Multidrug resistance in the embryos and larvae of the mussel Mytilus edulis

Identification of six mRNA sequences of genes related to multixenobiotic resistance (MXR) and biotransformation in Mytilus edulis

“…They were first identified in cancer cells, where they provide resistance to a broad spectrum of structurally and functionally unrelated drugs, thus causing the phenomenon known as multidrug resistance (Mdr) (Endicott & Ling 1989). An Mdrlike system called MXR (multixenobiotic resistance) has been identified in marine invertebrates (Kurelec et al 2000, McFadzen et al 2000. Beside these biotransformation and elimination systems, upregulated repair mechanisms like the HSP70 molecular chaperone can cause higher tolerance to general stress and xenobiotics (Tedengren et al 1999) and HSP70 induction is therefore a general marker often used in studies of stress-related effects.…”

Toxicology and Risk Assessment of Pharmaceuticals

“…This could potentially also have serious consequences with respect to mixture toxicity. Indeed the teratogenic effects of a range of compounds (vinblastine, mitomycin C, cadmium chloride, methylmethanesulfonate, chloroquine and colchicines) in mussel larvae, have been shown to be exacerbated with verapamil (20µM) co-exposure [50]. The question, however, remains as to the doses that are required for transport inhibition and whether these doses realistically are found in the environment at the same time with other pharmaceuticals or polar organic pollutants.…”

“…These tests should be carried out in accordance with the relevant OECD guidelines as outlined in Table 1. A standard base set of acute aquatic toxicity data at three trophic levels (algae, OECD 201; daphnia, OECD 211; fish early life stage, OECD 210 and activated sludge respiration, OECD 209) is also required in order to generate the PNEC via the application of an assessment factor (AF) to the lowest determined LC 50 , EC 50 or NOEC value. AFs are applied in order to account for the extrapolation from acute to chronic toxicity, interspecies variations in sensitivity, intraspecies variability and the extrapolation from laboratory to field scenarios.…”

“…This is strikingly illustrated by the findings of Ferrari and co-workers, who assessed the chronic and acute toxicity of three pharmaceuticals (carbamazepine, clofibric acid and diclofenac) in several different standard test systems [21]. Enormous differences in the EC 50 , NOEC and LOEC values for carbamazepine were apparent even in the acute assays (microtox, 30 min, D. Magna, 48 h, C. dubia, 48 h) depending on the type of test employed. Furthermore, test species were found to display stark variation in their relative sensitivity to the three substances tested, further illustrating that the choice of test system is critical for the generation of data which can be used to perform a reliable risk assessment for the aquatic environment.…”

“…The range of reported ecotoxicity effect concentrations from >15 000 mg/L for atropine sulfate (anticholinergic/mydriatic; LC 50 Artemia salina) to 0.003 mg/L for fluvoxamine (antidepressant; LOEC parturition Sphaerium striatinum) is extremely wide and illustrates that pharmaceutical compounds cannot be treated as a general class but must be looked at from the perspective of their mode of action and chemical properties. Indeed, the mode of action as suggested by the Specific Serotonin Reuptake Inhibitors (SSRI), fluoxetine and fluvoxamine, is maintenance of an unusually high level of serotonin over prolonged periods thus largely suppressing daily and/or seasonal fluctuations [33].…”