Uptake and bioaccumulation of ionizable pharmaceuticals in aquatic organisms

Marja L. Boström

Research output: ThesisDoctoral Thesis (compilation)

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Pharmaceuticals are found at low concentrations (ng/L) in aquatic environments but bioaccumulation may result in aquatic organisms reaching internal effect levels (µg/L). Environmental hazard assessments include standardized bioaccumulation tests but contrary to the model substances around which the frameworks are built most pharmaceuticals are designed to mimic endogenic chemicals, ionizable, and less lipophilic. Hence, if using the same frameworks one may over- or underestimate hazard. I used the serotonin reuptake inhibitors (SSRIs) fluoxetine and sertraline, both weak bases, and the non-steroidal anti-inflammatory drugs (NSAIDs) ketoprofen, naproxen, diclofenac and ibuprofen, all four weak acids to evaluate possible over- or underestimation in hazard assessments. Also, to quantify the pharmaceuticals in organism tissue I developed a hollow fiber liquid phase microextraction (HF-LPME) method. The enrichment factor was high, 1900-3000 times, thus, the method is applicable for quantification at environmentally relevant concentrations.
Misestimation of predicted pharmaceutical bioaccumulation may be due to: pH-dependent uptake. Degree of uncharged molecule uptake is greater than for ions and water pHs decreasing ionization will increase bioaccumulation and, thereby, also toxicity. Environmental pH typically ranges between 6 and 9 but hazard assessments are usually performed using toxicity data determined at one pH only. Using data from Daphnia magna toxicity testing at pH 7 and a pH distribution data set with over 4000 European running waters, I took a probabilistic modelling approach to study misestimations of hazard. European waters are often slightly basic and the model predicted underestimation by a median factor of 3 for the bases (90% of the results ranging from 1 to 6) and overestimation by a factor of 2 for acids (90% of the results ranging from 0.03 to 5). Because aquatic pH exhibited large variation both within and between countries, I advise the use of site-specific risk assessments for ionizable pharmaceuticals when making water management decisions. Organisms adapting to living in chronically polluted waters by reducing bioaccumulation. I compared fluoxetine bioaccumulation in a fish population (Rutilus rutilus) residing in a by wastewater polluted environment to a population living upstream the polluted site. Bioaccumulation in fish from the polluted site was 10% lower than in fish upstream, and this still remained after exposing detoxified fish. This indicates adaptation and because it was not temporary, suggests alterations on a heritable genetic level. Consideration of the influence of pollution history on bioconcentration in hazard assessments could be called for, as identical experimental and environmental external exposure concentrations may result in different internal exposure. The standardized hazard assessment test species not being the ones bioaccumulating the most. Dietary transfer is an important route of uptake for the early model substances and may result in trophic accumulation, but published data are inconclusive concerning such importance for pharmaceuticals. To study possible trophic transfer, I exposed two three-level aquatic food chains (leaf detritus, Acer platanoides; fed to Asellus aquaticus; in turn fed to Notonecta glauca or Pungitius pungitius) to the SSRIs. Bioaccumulation was 20-50% lower at higher trophic levels, indicating that dietary transfer is not of importance for internal concentrations. Organisms at low trophic levels had the highest internal concentrations, suggesting importance for their inclusion in hazard assessments.
My results conclude that to make informed water management decisions site specific conditions such as pH and history of pollution need to be considered if not to over- or underestimate hazard. Also, standardized bioaccumulation test species may not be the ones reaching the highest internal concentrations in the wild and hazard may, consequently, become underestimate.
Original languageEnglish
Awarding Institution
  • Department of Biology
  • Berglund, Olof, Supervisor
  • Jönsson, Jan Åke, Assistant supervisor
Award date2019 Dec 6
Place of PublicationLund
ISBN (Print)978-91-7895-302-8
ISBN (electronic) 978-91-7895-303-5
Publication statusPublished - 2019 Nov 3

Bibliographical note

Defence details
Date: 2019-12-06
Time: 09:00
Place: The Blue Hall, Ecology Building, Sölvegatan 37, Lund
External reviewer(s)
Name: Borgå, Katrine
Title: Professor
Affiliation: University of Oslo, Norway

Subject classification (UKÄ)

  • Biological Sciences

Free keywords

  • Antidepressant, BAF, BCF, Bioaccumulation, Bioconcentration, Biomagnification, CYP, Extraction technique, HF-LPME, Ionizable pharmaceutical, Metabolism, pH, Risk assessment, Tolerance, Wastewater


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