Are all EDC effects mediated via steroid hormone receptors?

Despite the surge of interest in the endocrine disruption field, there is still no globally accepted definition of the term. There is a great political will to test chemicals to determine whether they have endocrine disrupting potential. This is a huge task and the US Environmental Protection Agency has taken the lead by setting up an Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC), which with international co-operation, will ultimately deliver a validated testing strategy to detect endocrine disrupting chemicals (EDCs) in humans and wildlife. One of the major developments will be the use of high throughput pre-screening (HTPS) methods that will detect binding to steroid receptor hormones, although many other testing methods will be employed. This paper describes two mechanisms of EDC action that are not mediated via steroid receptors; firstly, the suppression of fetal testosterone synthesis in rodents by in utero exposure to phthalates; and secondly, the ability of several chemicals to interfere with steroid metabolism by inhibiting estrogen sulfotransferases. These examples will be discussed with reference to pertinent human disorders, which have been associated with exposure to EDCs. Issues and questions about how scientists and regulators can deal with these types of chemicals or potential mechanisms in a risk assessment paradigm are raised.