Assessing the risk of exposures to endocrine disrupting chemicals

The risk assessment process has been guided by principles of toxicology since it was developed some 50 years ago. These principles posit that toxicity decreases with decreasing doses. Thus, toxicity studies typically test chemicals starting at high doses and proceeding to progressively lower doses aiming to identify a dose at which no adverse effects are observed and extrapolating to predicted safe doses using additional factors to account for uncertainties in the accuracy of the animal model and test conditions. Thus the predicted safe dose is calculated but not tested. Over the last twenty years or so scientists have developed data showing that certain chemicals that disrupt endocrine signaling, e.g. endocrine disrupting Chemicals (EDCs), can act at low doses (in the range of low level environmentally relevant human exposures) in animal studies, and may show dose responses where the slope of the response changes direction i.e. non-monotonic dose responses (NMDR). If this scenario is true, the assumption that lower levels are safer may not be always correct.JRC.I.5-Systems Toxicolog

Statistical Approaches for Assessing Health Effects of Environmental Chemical Mixtures in Epidemiology: Lessons from an Innovative Workshop

Summary: Quantifying the impact of exposure to environmental chemical mixtures is important for identifying risk factors for diseases and developing more targeted public health interventions. The National Institute of Environmental Health Sciences (NIEHS) held a workshop in July 2015 to address the need to develop novel statistical approaches for multi-pollutant epidemiology studies. The primary objective of the workshop was to identify and compare different statistical approaches and methods for analyzing complex chemical mixtures data in both simulated and real-world data sets. At the workshop, participants compared approaches and results and speculated as to why they may have differed. Several themes emerged: a) no one statistical approach appeared to outperform the others, b) many methods included some form of variable reduction or summation of the data before statistical analysis, c) the statistical approach should be selected based upon a specific hypothesis or scientific question, and d) related mixtures data should be shared among researchers to more comprehensively and accurately address methodological questions and statistical approaches. Future efforts should continue to design and optimize statistical approaches to address questions about chemical mixtures in epidemiological studies

The Assessment of Repeated Dose Toxicity In Vitro: a Proposed Approach. The Report and Recommendations of ECVAM Workshop 56

This is the 56th report of a series of workshops organised by the European Centre for the Validation of Alternative Methods (ECVAM). The main goal of ECVAM, as defined in 1993 by its Scientific Advisory Committee, is to promote the scientific and regulatory acceptance of alternative methods which have scientific relevance and which reduce, refine or replace the use of laboratory animals. One of the first priorities set by ECVAM was the implementation of procedures that would enable it to become well informed about the stateof- the-art of non-animal test development and validation, and the potential for the possible incorporation of alternative tests into regulatory procedures. It was decided that this would be best achieved by the organisation of ECVAM workshops on specific topics, at which focused groups of invited experts would review the current status of non animal- based tests and their potential uses, and make recommendations about the best ways forward (1). The ECVAM workshop on repeated dose toxicity in vitro was held on 15–17 September 2004, at ECVAM in Ispra, Italy. The workshop was chaired by Walter Pfaller and Pilar Prieto, and was attended by pharmacologists and toxicologists from academia, industry and government, from different research backgrounds and with different ways of thinking. The main goal was to discuss and evaluate alternative approaches to in vivo repeated dose toxicity testing.JRC.I.2-Validation of biomedical testing method