Acute aquatic toxicity of organic solvents modeled by QSARs.

To limit in vivo experiments, the use of quantitative structure-activity relationships (QSARs) is advocated by REACH regulation to predict the required fish, invertebrate, and algae EC50 for chemical registration. The aim of this work was to develop reliable QSARs in order to model both invertebrate and algae EC50 for organic solvents, regardless of the mechanism of toxic action involved. EC50 represents the concentration producing the 50 % immobilization of invertebrates or the 50 % growth inhibition of algae. The dataset was composed of 122 organic solvents chemically heterogeneous which were characterized by their invertebrate and/or algae EC50. These solvents were described by physico-chemical descriptors and quantum theoretical parameters calculated via density functional theory. QSAR models were developed by multiple linear regression using the ordinary least squares method and descriptor selection was performed by the Kubinyi function. Invertebrate EC50 was well-described with LogP, dielectric constant, surface tension, and minimal atomic Mulliken charges while algae EC50 of organic solvents (except amines) was predicted with LogP and LUMO energy. To evaluate robustness and predictive performance of the QSARs developed, several strategies have been used to select solvent training sets (random, EC50-based selection and a space-filling design) and both internal and external validations were performed.

Quantitative structure-activity relationship to predict acute fish toxicity of organic solvents.

REACH regulation requires ecotoxicological data to characterize industrial chemicals. To limit in vivo testing, Quantitative Structure-Activity Relationships (QSARs) are advocated to predict toxicity of a molecule. In this context, the topic of this work was to develop a reliable QSAR explaining the experimental acute toxicity of organic solvents for fish trophic level. Toxicity was expressed as log(LC50), the concentration in mmol.L(-1) producing the 50% death of fish. The 141 chemically heterogeneous solvents of the dataset were described by physico-chemical descriptors and quantum theoretical parameters calculated via Density Functional Theory. The best subsets of solvent descriptors for LC50 prediction were chosen both through the Kubinyi function associated with Enhanced Replacement Method and a stepwise forward multiple linear regressions. The 4-parameters selected in the model were the octanol-water partition coefficient, LUMO energy, dielectric constant and surface tension. The predictive power and robustness of the QSAR developed were assessed by internal and external validations. Several techniques for training sets selection were evaluated: a random selection, a LC50-based selection, a balanced selection in terms of toxic and non-toxic solvents, a solvent profile-based selection with a space filling technique and a D-optimality onions-based selection. A comparison with fish LC50 predicted by ECOSAR model validated for neutral organics confirmed the interest of the QSAR developed for the prediction of organic solvent aquatic toxicity regardless of the mechanism of toxic action involved.

[The relationship between the rigorous practice of sports and addictions: results from a survey in south-eastern France]. / Pratique sportive intensive et addictions: une enquête en région PACA.

This study aimed to assess the prevalence of cigarette, alcohol and cannabis consumption among top-ranked French student athletes aged between 16-24 years old, and to identify correlating factors. Overall, 837 athletes participated in the study (82% response rate). Among females, the amount and duration of sporting activity in which they were engaged on a weekly basis had a negative correlation to cigarette smoking and the occasional use of cannabis. Among males, however, a positive correlation of these factors was observed for cigarette smoking. Other determinants of alcohol, tobacco and cannabis use were the level of athletic competition and whether the athlete practiced a team sport (as opposed to an individual one), with some gender variations. Two major risk factors for young adult athletes were the existence of high psychological distress (for both sexes) and a lack of family support (particularly in the case of males). Further research is needed to investigate the specific motives to use so-called "recreational" drugs among young athletes engaging in high-level competition.

Influence of Stacking on the Hydrogen Bond Donating Potential of Nucleic Bases.

Hydrogen bonding is the dominant interaction in the pairing of nucleic bases and largely determines the stability of the double-helical structure of DNA. In a previous study, we used the molecular electrostatic potential (MEP) near a hydrogen-bond (HB) acceptor to demonstrate that the intrastrand π-π stacking interaction influences the interstrand HB accepting capacity of DNA/RNA bases. In the present work, we first examined at the MP2/6-31G(d) level whether the MEP near a HB donating site of an aromatic or nucleic base can be used as a computationally inexpensive measure for its HB donating potential, quantified as the interaction energy with an HB acceptor probe, and whether this also holds in the presence of a stacking partner. A good correlation was found for substituted anilines in a vacuum, and this seemed to hold for cytosine, stacked with substituted benzenes. However, when stacked pairs of nucleic bases were studied, no correlation between the MEP and the HB strength was found. This turned out to be caused by the direct interaction of the HB donor's stacking partner with the probe molecule as well as its influence on the MEP. After this perturbation was eliminated, a significant correlation was found. The influence of stacking on the HB donating potential was shown to be dominated by the stacking geometry and not by the nature of the stacking partner. The present findings suggest that the π-π interaction on itself does not have an overall strengthening on H bonding in DNA.