Transformation of Tamoxifen and its Major Metabolites During Water Chlorination: Identification and in Silico Toxicity Assessment of Their Disinfection Byproducts
Abstract
The selective estrogen receptor modulator tamoxifen is the most commonly used drug for the treatment and prevention of breast cancer. Tamoxifen is considered as a pro-drug since it is known to exert its pharmacological effect through its major active metabolites, 4-hydroxy-tamoxifen and 4-hydroxy-N-desmethyl-tamoxifen, which are mainly excreted in the urine in the days following administration. In the present work, the reactivity of tamoxifen and its major active metabolites in free chlorine-containing water was investigated for the first time. Under the studied chlorination conditions, tamoxifen was fairly stable whereas its metabolites were quickly degraded. A total of thirteen chlorinated byproducts were tentatively identified by ultra-high performance liquid chromatography coupled to high-resolution hybrid quadrupole-Orbitrap tandem mass spectrometry. Time-course profiles of the identified byproducts were followed in real wastewater samples under conditions that simulate wastewater disinfection. A preliminary assessment of their acute aquatic toxicity at two trophic levels by means of quantitative structure-activity relationship models showed that the identified byproducts were up to 110-fold more toxic than the parent compounds.
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Common drugs including metformin, diclofenac, and tamoxifen entering freshwater sources are subject to direct chlorination causing drinking water contamination associated with largely unexplored implications for human health.
“For example, common drugs including metformin, diclofenac, and tamoxifen entering freshwater sources are subject to direct chlorination causing drinking water contamination associated with largely unexplored implications for human health (126–129).”
From Hypochlorous Acid: From Innate Immune Factor and Environmental Toxicant to Chemopreventive Agent Targeting Solar UV-Induced Skin Cancer (2022) · cites this paper as [129]
PPCPs introduced into the water supply are subject to HOCl-mediated chlorination and subsequent formation of CBPs.
“Additionally, PPCPs introduced into the water supply are subject to HOCl-mediated chlorination and subsequent formation of CBPs.”
From Hypochlorous Acid: From Innate Immune Factor and Environmental Toxicant to Chemopreventive Agent Targeting Solar UV-Induced Skin Cancer (2022) · cites this paper as [129]
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- Authors
- Negreira, N., Regueiro, J., López de Alda, M., & Barceló, D.
- Affiliations
- Institute of Environmental Assessment and Water Research (ES)
- Universidade de Vigo (ES)
- Universitat de Girona (ES)
- Venue
- Water Research
- Publisher
- Elsevier BV
- Published
- 2015-11
- Volume
- 85
- Pages
- 199-207
- ISSN
- 0043-1354 (ISSN-L)
- OpenAlex
- W1661314417
- Cited by
- 66
- References
- 39
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 8 · 2020: 13 · 2019: 3 · 2018: 4 · 2017: 9 · 2016: 7 · 2015: 1
- FWCI
- 4.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Water Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- CYTOTHREAT (265264)
- SOLUTIONS (603437)
- Generalitat de Catalunya (2014 SGR 418—Water and Soil Quality Unit, 2014 SGR 291—ICRA)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Water Treatment and Disinfection
- Physical Sciences › Environmental Science › Pollution › Pharmaceutical and Antibiotic Environmental Impacts
- Physical Sciences › Environmental Science › Water Science and Technology › Advanced oxidation water treatment
- Keywords
- tamoxifen, chlorination by-products, free chlorine, drug degradation, wastewater disinfection, aquatic toxicity, QSAR, estrogen receptor modulators, drug metabolites
- MeSH terms
- Chromatography, High Pressure Liquid, Disinfection, Tamoxifen, Water Pollutants, Chemical, Water Purification, Quantitative Structure-Activity Relationship, Tandem Mass Spectrometry, Halogenation
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