Identifying and Reducing Environmental Health Risks of Chemicals in Our Society: Workshop Summary (2014)

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A Glossary1 Adverse outcome pathway: a conceptual framework that portrays existing knowledge concerning the linkage between a direct molecular initiating event and an adverse outcome, at a level of biological organization relevant to risk assessment (EPA, 2013a). Alternative chemicals: chemicals within the same functional-use group across a consistent and comprehensive set of hazard end points that exhibit safer health and environmental profiles than chemicals of potential concern (EPA, 2013b). Bioaccumulation: general term describing a process by which chemicals are taken up by an organism either directly from exposure to a contaminated medium or by consumption of food containing the chemical (EPA, 2012b). Biological pathway altering dose: exposure level at the low end of the distribution of the pathway-altering dose that is calculated with standard risk assessment approaches and in vitro assays to quantitatively characterize the chemical with high-throughput methods and estimate the external dose that would be required to perturb a biological pathway (Judson et al., 2011). Certain internationally classified substances: are among those identified as priorities for action for the second phase of the Chemicals Management Plan in Canada. The selection of these internationally classified substances for action is based on the categorization process completed in 2006, and new information received as part of the first phase of the Chemicals Management Plan (Government of Canada, 2012a). 1 Most definitions in the glossary are direct quotations from the cited material. 137 

138 ENVIRONMENTAL HEALTH RISKS OF CHEMICALS Chemical Abstract Service Registry numbers (CAS numbers): a unique identifier assigned by the Chemical Abstract Service of the American Chemical Society to identify a chemical substance or molecular structure when there are many possible systematic, generic, proprietary, or trivial names. CAS numbers are used in public and private databases and on Material Data Safety Data Sheets (CAS, 2014). Chemical and Product Categories (CPCat): a database of information on how chemicals are used. The data are divided into types of uses and specific products the chemicals are used in (EPA, 2014b). Chemicals Management Plan: launched in 2006, the government of Canada uses the Chemicals Management Plan to set clear priorities for the assessment and management of chemical substances (Government of Canada, 2014). Clinical evaluation: an evaluation of the safety of specific concentrations and mixtures of ingredients in consumer products; scientists and clinicians look for adverse reactions, mixture interactions, and other safety considerations (Johnson & Johnson, 2014a). Co-exposures: contact or occurrence of more than one exposure (EPA, 2012a). Concentration at steady state (Css): the concentration of a drug or chemical in a body fluid—usually plasma—to achieve a steady state where rates of drug administration and drug elimination are equal (Boston University School of Medicine, 2004). Direct and indirect exposure: direct exposure involves physical contact made between the chemical agent and individual (e.g., skin, lungs, gut), whereas indirect exposure involves transport of the chemical from the source to the environment to the individual (e.g., consumption of fruits and vegetables with pesticide residues) (EPA, 2012a). Dose: total amount of a substance administered to, taken up, or absorbed by an organism, organ, or tissue (IUPAC, 2007). Dose–response relationship: association between dose and the incidence of a defined biological effect in an exposed population usually expressed as a percentage (IUPAC, 2007). 

