chem

When the United States first regulated industrial chemicals in the 1970s, policy-makers made a threshold decision: Rather than a “front-end” approach requiring proactive risk assessment before licensing a chemical for use, Congress chose a reactive approach of regulating chemical risks as they became manifest (1). This choice puts a premium on “back-end” research on exposure pathways and hazards of new chemical contaminants in situ.

Such research identifies contaminants in the environment, their source, where they go, and what harm they might cause (2). This knowledge is crucial for risk assessment and regulatory decisions. However, key features of the legislative design impede that essential research. Amid debate about how policymakers should apply existing scientific findings, these science-hindering features are easy to overlook. We highlight three of them: insufficient availability of chemical standards, limited public access to information, and excessive fragmentation of information within and among government agencies.

A recent survey found that 22 chemical databases and inventories worldwide included more than 350,000 registered chemicals or chemical mixtures, the vast majority of which are or were in commerce (3). About one-third are not fully identified, and about one-fifth—70,000 chemicals or mixtures—were registered in just the past decade (3). The number of chemicals continues to grow exponentially (4).
With ever more new chemicals and their degradation products possibly making their way into the environment, identifying emerging contaminants is both increasingly urgent and challenging (2). However, despite this urgency, several key features of US chemical regulation—also found to some extent in other regulatory systems—serve to frustrate and delay rather than facilitate the needed back-end research to identify, analyze, and assess new chemicals in the environment. A case study involving a group of chloroperfluoroether carboxylates (Cl-PFECAs) detected in New Jersey (5) highlights these issues (see the box).

Insufficient Availability of Chemical Standards

Given the pace of chemical innovation and the absence of much identifying information from registries, back-end research depends on a range of nontargeted analytical techniques to determine the presence of emerging and new contaminants (2). Chemical reference standards are important to this work (1, 6). Without a chemical standard, researchers are precluded from definitively identifying a chemical found in the environment. Even if a chemical can be identified, measuring its concentration requires a standard for comparison. In cases of complex mixtures of chemicals, the need for chemical standards is even more crucial to provide benchmarks for the research (2). Without chemical standards, this first step to back-end field research is always imprecise, labor-intensive, and time-consuming [(1); see supplementary materials (SM)].

Despite the critical importance of analytical reference standards to researchers, US law does not require manufacturers to provide a chemical standard as a condition to marketing a chemical (1). Sometimes chemical reference standards do exist but are classified as trade secrets (1, 6).

If a manufacturer does not share a reference standard of its chemical, field researchers generally have two options. First, under ideal conditions, scientists may be able to determine the identity (but not the concentration) of an unknown chemical in a complex mixture. However, this approach takes a great deal of additional time and may be available only to a subset of researchers who have high-end laboratory equipment and expertise (1). Alternatively, for a fee, researchers may be able to obtain standards of some chemicals purchased directly from third-party companies that synthesize and sell certified reference standards.

But even when intermediate groups sell these reference standards, legal impediments may still arise. In 2020, a manufacturer sent a cease-and-desist letter to a company selling a reference standard of its chemical, arguing that marketing the standard infringed the manufacturer’s patent (6). Given the relatively small profits from that particular reference standard, the standards company, which at the time was the sole provider of the standard, chose simply to stop selling the standard rather than agree to the manufacturer’s proposed licensing agreement (6, 7). The mere threat of legal action, whether based on a valid claim or not, can discourage companies as well as individual chemists from creating or selling certain chemical reference standards. And a chemical manufacturer can always argue that independently created standards are imprecise, unreliable, or even illegal (1). Under this legal design, manufacturers can effectively set “the rules for which chemicals environmental researchers can and can’t measure” (7).

