Environmental estrogens interact with and modulate the properties of plasma sex steroid-binding proteins in juvenile Atlantic salmon (<i>Salmo salar</i>)

Environmental chemicals may modulate the endocrine system through interaction with plasma sex steroid-binding proteins (SBP) and SBP-regulated processes. Some of these chemicals, which are known to interact with the estrogen receptor (ER), were found to bind competitively to the Atlantic salmon (Salmo salar) SBP and potentially disrupt the endocrine function of these proteins. Furthermore, both weakly acting (di-n-butyl phthalate) and potent estrogen mimics (ethynylestradiol), were able to induce a substantial up-regulation of circulating levels of SBP in vivo. Interestingly, modulation of SBP-levels was found to be a more sensitive endpoint than chemically induced interference with classical ER-mediated mechanisms for weakly acting estrogen mimics like di-(n-butyl) phthalate. Interference with the endocrine function of SBPs may thus introduce a novel mechanism for endocrine disruption, and give additional answers to the question why some weakly acting xenoestrogens are causing "estrogen-like" reproductive disturbances in developing males

Screening of the estrogenic activity of environmental samples using transgenic cyp19a1b-GFP zebrafish embryos

Due to the potential environmental hazards on reproduction and population development in the aquatic ecosystem by estrogenic substances, their hazard assessment play a paramount role for regulation of chemicals, biocides, pesticides and pharmaceuticals in the EU and worldwide. Furthermore, they are also highly relevant for biomonitoring within the EU Water Framework Directive. For the assessment of their potential adverse effects on the environment, biological test systems play an essential role. The identification of endocrine disrupters with the chemical analysis is limited due to the low but still biologically relevant concentration in the surface waters. Besides, assessing the environmental hazard of mixtures of endocrine disrupters through classical monitoring is not only expensive but also not easily predictable. For this reason, effect-directed analysis using bioassays can be an excellent supplement of the classical monitoring of aquatic ecosystems. Transgenic models appear to be a powerful tool for high- throughput screening of changes in the gene expression induced by estrogenic chemicals. Using the zebrafishcyp19a1b-GFP transgenic embryo, which expresses GFP under the control of the zebrafish cyp19a1b promoter, adds the complexity of a full organism to the simplicity and reproducibility of cellular reporter gene assays. In this study we present the first results using this transgenic line for effect-directed analysis of a contaminated sediment sample. In this sample from the Czech river Bilina a previous analysis using the yeast screening assay has identified fractions containing estrogenic compounds. We were able to confirm this study by means of the transgeniccyp19a1b-GFP zebrafish strain. The results were also validated by artificial mixtures of compounds, which were identified by the effect-directed analysis, resembling the compositions of the fractions. Our study also includes data on the validation of the transgenic zebrafish strain with known estrogenic substances and its confirmation using molecular and an in-vitro method. The transgenic cyp19a1b-GFP in-vivo assay proved to be an excellent screening method with high sensitivity and reproducibility for environmental samples

Oppdatering av regional konsekvensutredning for petroleumsvirksomheten i Nordsjøen. Regulære utslipp til luft - konsekvenser.

Rapporten gir oppdaterte effekter av utslipp til luft av nitrogenoksider og PAH fra offshore industrien i Nordsjøen. Rapporten er en del av oppdateringen av den regionale konsekvensutredningen for Nordsjøen

A European perspective on alternatives to animal testing for environmental hazard identification and risk assessment

Tests with vertebrates are an integral part of environmental hazard identification and risk assessment of chemicals, plant protection products, pharmaceuticals, biocides, feed additives and effluents. These tests raise ethical and economic concerns and are considered as inappropriate for assessing all of the substances and effluents that require regulatory testing. Hence, there is a strong demand for replacement, reduction and refinement strategies and methods. However, until now alternative approaches have only rarely been used in regulatory settings. This review provides an overview on current regulations of chemicals and the requirements for animal tests in environmental hazard and risk assessment. It aims to highlight the potential areas for alternative approaches in environmental hazard identification and risk assessment. Perspectives and limitations of alternative approaches to animal tests using vertebrates in environmental toxicology, i.e. mainly fish and amphibians, are discussed. Free access to existing (proprietary) animal test data, availability of validated alternative methods and a practical implementation of conceptual approaches such as the Adverse Outcome Pathways and Integrated Testing Strategies were identified as major requirements towards the successful development and implementation of alternative approaches. Although this article focusses on European regulations, its considerations and conclusions are of global relevanc