Publications by authors named "Thomas Heberer"

25 Publications

  • Page 1 of 1

Eight years of sales surveillance of antimicrobials for veterinary use in Germany-What are the perceptions?

PLoS One 2020 10;15(8):e0237459. Epub 2020 Aug 10.

Department Veterinary Drugs, Federal Office of Consumer Protection and Food Safety (BVL), Berlin, Germany.

A surveillance system for sales volumes of antimicrobial agents for veterinary use was established in Germany in 2011. Since then, pharmaceutical companies and wholesalers have been legally obliged to report annual volumes of veterinary antimicrobial products sold to veterinary practices or clinics located in Germany. The evaluation of sales volumes for eight consecutive years resulted in a considerable total decrease by 58% from 1706 tons to 722 tons. During the investigation period, two legally binding measures to control the risk of antimicrobial resistance resulting from the veterinary use of antimicrobials were introduced, a) the German treatment frequencies benchmarking in 2014 and b) the obligation to conduct susceptibility testing for the use of cephalosporins of the 3rd and 4th generation and of fluoroquinolones in 2018. Both had a marked impact on sales volumes. Nonetheless, the category of Critically Important Antimicrobials as defined by the World Health Organization kept accounting for the highest share on sales volumes in Germany in 2018 with 403 tons, despite an overall reduction by 53%. Sales surveillance is considered essential for data retrieval on a global scale and inter-country comparison. However, the usability of a surveillance system based on sales data for risk management of antimicrobial resistance has limitations. The German system does not include off-label use of antimicrobial products authorized for human medicine and does not allow for identification of areas of high risk according to animal species, farm and production types and indications for treatment. For further reduction and enhanced promotion of a prudent use of antimicrobials, targeted measures would be required that could only be deducted from use data collected at farm or veterinary practice level. A surveillance system based on use data is currently lacking in Germany but will be established according to Regulation (EU) 2019/6 on veterinary medicinal products.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237459PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416935PMC
October 2020

Ecotoxicological assessment of antibiotics: A call for improved consideration of microorganisms.

Environ Int 2015 Dec 25;85:189-205. Epub 2015 Sep 25.

Agriculture and Agri-Food Canada, London, Ontario, Canada. Electronic address:

Antibiotics play a pivotal role in the management of infectious disease in humans, companion animals, livestock, and aquaculture operations at a global scale. Antibiotics are produced, consumed, and released into the environment at an unprecedented scale causing concern that the presence of antibiotic residues may adversely impact aquatic and terrestrial ecosystems. Here we critically review the ecotoxicological assessment of antibiotics as related to environmental risk assessment (ERA). We initially discuss the need for more specific protection goals based on the ecosystem service concept, and suggest that the ERA of antibiotics, through the application of a mode of toxic action approach, should make more use of ecotoxicological endpoints targeting microorganisms (especially bacteria) and microbial communities. Key ecosystem services provided by microorganisms and associated ecosystem service-providing units (e.g. taxa or functional groups) are identified. Approaches currently available for elucidating ecotoxicological effects on microorganisms are reviewed in detail and we conclude that microbial community-based tests should be used to complement single-species tests to offer more targeted protection of key ecosystem services. Specifically, we propose that ecotoxicological tests should not only assess microbial community function, but also microbial diversity (‘species’ richness) and antibiotic susceptibility. Promising areas for future basic and applied research of relevance to ERA are highlighted throughout the text. In this regard, the most fundamental knowledge gaps probably relate to our rudimentary understanding of the ecological roles of antibiotics in nature and possible adverse effects of environmental pollution with subinhibitory levels of antibiotics.
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http://dx.doi.org/10.1016/j.envint.2015.09.013DOI Listing
December 2015

Analysis of the distribution of veterinary antimicrobial products to veterinarians in Germany in 2011 and 2012.

Berl Munch Tierarztl Wochenschr 2014 Sep-Oct;127(9-10):359-65

For the implementation of risk management measures against the development and spread of antimicrobial resistances it is important to gain a quantitative insight into the use of veterinary antimicrobial agents. Since 2011, all pharmaceutical companies and wholesalers in Germany are required to report their sales data of veterinary antimicrobial products (VAPs). In 2011, 1706 t of antimicrobially active substances were sold to veterinarians registered in Germany, in 2012 the amount decreased to 1619 t. Tetracyclines and penicillins had the largest shares in both years, followed by sulfonamides, macrolides and polypeptides. Amoxicillin alone accounted for more than a quarter of the total amounts of all sold antimicrobials. In regard to AMR it is most important to limit the use of critically important antimicrobials, namely fluoroquinolones and 3rd and 4th generation cephalosporins. While in both years these groups accounted for less than 1% of the amount of sold antimicrobials, this does not reflect adequately their use, since they are used in much lower doses. Furthermore, it is worrying that the sales of fluoroquinolones and 3rd generation cephalosporins increased by 26% and 14%, respectively, between 2011 and 2012, while the sales of 4th generation cephalosporins decreased only by 2%. More than 95% of the active substances were contained in VAPs intended for oral application; only fluoroquinolones, 3rd and 4th generation cephalosporins as well as fenicols were primarily or even exclusively applied by injection.
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April 2015

Human Health Risk Assessment (HHRA) for environmental development and transfer of antibiotic resistance.

