The DOI matches its Crossref record; 89 of the 89 references it cites were found in a registry or an index.
Pharmaceutical metabolites in the environment: Analytical challenges and ecological risks
Open accessAbstract
The occurrence of human and veterinary pharmaceuticals in the environment has been a subject of concern for the past decade because many of these emerging contaminants have been shown to persist in soil and water. Although recent studies indicate that pharmaceutical contaminants can pose long-term ecological risks, many of the investigations regarding risk assessment have only considered the ecotoxicity of the parent drug, with very little attention given to the potential contributions that metabolites may have. The scarcity of available environmental data on the human metabolites excreted into the environment or the microbial metabolites formed during environmental biodegradation of pharmaceutical residues can be attributed to the difficulty in analyzing trace amounts of previously unknown compounds in complex sample matrices. However, with the advent of highly sensitive and powerful analytical instrumentations that have become available commercially, it is likely that an increased number of pharmaceutical metabolites will be identified and included in environmental risk assessment. The present study will present a critical review of available literature on pharmaceutical metabolites, primarily focusing on their analysis and toxicological significance. It is also intended to provide an overview on the recent advances in analytical tools and strategies to facilitate metabolite identification in environmental samples. This review aims to provide insight on what future directions might be taken to help scientists in this challenging task of enhancing the available data on the fate, behavior, and ecotoxicity of pharmaceutical metabolites in the environment.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Occurrence of drugs in German sewage treatment plants and rivers
Ternes, T. A. (1998) · Water Research · doi:10.1016/s0043-1354(98)00099-2 · Cited by 3,425
Human Pharmaceuticals in the Aquatic Environment: A Challenge to Green Chemistry
Khetan, S. K., & Collins, T. J. (2007) · Chemical Reviews · doi:10.1021/cr020441w · Cited by 1,145
The ToxCast Program for Prioritizing Toxicity Testing of Environmental Chemicals
Dix, D. J., Houck, K. A., Martin, M. T., Richard, A. M., Setzer, R. W., & Kavlock, R. J. (2007) · Toxicological Sciences · doi:10.1093/toxsci/kfl103 · Cited by 1,012
Identification of Estrogenic Chemicals in STW Effluent. 2. In Vivo Responses in Trout and Roach
Routledge, E. J., Sheahan, D., Desbrow, C., Brighty, G. C., Waldock, M., & Sumpter, J. P. (1998) · Environmental Science & Technology · doi:10.1021/es970796a · Cited by 995
Occurrence and fate of pharmaceutical products and by-products, from resource to drinking water
Mompelat, S., Le Bot, B., & Thomas, O. (2009) · Environment International · doi:10.1016/j.envint.2008.10.008 · Cited by 950
Bendz, D., Paxéus, N. A., Ginn, T. R., & Loge, F. J. (2005) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2005.03.012 · Cited by 795
The Cytochrome P450 Superfamily: Biochemistry, Evolution and Drug Metabolism in Humans
P.B. Danielson, B. S. P. (2002) · Current Drug Metabolism · doi:10.2174/1389200023337054 · Cited by 772
Göbel, A., Thomsen, A., McArdell, C. S., Joss, A., & Giger, W. (2005) · Environmental Science & Technology · doi:10.1021/es048550a · Cited by 760
Ternes, T. A., Kreckel, P., & Mueller, J. (1999) · Science of The Total Environment · doi:10.1016/s0048-9697(98)00335-0 · Cited by 734
Glassmeyer, S. T., Furlong, E. T., Kolpin, D. W., Cahill, J. D., Zaugg, S. D., Werner, S. L., Meyer, M. T., & Kryak, D. D. (2005) · Environmental Science & Technology · doi:10.1021/es048120k · Cited by 708
Investigating the environmental transport of human pharmaceuticals to streams in the United Kingdom
Ashton, D., Hilton, M., & Thomas, K. V. (2004) · Science of The Total Environment · doi:10.1016/j.scitotenv.2004.04.062 · Cited by 689
Fate of natural estrogen conjugates in municipal sewage transport and treatment facilities
DASCENZO, G., DICORCIA, A., GENTILI, A., MANCINI, R., MASTROPASQUA, R., NAZZARI, M., & SAMPERI, R. (2003) · The Science of The Total Environment · doi:10.1016/s0048-9697(02)00342-x · Cited by 582
Determination of select antidepressants in fish from an effluent-dominated stream
