Determining global background soil PFAS loads and the fluorotelomer-based polymer degradation rates that can account for these loads.

In recent years, fluorotelomer-based polymers (FTPs) have been the dominant product of the fluorotelomer industry. For the last decade, whether FTPs degrade to toxic perfluorocarboxylates (PFCAs) has been vigorously contested, with early studies arguing that FTPs have half-lives >1000 years, and others concluding decadal half-lives. Given this FTP half-life discrepancy of 10- to >100-fold, here we investigate whether environmental loads of long-chain PFCAs might offer an independent approach to assess FTP half-lives. Specifically we: i) use surface soil-PFCA data to estimate terrestrial surface-soil background PFCA concentrations and loads; ii) extrapolate these data to generate global PFCA load estimates; iii) compare these estimates to published ocean-derived and industrial-emissions load estimates, finding agreement for perfluorooctanoate (C8), but an excess in longer-chain (C10,C12) PFCAs for ocean- and soil-derived loads relative to emissions; iv) model FTP degradation rates required to reconcile this discrepancy; and iv) compare our modeled estimates to existing experimental results. These findings show agreement for FTP half-lives at the decades-scale supporting existing laboratory studies that report decade-scale half-lives for FTPs. This suggests that global long-chain PFCA loads will increase for decades if legacy FTPs already manufactured are not contained upon disposal. These results suggest that FTPs comprised of novel poly- and perfluorinated alkyl substances (PFASs) now in production might constitute considerable sources to the environment of the new generation of PFASs.

History of EPI Suite™ and future perspectives on chemical property estimation in US Toxic Substances Control Act new chemical risk assessments.

Chemical property estimation is a key component in many industrial, academic, and regulatory activities, including in the risk assessment associated with the approximately 1000 new chemical pre-manufacture notices the United States Environmental Protection Agency (US EPA) receives annually. The US EPA evaluates fate, exposure and toxicity under the 1976 Toxic Substances Control Act (amended by the 2016 Frank R. Lautenberg Chemical Safety for the 21st Century Act), which does not require test data with new chemical applications. Though the submission of data is not required, the US EPA has, over the past 40 years, occasionally received chemical-specific data with pre-manufacture notices. The US EPA has been actively using this and publicly available data to develop and refine predictive computerized models, most of which are housed in EPI Suite™, to estimate chemical properties used in the risk assessment of new chemicals. The US EPA develops and uses models based on (quantitative) structure-activity relationships ([Q]SARs) to estimate critical parameters. As in any evolving field, (Q)SARs have experienced successes, suffered failures, and responded to emerging trends. Correlations of a chemical structure with its properties or biological activity were first demonstrated in the late 19th century and today have been encapsulated in a myriad of quantitative and qualitative SARs. The development and proliferation of the personal computer in the late 20th century gave rise to a quickly increasing number of property estimation models, and continually improved computing power and connectivity among researchers via the internet are enabling the development of increasingly complex models.

Characterizing fluorotelomer and polyfluoroalkyl substances in new and aged fluorotelomer-based polymers for degradation studies with GC/MS and LC/MS/MS.

Fluorotelomer-based polymers (FTPs), the dominant product of the fluorotelomer industry, are antistaining and antiwetting agents that permeate the products and surfaces of modern society. However, the degree to which these materials expose humans and the environment to fluorotelomer and perfluorinated compounds, including recalcitrant and toxic compounds such as perfluorooctanoic acid (PFOA), is ill-defined. The design intent of FTPs, to minimize interaction with other substances, including solvents, heretofore has stymied efforts to develop robust methods to characterize the content of monomers and associated compounds of new commercial FTPs, as well as commercial FTPs that have been aged in environmental media for degradation testing. Here we show that FTPs can be exhausted of these compounds and quantitated by (i) drying the FTP on a suitable substrate at elevated temperature to achieve low, constant monomer concentrations; (ii) serial extraction with MTBE for fluorotelomer-monomer analysis by GC/MS in PCI mode; followed by (iii) serial extraction with 90/10 ACN/H2O for polyfluorocompound analysis by LC/MS/MS in negative ESI mode. This approach yields exhaustive, internally consistent accounting of monomers and associated compounds for FTPs, either alone or in a soil matrix (representing an environmental medium), for both new and simulated-aged FTPs to allow degradation testing, and for fluorinated compounds at least as long as C12.

Use of the bioaccumulation factor to screen chemicals for bioaccumulation potential.

