There is a rich and growing literature on chemical substitution that dates from the early 1990s, when scientists and regulators in Europe and the United States (U.S.) began to categorize and prioritize chemicals of concern. Chemical alternatives assessment emerged from these regulatory efforts. It refers to a process for identifying, comparing, and selecting safer alternatives to chemicals of concern. The goal of chemical alternatives assessment is facilitating an informed consideration of the advantages and disadvantages of alternatives to a chemical of concern. Over time, government agencies, academic institutions, and professional organizations developed different alternatives assessment frameworks, each with a particular focus. The results from these assessments varied depending on whether the emphasis was on protecting workers, communities surrounding industrial plants, end users of products, or other interests.
RECENT DRIVERS RESULTING IN CHEMICAL ALTERNATIVES ASSESSMENT
Historically, regulations governing chemical use have often focused on the effects of widely used chemicals on human health including their potential to cause cancer and other adverse health effects. As scientific knowledge has expanded, awareness of the mechanisms through which chemicals may exert harmful effects on human health has increased, along with an understanding of their effects on other species and ecosystems. At the same time, many factors, including unprecedented access to information on the internet, have resulted in greater public awareness of potential hazards in the products they use. Along with scientific advances and public awareness, the U.S. Centers for Disease Control and Prevention (CDC) and the U.S. Environmental Protection Agency (EPA) are collecting more information on U.S. citizens’ exposure to chemicals. For example, the CDC’s Fourth National Report on Human Exposure to Environmental Chemicals published information about the levels of 212 xenobiotic compounds (substances that are not produced by the body) or metabolites in the blood and urine of U.S. study participants (CDC 2009). The report revealed widespread exposure to some commonly used industrial chemicals found in household products, including polybrominated diphenyl ethers (PBDEs), bisphenol A (BPA), and perfluorinated chemicals.
Certain regulatory agencies have identified so-called priority chemicals, those considered to be carcinogenic, mutagenic, reproductive toxicants, and/or fall into the category of PBTs: persistent, bioaccumulative, and toxic chemicals. Many of these chemicals are associated with industrial waste; can contaminate soil, sediment, groundwater, surface water, and air; and are found in plant, animal, and human tissue. In the U.S., examples of priority chemicals may be found on lists developed by some states, including Washington State (Reporting List of Chemicals of High Concern to Children) (WA Department of Ecology 2014) and California (Candidate Chemicals List) (CA DTSC 2010), the EPA’s National Waste Minimization program’s list of priority chemicals (EPA 2012a), and on lists developed by environmental action groups, retailers, and many manufacturers. The European Union’s Candidate List of Substances of Very High Concern for Authorisation (ECHA 2014a) serves a similar purpose abroad. High-priority chemicals are frequent targets for alternatives assessments. Identification of high-priority chemicals and other chemicals of concern has prompted a growing number of state and local governments, as well as major companies, to take steps beyond existing hazardous chemical federal legislation. Between 1990 and 2009, at least 18 states, 6 counties, and 6 city governments enacted laws restricting PBDEs, BPA, lead, chromated copper arsenate, phthalates, dioxin, perchloroethylene, or formaldehyde (Edwards 2009). For example, the Safer Consumer Product Regulations were developed by California’s Department of Toxic Substances Control to require manufacturers and other responsible entities to “seek safer alternatives to harmful chemical ingredients in widely used products” (CA DTSC 2013a). Europe’s Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Substances of Very High Concern list (ECHA 2014b) and Canada’s Chemicals Management Plan (Government of Canada 2014) are also driving
chemical substitution. In addition, several nongovernmental organizations (NGOs) are raising awareness of the need for chemical substitutions, and have developed approaches that have informed alternatives assessments. These efforts include Clean Production Action’s GreenScreen® for Safer Chemicals, which is explained later in this report.
