Comparative evaluation of subchronic toxicity of vehicle tire additive 6-PPD in Danio rerio and Xenopus laevis larvae


Güngördü A., Özhan Turhan D., Özmen N., Benli C. A., Özmen M.

59th Congress of the European Societies of Toxicology, Athens, Yunanistan, 14 - 17 Eylül 2025, cilt.411, ss.119-120, (Özet Bildiri)

  • Yayın Türü: Bildiri / Özet Bildiri
  • Cilt numarası: 411
  • Doi Numarası: 10.1016/j.toxlet.2025.07.303
  • Basıldığı Şehir: Athens
  • Basıldığı Ülke: Yunanistan
  • Sayfa Sayıları: ss.119-120
  • İnönü Üniversitesi Adresli: Evet

Özet

N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6-PPD) is an antioxidant component that has been used for many years to improve the durability and strength of vehicle tires. However, environmental toxicity of 6-PPD and its degradation byproduct, 6PPD-quinone, has become a matter of concern since it was reported to be an environmental contaminant that caused the mass mortality of coho salmon in 2021. Although the toxic effects of 6-PPD have been studied in many fish species, including Danio rerio, the information on its potential effects on amphibians is absent in the literature. In addition, most of the studies have focused on acute effects, and knowledge of the subchronic toxicity is still limited. For this purpose, 96-h median lethal concentration (LC50) of 6-PPD was determined in both zebrafish and Xenopus laevis using 17-day-old larvae to compare the response to 6-PPD toxicity. In addition, glutathione S-transferase (GST), glutathione reductase (GR) and acetylcholine esterase (AChE) activities were determined in larvae exposed to LC50/10, LC50/50 and LC50/100 concentrations of 6-PPD. The LC50s were calculated as 0.589 mg/L and 1.91 mg/L for larval D. rerio and larval X. laevis, respectively. During the 21-day exposure period, no mortality was observed in any exposure group of X. laevis larvae. In contrast, for D. rerio, pronounced toxic effects were observed in larvae for the LC50/10 concentration on day 10 of the experiment, and larvae exposed to the LC50/10 concentration on day 11 died in all containers. GST activity showed a concentration-dependent induction over the 7-day exposure period for both species, with enzyme induction ranging from 3-99% for X. laevis and 17-47% for D. rerio. In contrast, after 21 days of exposure, GST induction ranged from 10-87% in X. laevis, while no significant increase was observed in zebrafish compared to the control. Conversely, AChE activity showed no significant response to 6-PPD exposure in either species. GR activity was significantly induced in X. laevis larvae at the LC50/10 exposure for both 7 and 21 days. The results of the study indicate that D. rerio is more sensitive to 6-PPD toxicity during the larval developmental stages compared to X. laevis. This sensitivity was evident in both the LC50 concentrations and lethality levels observed after 21 days of exposure. The elevated levels of GST, a key detoxification enzyme, and GR, a key defense mechanism against oxidative stress, in X. laevis compared to D. rerio may also contribute to the observed higher tolerance in X. laevis larvae. On the other hand, it is thought that the substance is not effective on an acetylcholine-mediated stimulus in a possible neurotoxic effect due to 6-PPD toxicity.