INTRODUCTION

This article examines the Toxic Substances Control Act (TSCA) from the perspectives of law and science. We consider the legal and scientific shortcomings of TSCA, including those inherent in the Act and those revealed by implementation, and we conclude by reviewing approaches to chemicals regulation after TSCA, including the EU's REACH legislation. TSCA was the last major legislative statute enacted during the first wave of legislation after the US Environmental Protection Agency (EPA) was established, an extraordinary period between 1970 and 1975 that moved and extended regulatory authority from existing agencies and repaired much of the existing patchwork of law and policy (78).

A BRIEF HISTORY OF TSCA LEGISLATION

We describe some general background from before TSCA legislation and then identify some specific issues motivating passage of TSCA. The US Congress first passed laws in the 1970s to address environmental problems on a media-by-media basis, e.g., the Clean Air Act, the Clean Water Act, the Safe Drinking Water Act, without any general authority to address the toxicity of nonpesticidal substances regardless of media exposure.

TSCA came later, with the realization of a gap in EPA authority related to the large majority of chemicals in commerce. In 1971, the Council on Environmental Quality found that toxic substances were entering the environment, that they could have severe effects, that existing legal authorities were inadequate to address toxicity at the point of manufacture, and that, consequently, new legal authority was needed to address these issues (8). The first wave of legislation, while responsive to the issues of pesticide regulation and coverage of air and water pollution, did not provide EPA with authority to regulate industrial chemicals as distinct from pesticides. The experience with polychlorinated biphenyls (PCBs) stimulated awareness that chemicals not used as pesticides were not yet covered effectively by any existing law (49). By 1976, a large literature had demonstrated the hazards of PCBs with evidence for global human and ecosystem exposures (39, 59) as well as outbreaks of dramatic human poisonings (47). PCBs were persistent in both the environment and biota, including humans (with a half-life of about eight years for the most persistent compounds), and many were quite toxic. But PCBs were not pesticides. This lack of coverage helped motivate the creation of TSCA as a gap-filling statute, but the law was also meant to extend the lesson of PCBs more generally into prevention, as stated by Russell Train, EPA Administrator in 1976, just after the law passed (49). The regulations in TSCA on PCBs were meant as a more specific road map for action covering manufacture, use, storage, and waste disposal. However, implementing this law was to prove considerably more challenging than drafting it.

LEGAL OBSTACLES IN TSCA

TSCA exemplifies the use of legislation to respond to a substantial social concern with the additional intention to complete the fabric of environmental protection by extending regulation to both existing and new chemicals outside the pesticides statute. This represented a major change toward prevention in legal response to chemical hazards, different from the domains of criminal and tort law, both of which respond to harm done. However, similar to these existing legal institutions, TSCA was bound by legal burdens, which followed traditional assumptions of innocence and placing the burden on the prosecutor (i.e., EPA) to demonstrate risk prior to taking action.

Among the many procedural rules incorporated in TSCA, we focus on the burdens imposed on EPA for chemicals regulation because of their impacts on the success of the statute. Simply put, a burden of proof specifies which party—government or industry—must provide evidence or information related to the potential or actual risks of chemicals in commerce or proposed for manufacture. A standard of proof determines how difficult it is to carry out the assigned burden. Traditionally, both burdens and standards of proof predispose legal outcomes in accordance with historical and ethical norms (38), such as in criminal law, where the accused is assumed innocent until proven guilty beyond a reasonable doubt by the prosecutor, and in tort litigation, where the plaintiff has to demonstrate the nature and cause of injury by a preponderance of the evidence (more likely than not).

In environmental statutes, Congress has assigned the burden for regulation in several ways, unlike legislation related to drug safety. In 1962, immediately following reports on the teratogenic effects of thalidomide, Congress unanimously passed new drug safety laws that placed on the pharmaceutical industry the burden of showing both efficacy and safety, with final decisions made by the Food and Drug Administration (FDA) prior to drug registration. There was no debate about the public interest in drug safety and the costs imposed on industry for increased product testing. A similar assignment of the legal burden was embodied in FIFRA (the Federal Insecticide, Fungicide and Rodenticide Act), passed in 1972 to modernize laws enacted in 1910. Later legislation has empowered EPA to require periodic submissions of new data on pesticides in use in order for companies to maintain registration.

However, Congress adopted different approaches and burden assignments for nonpesticidal chemicals in the environment. The Clean Air Act, the Clean Water Act, and the Safe Drinking Water Act were influenced by nuisance laws, which in the past had covered smoke, dust, unpleasant odors, and loud noises, harms easily detected by human senses. Analogously, under the new environmental regulations, the state or an injured party had the burden to show harm even though chemical substances are usually not “noticeable” as nuisances because they are often not discernible by human senses (14, 49).

