Pharmaceutical, personal care and veterinary products, which have been found in wastewater and surface water, are likely to contaminate the aquatic environment, groundwater included. The purpose of this review is to examine current and new strategies for assessing the toxicological effects of this special class of xenobiotics on aquatic species. Aquatic sentinel species that bioaccumulate some of these drugs remain to be identified, but studies with mussels and plants have shown that some antibiotics significantly accumulate in tissues. Laboratory tests have been conducted with some success on several aquatic species, including bacteria, plants, invertebrates (molluscs and arthropods) and fish, with commonly found drugs both individually and in mixtures. These toxicity tests generally indicate that acute lethal effects are not likely to occur in the environment but that chronic or long-term effects are possible. In an attempt to measure the effects of pharmaceuticals and personal care products, two types of biomarkers are proposed. The first class, known as integrative biomarkers, consists of measuring ecologically relevant biomarkers that encompass the effects of drugs, such as oxidative stress or DNA damage. Biomarkers that have been shown to predict changes at both the individual and population levels, and that respond to these products, are particularly useful for taking into account the final effects of pollution on feral aquatic organisms. The second class of biomarkers, known as drug target-specific biomarkers, measures the state/integrity of drug targets likely to impede the organism’s health and reproduction. For example, prostaglandin synthase produces prostaglandins necessary to assist spawning in bivalves, and its activity could be blocked by non-steroidal anti-inflammatory drugs such as acetylsalicylate and ibuprofen. Finally, two case studies are presented to exemplify the use of biomarkers to assess drug target specific interactions and tissue damage in aquatic species. In the first case study, primary cultures of rainbow trout hepatocytes were used to assess the cytotoxicity of carbamazepine (CBZ), a drug commonly found in municipal wastewater, at µg/L range, after exposure for 48 h at 18oC. Results showed that CBZ induced the activity of cytochromes P4503A4 and 2B6 (benzyloxyresorufin as the substrate), known biotransformation enzymes for this drug class (iminostillbene), and was highly correlated with lipid peroxidation and cell viability at environmentally relevant concentrations. Lipid peroxidation and cell viability are considered integrative biomarkers, while cytochrome P4503A4/2B6 activity is a target-specific biomarker. The second case study concerns feral carp that had survived for four years in an aerated lagoon that treats domestic municipal effluent. Results showed that cytochrome P3A4 activity, as determined by dibenzyloxyfluorescein (another substrate specific for cytochromes P450 3A4, 3A5 and 2C9), was readily induced in the post-mitochondrial supernatant of liver homogenates. ATP-dependent dopamine transport activity in synaptosome preparations of brain tissues was shown to be significantly reduced. Increased cytochrome P450-related activities and reduced dopamine uptake suggest the pharmacological effects of opiate-like substances. Preliminary findings thus indicate that some aquatic species are likely to accumulate some drugs and that they are likely to produce harmful effects on fish. Further research is needed to validate such biomarkers and to relate changes in drug targets with their residual levels in tissues.
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