Cao, Yuexin
(2025)
Integrating Computational and Experimental Approaches to Evaluate the Potential Hazards of Per- and Polyfluoroalkyl Substances (PFAS) Used in Photolithography.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Per- and polyfluoroalkyl substances (PFAS) are a group of thousands of synthetic chemicals used extensively across industries, including photolithography, a critical process in semiconductor manufacturing. Semiconductors are ubiquitous, with significant increasing demand in the current era of advanced artificial intelligence technology and automative industry. Effective nonfluorinated alternatives are currently unavailable for advanced manufacturing of computer chips. Due to their extensive use, PFAS have been detected in manufacturing wastewater and surrounding water bodies, yet the hazards of most PFAS, including their toxicity and bioaccumulation potentials, remain underexplored. Therefore, this dissertation aims to address these gaps by integrating in silico and in vivo approaches to evaluate the potential hazards of photolithography-relevant PFAS. First, we identified 96 photolithography-relevant PFAS and integrated molecular dynamics and docking to conduct high-throughput screening of their interactions with five target proteins: liver fatty acid binding protein (LFABP), serum albumin (SA), peroxisome proliferator activated receptors alpha and gamma (PPARa & PPARg), and transthyretin (TTR). The model, validated against empirical binding affinities, revealed that 22 of the analyzed PFAS exhibited stronger binding to at least one protein than perfluorooctane sulfonic acid (PFOS), a known hazardous PFAS, suggesting potential toxicological concerns. To complement computational insights, we conducted developmental toxicity and transcriptional analyses on zebrafish larvae exposed to 9 photolithography-relevant PFAS. Findings indicated PFAS exposure led to delayed hatching, lethality, and various malformations, with specific genes, such as pparg and fgf10a, emerging as potential biomarkers for metabolic and developmental toxicity pathways. Finally, we selected the brain as a target organ for understanding PFAS impacts through integration of toxicokinetics and toxicodynamics. We reviewed 65 papers (2005-2020) on the absorption, accumulation, distribution and neurotoxic potential of PFAS in the brain from epidemiological, in vivo and in vitro perspectives. The results highlighted the need to clarify PFAS transport mechanisms into the brain and to link accumulation with neurotoxicity mechanisms. Overall, this work advances the understanding of PFAS toxicity and supports the development of safer PFAS alternatives for photolithography and related applications, contributing to sustainable semiconductor manufacturing practices.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
7 January 2025 |
| Date Type: |
Publication |
| Defense Date: |
11 November 2024 |
| Approval Date: |
7 January 2025 |
| Submission Date: |
30 October 2024 |
| Access Restriction: |
1 year -- Restrict access to University of Pittsburgh for a period of 1 year. |
| Number of Pages: |
194 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Swanson School of Engineering > Civil and Environmental Engineering |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
PFAS, Toxicity, Computational Toxicology, Molecular Dynamics, Molecular Docking, Zebrafish Embryo Assay |
| Date Deposited: |
07 Jan 2025 21:07 |
| Last Modified: |
07 Jan 2026 13:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/47048 |
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