In TSCA legislation, while chemicals regulation was systematized and the legal burden to establish a substance's toxicity was firmly assigned to EPA, Congress had a choice about how stringent to make this burden: It could have permitted EPA to require toxicity testing or to remove toxic products from commerce as long as its action was not “arbitrary or capricious,” a procedural legal burden that usually passes court scrutiny. Instead, it empowered EPA to take legal action only with “substantial evidence of the significance of harm,” a standard that invites greater court scrutiny and in practice often results in rejection of the proposed regulatory action. This burden has been heavy in terms of the threshold for proof as well as the resources and time required to gain evidence in support of proof (63). TSCA roughly requires a showing to an appellate court “substantial evidence of the significance of harm,” which is much more than a simple “preponderance of the evidence” as in tort law (where this means 50% plus a feather) but less than “proof beyond a reasonable doubt” as in criminal law. And because TSCA permits extensive judicial review, some EPA requests for information can take decades to resolve.

The legislative history reveals how some of these delays and burdens, resulting from requirements to develop quite an extensive scientific and economic record, occurred. The initial congressional sponsor of TSCA legislation endorsed assignment of burdens and standards for proof that resembled those for pharmaceuticals and pesticides, which require toxicity testing before commercialization (8, 50). However, according to McCubbins et al. (50, p. 268), environmentalists “only mildly supported” this proposal because they were more focused on “the clean air and water bills.” In addition, industry strongly opposed premarket testing provisions. Consequently, premarket testing and safety provisions were not incorporated into the law (50).

There were likely also substantive reasons for the differences in legislation related to industrial chemicals and pesticides. First, pesticides are similar to drugs in that both are designed to be biologically active, and thus toxicity is expected. Second, knowledge of the ubiquity of chemical exposures was underappreciated in 1975 despite the lessons of PCBs. Third, thousands of existing chemicals were already in commerce before TSCA was passed (similar to the condition confronting FDA in the 1970s), which generated a need to consider the burdens and costs on the private sector without instituting a shift in burden or accepting shortcuts in the task of evaluation. With respect to food additives, when regulation created the same challenge of catching up to new policies, FDA adopted the shortcut of “generally recognized as safe” (GRAS) as a means to reduce the burden on both industry and its own resources; for EPA, tens of thousands of substances were analogously “grandfathered in.” But the determination of what was deemed safe in the 1970s was based on evaluations before the recognition of chemical carcinogenicity (54) and more subtle harms below overt intoxication or disease that were yet to be studied in toxicology and medicine. The processes of “safe” designations, as recently reported, were rife with conflicts of interest (52). The economic interests of the chemical industry were also an important factor in constraining TSCA (49, 50). Imposition of costs was and continues to be raised in the debates about TSCA as it was in the European Union during passage and implementation of its new chemicals regulation, known as REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) (22).

The new chemicals provision was hailed as prevention in terms of new chemicals, but by failing to address the problem of the burden on EPA to request information, the novel elements of TSCA were also doomed to failure. TSCA requires companies to submit a premanufacture notification (PMN) prior to undertaking manufacture or changes in product use. However, the law did not require that any minimal toxicity information must be contained in PMNs. Perhaps more importantly, Congress sought to ensure that EPA could not generally require such data later by regulatory action: “TSCA forbids promulgation of blanket testing requirements for all new chemicals” (63, p. 4). In addition, EPA is unable to request further information unless it already has information sufficient to justify its request for more information. Although PMNs must include “all available data on chemical identity, production volume, by-products, use, environmental release, disposal practices, and human exposures” (9), the key word is “available.” If the company has no data available, there is by definition nothing to submit and EPA “must take what it is given” (2): EPA cannot deny approval on the basis of a lack of information. Ignorance, under TSCA, comes close to bliss by permitting industry to avoid regulation. Because of the uncertainties surrounding the toxicological data required in PMNs, companies often have grounds to challenge any test rule issued by EPA requesting more data (63). Lynn Goldman, former Administrator of Prevention, Pesticides and Toxic Substances of EPA, concurs: “It's almost as if…we have to, first prove that chemicals are risky before we can have the testing done to show whether or not the chemicals are risky” (63).

With respect to regulation of existing chemicals, TSCA has had little influence despite the roadmap provided in the statute for managing PCBs. This failure is most obvious in the inability of EPA to use TSCA to control polybrominated diphenyl ethers (PBDEs), chemicals used as flame retardants. PBDEs, like PCBs, were in commerce before TSCA was passed and are still marketed in the United States. In contrast, the European Union banned one of the most toxic members of this class, DecaBDE, in 2008 (24). EPA's attempt to ban all uses and manufacture of asbestos in the United States (a substance that is currently banned in 54 countries) failed badly in the courts, making it unlikely that it will be able to use its authority to regulate existing chemicals and other toxicants again (2, 11).

