posted on 2020-03-11, 19:33authored byQiuguo Fu, Davide Fedrizzi, Verena Kosfeld, Christian Schlechtriem, Vera Ganz, Samuel Derrer, Daniel Rentsch, Juliane Hollender
Biotransformation
plays a crucial role in regulating the bioaccumulation
potential and toxicity of organic compounds in organisms but is, in
general, poorly understood for emerging contaminants. Here, we have
used diclofenac as a model compound to study the impact of biotransformation
on the bioaccumulation potential and toxicity in two keystone aquatic
invertebrates: Gammarus pulex and Hyalella azteca. In both species, diclofenac was
transformed into several oxidation products and conjugates, including
two novel products, that is, diclofenac taurine conjugate (DCF-M403)
and unexpected diclofenac methyl ester (DCF-M310.03). The ratios of
biotransformation products to parent compound were 12–17 for
DCF-M403 and 0.01–0.7 for DCF-M310.03 after 24 h exposure.
Bioconcentration factors (BCFs) of diclofenac were 0.5 and 3.2 L kgww–1 in H. azteca and G. pulex, respectively, whereas
BCFs of DCF-M310.03 was 164.5 and 104.7 L kgww–1, respectively, representing a 25- to 110-fold increase. Acute toxicity
of DCF-M310.03 was also higher than the parent compound in both species,
which correlated well with the increased bioconcentration potential.
The LC50 of diclofenac in H. azteca was 216 mg L–1, while that of metabolite DCF-M310.03
was reduced to only 0.53 mg L–1, representing a
430-fold increase in acute toxicity compared to diclofenac. DCF-M403
is less toxic than its parent compound toward H. azteca, which may be linked to its slightly lower hydrophobicity. Furthermore,
the transformation of diclofenac to its methyl ester derivative was
explored in crude invertebrate extracts spiked with an S-adenosylmethionine cofactor, revealing possible catalysis by an S-adenosylmethionine-dependent carboxylic acid methyltransferase.
Methylation of diclofenac was further detected in fish hepatocytes
and human urine, indicating a broader relevance. Therefore, potentially
methylated metabolites of polar contaminants should be considered
for a comprehensive risk assessment in the future.