EDCs: negotiating the precautionary principle

Abstract

Few scientific issues are more complex or controversial than assessment of the effects of endocrine-disrupting chemicals (EDCs) on human wellbeing. Several scientific disciplines are involved—including toxicology, endocrinology, environmental science, paediatrics, obstetrics and gynaecology, and public health—each with different questions and priorities. Furore ensued earlier this year in response to a report from the Royal College of Obstetricians and Gynecologists (RCOG) stating that “the best approach for pregnant women is a ‘safety first’ approach, which is to assume there is risk present even when it may be minimal or eventually unfounded”: many thought that the report had taken the precautionary principle too far. As Dave Holmes reports in this issue of The Lancet Diabetes & Endocrinology, other groups have since stated what they believe should be the evidence threshold for tighter regulation. These statements are intended to stimulate changes in policies regulating EDCs, but lack of consensus means that decisions about when action should be taken are difficult to make. EDCs are natural or synthetic compounds found in consumer products and in the environment that modulate endocrine systems. An increasing number of reports have linked various EDCs with human disease—eg, a recent cross-sectional study based on National Health and Nutrition Examination Survey 2003–2010 data reported an association between childhood BMI and high urinary concentrations of the well-characterised EDC bisphenol A (BPA). However, unlike studies of wild animals—from which there is little doubt that EDCs cause harm—evidence that EDCs cause metabolic disease in human beings is far from solid. The conclusions of many epidemiological studies are contradictory. Many studies have not directly measured endocrine-active forms of EDCs and infer exposure from indirect assessments. Most cannot prove causation and few are generalisable. In view of the substantial differences in environments in different regions—because of differences in industry, society, electronic waste management, and population density—the amount and type of EDC exposure varies widely across the globe. Additionally, many low-income and middle-income countries with the greatest exposure to EDCs—and so with perhaps the greatest need for changes to EDC policy—have little data on which to base such changes. The biological complexities of EDCs also present major challenges for research. For example, native BPA (the endocrine-active form) is mildly lipophilic but, when ingested, is metabolised to a water-soluble form with modified endocrine activity and rapidly excreted. Thus, measurement of urinary BPA reflects recent intake but not necessarily systemic exposure. More generally, acknowledgment of the non-monotonic action of many EDCs is crucial to interpret associations with disease. Additionally, the effects of EDCs depend on developmental stage and tissue type, and outcomes attributed to one EDC might be caused by the combinatorial effects of several or an as-yet-unidentified EDCs. EDCs might also induce epigenetic effects that can be passed through generations. Finally, a biological effect in vitro, or even a pathological effect in an animal model, does not necessarily mean that a given EDC will be harmful to people. Designing a study that overcomes these challenges and provides the watertight evidence that some have argued is necessary for regulatory bodies to reassess or introduce policies on EDCs would be difficult, but this is not a reason for stasis. Consensus is needed about the type and strength of evidence that is required for policy change. As suggested in the RCOG paper, and also discussed by Martin van den Berg and Peter Sly in this issue, the precautionary principle should perhaps be most generous for fetuses and other populations at greatest potential risk. But with more than 800 EDCs identified to date, and the biological complexities inherent to each, regulation will be inescapably complex. It will also need to be balanced with potential implications for industries that rely on or make EDC-containing products. Removal of all EDCs from our environment will be impossible. Holmes highlights the huge scientific progress in understanding the effects of EDCs that has occurred in the past decade. In the next decade, this progress needs to continue to ensure that the acceptable threat of EDCs to human health is rigorously quantified and agreed on, a task that will require cooperation by all stakeholders. As we strengthen the evidence base, weighing the need to protect vulnerable populations against commercial interests will be a more attainable goal. Protecting the human fetus against effects of bisphenol AFew endocrine-disrupting compounds have generated as much debate during the past decade as bisphenol A (BPA). BPA was first synthesised in 1891, and was investigated for clinical use as a synthetic oestrogen in the 1930s. The first epoxy resins made with BPA went into commercial production in the 1950s and today resins and polycarbonates containing BPA are commonly used for coating food and beverage packages, leading to quantifiable human exposure via ingestion. Potential exposure of infants through baby bottles has been especially controversial, whereas less attention has been paid to prenatal exposure via maternal exposure. Full-Text PDF Endocrine disruptors cause toxic falloutA spat has erupted between endocrinologists and a group of toxicologists over how best to regulate endocrine-disrupting chemicals, as the European Commission prepares to release a new strategy on the issue. David Holmes reports. Full-Text PDF Molecular nutrition: the good, the bad, and the uncertainClinical endocrinology has changed substantially over the past few years, resulting in major advances in comprehensive patient care. Drivers of this process include the obesity and diabetes epidemics, changing economic and cultural landscapes, and novel biotechnologies, particularly in molecular medicine. As these factors and a renewed interest in nutrition conflate, a new discipline has emerged—molecular nutrition.1 Full-Text PDF