Is the step-wise tiered approach for ERA of pharmaceuticals useful for the assessment of cancer therapeutic drugs present in marine environment?

摘要: Methotrexate (MTX) and tamoxifen (TMX) cancer therapeutic drugs have been detected within the aquatic environment. Nevertheless, MTX TMX research is essentially bio-medically orientated, with few studies addressing question of its toxicity in fresh water organisms, none to its' effect marine To authors' knowledge, Environmental Risk Assessments (ERA) for pharmaceuticals has mainly designed freshwater terrestrial environments (European Medicines Agency-EMEA guideline, 2006). Therefore, purpose this was (1) assess organism using EMEA (2) develop an ERA methodology environment, (3) evaluate suitability including a biomarker approach Phase III. reach these aims, risk assessment performed following 2-tier during III, applying lysosomal membrane stability (LMS) as screening tier-1 battery biochemical biomarkers tier-2. Results from II indicated that not toxic bacteria, microalgae sea urchin at concentrations tested, thus no further required, while possible risk. III only TMX. Ruditapes philippinarum were exposed 14 days (0.1, 1, 10, 50 μg L(-1)). At end experiment, clams environmental concentration significant changes LMS compared control (p<0.01); second tier applied. A induction (activity Ethoxyresorufin O-deethylase [EROD], glutathione S-transferase [GST], peroxidase [GPX], lipid peroxidation [LPO] levels) observed digestive gland tissues (p<0.01). Finally, study concentration, whilst potentially biota. This shown necessity create specific guidelines order effects environment which includes sensitive endpoints. The inadequacy current guideline predict chemotherapy agents displayed usefulness other tests demonstrated. approach, applied appears be suitable