process are also listed in Appendix C. In general, these were sites requiring subscription/membership, sites that provided duplicative information, or sites that were not operational at the time of the search. The search was performed by going to all URLs in the gray literature sources list and searching for NMP-specific information. The search results were either PDF's or a URL describing the search result. Because each result did not have a pre-made citation that could appear in a bibliography, each search result was assigned as a specific "result ID", and the PDF was named to match that result ID. 3.3.4 Initial Lifecycle/Conceptual Model Targeted Search Specific sources from the gray literature search were used to inform the initial lifecycle diagram and initial conceptual models; these sources were chosen based on existing SOPs and expert judgment by engineers. The sources searched are denoted in Appendix C with an asterisk. In addition, the existing assessment for NMP was consulted for on-topic information. The results of the search are included in the "N-Methylpyrrolidone (NMP)(CASRN: 872-50-4) Bibliography: Supplemental File for the TSCA Scope Document". As with the broad gray literature search, the search was performed by going to the URLs and searching for NMP-specific information. The search results were either PDF's or a URL describing the search result. 3.4 Search Strategies for Environmental hazard For the ECOTOX database, the ecological literature was identified through comprehensive and well-documented literature searches using the ECOTOX SOPs12. These searches are conducted manually or electronically. Manual searches consist of skimming of reference sections of review or summary articles that are not the primary source of data, and papers that document test method procedures. Electronic searches consist of searching electronic abstracting services such as Science Direct, Agricola, Toxline, Scifinder, and Proquest. Sources and search terms are documented in Appendix D. 4 Step 3 and 4: Develop Inclusion/Exclusion Criteria and Tags to Categorize Search Results 4.1 Inclusion/Exclusion Criteria for Physical/Chemical Properties Pchem studies were eligible for inclusion if they provided values on the exact substance. If a value for the exact substance could not be found, then a close structural analog was located and a value was extrapolated to the substance in question. If no primary data or close analog data was available, computer estimation programs were used. All estimated values as well as measured ones are critically reviewed and deemed reasonable based on professional judgement. Studies were excluded from further consideration if they had the following characteristics: Lack of reporting data for the pchem property of interest, Inadequate reporting of methodology used to measure pchem property, 12 ECOTOX and related SOPs (https://cfpub.epa.gov/ecotox/help.cfm?helptabs=tab4) Page 12 of 83 ------- Inadequate characterization of the chemical substance of interest, including impurities. These general criteria were used to identify relevant studies reporting the pchem properties of NMP. 4.2 Inclusion/Exclusion Criteria for Conditions of Use Information from sources available to EPA/OPPT, including information reported to EPA/OPPT, trade publications, internet searches, public comments, stakeholder meetings, and public databases, among others, was eligible for inclusion if it provided data or information on: Manufacturing, processing, distribution, use or disposal data or relevant information about this chemical, Trends in manufacturing (including import) volumes of this chemical, Number and location of sites that manufacture, process, distribute, use, recycle, or dispose of this chemical, Functional uses for this chemical, Which industry sectors use this chemical, What concentrations (weight fraction) of this chemical are used in industrial, commercial, and consumer applications, What types of products or articles contain this chemical, Methods of distribution, e.g. internet sales, What volume of this chemical is used for each type of use, Which uses have been discontinued or phased out, The likelihood that other chemicals will replace this chemical and the names of the other chemicals,13 The likelihood that this chemical will replace other chemicals with similar functional uses,13 Uses for recycled materials containing this chemical and volume of material recycled, Approximate number and description of individuals who can be exposed to this chemical, e.g. industrial workers, commercial workers, high-frequency consumer use, low-frequency consumer use, children, The typical setting for uses (e.g. outdoors, indoors, industrial commercial, residential, vehicular). Data or information not within these characteristics were excluded for further consideration. 4.3 Inclusion/Exclusion Criteria and Tags for Fate, Engineering/Occupational Exposure, Exposure, and Human Health Hazard Because the searches were designed to be broad, they necessarily returned results that are not on topic for EPA/OPPT's risk evaluations. Based on the information needs identified in Step 1, EPA/OPPT developed specific criteria to determine which references should be tagged as "on- topic" (inclusion criteria) and "off-topic" (exclusion criteria). These were created for each topic area, with gray literature having additional inclusion/exclusion criteria for each source as 13 Information on alternative chemicals sometimes provides useful information for the exposure assessment. Page 13 of 83 ------- presented in Section 4.4. The gray literature source-specific criteria are in Appendix C. Specific inclusion/exclusion criteria were not developed for the lifecycle/conceptual model search; the search was conducted by engineers with experience developing lifecycle diagrams and conceptual models, and professional judgment was used to determine which resources were on-topic. Additional sub-categories (or sub-tags) were also included in the tagging structure to allow for additional categorization by source type (e.g., published peer reviewed article versus government report); data type (a primary data source versus a review article or assessment document); topic area (e.g., tagging general population exposure separately from consumer exposure), and chemical-specific and use-specific data or information. These sub-categories are described in Appendix E and will be used to organize the different streams of evidence during the stages of data evaluation and integration. These steps are not reported in the scope document but will be documented in the draft risk evaluation. Although these sub-categories are discussed in this document, they are not included in the in the "N-Methylpyrrolidone (NMP)(CASRN: 872-50-4) Bibliography: Supplemental File for the TSCA Scope Document" because EPA/OPPT is currently reviewing and refining the results of the categorization, including possible changes to the tagging structure. 4.4 Inclusion/Exclusion Criteria for Fate, Engineering/Occupational Exposure, Exposure, and Human Health Hazard Gray Literature The gray literature includes a diverse set of sources that were searched using either a manual or automated search technique. The following overall inclusion/exclusion criteria were applied to the gray literature in conjunction with judgment based on subject matter expertise. The ecological search results were assessed using different criteria. 1. General Inclusion Criteria for Gray Literature: Quantitative data retrieved from database searches Documents that contain quantitative information or assessments of the chemical of interest White papers, position papers, regulatory lists, and other information that summarizes how a particular government/agency prioritizes or characterizes the chemical of interest Data provided to the Agency by chemical companies and other stakeholders that is publicly available, Additional links within the website that link to sites within the same domain/agency Information about best practices for remediating or limiting exposure to the chemical 2. General Exclusion Criteria for Gray Literature: Documents not available to the public, including information stored within EPA's firewall that is not accessible on the EPA webpage (e.g., TSCA submissions), Confidential Business Information, and information requiring a paid subscription or membership for access Links that were broken at the time of the search Public comments (usually those without quantitative data) on documents other than the EPA/OPPT existing chemicals dockets Page 14 of 83 ------- High level fact sheets and PowerPoint presentations that primarily translate scientific information for the public Case studies (primarily occupational exposure) that do not have quantitative information Documents that do not explicitly mention the chemical of interest FR notices with no quantitative values Documents that describe analytical method development but provide no actual measurements useful for characterizing exposure Documents captured in searches of other sources Researcher CVs and contact information Documents reached via a link on the website that are from other government websites Landing pages with links, when those links are also captured by the search General lists of resources Peer-reviewed articles - peer reviewed literature was assumed to be captured in searches of the databases of peer-reviewed literature. Draft or earlier versions of documents previously captured Duplicate documents (same exact document found in two different result ID's for the same chemical) These criteria were applied to each gray literature resource, and that application required some judgment. Thus, Table A3.2 in Appendix C provides information specific to that source that indicates how the inclusion and exclusion criteria were interpreted and applied. 4.5 Inclusion/Exclusion Criteria and Tags for Environmental hazard On-topic (or applicable) ecological studies obtained through the ECOTOX literature search were required to meet specific acceptability criteria. Additionally, rejection criteria were developed and are documented through ECOTOX codes. Specific details concerning the inclusion/exclusion criteria for ecological studies are included in Appendix E. 5 Step 5: Screen Search Results 5.1 Screening and Tagging for Physical/Chemical Properties The screening of pchem studies was conducted by an experienced chemist, who applied the inclusion/exclusion criteria when reviewing the title and abstract, and if necessary, the full text, of the studies. Following the identification of relevant studies, the chemist reviewed the quality and acceptability of the studies. The included studies are cited in Section 2.2 and Table 2-1 of the scope document. No tagging was developed or incorporated for the information on pchem properties. 5.2 Screening and Tagging for Conditions of Use EPA/OPPT screened literature and publicly-available databases, among other sources, to identify information on this chemical's manufacturing, processing, distribution, use, and disposal. Preliminary information was included in the public use document. No tagging was done for this information on conditions of use. Page 15 of 83 ------- 5.3 Screening and Tagging for Fate, Engineering/Occupational Exposure, Exposure, and Human Health Hazard 5.3.1 Peer-Reviewed Literature Database Search Results Following the database search, the references were imported into DRAGON14, a database system used to manage aspects of the systematic review process, including literature screening, risk of bias evaluation, and data integration for screening and tagging. DRAGON was used to facilitate the title/abstract screening across a large team. DRAGON allows references to be assigned to different individuals for screening, it allows tracking of the status of screening, and it stores all of the screening decisions. DRAGON does not perform any of the screening; all screening is done manually by trained individuals. The title and abstract of each reference identified by the literature search was reviewed/screened, by a single reviewer, to determine if the study was on-topic or off-topic. On-topic references were then tagged, or categorized, using the topic area tags. All individuals who conducted the screening were trained and provided instructions and definitions of tags as shown in Appendix D. As part of the training process, a senior-level technical expert in the topic area of interest independently reviewed the appropriateness of the assigned tags for the first batch of studies reviewed by an individual screener and provided feedback to the screener. Necessary revisions or clarifications to the screening/tagging instructions and definitions were made and circulated to all screeners. Senior-level technical experts also provided feedback and guidance on specific references to the individual screeners as needed during the screening and tagging process. At the conclusion of the title and abstract review for all topic areas, all final tags applied to references were exported from DRAGON and then uploaded into the HERO database. 5.3.2 Gray Literature Search Results Screening and tagging for the gray literature was performed using Excel to organize and tag the unique search results. Because these types of references generally do not have titles and abstracts, screening and tagging was done on the full text. For references that were searched using the Google API, up to 100 unique results were retrieved for each URL searched. All 100 were then screened to determine if they were on-topic or off-topic. For references that had to be searched manually, the screener went to each URL and screened all available information for NMP on that site, preferentially searching by CAS number. During a pilot phase of the broad search, each screener tagged 10 references, which were independently reviewed by the senior level technical expert. Discrepancies between the screener and the technical expert were discussed generating specific feedback to the screener before he/she continued with tagging. After the pilot phase, the remaining results were reviewed and tagged according to the tagging structure. A targeted gray literature search was conducted and an experienced engineer screened the search results to support the development of the initial lifecycle diagram/conceptual models. 14 EPA/OPPT is in the process of migrating from DRAGON to Distiller for the next steps of the screening process, https://www.icf.com/solutions-and-apps/dragon-online-tool-svstematic-review Page 16 of 83 ------- 5.4 Screening and Tagging for Environmental hazard The ECOTOX inclusion/exclusion criteria were used to identify on-topic and off-topic ecological studies. Reviewers used codes to record the reasons for including or excluding studies. Additional details about the screening and coding procedures can be found in the document "ECOTOX Literature Searches, Citation, Identification and Skimming", https://cfpub.epa.gov/ecotox/blackbox/help/ECOTOXLiteratureSearchesCitationldentificationa ndSkimming.pdf. 6 Step 6. Quality Assessment Procedure for Screening and Tagging Before proceeding with systematic review and data evaluation, EPA/OPPT will assess the specificity and efficiency of the literature searches. Examples of how EPA/OPPT plans to evaluate the performance of the search strategies include: Comparison of the references cited in existing EPA/OPPT TSCA problem formulation and risk assessment documents against those identified by the initial search, Comparison of the references cited in the public use documents and supporting the life cycle diagrams against those found by the initial search, and Comparison of the references cited in review articles. EPA/OPPT will also assess the performance of the categorization (or tagging) conducted during the title/abstract screening for both the peer-reviewed and gray literature. As a result, some references may move from the on-topic to the off-topic category, and vice versa. Additional on- topic references could be identified and targeted supplemental searches may be conducted during the analysis phase (e.g., to locate specific information for exposure modeling). Page 17 of 83 ------- APPENDICES A. LITERATURE SEARCH INFORMATION NEEDS FOR N- METHYLPYRROLIDONE (NMP) A-l Fate Information Needs Table_Apx A-l. Fate Information Needs for N-Methylpyrrolidone (NMP) Objectives Information Needs All Objectives Fate and transport related pchem properties (e.g., octanol-water partition coefficient, organic carbon-water partition coefficient, Henry's Law constant), Bioaccumulation and bioconcentration, biodegradation and metabolism, abiotic degradation (e.g., hydrolysis, photolysis, abiotic reduction), Removal processes in wastewater treatment plants, and Environmental mobility A-2 Engineering/Occupational Exposure Information Needs Table_Apx A-2. Engineering/Occupational Exposure Information Needs for N- Methylpyrrolidone (NMP) Objectives Information Needs All Objectives (including both Occupational Exposure and Environmental Releases) Description of the life cycle of the chemical(s) of interest, from manufacture to end-of-life (e.g., each manufacturing, processing, or use step), and material flow between the industrial and commercial life cycle stages. The total annual US volume (Ib/yr or kg/yr) of the chemical(s) of interest manufactured, imported, processed, and used; and the share of total annual manufacturing and import volume that is processed or used in each life cycle step. Description of processes, equipment, unit operations, and material flows and frequencies (Ib/site-day or kg/site-day and days/yr; Ib/site-batch and batches/yr) of the chemical(s) of interest during each industrial/ commercial life cycle step. Note: if available, include weight fractions of the chemicals (s) of interest and material flows of all associated primary chemicals (especially water). Basic chemical properties relevant for assessing exposures and releases, e.g., molecular weight, normal boiling point, melting point, physical forms, and room temperature vapor pressure. Number of sites that manufacture, process, or use the chemical(s) of interest for each industrial/ commercial life cycle step and site locations. Occupational Exposures Description of worker activities with exposure potential during the manufacture, processing, or use of the chemical(s) of interest in each industrial/commercial life cycle stage. Potential routes of exposure (e.g., inhalation, dermal). Physical form of the chemical(s) of interest for each exposure route (e.g., liquid, vapor, mist) and activity. Breathing zone (personal sample) measurements of occupational exposures to the chemical(s) of interest, measured as time-weighted averages (TWAs), short-term exposures, or peak exposures in each occupational life cycle stage (or in a workplace scenario similar to an occupational life cycle stage). Page 18 of 83 ------- Area or stationary measurements of airborne concentrations of the chemical(s) of interest in each occupational setting and life cycle stage (or in a workplace scenario similar to the life cycle stage of interest). For solids, bulk and dust particle size characterization data. Dermal exposure data. Information needs associated with mathematical modeling (will be determined on a case-by- case basis). Exposure duration. Exposure frequency. Number of workers who potentially handle or have exposure to the chemical(s) of interest in each occupational life cycle stage. Personal protective equipment (PPE) types employed by the industries within scope. Engineering controls employed to reduce occupational exposures in each occupational life cycle stage (or in a workplace scenario similar to the life cycle stage of interest), and associated data or estimates of exposure reductions Environmental Releases Description of sources of potential environmental releases, including cleaning of residues from process equipment and transport containers, involved during the manufacture, processing, or use of the chemical(s) of interest in each life cycle stage. Estimated mass (lb or kg) of the chemical(s) of interest released from industrial and commercial sites to each environmental medium (air, water, land) and treatment and disposal methods (publicly owned treatment works (POTW), incineration, landfill), including: o Releases per site and aggregated over all sites; o Annual release rates; o Daily release rates; o Release or emission factors; and o Number of release days per year. Information needs associated with mathematical modeling (will be determined on a case-by- case basis). Waste treatment methods and pollution control devices employed by the industries within scope and associated data on release/emission reductions. A-3 