THE TORT LAW AS BACKUP TO TSCA

Tort law was the traditional legal framework for responding to harms caused by products or the activities of others. It can also importantly supplement regulatory law because it is the main legal device for providing the opportunity to compensate citizens for injuries suffered from risky behaviors or products (33). However, the tort law is retrospective, responding after harms have occurred. Consequently, there is only limited prospective discouragement of actions or products that put others at risk: The threat of tort law actions creates a general deterrent to risky actions, and when other companies lose tort trials this provides further deterrence by example. When harms have occurred, legal actions can typically result only after an impact is recognized and redress is sought by the injured individual. However, most people who have been injured are reluctant to pursue legal redress through torts (61). In addition, as under TSCA, the burden is on the party alleging injury (or chemical risk) to demonstrate causal associations between the behavior of a responsible party and the injury. In terms of public health, tort law is an inefficient approach because in most cases each instance of a tort must be litigated and adjudicated individually. Except in important or high-profile cases or through establishing legal precedents, success in one tort action does not extend redress beyond the individual case; other legal actions must occur. Exceptions have arisen; for example, the first successful tort case in California concerning diethylstilbestrol (DES) generated a nationwide series of lawsuits (69). Tort actions resulting from exposures to risky pharmaceuticals often result in class action lawsuits. There tend to be fewer class actions related to environmental contaminants, but the asbestos litigation and dioxin litigation in Times Beach, Missouri, are prominent examples. In tort law, apart from class actions (unsuccessfully) brought against paint manufacturers, typically each case of lead poisoning, for example, has been individually litigated. Sometimes when a single facility contributes to lead poisoning, a class action on behalf of all injured parties is brought (82). Despite these limits, the tort law serves as the last resort to compensate for failures in other areas of the law, indirectly protecting citizens from future harm by sending a deterrent message to others with risky products. This has been important in environmental health.

However, tort law is an increasingly difficult resource for individuals to access to obtain redress for environmental injuries. Beginning in 1993, the US Supreme Court significantly limited plaintiffs' access to redress through tort litigation by granting judges extensive “gatekeeping” responsibilities, authorizing limits on expert testimony and giving trial judges substantial discretion in how they carry out this task (13). Many scientists and lawyers have concluded that this decision has resulted in rulings that have excluded normative scientific methods from admission into court, such as the use of nonhuman data (widely used in chemicals regulation and preclinical drug testing) and typical scientific arguments and encouraged strangely rigid interpretations of epidemiological evidence (13, 14, 37, 42). These rulings have not had the intended effect of improving the quality of scientific testimony in environmental torts but often conveyed distorted conceptions of science. Consulting firms now employ experts paid to publish and promote poor-quality articles in order to defeat liability claims, such as cases involving chromium and asbestos (45, 81). Some hopeful changes have occurred on the basis of recent decisions in the First Circuit Court of Appeals and other venues (15, 51), but tort law is not the answer to failed regulation.

LEGISLATIVE APPROACHES AFTER TSCA

In the absence of effective chemical regulation under TSCA, other legislative approaches have been tried. Nonpesticide chemicals have been included in the environmental laws passed after 1976, which govern hazardous waste and air pollution, among other topics. Several of these laws have legislative hammers that compel EPA action, including listing chemicals as part of the law and stipulating deadlines for certain actions under the law. As noted by Shapiro and Glicksman (65), hammer provisions can reverse the incentives for delay by both regulated industries and government agencies. For example, five years after passage of the Superfund law (CERCLA) in 1980 with included multiple hammers, EPA had met its statutory deadlines for establishing reporting and cleanup requirements for 340 hazardous substances. By 1987, EPA had also assigned reportable quantities for 191 potential carcinogens (54).

States have also taken initiatives to move regulation of existing chemicals, notably under the California Safe Drinking Water Act of 1986 or Proposition 65 (denoting its origin as a citizen-based initiative passed by referendum). Proposition 65 provides incentives for industry to act in order to avoid unpleasant publicity (a strategy also used in the Toxics Release Inventory in the Emergency Planning and Community Right-to-Know Act of 1986) (32). Proposition 65 requires industry or sellers to place warnings on products or substances that expose the public to known reproductive or carcinogenic hazards. “Known” is defined as a classification made by the Governor of California following a determination by a scientific advisory panel or by other authoritative sources, such as the National Institutes of Health or the World Health Organization, for hazard identification. Thus Proposition 65 does not solve the problem of a lack of information, but, like hammers, it diminishes some incentives for delay by triggering actions on evidence reviewed by others and avoids the lengthy process of de novo risk assessment. Once a product is listed by Proposition 65 processes, it is illegal for a business in California to “intentionally expose any individual without first giving clear and reasonable warning to such individual.” To stimulate risk reduction, Proposition 65 offers industry several options in place of the requirement to disclose and warn: Generate additional data on hazard or exposure to contest the assumption of significant risk; take actions (such as product reformulation or conditions or use) to reduce exposure; or phase out the use of a toxic ingredient or of the product (L. Zeise, personal communication, 2000). Although Proposition 65 does not replace the need for TSCA to prevent population exposures to inadequately tested substances, the drafters of Proposition 65 hoped that many companies would opt to change or reformulate their products by eliminating the toxic chemical altogether or otherwise greatly reduce exposures—thus achieving many of the same effects hoped for in TSCA in terms of postmarket regulation (60). To some extent, this hope has been achieved: exposures to coal tar derivatives, lead, and arsenicals along with many others have been reduced in consumer products as have emissions of toxic air pollutants from heavy diesel trucks (57).

