# Developmental Toxicity of Photolithography-Relevant Per- and Polyfluoroalkyl Substances (PFAS) Reveals Concerns for Less-Studied Functional Groups

## TL;DR

This study shows that some PFAS used in semiconductor manufacturing harm zebrafish embryos and alter gene activity, suggesting they may be more toxic than previously known PFAS.

## Contribution

The study identifies new toxicological concerns for less-studied PFAS functional groups used in photolithography.

## Key findings

- Certain PFAS caused increased embryo death and malformations like yolk sac edema.
- Some PFAS significantly downregulated key genes (pparg and mttp) at low concentrations.
- Less-studied PFAS functional groups appear more toxic than traditional ones.

## Abstract

Per- and polyfluoroalkyl substances (PFAS) are used throughout
semiconductor manufacturing, including photolithography, yet many
remain toxicologically uncharacterized. This study used the zebrafish
embryo assay to assess developmental toxicity and gene expression
changes (fgf10a, igf1, fabp10a, pparg, and mttp) linked to growth
and lipid metabolism for nine legacy and emerging photolithography-relevant
PFAS. Exposure induced increased lethality and common malformations,
including failure of swim bladder inflation and yolk sac edema. Transcriptional
analysis revealed that certain PFAS, especially triphenylsulfonium
perfluoro-1-butanesulfonate, 1H,1H,2H,2H-perfluorooctane sulfonic
acid, perfluorooctanoic acid, and bis­(1,1,2,2,3,3,4,4,4-nonafluoro-1-butanesulfonyl)­imid,
significantly downregulated pparg and mttp expression, even at environmentally relevant concentrations. Our
findings raise concerns that certain PFAS actively used in photolithography,
including some with less-studied functional groups (e.g., perfluoroalkyl
dicarboxylic acids and perfluorosulfonamides), are more toxic than
equivalent-chain monocarboxylic acid and legacy PFAS, respectively,
providing mechanistic insight into PFAS-induced toxicity. These results
help inform the selection of safer chemicals in semiconductor manufacturing.