Exposure Information Needs Table_Apx A-3. Exposure Information Needs for N-Methylpyrrolidone (NMP) Objectives Information Needs Lifecycle, general population, and consumer exposures What products contain this chemical? What articles contain this chemical? How are products/articles typically disposed of? What are the use patterns/frequencies for different age groups for the products/articles? Are there existing assessments (including modeled data) looking at exposure to the general population? Are there existing assessments (including modeled data) looking at exposure to consumers? What specific activities have the potential for consumer exposures to chemicals? What are the likely routes of exposure? What are the number of consumers potentially exposed? Are any modeled exposures available? Presence in the environment/ Biomonitoring data Is there monitoring data for the concentration of this chemical in: o Foods, either individually or as a "market basket" o Drinking water in the United States, either from well water or public drinking water sources Page 19 of 83 ------- o Ambient Air o Indoor Air o Indoor Dust o Soil o Wastewater/sludge o Sediment o Plant life/crops/biota o Terrestrial Wildlife/livestock/fish/ aquatic wildlife o Blood (for US populations) o Urine (for US populations) o Cord blood (for US populations) o Human tissues (for US populations) Environmental Releases Are there documented populations near manufacturing facilities or in other hot spots receiving higher-than-average exposure? Is there chemical-specific emission rate data for the products/articles containing the chemical? A-4 Human Health Information Needs Table_Apx A-4. Human Health Information Needs for N-Methylpyrrolidone (NMP) Objectives Information Needs Overall Objectives Identify and document all health hazards associated with exposure to the chemical via all relevant routes, durations and sources/pathways of exposure, using hazard data from: o Animal and human (epidemiological and experimental) studies o Acute/immediate effects, delayed acute effects, chronic/long-term effects Identify critical health effect(s) such as acute effects, low-dose effects and/or severe effects (e.g., cancer, non-cancer target organ effects, reproductive/developmental effects) o Identify key studies for critical effect(s) o Identify dose (or concentration)-response data Identify points of departures (PODs) for critical effect(s) for each relevant exposure route (e.g., inhalation, oral, dermal) and exposure duration (e.g., acute, sub chronic and chronic) Toxicokinetics Identify toxicokinetic data, i.e. on absorption, distribution, metabolism, excretion (ADME): o Animal and human studies o In vitro studies o Modelled ADME data o Physiologically-based pharmacokinetic (PBPK) models Mode of Action (MOA) Identify studies that support a MOA for critical effects e.g., for threshold or non-threshold cancer and non-cancer effects from: Page 20 of 83 ------- o In vitro mechanistic studies o Genotoxicity studies o In vivo mechanistic studies o Experimental studies in humans o Studies that link exposure to a carcinogenic effect Occupational Exposures Characterization of health effects associated with occupational exposures: o Health effects associated with various exposure routes and/or physical forms of the chemical o For solid dusts - differences in health effects associated with particle size fraction Potentially Exposed and Susceptible Subpopulations Characterization of factors that may make humans more vulnerable to develop adverse effects B. DATABASE (PEER-REVIEWED) LITERATURE SEARCHES FOR FATE, ENGINEERING/OCCUPATIONAL EXPOSURE, EXPOSURE, AND HUMAN HEALTH HAZARD B-l N-methylpyrrolidone (NMP) Synonyms These are the synonyms of NMP that were considered during the development of the database searches for fate, engineering, exposure and human health hazard information. N-methylpyrrolidone N-methyl-gamma- NMP butyrolactam l-methyl-2-pyrrolidinone Methylpyrrolidone N-methyl-2-pyrrolidinone n-methyl-alpha-pyrrolidone 872-50-4 l-Methyl-2-pyrrolidon l-methyl-2-pyrrolidinone, l-Methyl-5-pyrrolidinone anhydrous l-metil-2-pirrolidona N-Methyl pyrrolidone 2-Pyrolidinone, 1-methyl- N-Methyl-2-pyrrolidone 2-Pyrrolidone, 1-methyl- N-Methyl-2-pyrrolidinone Microposit 2001 Methyl-pyrrolidone M-Pyrol NMP-EL N-Methyl-2-ketopyrrolidine NMP-T N-METHYL-2- N-methylpyrrolidnone PYRROLIDINONE N-methylpyrrolidinone N-METHYL-2-PYRROLIDON N-methylpyrrolid-2-one N-Methylbutyrolactam N-methylpyrolidone N-Methyl-a-pyrrolidinone l-Methyl-2-pyrrolidone N-Methyl-a-pyrrolidone 1-methylpyrrolidone N-Methyl-y-butyrolactam l-methylazacyclopentan-2- NSC 4594 one Pharmasolve Page 21 of 83 ------- Pyrol M PYRROLIDIN-2-ONE, 1- METHYL- 1-Methylpyrrolidinone N-methyl-alpha- pyrrolidinone N-methyl-alpha- pyrrolidone N-methyl-gamma- butyrolactam B-2 Literature Search Strategies for Database Literature Searches for Fate, Engineering/Occupational Exposure, and Exposure Table_Apx B-l. NMP Fate, Engineering/Occupational Exposure, and Exposure Search Strategy for Web of Science Search Search Strategy Chemical Terms* (l-Methyl-2-pyrrolidon OR l-Methyl-5-pyrrolidinone OR 1-methylpyrrolidone OR M- Pyrol OR N-Methyl-2-ketopyrrolidine OR N-methyl-alpha-pyrrolidinone OR N- Methylbutyrolactam OR N-methyl-gamma-butyrolactam OR l-methyl-2-pyrrolidinone OR l-Methyl-2-pyrrolidone OR 2-Pyrolidinone,-l-methyl- OR 2-Pyrrolidone,-l-methyl- OR 872-50-4 OR Methylpyrrolidone OR N-methyl-2-pyrrolidinone OR N-METHYL-2- PYRROLIDON OR N-Methyl-2-pyrrolidone OR N-methyl-alpha-pyrrolidone OR N- methylpyrolidone OR N-methylpyrrolidinone OR N-methylpyrrolidone OR N-Methyl- pyrrolidone OR N-Methyl-a-pyrrolidone OR Pharmasolve OR PYRROLIDIN-2-ONE,-l- METHYL) Use Terms AND (Acetylene-recovery OR agricultur* OR Batter* OR Bedding OR Belt* OR Bib* OR Bind* OR Blanket* OR Bodysuit* OR bond* OR Bone-graft OR Cast-nylon OR children OR Circuit-board OR clean* OR Clonitralide-mixture OR Cloth* OR Coalescing-agent* OR coating* OR Cumberbund* OR degreas* OR Doll OR dolls OR Dress* OR dye* OR electronic* OR Ethanolamine-salt OR Filler* OR Film-remov* OR finish* OR Flea* OR Foam-stabilizer OR Food-contact OR Footwear OR Gasket-remov* OR Gas-purification OR Glazing-material* OR Graffiti-remov* OR Granular-fungicide* OR Hair OR Herbicide* OR High-temperature-polymer* OR Hydraulic-frac* OR Ink OR Inkjet OR Insect* OR Insulation-remov* OR intermediate OR Laundry-detergent OR Leather OR Lube-oil OR Lubricant* OR Mascara OR Nail-adhesive OR Nail-polish OR Nail-salon OR Niclosamide* OR Paint* OR Parasiticide* OR Pet-care OR petrochemical* OR Pharmaceutical* OR Photoresist-remov* OR Pigment-dispersant* OR Pipe-cement OR Pisicide* OR plastic* OR Polamideimide* OR Polish OR Polyaramid* OR Polymeric-reside-remov* OR Polythersulfone* OR Polyurethane-curative OR Polyurethane-remov* OR Polyurethane- tag OR Print* OR resin* OR Rheology-additive* OR Rust-inhibit* OR Rust-preventive OR Seal* OR Shoes OR Shorts OR Skin OR Slimicide* OR Soldering-flux OR Solvent* OR Spinning-agent* OR Strip* OR Super-glue-remov* OR Textile* OR Thickener OR Tick* OR Tile-Grout OR Top-coat OR Toy OR toys OR Trouser* OR Underwear OR varnish OR Vitamin-E OR Waterborne-finish* OR Waterproof* OR Weed-killer* OR Wire-enamel OR Wood-preservative*) Exposure, Engineering, & Fate Terms OR ((OECD AND Guideline*) OR (OPPTS AND guideline*) OR (OCSPP AND Guideline*) OR abiotic OR absorb OR absorption OR accumulation-rate OR activi* OR adipose OR adsorp* OR aerob* OR aerosol OR aerosols OR aged OR aggregate OR air OR amount- used OR anaerob* OR analy* OR anoxic OR area-source OR atm-m3/mol OR automotive OR BAF OR BCF OR bioaccumulat* OR bioavail* OR bioconcentrat* OR biodegrad* OR biomagnification OR biomoni* OR biosolids OR biota OR biotrans* OR breakdown- product OR breakdown-products OR breastmilk OR breast-milk OR breathing-zone OR Page 22 of 83 ------- brush-applied OR BSAF OR BSAFs OR building-envelope OR chamber OR chelation OR children OR coagulation OR coating OR commercial OR complexation OR cone* OR consumer OR contamination OR controls OR crawling OR creatinine OR cultural OR cumulative OR decay-rate OR degrad* OR degreaser OR dermal OR detect OR diffusion- coefficient OR disadvantaged OR disease OR dispers* OR disposal OR dissolution OR distribution OR diy OR do-it-yourself OR dose OR drinking-water OR dust OR education- level OR effluent OR elderly OR emission OR emissions OR engineering-controls OR English-as-a-second-language OR environmental-fate OR environmental-justice OR ethnicity OR evaporation-from-water OR excretion OR exposure OR facili* OR Female OR Females OR fence-line-population OR fetal OR fetus OR fish* OR flocculation OR flux OR formula OR fugacity OR garage OR gas-phase-mass-transfer OR gender OR general- population OR genetic-polymorphism OR genetic-traits OR geography OR geophag* OR geriatric OR German-human-biomonitoring-values OR groundwater OR ground-water OR guns OR half-life OR hand-to-mouth OR health-status OR henry's-law OR hobb* OR homeless OR hydroly* OR illegal-immigrants OR immunocompromised OR import* OR incinerate OR incineration OR income OR indigenous OR indoor-outdoor-ratio OR industrial OR infants OR influent OR ingestion OR inhal* OR intake OR inter-individual OR inter-zonal-air-flow OR intra-individual OR KAW OR Kd OR kinetics OR KOA OR KOC OR lacquer OR lactat* OR landfill OR landfills OR leach* OR lifecycle OR life-cycle OR lifestage OR life-stage OR lifestages OR life-stages OR lifestyle OR liquid-phase-mass- transfer OR loading OR Male OR males OR manuf* OR mass-transfer-coefficient OR menopaus* OR metaboli* OR microcosm OR migrat* OR modified-state-space OR monitoring OR mouthing OR near-facility-population OR nutrition-status OR occupa* OR occur OR occurrence OR OCSPP OR ocular OR older-adults OR on-site-treatment OR oral OR overspray-fraction OR partic* OR particle-size OR particulate OR partition* OR pathway OR pathways OR penetration-factor OR penetration-ratio OR perinatal OR persisten* OR personal OR photoly* OR photostability OR pica OR placenta OR plasma OR plume OR PM-10 OR PM-2.5 OR point-source OR point-sources OR pore-water OR postnatal OR POTW OR PPE OR preexisting-disease OR pregnan* OR prenatal OR preparedness OR pretreatment-program OR process* OR product OR protective OR proximity OR race OR recover* OR recreation* OR recycling OR redox OR release OR releases OR remed* OR residential OR residual OR rolled OR route OR routes OR rural OR sample OR samples OR school-age* OR sediment OR senior OR seniors OR sensitiv* OR serum OR SES OR sewage-treatment OR short-term OR shower* OR single-parent OR single-parents OR sink OR sinks OR site OR sites OR skin OR sludge OR socioeconomic- status OR soil OR solvent OR solvents OR sorb* OR sorp* OR source OR sources OR spray-applied OR stress* OR subpopulation OR subsistence OR subsurface-intrusion OR Superfund OR surface-water-concentration OR susceptib* OR time-weighted-average OR toddler OR toddlers OR transfer OR transformation OR tribal OR trophic-magnification OR urban OR urine OR use OR uses OR vapor OR ventilat* OR volatil* OR volume OR vulnerab* OR wait-time OR wastewater-treatment OR water OR weight-fraction OR wildlife OR wipe OR women-of-childbearing-age OR Worker OR workers OR workplace OR WWTP OR young) Limits Refined by: RESEARCH AREAS: (AGRICULTURE OR GEOCHEMISTRY GEOPHYSICS OR CONSTRUCTION BUILDING TECHNOLOGY OR PUBLIC ENVIRONMENTAL OCCUPATIONAL HEALTH OR MARINE FRESHWATER BIOLOGY OR MATERIALS SCIENCE OR METEOROLOGY ATMOSPHERIC SCIENCES OR ENGINEERING OR MINING MINERAL PROCESSING OR ENVIRONMENTAL SCIENCES ECOLOGY OR WATER RESOURCES OR ZOOLOGY) lndexes=SCI-EXPANDED, SSCI Date of Search: 2/28/2017 'Synonyms not found in Web of Science were removed from search string Page 23 of 83 ------- B-3 Literature Search Strategies for Database Literature Searches for Human Health Table_Apx B-2. N-Methylpyrrolidone (NMP) Human Health Hazard Peer-Reviewed Literature Search Strategy Search Search Strategy Pub Med1 Chemical Terms (l-methyl-2-pyrrolidinone[tiab] OR l-methyl-2-pyrrolidinone[Supplementary Concept] OR l-Methyl-2-pyrrolidone[tiab] OR 2-Pyrolidinone,-l-methyl-[tiab] OR 2-Pyrrolidone,-l- methyl-[tiab] OR 872-50-4[rn] OR Methylpyrrolidone[tiab] OR N-methyl-2- pyrrolidinone[tiab] OR N-METHYL-2-PYRROUDON[tiab] OR N-Methyl-2-pyrrolidone[tiab] OR N-methyl-alpha-pyrrolidone[tiab] OR N-methylpyrolidone[tiab] OR N- methylpyrrolidinone[tiab] OR N-methylpyrrolidone[tiab] OR N-Methyl-pyrrolidone[tiab] OR N-Methyl-a-pyrrolidone[tiab] OR Pharmasolve[tiab] OR PYRROUDIN-2-ONE,-l- METHYL[tiab]) Health Effect Terms AND ((DNA[tiab] AND breaks[tiab]) OR absorption[tiab] OR absorption[mh] OR activate[tiab] OR activated[tiab] OR acute[tiab] OR adverse[tiab] OR adverse-effects[sh] OR Ames- assay[tiab] OR Ames-test[tiab] OR animal[tiab] OR blood[tiab] OR blood[mh] OR brain[mh] OR brain[tiab] OR cancer[tiab] OR carcinogen[tiab] OR carcinogenesis[tiab] OR carcinogenic[tiab] OR carcinogenicity[tiab] OR carcinogens[tiab] OR carcinogens[mh] OR cardiac[tiab] OR case-control[tiab] OR case-control-studies[mh] OR case-referent[tiab] OR case-report[tiab] OR case-reports[tiab] OR case-reports[pt] OR cell[tiab] OR cell- proliferation [mh] OR cells[tiab] OR cells[mh] OR chemokine[tiab] OR chemokines[tiab] OR chromosomal-aberration[tiab] OR chromosomal-aberration[tiab] OR chromosomal- aberrations[tiab] OR chromosomal-aberrations[mh] OR chronic[tiab] OR cognitive[tiab] OR cohort[tiab] OR cohort-studies[mh] OR congenital-abnormalities[mh] OR corrosion[mh] OR corrosion[tiab] OR crosslink[tiab] OR cytogenicity[tiab] OR cytokine[tiab] OR cytokines[tiab] OR cytokines[mh] OR cytotoxic[tiab] OR cytotoxicity[tiab] OR dam[tiab] OR dams[tiab] OR death[mh] OR death[tiab] OR dermal[tiab] OR detoxification[tiab] OR detoxify[tiab] OR development[tiab] OR developmental[tiab] OR diet[mh] OR diet [tiab] OR dietary[tiab] OR diets[tiab] OR distribution[tiab] OR DNA-adduct[tiab] OR DNA-adducts[mh] OR DNA-adducts[tiab] OR DNA-breaks[mh] OR DNA-damage[mh] OR DNA-damage[tiab] OR DNA-repair[mh] OR DNA-repair[tiab] OR dog[tiab] OR dogs[tiab] OR dogs[mh] OR dose[tiab] OR drinking- water[tiab] OR drinking-water[mh] OR eliminate[tiab] OR elimination[tiab] OR embryo[tiab] OR embryonic[tiab] OR embryos[tiab] OR employee[tiab] OR employees[tiab] OR endocrine[tiab] OR endpoint[tiab] OR endpoints[tiab] OR enteral- nutrition[mh] OR epidemiologic[tiab] OR epidemiological[tiab] OR epidemiology[mh] OR epidemiology[sh] OR epidemiology[tiab] OR epigenetic[tiab] OR epigenetics[tiab] OR epigenomics[tiab] OR epigenomics[mh] OR female[tiab] OR females[tiab] OR fetal[tiab] OR fetus[tiab] OR fetus[mh] OR fetuses[tiab] OR gavage[tiab] OR Gene[tiab] OR gene- expression[mh] OR genes[tiab] ORgenes[mh] OR genetic[tiab] OR genetics[tiab] OR genotoxic[tiab] OR genotoxicity[tiab] OR germ-line-mutation[tiab] ORgerm-line- mutation[mh] OR growth-and-development[mh] OR guinea-pig[tiab] ORguinea- pigs[tiab] OR guinea-pigs[mh] OR hamster[tiab] OR hamsters[tiab] OR hazard[tiab] OR heart[tiab] OR heart[mh] OR hemotoxic[tiab] OR hemotoxicity[tiab] OR hemotoxin[tiab] OR hemotoxins[tiab] OR hepatic[tiab] OR hepatotoxic[tiab] OR hepatotoxicity[tiab] OR hepatotoxin[tiab] OR hepatotoxins[tiab] OR human[tiab] OR humans[tiab] OR humans[mh] OR immunotoxic[tiab] OR immunotoxicity[tiab] OR immunotoxin[tiab] OR immunotoxins[tiab] OR immunotoxins[mh] OR incidence[tiab] OR incidences[tiab] OR individual[tiab] OR individuals[tiab] OR inflammation[tiab] OR inflammation[mh] OR inflammatory[tiab] OR inhalation[tiab] OR inhalation[mh] OR inhale[tiab] OR inhaled[tiab] OR inhibit[tiab] OR inhibited[tiab] OR inhibitory[tiab] OR interact[tiab] OR Page 24 of 83 ------- Search Search Strategy interacted[tiab] OR interaction[tiab] OR intestine[tiab] OR intestines[tiab] OR intestines[mh] OR in-vitro[tiab] OR in-vitro-techniques[mh] OR in-vivo[tiab] OR irritation[tiab] OR kidney[tiab] OR kidney[mh] OR LC50[tiab] OR LD50[tiab] OR lethal- concentration-50[tiab] OR Lethal-Dose-50[tiab] OR Lethal-Dose-50[mh] OR litter[tiab] OR litters[tiab] OR liver[tiab] OR liver[mh] OR LOAEC[tiab] OR LOAEL[tiab] OR LOEL[tiab] OR longitudinal[tiab] OR long-term-adverse-effects[mh] OR lung[tiab] OR lung[mh] OR male[tiab] OR malformation[tiab] OR malformations[tiab] OR malformed[tiab] OR malignancies[tiab] OR malignancy[tiab] OR malignant[tiab] OR margin-of-exposure[tiab] OR maternal[tiab] OR mechanism[tiab] OR mechanisms[tiab] OR mechanistic[tiab] OR metabolism[tiab] OR metabolism[mh] OR metabolism[sh] OR metastasis[tiab] OR metastasize[tiab] OR metastatic[tiab] OR mg/kg/day[tiab] OR mg/kg-bw/day[tiab] OR mg/L[tiab] OR mg/m3[tiab] OR mg-kg/day[tiab] OR mice[mh] OR mice[tiab] OR micronuclei[tiab] OR micronucleus[tiab] OR mode-of-action[tiab] OR monkey[tiab] OR monkeys[tiab] OR mortality[mh] OR mortality[tiab] OR mouse[tiab] OR mouth[tiab] OR mouth[mh] OR mutagen[tiab] OR mutagenesis[tiab] OR mutagenic[tiab] OR mutagens[mh] OR mutagens[tiab] OR mutation[tiab] OR mutation[mh] OR nasal[tiab] OR neoplasm[tiab] OR neoplasms[tiab] OR neoplasms[mh] OR neoplastic[tiab] OR nephrotoxic[tiab] OR nephrotoxicity[tiab] OR nephrotoxin[tiab] OR nephrotoxins[tiab] OR nested[tiab] OR neurobehavior[tiab] OR neurobehavioral[tiab] OR neurologic[tiab] OR neurological[tiab] OR neurophysiological[tiab] OR neuropsychological[tiab] OR neurotoxic[tiab] OR neurotoxicity[tiab] OR neurotoxin[tiab] OR neurotoxins[tiab] OR neurotoxins[mh] OR NOAEC[tiab] OR NOAEL[tiab] OR NOEL[tiab] OR nonmalignant[tiab] OR nonneoplastic[tiab] OR nose[tiab] OR nose[mh] OR OECD-Test-Guideline[tiab] OR OECD-Test-Guidelines[tiab] OR oncogene[tiab] OR oncogenes[tiab] OR oncogenes[mh] OR oncogenesis[tiab] OR oral[tiab] OR organ[tiab] OR organs[tiab] OR ototoxic[tiab] OR ototoxicity[tiab] OR oxidative-damage[tiab] OR oxidative-stress[tiab] OR oxidative- stress[mh] OR participant[tiab] OR participants[tiab] OR paternal[tiab] OR PBPK[tiab] OR people[tiab] OR perinatal[tiab] OR person[tiab] OR pharmacodynamic[tiab] OR pharmacodynamics[tiab] OR pharmacokinetic[tiab] OR pharmacokinetics[mh] OR pharmacokinetics[tiab] OR pharmacokinetics[sh] OR pharmacology[sh] OR pharmacology[mh] OR pharmacology[tiab] OR polyploid[tiab] OR polyploidy[tiab] OR polyploidy[mh] OR postnatal[tiab] OR pregnancy[mh] OR pregnancy[tiab] OR pregnancy- complications[mh] OR pregnant[tiab] OR prenatal[tiab] OR prevalence[tiab] OR prevalent[tiab] OR promote[tiab] OR promotion[tiab] OR pulmonary[tiab] OR rabbit[tiab] OR rabbits[tiab] OR rabbits[mh] OR rat[tiab] OR rats[mh] OR rats[tiab] OR registries[mh] OR registries[tiab] OR registry[tiab] OR renal[tiab] OR reproduction[tiab] OR reproduction[mh] OR reproductive[tiab] OR reprotoxic[tiab] OR reprotoxicity[tiab] OR respiration[mh] OR respiration[tiab] OR respiratory[tiab] OR rodent[tiab] OR rodents[tiab] OR SCE[tiab] OR sensitization[tiab] OR sensitized[tiab] OR sensitizer[tiab] OR sensitizing[tiab] OR sister-chromatid-exchange[mh] OR sister-chromatid- exchange[tiab] OR skeletal[tiab] OR skin [tiab] OR skin[mh] OR subchronic[tiab] OR sub- chronic[tiab] OR subject[tiab] OR subjects[tiab] OR systemic[tiab] OR teratogen[tiab] OR teratogenic[tiab] OR teratogens[tiab] OR teratogens[mh] OR toxic[tiab] OR toxicant[tiab] OR toxicants[tiab] OR toxicity[sh] ORToxicity[tiab] ORToxicity[sh] OR toxicodynamic[tiab] OR toxicodynamics[tiab] OR toxicokinetic[tiab] OR toxicokinetics[tiab] OR toxicokinetics[mh] OR toxicology[mh] OR toxicology[tiab] OR tumor[tiab] OR tumorigenic[tiab] OR tumors[tiab] OR weight[tiab] OR worker[tiab] OR workers[tiab] OR Adolescen*[tiab] OR Adult*[tiab] OR Age[tiab] OR aged[tiab] OR age- groups[mh] OR ages[tiab] OR Alcohol[tiab] OR At-risk[tiab] OR BMI[tiab] OR body-mass- index[tiab] OR body-mass-index[mh] OR boy[tiab] OR boys[tiab] OR child[tiab] OR children [tiab] OR cigar[tiab] OR Cigarette[tiab] OR cigarettes[tiab] OR cigars[tiab] OR Coexposure[tiab] OR co-exposure[tiab] OR Critical-window*[tiab] OR Diabetes[tiab] OR diabetes-insipidus[mh] OR diabetes-mellitus[mh] OR disadvantaged[tiab] OR Early- life[tiab] OR Elderly[tiab] OR Environmental-justice[tiab] OR Ethanol[tiab] OR Ethnic[tiab] OR ethnic-groups[mh] OR ethnicit*[tiab] OR Females[tiab] OR gastrointestinal- Page 25 of 83 ------- Search Search Strategy microbiome[mh] OR Gender[tiab] OR Genotype[tiab] OR genotype[mh] OR Genotypes[tiab] OR genotypic[tiab] OR Geriatric[tiab] OR gestation[tiab] OR gestational[tiab] OR girl[tiab] OR girls[tiab] OR Gut[tiab] OR Haplotype[tiab] OR Haplotypes[tiab] OR haplotypes[mh] OR Health-status[mh] OR Health-status[tiab] OR lnequalit*[tiab] OR Inequit*[tiab] OR infancy[tiab] OR infant[tiab] OR infants[tiab] OR In- utero[tiab] OR lifestage[tiab] OR Life-stage[tiab] OR lifestages[tiab] OR Life-stages[tiab] OR