Brooks, B. W., Chambliss, C. K., Stanley, J. K., Ramirez, A., Banks, K. E., Johnson, R. D., & Lewis, R. J. (2005) · Environmental Toxicology and Chemistry · doi:10.1897/04-081r.1 · Cited by 564
Relative Potencies and Combination Effects of Steroidal Estrogens in Fish
Thorpe, K. L., Cummings, R. I., Hutchinson, T. H., Scholze, M., Brighty, G., Sumpter, J. P., & Tyler, C. R. (2003) · Environmental Science & Technology · doi:10.1021/es0201348 · Cited by 514
Weigel, S., Berger, U., Jensen, E., Kallenborn, R., Thoresen, H., & Hühnerfuss, H. (2004) · Chemosphere · doi:10.1016/j.chemosphere.2004.04.015 · Cited by 469
Vanderford, B. J., & Snyder, S. A. (2006) · Environmental Science & Technology · doi:10.1021/es0613198 · Cited by 457
Batt, A. L., Bruce, I. B., & Aga, D. S. (2006) · Environmental Pollution · doi:10.1016/j.envpol.2005.10.010 · Cited by 449
Self-citationHuman Pharmaceuticals in the Aquatic Environment a Review
Jones, O. A. H., Voulvoulis, N., & Lester, J. N. (2001) · Environmental Technology · doi:10.1080/09593330.2001.11090873 · Cited by 426
Miao, X.-S., Yang, J.-J., & Metcalfe, C. D. (2005) · Environmental Science & Technology · doi:10.1021/es050261e · Cited by 409
Repeating History: Pharmaceuticals in the Environment
Ankley, G. T., Brooks, B. W., Huggett, D. B., & Sumpter, A. J. P. (2007) · Environmental Science & Technology · doi:10.1021/es072658j · Cited by 390
Sumpter, J. P., & Johnson, A. C. (2005) · Environmental Science & Technology · doi:10.1021/es048504a · Cited by 384
Peer Reviewed: When Synthetic Chemicals Degrade in the Environment
Boxall, A. B. A., Sinclair, C. J., Fenner, K., Kolpin, D., & Maund, S. J. (2004) · Environmental Science & Technology · doi:10.1021/es040624v · Cited by 373
Bedner, M., & MacCrehan, W. A. (2006) · Environmental Science & Technology · doi:10.1021/es0509073 · Cited by 366
Segner, H. (2006) · Environmental Science & Technology · doi:10.1021/es051791d · Cited by 361
Effects of Three Pharmaceutical and Personal Care Products on Natural Freshwater Algal Assemblages
Wilson, B. A., Smith, V. H., deNoyelles, F., & Larive, C. K. (2003) · Environmental Science & Technology · doi:10.1021/es0259741 · Cited by 348
Environmental Hazard Assessment of Pharmaceuticals
Henschel, K.-P., Wenzel, A., Diedrich, M., & Fliedner, A. (1997) · Regulatory Toxicology and Pharmacology · doi:10.1006/rtph.1997.1102 · Cited by 338
Miao, X.-S., & Metcalfe, C. D. (2003) · Analytical Chemistry · doi:10.1021/ac030082k · Cited by 330
Ogilvie, B. W., Zhang, D., Li, W., Rodrigues, A. D., Gipson, A. E., Holsapple, J., Toren, P., & Parkinson, A. (2006) · Drug Metabolism and Disposition · doi:10.1124/dmd.105.007633 · Cited by 330
Lienert, J., Güdel, K., & Escher, B. I. (2007) · Environmental Science & Technology · doi:10.1021/es0627693 · Cited by 329
Role of Metabolism in Drug-Induced Idiosyncratic Hepatotoxicity
Walgren, J. L., Mitchell, M. D., & Thompson, D. C. (2005) · Critical Reviews in Toxicology · doi:10.1080/10408440590935620 · Cited by 322
Liquid Chromatography – Mass Spectrometry: An Introduction
Ardrey, R. E. (2003) · Analytical Techniques in the Sciences · doi:10.1002/0470867299 · Cited by 315
Göbel, A., McArdell, C. S., Suter, M. J.-F., & Giger, W. (2004) · Analytical Chemistry · doi:10.1021/ac0496603 · Cited by 310
Hummel, D., Löffler, D., Fink, G., & Ternes, T. A. (2006) · Environmental Science & Technology · doi:10.1021/es061740w · Cited by 299
Occurrence of sulfonamide antimicrobials in private water wells in Washington County, Idaho, USA
Batt, A. L., Snow, D. D., & Aga, D. S. (2006) · Chemosphere · doi:10.1016/j.chemosphere.2006.01.029 · Cited by 298
Self-citationDrug Bioactivation Covalent Binding to Target Proteins and Toxicity Relevance
Zhou, S., Chan, E., Duan, W., Huang, M., & Chen, Y.-Z. (2005) · Drug Metabolism Reviews · doi:10.1081/dmr-200028812 · Cited by 274
Caldwell, D. J., Mastrocco, F., Hutchinson, T. H., Länge, R., Heijerick, D., Janssen, C., Anderson, P. D., & Sumpter, J. P. (2008) · Environmental Science & Technology · doi:10.1021/es800633q · Cited by 265
Human health risk assessment from the presence of human pharmaceuticals in the aquatic environment
Cunningham, V. L., Binks, S. P., & Olson, M. J. (2009) · Regulatory Toxicology and Pharmacology · doi:10.1016/j.yrtph.2008.10.006 · Cited by 263
Batt, A. L., Kostich, M. S., & Lazorchak, J. M. (2008) · Analytical Chemistry · doi:10.1021/ac800066n · Cited by 254
Pharmaceuticals in the Environment—A Human Risk?