Legislative hammers and innovative statutes such as Proposition 65 have reduced incentives for industry and government to delay risk reduction related to existing chemicals. In contrast, TSCA enables numerous incentives for businesses to keep product on the market as long as possible. One author of this article recalls being informed in 1975 by an official from DuPont that the industry resistance to banning lead additives in gasoline was based not on any disagreement over scientific evidence of harms to children but on their calculation that for every year of delay, the company stood to make billions of dollars in profit. Under Proposition 65, a company may still be attracted to this argument; however, if it does not post warnings and does nothing else to reduce exposures in a timely manner required by law, the fines for noncompliance are cumulative and substantial.

THE FAILURE OF SCIENCE IN TOXIC CHEMICALS REGULATION

TSCA has also failed scientifically to achieve its goals to introduce “preventive medicine for the environment” (49). Just as prevention has had a difficult time taking root in American medicine, the principle of prevention in TSCA is in a state of “failure to thrive.” A different interpretation of TSCA has characterized it as a “gap filling statute,” created to fill the gaps in protecting human health and the environment. To date, the most far-reaching actions of TSCA have focused on PCBs, the initial driver for this legislative innovation. However, years of inaction on PBDEs—almost chemical cousins of PCBs—belies that promise as well. Some actions have also been taken under TSCA to reduce exposures to lead, but the major actions on lead were taken under the Clean Air and Safe Drinking Water Acts and by other agencies (66).

This section asks whether problems inherent in toxicology have contributed to this failure or whether the legal constraints of TSCA inhibited the science of toxicology from resolving the burden of proof. We omit consideration of information on exposure: Since 1976, the challenges of demonstrating exposure (including prevalence and levels) have been more than met by other major government programs with required data submissions on chemical use and releases (such as the Toxics Release Inventory established in hazardous waste legislation) and through extensive environmental monitoring and national assessments of use and releases. Notably, through the Centers for Disease Control and Prevention (CDC)'s Human Biomonitoring Program, in place since 1991, our knowledge on exposures to many existing chemicals has become increasingly indisputable. In its latest report, the CDC reported on analysis of human biosamples for more than 300 agents, including industrial chemicals, pesticides, metals, and nutritional biomarkers (5). Industry must have assumed that information on demonstrated exposure would generate a pipeline of chemicals for regulatory attention because it has fought to constrain and defund this program as well as to thwart similar efforts by the National Institute of Environmental Health Sciences (NIEHS) to list chemicals associated with cancer (for example, Galbraith in 2005, who testified on behalf of the chemical industry) (27).

But there has been no solution for the obstacles that prevent the acquisition of information on hazard and risk of chemicals, which come largely from epidemiology and toxicology. Of these two disciplines, toxicology is the science that best supports prevention by generating information in advance of any human exposure and adverse effects (68). But not surprisingly, due to its linkage to regulation, toxicology has been a contested science, with extended debates over the fundamentals of toxicity testing methods and interpretations of their results. The relevance of nonhuman test systems continues to be debated (35), although these same methods are used to discover and test new molecules for drug development and marketing. The process of integrating toxicology into risk assessment is exceptionally tedious. Attempts have been made to expedite hazard and risk assessments through what may be called “toxicology lite,” using methods that require a minimum amount of actual biologically based information. Unfortunately, these attempts have opened up additional potholes in the road to adequate information because of the limitations of their heavily negotiated study designs and incompletely tested assumptions, as discussed below.