Males[tiab] OR Men[mh] OR Men[tiab] OR Metagenomic[tiab] OR metagenomics[tiab] OR metagenomics[mh] OR methylation[mh] OR Methylation[tiab] OR Microbiome[tiab] OR Microbiomes[tiab] OR Microbiota[tiab] OR minorities[tiab] OR minorities[tiab] OR Minority[tiab] OR minority-groups[mh] OR Modifying-factor[tiab] OR Modifying-factors[tiab] OR natal[tiab] OR newborn[tiab] OR newborns[tiab] OR Nicotine[tiab] OR nicotine[mh] OR nutritional-status[mh] OR nutritional-status[tiab] OR placenta[mh] OR placenta[tiab] OR placental[tiab] OR Polymorphism[tiab] OR polymorphism,-genetic[mh] OR polymorphisms[tiab] OR poverty[mh] OR Poverty[tiab] OR Preexisting[tiab] OR pre-existing[tiab] OR pregnant-women[mh] OR Preschool[tiab] OR preschooler[tiab] OR preschoolers[tiab] OR Race[tiab] OR Racial[tiab] OR racism[mh] OR racism[tiab] OR Sensitive-population[tiab] OR Sensitive-populations[tiab] OR SES[tiab] OR sex[mh] OR Sex[tiab] OR smoke[tiab] OR Smoke[mh] OR smoker[tiab] OR smokers[tiab] OR smoking[tiab] OR smoking[mh] OR Sociocultural[tiab] OR sociodemographic[tiab] OR Socioeconomic[tiab] OR socio-economic[tiab] OR socioeconomic-factors[mh] OR Susceptibilities[tiab] OR Susceptibility [tiab] OR Susceptible[tiab] OR teenager[tiab] OR teenagers[tiab] OR teens[tiab] OR Tobacco[tiab] OR tobacco-products[mh] OR toddler[tiab] OR toddlers[tiab] OR underserved[tiab] OR Vulnerabilities[tiab] OR Vulnerability [tiab] OR Vulnerable[tiab] OR vulnerable- populations[mh] ORWomen[mh] OR Women[tiab] OR cardiovascular[tiab]) Limits None Date of Search: 2/1 Chemical Terms 1/2017 Web of Science2 (l-Methyl-2-pyrrolidon OR l-Methyl-5-pyrrolidinone OR 1-methylpyrrolidone OR M- Pyrol OR N-Methyl-2-ketopyrrolidine OR N-methyl-alpha-pyrrolidinone OR N- Methylbutyrolactam OR N-methyl-gamma-butyrolactam OR l-methyl-2-pyrrolidinone OR l-Methyl-2-pyrrolidone OR 2-Pyrolidinone,-l-methyl- OR 2-Pyrrolidone,-l-methyl- OR 872-50-4 OR Methylpyrrolidone OR N-methyl-2-pyrrolidinone OR N-METHYL-2- PYRROLIDON OR N-Methyl-2-pyrrolidone OR N-methyl-alpha-pyrrolidone OR N- methylpyrolidone OR N-methylpyrrolidinone OR N-methylpyrrolidone OR N-Methyl- pyrrolidone OR N-Methyl-a-pyrrolidone OR Pharmasolve OR PYRROUDIN-2-ONE,-l- METHYL) Health Effect Terms AND ((DNA AND breaks) OR absorption OR activate OR activated OR acute OR adverse OR Ames-assay OR Ames-test OR animal OR blood OR brain OR cancer OR carcinogen OR carcinogenesis OR carcinogenic OR carcinogenicity OR carcinogens OR cardiac OR case- control OR case-referent OR case-report OR case-reports OR cell OR cells OR chemokine OR chemokines OR chromosomal-aberration OR chromosomal-aberration OR chromosomal-aberrations OR chronic OR cognitive OR cohort OR corrosion OR crosslink OR cytogenicity OR cytokine OR cytokines OR cytotoxic OR cytotoxicity OR dam OR dams OR death OR dermal OR detoxification OR detoxify OR development OR developmental OR diet OR dietary OR diets OR distribution OR DNA-adduct OR DNA-adducts OR DNA- damage OR DNA-repair OR dog OR dogs OR dose OR drinking-water OR eliminate OR elimination OR embryo OR embryonic OR embryos OR employee OR employees OR endocrine OR endpoint OR endpoints OR epidemiologic OR epidemiological OR epidemiology OR epigenetic OR epigenetics OR epigenomics OR female OR females OR fetal OR fetus OR fetuses OR gavage OR Gene OR genes OR genetic OR genetics OR genotoxic OR genotoxicity OR germ-line-mutation OR guinea-pig OR guinea-pigs OR hamster OR hamsters OR hazard OR heart OR hemotoxic OR hemotoxicity OR hemotoxin Page 26 of 83 ------- Search Search Strategy OR hemotoxins OR hepatic OR hepatotoxic OR hepatotoxicity OR hepatotoxin OR hepatotoxins OR human OR humans OR immunotoxic OR immunotoxicity OR immunotoxin OR immunotoxins OR incidence OR incidences OR individual OR individuals OR inflammation OR inflammatory OR inhalation OR inhale OR inhaled OR inhibit OR inhibited OR inhibitory OR interact OR interacted OR interaction OR intestine OR intestines OR in-vitro OR in-vivo OR irritation OR kidney OR LC50 OR LD50 OR lethal- concentration-50 OR Lethal-Dose-50 OR litter OR litters OR liver OR LOAEC OR LOAEL OR LOEL OR longitudinal OR lung OR male OR malformation OR malformations OR malformed OR malignancies OR malignancy OR malignant OR margin-of-exposure OR maternal OR mechanism OR mechanisms OR mechanistic OR metabolism OR metastasis OR metastasize OR metastatic OR mg/kg/day OR mg/kg-bw/day OR mg/L OR mg/m3 OR mg-kg/day OR mice OR micronuclei OR micronucleus OR mode-of-action OR monkey OR monkeys OR mortality OR mouse OR mouth OR mutagen OR mutagenesis OR mutagenic OR mutagens OR mutation OR nasal OR neoplasm OR neoplasms OR neoplastic OR nephrotoxic OR nephrotoxicity OR nephrotoxin OR nephrotoxins OR nested OR neurobehavior OR neurobehavioral OR neurologic OR neurological OR neurophysiological OR neuropsychological OR neurotoxic OR neurotoxicity OR neurotoxin OR neurotoxins OR NOAEC OR NOAEL OR NOEL OR nonmalignant OR nonneoplastic OR nose OR OECD-Test-Guideline OR OECD-Test-Guidelines OR oncogene OR oncogenes OR oncogenesis OR oral OR organ OR organs OR ototoxic OR ototoxicity OR oxidative-damage OR oxidative-stress OR participant OR participants OR paternal OR PBPK OR people OR perinatal OR person OR pharmacodynamic OR pharmacodynamics OR pharmacokinetic OR pharmacokinetics OR pharmacology OR polyploid OR polyploidy OR postnatal OR pregnancy OR pregnant OR prenatal OR prevalence OR prevalent OR promote OR promotion OR pulmonary OR rabbit OR rabbits OR rat OR rats OR registries OR registry OR renal OR reproduction OR reproductive OR reprotoxic OR reprotoxicity OR respiration OR respiratory OR rodent OR rodents OR SCE OR sensitization OR sensitized OR sensitizer OR sensitizing OR sister-chromatid-exchange OR skeletal OR skin OR subchronic OR sub-chronic OR subject OR subjects OR systemic OR teratogen OR teratogenic OR teratogens OR toxic OR toxicant OR toxicants OR Toxicity OR toxicodynamic OR toxicodynamics OR toxicokinetic OR toxicokinetics OR toxicology OR tumor OR tumorigenic OR tumors OR weight OR worker OR workers OR Adolescen* OR Adult* OR Age OR aged OR ages OR Alcohol OR At-risk OR BMI OR body-mass-index OR boy OR boys OR child OR children OR cigar OR Cigarette OR cigarettes OR cigars OR Coexposure OR co-exposure OR Critical-window* OR Diabetes OR disadvantaged OR Early-life OR Elderly OR Environmental-justice OR Ethanol OR Ethnic OR ethnicit* OR Females OR Gender OR Genotype OR Genotypes OR genotypic OR Geriatric OR gestation OR gestational OR girl OR girls OR Gut OR Haplotype OR Haplotypes OR Health-status OR Inequalit* OR Inequit* OR infancy OR infant OR infants OR In-utero OR lifestage OR Life- stage OR lifestages OR Life-stages OR Males OR Men OR Metagenomic OR metagenomics OR Methylation OR Microbiome OR Microbiomes OR Microbiota OR minorities OR minorities OR Minority OR Modifying-factor OR Modifying-factors OR natal OR newborn OR newborns OR Nicotine OR nutritional-status OR placenta OR placental OR Polymorphism OR polymorphisms OR Poverty OR Preexisting OR pre-existing OR Preschool OR preschooler OR preschoolers OR Race OR Racial OR racism OR Sensitive- population OR Sensitive-populations OR SES OR Sex OR smoke OR smoker OR smokers OR smoking OR Sociocultural OR sociodemographic OR Socioeconomic OR socio- economic OR Susceptibilities OR Susceptibility OR Susceptible OR teenager OR teenagers OR teens OR Tobacco OR toddler OR toddlers OR underserved OR Vulnerabilities OR Vulnerability OR Vulnerable OR Women OR cardiovascular) Limits Refined by: RESEARCH AREAS: (ALLERGY OR HEMATOLOGY OR PHARMACOLOGY PHARMACY OR BIOCHEMISTRY MOLECULAR BIOLOGY OR IMMUNOLOGY OR INFECTIOUS DISEASES OR CELL BIOLOGY OR PUBLIC ENVIRONMENTAL OCCUPATIONAL HEALTH OR REPRODUCTIVE BIOLOGY OR DERMATOLOGY OR Page 27 of 83 ------- Search Search Strategy ENDOCRINOLOGY METABOLISM OR TOXICOLOGY OR NEUROSCIENCES NEUROLOGY OR VETERINARY SCIENCES OR ONCOLOGY OR GENERAL INTERNAL MEDICINE) lndexes=SCI-EXPANDED, SSCI Date of Search: 2/1' Chemical Terms 1/2017 Toxline3 (872-50-4) Health Effect Terms Identical to Web of Science Health Effect Terms Limits Include CASRNs and synonyms Exclude PubMed records Date of Search: 2/14/2017 1 Synonyms not found in PubMed were removed from consideration in the search; [mh] searched in MeSH field; [tiab] searched in title or abstract fields; [sh] searched in subheading field. 2 Synonyms not found in Web of Science were removed from consideration in the search. 3 Synonyms searched automatically Page 28 of 83 ------- C. GRAY LITERATURE SEARCHES FOR FATE, ENGINEERING/OCCUPATIONAL EXPOSURE, EXPOSURE, AND HUMAN HEALTH HAZARD The gray literature search for fate, engineering, exposure, and human health hazard was done with a goal of efficiency. For this reason, websites were automatically searched wherever possible. After creating the list of sites to search, three categories of websites were identified that required a different search strategy as explained below. Websites that can be effectively searched using Google: these websites and corresponding subsites have relevant documents that can be searched using Google. EPA/OPPT used Google's API that allows the user to create custom searches restricted by both keyword list and URL list. This approach greatly increased the speed of the searches, since code was written to implement the searches automatically. The following key restrictions, however, were encountered during the search: The API returns the first 100 sites found, after sorting for predicted relevancy. As with all Google searches, Google attempts to rank the returned URLs in terms of overall relevancy to the search terms. However, if 3,600 sites are returned by the search, only the first 100 according to Google's ranked order are returned. The search strings in Google and the Google API are restricted to 128 characters. For NMP, the following search string was created to have the maximum number of chemical synonyms/CAS numbers without exceeding 128 characters: "872-50-4" OR "N-methyl-2-pyrrolidinone" OR "N-Methyl-2-pyrrolidone" OR "N-methylpyrrolidone" OR "N-methylpyrrolidinone" Websites that can be searched using custom code but not using Google: these websites have relevant data and/or information in the form of PDFs and the searches can be automated by developing custom code that locates and downloads (i.e., "scrapes") all of the targeted PDFs. ATSDR and NIOSH documents: ATSDR has a series of Public Health Assessments and Health Consultations, and NIOSH has a series of Human Hazard Evaluations that may have documents relevant for the TSCA risk evaluation. Each document is housed at specific URLs within the ATSDR and NIOSH websites. Python code was used to automatically download 100 documents from each site. EPA National Electronic Publications Information System (NEPIS) website: The EPA NEPIS website was another one that used custom code to search. NEPIS houses EPA reports and documents that can be searched by keyword. The NEPIS site uses its own search engine that is not retrievable using Google. Thus, python code was developed to directly access the website search engine and automatically pull the top 100 returned PDFs. Websites that are searched manually: a manual search is required because the websites house a database or they use their own search engine to retrieve information (e.g., ChemView, NHANES). The overall strategy for searching these sites is shown in Table_Apx C-l. The lists of sites that were searched (with site-specific inclusion/exclusion criteria) are provided in Table_Apx C-2 and Table_Apx C-3. The sites that were originally on the list but removed during curation are provided in Table_Apx C-4. Page 29 of 83 ------- Table_Apx C-l. Overview of Search Strategy for Gray Literature for Fate, Engineering/Occupational Exposure, Exposure, and Human Health Hazard Topic Areas Search Type How was List Created? Sub Search Type How Was Source Searched? Search Terms Date Limit Literature Search Notes US Government and International Websites Compiling list of sources, sources cited in existing problem formulation and assessment documents, and sources cited in the public use document Manual (sites that cannot be searched using Google) Searched manually "872-50-4" or "N- methylpyrrolidone" OR "N- methylpyrrolidinone" None Searched all sites and subsites using the NMP CAS number (872-50-4) or the substance name (N-methylpyrrolidone OR N-methyl pyrrolidinone) Pulled the most recent draft (either draft or final) for assessments. Automated, Google API Searched using Google API "872-50-4" OR "N-methyl-2- pyrrolidinone" OR "N-Methyl-2- pyrrolidone" OR "N- methylpyrrolidone" OR "N- methylpyrrolidinone" None Search string is 120 characters (below the 128 character limit) Google's API returns the top 100 hits from each site Automated, EPANEPIS Searched using code that pulls 100 subsites/pdfs Search 1: "pyrrolidinone" Search 2: "pyrrolidone" 1991 The NEPIS database is a warehouse for EPA documents and reports, and it is not accessible by Google. ICF wrote a custom search for that website. The site is searchable by keyword only, so two searches were done using "pyrrolidinone" and "pyrrolidone" The database was searched using a date limit of 1991 to prioritize the 100 most recent EPA documents. Automated, ATSDR and NIOSH Searched using code that pulls 100 subsites/pdfs "N-Methyl-2-pyrrolidone" None Both sources contain a large number of assessments on specific subsites Up to 100 documents were downloaded for each chemical Trade Association Websites Using National Association of Manufacturers members list and public use document Google API Searched using Google API "872-50-4" OR "N-methyl-2- pyrrolidinone" OR "N-Methyl-2- pyrrolidone" OR "N- methylpyrrolidone" OR "N- methyl pyrrolidinone" None Search string is 120 characters (below the 128 character limit) Google's API returns the top 100 hits from each site State Websites Searching for environ, quality/ management, environ, health/human health, and occupational health and safety subsites Google API Searched using Google API ("872-50-4" OR "N-methyl-2- pyrrolid* OR "N- methylpyrrolid*") AND (assessment OR data) None State sites tended to have a lot of regulatory or outreach documents which are expected to be less on-topic To focus on reports, assessments, and data, the search string was modified to include the words "data" and "assessment" Page 30 of 83 ------- Table_Apx C-2. Sources Used For Gray Literature Search for Fate, Engineering/Occupational Exposure, Exposure, and Human Health Hazard Topic Areas with Source-Specific Inclusion/Exclusion Criteria ID Trusted Source Category Source Source Address Manual or Automated Search by? Search Terms1 Source-Specific Inclusion Criteria Source-Specific Exclusion Criteria 1001 US EPA Resources Office of Water: EPA Water Regulations* https://www.ep a.gov/regulator v-information- topic/regulatorv -information- topic-water Manual Chemical CAS or chemical name Drinking water regulations under development or currently in place None 1006 US EPA Resources Drinking Water Standards and Health Advisories https://www.ep a.gov/sites/prod uction/files/201 5^ 09/documents/ dwstandards201 2.pdf Manual Chemical CAS or chemical name All chemicals covered by the 2012 standards None 1008 US EPA Resources Office of Water: STORETand WQX https://www.ep a.gov/waterdata /storage-and- retrieval-and- water-qualitv- exchange Manual Chemical CAS or chemical name The database was downloaded and text files with data specific to included chemicals (metadata and results) were saved in zip files. The website states that the data warehouse includes all data supplied to EPA since 1999. None 1010 US EPA Resources Office of Air Quality Planning and Standards (OAQPS) epa.gov/airquali tyZ Automated Chemical Google API terms Documents containing information about control technologies used to control emissions FR notices not directly pertaining to chemical of interest; broken links 1011 US EPA Resources Office of Air: Air Emission Factors* https://www.ep a.gov/air- emissions- factors-and- quantifi cation/a p-42- compilation-air- emission-factors Manual Industria I Sector Sectors and uses identified from public use document and Chemical Data Reporting data Reviewed chapters to identify information relevant to industrial sectors using professional experience/judgment None 1012 US EPA Resources Office of Air: Emission Inventory Improvement Program https://www.ep a.gov/air- emissions- inventories/emi Manual NAICS Code NAICS Code This source will be searched once the assessment team determines the list of NAICS codes to search the database likely during problem formulation. Page 31 of 83 ------- ssion-inventorv- improvement- program-eiip 1013 US EPA Resources Office of Air: National Emissions Inventory (NEI) https://www.ep a.gov/air- emissions- inventories/nati onal-emissions- inventorv Manual NAICS Code NAICS Code This source will be searched once the assessment team determines the list of NAICS codes to search the database likely during problem formulation. 1014 US EPA Resources Office of Air: Ambient Water Quality Criteria documents epa.gov/wac Automated Chemical Google API terms Most-recent water quality criteria human health tables and supporting documents Previous (priorto 2015) water quality criteria documents; documents not directly pertaining to the chemical of interest 1015 US EPA Resources Office of Air: HAPS epa.gov/haps/in itial-list- hazardous-air- pollutants- modifications Automated Chemical Google API terms None Lists of chemical classified as hazardous air pollutants covered in other sources (covered in the "Lists of Lists" source) 1016 US EPA Resources Office of Air: NESHAP* epa.gov/technic al-air-pollution- resources Automated Chemical Google API terms No results returned by search No results returned by search 1031 US EPA Resources Office of Air: Urban Air Toxics https://www.ep a.gov/u rban-air- toxics/urban- air-toxic- pollutants Manual Chemical CAS or chemical name List of chemicals classified as urban airtoxics None 1032 US EPA Resources OPPT: TRI, including TRI Guidance Documents* epa.gov/tri Automated Chemical Google API terms Statistics on emission reductions. Additional data supporting the lifecycle diagram/conceptual model was reviewed using professional judgment/experience. Fact sheets, reporting forms, grant program information, data (data is provided in a different source) 1038 US EPA Resources OPPT: TSCA Analog Identification Methodology (AIM) http://www.epa .gov/tsca- screening- tools/analog- identification- methodologv- aim-tool Manual Chemical CAS or chemical name The AIM tool was downloaded and searched to find records for NMP None 1059 US EPA Resources Significant New Alternatives Policy (SNAP) epa.gov/snap Automated Chemical Google API terms None Lists of substitutes in different use sectors that link to specific FR notices from the 1990's 1061 US EPA Resources Safer Choice epa.gov/saferch oice/ Automated Chemical Google API terms None Very high-level fact sheets or assessment overviews; assessments found in other sources; staff directories 1064 US EPA Resources Pollution Prevention epa.gov/p2/ Automated Chemical Google API terms None Very high-level fact sheets and case studies; contact information Page 32 of 83 ------- 1070 US EPA Resources Pesticide Chemical Search httos://iasoub.e Da.gov/aDex/oe sticides/f?D=che micalsearchil Manual Chemical CAS or chemical name The database was searched by CAS number and all information returned was included in PDFs Additional links on the search return page (included in other sources) 1073 US EPA Resources InertFinder httDs://iasoub.e Da.gov/aoex/De sticides/f?D=101 'Al Manual Chemical CAS or chemical name The database was searched by CAS number and all information returned was included in PDFs None 1075 US EPA Resources Pesticide Ingredients eoa.gov/ingredi ents-used- pesticide- Droducts Automated Chemical Google API terms None High level summaries supporting decisions about classifying inert ingredients 1078 US EPA Resources Hazardous Waste eoa.gov/hw/ Automated Chemical Google API terms Reports to Congress or other material supporting regulatory decisions Regulatory documents 1080 US EPA Resources Superfund chemical data matrix https://www.ep a.gov/superfund /superfund- chemical-data- matrix-scdm- querv Manual Chemical CAS or chemical name The database was searched by CAS number and all information returned was included in PDFs None 1081 US EPA Resources Superfund Enterprise Management System (SEMS) cumulis.epa.gov /suoercoad/curs ites Automated Chemical Google API terms Quantitative risk assessments performed for Superfund sites General Superfund site information that did not include quantitative measures of contaminant or exposure 1083 US EPA Resources CPCat httos://actor.eD a.gov/cocat/fac es/search.xhtml Manual Chemical CAS or chemical name The database was searched by CAS number and all information returned was included in PDFs None 1090 US EPA Resources NCEA IRIS eoa.gov/iris Automated Chemical Google API terms Supporting information for IRIS assessments Main IRIS landing pages and information from the IRIS Tracker 1097 US EPA Resources NCEA IRIS https://cfpub.ep a.gov/ncea/iris/ search/ Manual Chemical CAS or chemical name IRIS overview pages, summary pages, and full toxicological profiles None 1101 US EPA Resources ChemView (CDR/IUR)*, with links to hazard characterizations, substantial risk reports, chemical reporting data, chemical test rule data, High Production Volume Information System (HPVIS) data, and alternatives assessments. htto://iava.eoa. gov/chemview Manual Chemical CAS or chemical name The database was searched by CAS number and all information returned was included in PDFs, other than IRIS assessments that were returned from other sources None Page 33 of 83 ------- 1103 US EPA Resources Stationary Sources Air Pollution eDa.gov/station arv-sources-air- oollution/ Automated Chemical Google API terms Documents supporting NESHAP that may contain quantitative data NESHAP rules and FR notices (regulatory only) 1110 US EPA Resources Economic and cost assessment eDa.gov/econo mic-and-cost- analvsis-air- Dollution- regulations Automated Chemical Google API terms Documents containing quantitative data Documents not containing quantitative data 1113 US EPA Resources NSCEP documents (NEPIS) httDs://neDis.eD a.gov/Exe/ZvNE T.exe?ZvActionL =Register&User =anonvmous&P assword=anonv mous&Client=E PA&ln it=l Automated Chemical NEPIS Documents providing quantitative assessments or data Fact sheets; documents supporting rules that do not have quantitative data 1118 US EPA Resources Regulatory Development and Retrospective Review Tracker vosemite.eoa.go v/ooei/rulegate. nsf/ Automated Chemical Google API terms None Lists of regulations expected to affect particular interests 1120 US EPA Resources "List of Lists" httos://www.eD a.gov/sites/prod uction/files/201 5^ 03/documents/l ist of lists.pdf Manual Chemical CAS or chemical name List of chemicals covered by specific EPA programs None 1123 US EPA Resources TSCATS 2.0 https://vosemit e.eoa.gov/ooDts /eoatscat8.nsf/r eDortsearch?OD enform Manual Chemical CAS or chemical name The database was searched and all low detail report results were PDFed None 1125 US EPA Resources EPA Manufacturing/Use Search epa.gov for each manufacturing sector and use and key words for each manufacturing sector Manual NAICS Code NAICS Code This source will be searched once the assessment team determines the list of NAICS codes to search the database likely during problem formulation. 