In response to these drivers, major companies and retailers (e.g., Bissell, Dell, Hewlett-Packard (HP), Herman Miller, K-Mart, Nike, S.C. Johnson, Sears, Toys R Us, Wal-Mart, Whole Foods, and Volvo) and collective industry efforts (such as the textile industry’s Zero Discharge Coalition and the building industry’s LEED certification program) have adopted policies to eliminate or phase out particular chemicals. Other manufacturers report they will go beyond regulatory restrictions in selecting the chemicals they will use (Lavoie et al. 2010) as part of their sustainability programs. Other retailers certify that the products they sell exhibit superior environmental performance. Collectively, these activities represent a trend toward more market- and product-based considerations of chemical safety.
Interest in approaches and policies that ensure that any new substances substituted for chemicals of concern are assessed as carefully and thoroughly as possible has also burgeoned (Hogue 2013). The overarching goal of these approaches is to avoid regrettable substitutions. Regrettable substitutions occur when a toxic chemical is replaced by another chemical that later proved unsuitable because it, too, turned out to be a PBT, or because of other concerns. One example of a regrettable substitution occurred in the 1990s and involved the replacement of methylene chloride with n-hexane in automotive brake cleaners. Although n-hexane performed well as a brake cleaner, some auto mechanics exposed to n-hexane developed peripheral neuropathy (Wilson et al. 2007). Similarly, recent research has raised concerns about the toxicity and estrogenic activity of plastic materials that served as a replacement for BPA (Kuruto-Niwa et al. 2005; Viñas and Watson 2013).
GOVERNMENTAL EFFORTS TO DRIVE ADOPTION OF SAFER CHEMICALS
The U.S. government initiated efforts to drive adoption of safer chemicals as early as the 1950s (Lofstedt 2014). Over the years, both regulatory and non-regulatory policies have been enacted that require, conduct, or support the development of chemical alternatives assessments. U.S. government efforts include EPA’s Significant New Alternatives Policy (SNAP) program (EPA 2014a), which requires companies to seek approval for substitution of ozone-depleting substances. Also, the Pollution Prevention Act of 1990 includes “reformulation or redesign of products [and] substitution of raw materials” as an approach to reduce sources of pollution. The EPA’s Chemical Management program (EPA 2013a) is also affecting chemical substitution. Since December 2009, EPA has published action plans for ten chemicals or chemical classes, which include various recommendations for rule making under the 1976 Toxic Substances Control Act (TSCA) and recommendations for conducting alternatives assessments under EPA’s Design for the Environment program, which is specifically for BPA, PBDEs, hexabromocyclododecane, and phthalates (EPA 2012b). With a work plan for 83 chemicals, EPA now has a guide that will be used to focus its activities over the next several years.
At the state and local level, many jurisdictions have enacted requirements that government suppliers report on chemicals of concern and make substitutions. This practice enables government agencies to “lead by example” by using the least toxic alternatives for a particular chemical or product class. Examples of policies that establish requirements for use of safer alternatives in procurement include New York Executive Order No. 4, Establishing a State Green Procurement and Agency Sustainability Program. This policy “directs state agencies, public authorities and public benefit corporations to green their procurements and to implement sustainability initiatives” and establishes processes for agencies to follow in identifying preferred products, such as cleaning products. It also includes a list of chemicals to avoid when making purchasing decisions.
Also notable is the establishment of new organizational structures for government agencies that enable them to collaborate and share information on chemicals and alternatives and develop consistent approaches. For example, the Interstate Chemicals Clearinghouse (IC2) is an association of state, local, and tribal governments that shares information on chemical hazards and priorities, chemical use in products, and safer alternatives. One of the organization’s goals is to develop consistent frameworks for assessing chemical alternatives.
In addition to U.S. efforts, other countries have developed regulations that include the substitution principle and require industry to transition to safer alternatives if they are available. In addition to the European REACH program and Canada’s Chemicals
Management Plan mentioned above, the Swedish Non-Toxic Environment program (KEMI 2014) is another example. These policies and programs stipulate that replacements should be made, even in the absence of quantitative risk estimates, if changing a chemical substance or its design can reduce risks to the environment and human health (Hansson and Ruden 2007).
