Weight of evidence evaluation of the metabolism disrupting effects of triphenyl phosphate using an expert knowledge elicitation approach.

Identification of Endocrine-Disrupting Chemicals (EDCs) in a regulatory context requires a high level of evidence. However, lines of evidence (e.g.

Incorporation of Fast-Elimination Chemicals in Hair Is Governed by Pharmacokinetics-Implications for Exposure Assessment.

Mechanisms governing chemicals' incorporation in hair are incompletely understood, and gaps remain to link the concentration of chemicals in hair to level of exposure and internal dose present in the body. This study assesses the relevance of hair analysis for the biomonitoring of exposure to fast-elimination compounds and investigates the role of pharmacokinetics (PK) in their incorporation in hair. Rats were administered with pesticides, bisphenols, phthalates, and DINCH over 2 months.

Human Biomonitoring Guidance Values (HBM-GVs) for Bisphenol S and Assessment of the Risk Due to the Exposure to Bisphenols A and S, in Europe.

Within the European Joint Programme HBM4EU, Human Biomonitoring Guidance Values (HBM-GVs) were derived for several prioritised substances. In this paper, the derivation of HBM-GVs for the general population (HBM-GV) and workers (HBM-GV) referring to bisphenol S (BPS) is presented. For the general population, this resulted in an estimation of the total urinary concentration of BPS of 1.

Application of evidence-based methods to construct mechanism-driven chemical assessment frameworks.

The workshop titled “Application of evidence-based methods to construct mechanism-driven chemical assessment frameworks” was co-organized by the Evidence-based Toxicology Collaboration and the European Food Safety Authority (EFSA) and hosted by EFSA at its headquarters in Parma, Italy on October 2 and 3, 2019. The goal was to explore integration of systematic review with mechanistic evidence evaluation. Participants were invited to work on concrete products to advance the exploration of how evidence-based approaches can support the development and application of adverse outcome pathways (AOP) in chemical risk assessment.

Regulatory and academic studies to derive reference values for human health: The case of bisphenol S.

The close structural analogy of bisphenol (BP) S with BPA, a recognized endocrine-disrupting chemical and a substance of very high concern in the European Union, highlights the need to assess the extent of similarities between the two compounds and carefully scrutinize BPS potential toxicity for human health. This analysis aimed to investigate human health toxicity data regarding BPS, to find a point of departure for the derivation of human guidance values. A systematic and transparent methodology was applied to determine whether European or international reference values have been established for BPS.

Biomonitoring of fast-elimination endocrine disruptors - Results from a 6-month follow up on human volunteers with repeated urine and hair collection.

Background: The assessment of human exposure to fast-elimination endocrine disruptors (ED) such as phthalates, bisphenols or pesticides is usually based on urinary biomarkers. The variability of biomarkers concentration, due to rapid elimination from the body combined with frequent exposure is however pointed out as a major limitation to exposure assessment. Other matrices such as hair, less sensitive to short-term variations in the exposure, have been proposed as possible alternatives.

Recommendations for the conduct of systematic reviews in toxicology and environmental health research (COSTER).

Background: There are several standards that offer explicit guidance on good practice in systematic reviews (SRs) for the medical sciences; however, no similarly comprehensive set of recommendations has been published for SRs that focus on human health risks posed by exposure to environmental challenges, chemical or otherwise.

Objectives: To develop an expert, cross-sector consensus view on a key set of recommended practices for the planning and conduct of SRs in the environmental health sciences.

Methods: A draft set of recommendations was derived from two existing standards for SRs in biomedicine and developed in a consensus process, which engaged international participation from government, industry, non-government organisations, and academia.

The GOLIATH Project: Towards an Internationally Harmonised Approach for Testing Metabolism Disrupting Compounds.

The purpose of this project report is to introduce the European "GOLIATH" project, a new research project which addresses one of the most urgent regulatory needs in the testing of endocrine-disrupting chemicals (EDCs), namely the lack of methods for testing EDCs that disrupt metabolism and metabolic functions. These chemicals collectively referred to as "metabolism disrupting compounds" (MDCs) are natural and anthropogenic chemicals that can promote metabolic changes that can ultimately result in obesity, diabetes, and/or fatty liver in humans. This project report introduces the main approaches of the project and provides a focused review of the evidence of metabolic disruption for selected EDCs.