PROBLEMS IN THE SCIENTIFIC BASIS FOR TSCA IMPLEMENTATION: NEW CHEMICALS

Because TSCA's program for new chemicals is relatively simpler, we discuss it first. Some have asserted that the new chemical review process under TSCA has been successful, but this is largely the case because it is legislatively expedited in terms of reaching decisions, not necessarily in terms of generating information to protect public health and the environment. Vogel (79) compared the quicker start of chemicals regulation in the United States to a hare as contrasted with the slower tortoise of European policy; however, like the hare in the fable, the initial fast start of TSCA has proven to have little staying power. As noted above, EPA is unable to access or require meaningful data for new chemicals within the deadline for decisions on PMNs. Over time, EPA has reduced its burden by excluding certain categories of new chemicals from review (30). The rationale for the polymer exemption deserves quotation to reveal its ambiguity of motive:

This last sentence expresses the contradictions inherent in US chemicals policy.

For those new chemicals not exempted, assessment methods have been developed to fit the limitations on data submitted by most PMNs. These methods are less and less reliant on biologically based information (actual toxicity testing) and increasingly dependent on inferences based on largely chemical structure to infer both hazard (quality of toxicity) and risk (likelihood or severity of toxicity) (72). The “science” of what is called Quantitative Structure Activity Relationships (QSAR) was born from the need for rapid response to new chemical notifications devoid of much real data. The problems of applying these methods that are difficult to validate were noted by an EPA scientist early in the program's development (70). We do not consider QSAR a science because it is not possible to test its outcomes in terms of the accuracy of QSAR-based decisions about new chemicals. We have no way to know if in the postmarket world any of these QSAR-assessed and -approved chemicals have proven to be without significant risk of harm. Unlike drugs, there is no postmarket surveillance of industrial chemicals. Moreover, the rationale for QSAR has some validity only for certain end points, such as mutagenicity and carcinogenicity, which are based strongly on decades of research supporting specific and well-defined mechanisms (75). More complex and less well-understood outcomes—such as reproductive and developmental toxicity—involve multiple mechanisms, and under these conditions, approaches based on structure activity relationships (SAR) are considerably less justifiable on scientific grounds, as noted by Hadrup (31). For example, reproductive toxicity can involve maternal and paternal partners, intergenerational effects, and multiple events in each sex, including neuroendocrinological dysfunctions, structural problems in reproductive organs, and events affecting germ cell maturation and competence. Few of these end points have sufficient data to construct a prediction model based on QSAR or groupings based on assumed common mechanisms. In their review of matrix- and SAR-based assessments for endocrine disruptors, Cox et al. (12) clearly state that the value of these approaches extends only to a single mechanism of action, that is, androgen and estrogen receptor binding, whereas endocrine disruptors as a group are known to possess multiple mechanisms of action (84).

But EPA cannot escape the prison of QSAR without TSCA reform (28). The European Union adopted a different policy for evaluating new chemicals in its first response to TSCA (the Sixth Amendment) by requiring a minimum premarket data set for new chemicals. This pattern of requiring data for decision making continues to differentiate chemicals regulation policy in the European Union from that in the United States (22, 30).

EXISTING CHEMICALS

From the outset, TSCA implementation was hindered by the high standards of proof required on exposure and hazard that had to be sufficient to establish a “reasonable uncertainty of unreasonable risk.” These words were never clearly defined in the statute (49), and although there are mountains of judicial interpretation (63), to a scientist they remain devoid of meaning. EPA has interpreted them to require “the balancing of the probability that harm will occur and the magnitude and severity of that harm against the effect of a proposed regulatory action on the availability to society of the expected benefits of the chemical substance” (73). This interpretation balances health risks versus chemical benefits, which seems contrary to the concept of TSCA, which made no such findings in its discussion of PCBs.

In response to this situation, EPA has undertaken the development of ever more complex methods of risk assessment, to substantiate the “reasonable basis” claim, and quantitation of risk to support the unreasonable risk claim. Koch & Ashford (44) make a compelling case for the inhibitory effects of risk assessment on TSCA implementation, concluding that “an overly comprehensive and protracted risk assessment process may unjustifiably postpone the implementation of desirable risk reduction measures”; however, this is a vicious cycle started by the terms of the statute. In many ways, the precautionary principle is an understandable response to the Escher-like landscape of requiring information to get information by lowering the need for dispositive information (67). This strategy may be considered toxicology lite.

Two attempts have been made to reanimate TSCA process, first by the High Production Volume chemicals testing program of the Environment Program of the Organization for Economic Cooperation and Development (OECD) and second by the Endocrine Disruptor Screening and Testing program at EPA. One author of this paper (Silbergeld) was involved in both of these programs as a member of the US delegation to the OECD and an appointed expert to the Endocrine Disruptor Screening and Testing Program at EPA.