The fish bioconcentration factor (BCF), as calculated from controlled laboratory tests, is commonly used in chemical management programs to screen chemicals for bioaccumulation potential. The bioaccumulation factor (BAF), as calculated from field-caught fish, is more ecologically relevant because it accounts for dietary, respiratory, and dermal exposures. The BCFBAF™ program in the U.S. Environmental Protection Agency's Estimation Programs Interface Suite (EPI Suite™ Ver 4.10) screening-level tool includes the Arnot-Gobas quantitative structure-activity relationship model to estimate BAFs for organic chemicals in fish. Bioaccumulation factors can be greater than BCFs, suggesting that using the BAF rather than the BCF for screening bioaccumulation potential could have regulatory and resource implications for chemical assessment programs. To evaluate these potential implications, BCFBAF was used to calculate BAFs and BCFs for 6,034 U.S. high- and medium-production volume chemicals. The results indicate no change in the bioaccumulation rating for 86% of these chemicals, with 3% receiving lower and 11% receiving higher bioaccumulation ratings when using the BAF rather than the BCF. All chemicals that received higher bioaccumulation ratings had log K(OW ) values greater than 4.02, in which a chemical's BAF was more representative of field-based bioaccumulation than its BCF. Similar results were obtained for 374 new chemicals. Screening based on BAFs provides ecologically relevant results without a substantial increase in resources needed for assessments or the number of chemicals screened as being of concern for bioaccumulation potential.

Biodegradation of US premanufacture notice chemicals in OECD tests.

Biodegradation testing of commercial chemicals other than pesticides is generally performed using test guidelines of the Organization for Economic Cooperation and Development (OECD). We used test data submitted with US Premanufacture Notifications (PMNs) received from 1995 through 2005 to study performance of OECD biodegradation tests, as well as the overall testing strategy and guidance. Among the findings are that (1) ready biodegradation (RB) tests gave fairly consistent results relative to the pass/fail outcome, but not necessarily percent degradation; (2) the Zahn-Wellens test worked well in providing a quick measure of sorption potential, but aside from this, provided little useful information for the investigated chemicals beyond what was already available from RB tests; (3) the SCAS test sometimes gives lower % removal than continuous-feed simulation tests like OECD 303A; and (4) OECD 306 (marine biodegradation test) appeared less conservative than ordinary RB tests. Overall, the PMN data lend support to new OECD guidance that endorses the primary role of RB tests, but emphasizes simulation rather than inherent biodegradation tests as the next step.

Using Biowin, Bayes, and batteries to predict ready biodegradability.

Whether or not a given chemical substance is readily biodegradable is an important piece of information in risk screening for both new and existing chemicals. Despite the relatively low cost of Organization for Economic Cooperation and Development tests, data are often unavailable and biodegradability must be estimated. In this paper, we focus on the predictive value of selected Biowin models and model batteries using Bayesian analysis. Posterior probabilities, calculated based on performance with the model training sets using Bayes' theorem, were closely matched by actual performance with an expanded set of 374 premanufacture notice (PMN) substances. Further analysis suggested that a simple battery consisting of Biowin3 (survey ultimate biodegradation model) and Biowin5 (Ministry of International Trade and Industry [MITI] linear model) would have enhanced predictive power in comparison to individual models. Application of the battery to PMN substances showed that performance matched expectation. This approach significantly reduced both false positives for ready biodegradability and the overall misclassification rate. Similar results were obtained for a set of 63 pharmaceuticals using a battery consisting of Biowin3 and Biowin6 (MITI nonlinear model). Biodegradation data for PMNs tested in multiple ready tests or both inherent and ready biodegradation tests yielded additional insights that may be useful in risk screening.

Predicting ready biodegradability of premanufacture notice chemicals.

Chemical substances other than pesticides, drugs, and food additives are regulated by the U.S. Environmental Protection Agency (U.S. EPA) under the Toxic Substances Control Act (TSCA), but the United States does not require that new substances be tested automatically for such critical properties as biodegradability. The resulting lack of submitted data has fostered the development of estimation methods, and the BioWIN models for predicting biodegradability from chemical structure have played a prominent role in premanufacture notice (PMN) review. Until now, validation efforts have used only the Japanese Ministry of International Trade and Industry (MITI) test data and have not included all models. To assess BioWIN performance with PMN substances, we assembled a database of PMNs for which ready biodegradation data had been submitted over the period 1995 through 2001. The 305 PMN structures are highly varied and pose major challenges to chemical property estimation. Despite the variability of ready biodegradation tests, the use of at least six different test methods, and widely varying quality of submitted data, accuracy of four of six BioWIN models (MITI linear, MITI nonlinear, survey ultimate, survey primary) was in the 80+% range for predicting ready biodegradability. Greater accuracy (>90%) can be achieved by using model estimates only when the four models agree (true for 3/4 of the PMNs). The BioWIN linear and nonlinear probability models did not perform as well even when classification criteria were optimized. The results suggest that the MITI and survey BioWIN models are suitable for use in screening-level applications.