Trace determination of tamoxifen and 5-fluorouracil in hospital and urban wastewaters

Tauxe-Wuersch, Annick; Alencastro, Luiz Felippe De; Grandjean, Dominique; Tarradellas, J.

doi:10.1080/03067310500291502

Cited by 53 publications

(23 citation statements)

References 45 publications

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“…Three studies were found in which the chemists tried to measure 5FU in sewage effluents in Spain, Switzerland, and the United States, but these resulted in no detections [25,45,46]. The reported LODs were 15 ng/L to 21 ng/L; but using the prediction method described above, the mean effluent values would be expected to be 0.6 ng/L to 1.0 ng/L, which would…”

Section: Methodsmentioning

confidence: 99%

“…This is not an unreasonable exercise, given the common administration of chemotherapy in the outpatient departments of most city hospitals [7]. However, a high proportion of these studies failed to find the selected cytostatic drugs [19][20][21][22][23][24][25], leaving the reader not knowing whether the drug was not actually used in the city/country studied, was eliminated successfully in sewage treatment, or was present but at a concentration below the limit of detection (LOD).…”

Section: Introductionmentioning

confidence: 99%

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Predicting concentrations of the cytostatic drugs cyclophosphamide, carboplatin, 5‐fluorouracil, and capecitabine throughout the sewage effluents and surface waters of europe

Johnson

Oldenkamp

Dumont

et al. 2013

Enviro Toxic and Chemistry

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The present study evaluated the potential environmental concentrations of 4 cytostatic (also known as cytotoxic) drugs in rivers. The antimetabolite 5‐fluorouracil (5FU) and its pro‐drug capecitabine were examined based on their very high use rates, cyclophosphamide (CP) for its persistence, and carboplatin for its association with the metal element platinum. The study combined drug consumption information across European countries, excretion, national water use, and sewage removal rates to derive sewage effluent values across the continent. Results showed considerable variation in the popularity of individual cytostatic drugs across Europe, including a 28‐fold difference in 5FU use and 15‐fold difference in CP use. Such variations could have a major effect on the detection of these compounds in effluent or river water. Overall, capecitabine and CP had higher predicted levels in effluent than 5FU or carboplatin. Predicted effluent values were compared with measurements in the literature, and many non‐detects could be explained by insufficient limits of detection. Linking the geographic based water resources model GWAVA with this information allowed water concentrations throughout 1.2 million km of European rivers to be predicted. The 90th percentile (worst case) prediction indicated that, with the exception of capecitabine, more than 99% of Europe's rivers (by length) would have concentrations below 1 ng/L for these cytostatic drugs. For capecitabine, 2.2% of river length could exceed 1 ng/L. Environ Toxicol Chem 2013;32:1954–1961. © 2013 SETAC

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Predicting concentrations of the cytostatic drugs cyclophosphamide, carboplatin, 5‐fluorouracil, and capecitabine throughout the sewage effluents and surface waters of europe

Johnson

Oldenkamp

Dumont

et al. 2013

Enviro Toxic and Chemistry

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“…The dose‐dependent elimination half‐life of 5‐FU is 5 to 20 minutes. Depending on various references, about 10% (with a very wide range of 2–89%; cited by Weissbrodt et al 2009), less than 15% (Arzneimittelkompendium 2007a), or 11 to 20% (cited by Johnson et al 2008) of administered 5‐FU is excreted as 5‐FU, mainly by the renal pathway.…”

Section: Methodsmentioning

confidence: 99%

Combined environmental risk assessment for 5‐fluorouracil and capecitabine in Europe

Straub

2010

Integr Envir Assess & Manag

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An environmental risk assessment (ERA) was made for the old cytostatic active pharmaceutical ingredient 5-fluorouracil (5-FU) and for capecitabine (CAP), which is a prodrug of 5-FU. This ERA is based on published and company internal data as well as new test results for physicochemical, human metabolism, biodegradability, environmental partitioning and fate, and acute and chronic ecotoxicity properties of the active substance 5-FU as well as on use sales data for 5-FU and CAP in Europe. Predicted environmental concentrations (PECs) were extrapolated following the EMEA 2006 Guideline on ERA for human pharmaceuticals and the European Union 2003 Technical Guidance Document (TGD) for risk assessment as well as the TGD-based application EUSES v2.0. Actual amounts sold were taken from IMS Health Databases, in order to refine the default use and EMEA penetration factor as well as the PECs. Moreover, available measured environmental concentrations (MECs) were used to supplement PECs. A predicted no-effect concentration (PNEC) for 5-FU was derived from chronic ecotoxicity data. Except for the simplistic EMEA Phase I default PEC, the risk characterization by PEC:PNEC and MEC:PNEC ratios for various environmental compartments resulted in no significant risk. As the EMEA Phase I PEC does not integrate documented human metabolism and environmental degradation, in contrast to refined PEC derivations, it is inferred that the current use of CAP and 5-FU does not present any evident risk to the environment. An additional evaluation of persistence, bioaccumulation, and toxicity (PBT) properties supports the conclusion of no significant environmental risk for 5-FU and CAP.

