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The NSAID in vitro assay developed as a tool for environmental monitoring of pharmaceutical effects was validated for its suitability to detect COX inhibitor activity in surface water. A standard operation procedure based on solid phase extraction of aqueous samples was established by modifying a sampling protocol for the detection of estrogens with the aim to stabilize NSAIDs in the samples. In addition, the sensitivity of the NSAID in vitro assay was improved by minimizing matrix effects and improving the stability of the substrate arachidonic acid. The validation characteristics linearity, measurement range, accuracy, precision and limit of detection were evaluated. The test procedure was used for measuring 39 surface water samples taken at EU Watch List sampling sites in 14 EU member states and 4 Swiss cantons between autumn 2017 to spring 2018. Diclofenac equivalents measured by the NSAID in vitro assay were compared with data obtained by chemical analysis (LC-MS/MS) of diclofenac and other COX-inhibitors.

AbstractHuman pharmaceuticals are extensively studied and assessed before marketing approval. Since 2006, this also includes an assessment of environmental risks. In the European Union, this is based on the guideline on the environmental risk assessment of medicinal products for human use (EMEA/CHMP/SWP/4447/00 corr 2), which is currently under revision. For Germany, the German Environment Agency (UBA) is tasked with the evaluation of environmental risks of human pharmaceuticals. Applicants seeking approval of medicinal products need to submit fate and effect data, in case predicted environmental concentrations (PECs) exceed 10 ng/L in surface waters, or the substance is of specific concern through its mode of action or physico-chemical characteristics.Over the last decade, this regulatory work resulted in an internal agency database containing effect data on approximately 300 active pharmaceutical ingredients (APIs). A considerable part of this data is currently not publicly available due to property rights held by the respective applicants. The database was evaluated to draw conclusions on how the current assessment approach may be improved.The evaluation of aquatic effect data shows considerable variation in ecotoxic effect concentrations, but supports the current use of 10 ng/L as PEC action limit. For endocrine-active substances and antibiotics, a clear sensitivity profile was observed, which allows a more targeted assessment in the future. The conclusions drawn from terrestrial effect data are less clear, as the database itself is biased because information is only available for substances with high sorption. Further adaptations of the terrestrial assessment strategy, including action triggers, appear necessary. Fate data show a high persistence of many APIs: approximately 43% of all APIs are classified as very persistent; 12% of these show DT50 values in a range where abiotic or biotic degradation is not expected.Overall, the evaluation has shown that improvements of the current guideline are possible.

29 p., 3 tablas, 2 figuras y bibliografía ; Molluscs are sensitive species to the toxic effects of organotin compounds, particularly to masculinization, and both, tributyltin (TBT) and triphenyltin (TPT) have been recently shown to bind to molluscs RXR. Being RXR is involved in lipid homeostasis, exposure to TPT would have an immediate effect on lipid homeostasis. To test this hypothesis, the ramshorn snail Marisa cornuarietis was exposed to environmentally relevant concentrations of TPT (30, 125, 500 ng/L as Sn) in a semi-static water regime for 7-days. Percentage of lipids and total fatty acid content decreased significantly in TPT-exposed females while the activity of peroxisomal acyl-CoA oxidase, involved in fatty acid catabolism, increased. In addition, fatty acid profiles (carbon chain length and unsaturation degree) were significantly altered in exposed females but not in males. This work highlights the ability of TPT to disrupt lipid metabolism in M. cornuarietis at environmentally realistic concentrations and the higher susceptibility of females in comparison to males. ; This study was supported by the European Union (COMPRENDO-Project, EVK1-CT-2002-00129) and the Spanish National Plan for Research (Project Ref CGL2005-02846).

Tens of thousands of man-made chemicals are in regular use and discharged into the environment. Many of them are known to interfere with the hormonal systems in humans and wildlife. Given the complexity of endocrine systems, there are many ways in which endocrine-disrupting chemicals (EDCs) can affect the body's signaling system, and this makes unraveling the mechanisms of action of these chemicals difficult. A major concern is that some of these EDCs appear to be biologically active at extremely low concentrations. There is growing evidence to indicate that the guiding principle of traditional toxicology that "the dose makes the poison" may not always be the case because some EDCs do not induce the classical dose–response relationships. The European Union project COMPRENDO (Comparative Research on Endocrine Disrupters—Phylogenetic Approach and Common Principles focussing on Androgenic/Antiandrogenic Compounds) therefore aims to develop an understanding of potential health problems posed by androgenic and antiandrogenic compounds (AACs) to wildlife and humans by focusing on the commonalities and differences in responses to AACs across the animal kingdom (from invertebrates to vertebrates).

Tens of thousands of man-made chemicals are in regular use and discharged into the environment. Many of them are known to interfere with the hormonal systems in humans and wildlife. Given the complexity of endocrine systems, there are many ways in which endocrine-disrupting chemicals (EDCs) can affect the body's signaling system, and this makes unraveling the mechanisms of action of these chemicals difficult. A major concern is that some of these EDCs appear to be biologically active at extremely low concentrations. There is growing evidence to indicate that the guiding principle of traditional toxicology that "the dose makes the poison" may not always be the case because some EDCs do not induce the classical dose–response relationships. The European Union project COMPRENDO (Comparative Research on Endocrine Disrupters—Phylogenetic Approach and Common Principles focussing on Androgenic/Antiandrogenic Compounds) therefore aims to develop an understanding of potential health problems posed by androgenic and antiandrogenic compounds (AACs) to wildlife and humans by focusing on the commonalities and differences in responses to AACs across the animal kingdom (from invertebrates to vertebrates).

3 pages.-- PMID: 16818253 [PubMed].-- PMCID: PMC1874174. ; This article is part of the monograph "The Ecological Relevance of Chemically Induced Endocrine Disruption in Wildlife". ; Tens of thousands of man-made chemicals are in regular use and discharged into the environment. Many of them are known to interfere with the hormonal systems in humans and wildlife. Given the complexity of endocrine systems, there are many ways in which endocrine-disrupting chemicals (EDCs) can affect the body's signaling system, and this makes unraveling the mechanisms of action of these chemicals difficult. A major concern is that some of these EDCs appear to be biologically active at extremely low concentrations. There is growing evidence to indicate that the guiding principle of traditional toxicology that "the dose makes the poison" may not always be the case because some EDCs do not induce the classical dose–response relationships. The European Union project COMPRENDO (Comparative Research on Endocrine Disrupters—Phylogenetic Approach and Common Principles focussing on Androgenic/Antiandrogenic Compounds) therefore aims to develop an understanding of potential health problems posed by androgenic and antiandrogenic compounds (AACs) to wildlife and humans by focusing on the commonalities and differences in responses to AACs across the animal kingdom (from invertebrates to vertebrates). ; This project is funded by the European Union (COMPRENDO Project, contract EVK1-CT-2002-00129). ; Peer reviewed