Environ Health Perspect 2013 Sep 9;121(9):993-1001. Epub 2013 Jul 9.

US Environmental Protection Agency, Office of Research and Development, Cincinnati, Ohio 45268, USA.

Background: Only recently has the environment been clearly implicated in the risk of antibiotic resistance to clinical outcome, but to date there have been few documented approaches to formally assess these risks.

Objective: We examined possible approaches and sought to identify research needs to enable human health risk assessments (HHRA) that focus on the role of the environment in the failure of antibiotic treatment caused by antibiotic-resistant pathogens.

Methods: The authors participated in a workshop held 4-8 March 2012 in Québec, Canada, to define the scope and objectives of an environmental assessment of antibiotic-resistance risks to human health. We focused on key elements of environmental-resistance-development "hot spots," exposure assessment (unrelated to food), and dose response to characterize risks that may improve antibiotic-resistance management options.

Discussion: Various novel aspects to traditional risk assessments were identified to enable an assessment of environmental antibiotic resistance. These include a) accounting for an added selective pressure on the environmental resistome that, over time, allows for development of antibiotic-resistant bacteria (ARB); b) identifying and describing rates of horizontal gene transfer (HGT) in the relevant environmental "hot spot" compartments; and c) modifying traditional dose-response approaches to address doses of ARB for various health outcomes and pathways.

Conclusions: We propose that environmental aspects of antibiotic-resistance development be included in the processes of any HHRA addressing ARB. Because of limited available data, a multicriteria decision analysis approach would be a useful way to undertake an HHRA of environmental antibiotic resistance that informs risk managers.
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http://dx.doi.org/10.1289/ehp.1206316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3764079PMC
September 2013

Removal kinetics of organic compounds and sum parameters under field conditions for managed aquifer recharge.

Water Res 2011 Oct 22;45(16):4939-50. Epub 2011 Jul 22.

Berlin Centre of Competence for Water, gGmbH, Cicerostraße 24, 10709 Berlin, Germany.

Managed aquifer recharge (MAR) provides efficient removal for many organic compounds and sum parameters. However, observed in situ removal efficiencies tend to scatter and cannot be predicted easily. In this paper, a method is introduced which allows to identify and eliminate biased samples and to quantify simultaneously the impact of (i) redox conditions (ii) kinetics (iii) residual threshold values below which no removal occurs and (iv) field site specifics. It enables to rule out spurious correlations between these factors and therefore improves the predictive power. The method is applied to an extensive database from three MAR field sites which was compiled in the NASRI project (2002-2005, Berlin, Germany). Removal characteristics for 38 organic parameters are obtained, of which 9 are analysed independently in 2 different laboratories. Out of these parameters, mainly pharmaceutically active compounds (PhAC) but also sum parameters and industrial chemicals, four compounds are shown to be readily removable whereas six are persistent. All partly removable compounds show a redox dependency and most of them reveal either kinetic dependencies or residual threshold values, which are determined. Differing removal efficiencies at different field sites can usually be explained by characteristics (i) to (iii).
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http://dx.doi.org/10.1016/j.watres.2011.06.040DOI Listing
October 2011

High levels of polychlorinated dibenzo-dioxins/furans and dioxin like-PCBs found in monitoring investigations of sheep liver samples from Lower Saxony, Germany.

Chemosphere 2010 Feb 31;78(6):653-8. Epub 2009 Dec 31.

Lower Saxony Federal State Office of Consumer Protection and Food Safety (LAVES), Food Institute Oldenburg, Martin-Niemöller-Strasse 2, 26133 Oldenburg, Germany.

In this study, the occurrence of 17 toxicologically-relevant polychlorinated dibenzo-dioxins and furans (PCDD/PCDFs) and 12 dioxin-like polychlorinated biphenyls (dl-PCBs) was investigated in livers of sheep from Lower Saxony, Germany. The aim of the monitoring was to get a state-wide picture on the contamination level of sheep liver samples. Seventy two out of 77 investigated sheep liver samples exceeded the European maximum tolerance level for PCDD/PCDFs of 6.0 pg WHO-PCDD/F-TEQ g(-1) fat with measured average, median and maximum values of 23.9, 18.3 and 161 pg WHO-PCDD/F-TEQ g(-1) fat, respectively. Seventy-one samples also exceeded the cumulative maximum tolerance level of 12.0 pg WHO-PCDD/F-PCB-TEQ g(-1) fat set in the EU for the sum of PCDD/PCDFs and dl-PCBs in livers of sheep and derived products. Average, median and maximum measured values were 42.9, 33.9 and 204 pg WHO-PCDD/F-PCB-TEQ g(-1) fat, respectively. In the meat of the sheep only low amounts of PCDD/Fs or dl-PCBs were detected that never exceeded the respective maximum tolerance levels. The results did not show any significant differences in contamination between female or male sheep. Also no correlation was found between the age of the animals and the burden of their livers with PCDD/PCDFs or dl-PCBs. Health risks from the casual consumption of sheep livers are almost unlikely but can also not be excluded for individuals frequently consuming sheep livers with average contamination levels. Almost no difference was observed in the burden of contamination of sheep liver samples between rural and municipal areas or between areas located near or apart from waterways. In conclusion, the results yielded a picture of a varying but high level of contamination of sheep livers most likely caused by physiological differences compared to other animal species and by the ubiquitous environmental contamination primarily assignable to historic dioxin and PCB sources.
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http://dx.doi.org/10.1016/j.chemosphere.2009.12.014DOI Listing
February 2010

Occurrence and assessment of perfluorinated chemicals in wild fish from Northern Germany.