APPENDIX A 139 Eco exposome: the extension of exposure science from the point of contact between stressor and receptor inward into the organism and outward to the general environment, including the ecosphere (NRC, 2012). Embeddedness: a state of being located or secured within a larger entity or context (Mayhew, 2009). Endocrine Disruptor Screening Program: the 1996 amendments to the Safe Drinking Water Act authorized the U.S. Environmental Protection Agency (EPA) to screen substances that may be found in sources of drinking water for endocrine disruption potential. The EPA established the Endocrine Disruptor Screening Program, a scientific advisory committee, to advise the EPA on establishing a program to carry out Congress’s directives (EPA, 2011). EPA: the U.S. Environmental Protection Agency; mission to protect human health and the environment (EPA, 2014g). ExpoCast: the EPA evaluates the potential risks of the manufacture and use of thousands of chemicals. To assist with this evaluation, the EPA scientists developed a rapid, automated (high-throughput) model using off-the-shelf technology that predicts exposures for thousands of chemicals. These predictions are being used to prioritize the order in which chemicals should be evaluated further. The EPA refers to this research effort as ExpoCast (EPA, 2014d). Exposure: the concentration, amount, or intensity of a particular physical or chemical agent or environmental agent that reaches the target population, organism, organ, tissue, or cell, usually expressed in numerical terms of concentration, duration, and frequency. Process by which a substance becomes available for absorption by the target population, organism, organ, tissue, or cell, by any route (IUPAC, 2007). Global Aquatic Ingredient Assessment (GAIA): a tool from Johnson & Johnson used to assist its formulators with selecting ingredients that have reduced environmental impacts at the end of use phase (Johnson & Johnson, 2014b). 

140 ENVIRONMENTAL HEALTH RISKS OF CHEMICALS Globally Harmonized System of Classification and Labeling Chemicals (GHS): a system for addressing the classification of chemicals by types of hazard and proposing harmonized hazard communication elements, including labels and safety data sheets. It aims at ensuring that information on physical hazards and toxicity from chemicals be available in order to enhance the protection of human health and the environment during the handling, transport and use of these chemicals (UNECE, 2014). Grandfathered: a grandfather clause is a part of a law that says the law does not apply to certain people and things because of conditions that existed before the law was passed (Merriam-Webster, 2014). Green chemistry: the design of chemical products and processes that reduce or eliminate the generation of hazardous substances (EPA, 2014e). GreenScreen® for Safer Chemicals: a method for comparative chemical hazard assessment. It is used by a wide range of professionals, government bodies, nonprofits, businesses, formulators, and product developers, and anybody interested in assessing the inherent hazards of chemicals and their potential effect on human health and the environment (Clean Production Action, 2014). Hazard: set of inherent properties of a substance, mixture of substances, or a process involving substances that, under production, usage, or disposal conditions, make it capable of causing adverse effects to organisms or the environment, depending on the degree of exposure; in other words, it is a source of danger (IUPAC, 2007). High-content data: results from data-rich techniques, such as genomics, proteomics, and high-throughput screens (NRC, 2010). High Production Volume Challenge Program: the EPA program where companies are challenged to make health and environmental effects data publicly available on chemicals produced or imported in the United States in quantities of 1 million pounds or more per year (EPA, 2013c). High-throughput screening assays: in vitro biochemical- and cell-based assays and nonrodent animal models for toxicology testing that allow for much higher throughput at a much reduced cost. In some assays, many thousands of chemicals can be tested simultaneously in days (National Toxicology Program, 2014). 

APPENDIX A 141 In use testing: a review and evaluation of how volunteers use a product in their homes before the product can go to market (Johnson & Johnson, 2014a). In vitro potency: expression of relative toxicity of an agent involving isolated organ, tissue, cell, or biochemical systems as compared to a given or implied standard or reference (IUPAC, 2007). Intrinsic clearance rate: volume of plasma or blood from which a substance is completely removed in a period of time under unstressed conditions (IUPAC, 2007). Least burdensome: the Toxic Substances Control Act (TSCA) of 1976 indicates that the EPA should apply the least burdensome means of adequately protecting against the unreasonable risk. In developing a rule, TSCA directs the EPA to consider and publish a statement with respect to (1) the effect of the chemical substance being regulated on health and the magnitude of exposure of humans to the substance, (2) the effects of such substance on the environment and the magnitude of exposure of the environment to the substance, (3) the benefits of such substance for various uses and the availability of substitutes for such uses, and (4) the reasonably ascertainable economic consequences of the rule, after consideration of the effect on the national economy, small business, technological innovation, the environment, and public health (EPA, 2014j). Level of precaution: decisions employed to achieve a chosen level of health and environmental protection under conditions of uncertainty (WHO, 2004). Life-cycle assessment: a systems-based approach to quantifying the human health and environmental impacts associated with a product’s life from “cradle to grave.” A full life-cycle assessment addresses all stages of the product life cycle and should take into account alternative uses as well as associated waste streams, raw material extraction, material transport and processing, product manufacturing, distribution and use, repair and maintenance, and wastes or emissions associated with a product, process, or service as well as end-of-life disposal, reuse, or recycling (EPA, 2013d). 