The OECD became involved in chemicals regulation after the passage of TSCA and the EU Sixth Amendment because of the possibility that differing requirements for evaluating chemical safety could create nontariff barriers to trade (48). The High Production Volume (HPV) program was stimulated in 1999 following a report from the Environmental Defense Fund, a US nongovernmental organization, on a small subset of chemicals that indicated that most if not all these chemicals were likely to have insufficient toxicity information to assure safe manufacture, use, or disposal (21). EPA replicated these finding and the HPV program was adopted in response. It proposed a “work around” to the burden of proof in TSCA by inferring exposure on the basis of production volume, on the assumption that chemicals produced above a threshold limit (set at 1,000 metric tonnes) were inevitably associated with human exposure (a rebuttable presumption if sufficient information was presented to demonstrate that manufacture, use, and disposal were under so-called closed and controlled conditions). This tactic by itself reduced the number of existing chemicals needing assessment to fewer than 10,000.

The origins of the HPV program within the OECD also provided a shortcut around the second major challenge to the burden of proof in TSCA: how to assess and define toxicity. As part of its response to US and EU legislation in 1976 and 1979, the OECD undertook an international approach to harmonizing chemicals regulation through developing test guidelines for international acceptance and use (56). Although to many toxicologists these test guidelines are toxicology lite, the ability of the HPV program to utilize methods already accepted by governments and industries in the OECD countries was essential in defining what was termed a screening initial data set (SIDS). This strategy would provide some information relevant to assessing acute toxicity, repeat dose (or subchronic) toxicity, reproductive and developmental toxicity, genotoxicity, and ecotoxicity, along with information on environmental fate (40). Thus the obstacles in TSCA for obtaining information on both hazard of and exposure to existing chemicals as a prerequisite for further information seemed to be solved by a simple approach to information on both exposure and toxicity: exposure = production volume >10,000 kg, and toxicity = positive results on OECD test guidelines.

The output of the HPV program in terms of chemical assessments seems impressive in contrast with the sluggish performance of TSCA; however, like EPA's handling of new chemicals, this perceived success is deceptive. The program has not completed assessments for the original short list of HPV chemicals, and more importantly, it has not overcome the obstacles in the way of moving a chemical to the next steps in assessment. The OECD test guidelines generate limited information on toxicity because of the pressures exerted by member countries and their industries to reduce the costs of testing. Even toxicology lite was too much; under continued pressure from industry and governments, the HPV program quickly dropped the original concept of requiring any actual test data to determine hazard and risk and accepted the methods of QSAR, as described above, along with a so-called matrix model (77). The matrix model was proposed as a way to fill in gaps of information by employing inferences across chemicals with similar structures. However, when these matrices contain more gaps than data, it is difficult to understand how to read across to determine an end point. These approaches, like EPA's assessments of new chemicals under TSCA, rest on problematic assumptions about the predictive value of structural analysis and its integration into read-across matrices (83).

The Endocrine Disruptor Screening and Testing Program mandated by amendments to FIFRA also adopted toxicology lite in response to new legislation on pesticides in the United States. By law, EPA was required to convene the Endocrine Disruptor Screening and Testing Committee (EDSTAC) in 1996 to provide advice on how to identify and prioritize chemicals, not limited to pesticides, for endocrine-disrupting effects (25). At the time, there was (and remains) considerable scientific and political debate concerning the most appropriate methods to evaluate chemicals for these hazards. These are among the most complex systems and mechanisms in the field of toxicology, which confounds toxicology lite and inferential solutions to replace real data, as discussed above. But lightening the science of toxicology did not save HPV or EDSTAC, and both programs have been reduced to programs for prioritization, with no road map leading to robust risk assessment or risk management.

In retrospect, it is unlikely that TSCA could have succeeded. Many flaws are embedded in its original language, such as its handling of burden of proof and the vagueness of terms such as “significant risk” and others that were evident in implementation, which created a reward system for ignorance. These limitations also impeded the development of effective scientific methods to support chemicals regulation and encouraged a continuing metastasis of the “science” of risk assessment in place of science. New approaches, such as the Toxicity for the 21st Century movement (41), have yet to resolve the gap between the needs of regulatory programs and information developed in silico or with computational toxicology (43). As noted above in the discussion of other legislative approaches to chemical regulation, TSCA has by now largely lost its public constituency as other laws, some of which were equipped with hammers or other faster procedures, such as technology-based provisions, took over much of the work of regulating chemicals in air, water, and waste.

