Defining the Human-Biota Thresholds of Toxicological Concern for Organic Chemicals in Freshwater: The Proposed Strategy of the LIFE VERMEER Project Using VEGA Tools.

Several tons of chemicals are released every year into the environment and it is essential to assess the risk of adverse effects on human health and ecosystems. Risk assessment is expensive and time-consuming and only partial information is available for many compounds. A consolidated approach to overcome this limitation is the Threshold of Toxicological Concern (TTC) for assessment of the potential health impact and, more recently, eco-TTCs for the ecological aspect. The aim is to allow a safe assessment of substances with poor toxicological characterization. Only limited attempts have been made to integrate the human and ecological risk assessment procedures in a "One Health" perspective. We are proposing a strategy to define the Human-Biota TTCs (HB-TTCs) as concentrations of organic chemicals in freshwater preserving both humans and ecological receptors at the same time. Two sets of thresholds were derived: general HB-TTCs as preliminary screening levels for compounds with no eco- and toxicological information, and compound-specific HB-TTCs for chemicals with known hazard assessment, in terms of Predicted No effect Concentration (PNEC) values for freshwater ecosystems and acceptable doses for human health. The proposed strategy is based on freely available public data and tools to characterize and group chemicals according to their toxicological profiles. Five generic HB-TTCs were defined, based on the ecotoxicological profiles reflected by the Verhaar classes, and compound-specific thresholds for more than 400 organic chemicals with complete eco- and toxicological profiles. To complete the strategy, the use of in silico models is proposed to predict the required toxicological properties and suitable models already available on the VEGAHUB platform are listed.

In utero exposure to maternal diabetes impairs vascular expression of prostacyclin receptor in rat offspring.

OBJECTIVE: To evaluate modifications of arterial structure, gene expression, and function in our model of rats exposed to maternal diabetes. RESEARCH DESIGN AND METHODS: Morphometric analyses of elastic vessels structure and determination of thoracic aortic gene expression profile with oligonucleotide chips (Agilent, G4130, 22k) were performed before the onset of established hypertension (3 months). RESULTS: Arterial parameters of in situ fixed thoracic aorta were not significantly different between control mother offspring and diabetic mother offspring (DMO). The aortic gene expression profile of DMO is characterized by modifications of several members of the arachidonic acid metabolism including a twofold underexpression of prostacyclin receptor, which could contribute to decreased vasodilatation. This was confirmed by ex vivo experiments on isolated aortic rings. Pharmacological studies on conscious rats showed that systolic blood pressure decline in response to a PGI(2) analog was impaired in DMO rats. CONCLUSIONS: These results suggest an abnormal vascular fetal programming of prostacyclin receptor in rats exposed in utero to maternal hyperglycemia that is associated with impaired vasodilatation and may be involved in the pathophysiology of hypertension in this model.