142 ENVIRONMENTAL HEALTH RISKS OF CHEMICALS Material safety data sheet: compilation of information required under the Occupational Safety and Health Administration Communication Standard on the identity of hazardous substances, health and physical hazards, exposure limits, and precautions (IUPAC, 2007). Median lethal dose (LD50): statistically derived median dose of a chemical or physical agent expected to kill 50 percent of organisms in a given population under a defined set of conditions (IUPAC, 2007). Molecular epidemiology: the use of the techniques of molecular biology in the study of the distribution and determinants of disease occurrence in human populations (Foxman and Riley, 2001). NexGen: Advancing the Next Generation of Risk Assessment (NexGen) is a component of the EPA’s Chemical Safety for Sustainability Research program and is focused on fostering practical applications on new methods in risk assessment (EPA, 2013e). Pattern: information or data on human activity used in exposure assessments (EPA, 2012a). Persistence: attribute of a substance that describes the length of time that the substance remains in a particular environment before it is physically removed or chemically or biologically transformed (IUPAC, 2007). Pharos Project: a database that contains product and hazard information from more than 300 companies to help users locate materials to meet their current needs; a platform where users can discuss what products support environmental, health, and social equity practices (Pharos, 2014). Prioritization: organization of chemical substances in order of priority so the most important receives detailed evaluation and assessment. Many approaches consider the degree of hazard and extent of exposure potential when prioritizing chemicals (ACC, 2011). Production volume: volume of chemicals produced. REACH: the European Commission Regulation 1907/2006 on the Registration, Evaluation, Authorisation, and Restriction of Chemicals. REACH streamlines and improves the former legislative framework on chemicals of the European Union, and makes industry responsible for assessing and managing the risks posed by chemicals and providing appropriate safety information to their users (European Commission, 2013). 

APPENDIX A 143 Reverse engineering: the separation, identification, and quantitation of ingredients in a formulation (Chemir, 2014). Risk: probability of adverse effects caused under specified circumstances by an agent in an organism, a population, or an ecological system; probability of a hazard causing an adverse effect; and expected frequency of occurrence of a harmful event arising from such an exposure (IUPAC, 2007). Risk assessment: identification and quantification of the risk resulting from a specific use or occurrence of a chemical or physical agent, taking into account possible harmful effects on individuals or populations exposed to the agent in the amount and manner proposed and all the possible routes of exposure (IUPAC, 2007). SIN (Substitute It Now!) List: a nongovernmental organization driven project (led by ChemSec) to assist with the REACH legislative process and give guidance to companies on safer chemical substitutions for potentially hazardous chemicals (ChemSec, 2013). SNAcs: as part of the Chemical Management Plan, Environment Canada or Health Canada may place restrictions on reintroduction and new uses of existing chemical substances using Significant New Activity (SNAc) provisions. The SNAc provisions are very similar to SNURs issued by the EPA (Government of Canada, 2012b). SNUR: after issuing a Consent Order, the EPA generally promulgates a significant new use rule (SNUR) that binds all manufacturers and processors to the terms and conditions contained in the Consent Order. The SNUR requires that manufacturers (which include importers) and processors of certain substances notify the EPA at least 90 days before beginning any activity that the EPA has designated as a “significant new use.” This allows the EPA the opportunity to review and if necessary prevent or limit potentially adverse exposure to, or effects from, the new use of the substance (EPA, 2014f). Sourcing raw materials: the process of obtaining raw materials from suppliers (Johnson & Johnson, 2014a). 

