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Introduction

In the 1970s, flame retardants began to be added to synthetic materials to meet strict flammability standards. Over the years, a diverse array of flame retardants have been produced and used in various products. Some flame retardants have migrated out of the products and resulted in widespread human exposure and environmental contamination (Iqbal et al. 2017), and there is mounting evidence that many flame retardants are associated with adverse human health effects (Linares et al. 2015; Hou et al. 2016). As a result, some flame retardants have been banned, restricted, or voluntarily phased out of production and use.

In 2015, a petition was submitted to the Consumer Product Safety Commission (CPSC) to initiate regulatory action under the Federal Hazardous Substances Act (FHSA) that would ban nonpolymeric, additive organohalogen flame retardants (OFRs)¹ in four product categories (Gartner and Weintraub 2015). To decide whether a ban should be instituted, CPSC first conducts a hazard assessment to determine whether the chemical in question is “toxic” as defined in the FHSA and, if so, to conduct a quantitative risk assessment that considers dose–response relationships, bioavailability, and exposure to determine whether the chemical is a “hazardous substance” under the FHSA.² The petition was unique in that it requested action on an entire chemical class rather than a single chemical. Because of the complexities of conducting a hazard assessment of a chemical class, CPSC asked the National Academies of Sciences, Engineering, and Medicine (the National Academies) to develop a scoping plan for the hazard assessment of OFRs as a chemical class. As a result of the request, the National Academies convened the Committee to Develop a Scoping Plan to Assess the Hazards of Organohalogen Flame Retardants, which prepared this report.

CONCEPTUAL ADVANTAGES OF A CLASS APPROACH

Regulatory evaluation of chemical hazards and risks has traditionally relied on a chemical-by-chemical approach wherein a regulator reviews the full suite of available hazard, dose–response, and exposure data on an individual chemical and determines whether the information is sufficient to support an assessment of hazard or risk. If the information is sufficient, the process proceeds in a manner similar to that described in Risk Assessment in the Federal Government: Managing the Process (NRC 1983). If the regulator considers the available information to be insufficient, the assessment of hazard or risk is not conducted. Over the last decade, the National Academies and others have identified three main problems with that approach.

• Chemicals on which data are insufficient are often deemed not hazardous. Excluding from risk assessments chemicals that have been insufficiently tested was criticized in the report Science and Decisions: Advancing Risk Assessment (NRC 2009). The committee that wrote that report pointed out that “with few notable exceptions (for example, dioxin-like compounds), [chemicals on which data are insufficient] are treated as though they pose no risk that should be subject to regulation” (p. 194). That assumption was characterized by the committee as a “missing default” assumption in traditional regulatory risk assessment. The “no data, no risk” default assumption is used even if there are hazard predictors, such as structural similarities and biologic activity patterns analogous to those of chemicals that are known to be harmful.

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¹ The abbreviation OFRs in this report refers specifically to nonpolymeric, additive organohalogen flame retardants.

² The FHSA defines toxic as applying to “any substance that has the capacity to produce personal injury or illness through ingestion, inhalation, or absorption through any body surface [15 USC § 1261(g)]” and defines hazardous substance as having “the potential to cause substantial personal injury or substantial illness during or as a result of customary handling or use [15 USC § (f)(1)(A)]” (CPSC 2017, pp. 10 and 11).

• Untested chemicals are often substituted for known hazardous chemicals. In a regulatory system in which each chemical is evaluated separately, the responsible agency predictably moves slowly and deliberately through a sequence of discrete chemical assessments. In practice, observers have noted and described a risk of regrettable substitution (Wilson and Schwarzman 2009) in which a manufacturer responds to regulatory signals by phasing out the use of a specific chemical and replacing it with a substitute that is chemically similar and relatively untested (NRC 2014). In some cases, that practice has led to widespread introduction of substitutes about which little is known and that are not necessarily safer (Sartain and Hunt 2016).
• Cumulative exposure and risk are often ignored. An approach that addresses one chemical at a time does not consider cumulative risks that might be posed by exposure to multiple chemicals that act via a similar mechanism or that perturb the same biologic system. The report Phthalates and Cumulative Risk Assessment: The Tasks Ahead (NRC 2008) included the caution that “phthalates may not all act by the same mechanisms, and they do not have parallel dose–response curves. However, those facts do not negate the appropriateness of using general dose-addition methods in a cumulative risk assessment” (p. 9). The concern expressed by the committee that wrote that report applies to other classes of chemicals if chemicals in those classes have similar activity in biologic systems.