1141 US EPA Resources OECA Sector Notebooks The Sector Notebooks have been archived. Conduct an internet search Manual NAICS Code NAICS Code This source will be searched once the assessment team determines the list of NAICS codes to search the database likely during problem formulation. Page 34 of 83 ------- with the keyword "OECA sector notebook" to see whether there has been a Sector Notebook prepared for the relevant industry 1143 US EPA Resources EPA Generic Scenarios* Review the list of cu rrently approved Generic Scenarios for relevant information. The scenarios provide information on process descriptions and guidelines for release and exposure estimates for specific industry sectors. Manual Industria 1 Sector Sectors and uses identified from public use document and Chemical Data Reporting data Reviewed the list of currently approved Generic Scenarios for relevant information using professional judgment/experience. The scenarios provide information on process descriptions and guidelines for release and exposure estimates for specific industry sectors. Information that does not inform the lifecycle diagram or conceptual model. 1144 US EPA Resources HPV challenge submissions* cfpub.epa.gov/h pv-s/ Automated Chemical Google API terms Documents providing information relevant to the lifecycle diagrams and conceptual model using professional judgment/experience. Additional quantitative assessments or data were also pulled as part of the broad search. Broken links 1145 US EPA Resources OPPT Hazard Characterizations httDs://ofmoub. eoa.gov/oDDthD v/hov he chara cterization.get r eoort bv cas?d octvoe=2 [the list of chemicals that have hazard characterization s] with Manual Chemical CAS or chemical name No results returned by search No results returned by search Page 35 of 83 ------- supplemental search for the hazard characterization documents, which are published at httos://iava. epa.gov/chemvi ew (source id 1101) https://ofmpub. epa.gov/oppthp v/hpv he chara cterization.get r eport bv cas?d octvoe=2 1146 US EPA Resources EHPV Program Submissions httos://www.re gulations.gov/d ocket?D=EPA- HQ-OPPT-2006- 1020 Manual Chemical CAS or chemical name No results returned by search No results returned by search 1147 US EPA Resources CDAT httDs://iava.eoa .sov/oDDt chem ical search/ Manual Chemical CAS or chemical name The database was searched by CAS number and all information returned was included in PDFs None 1148 US EPA Resources OPPT Risk-Based Prioritizations https://iaspub.e pa.gov/oppthpv /existchem hov prioritizations.r eport [the list of chemicals that have prioritizations] with supplemental search for the prioritization reports, which are published at https://iava. eoa.gov/chemvi ew (source id 1101)httDs://ias Dub.eoa.gov/oD Manual Chemical CAS or chemical name No results returned by search No results returned by search Page 36 of 83 ------- Dthov/existche m hov crioritiz ations.reoorthtt Ds://iasDub.eoa. gov/oppthpv/ex istchem hpv pr ioritizations.rep ort 1149 US EPA Resources Office of Air: NATA https://www.ep a.gov/national- air-toxics- assessment/201 1-nata- assessment- resultsSoollutan t Manual Chemical CAS or chemical name The database was searched by CAS number and all information returned was included in zip files None 1150 US EPA Resources Office of Air: AQS htto://aasdrl.e pa.gov/aasweb/ aqstmp/airdata/ download files. html#Annual Manual Chemical CAS or chemical name The database was searched by CAS number and all information returned was included in csv files None 1151 US EPA Resources OPPT Monitoring Database Monitoring database Manual Chemical CAS or chemical name All monitoring data None 1152 US EPA Resources TSCA public use document and stakeholder input https://www.ep a.gov/assessing- and-managing- chemicals- under- tsca/evaluating- risk-existing- chemicals- under-tsca Manual Chemical CAS or chemical name Quantitative data, use information, and information in public input None 1153 US EPA Resources TSCA Problem Formulations, Risk Assessments, and Public Comments httos://www.eD a.gov/assessing- and-managing- chemicals- under- tsca/assessment s-tsca-work- plan-chemicals Manual Chemical CAS or chemical name Quantitative data, lifecycle information, production information, use information, and information in public comments None 2001 Other US Agency Resources National Institutes of Health (NIH) ChemlDplus http://chem.sis. nlm.nih.gov/che midolus/ Manual Chemical CAS or chemical name The database was searched by CAS number and the result page (with active links) PDFed The PDF has active links, but not all links were followed and subsequently tagged Page 37 of 83 ------- 2010 Other US Agency Resources NIH PubChem Compound Database httos://www.nc bi.nlm.nih.gov/o ccomoound Manual Chemical CAS or chemical name The database was searched by CAS number and the result page (with active links) PDFed The PDF has active links, but not all links were followed and subsequently tagged 2018 Other US Agency Resources NIH HazMap* httD://hazmao.n lm.nih.gov/inde x.html Manual Chemical CAS or chemical name The database was searched by CAS number and the result page (with active links) PDFed Additional data supporting the lifecycle diagram/conceptual model was reviewed using professional judgment/experience. The PDF has active links, but not all links were followed and subsequently tagged 2019 Other US Agency Resources NIH Household Products Database http://househol dproducts.nlm.n ih.gov/ Manual Chemical CAS or chemical name The database was searched by CAS number and the result page (with active links) PDFed The PDF has active links, but not all links were followed and subsequently tagged 2020 Other US Agency Resources NIH Hazardous Substance Data Bank (HSDB)* https://toxnet.n lm.nih.gov/newt oxnet/hsdb.htm Manual Chemical CAS or chemical name The database was searched by CAS number and the result page (with active links) PDFed Additional data supporting the lifecycle diagram/conceptual model was reviewed using professional judgment/experience. None 2021 Other US Agency Resources NIH LACTMED httos://toxnet.n lm.nih.gov/newt oxnet/lactmed.h tm Manual Chemical CAS or chemical name No results returned by search No results returned by search 2022 Other US Agency Resources NIH NLM Drug Information Portal https://druginfo .nlm.nih.gov/dr ugportal/ Manual Chemical CAS or chemical name The database was searched by CAS number and all information returned was included in zip files None 2027 Other US Agency Resources NTP Report on Carcinogens (RoC) https://ntp.nieh s.nih.gov/oubhe alth/roc/index- l.html#C Manual Chemical CAS or chemical name Report on Carcinogens substance profiles Fact sheets; scientific review documents (covered in another source) 2028 Other US Agency Resources NTP Report on Carcinogens (RoC) Supplemental Materials httos://ntD.nieh s.nih.gov/oubhe alth/roc/listings /index.html Manual Chemical CAS or chemical name Report on Carcinogens 2013 monograph, substance information sheets, nomination documents, and review documents Older Report on Carcinogens monographs (2013 document is comprehensive) 2039 Other US Agency Resources NTP Health Assessment and Translation Completed Reports httos://ntD.nieh s.nih.gov/pubhe alth/hat/noms/i ndex.html Manual Chemical CAS or chemical name NTP monographs for applicable chemicals from list of all documents. None 2100 Other US Agency Resources CDC ATSDRTox Profiles* http://www.ats dr.cdc.gov/toxpr ofiles/index.asp Manual Chemical CAS or chemical name ATSDR tox profiles None 2101 Other US Agency Resources CDC ATSDR Minimal Risk Levels (MRLs) for Hazardous Substances https://www.ats dr.cdc.gov/mrls/ mrllist.asD Manual Chemical CAS or chemical name Minimum risk levels None 2103 Other US Agency Resources CDC ATSDR atsdr.cdc.gov/ Automated Chemical ATSDR/ NIOSH Case studies; addendums to tox profiles Fact sheets; quantitative information already given in tox profiles; documents that do not provide quantitative data Page 38 of 83 ------- 2104 Other US CDC ATSDR Health www.atsdr.cdc. Automated Chemical ATSDR/ Health Hazard Consultations forthe chemicals None Agency Hazard Consultations gov/hac/oha/ NIOSH of interest Resources 2111 Other US Agency Resources CDC National Report on Human Exposure to Environmental Chemicals cdc.gov/exoosur ereoort/index.h tml Manual Chemical CAS or chemical name NHANES data summaries None 2113 Other US Agency Resources CDC NIOSH* cdc.gov/niosh/ Automated Chemical ATSDR/ NIOSH Documents providing quantitative data. Additional data supporting the lifecycle diagram/conceptual model was reviewed using professional judgment/experience. Documents captured in manual search; methods for detection (NMAM manuals); peer review articles captured in peer- reviewed literature search; draft versions of documents previously captured; letters; PowerPoint presentations for public; very high-level fact sheets and case studies; public comments; documents discussing TALC (asbestos free); case report on single occupational exposure; general lists of resources. 2115 Other US Agency CDC NIOSH* htto://www.cdc .gov/niosh/npg/ Manual Chemical CAS or chemical Selected entries from list by Chemical Name and CAS number; NIOSH Pocket Guide to None Resources npgdcas.html name Chemical Hazards captured for all chemicals. Additional data supporting the lifecycle diagram/conceptual model was reviewed using professional judgment/experience. 2116 Other US Agency Resources CDC NIOSH htto://www.cdc .gov/niosh/tooic s/chemical.html Manual Chemical CAS or chemical name Documents from chemical-topic pages. Methods for detection (NMAM manuals); documents captured in other NIOSH manual search; linked out documents from other government agencies. 2123 Other US CDC NIOSH Health httos://www2a. Manual Chemical CAS or Human hazard evaluation reports Human hazard evaluation reports that do not Agency Hazard Evaluations* cdc.gov/hhe/sea chemical measure chemicals of interest Resources rch.asp name 2125 Other US CDC NIOSH https://www.cd Manual Chemical CAS or Immediately Dangerous to Life or Health None Agency Immediately c.gov/niosh/idlh chemical summary pages captured for all chemicals, Resources Dangerous to Life or Health /intridW.html name selected from list. 2128 Other US CDC NIOHS https://www.cd Manual Chemical CAS or Searched by CAS number; International None Agency International c.gov/niosh/ipcs chemical Chemical Safety Cards (ICSC) captured for all Resources Chemical Safety Cards (ICSC) neng/nengcas.h tml name chemicals. 2200 Other US Agency Resources Bureau of Labor Statistics (BLS) bls.gov/ Automated Chemical Google API terms No results returned by search No results returned by search 2202 Other US Agency Census Bureau census.gov Automated NAICS Code NAICS Code This source will be searched once the assessment team determines the list of NAICS codes to search the database likely during problem formulation. Resources Page 39 of 83 ------- 2204 Other US Agency Resources Census Bureau: NAICS Determination* htto://www.cen sus.gov/eos/ww w/naics/ Manual NAICS Code NAICS Code Data supporting the lifecycle diagram/conceptual model was reviewed using professional judgment/experience. None 2205 Other US Agency Resources Census Bureau: SIC and NAICS codes htto://www.cen sus.gov/eos/ww w/naics/concor dances/concord ances.html Manual NAICS Code NAICS Code This source will be searched once the assessment team determines the list of NAICS codes to search the database likely during problem formulation. 2206 Other US Agency Resources Census Bureau: Current Industrial Reports http://www.cen sus.gov/manufa cturing/cir/inde x.html Manual NAICS Code NAICS Code This source will be searched once the assessment team determines the list of NAICS codes to search the database likely during problem formulation. 2207 Other US Agency Resources Census Bureau: Annual Survey of Manufacturers http://www.cen sus.gov/orogra ms- survevs/asm.ht ml: htto://www.cen sus.gov/manufa cturing/asm/ind ex.html Manual NAICS Code NAICS Code This source will be searched once the assessment team determines the list of NAICS codes to search the database likely during problem formulation. 2208 Other US Agency Resources Census Bureau: County Business Patterns http://www.cen sus.gov/progra ms- survevs/cbp.ht ml: htto://www.cen sus.gov/econ/cb o/index.html Manual NAICS Code NAICS Code This source will be searched once the assessment team determines the list of NAICS codes to search the database likely during problem formulation. 2210 Other US Agency Resources Census Bureau: Data Sources for Manufacturing from the US Census Bureau htto://www.cen sus.gov/econ/m anufacturing.ht ml Manual NAICS Code NAICS Code This source will be searched once the assessment team determines the list of NAICS codes to search the database likely during problem formulation. 2211 Other US Agency Resources Census Bureau: American Housing Survey https://www.ee nsus.gov/progra ms- survevs/ahs/dat a/interactive/ah stablecreator.ht ml#?s areas=aO Manual None CAS or chemical name This source will be searched once the assessment team determines the list of NAICS codes to search the database likely during problem formulation. OOOO&s vear=n 2015&S tableN ame=Tablel&s Page 40 of 83 ------- bvGrouol=al&s bvGrouo2=al& s filterGrouol=t l&s filterGrouo 2zgl 2212 Other US Agency Resources Census Bureau: American Community Survey http://www.cen sus.gov/acs/ww w/data/data- tables-and- tools/data- profiles/2015/ Manual None CAS or chemical name This source will be searched once the assessment team determines the list of NAICS codes to search the database likely during problem formulation. 2213 Other US Agency Resources Census Bureau: Commodity Flow Survey http://www.cen sus.gov/econ/cf sZ Manual NAICS Code NAICS Code This source will be searched once the assessment team determines the list of NAICS codes to search the database likely during problem formulation. 2214 Other US Agency Resources Census Bureau: Foreign Trade htto://www.cen sus.gov/foreign- trade/about/ind ex.html Manual NAICS Code NAICS Code This source will be searched once the assessment team determines the list of NAICS codes to search the database likely during problem formulation. 2215 Other US Agency Resources Census Bureau: Survey of Plant Capacity Utilization htto://www.cen sus.gov/manufa ctu ring/capacity L Manual NAICS Code NAICS Code This source will be searched once the assessment team determines the list of NAICS codes to search the database likely during problem formulation. 2216 Other US Agency Resources Census Bureau: Statistics of US Businesses http://www.cen sus.gov/progra ms- survevs/susb/da ta.html Manual NAICS Code NAICS Code This source will be searched once the assessment team determines the list of NAICS codes to search the database likely during problem formulation. 2217 Other US Agency Resources CPSC Consumer Product Safety Commission cosc.gov/ Automated Chemical Google API terms No results returned by search No results returned by search 2300 Other US Agency Resources FDA Food and Drug Administration fda.gov Automated Chemical Google API terms Chemicals of interest noted in drug labels, drug use, or other documents; guidance for industry documents; FR notices with helpful use/product information or quantitative values; Relevant GRAS notices; FDA Total Diet Study Survey results; list of prohibited chemicals for cosmetics. Documents captured in manual search; CV of FDA researchers, FR notices with no quantitative values; documents related to drugs for mesothelioma treatment; public comments with no quantitative data; documents that state chemical measured in product, but not detected; PowerPoint presentations for public; very high-level fact sheets; citizen petition. 2301 Other US Agency Resources FDA Databases accessdata.fda.g ovI Automated Chemical Google API terms Chemicals of interest noted in drug labels, drug use, production info or other relevant documents; FR notices with helpful use/product information or quantitative values. Documents captured in manual search; FR notices with no quantitative values; documents discussing TALC (asbestos free); documents with no chemical-specific information; DCM mentioned as used as a Page 41 of 83 ------- solvent; methods for detection; very high- level fact sheets. 2304 Other US FDA Cumulative http://www.acc Manual Chemical CAS or Searched by CAS number; all Cumulative None Agency Estimated Daily essdata.fda.gov/ chemical Estimates Daily Intakes captured for chemicals Resources Intake scripts/sda/sdN avigation.cfm?s d=edisrev name having this information. 2306 Other US FDA Everything htto://www.fda. Manual Chemical CAS or Database searched by CAS number; all entries None Agency Added to Food in the gov/Food/lngre chemical captured. Resources United States (EAFUS) dientsPackaging Labeling/FoodA dditiveslngredie nts/ucmll5326. htm name 2307 Other US FDA List of Indirect http://www.fda. Manual Chemical CAS or Database searched by CAS number; all entries None Agency Additives Used in gov/Food/lngre chemical captured. Resources Food Contact Substances dientsPackaging Labeling/Packag ingFCS/lndirect Additives/ucml 15333.htm name 2400 Other US OSHA Occupational osha.gov/ Automated Chemical Google API Regulatory limits; reports with quantitative Detection methods papers; factsheets and Agency Safety and Health terms data; data from the occupational chemical evaluation guidance Resources Administration database 2414 Other US OSHA Chemical https://www.os Manual Chemical CAS or OSHA PELs. Additional data supporting the None Agency Exposure Health ha.gov/ooengov chemical lifecycle diagram/conceptual model was Resources Data* /healthsamoles. html name reviewed using professional judgment/experience. 