144 ENVIRONMENTAL HEALTH RISKS OF CHEMICALS Substance Groupings Initiative: plan to assess and manage, where appropriate, the potential health and ecological risks associated with nine groupings of chemical substances (identified based on structural or functional similarities) selected for further action based on a categorization exercise completed as part of the Chemicals Management Plan (defined earlier) (Government of Canada, 2013). Substitution: the move from problematic chemicals to safer chemicals (alternative chemicals), while minimizing the likelihood of unintended consequences (EPA, 2014c). Surveillance: systematic ongoing collection, collation, and analysis of data and the timely dissemination of information to those who need to know in order that action can be taken to initiate investigative or control measures (IUPAC, 2007). Sustainability: creates and maintains the conditions under which humans and nature can exist in productive harmony, that permit fulfilling the social, economic, and environmental requirements of present and future generations (EPA, 2014k). Tox21: an interagency federal research program to use robotics technology to screen thousands of chemicals for potential toxicity, using screening data to predict the potential toxicity of chemicals and developing a cost-effective approach for prioritizing the thousands of chemicals that need toxicity testing (EPA, 2014a). ToxCastTM: a multiyear effort launched in 2007 that uses automated chemical screening technologies (high-throughput screening assays) to expose living cells or isolated proteins to chemicals. The cells or proteins are then screened for changes in biological activity that may suggest potential toxic effects and eventually potential adverse health effects (EPA, 2014i). Toxicity: capacity to cause injury to a living organism defined with reference to the quantity of substance administered or absorbed, the way the substance is administered and distributed in time (single or repeated doses), the type of severity of injury, the time needed to produce the injury, the nature of the organism(s) affected, and other relevant conditions (IUPAC, 2007). 

APPENDIX A 145 Toxicity assessment: the purpose of the toxicity assessment is to weigh available evidence regarding the potential for particular contaminants to cause adverse effects in exposed individuals and to provide, where possible, an estimate of the relationship between the extent of exposure to a contaminant and the increased likelihood and/or severity of adverse effects (EPA, 1989). Toxics Use Reduction Institute (TURI): established by the Massachusetts Toxics Use Reduction Act of 1989, TURI collaborates with businesses, community organizations, and government agencies to reduce the use of toxic chemicals, protect public health and the environment, and increase competitiveness of Massachusetts businesses (TURI, 2014). TOXLINE: Toxicology Literature Online; data network of references from toxicology (NLM, 2014). TSCA: the Toxic Substances Control Act (TSCA) of 1976 provides the EPA with authority to require reporting, record-keeping and testing requirements, and restrictions relating to chemical substances and/or mixtures. Certain substances are generally excluded from TSCA, including, among others, food, drugs, cosmetics, and pesticides (EPA, 2014h). Virtual tissue model: innovative paradigms for understanding disease progression in silico cross-scale models of cellular organization and emergent functions. Tissues are the clinically relevant level for diagnosing and treating the transition from normal to adverse states in chemical-induced toxicities leading to cancer, immune dysfunction, developmental defects, and more (EPA, 2013f). REFERENCES ACC (American Chemistry Council). 2011. ACC prioritization screening approach. Available at http://www.americanchemistry.com/Prioritization- Document (accessed April 4, 2014). Boston University School of Medicine. 2004. Glossary of terms and symbols used in pharmacology. Available at http://www.bumc.bu.edu/busm- pm/academics/resources/glossary/#c (accessed April 4, 2014). CAS (Chemical Abstracts Service). 2014. CAS: A division of the American Chemical Society. FAQs. Available at https://www.cas.org/about-cas/faqs (accessed April 4, 2014). 

