Advances and limits of two model species for ecotoxicological assessment of carbamazepine, two by-products and their mixture at environmental level in freshwater.

In order to evaluate the environmental impacts associated with the presence of low-level of pharmaceuticals in waters, chronic ecotoxicity of carbamazepine (CBZ), oxcarbazepine (OxCBZ) and acridine 9-carboxylic acid (9-CAA) and their mixture was investigated using two species from different trophic levels. Innovative approaches were developed by monitoring: (i) phytometabolites in the duckweed Lemna minor L. and, (ii) alterations at the population, cellular and molecular levels on the cnidarian Hydra circumcincta Schulze 1914, to assess the effects of 14-day chronic exposure. On H. circumcincta, the approach was conducted at 19.5 °C, the optimal growth temperature, and at 23 °C, to simulate global warming impact. In L. minor, results showed alterations of the nitrogen balance and the chlorophyll indices for OxCBZ and 9-CAA separately at environmental concentrations and for the mixture of the three studied products. However, phenolic compound index deeply varied depending on pharmaceuticals and time of exposure with no specific trend. In H. circumcincta, effects on morphology, reproduction and lipid peroxidation were observed at low level of CBZ. OxCBZ impacted the total antioxidant capacity of H. circumcincta, whereas exposure to 9-CAA affected all parameters, except the reproduction rate. Finally, 14-day exposure to the mixture of the three products also slowed the reproduction rate and altered the morphology of this cnidarian. Higher damages were detected when experiments were conducted at a temperature 3.5 °C above the optimum for Hydra growth, suggesting the relevance of taking into account possible ecotoxicological consequences of global warming. Our results confirmed the necessity of selecting sensitive organisms at different trophic levels to better assess ecotoxicity of pharmaceuticals and their mixture, especially at environmental levels and facing global changes.

Occurrence and ecotoxicological assessment of pharmaceuticals: Is there a risk for the Mediterranean aquatic environment?

Due to their pseudo-persistence and their biological activity, pharmaceuticals are emerging contaminants of major concern for the environment. The aim of this review is to provide an updated inventory of the contamination of aquatic environments by 43 drugs representing different classes of pharmaceuticals, such as antibiotics, anti-inflammatory drugs, anti-depressants, sex hormones, lipid regulators and beta-blockers. The data collected is focused on contamination levels reported in marine coastal waters and in waste and river waters flowing into the Mediterranean Sea. The most widely produced/prescribed classes of medicines are compared with the substances most widely searched for in the environment. Ranges of pollution levels according to the type of water body are also presented, to examine the fate in sewage treatment plants and the persistence in the environment of the targeted molecules. Levels of pharmaceuticals ranged from 100 to 10,000 or even 100,000 ng·L-1 in sewage waters, dropping to 1 to 10,000 ng·L-1 in rivers and to not detected to 3000 ng·L-1 in sea water. However, this paper evidences a lack of data for seawater and also for several countries along the southern coast of the Mediterranean Sea. In order to assess the risk for aquatic ecosystems associated with pharmaceuticals, experimental ecotoxicological values obtained using normalized acute and/or chronic bioassays carried out with different trophic levels were collected for each drug. Targeted biological species and associated bioassays are classified on the basis of their sensitivity to each class of compounds. Occurrence and ecotoxicology are then linked by using the Hazard Quotient (HQ) to assess the environmental risk caused by pharmaceuticals in the Mediterranean Basin. Correlations between HQ and frequency of detection of pharmaceuticals highlighted thirteen compounds that are cause for concern in Mediterranean fresh and sea waters, such as 17α-ethinylestradiol, metoprolol, 8 antibiotics and 3 analgesics/anti-inflammatories.