Endocrine disruptor screening: regulatory perspectives and needs

Abstract

National and international governments are in the process of establishing testing programs and strategies to assess the safety of currently used chemicals with regard to their potential to interact with the endocrine system of man and wildlife, resulting in potential impacts on reproduction, growth, and/or development. Specifically, the USA, Japan, EU, and OECD have established testing approaches and regulatory frameworks with aim to assess the risks associated with chemicals that have endocrine disrupting properties (EDCs). While there has been a large amount of efforts over the past two decades in context with the assessment of chemical safety, no comparable attempts to harmonize and mutually accept testing strategies and decision-making criteria for environmental monitoring and assessment exist to date for EDCs. In fact, many of the current environmental programs such as the European Water Framework Directive (WFD) or the US Clean Water Act do not explicitly test for EDCs, and considering the unique requirements and endpoints required to assess the endocrine potential of a sample, these programs are unlikely to appropriately address exposure to these chemicals. This is of great concern since EDCs are ubiquitous in the environment, especially in aquatic ecosystems. One of most important sources for EDCs in the environment is the effluent from sewage treatment plants. Many EDCs such as the natural and synthetic estrogens 17β-estradiol and 17α-ethinylestradiol, respectively, are not completely removed with conventional wastewater treatment systems. In recognition of these concerns, in Europe, there is increasing pressure to further develop advanced wastewater treatment methods, such as ozonation and activated carbon treatment for a broad application in municipal wastewater treatment. Another issue is the continuing lack of understanding of the environmental relevance of the phenomenon of ED. A great number of studies have been conducted to describe potential ED in wild and laboratory animals. Most of these studies relied on biomarkers of estrogenicity such as vitellogenin induction in males and mild histological alterations (e.g. occurrence of testicular oocytes), and to date - with few exceptions - no convincing evidence of population relevant impacts of exposure to EDC in the wild exist. In conclusion, while there has been a great deal of research and efforts in context with the hazard assessment and regulation of EDCs, there is still a large number of remaining uncertainties and issues. These range from animal rights concerns due to significant increases in the use of animals to fulfill testing requirements, associated needs for alternative testing concepts such as in vitro, in silico, and modeling approaches, lack of understanding of the relevance of the exposure of man and wildlife to EDCs, and the need for inclusion of EDCs in current environmental programs such as the WFD. In this article we attempted to summarize the current state-of-the-art of regulatory and scientific approaches in context with EDCs, and to identify issues and future needs to address current shortcomings in the field.