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Field testing of a fish bioconcentration model
proposed for risk assessment of human
pharmaceutical residues in aquatic environments
Jeffrey N. Brown†, Nicklas Paxéus*, Lars Förlin‡ and D.G. Joakim Larsson†
† Institute for Neuroscience and Physiology, the Sahlgrenska Academy at Göteborg University, Sweden. * Environmental Chemistry, Gryaab AB, Göteborg.
‡ Department of Zoology, Göteborg University. Email: [email protected]
A theoretical Fish Plasma Model (Fig. 1) has been proposed by Huggett et al.1 to assess the probability of a specific
target interaction of pharmaceuticals in fish given that the drug target is conserved. A specific target interaction
would not necessarily imply any adverse effects in aquatic organisms, but it would suggest a strong possibility and
guide further testing. As a part of the model, a QSAR developed for hydrophobic organic pollutants is used to
calculate fish bioconcentration but this QSAR is largely untested for pharmaceuticals, particularly in complex
environmental exposure scenarios.
To test the bioconcentration QSAR of the Fish Plasma Model using fish exposed to diluted sewage effluents.
Fish exposure via water
• BCFs varied considerably between
sites which could not be attributed to
differences in effluent
concentrations, pH, temperatures or
Human therapeutic plasma
Fish steady state plasma
• Modelled BCFs were accurate for
concentration giving known
effects (H PC)
some drugs and sites but were rather
far away for others. Reasons may be:
(1) the QSAR does not take into
Effect Ratio (ER) = H PC / F PC
account special characteristics of
pharmaceuticals; (2) active excretion
Low ER = likely pharmaceutical target interaction
and metabolism may lower plasma
levels; (3) actual drug bioavailability
High ER = target interaction less likely
may be significantly lower through
Fig. 1. The Fish Plasma Model1 utilises potency data gathered
partitioning to colloids and particles.
during pharmaceuticals efficacy and safety testing. If the level
• Ibuprofen bioconcentrated greatly
in fish blood plasma is near or greater than the human
above model predictions.
therapeutic plasma level pharmacological effects are
Max estimated BCF. Analyte not detected so plasma concentration set at 3
ng/ml detection limit to estimate maximal BCFs.
• Juvenile rainbow trout (O. mykiss
) were exposed in cages and tanks
• The lower the ER, the greater are
• Blood plasma was SPE extracted, derivatised and GC/MS analysed
the risks for pharmacological
for 4 non-steroidal anti-inflammatory drugs and the lipid regulator
effects in fish. The risk is highest
for the undiluted Gryaab effluent,
particularly for ibuprofen,
diclofenac and gemfibrozil.
• Diclofenac presents the highest
risk at all sites.
• Naproxen presents little risk.
Minimum estimated ER based on detection limit of 3 ng/ml plasma
1. Pharmaceuticals bioconcentrated from sewage effluents in to fish blood.
2. Significant differences in bioconcentration between sites shows the importance of field studies.
3. Diclofenac appears to present the highest risk for pharmacological effects in fish.
4. The Fish Plasma Model shows promising results but further refinement of the bioconcentration QSAR and
validation of the model are necessary.
1 Huggett, D. B., Cook, J. C., Ericson, J. F. and Williams, R. T. (2003). A theoretical model for utilizing mammalian pharmacology and safety data to prioritize potential impacts of human
pharmaceuticals to fish. Human and Ecological Risk Assessment, 9
2 Brown, J.N., Paxéus, N., Förlin, L. and Larsson, D.G.J. (2007). Variations in bioconcentration of human pharmaceuticals from sewage into fish blood plasma. Environmental Toxicology and Pharmacology, published online ahead of print June 2007, doi:10.1016/j.etap.2007.06.005.
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