Abstract
Global production of pharmacologically active compounds exceeds 100 000 tons annually, a proportion of which enters aquatic environments through patient use, improper medicine disposal, and production. These compounds are designed to have mode-of-action (MoA) effects on specific biological pathways, with potential to impact nontarget species. Here, we used MoA and trait-based approaches to quantify uptake and biological effects of fluoxetine, a selective serotonin reuptake inhibitor, in filter and deposit feeding marine worms (Hediste diversicolor). Worms exposed to 10 μg L(-1), accumulated fluoxetine with a body burden over 270 times greater than exposure concentrations, resulting in ∼10% increased coelomic fluid serotonin, a pharmacological effect. Observed effects included weight loss (up to 2% at 500 μg L(-1)), decreased feeding rate (68% at 500 μg L(-1)), and altered metabolism (oxygen consumption, ammonia excretion, and O/N from 10 μg L(-1)). Bioconcentration of fluoxetine was dependent on route of uptake, with filter feeding worms experiencing up to 130 times greater body burden ratios and increased magnitudes of effects than deposit feeders, a trait-based sensitivity likely as a consequence of fluoxetine partitioning to sediment. This study highlights how novel approaches such as MoA and trait-based methods can supplement environmental risk assessments of pharmaceuticals.
Highlights
Over 4000 pharmaceutical products are available worldwide for medicinal and veterinary purposes,[1] resulting in annual production exceeding 100 000 tons of pharmacologically active compounds
Pharmaceuticals are designed to have specific biological effects and are unlikely to exhibit acute lethality or general adverse effects as focused on by traditional environmental risk assessments (ERAs), emphasizing the importance of the reconsideration of traditional ecological risk assessment paradigms for these compounds.[3]
An environmental quality standard (EQS) value of interest for fluoxetine in the UK has been proposed by the water framework directive (WFD) as 0.01 μg L−1.6 Gardner et al.[7] identified that effluent from over 50% of UK sewage-treatment plants (STPs) exceeded this, with a median concentration of 0.023 μg L−1
Summary
Over 4000 pharmaceutical products are available worldwide for medicinal and veterinary purposes,[1] resulting in annual production exceeding 100 000 tons of pharmacologically active compounds. Fluoxetine hydrochloride is a selective serotonin reuptake inhibitor (SSRI) used to treat psychiatric disorders, predominantly depression. It was one of the most highly prescribed SSRIs in England in 2014 (>6.2 million prescriptions).[5] An environmental quality standard (EQS) value of interest for fluoxetine in the UK has been proposed by the water framework directive (WFD) as 0.01 μg L−1.6 Gardner et al.[7] identified that effluent from over 50% of UK sewage-treatment plants (STPs) exceeded this, with a median concentration of 0.023 μg L−1. Fluoxetine has a sorption coefficient (log Koc) value of 4.72 at pH 8,10 indicating it may preferentially partition to sediment and dissolved organic matter (DOM)
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