Chemosphere 2010 Feb 30;78(6):647-52. Epub 2009 Dec 30.

Technical University of Berlin, Institute for Food Technology and Food Chemistry, Sekr. TIB 4/3-1, Gustav-Meyer-Allee 25, 13355 Berlin, Germany.

Residues of the perfluorinated chemicals perfluorooctanesulfonate (PFOS) and perfluorooctanoicacid (PFOA) were investigated in wild fish caught from different German waters including the North and the Baltic Sea, Lake Storkow in Brandenburg, several rivers in Lower Saxony, and rivers and lakes in the city of Berlin. The sample locations represent waters with no, low, medium and high portions of treated municipal sewage discharges. The investigated fish filet samples included 51 wild eels, 44 bream, 5 herring, 5 mackerel, 3 carp and 4 trout. PFOA was not found in any of the investigated samples above the limit of quantitation of 0.27 microgkg(-1) fresh weight (fw.), whereas PFOS was detected with concentrations up to 225 microgkg(-1)fw. PFOS was found in the filet samples caught from densely populated regions at levels between 8.2 and 225 microgkg(-1)fw. In samples from marine or remote locations, PFOS was not detected or only detected at levels up to 50.8 microgkg(-1)fw. To date, a tolerable daily intake (TDI) for PFOS and PFOA has or could not finally be fixed by any official national or international organization. A provisional TDI of 150 microgkg(-1) body weight per day has, however, been proposed by the European Food Safety Authority to be used for a provisional risk assessment. Thus, the detected residues of PFOS found in 33 out of 112 examined fish samples might be classified as potential risks for the health of consumers with elevated fish consumption.
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http://dx.doi.org/10.1016/j.chemosphere.2009.12.015DOI Listing
February 2010

Development of a validated liquid chromatography/tandem mass spectrometry method for the distinction of thyronine and thyronamine constitutional isomers and for the identification of new deiodinase substrates.

Rapid Commun Mass Spectrom 2008 Oct;22(20):3286-96

Institut für Experimentelle Endokrinologie und Endokrinologisches Forschungszentrum der Charité EnForCé, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany.

Thyronines (THs) and thyronamines (TAMs) are two groups of endogenous iodine-containing signaling molecules whose representatives differ from each other only regarding the number and/or the position of the iodine atoms. Both groups of compounds are substrates of three deiodinase isozymes, which catalyze the sequential reductive removal of iodine from the respective precursor molecule. In this study, a novel analytical method applying liquid chromatography/tandem mass spectrometry (LC-MS/MS) was developed. This method permitted the unequivocal, simultaneous identification and quantification of all THs and TAMs in the same biological sample. Furthermore, a liquid-liquid extraction procedure permitting the concurrent isolation of all THs and TAMs from biological matrices, namely deiodinase (Dio) reaction mixtures, was established. Method validation experiments with extracted TH and TAM analytes demonstrated that the method was selective, devoid of matrix effects, sensitive, linear over a wide range of analyte concentrations and robust in terms of reproducible recoveries, process efficiencies as well as intra-assay and inter-assay stability parameters. The method was applied to study the deiodination reactions of iodinated THs catalyzed by the three deiodinase isozymes. With the HPLC protocol developed herein, sufficient chromatographic separation of all constitutional TH and TAM isomers was achieved. Accordingly, the position of each iodine atom removed from a TH substrate in a Dio-catalyzed reaction was backtracked unequivocally. While several established deiodination reactions were verified, two as yet unknown reactions, namely the phenolic ring deiodination of 3',5'-diiodothyronine (3',5'-T2) by Dio2 and the tyrosyl ring deiodination of 3-monoiodothyronine (3-T1) by Dio3, were newly identified.
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http://dx.doi.org/10.1002/rcm.3732DOI Listing
October 2008

Behaviour and redox sensitivity of antimicrobial residues during bank filtration.

Chemosphere 2008 Sep 26;73(4):451-60. Epub 2008 Aug 26.

Lower Saxony Federal State Office of Consumer Protection and Food Safety (LAVES), Food Institute Oldenburg, Martin-Niemöller-Strasse 2, 26133 Oldenburg, Germany.

