The U.S. Environmental Protection Agency (EPA) announced on March 25, 2024, that it has issued the fourth Toxic Substances Control Act (TSCA) test order requiring testing on per- and polyfluoroalkyl substances (PFAS) under its National PFAS Testing Strategy. According to EPA, the action requires the 3M Company (3M) and Wacker Chemical Corporation (Wacker) to conduct and submit testing on the physical-chemical properties of 2-(N-Methylperfluoro-1-octanesulfonamido)ethanol (NMeFOSE) (Chemical Abstracts Service Registry Number® (CAS RN®) 24448-09-7), including testing on the health effects following inhalation of this chemical. According to EPA, NMeFOSE “has been used widely in products, including clothing and carpet treatments as well as furniture coatings (paint and varnish).” EPA states that NMeFOSE has been found in the air and in biosolids, a byproduct of the water treatment processes often used on agricultural fields as fertilizer. EPA notes that studies have demonstrated that NMeFOSE can accumulate in indoor dust and air, as well as in outdoor environmental media.
EPA states that after thoroughly examining existing hazard and exposure data, it concluded that NMeFOSE may present an unreasonable risk of injury to health or the environment. According to EPA, the potential hazards from exposure to this chemical could include damage to the nervous system and immune system, as well as cancer. EPA expects the test order to help it better understand the potential hazards and potential exposures associated with NMeFOSE. EPA notes that the information received under the order “will not only improve the Agency’s understanding of human health effects of NMeFOSE, but also potential health effects of more than 100 PFAS that are structurally similar to NMeFOSE and add to the agency’s overall understanding of this category of PFAS.”
EPA states that the companies subject to the test order may either conduct the tests as described in the order or provide EPA with existing information that they believe EPA did not identify in its search, but which satisfies the order requirements. EPA encourages companies to conduct joint testing to avoid unnecessary duplication of tests. According to EPA, it will also consider possible combinations of tests that cover all required endpoints to diminish the amount of time, animal subjects, and costs required.
The order employs a tiered testing process, as required by TSCA. EPA issued the order on March 20, 2024, and it was effective March 25, 2024. The results of all the first-tier testing are required to be submitted to EPA within one year of the effective date of the order and will inform the decision as to which additional tests are necessary. EPA states that it will make the order and any data submitted in response to it publicly available, subject to confidentiality considerations under TSCA Section 14.
Commentary
Bergeson & Campbell, P.C. (B&C®) is surprised by EPA’s selection of NMeFOSE as a candidate substance for evaluation using EPA’s order authority under TSCA Section 4(a)(1). First, it is not clear that either 3M or Wacker currently manufactures NMeFOSE. 3M commented to the docket that it ceased to manufacture NMeFOSE decades ago. Nevertheless, EPA issued the order to 3M, but provides 3M with an opportunity to respond that it has not manufactured NMeFOSE in the past five years (and does not intend to going forward) and is therefore eligible for an exemption from the order.
Another issue that we see in the order is that EPA attributed a host of hazards to this substance, including ones that do not appear relevant based on the available information on substances identified by EPA as PFAS. For example, EPA summarized under the header for “Hazard and Exposure for PFAS” concerns for cardiac sensitization. This concern is, however, for volatile substances that in many cases do not satisfy EPA’s Office of Pollution Prevention and Toxics’ definition of PFAS (see, e.g., 1,2-dichloro-1,1-difluoroethane [HCFC-132b], CAS RN 1649-08-7, and 1,1-difluoroethane [HFC-152a], CAS RN 75-37-6). Neither of these is a PFAS, nor are they analogs to NMeFOSE, so they are of questionable relevance to a substance like NMeFOSE.
EPA stated in the test order that the expected biotransformation of NMeFOSE includes N-dealkylation of the N-methyl group and several subsequent steps that ultimately lead to the formation of perfluorooctane sulfonic acid (PFOS; CAS RN 1763-23-1) and hydroxylamine (CAS RN 7803-49-8). This is consistent with Health Canada’s findings in its 2006 assessment titled “Perfluorooctane Sulfonate, Its Salts and Its Precursors that Contain the C8F17SO2 or C8F17SO3 Moiety.” Health Canada stated that:
Since PFOS is likely the ultimate perfluorinated degradation or metabolic product of the group of substances listed in Appendix 1 [including NMeFOSE], the level of this compound [i.e., PFOS] in human tissue provides a useful indicator of exposure to this group of substances from all potential sources.
Health Canada also compared the available toxicity data on PFOS with the identified PFOS precursors and found that:
Available data indicate that effects associated with the PFOS precursors occur at exposures that are similar to or slightly higher than those for PFOS.
Health Canada provided data tables on a series of PFOS precursors, including N-ethylperfluorooctane sulfonamidoethanol (NEtFOSE, CAS RN 1691-99-2). NEtFOSE is a close analog to NMeFOSE and differs from NMeFOSE only by the presence of an N-ethyl group (-CH2CH3), rather than an N-methyl group (-CH3). NEtFOSE also has an extensive toxicological database, including, for example, acute oral and inhalation toxicity studies, subchronic and chronic oral toxicity studies, and reproductive and developmental toxicity studies.
Given that EPA has a close analog to NMeFOSE (i.e., NEtFOSE), PFOS is a primary degradant (PFOS) of both NMeFOSE and NEtFOSE, and NMeFOSE appears to not be currently manufactured, it is not clear why EPA issued a test order on NMeFOSE. EPA could have informed its evaluation of the potential hazards for NMeFOSE with the available data on NEtFOSE and its recent in-depth evaluation of PFOS. If EPA had aligned its evaluation in a manner comparable with that of Health Canada, this would have freed up resources within EPA to focus its test order activities on those PFAS with limited data sets and no suitable analogs.
Beyond the actual need for the test order on NMeFOSE, B&C notes that EPA stated in the test order that “a recipient is subject if it has manufactured or processed the chemical at any time during the 5 years preceding the date of this Order…or if they intend to manufacture or process the chemical within the period of testing provided by this Order.” We found this interesting because one of the order recipients informed EPA over five months ago that it had ceased manufacture of NMeFOSE “more than twenty years ago.” Yet, EPA still included this entity as a test order recipient. This is not, however, EPA’s first time with including questionably relevant recipients in its test orders. EPA was sued on August 15, 2022, by the National Foam, Inc. after being named as a recipient of EPA’s test order on 6:2 fluorotelomer sulfonamide betaine (6:2-FTSB), a PFAS. National Foam, Inc. was neither a manufacturer nor processor of 6:2-FTSB and provided “substantial evidence” to EPA in support of this, yet it took months of settlement discussions with EPA before it finally granted National Foam, Inc.’s exemption request. For discussion, see our memorandum dated January 5, 2024.
B&C encourages interested parties to review EPA’s test orders on NMeFOSE and other chemical substances. EPA’s test orders provide valuable insight on the types of data EPA is seeking through its ordered testing. The test orders also offer relevant information on the types of new approach methodologies (NAM) that EPA is embracing (e.g., in vitro respiratory toxicity testing). For discussion, see our memorandum dated January 23, 2023. Finally, we caution entities that receive pre-issuance notification of a pending test order to be diligent with providing evidence to EPA, particularly for those entities that are incorrectly identified as test order recipients.