2502 Other US Agency Resources NIST NIST.gov Automated Chemical Google API terms Conference proceedings that may not be in peer-reviewed search Peer-reviewed articles; detection method papers 2504 Other US NOAA CAMEO httDs://cameoc Manual Chemical CAS or The database was searched by CAS number and None Agency database hemicals.noaa.g chemical the result page PDFed Resources ov/ name 2507 Other US Protective Action httos://sD.eota. Manual Chemical CAS or The database was searched by CAS number and None Agency Criteria (PAC) energv.gov/oac/ chemical the result page PDFed Resources Database teel/search.html name 2509 Other US Agency Resources US Geological Survey usgs.gov Automated Chemical Google API terms Documents providing quantitative data. Peer reviewed papers; employee contact information; 2511 Other US Department of www.energv.go Automated Chemical Google API Medical Surveillance Program information and Fact sheets; documents containing no Agency Energy V terms needs assessments quantitative data Resources Page 42 of 83 ------- 2512 Other US Agency Resources PNNL Pacific Northwest National Laboratory Dnnl.gov/ Automated Chemical Google API terms Documents providing quantitative data. Fact sheets; employee contact information; documents that do not provide quantitative data 2513 Other US Agency Resources US Geological Survey publications httDs://oubs.er. usgs.gov/ Automated Chemical Google API terms Groundwater quality data; documents containing use information or quantitative data Peer reviewed papers; documents that do not provide quantitative data 3000 International Resources European Commission ec.europa.eu Manual Chemical CAS or chemical name Documents containing quantitative data or use information Documents not containing quantitative data or use information 3005 International Resources European Commission eur- lex.europa.eu/c ollection/eu- law.html Automated Chemical Google API terms Documents containing quantitative data or use information Documents not containing quantitative data or use information 3057 International Resources ECHA Documents echa.europa.eu/ documents/ Manual Chemical CAS or chemical name Documents containing quantitative data or use information Documents not containing quantitative data or use information 3100 International Resources IARC Monograph http://monogra phs.iarc.fr/ENG/ Monographs/PD Fs/index.oho Manual Chemical CAS or chemical name Most-recent IARC monographs Previous (not current) IARC monographs 3150 International Resources OECD HPV Programme htto://webnet.o ecd.org/hov/ui/ Search.asox Manual Chemical CAS or chemical name Initial assessments, final assessments, and recommendations None 3155 International Resources OECD Emission Scenario Documents* oecd.org/chemi calsafetv/risk- assessment/emi ssionscenariodo cuments.htm Manual NAICS Code NAICS Code Data supporting the lifecycle diagram/conceptual model was reviewed using professional judgment/experience. None 3156 International Resources OECD Substitution and Alternatives Assessment Tool Selector - Case Studies oecdsaatoolbox. org/Home/Case Manual Chemical CAS or chemical name The database was searched by CAS number and the result page PDFed None Studies 3200 International Resources United Nations Environment Program (UNEP) uneo.org/ Automated Chemical Google API terms No results returned by search No results returned by search 3250 International Resources WHO Institutional Repository for Information Sharing (IRIS) apps.who.int/iri sL Automated Chemical Google API terms Documents containing quantitative data or use information Documents not containing quantitative data or use information 3253 International Resources World Health Organization- Regional Office for Europe euro.who.int/en /home Automated Chemical Google API terms None Fact sheets Page 43 of 83 ------- 3300 International Resources Stockholm Convention on Persistent Organic Pollutants htto://chm.DODS .int/TheConvent ion/ThePOPs/Lis tingofPOPs/tabi d/2509/Default. aspx Manual Chemical CAS or chemical name Risk Profiles None 3350 International Resources Australian Government: Department of Health, National Industrial Chemicals; NICNAS nicnas.gov.au/ Automated Chemical Google API terms Chemical profiles; public reports with quantitative data; Regulatory lists; fact sheets; reports with no quantitative data 3421 International Resources Canada Chemicals Portal chemicalsubsta nceschimiaues.g c.ca/index- eng.php Manual Chemical CAS or chemical name Screening assessments and general descriptions of Canada's actions on chemicals of interest Documents not containing quantitative data or use information 3425 International Resources Carex Canada carexcanada.ca/ en/ Automated Chemical Google API terms Documents containing quantitative data or use information Documents not containing quantitative data or use information 3450 International Resources GESTIS Database http://limitvalue .ifa.dguv.de/ Manual Chemical CAS or chemical name Lists of international regulatory limits None 3520 International Resources Government of Japan: Ministry of the Environment env.go.ip/en/ Automated Chemical Google API terms Documents containing quantitative data or use information Documents not containing quantitative data or use information 3600 International Resources Substances in Preparations in Nordic Countries (SPIN) Database httD://www.soi n2000.net/spin myphp/ Manual Chemical CAS or chemical name The database was searched by CAS number and the result page PDFed None 5000 Other Resources Lowell Center for Sustainable Production sustainableprod uction.org Automated Chemical Google API terms Documents containing quantitative data or use information; recommendations or overall chemical summaries Fact sheets; press releases; older versions of current reports (e.g., causes of cancer) 5011 International Resources eChemPortal htto://www.ech emportal.org/ec hemportal/inde x?pagelD=0&re quest locale=en Manual Chemical CAS or chemical name The database was searched by CAS number and the result page PDFed None 5014 Other Resources Toxicology Excellence for Risk Assessment http://www.ter a.org/ Manual Chemical CAS or chemical name Documents containing quantitative data or recommendations for analysis Documents not containing quantitative data or recommendations for analysis 5019 Other Resources Consumer Products Information Database (CPID) https://www.w hatsinproducts.c om/chemicals/i ndex/1 Manual Chemical CAS or chemical name The database was searched by CAS number and the result page PDFed None 5020 Other Resources Pollution Prevention Infohouse infohouse.p2ric. org/ Automated Chemical Google API terms Documents containing quantitative data or regulatory lists of chemicals by state Documents not containing quantitative data or regulatory lists of chemicals by state Page 44 of 83 ------- 5027 Other Resources Kirk Othmer Encyclopedia* Book Manual Chemical CAS or chemical name Searched by chemical name in volume index. Captured all entries pertaining to chemical of interest. Brief mentions of chemical in entries for other chemicals not included in this search 5028 Other Resources Ashford's Dictionary of Industrial Chemicals, 2001 Book Manual Chemical CAS or chemical name Searched by chemical name in index. Captured dictionary entries for chemical of interest. None 5029 Other Resources Hawley's Chemical Dictionary, 2016 Book Manual Chemical CAS or chemical name Searched by chemical name in index. Captured dictionary entries for chemical of interest. None 6000 States Custom search engine using States sites (see separate table) multiple Automated Chemical States Documents containing quantitative data or regulatory lists of chemicals by state Documents not containing quantitative data or regulatory lists of chemicals by state, including fact sheets 7141 Trade/ Professional American Composites Manufacturers Association www.acmanet.o Ig Automated Chemical Google API terms Trade association websites were searched by search strings containing CAS number and common chemical synonyms. If a search result Documents such as news releases that do not contain quantitative data beyond general use information. Documents describing analytical 7142 Trade/ Professional Aerospace Industries Association of America www.aia- aerospace.org Automated Chemical Google API terms was a pdf file it was captured automatically, otherwise a webpage with active links was captured. On-topic documents included processes where chemical was used in apparatus, reagent, or reference material. Documents describing non-current use such 7144 Trade/ Professional American Chemistry Council www.americanc hemistrv.com Automated Chemical Trade association terms industrial processes and uses, production and trade data, court proceedings, regulatory response from industry, and regulatory as pre 1980 uses of asbestos. Documents describing alternative use compounds to the chemical being searched. 7146 Trade/ Professional Asphalt Roofing Manufacturers Association www.asohaltroo fing.org Automated Chemical Trade association terms guidance documents. 7153 Trade/ Professional Chemistry Industry Association of Canada www.canadianc hemistrv.ca Automated Chemical Trade association terms 7156 Trade/ Professional European Flame Retardant Association www.cefic- efra.com Automated Chemical Trade association terms 7159 Trade/ Professional Consumer Specialty Products Association www.cspa.org Automated Chemical Trade association terms 7163 Trade/ Professional European Brominated Flame Retardant Industry Panel www.ebfrip.org Automated Chemical Trade association terms 7172 Trade/ Professional Juvenile Products Manufacturers Association www.ipma.org Automated Chemical Trade association terms 7176 Trade/ Professional National Association of Manufacturers www.nam.org Automated Chemical Trade association terms 7200 Trade/ Professional Phosphorous, Inorganic, & Nitrogen www.pinfa.org Automated Chemical Trade association terms Page 45 of 83 ------- Flame Retardants Association 7201 Trade/ Professional Plastic Pipes Institute www.plasticpip e.org Automated Chemical Trade association terms 7209 Trade/ Professional Structural Insulated Panel Association www.sips.org Automated Chemical Trade association terms 7210 Trade/ Professional Society of Chemical Manufacturers and Affiliates www.socma.co m Automated Chemical Trade association terms 7224 Trade/ Professional American Composites Manufacturers Association www.acmanet.o Ig Automated Chemical Trade association terms 7233 Trade/ Professional American Fiber Manufacturers Association www.afma.org Automated Chemical Trade association terms 7235 Trade/ Professional American Foundry Society www.afsinc.org Automated Chemical Trade association terms 7237 Trade/ Professional American Gas Association www.aga.org Automated Chemical Trade association terms 7242 Trade/ Professional Air-Conditioning, Heating, & Refrigeration Institute www.ahrinet.or g Automated Chemical Trade association terms 7245 Trade/ Professional Aluminum Association www.aluminum. org Automated Chemical Trade association terms 7247 Trade/ Professional Association for Manufacturing Excellence www.ame.org Automated Chemical Trade association terms 7250 Trade/ Professional American Chemistry Council www.americanc hemistrv.com Automated Chemical Trade association terms 7254 Trade/ Professional American National Standards Institute www.ansi.org Automated Chemical Trade association terms 7256 Trade/ Professional American Petroleum Institute www.aoi.org Automated Chemical Trade association terms 7260 Trade/ Professional The Adhesive and Sealant Council www.ascouncil. org Automated Chemical Trade association terms Page 46 of 83 ------- 7266 Trade/ Professional American Wood Council www.awc.org Automated Chemical Trade association terms 7274 Trade/ Professional Business & Institutional Furniture Mfrs Association www.bifma.org Automated Chemical Trade association terms 7281 Trade/ Professional Can Manufacturers Institute www.cancentral .com Automated Chemical Trade association terms 7295 Trade/ Professional European Chlorinated Solvents Association www.chlorinate d-solvents.eu Automated Chemical Trade association terms 7298 Trade/ Professional Council of Industrial Boiler Owners www.cibo.org Automated Chemical Trade association terms 7300 Trade/ Professional American Cleaning Institute www.cleaningin stitute.org Automated Chemical Trade association terms 7304 Trade/ Professional Copper Development Association Inc www.copper.or g Automated Chemical Trade association terms 7308 Trade/ Professional Consumer Specialty Products Association www.csoa.org Automated Chemical Trade association terms 7346 Trade/ Professional Flexible Packaging Association www.flexoack.o Ig Automated Chemical Trade association terms 7354 Trade/ Professional Gasket Fabricators Association www.gasketfab. com Automated Chemical Trade association terms 7358 Trade/ Professional Global Automakers www.globalauto makers.org Automated Chemical Trade association terms 7359 Trade/ Professional Grocery Manufacturers Association www.gmaonline ฆorg Automated Chemical Trade association terms 7374 Trade/ Professional Halogenated Solvents Industry Alliance, Inc. (HSIA) www.hsia.org Automated Chemical Trade association terms 7382 Trade/ Professional Independent Lubricant Manufacturers Association www.ilma.org Automated Chemical Trade association terms 7386 Trade/ Professional Association of Nonwoven Fabrics Industry www.inda.org Automated Chemical Trade association terms Page 47 of 83 ------- 7392 Trade/ Professional Association Connecting Electronics Industries www.ioc.org Automated Chemical Trade association terms 7395 Trade/ Professional Institute of Scrap Recycling Industries www.isri.org Automated Chemical Trade association terms 7396 Trade/ Professional The Worldwide Cleaning Industry Association www.issa.com Automated Chemical Trade association terms 7398 Trade/ Professional Juvenile Products Manufacturers Association www.ipma.org Automated Chemical Trade association terms 7419 Trade/ Professional Motor & Equipment Manufacturers Association www.mema.org Automated Chemical Trade association terms 7433 Trade/ Professional National Association for Surface Finishing www.nasf.org Automated Chemical Trade association terms 7440 Trade/ Professional National Electrical Manufacturers Association www.nema.org Automated Chemical Trade association terms 7444 Trade/ Professional Natural Gas Supply Association www.ngsa.org Automated Chemical Trade association terms 7453 Trade/ Professional N-Methylpyrrolidone Producers Group, Inc. www.nmpgroup .com Automated Chemical Trade association terms 7471 Trade/ Professional Petroleum Equipment Institute www.pei.org Automated Chemical Trade association terms 7473 Trade/ Professional Personal Care Products Council www.personalc arecouncil.org Automated Chemical Trade association terms 7483 Trade/ Professional Precision Machined Products Association www.Dmoa.org Automated Chemical Trade association terms 7485 Trade/ Professional Power Tool Institute, Inc. www.oowertool institute.com Automated Chemical Trade association terms 7489 Trade/ Professional Printing Industries of America www.orinting.or g Automated Chemical Trade association terms 7490 Trade/ Professional Pressure Sensitive Tape Council www.ostc.org Automated Chemical Trade association terms Page 48 of 83 ------- 7498 Trade/ Professional Roof Coatings Manufacturers Association www. roof co at in fis-org Automated Chemical Trade association terms 7502 Trade/ Professional Specialty Equipment Market Association www.sema.org Automated Chemical Trade association terms 7511 Trade/ Professional Society of Manufacturing Engineers www.sme.org Automated Chemical Trade association terms 7513 Trade/ Professional Society of Chemical Manufacturers & Affiliates www.socma.co m Automated Chemical Trade association terms 7516 Trade/ Professional Steelworks www.steel.org Automated Chemical Trade association terms 7520 Trade/ Professional Textile Care Allied Trades Association www.tcata.org Automated Chemical Trade association terms 7531 Trade/ Professional Textile Rental Services Association of America www.trsa.org Automated Chemical Trade association terms 7541 Trade/ Professional Vinyl Siding Institute www.vinvlsiding ฆorg Automated Chemical Trade association terms 7554 Trade/ Professional Extruded Polystyrene Foam Association www.xpsa.com Automated Chemical Trade association terms * Asterisk denotes sources that were part of the lifecycle/conceptual model search. 1 See Table_Apx C-l for list of search terms and keywords Page 49 of 83 ------- Table_Apx C-3. List of State Websites Included in the "States" Search for Fate, Engineering/Occupational Exposure, Exposure, and Human Health Hazard Topic Areas State Type Title URL Alabama Environment Alabama Department of Environmental Management www.adem.state.al.us Alabama Occupational Health Alabama Occupational Safety and Health www.labor.alabama.sov Alabama Environmental Health/Health Environmental - Home - Alabama Department of Public Health www.adDh.ors/environmental Alaska Environment Alaska Department of Environmental Conservation - State of Alaska www.dec.alaska.gov Alaska Environment Environment - Environment Alaska www.environmentalaska.us Alaska Occupational Health Alaska Occupational Safety and Health Section - Alaska Department... www.labor.state.ak.us/lss/oshhome.htm Arizona Environment ADEQ Arizona Department of Environmental Quality | Our mission is ... www.azdea.gov Arizona Occupational Health ADOSH Main Page | Industrial Commission of Arizona www.azica.gov/our-organization/adosh Arizona Environmental Health/Health Arizona Department of Health Services www.azdhs.gov Arizona Environmental Health/Health ADEQ Arizona Department of Environmental Quality | Our mission is ... www.azdea.sov Arizona Environmental Health/Health Arizona Children's Environmental Health Program www.lesacv.azdea.sov/ceh/ Arkansas Environment Arkansas Department of Environmental Quality (ADEQ) www.adea.state.ar.us Arkansas Occupational Health Occupational Health and Safety Compliance Program www.labor.arkansas.sov/occuoational- safetv-and-health-compliance-program- aosh Arkansas Environmental Health/Health ADH: Environmental Health - Arkansas Department of Health www.healthv.arkansas.Eov California Environment California Environmental Protection Agency: CalEPA www.calepa.ca.Eov California Environment California Department of Conservation www.conservation.ca.Eov California Environment California Department of Toxic Substances Control www.dtsc.ca.Eov California Occupational Health Occupational Health Branch main page - California Department of ... www.cdph.ca.Eov California Occupational Health Cal/OSHA - Division of Occupational Safety and Health - Home Page www.dir.ca.Eov/dosh California Environmental Health/Health Biomonitoring California www.biomonitorins.ca.Eov California Environmental Health/Health Office of Environmental Health Hazard Assessment www.oehha.ca.sov California Environmental Health/Health Department of Public Health: Environmental Health www.cdDh.ca.Eov/Drosrams/Pases/Center EnvironmentalHealth.aspx Colorado Environmental Health/Health Colorado Department of Public Health and Environment www.cdohe.state.co.us Connecticut Environment Connecticut Department of Energy & Environmental Protection www.ct.sov/deo/ Connecticut Occupational Health DPH: Occupational Health Unit - CT.gov www.ct.Eov/doh/occuoationalhealth Page 50 of 83 ------- Connecticut Occupational Health Occupational Safety & Health (CONN-OSHA) - State of Connecticut... www.ctdol.state.ct.us/osha/osha.htm Connecticut Environmental Health/Health Department of Public Health: Environmental Health www.ct.Eov/doh/ Delaware Environment Delaware Department of Natural Resources and Environmental... www.dnrec.state.de.us Delaware Environment State of Delaware - Topics - Environment www.delaware.gov/topics/environment Delaware Occupational Health Delaware Office of Occupational Health www.dhss.delaware.gov/dph/hsp/oh.html Delaware Environmental Health/Health Division of Public Health - Delaware Health and Social Services ... www.dhss.delaware.gov/dhss/dph/ Florida Environment Welcome | Florida Department of Environmental Protection (DEP) www.dep.state.fl.us Florida Environmental Health/Health Environmental Health www.floridahealth.gov/environmental- health/ Georgia Environment Environmental Protection Division | A Division of the Georgia ... www.epd.georgia.gov Georgia Occupational Health Georgia Occupational Health and Safety Surveillance Program ... www.dph.georgia.gov/georgia- occuoational-health-and-safetv- surveillance-program Georgia Environmental Health/Health Environmental Health | Georgia Department of Public Health www.dDh.seorsia.sov/environmental- health Hawaii Environment Office of Environmental Quality Control (OEQC) - Hawaii Department... www.health.hawaii.sov Hawaii Occupational Health Hawaii Occupational Safety and Health - Department of Labor and ... www.labor.hawaii.sov Hawaii Environmental Health/Health Hawaii Environmental Health Portal www.eha-cloud.doh.hawaii.sov Idaho