The behaviour of residues of antibiotic drugs during bank filtration was studied at a field site in Berlin, Germany, where bank-filtered water is used for the production of drinking water. The neighbouring surface water used for bank filtration is under the influence of treated municipal wastewater. Seven out of 19 investigated antimicrobial residues were found in the surface water with median concentrations between 7 and 151ngL(-1). Out of the seven analytes detected in the surface water only three (anhydroerythromycin, clindamycin and sulfamethoxazole) were found with median concentrations above their limits of quantitation in bank filtrate with a travel time of one month or less. With the exception of sulfamethoxazole, none of the 19 analytes were present in bank filtrate with a residence time larger than one month or in the water-supply well itself. Sulfamethoxazole found with a median concentration of 151ngL(-1) in the surface water was the most persistent of all antimicrobial residues. Nevertheless, it was also removed by more than 98% and only found with a median concentration of 2ngL(-1) in the water-supply well. The degradation of clindamycin and sulfamethoxazole appear to be redox-dependent. Clindamycin was eliminated more efficiently under oxic infiltration conditions while sulfamethoxazole was eliminated more rapidly under anoxic infiltration conditions. A slight preference for an improved degradation under oxic (clarithromycin and roxithromycin) or anoxic (anhydroerythromycin) conditions was also observed for the macrolide antibiotics. Nevertheless, all macrolides were readily removable by bank filtration both under oxic and anoxic conditions.
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http://dx.doi.org/10.1016/j.chemosphere.2008.06.056DOI Listing
September 2008

Occurrence of residues of the veterinary drug malachite green in eels caught downstream from municipal sewage treatment plants.

Chemosphere 2008 Aug 3;72(11):1664-70. Epub 2008 Jul 3.

Federal Institute for Risk Assessment (BfR), Section for Residues of Medicinal Products, Diedersdorfer Weg 1, 12277 Berlin, Germany.

Residues of malachite green (MG), a veterinary drug illegally used for the treatment of aquacultured fish, have been found in wild eels caught from surface waters downstream from the sewers of different municipal sewage treatment plants (STPs). MG and its metabolite leucomalachite green (LMG) were detected with total concentrations up to 0.765 microg kg(-1) fresh weight in the tissues of 25 out of 45 eels caught from different lakes, a river and a canal in Berlin, Germany. In all cases, the occurrence of the residues could directly be linked to the presence of discharges by municipal STPs into the receiving surface waters. MG is a multiple-use compound that is also used to color materials. Thus, it appears to be reasonable that the residues of MG found in the eel samples originate from such uses, e.g. by wash off from clothes or paper towels colored with MG. Additional loads from legal uses of MG as veterinary drug for the treatment of ornamental fish (private aquaria) are possible. The results obtained from this study are the first proof of background contaminations of a veterinary drug found in samples of fish not intentionally treated with such agents. MG and LMG are regarded as potential genotoxic carcinogens making it impossible to establish a tolerable daily intake. A margin of exposure (MOE) approach was applied to evaluate the human health risk associated with the consumption of the eels investigated in this study. With a MOE of 3.4 million the chronic risk was classified as being very low. Nevertheless, due to their potential to act as genotoxic carcinogens, any oral exposure to residues of MG and LMG should be avoided. According to European Union law, zero tolerance applies to all residues of MG and LMG found in food for human consumption as MG is not registered for use as veterinary drug.
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http://dx.doi.org/10.1016/j.chemosphere.2008.05.036DOI Listing
August 2008

Behaviour and redox sensitivity of pharmaceutical residues during bank filtration - Investigation of residues of phenazone-type analgesics.

Chemosphere 2008 Apr 14;71(8):1476-85. Epub 2008 Feb 14.

Freie Universität Berlin, Institute of Geological Sciences, Hydrogeology Group, Malteserstrasse 74-100, 12249 Berlin, Germany.

The behaviour of residues of phenazone-type pharmaceuticals during bank filtration was investigated at a field site in Berlin, Germany, where bank-filtered water is used for drinking water production. The concentrations of the pharmaceutical residues in the shallow, young bank filtrate (travel times
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http://dx.doi.org/10.1016/j.chemosphere.2007.12.017DOI Listing
April 2008

Occurrence, fate and assessment of polar metamizole (dipyrone) residues in hospital and municipal wastewater.

Chemosphere 2008 Apr 31;71(9):1754-64. Epub 2007 Dec 31.

Institute of Food Chemistry, Technical University Berlin, Sekr. TIB4/3-1, Gustav-Meyer Allee 25, 13355 Berlin, Germany.