Legislative attempts at TSCA reform have gained some momentum since 2009, with several bills under discussion in the Congress (4, 46). In 2010, four former Assistant Administrators for Pesticides and Toxic Chemicals at EPA (from both Republican and Democratic administrations), urged reforms based on what was learned from the accomplishments, failures, and challenges to TSCA in its present form: incorporating policy mandates from the Food Quality Protection Act (FQPA) (such as proactive decisions in the face of data gaps); improving EPA organizational capacity, to a level that reflects the numbers of chemicals that require testing (86,000 of the TSCA inventory); recognizing and incorporating relevant international activities (such as REACH and the Global Harmonized System, as well as international treaties and conventions such as the Long Range Transboundary Air Pollution and the Stockholm and Rotterdam Conventions); and ensuring flexibility in order to evolve with changes in science, technology, and regulations (1). Industry has also been heavily engaged in TSCA reform as exemplified by its lobbying expenditures. A report based on lobbying disclosure forms filed with the House of Representatives and Senate showed that six chemical companies and the American Chemistry Council, the industry trade association, spent $63 million on lobbying Congress in 2013, $13.7 million of which made explicit reference to the Chemical Safety Improvement Act or “Toxic Substances Control Act Modernization” (26). As of December 2014, we feel it is difficult to predict the likelihood of meaningful TSCA reform and recent changes in the US Congress are not encouraging of support for this prospect.

THE CHALLENGE OF REACH

Since 1975, there has been an interactive history between the United States and the European Union in terms of chemical regulation. With the passage of REACH in 2007, the European tortoise has clearly become the hare in terms of innovation and advances in the philosophy and methods for chemical regulation (79). Regulation (EC) 1907/2006 REACH was enacted in the European community, requiring producers or importers to provide actual data (http://iuclid.eu/index.php?fuseaction=home.project) in support of chemicals registration required for authorizing sales and use of chemicals in the European Union. REACH is based on the principle “no data, no market”; industry has the burden of proof to demonstrate safety prior to authorization to market its products. As noted above, in 1979 the EU chemicals law had already required testing prior to marketing new chemicals; REACH essentially applies the same requirements to existing chemicals. Industry is required to provide data related to safety and to pay for the costs of acquiring these data, and European Chemical Agency (ECHA) is responsible for evaluating and verifying the correctness of the information submitted for registration. This is not a passive process: By law, ECHA must check at least 5% of the registration dossiers (20). Most importantly, on the basis of this assessment, ECHA has sufficient authority to take actions or request further test data or other information. Companies that do not submit registration dossiers or additional information on request may be fined or face civil and criminal prosecution, depending on the importance of the case.

Based on information it receives, ECHA can also take immediate actions by listing a chemical as a substance of very high concern (SVHC) if the data are sufficient to meet one or more of the following criteria: (a) carcinogenicity; (b) mutagenicity; (c) reproductive toxicity; (d) persistence and bioaccumulation in addition to toxicity; or (e) “scientific evidence of probable serious effects to human health or the environment which give rise to an equivalent level of concern” (18). This part of REACH is similar to the disclosure provision of Proposition 65 as discussed above, but there are more significant consequences for listing beyond warning, including restrictions imposed by some member countries and requirements on transport and storage. There are currently 155 candidate SVHCs proposed by ECHA (19).

REACH has influenced chemical policy in other countries. China, Turkey, Japan, Taiwan, and South Korea have recently adopted similar regulations in a similar pattern. Of these countries, we focus on Chinese chemical policy because China is now the worldwide leader in chemical sales (6).

In 2010, the Ministry of Environmental Protection (MEP) of China released a revised version of the Provisions on Environmental Administration of New Chemical Substances under which companies are required to submit new chemical substance notifications to the Chemical Registration Center (CRC) of the MEP for new chemicals irrespective of annual production tonnage. This regulation is also known as China REACH, although the regulation is substantially different from EU REACH, most notably in its lack of coverage for existing chemicals (76).

Like TSCA, China REACH has no requirements for registration (with data) for the 45,612 chemicals already listed in the Chinese existing chemicals inventory. There are also 3,270 confidential substances, with no Chemical Abstracts Service (CAS) identifier or molecular structure disclosed, listed in the inventory. Finally, in China REACH, some ecotoxicological tests must be carried out on Chinese-specific creatures in certified Chinese laboratories (10).

In the United States, there has been no new chemicals legislation since 1976 and there has been pushback on REACH from US industry (62) and from some scientists because of the costs and resources that will be necessary to fulfill its requirements. Hartung & Rovida (36), for example, have claimed that at least 54 million vertebrate animals will need to be tested to meet the requirements of registration, with testing costs totaling 9.5 billion euros. These claims have been disputed by ECHA and others (17) as well as by Denison (16). Regardless of the accuracy of these claims, any consideration of costs must be balanced by an evaluation of expected benefits. The European Commission has undertaken evaluations of the impacts of REACH implementation, which have estimated costs as totaling between 2.1 and 5.2 billion euros, and the monetized health benefits as totaling between 4.8 and 283 billion euros over 20 years (29). A more comprehensive independent analysis of several studies on the benefits of REACH by Reihlen & Lüskow (58) also demonstrated significant benefits for several sectors, including industry, environment, and human health (both for workers and for the public more generally). Some of these calculations reflect similar work by Porter & van der Linde (55) on the positive effects of regulation on innovation and competitiveness.

