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

Despite 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 < 1 mg L-1) and the least (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.

Toxicities of 48 pharmaceuticals and their freshwater and marine environmental assessment in northwestern France.

A risk assessment for freshwater and marine ecosystems is presented for 48 pharmaceutical compounds, belonging to 16 therapeutic classes, and prescribed in northwestern France. Ecotoxicity data were obtained on two freshwater organisms, i.e., crustacean Daphnia magna and the green algae Pseudokirchneriella subcapitata, and on two marine organisms, i.e., the crustacean Artemia salina and the diatom Skeletonema marinoi. Measured environmental concentrations (MEC), in the Orne River and sea off Merville-Franceville in the Basse-Normandie region, were compared to the predicted environmental concentrations (PEC). Predicted no-effect concentrations (PNEC) were derived from acute data for each compound. Then, a risk assessment for each compound and the mixture was performed by calculating risk quotients (RQ as PEC or MEC/PNEC ratio). Results showed that no immediate acute toxicities were expected even if some compounds displayed strong toxicities at very low concentrations. Antibiotics, antidepressants, and antifungals would deserve attention because of their high or median ecological risk suspected on marine and freshwater ecosystems. Marine ecosystems would be more sensitive to pharmaceutical residues.

Comparison of the sensitivity of seven marine and freshwater bioassays as regards antidepressant toxicity assessment.

The hazards linked to pharmaceutical residues like antidepressants are currently a major concern of ecotoxicology because they may have adverse effects on non-target aquatic organisms. Our study assesses the ecotoxicity of three antidepressants (fluoxetine, sertraline and clomipramine) using a battery of marine and freshwater species representing different trophic levels, and compares the bioassay sensitivity levels. We selected the following bioassays: the algal growth inhibition test (Skeletonema marinoi and Pseudokirchneriella subcapitata), the microcrustacean immobilization test (Artemia salina and Daphnia magna), development and adult survival tests on Hydra attenuata, embryotoxicity and metamorphosis tests on Crassostrea gigas, and in vitro assays on primary cultures of Haliotis tuberculata hemocytes. The results showed high inter-species variability in EC50-values ranging from 43 to 15,600 µg/L for fluoxetine, from 67 to 4,400 µg/L for sertraline, and from 4.70 µg/L to more than 100,000 µg/L for clomipramine. Algae (S. marinoi and P. subcapitata) and the embryo-larval stages of the oyster C. gigas were the most sensitive taxa. This raises an issue due to their ecological and/or economic importance. The marine crustacean A. salina was the least sensitive species. This difference in sensitivity between bioassays highlights the importance of using a test battery.

Assessment of cytotoxic and immunomodulatory properties of four antidepressants on primary cultures of abalone hemocytes (Haliotis tuberculata).

Pharmaceutical compounds like antidepressants found in surface waters raise concerns due to their potential toxicity on non-target aquatic organisms. This study aimed at investigating the in vitro cytotoxicity and immunomodulatory properties of four common antidepressants, namely Amitriptyline, Clomipramine, Citalopram and Paroxetine, on primary cultures of abalone hemocytes (Haliotis tuberculata), after 48 h-exposure. Effects on immunocompetence (phagocytosis, levels of reactive oxygen species, esterase activity and lysosomal membrane destabilization) were assessed. Results obtained by MTT assays revealed that acute toxicity is unlikely to occur in the environment since the LC50s of the four antidepressants are at the mg/L level. The different immunological endpoints displayed a biphasic response, with an increase at the lowest concentration (i.e. 1 µg/L) followed by a decrease at higher concentrations. Overall, Amitriptyline and Clomipramine, the two tricyclic antidepressants, had higher immunomodulatory capacities than the two selective serotonin reuptake inhibitors Citalopram and Paroxetine. Amitriptyline was the most potent and Citalopram the least potent drug in altering immune function in H. tuberculata.

Assessment of the genotoxic and carcinogenic potentials of 3-aminothiophene derivatives using in vitro and in silico methodologies.

Thiophene derivatives, a class of compounds widely used in products such as pharmaceuticals, agrochemicals or dyestuffs, represent chemicals of concern. Indeed, the thiophene ring is often considered as a structural moiety that may be involved in toxic effects in humans. We primarily focus on the genotoxic/mutagenic and carcinogenic potentials of the methyl 3-amino-4-methylthiophene-2-carboxylate (1), a precursor of the articaine local anesthetic (4) which falls within the scope of the European REACH (Registration, Evaluation, Authorisation and restriction of CHemicals) legislation. To discern some structure-toxicity relationships, we also studied two related compounds, namely the 3-amino 4-methylthiophene (2) and the 2-acetyl 4-chlorothiophene (3). Techniques employed to assess mutagenic and DNA-damaging effects involved the Salmonella mutagenicity assay (or Ames test) and the single-cell gel electrophoresis assay (or Comet assay). In the range of tested doses, none of these derivatives led to a positive response in the Ames tests and DNA damage was only observed in the Comet assay after high concentration exposure of 2. The study of their carcinogenic potential using the in vitro SHE (Syrian Hamster Embryo) cell transformation assay (CTA) highlighted the activity of compound 2. A combination of experimental data with in silico predictions of the reactivity of thiophene derivatives towards cytochrome P450 (CYP450), enabled us to hypothesize possible pathways leading to these toxicological profiles.

Introduction of jumping fragments in combination with QSARs for the assessment of classification in ecotoxicology.

Starting from a random set of structures taken from the European Chemical Bureau (ECB) Web site, an estimation of the classification by acute category in ecotoxicology was carried out. This estimation was based on two approaches. One approach consists in starting with global quantitative structure-activity relationship (QSAR) equations, analyzing the results and defining an interpretation in terms of overall results and mode of action. The other starts with the notion of emerging fragments and more specifically with the introduction of a particular concept: the jumping fragments. This publication studies the scopes and limitations of each approach for the classification of the derivatives. A promising combination of the two methods is proposed for the classification and also for bringing new information about the importance, for the ecotoxicity, of specific chemical fragments considered alone or in association with others.