The occurrence and fate of residues from the therapeutic use of the non-steroidal anti-inflammatory drug metamizole have been studied in investigations of sewage effluents from a military hospital, municipal sewers and a sewage treatment plant (STP) in Berlin, Germany. The loads of the metabolites aminoantipyrin (AA), 4-acetylaminoantipyrin (AAA) and 4-formyl-aminoantipyrin (FAA), rapidly formed after the application of metamizole, were predicted from pharmacokinetic data and based on the evaluation of extensive data sets of on the administration in hospitals and private households. In parallel, the actual concentrations were measured within three field trials. For the military hospital, the estimated average annual discharges of AA/AAA and FAA were 10.5 and 3.2 kg, respectively. For the STP, annual loads of 333 and 133 kg were determined for AA/AAA and FAA, respectively. During sewage treatment, an average decrease of 26% of the loads was measured for AA/AAA whereas no changes were observed for FAA. Generally, the prediction of the loads resulted in an overestimation of the residue levels compared to those measured in the respective sewers. Thus, modeling of predicted loads or concentrations alone will not be sufficient for a realistic assessment. Concerns for human or other mammals' health are not expected from the occurrence of metamizole residues in the aquatic system measured at concentrations up to 7 microg l(-1) in STP effluents. However, a rest of uncertainty remains as it was not possible to derive a no observed effect level for the induction of rare but potentially fatal toxicological side effects reported for metamizole.
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http://dx.doi.org/10.1016/j.chemosphere.2007.11.032DOI Listing
April 2008

Zero tolerances in food and animal feed -- are there any scientific alternatives? A European point of view on an international controversy.

Toxicol Lett 2007 Dec 10;175(1-3):118-35. Epub 2007 Oct 10.

Federal Institute for Risk Assessment, Section 55, - Residues of Medicinal Products, Diedersdorfer Weg 1, 12277 Berlin, Germany.

A number of zero tolerance provisions are contained in both food and animal feed law, e.g. for chemical substances whose occurrence is not permitted or is directly prohibited in food or animal feed. In the European Union, bans of this kind were introduced to give consumers and animals the greatest possible protection from substances with a possible hazard potential within the intendment of the hazard prevention principles and current precautionary measures. This also applies to substances for which an acceptable daily intake cannot be derived and a maximum residue limit cannot, therefore, be established, e.g. due to missing or inadequate toxicological data. Zero tolerances are also under discussion as trade barriers because their use has triggered numerous legal disputes. This paper draws together the results of an evaluation of alternative risk assessment methods to be used for the risk assessment of substances to which currently only zero tolerances apply. It will demonstrate that, depending on the available toxicological data, a scientifically sound risk assessment may still be possible. In this context, the two concepts - margin of exposure and threshold of toxicological concern - are very promising approaches. Until the scientific and sociopolitical discussions have been completed, it is essential that the principle of zero tolerances be upheld, especially for those substances which may be genotoxic carcinogens. In microbiology, there is no legal room for manoeuvre with regard to food safety criteria established for reasons of consumer health protection on the basis of scientific assessments.
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http://dx.doi.org/10.1016/j.toxlet.2007.10.002DOI Listing
December 2007

Investigation of the behavior and metabolism of pharmaceutical residues during purification of contaminated ground water used for drinking water supply.

Chemosphere 2007 Nov 26;69(11):1673-80. Epub 2007 Jul 26.

Institute of Environmental Research, University of Dortmund, 44221 Dortmund, Germany.

Residues of phenazone-type pharmaceuticals originating from spills of a former pharmaceutical production plant have recently been detected in ground water in Berlin, Germany. The degradation pathways of phenazone, propyphenazone, and dimethylaminophenazone (DMAA) during water purification were enlightened in batch experiments with groundwater and filter material obtained from operating waterworks. For phenazone and propyphenazone a complete biological transformation into their respective metabolites 1,5-dimethyl-1,2-dehydro-3-pyrazolone (DP) and 4-(2-methylethyl)-1,5-dimethyl-1,2-dehydro-3-pyrazolone (PDP) was observed. Generally, removal of phenazone-type pharmaceutical residues during rapid sand filtration was almost exclusively caused by microorganisms only present in polluted raw water. DMAA applied to fresh filter materials was rapidly degraded into its metabolites 1-acetyl-1-methyl-2-phenylhydrazide (AMPH), acetoaminoantipyrine (AAA), formylaminoantipyrine (FAA), and 1-acetyl-1-methyl-2-dimethyloxamoyl-2-phenylhydrazide (AMDOPH). DMAA, AAA, and FAA were, however, only detected at low levels in a few samples of purified water from an operating water works. Whereas, the metabolites AMDOPH and DP were detected up to 1 microg l(-1). Propyphenazone was rapidly removed and AMPH, phenazone, and PDP were only measured with concentrations in the low ng l(-1) range. The concentrations of the metabolites DP and PDP are even higher in the purified water than in the raw water caused by their formation during degradation of phenazone and propyphenazone. Reduction of filtration velocity on an experimental filter from 5 m h(-1) down to 2 m h(-1) resulted in improved removal of phenazone, propyphenazone and their metabolites DP and PDP, respectively. AMDOPH, however, was highly persistent in all experiments independent from filtration velocities and contact times.
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http://dx.doi.org/10.1016/j.chemosphere.2007.06.020DOI Listing
November 2007

Mobility of pharmaceuticals carbamazepine, diclofenac, ibuprofen, and propyphenazone in miscible-displacement experiments.

J Contam Hydrol 2006 Feb 15;83(1-2):53-69. Epub 2005 Dec 15.

Institute of Applied Geosciences, Technical University of Berlin, Ackerstr. 71-76, 13355 Berlin, Germany.