GROWTH IN EVALUATIVE APPROACHES
Over the past decade, the number of approaches for evaluating chemical toxicity has grown substantially in response to many factors, ranging from advances in molecular biology to public pressure. Alternatives assessment policies have also evolved as governments grapple with developing procedures to avoid regrettable substitutions. Earlier alternatives assessment policies did not always address the issue of which alternatives should be allowed to replace a chemical of concern or how alternatives should be evaluated.
TSCA Reform and the EPA’s Development of Tools
Running in parallel with other efforts to drive safer chemical adoption are attempts to reform TSCA. This law “authorizes the EPA to regulate chemicals that pose an unreasonable risk to human health or the environment” (GAO 2005). However, the agency has had difficulty demonstrating that specific chemicals pose an unreasonable risk, leading to questions about whether TSCA provides the agency with enough regulatory force to protect people and the environment against chemical hazards.
In recent years, the EPA has begun implementing new ideas for managing toxic chemicals under its existing TSCA authority, drawing on more than 20 years of scientific effort to develop tools to predict toxicity of chemicals. The EPA, in collaboration with other federal entities (Collins et al. 2008), is also conducting research and developing toxicity testing and in silico5 approaches to characterize, predict, and communicate the potential of existing and new chemicals to pose human health and ecological risks. These data, methods, and tools are resulting in an increased ability to conduct chemical alternatives assessments. Because the universe of untested chemicals is vast, even if TSCA is eventually reformed, the approaches being developed are likely to be used by the EPA and other stakeholders, including industry, to ensure chemical safety in the short and intermediate term. By making more chemical data, including information about exposure, hazard, and dose-response relationships, more easily accessible through a variety of databases and dashboards, the EPA is improving the ability of interested parties to evaluate chemical substitutes. Having more institutions and companies complete chemical substitution assessments helps enhance the EPA’s objective of ensuring safer chemistry.
Green Chemistry
Another influence on how alternative chemicals are considered is the growing “green chemistry” movement, recognized through the EPA’s Presidential Green Chemistry Challenge Awards. These awards recognize the use of green chemistry, defined by the EPA as the “design of chemical products and processes that reduce or eliminate the use or generation of hazardous substances” (EPA 2014b). One goal of green chemists is to design new chemicals that are inherently safer. This involves a consideration of safer chemical synthesis approaches, the environmental and biological fate of chemicals, and how and where a chemical is transported. According to Paul Anastas, one of the green chemistry movement’s advocates, chemists who follow these principles can simultaneously “bring about environmental improvement benefiting human health and economics and profitability” (Harris 2012).
Members of the Committee on the Design and Evaluation of Safer Chemical Substitutions—A Framework to Inform Government and Industry Decisions were selected for their expertise in chemistry, chemical engineering, computational modeling, toxicology, ecotoxicology, risk assessment, and public health. The committee was specifically asked to accomplish the following task:
An ad hoc committee shall develop and demonstrate a decision framework for evaluating potentially safer substitute chemicals as determined by human health and ecological risks. The committee shall
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5 The term in silico is used in this report to describe prediction and modeling (typically computational modeling) of effects based on information about a chemical’s structure or physicochemical characteristics, including but not limited to structural alerts and structure-activity relationship analysis.
identify the scientific information and tools required by regulatory agencies and industry to improve and increase consideration of potential health and environmental impacts early in the chemical design process. The decision framework shall be capable of integrating multiple and diverse data streams to support early consideration of potential health and environmental impacts as a part of fit-for-purpose decision making.
The framework shall discuss how risk (hazard and potential for human exposure and toxicity) and environmental impact (ecological risks) can be characterized for chemical substitutions within the context of the full range of benefits and shortcomings of substitutes, and how tradeoffs between these risks and factors such as product functionality, product efficacy, process safety and resource use can be quantified.
