Ecotoxicology and Human Environmental Health Multigenerational Disruption of Thyroid Endocrine System in Marine Medaka after A Life-Cycle Exposure to Perfluorobutane Sulfonate ( PFBS )

32 Accumulation of perfluorobutane sulfonate (PFBS) is frequently detected in biota, 33 raising concern about its ecological safety. However, hazardous effects of PFBS 34 remain largely unexplored, especially for endocrine disrupting potency. In the 35 present study, the multigenerational endocrine disrupting potential of PFBS was 36 investigated by exposing F0 marine medaka eggs to PFBS at different 37 concentrations (0, 1.0, 2.9 and 9.5 μg/L) until sexual maturity. The F1 and F2 38 generations were reared without continued exposure. Thyroidal disturbances were 39 examined in all three generations. PFBS exposure decreased the levels of 40 3,5,3’-triiodothyronine (T3) in F0 female blood, however, increased T3 or thyroxine 41 (T4) levels in F0 brains, which hyperthyroidism suppressed local transcription of 42 5'-deiodinase 2 (Dio2). Obviously decreased T3 was transferred to F1 eggs, although 43 the parental influences were reversed in F1 larvae. Delayed hatching was coupled 44 with elevated T3 levels in F1 larvae. F1 adult showed comparable symptoms of 45 thyroidal disruption with F0 adult. A slight recovery was noted in F2 generation, 46 although F2 larvae still exhibited thyroid disruption and synthesized excessive T4. 47 Our results suggested that the offspring suffered more severe dysfunction of 48 thyroidal axis albeit without direct exposure. This study provided the first molecular 49 insight about PFBS toxicology on thyroid, beneficial to human and environmental 50 risk assessment. 51 52 3 Page 3 of 34 ACS Paragon Plus Environment Environmental Science & Technology