Data compiled by the EU chemical industry indicate that implementation of REACH has been favorable to industry by increasing sales from 1992 to 2012. The European Union was also the leading importer and exporter of chemicals worldwide in 2012 (7). Moreover, according to these same industry data, the costs for EU REACH implementation (highest estimate 500 million euros per year) represent 1/1,000 of the revenues from sales (558 billion euros per year), and the aggregate benefits (50 billion euros for all stakeholders, including industry) exceeded costs by 100-fold.

On the basis of this experience, we next consider economic arguments for incentivizing changes in US chemicals regulation in response to REACH. Despite more than three years of discussion about the possibility of revitalizing and reforming TSCA, there has been little legislative progress in TSCA reform (80). Events as exceptional and compelling as the recent chemical spill in West Virginia in January 2014 have not generated sufficient political support for reform. In light of this, we suggest three potential economic incentives for change. First, at present, the United States is essentially a free rider benefitting from investments made by EU industry in meeting REACH because data relevant to chemical safety generated by companies doing business in the European Union are available without cost to US industry and government. This condition will not likely be tolerated for long, and the European Union may consider economic actions to punish US producers for failing to bear an equal burden. Second, environmental regulations such as REACH can stimulate innovation and thus contribute to the competitive advantage of nations, particularly those that are early adopters of regulation (55). Porter and others have referred to pollution as evidence of inefficiencies in production. Second, to the extent that regulations effectively reduce externalized costs such as adverse impacts on human health and the environment, these costs—which are borne by societies at large—are also reduced (3). Third, there are some immediate incentives for the United States to improve chemical regulation. The United States lives in a different “chemical world” in terms of trade and economics from that of the 1970s to 2010, when the two major regions of chemical production and use were North America and the European Union. China, now predicted to become the world's leading economy, is the leading worldwide producer and seller of chemicals and products containing chemicals (6). Thus the old transatlantic dynamic that drove productive and progressive changes in chemicals regulation beginning with TSCA and the Sixth Amendment is no longer the only game in town. We are also in the post-WTO (World Trade Organization) world, where nontariff barriers to trade are rigorously scrutinized and barriers to trade can be justified only on the basis of scientifically based claims for unequal treatment on the basis of health and other considerations. Under the present system, the United States generates very little data on chemical safety, which would jeopardize any claims brought under WTO. In this new landscape, the United States is positioned in the middle in terms of the current state of chemicals regulation and trade. In this position, the United States has an interest in preventing inadequately tested or untested chemicals and products from entering its market from China, as well as an interest in assuring a market for American chemicals and products in the European Union. The United States is unlikely to sustain an argument for blocking Chinese imports and opening up US exports of chemicals.

This dynamic supports economic arguments for bringing US regulation and practice closer to the EU REACH model; after an extensive attempt at lobbying the EU Commission to prevent enactment of REACH, there is little alternative left to living with it. Moreover, there are monetizable benefits to increasing chemical safety in the United States, which would also result in higher standards of regulation in China. Given that products, wastes, and releases flow globally, ensuring the highest level of common practice is a global benefit for all societies. Current discussions (2014) between the United States and the European Union concerning a Transatlantic Trade and Investment Partnership (TTIP) may be an appropriate framework to consider the advantages of common regulatory standards for the European Union and the United States, which will concurrently enhance the economic and health/safety interests of both parties (23). In the “EU Position on Chemicals,” the European Union notes that it is impossible to harmonize chemical regulations under current US and EU laws (TSCA and REACH). The value of partnerships in other areas of public health has been demonstrated, such as the successful example of the Secure Supply Chain Pilot Program for pharmacovigilance involving the European Medicines Agency and FDA (71). This experience supports expansion to chemical management to meet the challenge of ensuring “sound regulatory practices in todays interconnected world” (53, p. XI). Without globally harmonized systems of chemical and product safety, importing nations cannot protect the health and safety of their citizens solely through inspection systems at the border, particularly when the volume of importation is very great (34). In addition, imported products from sources will lower levels of regulation and also imperil domestic markets and workforces by undercutting the price of domestic production (64).

The United States as an exporter and importer of chemicals and products has much to gain by moving its regulatory systems to the highest level of practice. The harmonization of international requirements reduces uncertainty as well as costs in terms of liability, health care expenditures, national productivity, and loss of environmental services. Moreover, the ability to block the entrance of unsafe goods, whose reduced price is in part related to a lack of health and safety requirements, depends on the existence and implementation of high levels of health and safety regulation. The remarkably successful early implementation of REACH challenges the United States to regain its momentum in leading environmental health policy and, at the same time, to maintain its economic position in globalized markets.

disclosure statement

The authors are not aware of any affiliations, memberships, funding, or financial holdings that might be perceived as affecting the objectivity of this review.