In its report, the committee shall describe the framework and provide at least two examples that demonstrate how different users in contrasting decision contexts with diverse priorities can apply the framework. These examples shall include demonstration of how high throughput and high content data streams could inform assessment of potentially safer substitutes early in the chemical development process.
Approach to the Study
Two recent National Research Council (NRC) reports that explored new approaches to assessing chemical safety influenced the committee’s development of its alternatives assessment framework. The NRC’s 2007 report, Toxicity Testing in the 21st Century: A Vision and a Strategy, provides a synopsis of how advances in systems biology, in vitro testing in cells and tissues, and related fields could fundamentally change chemical hazard assessment. This new approach to toxicity testing shifts the focus from animal studies to the use of human cells or cellular components (i.e., in vitro testing) to study chemicals’ effects on biological processes. While this approach is not without its critics, the report (NRC 2007) and its advocates state that it has the potential to provide information about toxicity much more quickly than conventional animal-based testing.
The committee also considered the NRC’s 2009 report, Science and Decisions: Advancing Risk Assessment, which concluded that the risk assessment process used by the EPA to estimate the effects of exposure to chemicals was often hindered by disconnects between available scientific data and the information needs of regulators. The report recommended that the EPA streamline the risk assessment process to allow for the appropriate use of available scientific data and ensure that assessments are tailored to meet the specific needs of the problem. To do so, the report recommended that the EPA adopt a three-phase framework that begins with enhanced problem formulation and scoping, a step that identifies the types of technical analyses needed to evaluate and discriminate among the available risk management options (NRC 2009).
In evaluating the literature, the committee found that various definitions have been applied to the terms alternatives assessment and alternatives analysis. For this report, the committee has used these terms interchangeably to describe the framework for safer chemical substitutions as a structured approach for considering human health and environmental hazards associated with different chemicals or chemical-dependent processes. Safer chemical substitutions can involve two chemical-based approaches: (1) substituting a chemical with another existing one or (2) synthesizing a new chemical to meet the original chemical’s functional role. The second approach illustrates how the principles of green chemistry have become an integral component of alternatives assessment. The committee’s framework incorporates elements of this philosophy.6
Many assessments focus on the intended use or functionality of the chemical (e.g., surfactant, solvent, anti-oxidant). In these cases, manufacturers and other parties select chemical alternatives to obtain the same or similar functionality. The ultimate goal of this process is to lessen the risk by reducing the inherent hazard associated with a chemical or chemical-based process. In some cases, manufacturing or synthetic methods can be redesigned in order to remove the need for a hazardous chemical or process. Therefore, the committee also sought to develop a framework that
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6 Although changes to materials or designs might also provide alternatives to chemicals of concern, the Statement of Task specifically directs that the framework should address safer substitute chemicals, and thus the committee’s framework is focused on the case of chemical substitution. Finding a non-chemical approach to achieve the desired function was not the committee’s focus but is touched on in Chapter 13.
could consider the intended use of a chemical in a manufacturing process or end product.
Box 1-1 is a more detailed description of the committee’s definition of alternatives assessments and chemical substitution.
The committee also developed working definitions for the following terms that are used throughout the report:
- Framework: As used by the committee, a framework is a high-level organizational approach to rigorously compare chemical alternatives to determine which substitute(s) are safer. A framework conventionally involves a sequential series of steps or a process flowchart. Both the decision points and the order that the steps must be carried out are generally fixed. Frameworks for chemical substitution include steps and may prescribe which tools are used. Some frameworks disclose their underlying logic.
- Step: A step is a series of task(s) that need(s) to be completed in a given step or box in the analysis framework. A step is often an established method or approach that also can be used—and is usually valid—as a stand-alone analysis. Examples of steps include performance assessment, hazard assessment, analyses of cost and availability, analysis of life cycle impacts, and assessments of social impacts.
