Low-dose effects and biphasic effect profiles: is trenbolone a genotoxicant?

Over the last years, extensive research has documented endocrine-disrupting activities for a significant number of substances including, among others, hormones, pharmaceuticals, pesticides and surfactants. Nonetheless, for most endocrine disruptors, toxicological profiles are still incomplete or even lacking. A systematic review has shown that a number of endocrine disruptors with steroid-modulating effects may also exert mutagenic and carcinogenic activities. For trenbolone, an androgenic compound, there is controversy about its genotoxic properties in the literature, apparently with a strong dependence on the choice of the test system. Since fish and other aquatic animals are at risk of exposure to run-offs from cattle feedlots or sewage-discharge sites containing trenbolone, potential consequences to aquatic ecosystems need to be assessed. To this end, the potential genotoxic hazard of trenbolone was tested in vitro in the permanent rainbow trout-liver cell-line RTL-W1, as well as in primary cell cultures derived from zebrafish (Danio rerio) embryos after in vivo exposure. In either test system, a potential genotoxic hazard characterized by biphasic dose-response curves could be documented even at exposure concentrations of 30μg/L. These results thus confirm the conclusion that the steroid trenbolone may act as a genotoxic substance.