An evidence-based appraisal of the role of the fish sex ratio as an endpoint in environmental risk assessment.

Since the issue of endocrine disruption came to light in the 1980s, a diverse array of chemicals has been shown to have the potential to modify vertebrate endocrine regulation and alter normal reproductive development and function. To date, there have been few documented cases of adverse effects on heath or the environment resulting from exposure to endocrine disruptors. However, knowledge that many products in daily use contain substances with endocrine disrupting properties and that some endocrine disruptors are prevalent environmental contaminants has prompted extensive coverage of endocrine disruption in the media. This has resulted in increasing pressure to develop legislations controlling the manufacture, use and release of chemicals with potential endocrine disrupting effects. As a consequence dossiers concerning potential endocrine disrupting effects are currently being assessed under REACH; a number of substances have already been removed from the market under the Plant Protection Regulation on grounds of possible effects on the endocrine system (Cefic, 2012).

The European Commission Endocrine Disruptors Expert Advisory Group recently published a report (2013) suggesting that both mode of action and adversity should be demonstrated for endocrine disruption to have occurred; adversity constitutes an endpoint that should have the potential to impact at the population level. Among the test guidelines recently adopted by OECD, within their Conceptual Framework for testing and assessment of potential endocrine disruptors, only the Fish Sexual Development Test (FSDT) has been identified as providing information on both mode of action and adverse effects relevant to endocrine disruption. This places a high scientific value on the FSDT and the use of sex ratio as a measure of adverse effects. There are, however, concerns associated with the use of sex ratio as an end-point. These relate to the underlying plasticity of sex determination in fish, which can be altered by environmental temperature in early life (Sfakianakis et al, 2012), by inbreeding (Brown et al., 2012) and by population density (Spence and Smith, 2005). Further, for at least one of the guideline OECD species (Zebrafish) the process of sexual determination is not understood (Anderson et al., 2012). Concerns have also been raised that where significant changes in sex ratio following exposure to an endocrine disruptor are observed, the quantal nature of the measurements may call the statistical analysis into question. Moreover, there is little evidence that a minor, if significant, change in the sex ratio of a population will have long-term detriment on the capacity of that population to remain stable; this may only be the case if the sex of one gender is completely reversed but, even then, there is some evidence that sex changes are reversible.

The aim of this Fellowship is to conduct an evidence-based appraisal to assess whether basing a judgement of adversity on sex-ratio in fish is a safe path to risk assessment. Given that the placement of the FSDT within the OECD conceptual framework will drive its application for this use in environmental protection there is an urgent need for such an appraisal. Through exchange of practical and theoretical expertise a guidance document will be developed that highlights any weakness in the conceptual framework for endocrine effects in ecotoxicology, identifies gaps in our current understanding and suggests routes to better addressing the interpretation of sex ratio in fish based assessments. This will provide an important step towards improving the uptake of the endocrine disruption testing strategy framework at the Food and Environment Research Agency (FERA) and assist FERA in advising government and regulators on the further use and implementation of adopted OECD tests.