Wastewaters: occurrence of pharmaceutical substances and genotoxicity

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either at home or under medical supervision in hospitals, and to a lesser extent by the disposal of unwanted or out of date drugs.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<10%) and limits of detection (LOD≤15 ng/l). Wastewaters from a residential area, an hospital, and two sewage treatment plants (STPs) were analysed with the analytical methods developed in this study. Tamoxifen was detected in wastewaters of the hospital, residential area and influent of STPs, but not in treated wastewaters. All wastewaters showed no contamination with 5-Fluorouracil. The risk evaluation was not possible for these drugs, since no ecotoxicity data (even acute data) is available. The third part of this research is dedicated to toxicity and mutagenicity of wastewaters (Chapter 4). As pharmaceutical compounds, including anticancer drugs that are genotoxic, are discharged in wastewaters, the mutagenic potential of wastewaters from various origins (hospital, two different sewage treatment plants (STPs) and a residential area) was evaluated using the Ames test. The samples were not concentrated prior the analysis to determine the overall effects of these waters. The survival and the reversion frequencies of strains TA98, TA100, TA102 and TA1538 following treatment with the different wastewaters were determined. Survival was obtained by two methods. The first method was by comparing the number of reversions induced by a known mutagen in the presence and absence of wastewater. The second was by determining the colony forming ability of dilutions of treated and non-treated cultures. The samples from the hospital were on the whole more toxic than samples from the STPs and residential area. The different strains showed varying sensitivities to the toxic effects of the wastewater, with TA98 exhibiting the highest sensitivity (<5% survival). The results from the reversion assays indicated that TA102 was the most sensitive, followed by TA1538 and TA100. More hospital wastewater than influents of sewage treatment plants were mutagenic, indicating a higher mutagenic activity in the wastewater of the hospital. These wastewaters have not to be released in the environment without an adequate treatment. Comparison of the mutagenicity of the influents and effluents of the STPs showed that less effluent samples were mutagenic. This result indicates that biological treatments were relatively efficient in decreasing the mutagenicity of wastewaters. Due to their beneficial health effects and economic importance, the actions taken to reduce inputs of drugs into the environment are much debated. The use of pharmaceutical compounds is expected to grow with the increasing age of the population. A solution for pollution control is to add sewage treatments in hospital and to avoid that municipal wastewaters are released without any treatment. Another solution is to focus on reduction at source, by developing a clear labeling on medicinal products, guidelines for the disposal and awareness campaign. These recommendations would have the potential benefit of improved consumer health (by minimizing the intake of active substances), as well as reduced health care spending.

    Thèse École polytechnique fédérale de Lausanne EPFL, n° 3280 (2005)
    Section des sciences et ingénierie de l'environnement
    Faculté de l'environnement naturel, architectural et construit
    Institut des sciences et technologies de l'environnement
    Laboratoire de chimie environnementale et écotoxicologie
    Jury: Luiz Felippe De Alencastro, Georg Karlaganis, André Mermoud, Phaik-Mooi Morgenthaler-Leong, Marc Parlange, Jean-Luc Veuthey

    Public defense: 2005-7-8


    Record created on 2005-05-25, modified on 2016-08-08

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