Suchergebnisse

The concept that developmental events shape adult health and disease was sparked by the recognition of a link between maternal undernutrition and coronary disease in adults. From that beginning, a new field—the developmental origins of health and disease—emerged, and attention has focused on the effects of a wide array of developmental perturbations. Exposure to endocrine-disrupting chemicals has been of particular interest, and a ubiquitous environmental contaminant bisphenol A (BPA) has become the endocrine-disrupting chemical poster child. Bisphenol A has been the subject of intense investigation for nearly two decades, and exposure effects have been described in hundreds of experimental, epidemiological, and clinical studies. From the standpoint of reproductive health, the findings are particularly important, as they suggest that the ovary, testis, and reproductive tract in both sexes are targets of BPA action. The findings and the media and regulatory attention garnered by them have generated increasing public concern and resulted in legislative bans on BPA in some countries. The subsequent introduction of BPA-free products, although a masterful marketing strategy, is in reality only the beginning of a new and complex chapter of the BPA story. In this review we attempt to summarize what we have learned about the reproductive effects of BPA, present the reasons why studying the effects of this chemical in humans is no longer sufficient, and outline the challenges that the growing array of next generation bisphenols represents to clinicians, researchers, federal agencies, and the general public.

This issue of Toxicological Sciences features several exciting changes: a redesigned cover, revised category subheadings, and this "Look Inside ToxSci" feature. Together with my esteemed colleagues in the field of green chemistry, we have outlined some exciting opportunities for the field of toxicology in the editorial on green chemistry and toxicology. There are insightful articles on the regulatory challenges regarding mixtures that are being addressed by the European Union and on risk assessment of carbon nanotubes. In the past, we have highlighted a single article from each issue. It has become increasingly difficult to select just one article from the volume of high quality work, so beginning this month we will highlight multiple articles in each issue here in "Look Inside ToxSci." From solvents, pesticides, and nanoparticles to the microbiome, the highlighted articles span the breadth of our field. Of course, this issue contains something that will never change; our raison d'etre …the best original research in the field of toxicology. -Gary W. Miller.

This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI. ; BACKGROUND In their safety evaluations of bisphenol A (BPA), the U.S. Food and Drug Administration (FDA) and a counterpart in Europe, the European Food Safety Authority (EFSA), have given special prominence to two industry-funded studies that adhered to standards defined by Good Laboratory Practices (GLP). These same agencies have given much less weight in risk assessments to a large number of independently replicated non-GLP studies conducted with government funding by the leading experts in various fields of science from around the world. OBJECTIVES We reviewed differences between industry-funded GLP studies of BPA conducted by commercial laboratories for regulatory purposes and non-GLP studies conducted in academic and government laboratories to identify hazards and molecular mechanisms mediating adverse effects. We examined the methods and results in the GLP studies that were pivotal in the draft decision of the U.S. FDA declaring BPA safe in relation to findings from studies that were competitive for U.S. National Institutes of Health (NIH) funding, peer-reviewed for publication in leading journals, subject to independent replication, but rejected by the U.S. FDA for regulatory purposes. DISCUSSION Although the U.S. FDA and EFSA have deemed two industry-funded GLP studies of BPA to be superior to hundreds of studies funded by the U.S. NIH and NIH counterparts in other countries, the GLP studies on which the agencies based their decisions have serious conceptual and methodologic flaws. In addition, the U.S. FDA and EFSA have mistakenly assumed that GLP yields valid and reliable scientific findings (i.e., "good science"). Their rationale for favoring GLP studies over hundreds of publically funded studies ignores the central factor in determining the reliability and validity of scientific findings, namely, independent replication, and use of the most appropriate and sensitive state-of-the-art assays, neither of which is an expectation of industry-funded GLP research. CONCLUSIONS Public health decisions should be based on studies using appropriate protocols with appropriate controls and the most sensitive assays, not GLP. Relevant NIH-funded research using state-of-the-art techniques should play a prominent role in safety evaluations of chemicals.