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“…Few data are available for the environmental occurrence of tamoxifen, although concentrations reported in UK estuarine surface waters ranged from 27 to 212 ng/L [38], significantly lower than the overall adverse NOEC and LOEC values reported in the present study. Tamoxifen was detected in hospital wastewater, residential area, and influents to sewage treatment plants at concentrations ranging from 1 to 4 ng/L [39]; degradation and adsorption of tamoxifen to particles were suggested as potential mechanisms for removal from wastewaters. Although no acute LC50 value is available for tamoxifen citrate to fathead minnows, the most acutely sensitive fish species from available data (bluegill sunfish) has a 96‐h LC50 value of 230 μg/L (AstraZeneca, Brixham Environmental Laboratory, Devon, UK, unpublished data).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the reproductive effects of tamoxifen citrate in partial and full life‐cycle studies using fathead minnows (Pimephales Promelas)

Williams

Caunter

Lillicrap

et al. 2007

Enviro Toxic and Chemistry

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Laboratory studies were conducted to investigate potential adverse effects on development, growth, reproduction and biomarker responses (vitellogenin [VTG] and gonad histology) in fathead minnows (Pimephales promelas) exposed to tamoxifen citrate. Based on the results of a partial life cycle study (nominal [mean measured] concentrations ranged from 0.18 [0.11] to 18 [15.74] microg/L), a 284-d fish full life-cycle (FFLC) flow-through study was conducted using newly fertilized embryos (<24 h postfertilization) exposed to nominal (mean measured) concentrations of 14C-tamoxifen citrate that ranged from 0.01 (0.007) to 5.12 (4.08) microg/L. Triethylene glycol (2.0 microl/L) was used as a solvent carrier, with 17beta-estradiol (E2) as a positive control (nominal 0.1 microg/L). Among the biomarkers measured, significant effects on VTG and gonad histology were observed, although these results required care in their interpretation. Among important population-relevant endpoints, no effects on reproduction were observed at nominal concentrations < or = 5.12 microg/L. Effects on growth (length and weight) were observed in some treatments; however, some of these showed irregular concentration-response relationships, which made interpretation uncertain, or were deemed transient in nature (e.g., reduction in growth of F1 28-d posthatch larval fish at nominal concentrations of 0.08, 0.64, and 5.12 microg/L) and judged not to be biologically significant. Interpretation of results from fish chronic studies is challenging and frequently calls for scientific judgement about statistical and biological significance and what constitutes an adverse effect. Using the principles used in mammalian toxicology studies, data from partial and FFLC studies were evaluated from both statistical and biological perspectives in order to determine no-observed-adverse effect concentrations (expressed as (adverse)NOEC) for use in environmental risk assessment. Careful consideration of both biological and statistical outcomes from these studies suggested overall (adverse)NOEC concentration and lowest-observed-effect concentration ((adverse)LOEC) values for tamoxifen citrate of 5.12 microg/L and 5.6 microg/L, respectively.

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Trace determination of tamoxifen and 5-fluorouracil in hospital and urban wastewaters

Cited by 53 publications

References 45 publications

Predicting concentrations of the cytostatic drugs cyclophosphamide, carboplatin, 5‐fluorouracil, and capecitabine throughout the sewage effluents and surface waters of europe

Predicting concentrations of the cytostatic drugs cyclophosphamide, carboplatin, 5‐fluorouracil, and capecitabine throughout the sewage effluents and surface waters of europe

Combined environmental risk assessment for 5‐fluorouracil and capecitabine in Europe

Evaluation of the reproductive effects of tamoxifen citrate in partial and full life‐cycle studies using fathead minnows (Pimephales Promelas)

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