Ultimately, the sheer number of chemicals in use today demands a new approach to risk assessment. As articulated by NRC (2011), “the great number of chemicals of potential concern is always increasing. The vast array of chemicals that are potential environmental contaminants include… [too many] to address by the chemical-by-chemical approach of toxicity testing in animals of each health effect of concern and then predicting human risk” (p. 83).

If scientifically supportable approaches, such as read-across and evaluation of chemicals by category or class, can allow extrapolation from relatively well-studied chemicals to data-poor chemicals, the problem of regrettable substitution can begin to be addressed. Assessing chemicals as classes would also make regulatory hazard and risk assessment much more efficient. Finally, if the “no data, no risk” presumption were no longer the default, those wishing to continue manufacturing or using a chemical would have greater incentives to generate data to demonstrate safety. The movement toward a class approach to hazard or risk assessment provides the basis of the petition submitted to CPSC to ban OFRs.

PETITION TO BAN ORGANOHALOGEN FLAME RETARDANTS IN SELECTED CONSUMER PRODUCTS

OFRs have been used in various consumer products, and the petition submitted to CPSC in 2015 specified four product categories containing OFRs: infant, toddler, or children’s products; upholstered furniture; mattresses; and plastic electronic casings. The petitioners argued that the chemicals as a class are toxic and that consumers are exposed to them because the chemicals “migrate out of the products regardless of how the product is used” (CPSC 2017, p. 31). Therefore, their use poses a risk to consumers.

CPSC staff investigated various aspects of the petition and concluded that OFRs constitute a broad chemical class that is defined primarily by function—to suppress combustion and increase the probability of escape from fire—rather than by any specific toxicity characteristic or chemical functional group other than a halogen. Furthermore, there are no (or too little) data on many OFRs to base a decision about toxicity. Regarding exposure, CPSC staff noted that biomonitoring data and house-dust samples show that humans are exposed to OFRs, but the data do not indicate the exposure source. Thus, one cannot link the exposure data to the products noted in the petition. CPSC staff also noted that substantial resources would be required to develop test protocols for all OFRs—protocols that would be needed to conduct a market survey to support regulatory action. For those and other reasons, CPSC staff recommended that the commission deny the petition. The commission voted on September 20, 2017, however, to grant the petition and directed

Given the complexity of the task to assess the hazards posed by OFRs as a class, CPSC has asked the National Academies to develop a scoping plan for doing so.

STATEMENT OF TASK

The committee that was convened as a result of the CPSC request included experts in toxicology, epidemiology, pharmacology, computational toxicology and chemistry, and risk assessment. Biographic information on the committee is provided in Appendix A. The committee was asked to survey the hazard data available on OFRs,

to identify at least one scientifically based approach to evaluate OFRs as a class for hazard assessment, and to recommend approaches for conducting research needed to evaluate OFRs under the FHSA. The verbatim statement of task is provided in Box 1-1.

COMMITTEE’S APPROACH TO ITS TASK

To complete its task, the committee held four meetings, which included two open sessions at which the committee heard from the sponsor and interested stakeholders. In interpreting its task, the committee considered what it meant to conduct a class approach for hazard assessment. There is no consensus in the literature on exactly what constitutes a class approach, and there are few examples of the use of such an approach, although the list is growing. The committee concluded that a science-based class approach does not necessarily require one to evaluate a large chemical group as a single entity for hazard assessment. That is, an approach that divides a large group into smaller units (or subclasses) to conduct the hazard assessment is still a class approach for purposes of hazard or risk assessment. The committee also uses several terms in this report that might be unfamiliar to some readers or that have been defined in varied ways in the scientific literature. For convenience, those terms are provided in Box 1-2 and defined as used in this report.

As directed in the task statement, the committee focused on hazard assessment—one component of risk assessment—and therefore did not consider exposure in its scoping plan. However, it was asked to develop the scoping plan with the assumption that the hazard assessment will need to be integrated with a separate quantitative exposure assessment to complete a human health risk assessment. Chapter 2 considers the implications of the class-based hazard assessment for the other components of risk assessment.

ORGANIZATION OF THIS REPORT

The report is organized into three chapters and four appendixes. Chapter 2 provides the committee’s scoping plan for a class approach to hazard assessment and discusses the implications of a class approach for the other components of risk assessment (dose–response assessment, exposure assessment, and risk characterization) and for efficiency and cost. Chapter 3 provides examples or case studies to illustrate various steps in the committee’s scoping plan. Appendix A provides biographic information on the committee members. Appendix B provides de-

tails of the committee’s class analysis of OFRs, and Appendix C provides the details of the committee’s literature survey and searches. Appendix D provides details of zebrafish studies on selected OFRs discussed in Chapter 3.

REFERENCES