146 ENVIRONMENTAL HEALTH RISKS OF CHEMICALS Chemir. 2014. Definitive deformulation. Available at http://www.chemir.com/ deformulation.html (accessed April 4, 2014). ChemSec. 2013. What we do: SIN List. Available at http://www.chemsec.org/ what-we-do/sin-list (accessed April 4, 2014). Clean Production Action. 2014. GreenScreen® for Safer Chemicals. Available at http://www.greenscreenchemicals.org (accessed April 4, 2014). EPA (U.S. Environmental Protection Agency). 1989. Chapter 7: Toxicity assessment. In Risk assessment guidance for Superfund Volume I human health evaluation manual (Part A). Washington, DC: EPA. Available at http://www.epa.gov/oswer/riskassessment/ragsa/pdf/rags_a.pdf (accessed April 4, 2014). EPA. 2011. Endocrine Disruptor Screening Program (EDSP): EDSP background. Available at http://www.epa.gov/scipoly/oscpendo/pubs/edsp overview/background.htm (accessed April 4, 2014). EPA. 2012a. Thesaurus of terms used in microbial risk assessment—5.5 exposure. Available at http://water.epa.gov/scitech/swguidance/standards/ criteria/health/microbial/t55.cfm#T55030 (accessed April 4, 2014). EPA. 2012b. Waste and cleanup risk assessment glossary. Available at http://www.epa.gov/oswer/riskassessment/glossary.htm#c (accessed April 4, 2014). EPA. 2013a. Adverse outcome pathway (AOP) wiki. Available at http://www.epa. gov/research/priorities/docs/aop-wiki.pdf (accessed April 4, 2014). EPA. 2013b. Chemical alternatives assessment. Available at http://www.epa. gov/sustainability/analytics/chem-alt.htm (accessed April 4, 2014). EPA. 2013c. High Production Volume (HPV) challenge. Available at http://www.epa.gov/hpv (accessed April 4, 2014). EPA. 2013d. Life-cycle assessment. Available at http://www.epa.gov/sustain ability/analytics/life-cycle.htm (accessed April 4, 2014). EPA. 2013e. NexGen: Advancing the next generation of risk assessment. Available at http://www.epa.gov/risk/nexgen (accessed April 4, 2014). EPA. 2013f. What are virtual tissues? Available at http://www.epa.gov/ncct/ virtual_tissues/what.html (accessed April 4, 2014). EPA. 2014a. Computational toxicology research: Tox21. Available at http://epa.gov/ncct/Tox21 (accessed April 4, 2014). EPA. 2014b. CPCat: Chemical and product categories. Available at http://actor.epa.gov/cpcat/faces/basicInfo.xhtml (accessed April 4, 2014). EPA. 2014c. Design for the environment: Alternatives assessment. Available at http://www.epa.gov/dfe/alternative_assessments.html (accessed April 4, 2014). EPA. 2014d. ExpoCastTM. Available at http://www.epa.gov/ncct/expocast (accessed April 4, 2014). EPA. 2014e. Green chemistry. Available at http://www2.epa.gov/green- chemistry (accessed April 4, 2014). 