Limited Public Access to Information

Once a chemical in the environment is identified, field researchers will attempt to learn how, where, when, and why it is produced and released. At this second step, the field researcher can encounter another legal obstacle: limited public access to crucial information, even if the information is somewhere in a government agency’s files. The law keeps some submitted information secret and allows other information to be submitted in a form too imprecise to be truly useful.
The best-known impediment to accessing information arises when a manufacturer classifies some or most of a submission as a protected trade secret or confidential business information (CBI). Under the Toxic Substances Control Act (TSCA), CBI protection can even apply to the identity of the chemical itself, precluding researchers from learning whether the chemical has been registered with the US Environmental Protection Agency (EPA) (1). As of August 2021, the identities of nearly 20% of the active chemicals on the EPA’s TSCA inventory—more than 8200 chemicals—were classified as CBI (see SM). And even for publicly listed chemicals, a great deal of information can be classified, including the name of the manufacturer, the location of its operations, chemical trade names, and process information (see SM).

Not all information on a chemical may be protected as a trade secret; the TSCA provides that health and safety information on a chemical cannot be classified as CBI because of its public import. Notwithstanding this limitation, however, the toxicity data may be effectively shielded from public view if the chemical identity itself is deemed CBI. In the case of Cl-PFECAs, toxicology studies in the EPA’s files came to light only after Washington et al. (5) publicly described the chemicals and a journalist filed a Freedom of Information Act request that triggered an internal EPA review of the manufacturer’s existing CBI claims.

In designing the TSCA in 1976, Congress sought to encourage chemical innovation in part by providing generous legal protections for information that, according to manufacturers, must be kept secret to maintain a competitive edge (1, 8). Under this law, manufacturers face no consequences for overclaiming trade-secret protection. Indeed, historically, manufacturers were not even required to substantiate or justify their claims in advance (9). By contrast, manufacturers irrevocably lose the legal right to confidential treatment of any information submitted without a trade-secret claim (9). Faced with these asymmetrical incentives, many manufacturers historically overclassified information as trade secret–protected (9). Even after the TSCA’s 2016 amendments, which required more substantiation of some CBI claims, it is up to the EPA to assess the legitimacy of each CBI claim and to take appropriate action if the agency believes a claim is unwarranted. Generally speaking, substantiation requires an explanation of how disclosure could harm a submitter’s competitive position and of the steps a submitter has taken to keep the information secret (see SM). For CBI claims that the EPA has reviewed since 2016, more than 32% were considered unsubstantiated and hence rejected (10).

From the standpoint of non-EPA scientists researching the chemical fate of new chemicals in the field, these trade-secret protections can serve as a barrier to important data and related information about the chemical (11). Even EPA scientists are not able to access CBI information unless they have been legally cleared to view CBI materials [(9); see SM]. Yet clearance to view classified information is a double-edged sword. The law prohibits a researcher from disclosing the confidential information in subsequent publications, even indirectly. So, if a manufacturer can make a case that a government employee somehow disclosed CBI, or disclosed information that could have been uncovered only with foreknowledge of CBI, then that employee may be subject to civil lawsuits or criminal prosecution and potential imprisonment (8, 9). As Richter et al. report, “The penalties for violating CBI policy transform basic types of scientific inquiry into potentially non-normative, criminal behavior” [(1), p. 12].

A second set of impediments to scientists’ efforts to access chemical information in government files arises because regulatory regimes tolerate substantial ambiguities in the identification of some subsets of chemical substances (3). These imprecisions tend to arise early in the regulatory process, when manufacturers first register a substance with an agency. For example, manufacturers may identify substances of unknown or variable composition, complex reaction products, or biological materials (UVCBs) with a generic name that does not reveal such substances’ composition (3). Scientists may similarly search in vain for information on a substance that they have identified if the manufacturer registered and submitted data on a slightly different structure or composition and thus a different Chemical Abstracts Service (CAS) number: an anion versus a salt, for example (as with Cl-PFECAs), or salts with different cations. Addressing these additional information gaps is “an important next step to advance the current chemical registration and assessment schemes” [(3), p. 2580)].