Christensen, F. M. (1998) · Regulatory Toxicology and Pharmacology · doi:10.1006/rtph.1998.1253 · Cited by 243
Topp, E., Monteiro, S. C., Beck, A., Coelho, B. B., Boxall, A. B. A., Duenk, P. W., Kleywegt, S. M., Lapen, D. R., Payne, M., Sabourin, L., et al. (2008) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2008.02.011 · Cited by 238
Reddersen, K., Heberer, T., & Dünnbier, U. (2002) · Chemosphere · doi:10.1016/s0045-6535(02)00387-9 · Cited by 234
Environmental assessment of Norwegian priority pharmaceuticals based on the EMEA guideline
Grung, M., Källqvist, T., Sakshaug, S., Skurtveit, S., & Thomas, K. V. (2008) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2007.10.015 · Cited by 225
Effects and Interactions in an Environmentally Relevant Mixture of Pharmaceuticals
Pomati, F., Orlandi, C., Clerici, M., Luciani, F., & Zuccato, E. (2007) · Toxicological Sciences · doi:10.1093/toxsci/kfm291 · Cited by 224
Corcoran, O., & Spraul, M. (2003) · Drug Discovery Today · doi:10.1016/s1359-6446(03)02749-1 · Cited by 214
Fate of Pharmaceutical and Trace Organic Compounds in Three Septic System Plumes, Ontario, Canada
Carrara, C., Ptacek, C. J., Robertson, W. D., Blowes, D. W., Moncur, M. C., Sverko, E., & Backus, S. M. (2008) · Environmental Science & Technology · doi:10.1021/es070344q · Cited by 210
Determination of Steroidal Hormone Profiles along the Jalle d'Eysines River (near Bordeaux, France)
Labadie, P., & Budzinski, H. (2005) · Environmental Science & Technology · doi:10.1021/es048443g · Cited by 194
Comeau, F., Surette, C., Brun, G. L., & Losier, R. (2008) · Science of The Total Environment · doi:10.1016/j.scitotenv.2008.02.031 · Cited by 193
Metabolic Activation of Diclofenac by Human Cytochrome P450 3A4: Role of 5-Hydroxydiclofenac
Shen, S., Marchick, M. R., Davis, M. R., Doss, G. A., & Pohl, L. R. (1999) · Chemical Research in Toxicology · doi:10.1021/tx9802365 · Cited by 183
Use of the Chiral Pharmaceutical Propranolol to Identify Sewage Discharges into Surface Waters
Fono, L. J., & Sedlak, D. L. (2005) · Environmental Science & Technology · doi:10.1021/es047965t · Cited by 179
LC–NMR coupling technology: recent advancements and applications in natural products analysis
Exarchou, V., Krucker, M., van Beek, T. A., Vervoort, J., Gerothanassis, I. P., & Albert, K. (2005) · Magnetic Resonance in Chemistry · doi:10.1002/mrc.1632 · Cited by 178
In Vitro Assessment of Modes of Toxic Action of Pharmaceuticals in Aquatic Life
Escher, B. I., Bramaz, N., Eggen, R. I. L., & Richter, M. (2005) · Environmental Science & Technology · doi:10.1021/es048590e · Cited by 168