Many pharmaceuticals pass the unsaturated zone before reaching an aquifer. Therefore, laboratory sand column transport experiments were conducted to study the transport behavior of carbamazepine, diclofenac, ibuprofen, and propyphenazone under unsaturated conditions. The test water was artificial sewage effluent to simulate the infiltration of reused wastewater. The test water was spiked with the pharmaceutically active compounds and the tracer LiCl. Afterwards it was passed through laboratory sand columns, one experiment for each pharmaceutical. The physical and chemical parameters were recorded and general ions measured. Pharmaceuticals were measured using solid phase extraction, derivatization, and detection with GC-MS. The column experiments indicate a significant elimination of ibuprofen (54%), propyphenazone (55%), and diclofenac (35%), whereas carbamazepine was not eliminated. Retardation factors varied between 1.84 for carbamazepine, 2.51 for propyphenazone, 3.00 for ibuprofen, and 4.80 for diclofenac. These results show that mobility and elimination of diclofenac, ibuprofen, and propyphenazone is about in the same range as for experiments under saturated conditions whereas carbamazepine had a significantly lower sorption and elimination under unsaturated conditions.
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http://dx.doi.org/10.1016/j.jconhyd.2005.11.002DOI Listing
February 2006

Contribution of effluents from hospitals and private households to the total loads of diclofenac and carbamazepine in municipal sewage effluents--modeling versus measurements.

J Hazard Mater 2005 Jul 19;122(3):211-8. Epub 2005 Apr 19.

Institute of Food Chemistry, Technical University of Berlin, Sekr. TIB 4/3-1, Berlin, Germany.

The anti-epileptic drug carbamazepine and the non-steroidal anti-inflammatory drug diclofenac are frequently found as residues in the aquatic environment and also in samples of ground and drinking water. For both compounds, their loads occurring in the effluents from a military hospital and in the combined (household and hospital) sewage of a sewage pumping station (SPS) and a large municipal sewage treatment plant (STP) were predicted and measured within a field trial by collecting and analyzing defined composite samples over a time period of 1 week. The use of pharmacokinetic data and precise information on the administration of the individual medicinal formulation was found to be essential for the validity of the predicted data. The measured data confirmed the validity of the predicted loads with recoveries between 63 and 102% for carbamazepine and around 35% for diclofenac in the hospital wastewater. A comparison of the weekly loads predicted and measured in the influents and effluents of a STP in Berlin (Germany) yielded a very low removal rate for diclofenac (less than 15%) and a removal rate of up to 40% for carbamazepine. In total, 2.0 kg of carbamazepine per week (105 kg/a) and 4.4 kg of diclofenac per week (226 kg/a) were discharged into Berlin's surface water by the municipal STP, which treats both household sewage from approximately one million inhabitants and large amounts of hospital effluents (approximately 12,060 hospital beds).
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http://dx.doi.org/10.1016/j.jhazmat.2005.03.007DOI Listing
July 2005

Determination of sorption coefficients of pharmaceutically active substances carbamazepine, diclofenac, and ibuprofen, in sandy sediments.

Chemosphere 2005 Jul;60(2):245-53

Institute of Applied Geosciences, Technical University Berlin, Ackerstr. 71-76, 13355 Berlin, Germany.

Laboratory batch studies were conducted to characterize the sorption behavior of three pharmaceutically active substances (carbamazepine, diclofenac, and ibuprofen) in different sediment types. The sediments were natural sandy sediments from the water saturated zone and the unsaturated zone in the Berlin (Germany) area. They are characterized as medium and fine-grained sands, both with low organic carbon content. The results of the experiments show that sorption coefficients were generally quite low. Distribution coefficients (K(d) values) determined by the batch experiments varied from 0.21 to 5.32 for carbamazepine, 0.55 to 4.66 for diclofenac, and 0.18 to 1.69 for ibuprofen. Comparison of the organic carbon normalized sorption coefficient K(OC) values based on correlation equations with actual experimental data revealed that the calculated data for carbamazepine is of the same order as the experimental data. For diclofenac and ibuprofen the calculated values are much higher than the experimental data, showing a much higher mobility of diclofenac and ibuprofen in natural aquifer sediments than indicated by correlation equations based on octanol water distribution coefficients.
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http://dx.doi.org/10.1016/j.chemosphere.2004.12.042DOI Listing
July 2005

Rejection of emerging organic micropollutants in nanofiltration-reverse osmosis membrane applications.

Water Environ Res 2005 Jan-Feb;77(1):40-8

Environmental Science and Engineering Division, Colorado School of Mines, Golden 80401-1887, USA.