Searching for answers, coming up empty

In May 2020, a team of researchers (5) from the US Environmental Protection Agency (EPA) and the New Jersey Department of Environmental Protection identified a group of chloroperfluoroether carboxylates (Cl-PFECAs) in soil samples from parts of New Jersey. These particular per- and polyfluoroalkyl substances (PFAS) were unknown to the EPA members of the research team, who used nontargeted methods to perform analytical work. Using semiquantitative techniques in the absence of an analytical standard, they plotted contours that showed Cl-PFECA concentrations descending with increasing distance from a putative source facility. But the EPA chemists could learn very little else about what they had found, even though they were able to find a Chemical Abstracts Service (CAS) number associated with these Cl-PFECAs.

We attempted to merge Washington et al.’s (5) discovery with existing regulatory information. Our searches of US government databases for these CI-PFECAs by CAS number came up empty, although the substance had been approved by the European Food Safety Authority (EFSA) for use in manufacturing nonstick coatings and is subject to the European Union (EU)’s chemical labeling regulation (5). We ultimately learned from Freedom of Information Act requests filed by others and by us that the anions that Washington et al. described are not registered in the United States, although at least three related Cl-PFECA salts and esters are known to the EPA—only one of which could be found in the EPA’s public database of regulated chemicals [see supplementary materials (SM)]. We also learned that two of the substances have been linked to evidence of potential bioaccumulation in the blood of workers documented by the manufacturer since 2011 (see SM).

To our knowledge, but for the filing of formal information requests, all this information would still be treated confidentially and concealed from the public. But even after formal information requests were fulfilled, many mysteries remained in the redacted information released by state and federal agencies (see SM). For example, researchers still cannot learn the who, what, where, why, and when of the use or production of these compounds. Even the toxicological studies are partly redacted and hence incomplete.
This situation is not specific to the EPA or to US law. The three toxicology studies that we received from the EU’s EFSA, about 3 months after requesting them, were similarly redacted (see SM). And under the EU chemicals regulation Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH), manufacturers that register chemicals are required to submit only “robust summaries” of toxicity studies, not the studies themselves (3). Even if the full, unredacted studies were ultimately available, however, it is unclear whether scientists interested in replicating or critically reviewing the research would be able to do so (15).

Excessive Fragmentation of Information Within and Among Government Agencies

Scientists doing “back-end” environmental research would, ideally, have full access to all available information on toxicity and environmental fate and transport (2). But even when this essential information exists (which is by no means assured, because manufacturers generally have no legal duty to produce it), the information is badly fragmented and siloed (12). Different agencies at different levels of government, and even different offices within the EPA, each receive different bits of information as a result of a series of disconnected legal requirements. Obtaining a comprehensive picture of a chemical thus requires effective coordination within and among agencies and, in many cases, considerable ingenuity of researchers.

For example, for chemical registration purposes, the TSCA requires manufacturers to submit toxicity information to the federal EPA, but that information does not necessarily reach state governments responsible for public safety in the places where registered chemicals are used. Indeed, information submitted to the EPA’s chemical regulation office may not even reach other offices within the EPA, such as the air and water pollution program offices. Conversely, if a chemical in commerce is classified as hazardous, a different law requires facilities to inform state and local agencies, but not the federal EPA, if the chemical is present at the facility above threshold amounts (see SM). Other state and local legal authorities may allow some agencies to obtain information on an ad hoc basis, as New Jersey did with Cl-PFECAs (see SM). The result is a patchwork in which, for a given chemical, individual EPA offices and states may get different toxicity information; states but not the EPA may get information about where the chemical is used (but states might not learn the chemical’s identity); and only if the chemical has already officially been deemed toxic do both states and the EPA get information about releases above a threshold amount.

