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Evaluating the bioactivity of the ubiquitous tire preservative 6PPD and degradant, 6PPD-quinone

ABSTRACT: N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-quinone; 6PPD-Q), a transformation product of an antiozonant chemical widely used in automobile tires (6PPD; N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine) was identified as the causative agent for pre-spawn mortality in coho salmon resulting from exposure to stormwater run-off. This study employed a 24 h, 96-well plate based, exposure to larval fathead minnows (5 days post-fertilization) to examine the effects of 6PPD and 6PPD-Q exposure on global gene expression. Concentration-response modeling of the resulting gene expression changes identified a transcriptomic point of departure of 1.3 uM for 6PPD and 2.5 uM for 6PPD-Q, although they are effectively equivalent considering the range of uncertainty. Examination of the functional roles of differentially expressed genes provided little insight into the mechanism of idiosyncratic toxicity observed in coho salmon and certain other salmonid species. Overall, larval fathead minnows do not appear sensitive to the same mechanisms.

ORGANISM(S): Pimephales promelas

PROVIDER: GSE241136 | GEO | 2025/07/30

REPOSITORIES: GEO

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Project description:Traditional toxicity testing has been unable to keep pace with the introduction of new chemicals into commerce. Consequently, there are limited or no toxicity data upon which to base a risk assessment for many chemicals to which fish and wildlife may be exposed. Per- and polyfluoroalkyl substances (PFAS) are emblematic of this issue in that most the ecological hazards of most PFAS remain uncharacterized. The present study employed a high throughput assay to identify the concentration at which 20 PFAS, with diverse properties, elicited a concerted gene expression response in larval fathead minnows (Pimephales promelas, 5-6 days post-fertilization) exposed for 24 h. Based on a reduced transcriptome approach that measured whole body expression of 1832 genes, the median transcriptomic point of departure (tPOD) for the 20 PFAS tested was 10 µM. Longer chain carboxylic acids (12-13 C-F) and an eight C-F di-alcohol, N-alkyl sulfonamide, and telomer sulfonic acid were among the most potent PFAS, eliciting gene expression responses at concentrations below 1 µM. With a few exceptions, larval fathead minnow tPODs were concordant with those based on whole transcriptome response in human cell lines. However, larval fathead minnow tPODs were often greater than those for Daphnia magna exposed to the same PFAS. The tPODs overlapped concentrations at which other sub-lethal effects have been reported in fish (available for 10 PFAS; including a range of species, life stages, and study designs). Nonetheless, fathead minnow tPODs were all orders of magnitude higher than aqueous PFAS concentrations detected in tributaries of the North American Great Lakes suggesting a substantial margin of safety in those systems, even for PFAS with significant potential for bioaccumulation. Overall, results broadly support the use of a fathead minnow larval transcriptomics assay to derive screening level potency estimates for use in ecological risk-based prioritization. Traditional toxicity testing has been unable to keep pace with the introduction of new chemicals into commerce. Consequently, there are limited or no toxicity data upon which to base a risk assessment for many chemicals to which fish and wildlife may be exposed. Per- and polyfluoroalkyl substances (PFAS) are emblematic of this issue in that most the ecological hazards of most PFAS remain uncharacterized. The present study employed a high throughput assay to identify the concentration at which 20 PFAS, with diverse properties, elicited a concerted gene expression response in larval fathead minnows (Pimephales promelas, 5-6 days post-fertilization) exposed for 24 h. Based on a reduced transcriptome approach that measured whole body expression of 1832 genes, the median transcriptomic point of departure (tPOD) for the 20 PFAS tested was 10 µM. Longer chain carboxylic acids (12-13 C-F) and an eight C-F di-alcohol, N-alkyl sulfonamide, and telomer sulfonic acid were among the most potent PFAS, eliciting gene expression responses at concentrations below 1 µM. With a few exceptions, larval fathead minnow tPODs were concordant with those based on whole transcriptome response in human cell lines. However, larval fathead minnow tPODs were often greater than those for Daphnia magna exposed to the same PFAS. The tPODs overlapped concentrations at which other sub-lethal effects have been reported in fish (available for 10 PFAS; including a range of species, life stages, and study designs). Nonetheless, fathead minnow tPODs were all orders of magnitude higher than aqueous PFAS concentrations detected in tributaries of the North American Great Lakes suggesting a substantial margin of safety in those systems, even for PFAS with significant potential for bioaccumulation. Overall, results broadly support the use of a fathead minnow larval transcriptomics assay to derive screening level potency estimates for use in ecological risk-based prioritization.

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Evaluating the bioactivity of the ubiquitous tire preservative 6PPD and degradant, 6PPD-quinone

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