The rejection of emerging trace organics by a variety of commercial reverse osmosis (RO), nanofiltration (NF), and ultra-low-pressure RO (ULPRO) membranes was investigated using TFC-HR, NF-90, NF-200, TFC-SR2, and XLE spiral membrane elements (Koch Membrane Systems, Wilmington, Massachusetts) to simulate operational conditions for drinking-water treatment and wastewater reclamation. In general, the presence of effluent organic matter (EfOM) improved the rejection of ionic organics by tight NF and RO membranes, as compared to a type-II water matrix (adjusted by ionic strength and hardness), likely as a result of a decreased negatively charged membrane surface. Rejection of ionic pharmaceutical residues and pesticides exceeded 95% by NF-90, XLE, and TFC-HR membranes and was above 89% for the NF-200 membrane. Hydrophobic nonionic compounds, such as bromoform and chloroform, exhibited a high initial rejection, as a result of both hydrophobic-hydrophobic solute-membrane interactions and steric exclusion, but rejection decreased significantly after 10 hours of operation because of partitioning of solutes through the membranes. This resulted in a partial removal of disinfection byproducts by the RO membrane TFC-HR. In a type-II water matrix, the effect of increasing feed water recoveries on rejection of hydrophilic ionic and nonionic compounds was compound-dependent and not consistent for different membranes. The presence of EfOM, however, could neutralize the effect of hydrodynamic operating condition on rejection performance. The ULPRO and tight NF membranes were operated at lower feed pressure, as compared to the TFC-HR, and provided a product water quality similar to a conventional RO membrane, regarding trace organics of interest.
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http://dx.doi.org/10.2175/106143005x41609DOI Listing
May 2005

Determination of estrogenic steroids in surface water and wastewater by liquid chromatography-electrospray tandem mass spectrometry.

J Sep Sci 2005 Jan;28(1):52-8

Institute of Food Chemistry, Technical University Berlin, Gustav-Meyer-Allee 25, 13355 Berlin, Germany.

An analytical method is presented which permits trace level determination of 17alpha-ethynylestradiol (EE2), 17beta-estradiol (E2), and estrone (E1). Using this method, the estrogenic steroids were analyzed in drinking water, surface water, and wastewater (sewage influents and effluents) at concentrations down to 0.1 ng/L. Sample volumes between 100 and 500 mL are concentrated using automated solid-phase extraction. Analysis is performed by liquid chromatography with detection by tandem mass spectrometry. Applying simple clean-up procedures and internal standard calibration, recovery losses resulting from matrix-dependent ion suppression during electrospray ionization could be compensated for all of the investigated compounds. Recoveries around 100% were obtained for all analytes after correction using the internal standards. Limits of quantification (LOQ) were between 0.1 and 0.4 ng/L for purified sewage, surface, ground, and drinking water and between 1 and 2 ng/L in the case of raw sewage. Water treatment by wastewater treatment plants (WWTPs) or by a surface water treatment plant affected the removal of all estrogenic steroids. Thus, E1, E2, and EE2 were removed in the municipal WWTPs to the extent of 93%, 93%, and 80%, respectively. In the effluents of the WWTP in Ruhleben (Berlin, Germany), E1, E2, and EE2 were detected at the low ng/L level. E2 and EE2 were, however, not present in the Berlin surface water above the LOQ (0.2 ng/L). E1 was the only compound that could be detected in surface water samples. After additional surface water treatment it was still detectable but only at trace-level concentrations with a mean value of 0.16 ng/L.
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http://dx.doi.org/10.1002/jssc.200301727DOI Listing
January 2005

Determination of polar drug residues in sewage and surface water applying liquid chromatography-tandem mass spectrometry.

Anal Chem 2004 Nov;76(22):6548-54

Institute of Food Chemistry, Technical University Berlin, Gustav-Meyer-Allee 25, 13355 Berlin, Germany.

A simple and rapid method is presented for the trace-level analysis of 10 polar pharmaceutical residues in various types of water samples from the aquatic environment. Using this method, the pharmaceuticals and several drug metabolites can be analyzed in drinking and surface waters and in wastewater (treated and untreated sewage) at concentrations down to 0.01 microg/L. Samples are prepared by a simple in situ derivatization enabling the preconcentration of very polar metabolites by automated solid-phase extraction. The analytes were separated by liquid chromatography with tandem mass spectrometric detection and quantified by comparison with an internal standard. Limits of quantification were between 0.01 and 0.02 microg/L for three phenazone-type pharmaceuticals, six of their metabolites, and the antiepileptic drug carbamazepine. Except for dimethylaminophenazone, recoveries for all analytes were between 87 and 117% for raw and purified sewage, groundwater, and surface and drinking water. Investigations of some environmental samples revealed that sewage and surface water treatment causes a slight reduction of the concentrations of some analytes whereas other compounds were persistent during water treatment. Thus, some compounds were detected at the low-microgram per liter level in sewage effluents of wastewater treatment plants in Berlin (Germany) and were also found at high-nanogram per liter concentrations in Berlin surface water samples.
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http://dx.doi.org/10.1021/ac049324mDOI Listing
November 2004

Detection and identification of phenazone-type drugs and their microbial metabolites in ground and drinking water applying solid-phase extraction and gas chromatography with mass spectrometric detection.

J Chromatogr A 2004 Oct;1050(2):201-9

Institute of Food Chemistry, Technical University Berlin, Sekr TIB 4/3-1, Gustav-Meyer-Allee 25, 13355 Berlin, Germany.

