Fish Sexual Development Test (FSDT) (OECD TG 234)

406. Modality detected/endpoints: estrogens (♀ and ♂ VTG ↑; phenotypic sex ratio ♀↑); anti-estrogens (♀ VTG ↓; phenotypic sex ratio ♂↑; sexually undifferentiated fish ↑); androgens (phenotypic sex ratio ♂↑; ♀ VTG ↓); anti-androgens (intersex fish ↑; ♀ VTG ↑; phenotypic sex ratio ♀↑); aromatase inhibitors (♀ VTG ↓; phenotypic sex ratio ♂↑); (optional endpoints – gonadal histopathology; genetic sex in medaka and stickleback). OECD TG 234 (FSDT) has been fully validated for Japanese medaka, zebrafish and stickleback. The test may also be responsive to certain thyroid-disrupting chemicals. It is known that thyroid hormone receptors TRα and TRβ are both present in fish early embryos and larvae (Power et al., 2001), and that maternally derived thyroxine (T4) is important for thyroiddependent processes in fish early life stages (Nelson et al., 2014). One of these processes is swimbladder inflation, an endpoint which could be recorded in the FSDT test, and which is vital for the survival of fish fry. It has been shown, for example, that fathead minnow embryos exposed to a thyroid peroxidase (TPO) inhibitor (2-mercaptobenzothiazole) do not develop inflated swimbladders, probably because inhibition of TPO leads to decreased thyroid hormone synthesis (Villeneuve et al., 2013; Nelson et al., 2014). Also, Liu and Chan (2002) have shown that metamorphosis from embryo to larva in zebrafish is arrested by exposure to amiodarone (a TR antagonist) and by the goitrogen methimazole. Furthermore, Shi et al. (2008) demonstrated that the thyroid disrupter perfluorooctanesulfonic acid (PFOS) is able to delay hatching and cause developmental malformations in zebrafish embryos while upregulating two thyroid-related developmental genes, hhex and pax8. However, it is important to note that many non-ED chemicals will also cause these types of apical response, but by different mechanisms.