Environment Idaho Department of Environmental Quality: Home www.dea.idaho.sov Idaho Environmental Health/Health Environmental Health - Idaho Department of Health and Welfare www.healthandwelfare.idaho.sov Illinois Environment Illinois Environmental Protection Agency www.eoa.illinois.Eov Illinois Occupational Health Illinois OSHA: Illinois OSHA www.osha.illinois.Eov Illinois Environmental Health/Health Illinois Department of Public Health www.www.idph.state.il.us Indiana Environment Indiana Department of Environmental Management - IN.gov www.in.Eov/idem/ Indiana Occupational Health IOSHA-IN.gov www.in.Eov/dol/iosha.htm Indiana Environmental Health/Health Indiana Environmental Health Website www.in.Eov/isdh Iowa Environment Environmental Protection - Iowa Department of Natural Resources www.iowadnr.Eov Iowa Occupational Health Iowa OSHA | www.iowadivisionoflabor.gov www.iowaosha.sov Iowa Environmental Health/Health EHS - Home - Iowa Department of Public Health - lowa.gov www.idoh.iowa.sov/ehs Kansas Environment Kansas Department of Health & Environment: Division of Environment www.kdheks.sov/environment/ Kansas Occupational Health Kansas Department of Labor: workplace safety www.dol.ks.sov/Safetv Kansas Environmental Health/Health Kansas Department of Health & Environment: Division of Public Health www.kdheks.sov Page 51 of 83 ------- Kentucky Environment Department for Environmental Protection | Welcome - Kentucky.gov www.deo.kv.Eov Kentucky Environment Kentucky Environmental Quality Commission | Welcome to the EQC www.eac.kv.sov Kentucky Environment Energy and Environment Cabinet | Welcome - Kentucky.gov www.eec.kv.sov Kentucky Occupational Health Kentucky Labor Cabinet - Occupational Safety and Health Program www.labor.kv.Eov/dows/oshp/PaEes/Occu pational-Safetv-and-Health-ProEram.aspx Kentucky Environmental Health/Health Kentucky: Cabinet for Health and Family Services - DPH Home www.chfs.kv.sov/doh/ Louisiana Environment Louisiana Department of Environmental Quality > HOME www.dea.louisiana.Eov Louisiana Environmental Health/Health About Environmental Health - Louisiana Department of Health and ... www.dhh.louisiana.Eov Louisiana Environmental Health/Health Health Data Portal www.healthdata.dhh.la.Eov Maine Environment Maine Department of Environmental Protection (DEP) - Maine.gov www.maine.Eov/dep/ Maine Occupational Health Maine Department of Labor: Workplace Safety and Health - Maine.gov www.maine.Eov/labor/workplace safety/ Maine Environmental Health/Health Division of Environmental Health - Maine CDC: DHHS ... - Maine.gov www.maine.Eov/dhhs/mecdc/environment al-health/el/ Maine Environmental Health/Health Maine DHHS - Environmental Health - Maine.gov www.maine.Eov/dhhs/environmental heal th.shtml Maryland Environment Maryland Department of the Environment www.mde.state.md.us Maryland Occupational Health Maryland Occupational Safety and Health (MOSH) - Division of ... www.dllr.state.md.us Maryland Environmental Health/Health Environmental Health - Maryland Department of Health and Mental... www.dhmh.marvland.Eov Maryland Environmental Health/Health Environmental Health - Prevention and Health Promotion ... www.phpa.dhmh.marvland.Eov Massachusetts Environment Massachusetts Department of Environmental Protection | MassDEP www.mass.Eov/eea/asencies/massdeo/ Massachusetts Occupational Health Occupational Health Surveillance Program - Mass.Gov www.mass.Eov/doh/ohso Massachusetts Environmental Health/Health Environmental Health - Mass.Gov www.mass.Eov/eohhs/sov/deoartments/d oh/oroErams/environmental-health/ Michigan Environment DEQ - Department of Environmental Quality - State of Michigan www.michisan.sov/dea/ Michigan Occupational Health Ml Occupational Safety & Health Administration - State of Michigan www.michisan.sov/lara/ Michigan Environmental Health/Health MDHHS - Public Safety & Environmental Health - State of Michigan www.michisan.sov/mdhhs/ Minnesota Environment Minnesota Pollution Control Agency www.oca.state.mn.us Minnesota Environment Minnesota Environmental Quality Board www.eab.state.mn.us Minnesota Occupational Health Minnesota Center for Occupational Health and Safety www.health.state.mn.us/occhealth/ Minnesota Environmental Health/Health Environmental Health - Minnesota Dept. of Health www.health.state.mn.us Minnesota Environmental Health/Health Environmental Safety - Minnesota.gov www.mn.sov/oortal/health-and- safetv/environmental-safetv/ Mississippi Environment Mississippi Department of Environmental Quality www.dea.state.ms.us Page 52 of 83 ------- Mississippi Occupational Health Occupational Health - Mississippi State Department of Health www.msdh.ms.sov Missouri Environment Division of Environmental Quality - Missouri Department of Natural... www.dnr.mo.sov/env Missouri Occupational Health Workplace Safety | Missouri Labor www.labor.mo.sov/DLS/workDlaceSafetv Missouri Environmental Health/Health Environmental Health Operational Guidelines | Missouri Department... www.health.mo.Eov Missouri Environmental Health/Health Missouri Environmental Public Health Tracking www.ephtn.dhss.mo.Eov Missouri Environmental Health/Health Environmental Public Health www.kcmo.Eov/health/environmental- health-services/e Montana Environment Air - Montana DEQ > Home - Montana.gov www.dea.mt.Eov Montana Occupational Health Occupational Safety and Health - Employment Relations Division www.erd.dli.mt.Eov/safetv- health/occuoational-safetv-and-health Montana Environmental Health/Health Environmental Health - DPHHS Home - Montana.gov www.dphhs.mt.Eov/publichealth/Environm ental-Health Nebraska Environment Nebraska Department of Environmental Quality www.dea.state.ne.us Nebraska Occupational Health Department of Labor Office of Safety www.dol.nebraska.Eov/Safetv/ Nebraska Environmental Health/Health Nebraska DHHS: Environmental Health www.dhhs.ne.Eov Nevada Environment Nevada Division of Environmental Protection www.ndep.nv.Eov Nevada Occupational Health Department of Industrial Relations, OSHA www.dir.nv.Eov/OSHA/Home/ Nevada Environmental Health/Health Nevada Division of Public and Behavioral Health - State of Nevada, Environmental Health Section www.dpbh.nv.Eov New Hampshire Environment Welcome | NH Department of Environmental Services www.des.nh.Eov New Hampshire Environment Environmental Protection Bureau | NH Department of Justice www.doi.nh.Eov/environmental- orotection/index.htm New Hampshire Occupational Health Occupational Health Surveillance Program at University of New Hampshire, in conjunction with the state www.iod.unh.edu/proiects/occupational- health-surveillance-Drosram New Hampshire Environmental Health/Health Welcome | New Hampshire Environmental Public Health Tracking Program www.nh.Eov/epht New Jersey Environment NJDEP New Jersey Department of Environmental Protection www.ni.Eov/dep New Jersey Occupational Health and Environmental Health Department of Health, The Consumer, Environmental and Occupational Health Service www.ni.Eov/health/ceohs/ New Mexico Environment New Mexico Environment Department Home Web Site Homepage ... www.env.nm.Eov New York Environment New York State Department of Environmental Conservation www.dec.nv.Eov New York Occupational Health NYS Occupational Health Clinic Network - New York State ... www.health.nv.Eov/environmental/workpl ace/ North Carolina Environment NC DEQ www.dea.nc.Eov North Carolina Occupational Health N.C. Department of Labor, Occupational Health Division www.nclabor.com/osha/ Page 53 of 83 ------- North Carolina Environmental Health/Health State of North Carolina: Environmental Health www.nc.sov/asencv/environmental-health North Dakota Environment Environmental Services - nd.gov: Official Portal for North Dakota ... www.nd.sov North Dakota Environment Environmental and Transportation Services Division - North Dakota ... www.dot.nd.sov/Dublic/divdist/environme ntal.htm North Dakota Environmental Health/Health Environmental Health Air Quality Section www.ndhealth.sov/aa/ North Dakota Environmental Health/Health Environmental Health Section - North Dakota Department of Health www.ndhealth.sov/ehs/ Ohio Environment Ohio EPA Home www.epa.state.oh.us Ohio Occupational Health Ohio Bureau of Workers Compensation, Division of Safety & Hygiene services www.bwc.ohio.Eov/emplover/proErams/sa fetv/ Ohio Environmental Health/Health Environmental Health - Ohio Department of Health www.odh.ohio.Eov/environmentalhealth Oklahoma Environment Welcome to the Oklahoma Department of Environmental Quality www.dea.state.ok.us Oklahoma Occupational Health Oklahoma Department of Labor - Safety and Health (PEOSH) www.ok.Eov/odol/Services/Safetv and He alth (PEOSH) Oregon Environment State of Oregon: Department of Environmental Quality - Home www.oreEon.Eov/DEQ/ Oregon Occupational Health State of Oregon: Oregon OSHA - Home www.osha.oreEon.Eov Oregon Environmental Health/Health Healthy Environments - Oregon Public Health Division - Oregon.gov www.public.health.oreEon.Eov/HealthvEnvi ronments Pennsylvania Environment Pennsylvania Department of Environmental Protection www.dep.pa.Eov Pennsylvania Occupational Health Occupational and Industrial Safety - PA Department of Labor... www.dli.pa.Eov/lndividuals/Labor- Manasement- Relations/bois/Pages/default.aspx Pennsylvania Environmental Health/Health Pennsylvania Department of Health www.health.pa.Eov/Mv%20Health/Environ mental%20Health/Pases/default.asDX#.WL dHiW vtJ8 Rhode Island Environment Home- Rhode Island -Department of Environmental Management www.dem.ri.sov Rhode Island Occupational Health Occupational Safety, Workforce Regulation and Safety, Rl ... www.dlt.ri.sov/occusafe/ Rhode Island Environmental Health/Health Environmental Health, Division of - Rhode Island Department of Health www.health.ri.Eov/Drosrams/detail.DhD?DE m id=1052 South Dakota Environment South Dakota Department of Environment and Natural Resources www.denr.sd.sov South Dakota Environmental Health/Health South Dakota Environmental Health Laboratory www.doh.sd.Eov/lab/environmental/ South Carolina Environment Environment - SC.gov www.sc.sov/HealthAndSafetv/Pases/Enviro nment.aspx South Carolina Occupational Health South Carolina Occupational Safety and Health Administration www.scosha.llronline.com/ South Carolina Environmental Health/Health S.C. Department of Health & Environmental Control www.scdhec.Eov Page 54 of 83 ------- Tennessee Environment Department of Environment & Conservation - State of Tennessee www.tennessee.sov/environment/ Tennessee Environment Division of Water Resources - TN.Gov www.tn.gov/environment/section/wr- water-resources Tennessee Occupational Health Tennessee Occupational Safety and Health Administration - TN.Gov www.tn.gov/workforce/section/tosha Tennessee Environmental Health/Health Tennessee Department of Health - TN.Gov www.tn.sov/health/section/eh Texas Environment TCEQ Homepage - TCEQ - www.tceq.texas.gov www.tceq.texas.gov Texas Occupational Health OSHA - Workplace Safety and Health Requirements www.twc.state.tx.us Texas Occupational Health OSHCON: Occupational Safety and Health Consultation Program www.tdi.texas.sov Texas Environmental Health/Health Texas Department of State Health Services, Texas Environmental Health Institute www.dshs.texas.Eov Utah Environment Utah Department of Environmental Quality www.deq.utah.Eov Utah Environment Utah DEQ: Division of Air Quality www.airaualitv.utah.sov Utah Occupational Health Utah Occupational Safety and Health www.laborcommission.utah.Eov/divisions/ UOSH/ Utah Environmental Health/Health UT-EPHT - Welcome to Utah's Environmental Public Health Tracking ... www.epht.health.utah.Eov Vermont Environment Vermont Department of Environmental Conservation www.dec.vermont.sov Vermont Environment Department of Environmental Conservation - Vermont Agency of ... www.anr.vermont.Eov Vermont Occupational Health VOSHA | Vermont Department of Labor www.labor.vermont.sov Vermont Environmental Health/Health Vermont Department of Health www.healthvermont.Eov Vermont Environmental Health/Health Vermont Department of Health www.han.vermont.Eov Virginia Environment The Virginia Department of Environmental Quality: Virginia DEQ www.dea.virsinia.sov Virginia Occupational Health Office of Occupational Safety and Health Home www.va.Eov/vasafetv Virginia Environmental Health/Health Virginia Department of Health www.vdh.virsinia.sov Washington Environment Access Washington - Environment www.access.wa.Eov/topics/environment Washington Environment Washington State Department of Ecology www.ecv.wa.sov Washington Occupational Health Department of Labor and Industries: Centers of Occupational Health and Education www.cohe.lni.wa.sov Washington Environmental Health/Health Environmental Public Health :: Washington State Department of Health www.doh.wa.Eov West Virginia Environment WV Department of Environmental Protection www.dep.wv.Eov West Virginia Environmental Health/Health Welcome to the Bureau for Public Health - West Virginia Department... www.dhhr.wv.Eov/boh Wisconsin Environment The State of Wisconsin's Environment - Wisconsin Department of ... www.dnr.wi.Eov Page 55 of 83 ------- Wisconsin Occupational Health Wisconsin Occupational Health Program | Wisconsin Department of ... www.dhs.wisconsin.Eov/occuoational- health/ Wisconsin Environmental Health/Health www.dhs.wisconsin.sov/environmental/ Wyoming Environment DEQ Wyoming Department of Environmental Quality www.dea.state.wv.us Wyoming Environment Air Quality | Wyoming Department of Environmental Quality www.dea.wvomins.sov Wyoming Occupational Health www.wvominEworkforce.orE/businesses/o sha/ Wyoming Environmental Health/Health Wyoming Department of Health: Home Page www.health.wyo.Eov Page 56 of 83 ------- Table_Apx C-4. List of Gray Literature Sources Removed from Search During Curation for Fate, Engineering/Occupational Exposure, Exposure, and Human Health Hazard Topic Areas Searched ID Description URL Reason 1007 Office of Water Effluent Guidelines https://www.epa.gov/eg Provides a list of chemicals only 1009 Water Quality Criteria 1986 Outdated 1018 Government Publishing Office (GPO) https://www.gpo.gov/ Search this last because most hits will be duplicates 1077 Greener products and services https://www.epa.gov/greenerproducts/identifv-greener-products-and-services Public fact sheets without sufficient level of detail 1089 ECOTOX Database https://cfpub.epa.gov/ecotox/auick auerv.htm Removed because ecotox team is covering this reference 1121 US EPA Resources Fact Sheets Public fact sheets without sufficient level of detail 1123 EPA Reports Search epa.gov for each chemical with the key word "report"; only keep those that wouldn't be caught by other sources Other searches caught this information 1125 EPA Manufacturing/Use Search epa.gov for each manufacturing sector and use and key words "fact sheet" or "report" Other searches caught this information 1130 Substance Registry Services (SRS) https://iaspub.epa.gov/sor internet/registrv/substreg/searchandretrieve/subs Site provides links to other trusted sources; was used to ensure no part of SRS was excluded from overall trusted source list tancesearch/search.do 1142 EPA Existing Chemicals Engineering Files EPA has an archive of hardcopy engineering assessments from previous Existing Chemicals assessments. If directed by the EPA Task Manager, ERG will contact the EPA WA COR to inquire as to the location of these hardcopy files and will review them for relevant information. This information is internal to OPPT and not public; it may be searched in the future 2023 NTP National Toxicology Program ntp.niehs.nih.gov/ Too general; refined search strategy to target specific subsites 2024 NTP National Toxicology Program - Search http://ntpsearch.niehs.nih.gov/ Too general; refined search strategy to target specific subsites 2025 NTP National Toxicology Program - Substances studied by NTP httDs://ntD.niehs.nih.sov/testins/status/asents/ts-11297-e.html All NTP studies are captured in Toxline 2033 NTP Genetically Modified Model Report Series https://ntp.niehs.nih.gov/testing/tvpes/altmodels/reports/index.html All NTP studies are captured in Toxline 2034 NTP Technical Report Series https://ntp.niehs.nih.gov/results/pubs/longterm/reports/longterm/index.html All NTP studies are captured in Toxline 2035 NTP Toxicity Report Series https://ntp.niehs.nih.gov/results/pubs/shortterm/reports/index.html All NTP studies are captured in Toxline Page 57 of 83 ------- 2036 NTP Developmental Toxicity Study Abstracts httDs://ntD.niehs.nih.sov/testins/tvDes/dev/abstracts/index.html All NTP studies are captured in Toxline 2037 NTP Immunotoxicity Study Abstracts httDs://ntD.niehs.nih.sov/testins/tvDes/imm/abstracts/index.html All NTP studies are captured in Toxline 2038 NTP Reproductive Assessment by Continuous Breeding Study Abstracts httDs://ntD.niehs.nih.sov/testins/tvDes/reDro/abstracts/index.html All NTP studies are captured in Toxline 2040 NTP- Chemical Effects in Biological Systems (CEBS) database httDs://tools.niehs.nih.sov/cebs3/ui/ All NTP studies are captured in Toxline 2102 CDC ATSDR Public Health Statements https://www.atsdr.cdc.gov/phs/phs.asp?id=953&tid=199 Already covered by the ATSDR tox profiles in ID 2100 2112 CDC NHANES https://www.cdc.gov/nchs/nhanes/ Other searches caught this information 2124 CDC NIOSH https://www.cdc.gov/niosh/ A targeted NIOSH search was done instead 2126 CDC NIOSH Pocket Guide to Chemical Hazards https://www.cdc.gov/niosh/npg/search.html Already covered under ID 2116 (Pocket guide to chemical hazards) 2201 Bureau of Labor Statistics: American Time Use Survey https://www.bls.gov/tus/tables.htm Does not provide chemical-specific information and is already incorporated into OPPT generic exposure scenarios 2209 Census Bureau: American Fact httDs://factfinder.census.sov/faces/nav/isf/Dases/searchresults.xhtml?refresh Does not provide chemical-specific information and is Finder Database ฃt already incorporated into OPPT generic exposure scenarios 2225 Electronic Code of Federal Regulations httD://www.ecfr.sov/ This provides regulatory information only 2401 OSHA Permissible Exposure Limits Table Z-l httDs://www.osha.sov/dss/annotated-Dels/tablez-l.html Other searches caught this information 2402 OSHA Permissible Exposure Limits Table Z-2 httDs://www.osha.sov/dss/annotated-Dels/tablez-2.html Other searches caught this information 2403 OSHA Permissible Exposure Limits Table Z-3 httDs://www.osha.sov/dss/annotated-Dels/tablez-3.html Other searches caught this information 2503 NOAA National Oceanic and Atmospheric Administration www.noaa.gov Data provided in cameo database already 2508 US International Trade Commission https://www.usitc.gov/ Provides export information, which is not on topic for this search 2510 USGS US Geological Survey, National Water Information System http://waterdata.usgs.gov/nwis Included in EPA OPPT monitoring database 2511 CDC National Report on Human Exposure to Environmental Chemicals cdc.gov/exposurereport/index.html Moved from automated to manual search Page 58 of 83 ------- 3050 ECHA echa.eurooa.eu/ Too general; refined search strategy to target specific subsites 3056 Japan NITE CHEmicals Collaborative Knowledge database httD://www.safe.nite.so.iD/icheck/search.action?reauest locale=en Other searches caught this information 3075 International Resources https://echa.europa.eu/registration-dossier/ Other searches caught this information 3149 OECD http://webnet.oecd.org/CCRWEB/Search.aspx This is captured by the echemportal.org site which also provides record for Japan, Finland, Australia, The Netherlands 3154 OECD eChemPortal http://www.echemportal.org/echemportal/index?pagelD=0&reauest locale=e This is a duplicate n 3255 WHO International Program on Chemical Safety (UN) http://www.who.int/ipcs/en/ These data appear in inchem, which is in echemportal 3400 Environment Canada http://www.ec.gc.ca/default.asp?lang=En&n=FD9B0E51-l Chemical Substances page links to relevant pages at this site 3411 Health Canada http://www.hc-sc.gc.ca/index-eng.php Chemical Substances page links to relevant pages at this site 3430 Government of Alberta, Canada httD://work.alberta.ca Other provinces were not searched, so this was eliminated for consistency 3500 Japan Chemical Risk Information Platform (CHIRP) httD://www.nite.so.iD/en/chem/chriD/chriD search/svstemToo Other searches caught this information 5002 Toxic Use Reduction Institute httD://www.turi.ors Links back to regulatory documents captured in other sources 5005 Environmental Fate Database (EFDB) htto://www.srcinc.com/what-we-do/efdb.asox No longer exists 5004 SRI International - Paid access to market reports only 5006 SRC FatePointers Search Module PHYSPROP htto://esc.svrres.com/fateoointer/search.asD Provides information captured in other sources 5010 ChemSpider http://www.chemspider.com