A new analytical method applying in situ derivatization was developed to enable the extraction of polar drug metabolites from water samples by solid-phase extraction (SPE). An additional derivatization by silylation was used to enhance the sensitivity of analyte detection by gas chromatography-mass spectrometry (GC-MS). Thus, the two metabolites 1,5-di-methyl-1,2-dehydro-3-pyrazolone (DP) and 4-(2-methylethyl)-1,5-dimethyl-1,2-dehydro-3-pyrazolone (PDP), postulated for the degradation of phenazone and propyphenazone, were identified and detected up to the microg/L level in raw and drinking water samples from public water supply.
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http://dx.doi.org/10.1016/j.chroma.2004.08.051DOI Listing
October 2004

Transport of pharmaceutically active compounds in saturated laboratory columns.

Ground Water 2004 Sep-Oct;42(5):767-73

Institute of Applied Geosciences, Technical University Berlin, Ackerstr. 71-76, D-13355 Berlin, Germany.

Occurrences of pharmaceutically active compounds in surface water and sewage water have been widely reported. Investigations show the presence of several classes of pharmaceuticals such as antirheumatics (e.g., diclofenac), analgesics (e.g., propyphenazone), and blood lipid regulators (clofibric acid), even in ground water. Compared to their occurrences in surface water, however, the reported incidences of drugs in ground water are much rarer. This may be due to the input, but also to transport processes and degradation in the aquifer. In field studies investigating ground water sampled at a bank infiltration site at Lake Tegel, Berlin, Germany, clofibric acid was found at concentrations up to 290 ng/L, and propyphenazone up to 250 ng/L, whereas concentrations of diclofenac were around the detection limit. The aim of this study was to investigate the ground water transport behavior of the pharmaceuticals clofibric acid, propyphenazone, and diclofenac with a laboratory soil column experiment. Results show that clofibric acid exhibits no degradation and almost no retardation (Rf = 1.1). Diclofenac (Rf = 2.0) and propyphenazone (Rf = 1.6) are retarded, whereas significant degradation was not observed for both pharmaceuticals under the prevailing conditions in the soil column. We conclude that the concentration distribution of the pharmaceuticals at the bank filtration site at Lake Tegel is controlled by sorption, desorption, and input variation, rather than by degradation.
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http://dx.doi.org/10.1111/j.1745-6584.2004.tb02730.xDOI Listing
December 2004

Identification and significance of phenazone drugs and their metabolites in ground- and drinking water.

Chemosphere 2002 Nov;49(6):539-44

Residues of three phenazone-type pharmaceuticals have been identified in routine analyses of groundwater samples from selected areas in the north-western districts of Berlin, Germany. Phenazone, propiphenazone, and dimethylaminophenazone have been detected in some wells at concentrations up to the low microg/l-level. Additionally, three phenazone-type metabolites namely 1-acetyl-1-methyl-2-dimethyl-oxamoyl-2-phenylhydrazide (AMDOPH), 1-acetyl-1-methyl-2-phenylhydrazide, and dimethyloxalamide acid-(N'-methyl-N-phenyl)-hydrazide have also been identified in these groundwater samples. The residues are suspected to originate from former production spills of a pharmaceutical plant located in a city north of Berlin. It was observed that with the exception of AMDOPH all other residues were efficiently removed during conventional drinking water treatment. The drug metabolite AMDOPH deriving from dimethylaminophenazone residues was found at concentrations of 0.9 microg/l in finished drinking water. However, a following study on the toxicological relevance of the AMDOPH residues has shown that there is no toxicological harm for humans at the low concentrations of AMDOPH observed in Berlin drinking water.
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http://dx.doi.org/10.1016/s0045-6535(02)00387-9DOI Listing
November 2002

Occurrence, fate, and removal of pharmaceutical residues in the aquatic environment: a review of recent research data.

Authors:
Thomas Heberer

Toxicol Lett 2002 May;131(1-2):5-17

Institute of Food Chemistry, Technical University of Berlin, Sekr. TIB 4/3-1, Gustav-Meyer-Allee 25, 13355 Berlin, Germany.

The occurrence and fate of pharmaceutically active compounds (PhACs) in the aquatic environment has been recognized as one of the emerging issues in environmental chemistry. In some investigations carried out in Austria, Brazil, Canada, Croatia, England, Germany, Greece, Italy, Spain, Switzerland, The Netherlands, and the U.S., more than 80 compounds, pharmaceuticals and several drug metabolites, have been detected in the aquatic environment. Several PhACs from various prescription classes have been found at concentrations up to the microg/l-level in sewage influent and effluent samples and also in several surface waters located downstream from municipal sewage treatment plants (STPs). The studies show that some PhACs originating from human therapy are not eliminated completely in the municipal STPs and are, thus, discharged as contaminants into the receiving waters. Under recharge conditions, polar PhACs such as clofibric acid, carbamazepine, primidone or iodinated contrast agents can leach through the subsoil and have also been detected in several groundwater samples in Germany. Positive findings of PhACs have, however, also been reported in groundwater contaminated by landfill leachates or manufacturing residues. To date, only in a few cases PhACs have also been detected at trace-levels in drinking water samples.
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http://dx.doi.org/10.1016/s0378-4274(02)00041-3DOI Listing
May 2002
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