Tributyltin and perfluorooctane sulfonate play a synergistic role in promoting excess fat accumulation in Japanese medaka (Oryzias latipes) via in ovo exposure

Chemosphere. 2019 Apr;220:687-695. doi: 10.1016/j.chemosphere.2018.12.191. Epub 2018 Dec 29.


The ubiquitous environmental obesogens tributyltin (TBT) and perfluorooctane sulfonate (PFOS) may accumulate in parent and be transferred to their offspring, resulting in trans-generational adverse effects. In this study, we investigated the combined toxic and obesogenic effects of TBT and PFOS on the early life stages of Japanese medaka (Oryzias latipes). In ovo nanoinjection was used to simulate the maternal transfer process. Doses were controlled at 0, 0.05, 0.5, and 2.5 ng/egg (TBT) and at 0, 0.05, 0.5, and 5.0 ng/egg (PFOS), with a full factorial design for mixture formulations. Relatively high doses of agents in mixtures were needed to induce significant mortality (TBT ≥ 0.5 ng/egg) or delayed hatching (PFOS = 5.0 ng/egg) of embryos. The interaction between TBT and PFOS in mixtures had significant effects on the observed hatching delay, but not on acute mortality. Compared with controls, separate exposure to TBT (or PFOS) notably elevated adipose areas at the doses of 0.05 and 0.5 ng/egg, but not at the highest doses. Combined exposure significantly promoted the fat accumulation in newly hatched larvae, even when the doses of TBT and PFOS were both at the levels that did not show obesogenic effect. The interactive effect of TBT and PFOS could aggravate the total obesogenic effect of their mixtures, indicating a synergistic interaction. These results highlight the importance of paying close attention to interaction effects when addressing the impacts of mixtures of environmental obesogens.

Keywords: Accelerated failure time (AFT) model; In ovo nanoinjection; Obesogenic effects; Piecewise regression; Synergistic effect.

MeSH terms

  • Adipose Tissue / drug effects*
  • Adipose Tissue / growth & development
  • Alkanesulfonic Acids / pharmacology*
  • Animals
  • Drug Synergism
  • Embryo, Nonmammalian / drug effects
  • Female
  • Fluorocarbons / pharmacology*
  • Larva / drug effects
  • Maternal Exposure / adverse effects
  • Obesity / chemically induced
  • Oryzias / embryology
  • Oryzias / metabolism*
  • Trialkyltin Compounds / pharmacology*


  • Alkanesulfonic Acids
  • Fluorocarbons
  • Trialkyltin Compounds
  • tributyltin
  • perfluorooctane sulfonic acid