- Tools: The technical methods, approaches, software, or databases used to execute each step in the committee’s Safer Chemical Substitution framework are considered tools. Which tools can be used to complete a given step may or may not be defined by the framework. Examples of applicable tools include the freely available GreenScreen® for Safer Chemicals, which can be used for hazard screening, and SimaPro, which can be used for evaluating life cycle impacts.
- Transparency: The committee adapted the EPA’s description of transparency in risk assessment to alternatives assessment: Transparency is “fully and explicitly disclos[ing] the assessment methods, default assumptions, logic, rationale, extrapolations, uncertainties, and overall strength of each step in the alternative assessment” (EPA 2012c).
BOX 1-1
CHEMICAL ALTERNATIVES ASSESSMENT
What is a Chemical Alternatives Assessment?
The committee defined alternatives assessment as a process for identifying, comparing, and selecting safer alternatives to chemicals of concern on the basis of their hazards, comparative exposure, performance, and economic viability.a A chemical of concern can be a chemical in any material, process, or technology. A safer alternative represents an option that is less hazardous to humans and the environment than the existing chemical or chemical process. A safer alternative to a particular chemical of concern may include a chemical substitute or a change in materials or design that eliminates the need for a chemical alternative.
The Differences between Alternatives Assessment and Other Approaches
To further clarify its task, the committee noted the differences between an alternatives assessment and other approaches. The definitions below explain three other assessments used. Typically, alternatives assessments do not include these factors.
- A safety assessment is when the primary goal is to ensure that exposure to a particular substance is below some prescribed standard.
- A risk assessment is a calculation of the risk associated with a given level of exposure.
- A sustainability assessment examines all aspects of the life cycle of a chemical and alternatives, including energy and material use. Ideally, in an alternatives assessment, it is important to at least consider all life cycle segments that would be affected by chemical substitutions to get the most comprehensive view of potential impacts and trade-offs. However, such a detailed assessment is rarely attainable given the limits in current life cycle assessment tools and could potentially lead to inaction.
a This definition, with the addition of comparative exposure, builds upon but significantly modifies the definition from the meeting, Building a Chemical Commons: Data Sharing, Alternatives Assessment and Communities of Practice (BizNGO 2013).
Transparency promotes broad participation by stakeholders in the alternatives assessment. The committee recognizes that while transparency is a goal to strive for, it cannot always be expected from private entities. In any case, the committee calls for internal documentation of the assessment methods, default assumptions, logic, rationale, extrapolations, uncertainties, and overall strength of each step in the alternatives
assessment even if the documentation is not publicly disclosed.
The committee also considered existing alternatives assessment frameworks and tools. Rather than conduct a systematic review of the literature, the committee took advantage of several recently published reviews. For example, several frameworks and tools were identified in the Organisation for Economic Development (OECD) report, Current Landscape of Alternatives Assessment Practice: A Meta-Review (OECD 2013a). In this report, the OECD’s Ad Hoc Group on Substitution of Harmful Chemicals compiled extensive information on frameworks, methods, and tools that can be used for assessing alternatives to chemicals of concern (OECD 2013a). Another recent literature review examined more than 20 alternatives assessment frameworks (Edwards et al. 2011). Based on the committee’s analysis of these reviews, a subset of existing frameworks were identified for more detailed consideration; this selection was based on: (1) availability in the public domain, (2) consideration of one or more elements (e.g., human toxicity, ecotoxicity) deemed important to the committee, and (3) use by one or more regulatory body.
