PNNL

Abstract

Per- and polyfluoroalkyl substances (PFAS) are a widespread and persistent class of contaminants posing significant environmental and human health concerns. Comprehensive understanding of the modes of action underlying toxicity among structurally diverse PFAS is mostly lacking. To address this need, we recently reported on our application of developing zebrafish to evaluate a large library of PFAS for developmental toxicity. In the present study, we prioritized 15 bioactive PFAS from the library that induced significant morphological effects and performed RNA-sequencing to characterize early transcriptional responses at 48 hours post fertilization after early developmental exposures (8 hours post fertilization). Internal concentrations of 5 select PFAS within pooled whole fish samples and additional temporal transcriptomics for nafion byproduct 2 were assessed across developmental stages ranging from 24 to 120 hours post fertilization. A broad range of differentially expressed gene counts were identified across the PFAS exposures. Most PFAS that elicited robust transcriptomic changes affected the expression of genes related to biological processes of the brain and nervous system development. While PFAS disrupted unique processes, we also found that similarities in some functional head groups of PFAS were associated with the disruption of the expression of similar gene sets. Body burdens after early developmental exposures to select sulfonic acid PFAS and nafion byproduct 2 increased from the 24 to 96 hours post fertilization sampling timepoints and were greater than those of sulfonamide PFAS of similar chain lengths. In parallel, the nafion byproduct 2-induced transcriptional responses increased between 48 and 96 hours post fertilization. PFAS characteristics based on toxicity, transcriptomic effects, and modes of action will contribute to further prioritization of PFAS structures for testing and informed hazard assessment.