Removing critical gaps in chemical test methods by developing new assays for the identification of thyroid hormone system-disrupting chemicals—the athena project

The test methods that currently exist for the identification of thyroid hormone system-disrupting chemicals are woefully inadequate. There are currently no internationally validated in vitro assays, and test methods that can capture the consequences of diminished or enhanced thyroid hormone action on the developing brain are missing entirely. These gaps put the public at risk and risk assessors in a difficult position. Decisions about the status of chemicals as thyroid hormone system disruptors currently are based on inadequate toxicity data. The ATHENA project (Assays for the identification of Thyroid Hormone axis-disrupting chemicals: Elaborating Novel Assessment strategies) has been conceived to address these gaps. The project will develop new test methods for the disruption of thyroid hormone transport across biological barriers such as the blood–brain and blood–placenta barriers. It will also devise methods for the disruption of the downstream effects on the brain. ATHENA will deliver a testing strategy based on those elements of the thyroid hormone system that, when disrupted, could have the greatest impact on diminished or enhanced thyroid hormone action and therefore should be targeted through effective testing. To further enhance the impact of the ATHENA test method developments, the project will develop concepts for better international collaboration and development in the area of thyroid hormone system disruptor identification and regulation

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. Objective methods are needed for integrating the multiple streams of evidence (epidemiology, wildlife, laboratory animal, in vitro, and in silico data) that are relevant in assessing EDCs. Methods - We have developed a framework for the systematic review and integrated assessment (SYRINA) of EDC studies. The framework was designed for use with the International Program on Chemical Safety (IPCS) and World Health Organization (WHO) definition of an EDC, which requires appraisal of evidence regarding 1) association between exposure and an adverse effect, 2) association between exposure and endocrine disrupting activity, and 3) a plausible link between the adverse effect and the endocrine disrupting activity. Results - Building from existing methodologies for evaluating and synthesizing evidence, the SYRINA framework includes seven steps: 1) Formulate the problem; 2) Develop the review protocol; 3) Identify relevant evidence; 4) Evaluate evidence from individual studies; 5) Summarize and evaluate each stream of evidence; 6) Integrate evidence across all streams; 7) Draw conclusions, make recommendations, and evaluate uncertainties. The proposed method is tailored to the IPCS/WHO definition of an EDC but offers flexibility for use in the context of other definitions of EDCs. Conclusions - When using the SYRINA framework, the overall objective is to provide the evidence base needed to support decision making, including any action to avoid/minimise potential adverse effects of exposures. This framework allows for the evaluation and synthesis of evidence from multiple evidence streams. Finally, a decision regarding regulatory action is not only dependent on the strength of evidence, but also the consequences of action/inaction, e.g. limited or weak evidence may be sufficient to justify action if consequences are serious or irreversible.The workshops that supported the writing of this manuscript were funded by the Swedish Foundation for Strategic Environmental Research “Mistra”. LNV was funded by Award Number K22ES025811 from the National Institute of Environmental Health Sciences of the National Institutes of Health. TJW was funded by The Clarence Heller Foundation (A123547), the Passport Foundation, the Forsythia Foundation, the National Institute of Environmental Health Sciences (grants ES018135 and ESO22841), and U.S. EPA STAR grants (RD83467801 and RD83543301). JT was funded by the Academy of Finland and Sigrid Juselius. UH was funded by the Danish EPA. KAK was funded by the Canada Research Chairs program grant number 950–230607

Temporal trends of phthalate exposures during 2007–2010 in Swedish pregnant women

Background: The general population is exposed to phthalates, a group of chemicals with strong evidence for endocrine disrupting properties, commonly used in a large number of consumer products. Based on published research and evidence compiled by environmental agencies, certain phthalate applications and products have become restricted, leading to an increasing number of “new generation compounds” coming onto the market during recent years replacing older phthalates. Some examples of such newer compounds are di-iso-nonyl phthalate (DiNP), di-iso-decyl phthalate (DiDP), and most recently di-isononyl-cyclohexane-1,2-dicarboxylate (DiNCH). Objectives: In order to evaluate temporal trends in phthalate exposure, first trimester urinary biomarkers of phthalates were measured in the Swedish SELMA study over a period of 2.5 years (2007–2010). Methods: We collected first morning void urine samples around week 10 of pregnancy from 1651 pregnant women. Spot samples were analyzed for 13 phthalate metabolites and one phthalate replacement and least square geometric mean (LSGM) levels of the metabolites were compared between the sampling years when adjusted for potential confounders. Results: All 14 metabolites were detectable in more than 99% of the SELMA subjects. The levels were generally comparable to other studies, but the SELMA subjects showed slightly higher exposure to butyl-benzyl phthalate (BBzP) and di-butyl phthalate (DBP). Di-ethyl-hexyl phthalate (DEHP) metabolites levels decreased while DiNP, DiDP/di-2-propylheptyl phthalate (DPHP), and DiNCH metabolites levels increased during the sampling period. Conclusions: Urinary metabolite levels of the older phthalates and more recently introduced phthalate replacement compound changed during the short sampling period in this Swedish pregnancy cohort. Our results indicate that replacement of phthalates can make an impact on human exposure to these chemicals. During this particularly vulnerable stage of life, phthalate exposures are of particular concern as the impacts, though not immediately noticeable, may increase the risk for health effects later in life

Eczema in early childhood is strongly associated with the development of asthma and rhinitis in a prospective cohort

<p>Abstract</p> <p>Background</p> <p>This study aimed to estimate the association between eczema in early childhood and the onset of asthma and rhinitis later in life in children.</p> <p>Methods</p> <p>A total of 3,124 children aged 1–2 years were included in the Dampness in Building and Health (DBH) study in the year 2000, and followed up 5 years later by a parental questionnaire based on an International Study of Asthma and Allergies in Childhood protocol. The association between eczema in early childhood and the incidence of asthma and rhinitis later in life was estimated by univariable and multivariable logistic regression modelling.</p> <p>Results</p> <p>The prevalence of eczema in children aged 1–2 years was 17.6% at baseline. Children with eczema had a 3-fold increased odds of developing asthma (adjusted odds ratio [aOR], 3.07; 95% confidence interval (CI) 1.79–5.27), and a nearly 3-fold increased odds of developing rhinitis (aOR, 2.63; 1.85–3.73) at follow-up compared with children without eczema, adjusted for age, sex, parental allergic disease, parental smoking, length of breastfeeding, site of living, polyvinylchloride flooring material, and concomitant allergic disease. When eczema was divided into subgroups, moderate to severe eczema (aOR, 3.56; 1.62–7.83 and aOR, 3.87; 2.37–6.33, respectively), early onset of eczema (aOR, 3.44; 1.94–6.09 and aOR, 4.05; 2.82–5.81; respectively), and persistence of eczema (aOR, 5.16; 2.62–10.18 and aOR, 4.00; 2.53–6.22, respectively) further increased the odds of developing asthma and rhinitis. Further independent risk factors increasing the odds of developing asthma were a parental history of allergic disease (aOR, 1.83; 1.29–2.60) and a period of breast feeding shorter than 6 months (aOR, 1.57; 1.03–2.39). The incidence of rhinitis was increased for parental history of allergic disease (aOR, 2.00; 1.59–2.51) and polyvinylchloride flooring (aOR, 1.60; 1.02–2.51).</p> <p>Conclusion</p> <p>Eczema in infancy is associated with development of asthma and rhinitis during the following 5-year period, and eczema is one of the strongest risk factors. Early identification is valuable for prediction of the atopic march.</p