Wastewaters

The major pathways of human pharmaceuticals into the environment are from their use by individuals either at home or under medical supervision in hospitals, and to a lesser extent by the disposal of unwanted or out of date drugs. The administered pharmaceuticals will be excreted as the parent compound, metabolite or conjugate and will be transported to sewage treatment works. In sewage treatment, the compound may be degraded or partially degraded, adsorbed to sludge if lipophilic, be deconjugated or pass through sewage treatment unchanged. Once in the environment the substance will be subject to further degradation processes. The first part of this research is dedicated to the occurrence and fate of five substances widely consumed in Switzerland: Clofibric acid (metabolite), Ibuprofen, Ketoprofen, Mefenamic acid and Diclofenac (Chapter 2). These acidic drugs were analyzed in three sewage treatment plants (STPs) over four to seven consecutive days. Ibuprofen, Ketoprofen, Mefenamic acid and Diclofenac are non-steroidal anti-inflammatory drugs (NSAIDs). Clofibric acid is an active metabolite of Clofibrate, Etofibrate, Etofyllinclofibrate which are drugs used as blood lipid regulators. The anti-inflammatory drug Ibuprofen and Mefenamic acid are the most sold substances of this study with 17 tons per year and per substance in Switzerland. Recoveries after filtration, extraction, derivatisation and clean-up generally exceeded 70%. Limits of detection (5-15 ng/l) and quantification (15-50 ng/l) were in a range which allows the detection and the quantification of these compounds in wastewaters. The results of samples analysis point out that the five substances were persistent in wastewater effluents after municipal wastewater treatment. At the most, half of Mefenamic acid was eliminated. Ibuprofen was well removed (80%) by one sewage treatment plant. The removal of Ibuprofen is depending on the residence time of wastewater in the STPs. A long raining period induce a important decrease of removal of Ibuprofen and Ketoprofen. Removal rates showed a great variability according to sewage treatment plants and types of treatments (e.g. biological, physico-chemical). The concentrations of Ibuprofen, Mefenamic acid and Diclofenac were relatively high in the effluents (150-2000 ng/l), showing a potential contamination of surface water. An environmental risk assessment is presented. Mefenamic acid seems to present the most important risk, followed by Ibuprofen, Clofibric acid, Diclofenac and Ketoprofen. But the risk ratio for surface water calculated with a dilution factor was above one only for Mefenamic acid. Since that toxicity of a single drug might be enhanced by the occurrence of other pharmaceuticals with similar activity, the overall risk of these drugs could be significant. To our knowledge, chronic ecotoxicity data are available only for Diclofenac and Clofibric acid. These kind of data are needed for the other chemicals to confirm our results. The second part of this thesis is dedicated to anticancer drugs (Chapter 3). Since the occurrence of anticancer drugs in the environment are few studied and that these substances are extremely toxic (teratogen, mutagen, etc.), it was interesting to evaluate the contamination of wastewaters by two of the most used anticancer drugs. Two methods were set up to analyse Tamoxifen and 5-Fluorouracil in wastewaters. A Liquid-liquid extraction (LLE) followed by a purification on OASIS® MCX cartridge and gas chromatography and mass spectrometry detection (GC-MS) were used for the analysis of Tamoxifen. 5-Fluorouracil was extracted with an ENV+ (Isolute) cartridge (solid-phase extraction), derivatised with pentafluorobenzyl bromide (PFBBr) and detected by GC-MS. Both methods showed good recoveries (>70%), reproducibility (RSD