Toxicity screening of ubiquitous rubber antioxidants and their ozonation products using fish cell lines: Implications for environmental health and potential alternatives

This work investigated the toxicity of four p-phenyldiamine (PPD) compounds, commonly used as antioxidants in tire rubber, and their quinone derivatives (PPD-quinone) formed upon ozonation, on two Rainbow Trout cell lines: RTbrain and RTgill-W1. The primary goal of this study was to assess the potential threat posed by these PPDs and PPD-quinones to aquatic life through a toxicity screening, as well as their potential as safer alternatives to the use of 6PPD in tire rubber. The secondary goal was to use these results to gain insight into the specific toxicity mechanism of 6PPD-quinone. While DPPD, CPPD and IPPD displayed similar toxicity profiles across the two cell lines, their corresponding PPD-quinones showed no sign of toxicity. 6PPD-Q however exhibited high selective toxicity towards the RTbrain cell line. The results obtained appeared to point towards a non-specific toxicity of DPPD, CPPD and IPPD, whose EC50s were nonetheless at least three orders of magnitude above environmental concentrations. Insights from the toxicity screening furthermore suggested that 6PPD-Q's highly selective toxicity could be linked to its unique molecular structure. Overall, this study highlighted the potential of DPPD, CPPD and IPPD as potential safer alternatives to the use of 6PPD in tire rubber, as their respective PPD-quinones showed no toxicity towards RTgill-W1 and RTbrain cell lines. 6PPD-Q's highly specific toxicity towards RTbrain cells furthermore emphasized its unique mechanism and likely interactions in the brain of sensitive fish.