Endocrine Abstracts

Chemical contaminants from human activity are omnipresent in the environment. A great number of common industrial compounds are detected in human blood and urine. Common chemicals such as bisphenols, phthalates and parabens that can interfere with endocrine signaling are classified as endocrine disruptive compounds (EDCs). The sex steroid hormonal signaling pathway is complex and sensitive to interference, as circulating concentrations of these hormones are low. Even miniscule amounts of an active chemical could therefore result in endocrine disruption and cause adverse effects on development, brain function, and the reproductive- and immune systems. Industrial chemical production require risk assessments that balance societal benefits to potential negative effects on human- and environmental health. These risk assessments are based on observations in short term single-chemical exposure studies, which is not reflective of real-life scenarios where exposure to different chemicals and classes from many sources occurs simultaneously. Additive or synergistic effects are a concern, since the toxicity of different compounds in the biological system could interact and produce an unexpected and exaggerated toxicological response. The single compound approach therefore run the risk to potentially underestimate the biological impact of mixture effects. We have set up a small chemical library of environmental contaminants and employ liquid handling dispensing to reproduce real-world mixtures for screening of toxic effects. The endocrine disruptive potential of these mixtures is investigated by using OECD-validated in vitro cell-based methods that assess effects on steroidogenesis and androgen- and estrogen receptor interactions. Our aim is to establish medium or high throughput (MTS/HTS) micro plate-based screening methods for toxicological investigation of the complex chemical mixtures. This set-up will later be applied to investigate the effects of reconstructed individual exposomes based on chemical profiles detected by advanced mass spectrometry analysis of serum collected from a Swedish cohort. This will aid in the development of highly relevant risk assessments for chemical mixtures, in order to protect the general population from endocrine disruptive mixture toxicity.