APPENDIX A 147 EPA. 2014f. New chemical consent orders and significant new use rules (SNURs). Available at http://www.epa.gov/oppt/newchems/pubs/cnosnurs.htm (accessed April 4, 2014). EPA. 2014g. Our mission and what we do. Available at http://www2.epa.gov/ aboutepa/our-mission-and-what-we-do (accessed April 4, 2014). EPA. 2014h. Summary of the Toxic Substances Control Act. Available at http://www2.epa.gov/laws-regulations/summary-toxic-substances-control-act (accessed April 4, 2014). EPA. 2014i. ToxCastTM: Advancing the next generation of chemical safety evaluation. Available at http://www.epa.gov/ncct/toxcast (accessed April 4, 2014). EPA. 2014j. TSCA Section 6 actions. Available at http://www.epa.gov/oppt/ existingchemicals/pubs/sect6.html (accessed April 4, 2014). EPA. 2014k. What is sustainability? Available at http://www.epa.gov/sustainability/ basicinfo.htm (accessed April 4, 2014). European Commission. 2013. REACH: Registration, evaluation, authorization, and restriction of chemicals. Available at http://ec.europa.eu/enterprise/ sectors/chemicals/reach/index_en.htm (accessed April 4, 2014). Foxman, B., and L. Riley. 2001. Molecular epidemiology: Focus on infection. American Journal of Epidemiology 153(12):1135–1141. Government of Canada. 2012a. Internationally classified substance groups. Available at http://www.chemicalsubstanceschimiques.gc.ca/group/internat/ index-eng.php (accessed April 4, 2014). Government of Canada. 2012b. The Significant New Activity (SNAc) approach. Available at http://www.chemicalsubstanceschimiques.gc.ca/plan/approach- approche/snac-nac-eng.php (accessed April 4, 2014). Government of Canada. 2013. The Substance Groupings Initiative. Available at http://www.chemicalsubstanceschimiques.gc.ca/group/index-eng.php (accessed April 4, 2014). Government of Canada. 2014. Chemicals Management Plan. Available at http://www.chemicalsubstanceschimiques.gc.ca/plan/index-eng.php (accessed April 4, 2014). IUPAC (International Union of Pure and Applied Chemistry). 2007. Glossary of terms used in Toxicology, 2nd edition. Pure and Applied Chemistry 79(7):1153–1344. Available at http://sis.nlm.nih.gov/enviro/iupacglossary/ glossarym.html (accessed April 2, 2014). Johnson & Johnson. 2014a. Our five-level safety assurance process. Available at http://www.safetyandcarecommitment.com/safety-promise (accessed April 4, 2014). Johnson & Johnson. 2014b. Product disposal: End of use. Available at https://www.jnj.com/caring/citizenship-sustainability/strategic-framework/ end-of-life (accessed April 4, 2014). 

148 ENVIRONMENTAL HEALTH RISKS OF CHEMICALS Judson, R. S., R. J. Kavlock, R. W. Setzer, E. A. Hubal, M. T. Martin, T. B. Knudsen, K. A. Houck, R. S. Thomas, B. A. Wetmore, and D. J. Dix. 2011. Estimating toxicity-related biological pathway altering doses for high- throughput chemical risk assessment. Chemical Research in Toxicology 24(4):451–462. Mayhew, S. 2009. A dictionary of geography. Oxford: Oxford University Press. Merriam-Webster. 2014. Grandfather clause. Available at http://www.merriam- webster.com/dictionary/grandfather%20clause (accessed April 4, 2014). National Toxicology Program. 2014. Tox21. Available at http://ntp.niehs.nih. gov/?objectid=06002ADB-F1F6-975E-73B25B4E3F2A41CB (accessed April 4, 2014). NLM (U.S. National Library of Medicine). 2014. Toxicology Literature Online (TOXLINE). Available at http://toxnet.nlm.nih.gov/html/TOXLINE.htm (accessed April 4, 2014). NRC (National Research Council). 2010. Toxicity pathway-based risk assessment: Preparing for paradigm change: A symposium summary. Washington, DC: The National Academies Press. NRC. 2012. Exposure science in the 21st century: A vision and a strategy. Washington, DC: The National Academies Press. Pharos. 2014. About Pharos. Available at http://www.pharosproject.net/about/ index (accessed April 4, 2014). TURI (Toxics Use Reduction Institute). 2014. About: Who we are. Available at http://www.turi.org/About (accessed April 4, 2014). UNECE (United Nations Economic Commission for Europe). 2014. Globally Harmonized System of Classification and Labeling of Chemicals (GHS). Available at http://www.unece.org/trans/danger/publi/ghs/ghs_welcome_e.html (accessed April 4, 2014). WHO (World Health Organization). 2004. The precautionary principle: Protecting public health, the environment, and the future of our children. Copenhagen: WHO. Available at http://www.euro.who.int/__data/assets/ pdf_file/0003/91173/E83079.pdf (accessed April 4, 2014).