Abstract
Ill-defined, multi-component mixtures of steroidal pharmaceuticals are present in the aquatic environment. Fish are extremely sensitive to some of these steroids. It is important to know how fish respond to these mixtures, and from that knowledge develop methodology that enables accurate prediction of those responses. To provide some of the data required to reach this objective, pairs of fish were first exposed to five different synthetic steroidal pharmaceuticals (one estrogen, EE2; one androgen, trenbolone; one glucocorticoid, beclomethasone dipropionate; and two progestogens, desogestrel and levonorgestrel) and concentration-response data on egg production obtained. Based on those concentration-response relationships, a five component mixture was designed and tested twice. Very similar effects were observed in the two experiments. The mixture inhibited egg production in an additive manner predicted better by the model of Independent Action than that of Concentration Addition. Our data provide a reference case for independent action in an in vivo model. A significant combined effect was observed when each steroidal pharmaceutical in the mixture was present at a concentration which on its own would produce no statistically significant effect (something from ‘nothing’). Further, when each component was present in the mixture at a concentration expected to inhibit egg production by between 18% (Beclomethasone diproprionate) and 40% (trenbolone), this mixture almost completely inhibited egg production: a phenomenon we term ‘a lot from a little’. The results from this proof-of-principle study suggest that multiple steroids present in the aquatic environment can be analysed for their potential combined environmental risk.
Highlights
A very high number of anthropogenic chemicals are present in the environment across the entire world
Data from previous studies of EE2 and Levonorgestrel on egg production have already been demonstrated to be suitable for mixture studies (Runnalls et al, 2015), and the remaining three chemicals, namely trenbolone, beclomethasone dipropionate and desogestrel, all inhibited egg production in a clear concentration-dependant manner, which allowed the estimation of concentration-response regression curves (Fig. 2)
We have shown that a mixture of five steroidal pharmaceuticals considered to have distinctly different modes of action (MoA)'s can inhibit egg production of fish in a manner accurately predicted by the additivity model IA
Summary
A very high number of anthropogenic chemicals are present in the environment across the entire world. If any, of these chemicals were present a century or more ago; some, such as nanomaterials, have appeared in the environment very recently. Any specific environment will probably contain a unique range and concentrations of chemicals. It is clear that probably all living organisms on earth are presently exposed to highly complex, ill-defined mixtures of anthropogenic chemicals, as well as many natural chemicals that have probably been present in the environment for a very long time. If we are to understand the effects of anthropogenic chemicals on wildlife, we need to know if these complex mixtures of chemicals have any effects, and if they do, what these effects are, and how adverse (or not) they are. If we can adequately answer that question can we put exposure to chemicals as a stressor into context with the many other stressors wildlife face (e.g. habitat loss, introduced diseases, alien species), and use that knowledge wisely to focus our attention on the greatest threat(s) (Sumpter, 2009; Johnson and Sumpter, 2014)
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