Biotransformation Changes Bioaccumulation and Toxicity of Diclofenac in Aquatic Organisms

Abstract

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 kg ww −1 in H. azteca and G. pulex, respectively, whereas BCFs of DCF-M310.03 was 164.5 and 104.7 L kg ww −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 LC 50 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.

Comparison of Alternative Methods for Bioaccumulation Assessment: Scope and Limitations of In Vitro Depletion Assays with Rainbow Trout and Bioconcentration Tests in the Freshwater Amphipod Hyalella azteca

“…Furthermore, the in vitro system could potentially be limited in cofactors to provide for conjugation as well, explaining why the metabolite pattern of the hepatocytes could be less diverse for some substances. In other studies, a larger number of metabolites could be identified in both H. azteca and hepatocyte samples (Fu et al 2020). A more detailed metabolite pattern might have been detected in case a radiolabel had been used.…”

Construction of Built‐In Electric Field within Silver Phosphate Photocatalyst for Enhanced Removal of Recalcitrant Organic Pollutants

“…[ 3,4 ] For instance, the pharmaceutical diclofenac is one of the most popular non‐steroidal anti‐inflammatory drugs with a global annual consumption of up to 1000 tons, and it is frequently detected in the treated wastewater, rivers, lakes, and even drinking water. [ 5,6 ] Norfloxacin is a kind of fluoroquinolone antibiotics used in the treatment of bacterial infections, aquaculture industry, and livestock, which is often detected in wastewater effluents. [ 7 ] Because these chemical productions are toxic and refractory to traditional biological treatment, it is urgent to develop efficient and environment‐friendly treatment technology.…”

Electrochemical degradation of DCF by boron-doped diamond anode: degradation mechanism, pathways and influencing factors

“…Its testicular and epididymal toxicity also attract people's attention (Owumi et al 2020). Fu et al (2020) found DCF residue in water to be biotransformed by Gammarus pulex and Hyalella Azteca, representing a 25 to 110-fold increase of bioconcentration factors. Thus, the safe and effective removal of DCF residue has been a rising concern.…”