Transformation of the X-ray Contrast Medium Iopromide In Soil and Biological Wastewater Treatment
Schulz, M., Löffler, D., Wagner, M., & Ternes, T. A. (2008) · Environmental Science & Technology · doi:10.1021/es800789r · Cited by 161
The potential of LC-NMR in phytochemical analysis
Wolfender, J., Ndjoko, K., & Hostettmann, K. (2001) · Phytochemical Analysis · doi:10.1002/1099-1565(200101/02)12:1<2::aid-pca552>3.0.co;2-k · Cited by 159
Endocrine-Modulating Substances in the Environment: Estrogenic Effects of Pharmaceutical Products
Arcand‐Hoy, L. D., Nimrod, A. C., & Benson, W. H. (1998) · International Journal of Toxicology · doi:10.1080/109158198226675 · Cited by 159
Gibson, R., Becerril, E., Silva-Castro, V., & Jiménez, B. E. (2007) · Journal of Chromatography A · doi:10.1016/j.chroma.2007.08.056 · Cited by 154
Besse, J.-P., Kausch-Barreto, C., & Garric, J. (2008) · Human and Ecological Risk Assessment An International Journal · doi:10.1080/10807030802235078 · Cited by 150
Reddy, S., Iden, C. R., & Brownawell, B. J. (2005) · Analytical Chemistry · doi:10.1021/ac050699x · Cited by 150
Application of Mass Spectrometry for Metabolite Identification
Ma, S., Chowdhury, S. K., & Alton, K. B. (2006) · Current Drug Metabolism · doi:10.2174/138920006777697891 · Cited by 149
Health Impacts of Estrogens in the Environment, Considering Complex Mixture Effects
Filby, A. L., Neuparth, T., Thorpe, K. L., Owen, R., Galloway, T. S., & Tyler, C. R. (2007) · Environmental Health Perspectives · doi:10.1289/ehp.10443 · Cited by 147
Residue Analysis of the Pharmaceutical Diclofenac in Different Water Types Using ELISA and GC−MS
Deng, A., Himmelsbach, M., Zhu, Q., Frey, S., Sengl, M., Buchberger, W. W., Nießner, R., & Knopp, D. (2003) · Environmental Science & Technology · doi:10.1021/es0341945 · Cited by 145
Gröning, J. A. D., Held, C., Garten, C., Claußnitzer, U., Kaschabek, S. R., & Schlömann, M. (2007) · Chemosphere · doi:10.1016/j.chemosphere.2007.03.037 · Cited by 145
Kasprzyk-Hordern, B., Dinsdale, R., & Guwy, A. (2008) · Talanta: The International Journal of Pure and Applied Analytical Chemistry · doi:10.1016/j.talanta.2007.08.037 · Cited by 144
Sanderson, H., & Thomsen, M. (2009) · Toxicology Letters · doi:10.1016/j.toxlet.2009.02.003 · Cited by 137
Zhou, S. N., Oakes, K. D., Servos, M. R., & Pawliszyn, J. B. (2008) · Environmental Science & Technology · doi:10.1021/es8001162 · Cited by 133
Hernando, M. D., Mezcúa, M., Gómez, M. J., Malato, O., Agüera, A., & Fernández‐Alba, A. R. (2004) · Journal of Chromatography A · doi:10.1016/j.chroma.2004.06.123 · Cited by 131
Quantitative account of propranolol metabolism in urine of normal man.