Frameworks considered by the committee included:
- BizNGO Alternatives Assessment Protocol (Rossi et al. 2012)
- California Safer Consumer Products Regulation (CA DTSC 2013a)
- Design for the Environment Chemical Alternatives Assessments (EPA 2014c)
- German Guide on Sustainable Chemicals (Reihlen et al. 2011)
- Interstate Chemicals Clearinghouse Alternatives Assessment Guide (IC2 2013)
- Lowell Center Alternatives Assessment Framework (Rossi et al. 2006)
- REACH Guidance on the Preparation of An Application for Authorisation (ECHA 2011)
- TURI Alternatives Assessment Process Guidance (TURI 2006a)
- UNEP Persistent Organic Pollutants Review Committee General Guidance on Alternatives (UNEP 2009)
In addition to these frameworks, the committee considered two tools. The committee looked at the GreenScreen® for Safer Chemicals tool in detail because it is integral or related to several of the frameworks and is specifically intended for comparative chemical hazard assessment (Clean Production Action 2014). The committee also considered the University of California at Los Angeles (UCLA) multi-criteria decision analysis tool (Malloy et al. 2011).
The structure of each framework was evaluated and helped guide the development of the committee’s framework. Throughout the process, several key decisions, listed below, were made, which also helped determine the framework’s structure.
- The framework is to be used by a multidisciplinary team of individuals with training and expertise in toxicology (human health and ecotoxicology), exposure assessment, chemistry, and life cycle assessment. Additional expertise in engineering, epidemiology, social sciences, economics, and cost analysis may also be required. Assessors without such expertise, such as small- and medium-sized firms, may need user-friendly assessment tools or technical support to carry out parts of the committee’s framework.
- The framework should provide maximum flexibility to the user while identifying critical steps that should be retained in all alternatives assessments.
- The framework should not be overly prescriptive by specifying all steps or tools needed to conduct an alternatives assessment. This approach provides the greatest flexibility to end users, allowing them to incorporate different steps and tools into the framework.
- The committee decided to focus its attention on technical aspects of the framework rather than offer opinions on policy decisions that are inherent in alternatives assessment.
- Certain activities, while important to alternatives assessment, were deemed to be beyond the scope of the current project or were not well suited to the committee’s scientific expertise. The committee provides sufficient information for the reader to understand the general approach needed, but is directed to more detailed references for additional information on topics such as:
- The criteria and processes used for identifying chemicals of concern.
- A complete discussion of life cycle analysis (LCA) practice.
- A detailed guidance on conducting economic or social impact assessments.
Organization of Report
The report is organized into 13 chapters and four appendices. Chapter 2 provides an overview of the frameworks that were considered by the committee. Chapter 3 introduces the overall structure of the committee’s framework. Chapter 4 details the initial steps (scoping, problem formulation, and initial screening) of an alternatives assessment, after a chemical of concern has been identified. Chapter 5 addresses physicochemical properties that should be considered during an alternatives assessment. Chapter 6 presents the concept of comparative exposure, a key part of the committee’s framework that differentiates it from other approaches. Chapters 7 and 8 address hazard assessment for ecotoxicity and human health, respectively. Chapter 9 discusses how to integrate the information about the chemical and its potential alternatives to make informed decisions. This is followed by Chapter 10, which presents an overview of contextual information that the committee did not comment on in great detail, including how to consider the impact of alternatives at various stages of the life cycle and impacts that are broader than human and ecological hazard. Chapter 11 describes the final steps in the framework: identifying acceptable alternatives, selecting final or preferred ones from the options, and implementing the selected alternatives. In Chapter 12, two examples of how to implement the committee’s thinking are presented in an alternatives analysis of glitazone and decabromodiphenyl ether. Finally, Chapter 13 describes innovation in process and chemical design, including specifics on how to consider properties upfront when developing new chemical entities. Appendix A provides biographic information on the committee. Appendix B accompanies Chapter 6 and provides an overview of how other frameworks considered ecotoxicity. Appendix C describes the visualization tool ToxPi. Appendix D is a supplement to Chapter 8, providing additional information on the United Nations Economic Commission for Europe’s Globally Harmonized System of Classification and Labelling of Chemicals (GHS).
