Pharmaceuticals in the environment

International audienc

Joint effects of nine antidepressants on Raphidocelis subcapitata and Skeletonema marinoi : A matter of amine functional groups

International audienceAntidepressants are among the most prescribed pharmaceuticals throughout the world. Their presence has already been detected in several aquatic ecosystems worldwide and their effects on non-target organisms justify the growing concern of both the public and regulatory authorities. These emerging pollutants do not occur as isolated compounds but rather as multi-component mixtures, which may lead to increased adverse effects compared to individual compounds. Freshwater and marine algae seem particularly sensitive to pharmaceuticals, including antidepressants. Studies assessing the toxicity of antidepressant mixture to algae focused mainly on binary mixtures of selective serotonin reuptake inhibitors. In the present experiment, the freshwater algae Raphidocelis subcapitata (formerly known as Pseudokirchneriella subcapitata) and the marine diatom Skeletonema marinoi were exposed to equitoxic mixtures of 9 antidepressants (fluvoxamine, fluoxetine, sertraline, duloxetine, venlafaxine, clomipramine, amitriptyline, and citalopram) at different concentrations. The growth inhibition was measured.Results showed that the toxicity of this mixture was higher than the effects of each individual component, highlighting simple additivity or synergistic effects, whereas tested concentrations were below the 10% inhibition concentration (IC10) of each compound. Moreover, the QSAR analysis highlighted that antidepressants would act through narcosis (non-specific mode of action) towards the two species of algae. However, more specific effects can be observed by differentiating compounds with a primary/secondary amine from those with a tertiary amine. These mixture effects on algal species have to be assessed, especially since any impacts on phytoplankton could ultimately impact higher trophic levels (less food, secondary poisoning

Toxicity assessment of five emerging pollutants, alone and in binary or ternary mixtures, towards three aquatic organisms

International audienceDespite a growing scientific attention on ecological impact of emerging pollutants (EPs) such as pharmaceuticals, personal care products, and pesticides, knowledge gaps remain regarding mixture toxicity and effects on aquatic organisms. Several EPs were screened in seawater (Normandy, France), and the ecotoxicity of five compounds, chosen on their occurrence in ecosystems and use worldwide, was assessed and were the biocides methylparaben (MP) and triclosan (TCS), a pesticide degradation product (AMPA), and the pharmaceuticals venlafaxine (VEN) and carbamazepine (CBZ). The acute or sub-chronic toxicity, alone or in binary/ternary mixtures of three of them (CBZ, AMPA, and MP), was assessed on one marine and two freshwater organisms: Crassostrea gigas, Pseudokirchneriella subcapitata, and Daphnia magna. TCS and AMPA were, respectively, the most (EC50 50 mg L-1) toxic chemicals for the four endpoints (algal growth inhibition, daphnia immobilization, oyster embryotoxicity, and metamorphosis). The anxiolytic VEN (EC50 < 1 mg L-1) was particularly toxic to oyster larvae showing sensitivity difference between freshwater and marine organisms. If all the mixtures appeared to be in the same range of toxicity, the joint-toxic effects mainly led to synergistic or antagonistic interactions compared to single-compound toxicity. The data also highlighted species-dependent differing models of toxicity and underscored the need for an awareness of cocktail effects for better ecological risk assessment

Quantile regression model for a diverse set of chemicals: Application to acute toxicity for green algae

International audienceThe potential of Quantile Regression (QR) and Quantile Support Vector Machine Regression (QSVMR) was analyzed for the definitions of QSAR (Quantitative Structure-Activity Relationship) models associated with a diverse set of chemicals towards a particular endpoint. This study focused on a specific sensitive endpoint (acute toxicity to algae) for which even a narcosis QSAR model is not actually clear. An initial dataset including more than 401 ecotoxicological data for one species of algae (Selenastrum capricornutum) was defined. This set corresponds to a large sample of chemicals ranging from classical organic chemicals to pesticides. From this original data set, the selection of the different subsets was made in terms of the notion of Toxic Ratio (TR), a parameter based on the ratio between predicted and experimental values. The robustness of QR and QSVMR to outliers was clearly observed, thus demonstrating that this approach represents a major interest for QSAR associated with a diverse set of chemicals. We focused particularly on descriptors related to molecular surface properties

Acute toxicities of pharmaceuticals toward green algae. mode of action, biopharmaceutical drug disposition classification system and quantile regression models

International audienceThe acute toxicities of 36 pharmaceuticals towards green algae were estimated from a set of quantile regression models representing the first global quantitative structure–activity relationships. The selection of these pharmaceuticals was based on their predicted environmental concentrations. An agreement between the estimated values and the observed acute toxicity values was found for several families of pharmaceuticals, in particular, for antidepressants. A recent classification (BDDCS) of drugs based on ADME properties (Absorption, Distribution, Metabolism and Excretion) was clearly correlated with the acute ecotoxicities towards algae. Over-estimation of toxicity from our QSAR models was observed for classes 2, 3 and 4 whereas our model results were in agreement for the class 1 pharmaceuticals. Clarithromycin, a class 3 antibiotic characterized by weak metabolism and high solubility, was the most toxic to algae (molecular stability and presence in surface water)

Consensus QSAR Related to Global or MOA Models: Application to Acute Toxicity for Fish

International audienc

Development of an exposure protocol for toxicity test (FEET) for a marine species: the European sea bass (Dicentrarchus labrax)

International audienceRegulatory assessment of the effects of chemicals requires the availability of validated tests representing different environments and organisms. In this context, developing new tests is particularly needed for marine species from temperate environments. It is also important to evaluate effects that are generally poorly characterized and seldom included in regulatory tests. In this study, we designed an exposure protocol using European sea bass (Dicentrarchus labrax) larvae. We examined classical toxicological values (LCx) as well as behavioral responses. By comparing different hatching and breeding strategies, we defined the optimal conditions of exposure as non-agitated conditions in 24- or 48-well microplates. Our exposure protocol was then tested with 3,4-dichloroaniline (3,4-DCA), a recommended reference molecule. Based on our results, the 96 h LC50 for 3,4-DCA corresponded to 2.04 mg/L while the 168 h LC50 to 0.79 mg/L. Behavioral analyses showed no effect of 3,4-DCA at low concentration (0.25 mg/L). In conclusion, the present work established the basis for a new test which includes behavioral analysis and shows that the use of sea bass is suitable to early-life stage toxicity tests

Despite great expectations in the Seine River Basin, the WFD did not reduce diffuse pollution

International audienceEuropean stakeholders engaged in combatting the eutrophication of the North Sea welcomed three Water Framework Directive innovations: a more holistic approach to quality, the binding nature of WFD objectives, and greater public participation. Twenty years later, however, there has been a disappointing amount of progress in the reduction of diffuse pollution. In the Seine River Basin, the amount of livestock rearing is low; yet the basin is subject to significant diffuse pollution due to agriculture. This paper reports our study of this case; we examine the literature on WFD implementation policy in order to identify the physical and social causes of this failure to reduce diffuse pollution. We show that the nitrates, phosphorus, and pesticides that affect ground, surface and marine waters are attributable to structural changes in agricultural production rather than to inefficient farming practices. We describe how a series of instruments that were designed to combat the diffuse agricultural origins of pollutants have had little effect. We identify the main obstacles to improvement as being the dispersion of the targeted public and the dispersion of benefits, given the current nature of legitimacy in the European Union. This case illustrates the fact that intensive agricultural production has an impact on water quality far beyond the problem of excess manure from livestock production