The U.S. Environmental Protection Agency (EPA) announced on October 5, 2022, a new effort under the Toxic Substances Control Act (TSCA) to implement a streamlined and more efficient process under the New Chemicals Program to assess risk and apply mitigation measures, as appropriate, for new chemicals with applications in batteries, electric vehicles, semiconductors, and renewable energy generation. The new process is for mixed metal oxides (MMO), including new and modified cathode active materials (CAM). EPA states that MMOs are innovative chemistries and have numerous electrical applications in batteries, as well as use as catalysts, adsorbents, and in ceramics. According to EPA, MMOs, including CAMs, are notably a key component in lithium-ion batteries used in electric vehicles, “a growing and important industry.” New MMOs can also be used for semi-conductors, and renewable energy generation and storage, such as solar cells and wind power turbines. They typically consist of lithium, nickel, cobalt, and other metals, and they are the key material used in the production of the cathode in battery cells, which are subsequently assembled into a battery.

EPA notes that like all chemical substances not listed on the TSCA Inventory, MMOs, including new and modified CAMs, are subject to TSCA Section 5, which requires manufacturers (including importers) of new chemical substances to provide EPA with notice before initiating the activity by submitting a premanufacture notice (PMN). When EPA receives a PMN, TSCA requires the Agency to assess fully all the potential hazards and exposures of the new chemical substance, make a determination as to whether it presents an unreasonable risk to human health or the environment, and take steps to address that risk before it can enter commerce.

EPA states that it has reviewed “hundreds” of TSCA Section 5 submissions for MMOs, including CAMs and modified CAMs, since the 1980s. To describe this new effort further, EPA will launch outreach and training for interested stakeholders to outline the new streamlined approach to reviewing MMOs, basics of TSCA statutory and regulatory requirements, and steps for navigating the new chemicals submission process. Stakeholders can subscribe to the EPA Office of Chemical Safety and Pollution Prevention’s (OCSPP) news releases to receive notices about upcoming webinars.

EPA supplemented its announcement with the release of a Compliance Advisory that reaffirms that new MMOs, including CAMs and modified CAMs, are new chemical substances subject to TSCA. EPA states that anyone who plans to manufacture (including import) a CAM or modified CAM that is not on the TSCA Inventory must comply with the TSCA Section 5 new chemical requirements and implementing regulations.

As reported in our January 24, 2022, blog item, in January 2022, EPA launched a similar effort to streamline the review of “dozens” of PMNs for biofuels that could be used to displace current, higher greenhouse gas (GHG) emitting transportation fuels. EPA states that under this effort, it has completed about 95 percent of all biofuel PMNs submitted since the initiative was announced. More information on the biofuels initiative is available in our April 7, 2022, memorandum.

Commentary

We applaud EPA for reinvigorating its category approach to new chemical reviews. EPA has, for decades, used its experience with reviewing new chemicals to group substances by category to streamline its decision-making and, if necessary, to take regulatory action. This practice continued with TSCA reform in 2016. Since this time, EPA initiated the development of four lung effect categories (i.e., polycationic substances, general surfactants, waterproofing agents, and insoluble polymer lung overload), one category on over 100 structurally similar tracer chemicals, and several structural categories on perfluorinated chemicals. Despite resource and staffing limitations, EPA completed its tiered-testing strategy on the photo-acid generators (PAG) category in June 2017. It also advanced two of the lung effect categories on surfactants and poorly soluble low-toxicity (PSLT) polymers (previously the insoluble polymer lung overload category), which EPA’s senior scientists presented at the Society of Toxicology Meeting in March 2021. Further, in October 2021, EPA issued its National PFAS Testing Strategy. The foregoing examples are commendable and provide EPA with recent experience and lessons learned, which it may carry forward with developing chemical categories for MMOs. Bergeson & Campbell, P.C. (B&C^®) does, however, caution interested parties to monitor this initiative closely due to some of the outstanding and outdated approaches EPA has used specifically with MMOs and generally with poorly soluble particles, as discussed below.

EPA issued its most recent TSCA New Chemicals Program (NCP) Chemical Categories document in August 2010. Under the category titled “Respirable, Poorly Soluble Particulates,” EPA derived a new chemical exposure limit (NCEL) for a MMO (i.e., “PMN 96-175, Lithium Manganese Oxide”) of 0.04 mg/m³. EPA derived this value using the no-observed-adverse-effect-level (NOAEL) of 4 mg/m³ from a 90-day inhalation toxicity study in rats and applied an uncertainty factor of 100 (i.e., 4 mg/m³ ÷ 100 = 0.04 mg/m³). EPA did not, however, apply dosimetric adjustments to the rat inhalation NOAEL to calculate a human equivalent concentration (HEC), even though the best available science both today and at that time supported doing so.

We mention the issue of dosimetry because EPA has issued numerous NCELs on MMOs that will have to be re-evaluated using the best available science if, for example, EPA identifies subcategory-specific MMOs as comparator substances to new chemical submissions on MMOs. Further, we note that EPA will need to provide the scientific justification for the dosimetric adjustment and its use of “deposited dose” or “retained dose” as the dose metric. This is an important consideration, given that EPA used “deposited dose” in the final risk evaluation on C.I. Pigment Violet 29 (PV29), a PSLT particle, despite the best available science supporting use of the “retained dose.” More information on the scientific issues with the final PV29 risk evaluation is available in our September 9, 2022, memorandum.

Beyond identifying points of departure (POD) and calculating NCELs, we note that EPA’s methods for calculating margins of exposure (MOE) for new chemical substances should also be scrutinized. For example, EPA routinely uses an acute potential dose rate (PDR) as the exposure metric for assessing potential risks to workers under occupational conditions of use. Though this is a pragmatic initial screen for unreasonable risks, EPA does not perform refinements to its new chemical risk assessments when it does identify unreasonable risks using the PDR, again an acute exposure value, for hazard concerns that are chronic in nature. An example of such a refinement would be calculating the average daily concentration (ADC), which EPA did in the final PV29 risk evaluation.

The above dose- and exposure-metric issues lead to delays in new chemical reviews and determinations, which create barriers to market entry -- and concomitant commercial benefits -- of MMOs, as well as other novel chemistries. Research into MMOs, especially with how the performance of MMOs can change with minor components (dopants), is fast-moving. Given the common properties of MMOs and EPA’s experience evaluating these chemistries, it makes sense for EPA to take a categorial approach. Minor changes in these chemistries, however, may alter the toxicological properties of these substances, for example, from a PSLT particle to a poorly soluble cytotoxic particle. Therefore, we are hopeful that EPA will build off its scholarship on more recent chemical categories, in particular the PSLT polymer category, which utilized new approach methodologies (NAM) for determining whether a chemical substance should be included in the PSLT polymer category or excluded, for example, due to water extractability or reactivity. In the absence of doing so, EPA’s streamlined and efficient process may end being nothing more than a faster conclusion to “insufficient information” and a recommendation for conducting a 90-day subchronic inhalation toxicity study in rats.

We encourage readers to consider the above, non-exhaustive list, of issues and to comment to EPA as appropriate. MMOs are representative chemistries that can provide significant benefits to human health and the environment (e.g., renewable energy generation), however, these chemistries must also be evaluated in a manner consistent with the scientific standards under TSCA Section 26 to determine whether they may present an unreasonable risk to human health or the environment. Doing so requires transparency and public participation, given that these determinations can be skewed by using outdated information/practices or pre-decisional conclusions of risk, which may unnecessarily lead to incorrect unreasonable risk conclusions.