Galaxolide and Irgacure 369 are novel environmental androgens

Abstract

Endocrine disruptors are environmental chemicals that can interfere with the endocrine system. However, research on endocrine disruptors that interfere with androgen's actions is still limited. The purpose of this study is to use in silico computation, i.e., molecular docking to facilitate the identification of environmental androgens. Computational docking was used to study the binding interactions of environmental/industrial compounds with the three dimensional structure of human androgen receptor (AR). Then reporter assay and cell proliferation assay using AR-expressing LNCaP prostate cancer cells were used to determine their in vitro androgenic activity. Animal studies using immature male rats were also carried out to test their in vivo androgenic activity. Two novel environmental androgens were identified. As a photoinitiator, 2-benzyl-2-(dimethylamino)-4′-morpholinobutyrophenone (Irgacure 369, abbreviated as IC-369) is widely used in the packaging and electronics industries. Galaxolide (HHCB) is widely used in the production of perfume, fabric softeners and detergents. We found that both IC-369 and HHCB could activate AR transcriptional activity and promote cell proliferation in AR-sensitive LNCaP cells. Furthermore, IC-369 and HHCB could induce cell proliferation and histological changes of seminal vesicles in immature rats. RNA sequencing and qPCR analysis showed that androgen-related genes in seminal vesicle tissue were up-regulated by IC-369 and HHCB. In conclusion, IC-369 and HHCB are new environmental androgens that bind AR and induce AR transcriptional activity, thereby exerting toxicological effects on the development of male reproductive organs.