Not needed since we have chemidplus 5012 inchem inchem.ore Captured in 5011 results echemportal 5015 ITER iter.ctc.com/DublicURL/oub search list.cfm Provides information captured in other sources 5017 Global Science Gateway htto://www.worldwidescience.ors Other searches caught this information 5018 Cambridge University htto://www-ims.ch.cam.ac.uk/cil/SGTL/database/ Access only granted to Cambridge researchers and students 5022 Lowell Center for Sustainable Production httoV/www.chemicalsDolicv.ors/chemicalsoolicv. us.state.database.oho Only provides regulatory information 5023 ACGIH Search the ACGIH handbook to determine whether ACGIH Threshold Limit Value (TLV) has been established for specific chemicals of interest Only provides regulatory information Page 59 of 83 ------- 5024 Pollution Prevention Reference Manual httD://infohouse.D2ric.ors/ Other searches caught this information 7264 ASTM International www.astm.ors Paid access to standard methods only 7381 IHS Market www.ihs.ors Paid access to market reports only 7467 American Coatings Association www.Daint.ors Documents restricted to members only Regulations.gov resulations.sov Assumed that technical support documents will be caught using other methods Federal Register www.federalresister.sov Assumed that technical support documents will be caught using other methods Page 60 of 83 ------- D. LITERATURE SEARCHES FOR ENVIRONMENTAL HAZARD The sources searched in the environmental hazard literature search are provided in Table_Apx D-l. The specific search strategies are provided in the remainder of Appendix D. Page 61 of 83 ------- Table_Apx D-l. Sources Used For Gray Literature Search for the Ecotoxicity Topic Area Trusted Source Category Source Manual or Automated? Searched By: Keywords Source Address Other US Agencies eChemPortal Manual Chemical CAS Number or chemical name http://www.echemportal.ors/echemportal/participant/paEe.action?paselD=9 International Resources OECD HPV/SIDS/IUCLID Manual Chemical CAS Number or chemical name http://webnet.oecd. ors/hpv/ui/Search.aspx International Resources ECHA information on Registered Substances Manual Chemical CAS Number or chemical name http://echa.europa.eu/information-on-chemicals/resistered-substances International Resources ECHA Information from the Existing Substances Regulation (ESR) Manual Chemical CAS Number or chemical name http://echa.europa.eu/information-on-chemicals/information-from-existins-substances- resulation International Resources Environment Canada Manual Chemical CAS Number or chemical name http://www.ee.sc.ca/default.asp?lans=En&n=ECD35C36 International Resources Environment Canada: Toxic Substances Managed Under CEPA Manual Chemical CAS Number or chemical name http://www.ee.sc.ca/toxiaues-toxics/Default.asp?lans=En&n=98E80CC6-l International Resources Environment Canada: Draft and Final CEPA Assessments Manual Chemical CAS Number or chemical name http://www.ee. sc. ca/lcpe-cepa/default.asp?lans=En&xml=09F567A7-BlEE-lFEE-73DB- 8AE6C1EB7658 http://www.ee.sc.ca/lcpe-cepa/default.asp?lans=En&xml=6892C255-5597-C162-95FC- 4B905320F8C9 Page 62 of 83 ------- A. Chemical verification process 1. Verify the chemical substance using chemical verification sources as noted in the ECOTOX Chemical Verification and Entry Procedure (https://cfpub.epa.qov/ecotox/help.cfm?helptabs=tab4). Chemical verification ensures that the chemical name and CAS Number for the chemical substance linked and correct. Chemical verification sources are searched by the name and/or CAS Number and are cross-checked to ensure the chemical name - CAS Number relationship is valid. Additional information including synonyms and molecular formulas are also located in the verification sources. Once the name and CAS Number have been verified, they are entered into the U.S.EPA's ECOTOX chemical file for use. The primary source for chemical verification is STN International, http://www.stn-international.com (operated by Chemical Abstract Services) and contains information on all classes of chemicals, organic, pesticides, inerts, solvents, etc. The chemical verification sources include: Online Databases, e.g. STN International (http://www.stn-international.com) Chemical Compendiums, e.g. Dictionary of Organic Chemicals, Registry of Toxic Effects of Chemical Substances Chemical Catalogs, e.g. Sigma-Aldrich (https://www.sigmaaldrich.com) Internet websites, e.g. company websites displaying chemical MSDS and label Information 2. Find related chemicals that may be of interest to OPPT RAD (the relationship of the chemicals are noted in Table_Apx D-2, column headed Relationship, e.g. Parent, is the chemical substance requested, Degradates (chemicals formed as the chemical substance is degraded), and Related compounds (similar in structure to the chemical substance requested, e.g. isomers)), if located. Synonym names and trade names to include in the literature search strategy are also located. Sources for related chemicals and synonym chemical names are at: PAN: The Pesticide Action Network (http://www.pesticideinfo.org) is a site that provides information about pesticides and also includes inerts and solvents used in chemical formulations. After entering a name or CAS number into the search field, choose the chemical of interest from the search results and scroll down to the bottom of the page. Related chemicals will be listed here along with a reason. Parent chemicals, derivatives, and degradates/metabolites can be found here. PFATE: EPA's Pesticide Fate Database (located at the contractor's site) is a database that provides degradates for chemicals, mostly pesticides. Searching on a chemical name returns associated degradates. DOC: Dictionary of Chemical Names and Synonyms for synonym names. STN should also be used for the synonym search if a search was conducted to verify the chemical. ECOTOX: Search the U.S. EPA's ECOTOX chemical database for chemical synonyms and related chemicals, (www.epa.gov/ecotox) Page 63 of 83 ------- Additional chemical verification sources, if needed from Appendix A from the ECOTOX Chemical Verification and Entry Procedure (https://cfpub.epa.qov/ecotox/help.cfm?helptabs=tab4) contains a list of approved sources of verification for chemical names and structures. Common sources searched may include: ฆ Registry of Toxic Effects of Chemical Substances ฆ TSCA Chemical Substances Inventory ฆ Compendium of Pesticide Common Names ฆ California Department of Pesticide Regulation If the chemical cannot be found on these websites or any other approved sources, an Internet search is performed to locate additional information. B. UNIFY Chemical Report Setup Worksheet Step 1. Identifying the chemical name(s). CAS number(s) and related chemicals. If related chemicals are located, add a line Table_Apx D-2. Chemical requested: N-methylpyrrolidone STN International fSTN) - http://www.stn-international.com CAS # 872-50-4 2-Pyrrolidinone, 1-methyl- 1-Methyl-2-pyrrolidinone 2-Pyrrolidone, 1-methyl- (3CI) l-Methyl-2-pyrrolidone l-Methyl-5-pyrrolidinone l-Methylazacyclopentan-2-one AgsolEx 1 M 0418 M-Pyrol Microposit 2001 N 0131 N-Methyl-alpha-pyrrolidinone N-Methyl-alpha-pyrrolidone N-Methyl-gamma-butyrolactam N-Methyl-2-ketopyrrolidine N-Methyl-2-pyrrolidinone N-Methyl-2-pyrrolidone N-Methylbutyrolactam N-Methylpyrrolidine-2-one N-Methylpyrrolidinone N-Methylpyrrolidone NMP NSC 4594 Pharmasolve Page 64 of 83 ------- Pyrol M SL1332 N-Methylpyrrolidone- 872-50-4(Parent compound) Chemical Uses: PAN - not reported l-Methyl-2-pyrrolidinone , 2684 (CA DPR Chem Code)), 872-50-4 (CAS number), 872504 (CAS number without hyphens), N-methyl-2-pyrrolidone, N-METHYL-2-PYRROLIDONE (CA DPR Chem Code Text), N- Methylpyrrolidone, Nmethyl2pyrrolidone PFATE No additional or related chemical information located. ECOTOX Chemical database Contains "Methylpyrrolidone" No additional or related chemical information located. Online - http://www.who.int/ipcs/publications/cicad/en/cicad35.pdf Related Chemical: 5-hydroxy-N-methyl-2-pyrrolidone, CAS# 41194-00-7 Related Chemical: N-methylsuccinimide, CAS# 1121-07-9 Related Chemical: 2-hydroxy-N-methylsuccinimide (Unable to Verify) Table_Apx D-2. Chemical(s) located for N-Methylpyrrolidone (NMP) *Related compounds were not included in the search per EPA. Chemical Name CAS# Relationship (e.g.,Pa rent, Degradate) and Source 5-hydroxy-N-methyl-2- pyrrolidone 41194007 Related (Online) N-methylsuccinimide 1121079 Related (Online) 2-hydroxy-N- methylsuccinimide Unable to Verify Related (Online) Step 2. Create a unique list of Chemical Search Terms From the searches conducted in Step 1, chemical terms from searches are listed below, create a unique list of chemical terms to be used for the Chemical of Concern literature search. Non-English, long scientific chemical names and terms documented to cause false hits are not used and are not in bold. Note that if one term is part of another term, e.g. Tetrachloromethane and 1,1,1,1- Tetrachloromethane, only the first term is used, e.g. Tetrachloromethane. Terms used to generate the final list of chemical terms are in BOLD. 1. STN Page 65 of 83 ------- 2-Pyrrolidinone, 1-methyl- 1-Methyl-2-pyrrolidinone 2-Pyrrolidone, 1-methyl- (3CI) l-Methyl-2-pyrrolidone l-Methyl-5-pyrrolidinone l-Methylazacyclopentan-2-one AgsolEx 1 M 0418 M-Pyrol Microposit 2001 N 0131 N-Methyl-alpha-pyrrolidinone N-Methyl-alpha-pyrrolidone N-Methyl-gamma-butyrolactam N-Methyl-2-ketopyrrolidine N-Methyl-2-pyrrolidinone N-Methyl-2-pyrrolidone N-Methylbutyrolactam N-Methylpyrrolidine-2-one N-Methylpyrrolidinone N-Methylpyrrolidone NMP NSC 4594 Pharmasolve Pyrol M SL1332 Related Chemicals from STN (not included per EPA) 41194-00-7 5-Hydroxy-l-methyl-2-pyrrolidinone 5-Hydroxy-l-methylpyrrolidin-2-one 5-Hydroxy-N-methyl-2-pyrrolidone 1121-07-9 2,5-Pyrrolidinedione, 1-methyl- 1-Methyl-2,5-pyrrolidinedione N-Methyl-2,5-pyrrolidinedione N-Methylsuccinimide NSC 11324 Chemical unable to verify 2-Hydroxy-N-methylsuccinimide 2. PAN l-Methyl-2-pyrrolidinone , 2684 (CA DPR Chem Code)), 872-50-4 (CAS number), 872504 (CAS number without hyphens), N-methyl-2-pyrrolidone, N-METHYL-2-PYRROLIDONE (CA DPR Chem Code Text), N- Methylpyrrolidone, Nmethyl2pyrrolidone Page 66 of 83 ------- Final chemical terms to use for the Chemical of Concern Literature search derived from the chemical lists above. CAS Number(s): 872-50-4 Chemical Names: l-Methyl-2-pyrrolidinone l-Methyl-5-pyrrolidinone l-Methylazacyclopentan-2-one AgsolEx 1 M 0418 Microposit 2001 M-Pyrol N 0131 N-Methyl-2-ketopyrrolidine N-Methyl-2-pyrrolidinone N-Methyl-2-pyrrolidone N-Methylbutyrolactam N-Methylpyrrolidine-2-one N-Methylpyrrolidinone N-Methylpyrrolidone NSC 4594 Pharmasolve Pyrol M SL1332 GENERAL: These are the search terms compiled from the Chemical Report for N-methylpyrrolidone to be used in the search strategies for each of the databases listed below. 1-Methyl-2-pyrrolidinone OR l-Methyl-5-pyrrolidinone OR l-Methylazacyclopentan-2-one OR AgsolEx 1 OR M 0418 OR M-Pyrol OR Microposit 2001 OR N 0131 OR N-Methyl-2- ketopyrrolidine OR N-Methyl-2-pyrrolidinone OR N-Methyl-2-pyrrolidone OR N- Methylbutyrolactam OR N-Methylpyrrolidine-2-one OR N-Methylpyrrolidinone OR N- Methylpyrrolidone OR NSC 4594 OR Pharmasolve OR Pyrol M OR SL 1332 Based upon the online search manuals for the respective databases below, it was necessary to construct searches as follows: SCIENCE DIRECT: (www.sciencedirect.com) General Search Terms applied to the search strategy for Science Direct Date Searched: 01/13/2017 Date Range of Search: 1823 to Present N=246 Tak("l-Methyl-2-pyrrolidinone" OR "l-Methyl-5-pyrrolidinone" OR "l-Methylazacyclopentan-2-one" OR "AgsolEx 1" OR "M 0418" OR "M-Pyrol" OR "Microposit 2001" OR "N 0131" OR "N-Methyl-2- Page 67 of 83 ------- ketopyrrolidine" OR "N-Methyl-2-pyrrolidinone" OR "N-Methyl-2-pyrrolidone" OR "N- Methylbutyrolactam" OR "N-Methylpyrrolidine-2-one" OR "N-Methylpyrrolidinone" OR "N- Methylpyrrolidone" OR "NSC 4594" OR Pharmasolve OR "Pyrol M" OR "SL 1332") AND NOT key(human* or child* or occupat* OR infant* OR homind* OR woman OR women OR patient* OR OSHA OR chromatograph* OR Spectrometr* OR pediatric*) AGRICOLA: (www.nal.usda.gov) General Search Terms applied to the search strategy for Agricola. The Agricola database contains a significant amount of gray literature including proceedings, symposia, and progress reports from government and educational institutions. This database categorizes literature as an "article " or a "book. " Date Searched: 01/13/2017 Date Range of Search: 15th Century to Present N=170 Agricola limits the search to 383 characters and therefore it is searched in sections to cover all of the compiled General Terms. Articles: "l-Methyl-2-pyrrolidinone" OR "l-Methyl-5-pyrrolidinone" OR "l-Methylazacyclopentan-2-one" OR "AgsolEx 1" OR "M 0418" OR "M-Pyrol" OR "Microposit 2001" OR "N 0131" OR "N-Methyl-2- ketopyrrolidine" OR "N-Methyl-2-pyrrolidinone" OR "N-Methyl-2-pyrrolidone" OR "N- Methylbutyrolactam" OR "N-Methylpyrrolidine-2-one" OR "N-Methylpyrrolidinone" OR "N- Methylpyrrolidone" OR "NSC 4594" Search Results: Displaying 1 through 100 of 169 entries. Articles: Pharmasolve OR "Pyrol M" OR "SL 1332" Search Results: Displaying 1 of 1 entries Books: "l-Methyl-2-pyrrolidinone" OR "l-Methyl-5-pyrrolidinone" OR "l-Methylazacyclopentan-2-one" OR "AgsolEx 1" OR "M 0418" OR "M-Pyrol" OR "Microposit 2001" OR "N 0131" OR "N-Methyl-2- ketopyrrolidine" OR "N-Methyl-2-pyrrolidinone" OR "N-Methyl-2-pyrrolidone" OR "N- Methylbutyrolactam" OR "N-Methylpyrrolidine-2-one" OR "N-Methylpyrrolidinone" OR "N- Methylpyrrolidone" OR "NSC 4594" Search resulted in no hits. Books: Pharmasolve OR "Pyrol M" OR "SL 1332" Search resulted in no hits. TOXNET: (toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?TOXLINE) General Search Terms applied to the search strategy for TOXNET. Date Searched: 01/13/2017 Date Range of Search: 1900 to Present Page 68 of 83 ------- N=410 872-50-4 Search Database Time iResult Query t( "1 methyl 2 pyrrolidinone" OR "n methyl 2 pyrrolidone" OR l"n methyl 2 pyrrolidinone" OR "n methylpyrrolidone" OR |"n methylpyrrolidinone" OR "methylpyrrolidone nf " "1 toxline [methyl 2 pyrrolidone" OR "m pyrol" |l0:08:02 [ 410 joR methylpyrrolidone OR 872-50-4 [rn] ) AND 1900:2017 [yr] |AND ( eng [la] ) AND ( BIOSIS [org] OR NTIS [org] OR PESTAB [[org] OR PUBMED [org] ORTSCATS [org] ) PROQUEST CSA: (www.csa.com) General Search Terms applied to the search strategy for ProQuest CSA. Date Searched: 01/13/2017 Date Range of Search: 1900 to Present N=33 ALL("l-Methyl-2-pyrrolidinone" OR "l-Methyl-5-pyrrolidinone" OR "l-Methylazacyclopentan-2-one" OR "AgsolEx 1" OR "M 0418" OR "M-Pyrol" OR "Microposit 2001" OR "N 0131" OR "N-Methyl-2- ketopyrrolidine" OR "N-Methyl-2-pyrrolidinone" OR "N-Methyl-2-pyrrolidone" OR "N- Methylbutyrolactam" OR "N-Methylpyrrolidine-2-one" OR "N-Methylpyrrolidinone" OR "N- Methylpyrrolidone" OR "NSC 4594" OR Pharmasolve OR "Pyrol M" OR "SL 1332") AND STYPE("Scholarly Journals" OR Reports OR Thesis OR "Government Documents") AND(su(toxicity OR toxicology OR bioassay* or lethal OR bioaccum*) OR cc(01504 or 08504 or "D 047*" or "X 241*") OR (LC NEAR/3 50)) NOT IF(m?n or human* or child* or occupant* or infant* or wom?n or patient* or pediatric) AND LA(ENG) PROQUEST DISSABS: (search.proquest.com) General Search Terms applied to the search strategy for ProQuest DISSABS. Date Searched: 01/13/2017 Date Range of Search: 1900 to Present N=8 ALL("l-Methyl-2-pyrrolidinone" OR "l-Methyl-5-pyrrolidinone" OR "l-Methylazacyclopentan-2-one" OR "AgsolEx 1" OR "M 0418" OR "M-Pyrol" OR "Microposit 2001" OR "N 0131" OR "N-Methyl-2- ketopyrrolidine" OR "N-Methyl-2-pyrrolidinone" OR "N-Methyl-2-pyrrolidone" OR "N- Methylbutyrolactam" OR "N-Methylpyrrolidine-2-one" OR "N-Methylpyrrolidinone" OR "N- Methylpyrrolidone" OR "NSC 4594" OR Pharmasolve OR "Pyrol M" OR "SL 1332") NOT IF(m?n or human* or child* or occupant* or infant* or wom?n or patient* or pediatric) AND LA(ENG) CURRENT CONTENTS: (https://access.webofknowledge.com/) General Search Terms applied to the search strategy for Current Contents. Date Searched: 01/13/2017 Date Range of Search: 1970 to Present N=373 Page 69 of 83 ------- TS=("1-Methyl-2-pyrrolidinone" OR "l-Methyl-5-pyrrolidinone" OR "l-Methylazacyclopentan-2-one" OR "AgsolEx 1" OR "M 0418" OR "M-Pyrol" OR "Microposit 2001" OR "N 0131" OR "N-Methyl-2- ketopyrrolidine" OR "N-Methyl-2-pyrrolidinone" OR "N-Methyl-2-pyrrolidone" OR "N- Methylbutyrolactam" OR "N-Methylpyrrolidine-2-one" OR "N-Methylpyrrolidinone" OR "N- Methylpyrrolidone" OR "NSC 4594" OR Pharmasolve OR "Pyrol M" OR "SL 1332") ECOTOX (production.ecodev.csgov.com/unify/) Results from the ECOTOX search strategy. These results are derived from the publications that are available in the ECOTOX database. This website is not accessible to the public. Date Searched: 01/13/2017 Date Range of Search: 01/01/1900 to 01/13/2017 N=8 The two sources listed below are used if very few articles are identified in the searches above. The two sources listed below have very high non-applicability rates and not cost effective in most cases. SCIFINDER: (www.cas.org/) SciFinder search was not run. PUB MED: (www.ncbi.nlm.nih.gov/PubMed/) PubMed search was not run. E. DEVELOPMENT OF TAGS WITH INCLUSION/EXCLUSION CRITERIA E-l Inclusion/Exclusion Criteria and Tags for the Fate Literature Table_Apx E-l. Tags and Inclusion/Exclusion Criteria for N-Methylpyrrolidone (NMP) for the Fate Topic Area Tag Inclusion/Exclusion Criteria Example Keywords ON TOPIC, GENERAL FATE TAGS Fate and Transport Data INCLUDE: Studies providing pchem property data that describe/impact fate and transport EXCLUDE: Laboratory experiments using laboratory-derived chemicals or laboratory simulations, not using environmental samples, unless rate constant or coefficient is derived; Laboratory experiments using environmental sample under non- natural conditions or added Koa, Kow, Kaw, Koc, Kd, partitioning coefficient, fugacity, flux, groundwater, migration, sediment, leach, soil, sorb, sorption, adsorption, dust, particles, aerosol, volatility, solubility Page 70 of 83 ------- substrates, not naturally occurring in environment Environmental Persistence INCLUDE: Studies that indicate persistence, transformation, and degradation in the environment Persistence, half-life, hydrolysis, photolysis, photostability, biodegradation, aerobic, anaerobic, metabolism, reduction, degradation, transformation Bioaccumulation INCLUDE: studies pertaining to bioaccumulation, bioconcentration, and trophic magnification EXCLUDE: Studies where chemical is given to animal in lab setting where conditions where conditions are clearly not relevant to naturally- occurring conditions Studies in humans, these can fall under Human Health, ADME BCF, BAF, BSAF, trophic magnification, biomagnification, bioaccumulation, bioconcentration, biota sediment accumulation factor, biotransfer Wastewater Removal INCLUDE: sewage or wastewater treatment, treatment facilities, and effluent EXCLUDE: test systems, laboratory experiments, or demonstrations where conditions are clearly not relevant to naturally-occurring conditions Sewage or wastewater treatment, WWTP, POTW, sludge, effluent Other supporting fate and transport INCLUDE: studies supporting or possibly supporting fate and transport, but not a study that can be included in one or more of the preceding relevant categories ON TOPIC, GENERAL STUDY TAGS Data Type INCLUDE: Empirical Modeled Empirical: measured Modeled: simulated, estimated, modeled Source Type INCLUDE: Database Search Gray Literature o EPA Source Determination of source type of database search or gray literature is by search type, rather than keyword. Primary Source: Novel, experimental, modeling o Other Government Source Secondary Source: Review o Industry-Specific Source Page 71 of 83 ------- o Peer-reviewed Literature o Direct Communications Primary Source Secondary Source Use Specific INCLUDE: Source contains use-specific data or information dye, electronics, nail polish, paint Chemical Specific INCLUDE: Source contains information specific to the chemical of interest NMP and synonyms Regulatory INCLUDE: Source contains a regulatory value/limit Water quality criteria, NAAQS2, IRIS2 OFF TOPIC Off Topic INCLUDE: Off topic in context of identified information needs OTHER Not peer- reviewed INCLUDE: Published without formal peer review. Use in addition to relevant or not relevant (not an exclusive tag). Foreign language INCLUDE: Full-text published in non-English language. Use in addition to relevant or not relevant (not an exclusive tag). National Ambient Air Quality Standard integrated Risk Information System Page 72 of 83 ------- E-2 Inclusion/Exclusion Criteria and Tags for the