Bioactivity of the ubiquitous tire preservative 6PPD and degradant, 6PPD-quinone in fish- and mammalian-based assays

• DOI: 10.1093/toxsci/kfaf008
• Publication Date: 2025-01-23T01:40:16Z
• Authors: Mark D Jankowski; Amy F Carpenter; Joshua A Harrill; Felix R Harris; Bridgett Hill; Rochelle Labiosa; Sergei S Makarov; Dalma Martinović-...; Jo Nyffeler; Stephanie Padilla; Timothy J Shafer; Marci G Smeltz; Daniel L Villeneuve
• Keywords: Neurotoxicity

Abstract 6PPD-quinone (N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone), a transformation product of the antiozonant 6PPD (N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine) is likely causative agent coho salmon (Oncorhynchus kisutch) pre-spawn mortality. Stormwater runoff transports into freshwater streams, rapidly leading to neurobehavioral, respiratory distress, and rapid mortality in laboratory exposed salmon, but causing no many laboratory-tested species. Given this identified hazard, potential for environmental exposure, we evaluated set U.S. Environmental Protection Agency’s high throughput assays their capability detect large potency difference between observed screen bioactivities concern. Assays included transcriptomics larval fathead minnow (FHM), developmental behavioral toxicity zebrafish, phenotypic profiling rainbow trout gill cell line, acute neurotoxicity mammalian cells, reporter transcription factor activity HepG2 cells. was more consistently bioactive across assays, with distinct assay (mean 50th centile concentration = 0.91 µM). While less potent FHM displayed minimal neurotoxic it highly altering organelle morphology RTgill-W1 cells (phenotype 0.024 µM compared 0.96 6PPD). Although vitro sensitivity may not be as sensitive intact Coho promising approach test chemicals 6PPD-quinone-like activities. The other each unique 6PPD, neurobehavioral being most affected, indicating need further assessment chemical.