| Category |
Text Publication |
| Reference Category |
Journals |
| DOI |
10.1093/toxsci/kfaf008
|
| Title (Primary) |
Bioactivity of the ubiquitous tire preservative 6PPD and degradant, 6PPD-quinone in fish- and mammalian-based assays |
| Author |
Jankowski, M.D.; Carpenter, A.F.; Harrill, J.A.; Harris, F.R.; Hill, B.; Labiosa, R.; Makarov, S.S.; Martinović-Weigelt, D.; Nyffeler, J.; Padilla, S.; Shafer, T.J.; Smeltz, M.G.; Villeneuve, D.L. |
| Source Titel |
Toxicological Sciences |
| Year |
2025 |
| Department |
ETOX |
| Volume |
204 |
| Issue |
2 |
| Page From |
198 |
| Page To |
217 |
| Language |
englisch |
| Topic |
T9 Healthy Planet |
| Keywords |
storm water contaminants; high-throughput screening; neurotoxicity; cell painting |
| 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 a likely causative agent of coho salmon (Oncorhynchus kisutch)
pre-spawn mortality. Stormwater runoff transports 6PPD-quinone into
freshwater streams, rapidly leading to neurobehavioral, respiratory
distress, and rapid mortality in laboratory-exposed coho salmon, but
causing no mortality in many laboratory-tested species. Given this
identified hazard, and potential for environmental exposure, we
evaluated a set of U.S. Environmental Protection Agency’s
high-throughput assays for their capability to detect the large potency
difference between 6PPD and 6PPD-quinone observed in coho salmon and
screen for bioactivities of concern. Assays included transcriptomics in
larval fathead minnow (FHM), developmental and behavioral toxicity in
larval zebrafish, phenotypic profiling in a rainbow trout gill cell
line, acute and developmental neurotoxicity in mammalian cells, and
reporter transcription factor activity in HepG2 cells. 6PPD was more
consistently bioactive across assays, with distinct activity in the
developmental neurotoxicity assay (mean 50th centile activity
concentration = 0.91 µM). Although 6PPD-quinone was less potent in FHM
and zebrafish, and displayed minimal neurotoxic activity in mammalian
cells, it was highly potent in altering organelle morphology in
RTgill-W1 cells (phenotype-altering concentration = 0.024 µM compared
with 0.96 µM for 6PPD). Although in vitro sensitivity of RTgill-W1 cells
may not be as sensitive as intact Coho salmon, the assay may be a
promising approach to test chemicals for 6PPD-quinone-like activities.
The other assays each identified unique bioactivities of 6PPD, with
neurobehavioral and developmental neurotoxicity being most affected,
indicating a need for further assessment of this chemical.
Our
results demonstrate that the common tire additive, 6PPD, is bioactive
in a broader set of assays than the environmental transformation product
6PPD-quinone and that it may be a developmental neurotoxicant in
mammals, whereas 6PPD-quinone was much more potent than 6PPD in altering
the intracellular phenotype of rainbow trout gill cells. Application of
the set of high-throughput and high-content bioassays to test the
bioactivity of this emerging pollutant has provided data to inform both
ecological and human health assessments.
|
| Persistent UFZ Identifier |
https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=30515 |
Jankowski, M.D., Carpenter, A.F., Harrill, J.A., Harris, F.R., Hill, B., Labiosa, R., Makarov, S.S., Martinović-Weigelt, D., Nyffeler, J., Padilla, S., Shafer, T.J., Smeltz, M.G., Villeneuve, D.L. (2025):
Bioactivity of the ubiquitous tire preservative 6PPD and degradant, 6PPD-quinone in fish- and mammalian-based assays
Toxicol. Sci. 204 (2), 198 - 217 10.1093/toxsci/kfaf008 |