Engineering/Occupational Exposure Literature Table_Apx E-2. Tags and Inclusion/Exclusion Criteria for N-Methylpyrrolidone (NMP) for the Engineering/Occupational Exposure Topic Area Tag Inclusion/Exclusion Criteria Example Keywords ON TOPIC, GENERAL ENGINEERING TAGS Process Info INCLUDE: Studies pertaining to chemical processes containing information on life cycle, production volume, descriptions of processes, and manufacturing sites EXCLUDE: Studies involving Superfund sites, these might fall under Exposure Life cycle, production volume, use volume, import, process description, process flow diagram, product concentration, sites, manufacture, process Occupational Exposure INCLUDE: Occupational exposure studies that contain or may contain information on worker activities, amount of workers exposed, routes of exposure, personal and work area monitoring data (job titles), exposure modeling, and/or interventions to reduce exposure such as PPE or engineering controls Worker, worker activities, worker exposure, occupational exposure, inhalation, dermal, personal sample, time-weighted average, breathing zone, PPE, personal protective equipment, engineering controls, exposure reduction, ventilation Environmental Releases INCLUDE: Studies pertaining to releases from manufacturing waste streams and end of life cycle processing Release, emission, release rate, release frequency, point source, area source, air, water, landfill, incineration, POTW, on-site treatment, disposal, pretreatment program, recycling, air concentration Other supporting INCLUDE: Studies supporting or possibly supporting engineering sections, but not a study included in one or more of the preceding relevant categories ON TOPIC, GENERAL STUDY TAGS Data Type INCLUDE: Empirical Modeled Empirical: measured Modeled: simulated, estimated, modeled Source Type INCLUDE: Database Search Gray Literature o EPA Source o Other Government Source Determination of source type of database search or gray literature is by search type, rather than keyword. Primary Source: Novel, experimental, modeling Secondary Source: Review Page 73 of 83 ------- o Industry-Specific Source o Peer-reviewed Literature o Direct Communications Primary Source Secondary Source Use Specific INCLUDE: Source contains use-specific data or information dye, electronics, nail polish, paint Chemical Specific INCLUDE: Source contains information specific to the chemical of interest NMP and synonyms Regulatory INCLUDE: Source contains a regulatory value/limit Water quality criteria, NAAQS2, IRIS2 OFF TOPIC Off topic INCLUDE: Off topic in context of identified information needs OTHER Not peer- reviewed INCLUDE: Published without formal peer review. Use in addition to relevant or not relevant (not an exclusive tag). Foreign language INCLUDE: Full-text published in non-English language. Use in addition to relevant or not relevant (not an exclusive tag). National Ambient Air Quality Standard integrated Risk Information System. Page 74 of 83 ------- E-3 Inclusion/Exclusion Criteria and Tags for the Exposure Literature Table_Apx E-3. Exposure Inclusion/Exclusion Criteria N-Methylpyrrolidone (NMP) and Tags Tag Inclusion/Exclusion Criteria Example Keywords ON TOPIC, GENERAL EXPOSURE TAGS Ecological INCLUDE: Covers ecological exposure, including exposure to flora and fauna EXCLUDE: Studies limited to describing concentrations in mineral deposits only Pchem properties of environmental sample or chemical structure without concentration data concentration, mammal, avian, fish, aquatic General Population INCLUDE: Covers exposure to the general population due to ambient concentrations in environmental media/food EXCLUDE: Studies involving exposures to laboratory-produced chemical or chemical mixture in a lab setting, rather than environmentally-derived samples Studies without measured or modeled concentrations Studies involving measured dust concentrations from consumer products, these should be tagged to Consumer Exposure general population exposure/dose, releases, background levels, ambient/outdoor air, deposition, surface water, drinking water, ground water, soil, sediment, sludge, disposal, life cycle Consumers INCLUDE: Covers exposure to consumers who use a product or article containing the chemical EXCLUDE: Studies involving exposures to laboratory-produced chemical, rather than environmentally-derived samples consumer product exposure/dose, indoor/residential, product, article, aerosol, dust, indoor air, hand-to-mouth, surface, shower, dermal loading Page 75 of 83 ------- Susceptible Population INCLUDE: Covers exposure for a particular potentially exposed and susceptible subpopulation susceptible/sensitive subpopulation, infants, children, pregnancy, senior, aged, elderly, older women, men, gender, immunocompromised, diseased population, preexisting disease, genetics, socioeconomic status, race Highly Exposed Population INCLUDE: Covers a population exposed at a level higher than the general population highly-exposed sub population, near-facility population, higher-than-average exposure, above background, populations near manufacturing facilities Other Exposure INCLUDE: Mentions uses or regulatory limits but does not contain exposure values/estimates; tag also to regulatory or use-specific if applicable Studies supporting or possibly supporting exposure sections, but not a study included in one or more of the preceding relevant categories ON TOPIC, GENERAL STUDY TAGS Data Type INCLUDE: Empirical Modeled Empirical: measured Modeled: simulated, estimated, modeled Source Type INCLUDE: Database Search Gray Literature o EPA Source o Other Government Source o Industry-Specific Source o Peer-reviewed Literature o Direct Communications Primary Source Secondary Source Determination of source type of database search or gray literature is by search type, rather than keyword. Primary Source: Novel, experimental, modeling Secondary Source: Review Use Specific INCLUDE: Source contains use-specific data or information dye, electronics, nail polish, paint Chemical Specific INCLUDE: Source contains information specific to the chemical of interest NMP and synonyms Regulatory INCLUDE: Source contains a regulatory value/limit Water quality criteria, NAAQS2, IRIS3 OFF TOPIC Off topic INCLUDE: Off topic in context of identified information needs Human Health INCLUDE: Page 76 of 83 ------- Contains information that is potentially on-topic for the human health hazard topic area OTHER Not peer- reviewed INCLUDE: Published without formal peer review. Use in addition to relevant or not relevant (not an exclusive tag). Foreign language INCLUDE: Full-text published in non-English language. Use in addition to relevant or not relevant (not an exclusive tag). Ecological search results may overlap with environmental hazard search results. EPA intends to harmonize results during the refinement phase. 2National Ambient Air Quality Standard integrated Risk Information System Page 77 of 83 ------- E-4 Inclusion/Exclusion Criteria and Tags for the Human Health Hazard Literature Table_Apx E-4. Human Health Hazard Inclusion/Exclusion Criteria and Tags Tag Category Inclusion/Exclusion Criteria Example Keywords ON TOPIC, GENERAL HUMAN HEALTH TAGS Human Hazard ID INCLUDE: Studies evaluating human health effects resulting from exposure to the chemical. Includes epidemiology studies (measure an adverse outcome in an exposed population), experimental studies (e.g. individuals exposed to chemical in a controlled study) and case studies (e.g. individual case report on accidental exposure to chemical) Acute, subchronic, and chronic exposures **Also choose applicable health effect tags in next section "N-Methylpyrrolidone (NMP) Health Effect Tags" case-control study; cohort study; odds ratio; risk ratio; incidence; prevalence Animal Hazard ID INCLUDE: Studies evaluating animal health effects resulting from controlled exposure to the chemical in mammals such as primates, rodents, dog, rabbit, and mink. **Also choose applicable health effect tags in next section "N-Methylpyrrolidone (NMP) Health Effect Tags" EXCLUDE: Studies in birds and fish; these can be tagged to MOA and/or ADME if applicable chronic; developmental; incidence; NOEL/LOEL; NOAEL/LOAEL; dose; response ADME INCLUDE: Studies describing the absorption, distribution, metabolism and elimination (ADME) of the chemical. This may include in vitro studies absorption, distribution, metabolism, elimination, bioavailability, tissue burden, metabolites, analytes, excretion, elimination rates, clearance, half- life, dose-duration, km, ki, vmax, lactational transfer, inhalation pharmacokinetics, toxicokinetics, PBPK, PBTK accumulation or retention in breast milk, serum, plasma, blood, urine, feces, adipose tissue Page 78 of 83 ------- MOA INCLUDE: Studies evaluating the mode of action (MOA) of a chemical (i.e., molecular events occurring after exposure that may contribute to the development of adverse health effects) in animals and humans Evaluation of specific pathways (e.g., through the use of antioxidants to determine importance of ROS in hepatic effects) Studies in knockout mice Assessment of hormone levels or gland function, immune system parameters in vitro models, genomics, proteomics, genotoxicity, indirect genotoxicity, changes in gene expression or mRNA levels Susceptibility INCLUDE: Studies that specifically evaluate genetic traits or variations, subpopulations or lifestages, in relation to N-Methylpyrrolidone (NMP) exposure/effects EXCLUDE: Studies using knock-out mice influence of genetic traits, variations, genetic polymorphisms (e.g. single nucleotide polymorphisms; SNPs) on health effects relating to the chemical ON TOPIC, N-METHYLPYRROLIDONE (NMP) HEALTH EFFECT TAGS Hepatic non-cancer INCLUDE: Studies evaluating hepatic effects in the liver, biliary tract, gall bladder fatty degeneration, cirrhosis, fibrosis, necrosis, hypertrophy, hyperplasia, proliferation, increased/decreased liver enzymes, bile acids, cholesterol and triglycerides in serum/blood, increased/decreased liver weight, jaundice, vacuolization Renal non-cancer INCLUDE: Studies evaluating renal effects in the kidney, bladder, ureter and related nephropathy, oliguria, increased/decreased blood urea nitrogen, nephritis, nephrosis, hyaline droplet formation, necrosis and regeneration of proximal tubules, markers of kidney damage e.g. excretion of proteins/blood in urine, alpha 2U globulin Neurological non-cancer INCLUDE: Studies evaluating effects in the central nervous system (CNS) or peripheral nervous system (PNS), brain, nerves, behavior, neurochemical alterations, sensory effects, neurodevelopmental effects in exposed infants and children changes in brain pathology, CNS depression (dizziness, drowsiness, sleepiness, loss of consciousness/ anesthesia, hypo activity, ataxia, lethargy, impaired coordination or balance, narcosis), nerve/neuronal injury and/or degeneration, neuropsychological outcomes (e.g. mood/personality changes), changes in neurobehavioral tests (cognitive, motor function) and Page 79 of 83 ------- neurophysiological effects (visual and auditory function), memory Reproductive/Developmental non-cancer INCLUDE: Studies examining reproductive outcomes, offspring and/or studies examining developmental effects Notes: Developmental neurotoxicity effects are categorized in the Reproductive/Developmental non- cancer tag and Neurological non-cancer tag reduced fertility, effects on reproductive organs, sperm, estrous cycle, increased resorption and post implantation loss, viability, fetal death, birth weight, growth, maturation, teratogenicity, birth defects, visceral and/or skeletal malformations, follicle counts Hematological/Immunological non-cancer INCLUDE: Studies examining susceptibility or resistance to infection or disease, function of innate or adaptive immunity; Studies examining changes in blood parameters hemoglobin, red blood cell count, platelet count, hematocrit, hypersensitization, increased/decreased white blood cells, prothrombin time, effects on the spleen Bone non-cancer INCLUDE: Studies that evaluate effects on bone bone marrow hypoplasia, increase/decrease in numbers of bone marrow cells, modulation of osteoblast and osteoclast differentiation Other health effect INCLUDE: Studies in which any other non-cancer or cancer health effects, not defined by the categories above, were examined NA ON TOPIC, GENERAL STUDY TAGS Source Type INCLUDE: Database Search Gray Literature o EPA Source o Other Government Source o Industry-Specific Source o Peer-reviewed Literature o Direct Communications Primary Source Secondary Source Determination of source type of database search or gray literature is by search type, rather than keyword Primary Source: Novel, experimental, modeling Secondary Source: Review NOT ON TOPIC Not on topic INCLUDE: Reference is not on topic in the context of any of the outlined categories (or tags) NA Exposure1 INCLUDE: Reference contains exposure information only, i.e., without associated information on health effects (e.g. clinical signs or symptoms in exposed population) and will be evaluated by that team. Notes: industrial hygiene surveys, general populations exposures (e.g. measured in air, water and food) Page 80 of 83 ------- Levels of the chemical in biological tissues or fluids were considered related to the human health discipline and categorized under the ADME tag OTHER Foreign language study INCLUDE: Full-text reference published in non- English language. Use in addition to "on topic" or "off topic tags" Title will likely be in brackets or journal title will be in foreign language only 1An exposure tag was included to capture references potentially relevant to the exposure topic area to be reviewed by exposure experts E-5 Inclusion/Exclusion Criteria for the Environmental Hazard Literature The following are the inclusion criteria used for the results of the ECOTOX literature search. Studies that meet the acceptability criteria are considered on-topic (or applicable). 1. The paper reports toxicology information for the chemical of interest. 2. The article is published in the English language. 3. The study is presented as a full article. 4. The paper is a publicly available document. 5. The paper is the primary source of the data. 6. The paper reports a calculated endpoint. 7. The paper reports that treatment(s) were compared to an acceptable control. 8. The paper reports an explicit duration of exposure. 9. The paper reports a concurrent environmental chemical concentration/dose or application rate. 10. The paper reports the location of the study (e.g., laboratory vs. field). 11. The paper reports a biological effect. 12. The paper reports the species that was tested; and this species can be verified in a reliable source. 13. The paper reports effects associated with a single chemical exposure. For more information, refer to the document "ECOTOX Literature Searches, Citation Identification and Skimming" (https://cfpub.epa.gov/ecotox/blackbox/help/ECOTOXLiteratureSearchesCitationldentificationandSkim ming.pdf). The following is a list of ECOTOX rejection codes, exclusion terms and definitions utilized under the ECOTOX database efforts. Each citation that is identified as off topic (or not applicable) to the ECOTOX database will have one or more of these codes. For more information, refer to the document ECOTOX Literature Searches, Citation, Identification and Skimming (https://cfpub.epa.gov/ecotox/blackbox/help/ECOTOXLiteratureSearchesCitationldentificationandSkim ming.pdf) under Appendix C: Unify References Data Fields and Codes. Page 81 of 83 ------- Table_Apx E-5. ECOTOX Codes Denoting Exclusion Criteria Keyword Description ABSTRACT Study results published as an abstract only. ADDENDUM Publication is a supplement to another publication and attach to that full publication (erratum or addendum). BACTERIA Bacteria and microbes - for microbes, enter bacteria as keyword, Includes microbes and Microtox tests. BENEFICIAL EFFECT Studies that result in a positive effects (improving the health of the organism BIOLOGICAL TOXICANT General biological toxicants including venoms, fungal toxins, Bacillus thuringiensis, and other plant, animal or microbial extracts or toxins not purified. CAS# UNAVAILABLE Chemical is not verifiable or no CAS # available. CHEM METHODS The description of chemical analysis procedures and measurements in a laboratory setting. No organism or biochemical measurements are reported in the paper. ECOCHEM VERIFICATION Publication used to verify chemical CAS or physical/chemical properties. SOURCE EFFLUENT Includes sewage and polluted runoff. Used in aquatic publications. Terrestrial categorized under MIXTURE keyword. FATE Chemical distribution in natural media (water, soil, air) and residue not measured in the organism or valid ECOTOX organism not present. FOOD Test organism is dead or harvested in the form of consumer-ready food products. Frequently studies include analyses of fresh meat or produce purchased in a market, or processed and packaged foods (e.g., wine, cheese, canned fish, sausages, packaged milk, or cereal products). This includes market studies used to enhance the marketability of an organism and maximize a producer's profit. Optimum marbling of meat, color of apple skins, and firmness of bananas for durability in shipping. HUMAN HEALTH Studies with human subjects or with surrogate animal subjects for human health risk assessment. If a surrogate laboratory rodent (RODE) or domestic animal (DOM,DOMA) is tested, citations will be rejected unless the effect is GRO, MOR, POP, BEH (feeding/reproductive behavior only) or REP. INCIDENT Reports of animal deaths by poison, which lacks a usable concentration and/or duration. INCOMPLETE CITATION Citation is not complete; order status ARCHIVE. INCORRECT CITATION Citation is wrong; order status ARCHIVE. INHALE Inhalation dose route only. Keyword also used for intratracheal instillation of a chemical directly into the lungs. METHODS Publication provides documentation for toxicology test methods, experimental design, statistical methods, standard terminology, recently developed test methods. MIXTURE No single chemical tests reported. The exception for In Situ studies (field studies of chemicals mixtures) are coded for bioaccumulation, if the exposure duration and concentrations of any specific chemical component of the ambient water or effluent is given for caged or transplanted organisms. MODELING Modeling only, no new organism exposure data; modeling studies may report original toxicity tests performed as comparisons or as a basis for extrapolation, if so, papers are ordered. NO CONC No usable dose or concentration reported after examination of the entire paper; includes lead shot studies lacking dose information and which report only the number of pellets. Concentrations reported in log units only are not coded. NO DURATION No duration reported (entire publication examined). NO EFFECT No organism effect reported. Chemical metabolism is included (defined as biological effect on the chemical). NO SOURCE Source of publication undetermined; order status ARCHIVE (includes internal chemical company document and personal communication citations). NO TOXICANT No chemical toxicant added or not ecotoxicologically relevant chemical. Page 82 of 83 ------- - includes ambient air component chemicals (ozone, C02, S02) and pollution -other ambient conditions including changes in conditions (other than chemical addition), including radioactivity, ultraviolet light (UV), temperature, pH, salinity, dissolved oxygen (DO), or other water, air or soil parameters NON-ENGLISH Paper's full text language other than English - (these papers do not receive ECOREF numbers). NUTRIENT In situ chemicals tested as nutrients. OIL Oil and petroleum products PUBLAS Paper (by same author/study) was published in another journal or book, ECOREF number of other paper listed in References citation. Ex. Publ As ##### QSAR Quantitative Structure Activity Relationships. REFS CHECKED References in a REVIEW have been checked. RETRACTED Retracted article from publication by journal. REVIEW All toxicity tests reported elsewhere; REVIEW bibliography may be skimmed to identify relevant citations. SEDIMENT CONC Chemical concentration reported in sediment only (if pore or overlying water concentrations reported, then applicable). SKIMMED Used to show that publication has been skimmed for applicable sections. SPECIES VERIFICATION Publication used to verify species common or scientific name. SOURCE SURVEY Measured chemical present in organism, but lacking quantification of exposure; lacks usable concentration and/or duration. VIRUS Virus used as a test organism. YEAST Yeast used as test organism. Page 83 of 83 ------- |