Walle, T., Walle, U. K., & Olanoff, L. S. (1985) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(25)08146-2 · Cited by 127
Eichhorn, P., Ferguson, P. L., Pérez, S., & Aga, D. S. (2005) · Analytical Chemistry · doi:10.1021/ac050141p · Cited by 112
Self-citationHargus, S. J., Amouzedeh, H. R., Pumford, N. R., Myers, T. G., McCoy, S. C., & Pohl, L. R. (1994) · Chemical Research in Toxicology · doi:10.1021/tx00040a014 · Cited by 107
Reddersen, K., & Heberer, T. (2003) · Journal of Separation Science · doi:10.1002/jssc.200301533 · Cited by 97
Pérez, S., Eichhorn, P., Celiz, M. D., et al. (2006) · Analytical Chemistry · doi:10.1021/ac0518809 · Cited by 96
Self-citationMass spectrometry for identifying pharmaceutical biotransformation products in the environment
Kosjek, T., Heath, E., Petrović, M., & Barceló, . (2007) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2007.10.005 · Cited by 93
Morley, N. J. (2008) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2008.11.004 · Cited by 91
Zuehlke, S., Duennbier, U., & Heberer, T. (2007) · Chemosphere · doi:10.1016/j.chemosphere.2007.06.020 · Cited by 85
Zhao, X., & Metcalfe, C. D. (2008) · Analytical Chemistry · doi:10.1021/ac701633m · Cited by 79
Koehler, A., Hellweg, S., Escher, B. I., & Hungerbühler, K. (2006) · Environmental Science & Technology · doi:10.1021/es060555f · Cited by 74
Yang, Z. (2005) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2005.10.002 · Cited by 72
Skotnicka-Pitak, J., Khunjar, W., Love, N. G., & Aga, D. S. (2009) · Environmental Science & Technology · doi:10.1021/es8026659 · Cited by 68
Self-citationMarques, C. R., Abrantes, N., & Gonçalves, F. J. M. (2004) · Environmental Toxicology · doi:10.1002/tox.20060 · Cited by 65
Matějíček, D., Pelcová, P., & Kubáň, V. (2007) · Journal of Chromatography A · doi:10.1016/j.chroma.2007.09.053 · Cited by 62
Eichhorn, P., & Aga, D. S. (2004) · Analytical Chemistry · doi:10.1021/ac0494127 · Cited by 60
Self-citationTeratogenicity of carbamazepine-10, 11-epoxide and oxcarbazepine in the SWV mouse.
Bennett, G. D., Amore, B. M., Finnell, R. H., et al. (1996) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)21282-4 · Cited by 58
Nałęcz‐Jawecki, G. (2007) · Chemosphere · doi:10.1016/j.chemosphere.2007.07.035 · Cited by 58
Wilson, I. D. (2000) · Journal of Chromatography A · doi:10.1016/s0378-4347(00)00071-2 · Cited by 56
Meng, L.-J., & Sjövall, J. (1997) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/s0378-4347(97)88051-6 · Cited by 41
Applicability and Limitation of QSARs for the Toxicity of Electrophilic Chemicals
Harder, A., Escher, B. I., & Schwarzenbach, R. P. (2003) · Environmental Science & Technology · doi:10.1021/es0341992 · Cited by 38
Novel Drug Metabolites Produced by Functionalization Reactions: Chemistry and Toxicology
Testa, B., & Jenner, P. G. (1978) · Drug Metabolism Reviews · doi:10.3109/03602537808993771 · Cited by 28
Evaluation of in vitro biotransformation of propranolol with HPLC, MS/MS, and two bioassays
Nałęcz‐Jawecki, G., Wójcik, T., & Sawicki, J. (2008) · Environmental Toxicology · doi:10.1002/tox.20310 · Cited by 23
Diagnosis of allergic reactions to sulfonamides
Gruchalla, R. S. (1999) · Allergy · doi:10.1111/j.1398-9995.1999.tb04745.x · Cited by 18
Clement, B., Behrens, D., Amschler, J., Matschke, K., Wolf, S., & Havemeyer, A. (2005) · Life Sciences · doi:10.1016/j.lfs.2004.12.028 · Cited by 14
Cited by
Krauss, M., Singer, H., & Hollender, J. (2010) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-010-3608-9 · Cited by 743
Nanocatalysts and other nanomaterials for water remediation from organic pollutants
Lu, F., & Astruc, D. (2020) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2020.213180 · Cited by 682
Karić, N., Maia, A. S., Teodorović, A., Atanasova, N., Langergraber, G., Crini, G., Ribeiro, A. R. L., & Đolić, M. (2022) · Chemical Engineering Journal Advances · doi:10.1016/j.ceja.2021.100239 · Cited by 466
Schaider, L. A., Rudel, R. A., Ackerman, J. M., Dunagan, S. C., & Brody, J. G. (2014) · Science of The Total Environment · doi:10.1016/j.scitotenv.2013.08.067 · Cited by 304
Hejna, M., Kapuścińska, D., & Aksmann, A. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19137717 · Cited by 279
Metadata
- Authors
- Celiz, M. D., Tso, J., & Aga, D. S.
- Venue
- Environmental Toxicology and Chemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-12-01
- Volume
- 28
- Issue
- 12
- Pages
- 2473-2484
- ISSN
- 0730-7268 (ISSN-L)
- 1552-8618
- OpenAlex
- W2111414121
- Cited by
- 339
- References
- 89
- FWCI
- 14.20
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.