Assessing the risks of capecitabine and its active metabolite 5-fluorouracil to freshwater biota

Abstract

Capecitabine (CAP, prodrug) and 5-fluorouracil (5-FU, its active metabolite) are two of the most prominent cytostatics, for which no clear picture can be drawn regarding potential concentrations of effect for freshwater biota, with CAP being grouped in the least studied cytostatic, whereas 5-FU has been classified as of no and of high environmental risk. Accordingly, the present work aimed to assess the ecotoxicity of CAP and 5-FU in three freshwater species, which included a 72-h assay with the producer Raphidocelis subcapitata; a 96-h assay with the invertebrate secondary consumer Hydra viridissima; and a 96-h assay with embryos of the vertebrate secondary consumer Danio rerio. The following endpoints were monitored: yield and population growth rate for the algae; mortality, morphological alterations, and post-exposure feeding rates for the cnidarian; and mortality, hatching, and malformations for the fish. Overall, organisms’ sensitivity to CAP decreased in the following order: R. subcapitata > H. viridissima > D. rerio, whereas for 5-FU, it decreased in the following order: H. viridissima > D. rerio > R. subcapitata. For CAP, no median lethal effective concentrations (LC/EC50) were possible to compute for D. rerio, with no significant mortality or malformations registered in embryos exposed at concentrations up to 800 mg L−1. For R. subcapitata, the EC50s were 0.077 and 0.63 mg L−1 for yield and growth rate, respectively, and for H. viridissima, the EC50,30 min for feeding was 22.0 mg L−1. For 5-FU, no EC50s could be computed for R. subcapitata, whilst the EC50s for H. viridissima mortality and feeding were 55.4 and 67.9 mg L−1, respectively, and for D. rerio, the LC50,96 h and EC50,96 h (hatching and abnormalities) were 4546, 4100, and 2459 mg L−1, respectively. Assuming similar modes of action for both compounds and their co-occurrence, the combined risk quotient of the two chemicals was determined to be 7.97, which represents a risk for freshwater biota. Anticipating the increased consumption of these compounds and cancer development trends worldwide, these impacts may be further aggravated.

Features of the microalga Raphidocelis subcapitata: physiology and applications

“…Considering that in nature toxics are not present single but in a complex matrix of chemical species that can interact with each other leading to synergistic, antagonistic, or and unpredictable effects, R. subcapitata has been used in the evaluation of mixtures (mainly binary) of toxics (Chèvre and Gregorio 2013 ). These studies started with the evaluation of pesticides (Mansano et al 2017 ; Moreira et al 2020 ) and have been extended to other classes of toxics, such as metals (Reis et al 2021 ; Gebara et al 2023 ), antibiotics (Chang et al 2022 ), cytostatic drugs (Venâncio et al 2023 ), biocides (Yang et al 2008 ), and PAHs (Kreutzer et al 2022 ).…”

Adsorption of 5-fluorouracil, an anticancer drug, in faujasite-type zeolites: understanding storage and release with density functional theory calculations

“…50 The toxicity (including genotoxicity) of 5-FU, alone and in mixtures, has been investigated for various aquatic organisms, and estimations of the arising environmental hazard potential generally agree that its potential environmental impact is non-negligible. 51–55 This highlights the need to develop efficient removal strategies from contaminated waters, especially hospital effluents. Among other technological options, adsorption-based processes using activated carbons have been proposed for 5-FU removal.…”

Adsorption of the anticancer drug 5-fluorouracil in faujasite-type zeolites studied with density functional theory calculations

“…46 The toxicity (including genotoxicity) of 5-FU, alone and in mixtures, has been investigated for various aquatic organisms, and estimations of the arising environmental hazard potential generally agree that its potential environmental impact is non-negligible. [47][48][49][50][51] This highlights the need to develop efficient removal strategies from contaminated waters, especially hospital effluents. Among other technological options, adsorption-based processes using activated carbons have been proposed for 5-FU removal.…”