A path forward in the debate over health impacts of endocrine disrupting chemicals

Several recent publications reflect debate on the issue of “endocrine disrupting chemicals” (EDCs), indicating that two seemingly mutually exclusive perspectives are being articulated separately and independently. Considering this, a group of scientists with expertise in basic science, medicine and risk assessment reviewed the various aspects of the debate to identify the most significant areas of dispute and to propose a path forward. We identified four areas of debate. The first is about the definitions for terms such as “endocrine disrupting chemical”, “adverse effects”, and “endocrine system”. The second is focused on elements of hormone action including “potency”, “endpoints”, “timing”, “dose” and “thresholds”. The third addresses the information needed to establish sufficient evidence of harm. Finally, the fourth focuses on the need to develop and the characteristics of transparent, systematic methods to review the EDC literature. Herein we identify areas of general consensus and propose resolutions for these four areas that would allow the field to move beyond the current and, in our opinion, ineffective debate

An Effective Assessment of Simvastatin-Induced Toxicity with NMR-Based Metabonomics Approach

BACKGROUND: Simvastatin, which is used to control elevated cholesterol levels, is one of the most widely prescribed drugs. However, a daily excessive dose can induce drug-toxicity, especially in muscle and liver. Current markers for toxicity reflect mostly the late stages of tissue damage; thus, more efficient methods of toxicity evaluation are desired. METHODOLOGY/PRINCIPAL FINDINGS: As a new way to evaluate toxicity, we performed NMR-based metabonomics analysis of urine samples. Compared to conventional markers, such as AST, ALT, and CK, the urine metabolic profile provided clearer distinction between the pre- and post-treatment groups treated with toxic levels of simvastatin. Through multivariate statistical analysis, we identified marker metabolites associated with the toxicity. Importantly, we observed that the treatment group could be further categorized into two subgroups based on the NMR profiles: weak toxicity (WT) and high toxicity (HT). The distinction between these two groups was confirmed by the enzyme values and histopathological exams. Time-dependent studies showed that the toxicity at 10 days could be reliably predicted from the metabolic profiles at 6 days. CONCLUSIONS/SIGNIFICANCE: This metabonomics approach may provide a non-invasive and effective way to evaluate the simvastatin-induced toxicity in a manner that can complement current measures. The approach is expected to find broader application in other drug-induced toxicity assessments

Scientifically unfounded precaution drives European Commission's recommendations on EDC regulation, while defying common sense, well-established science and risk assessment principles

We, the undersigned editors of prominent journals of pharmacology and toxicology, are drawing your attention to the imminent decisions by the European Commission to enforce a regulatory framework for so-called endocrine disrupting chemicals (EDCs). The currently drafted framework is based on virtually complete ignorance of all well-established and taught principles of pharmacology and toxicology, of opinions raised by the European Commission’s own competent expert authority (European Food Safety Authority (EFSA, 2013)), and of critical statements made by member countries, while avoiding asking for support from the European Commission’s own scientific expert committees