Evidence for Bisphenol B Endocrine Properties: Scientific and Regulatory Perspectives.

Background: The substitution of bisphenol A (BPA) by bisphenol B (BPB), a very close structural analog, stresses the need to assess its potential endocrine properties.

Objective: This analysis aimed to investigate whether BPB has endocrine disruptive properties in humans and in wildlife as defined by the World Health Organization (WHO) definition used in the regulatory field, that is, ) adverse effects, ) endocrine activity, and ) plausible mechanistic links between the observed endocrine activity and adverse effects.

Methods: We conducted a systematic review to identify BPB adverse effects and endocrine activities by focusing on animal models and mechanistic studies.

Alteration of mammary gland development by bisphenol a and evidence of a mode of action mediated through endocrine disruption.

The development and function of the mammary gland are endocrine-dependent processes, depending on the stage of development. Foetal and/or postnatal exposure to low doses of BPA alters tissue organisation through epithelial proliferation and stroma-epithelial interactions. BPA also alters the expression of E2-dependent epithelial and stroma transcriptomes.

Effects of bisphenol A on metabolism and evidences of a mode of action mediated through endocrine disruption.

Based on rodent studies after prenatal and/or perinatal or adult exposure, there is now evidence that BPA may increase metabolic disturbances eventually leading to type-2 diabetes development via an ED MoA. In particular, BPA has been shown to alter insulin synthesis and/or release by pancreatic β-cells, and insulin signaling within insulin-sensitive organs (i.e.

Concerns related to ED-mediated effects of Bisphenol A and their regulatory consideration.

The extensive database on BPA provides strong evidence of its adverse effects on reproductive, neurobehavioural, metabolic functions and mammary gland. Disruption of estrogenic pathway is central in the mediation of these effects although other modes of action may be involved. BPA has a weak affinity for ERα/β but interaction with extranuclearly located pathways activated by estrogens such as ERRγ and GPER reveals how BPA can act at low doses.

Regulatory identification of BPA as an endocrine disruptor: Context and methodology.

BPA is one of the most investigated substances for its endocrine disruptor (ED) properties and it is at the same time in the center of many ED-related controversies. The analysis on how BPA fits to the regulatory identification as an ED is a challenge in terms of methodology. It is also a great opportunity to test the regulatory framework with a uniquely data-rich substance and learn valuable lessons for future cases.

Migration limits for children's toys are nothing to play with.

The European Commission and its independent Scientific Committee on Health and Environmental Risks (SCHER) published their final Opinion on estimates of the amount of toy materials ingested by children. The SCHER was asked to review available data on the ingestion of the following three types of toy material by children, and evaluate whether the ingestion amounts which formed the basis for the migration limits of 19 elements in the Toy Safety Directive are still appropriate or whether they should be changed. In the final Opinion the SCHER considers the ingestion amounts mentioned above to be appropriate, and that these ingestion amounts should remain classified as daily amounts rather than weekly.

A proposed framework for the systematic review and integrated assessment (SYRINA) of endocrine disrupting chemicals.

Background: The issue of endocrine disrupting chemicals (EDCs) is receiving wide attention from both the scientific and regulatory communities. Recent analyses of the EDC literature have been criticized for failing to use transparent and objective approaches to draw conclusions about the strength of evidence linking EDC exposures to adverse health or environmental outcomes. Systematic review methodologies are ideal for addressing this issue as they provide transparent and consistent approaches to study selection and evaluation.

Non-monotonic dose-response relationships and endocrine disruptors: a qualitative method of assessment.

Experimental studies investigating the effects of endocrine disruptors frequently identify potential unconventional dose-response relationships called non-monotonic dose-response (NMDR) relationships. Standardized approaches for investigating NMDR relationships in a risk assessment context are missing. The aim of this work was to develop criteria for assessing the strength of NMDR relationships.

Low dose effects and non-monotonic dose responses for endocrine active chemicals: science to practice workshop: workshop summary.

A workshop was held in Berlin September 12-14th 2012 to assess the state of the science of the data supporting low dose effects and non-monotonic dose responses ("low dose hypothesis") for chemicals with endocrine activity (endocrine disrupting chemicals or EDCs). This workshop consisted of lectures to present the current state of the science of EDC action and also the risk assessment process. These lectures were followed by breakout sessions to integrate scientists from various backgrounds to discuss in an open and unbiased manner the data supporting the "low dose hypothesis".