Targeted Per- and Polyfluoroalkyl substances (PFAS) assessments for high throughput screening: Analytical and testing considerations to inform a PFAS stock quality evaluation framework

• Published in: Toxicology and applied pharmacology Vol. 459; p. 116355
• Main Authors: Smeltz, Marci G., Clifton, M. Scott, Henderson, W. Matthew, McMillan, Larry, Wetmore, Barbara A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.01.2023
• Subjects: Chemical quality; Computer Simulation; Dimethyl Sulfoxide; Excipients; Fluorocarbons - toxicity; High-throughput screening; High-Throughput Screening Assays; In vitro toxicity testing; Mass spectrometry; New approach methods; PFAS; Chemical quality; High-throughput screening; PFAS; Mass spectrometry; New approach methods; In vitro toxicity testing
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2022.116355

Per- and polyfluoroalkyl substances (PFAS) represent a large chemical class lacking hazard, toxicokinetic, and exposure information. To accelerate PFAS hazard evaluation, new approach methodologies (NAMs) comprised of in vitro high-throughput toxicity screening, toxicokinetic data, and computational modeling are being employed in read across strategies to evaluate the larger PFAS landscape. A critical consideration to ensure robust evaluations is a parallel assessment of the quality of the screening stock solutions, where dimethyl sulfoxide (DMSO) is often the diluent of choice. Challenged by the lack of commercially available reference standards for many of the selected PFAS and reliance on mass spectrometry approaches for such an evaluation, we developed a high-throughput framework to evaluate the quality of screening stocks for 205 PFAS selected for these NAM efforts. Using mass spectrometry coupled with either liquid or gas chromatography, a quality scoring system was developed that incorporated observations during mass spectral examination to provide a simple pass or fail notation. Informational flags were used to further describe findings regarding parent analyte presence through accurate mass identification, evidence of contaminants and/or degradation, or further describe characteristics such as isomer presence. Across the PFAS-DMSO stocks tested, 148 unique PFAS received passing quality scores to allow for further in vitro testing whereas 57 received a failing score primarily due to detection issues or confounding effects of DMSO. Principle component analysis indicated vapor pressure and Henry's Law Constant as top indicators for a failed quality score for those analyzed by gas chromatography. Three PFAS in the hexafluoropropylene oxide family failed due to degradation in DMSO. As the PFAS evaluated spanned over 20 different structural categories, additional commentary describes analytical observations across specific groups related to PFAS stock composition, detection, stability, and methodologic considerations that will be useful for informing future analytical assessment and downstream HTS efforts. The high-throughput stock quality scoring workflow presented holds value as a tool to evaluate chemical presence and quality efficiently and for informing data inclusion in PFAS or other NAM screening efforts. [Display omitted] •205 unique PFAS in organic solvents analyzed for stock quality by mass spectrometry.•Pass/fail score and informational flags assigned to 471 PFAS stock solutions.•Failed stocks due to solvent degradation and/or failure to detect the analyte.•Stock quality assessment advises in vitro toxicological data interpretation.