Trade-secret claims further complicate the statutes’ built-in information fragmentation. The 2016 amendments to the TSCA clarified that the EPA may share CBI with state, Tribal, and local authorities that need the information for implementation or enforcement of a law. To our knowledge, however, no state agency has finalized an intergovernmental agreement with the EPA that would enable sharing CBI as a matter of course. On the federal level, the EPA and the Occupational Safety and Health Administration entered into an agreement to share confidential business information only in January 2021 (see SM). We could not locate any international sharing agreements and therefore expect that access to CBI-protected information is likely fragmented internationally as well.

The statutory design thus requires entrepreneurial engagement by researchers, well beyond the usages of ordinary scientific collaboration, to ensure that all available information is accessible to them. Nongovernment investigators, in particular, may not understand that federal and state agencies hold different data or might not know which state or EPA office to ask for the data, if the presence of a chemical at a specific facility is a protected trade secret. The extra coordination burdens may inhibit or limit some research projects. Even if researchers are willing to make the effort, the problem persists: If the chemical identity information is classified, even agency staff may not know to look for it.

Reform

Explanations for why these legal impediments have arisen are incomplete. Based on the current literature, the leading hypothesis is that the manufacturing community was very involved in the development of both the original 1976 TSCA statute and the 2016 amendments and carefully secured some benefits in the legislation that enabled industry to retain control over certain key information (1).
How can these legal impediments to back-end research be overcome? More research, and probably legislative action, is needed to craft comprehensive solutions. We propose some interim measures that the EPA might take in the meantime.
For the lack of analytical reference standards, the solution seems obvious. The EPA should require manufacturers to provide a standard, to be made generally available to the public, for each registered chemical—perhaps as a mandatory condition of registration but certainly, at least, upon request (1, 7). A mandatory requirement for reference standards has long been in place for pesticides found in residues on foodstuffs, which, to our knowledge, has neither imposed expensive burdens on the manufacturers nor proved difficult to administer (13).

To begin addressing the problem of limited public access to information on file with a government, the EPA could take several stopgap measures using its legal authority under the TSCA (8). First, the EPA should help educate researchers by providing more accessible information about the extent of CBI claims and the sources of imprecision in chemical identification. Second, the EPA should interpret the TSCA to allow the automatic release of toxicological information on all chemicals, including those with CBI-protected identities (see SM). Third, the EPA should provide needed information to researchers by making better use of section 14(d) of the TSCA, which allows disclosure of CBI to protect against “an unreasonable risk of injury to health or the environment” (see SM). Finally, the EPA should develop more systematic and consistent chemical identification methods (3). All of these measures would help, but the legal treatment of CBI claims about chemicals, and the challenges of chemical identification, merits systemic legislative reform (8, 9).

Finally, to address the problem of fragmented information, the EPA should use its own authorities and collaborate with states. An example of at least a partial solution is already in the regulatory pipeline. Acting pursuant to a new and specific statutory directive, the EPA has proposed to require manufacturers of more than 1000 per- and polyfluoroalkyl substances (PFAS) to report to the EPA both past (back to 2011) and future information on the production, use, disposal, releases, exposures, and toxicity of these substances (14). This type of broader reporting requirement could simply be extended to manufacturers of all chemicals, not limited to PFAS, produced in quantities above a low threshold amount (see SM). States (after an initial request) could be automatically notified of all toxicological information obtained by the EPA. Conversely, states could provide the EPA with facility-level data that the states receive (see SM). These steps would not ensure that agencies take a comprehensive view of chemical regulation, but they would help alleviate the information fragmentation problem.

These are preliminary suggestions for measures to provide researchers with greater access to information that is essential for back-end research while still protecting legitimate confidentiality interests. We have not comprehensively analyzed approaches taken in other countries, but our research suggests that the impediments we discuss here are not wholly specific to the United States. Specific reforms must, of course, be tailored to each government’s structure and procedures. Regardless of such details, the most essential next step is to engage in an interdisciplinary investigation of impediments to research on chemicals in the United States and abroad.

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SCIENCE • 13 Jan 2022 • Vol 375, Issue 6577

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