Uptake and Disposition of Select Pharmaceuticals by Bluegill Exposed at Constant Concentrations in a Flow-Through Aquatic Exposure System

Abstract

The increasing use of pharmaceuticals has led to their subsequent input into and release from wastewater treatment plants, with corresponding discharge into surface waters that may subsequently exert adverse effects upon aquatic organisms. Although the distribution of pharmaceuticals in surface water has been extensively studied, the details of uptake, internal distribution, and kinetic processing of pharmaceuticals in exposed fish have received less attention. For this research, we investigated the uptake, disposition, and toxicokinetics of five pharmaceuticals (diclofenac, methocarbamol, rosuvastatin, sulfamethoxazole, and temazepam) in bluegill sunfish (Lepomis macrochirus) exposed to environmentally relevant concentrations (1000-4000 ng L) in a flow-through exposure system. Temazepam and methocarbamol were consistently detected in bluegill biological samples with the highest concentrations in bile of 4, 940, and 180 ng g, respectively, while sulfamethoxazole, diclofenac, and rosuvastatin were only infrequently detected. Over 30-day exposures, the relative magnitude of mean concentrations of temazepam and methocarbamol in biological samples generally followed the order: bile ≫ gut > liver and brain > muscle, plasma, and gill. Ranges of bioconcentration factors (BCFs) in different biological samples were 0.71-3960 and 0.13-48.6 for temazepam and methocarbamol, respectively. Log BCFs were statistically positively correlated to pH adjusted log K (that is, log D), with the strongest relations for liver and brain (r = 0.92 and 0.99, respectively), implying that bioconcentration patterns of ionizable pharmaceuticals depend on molecular status, that is, whether a pharmaceutical is un-ionized or ionized at ambient tissue pH. Methocarbamol and temazepam underwent rapid uptake and elimination in bluegill biological compartments with uptake rate constants (K) and elimination rate constants (K) at 0.0066-0.0330 h and 0.0075-0.0384 h, respectively, and half-lives at 18.1-92.4 h. Exposure to mixtures of diclofenac, methocarbamol, sulfamethoxazole, and temazepam had little or no influence on the uptake and elimination rates, suggesting independent multiple uptake and disposition behaviors of pharmaceuticals by fish would occur when exposed to effluent-influenced surface waters.

Critical review: Grand challenges in assessing the adverse effects of contaminants of emerging concern on aquatic food webs

“…Similarly, malformations in zebrafish embryos were linked to maternal PFOS transfer to embryological development (Du et al ). Little is known about maternal transfer of pharmaceuticals but several studies have reported bioaccumulation of these CECs in exposed organisms (Schultz et al ; Clairardin et al ; Zhao et al ()), suggesting that maternal transfer to eggs is plausible and has been observed for other pollutants (Marsh‐Matthews et al ).…”

“…However, PFOS has been known to bioaccumulate in aquatic organisms (Du et al 2009;Haddad et al 2017) and may lead to adverse outcome for first filial generation offspring of exposed parental organisms (Du et al 2009). Similarly, some pharmaceuticals have been reported to bioaccumulate in tissues with little knowledge of the long-term consequences (Zhao et al (2017)). Given the chemical diversity of pharmaceuticals, it is not surprising that bioaccumulation varies for these CECs.…”

“…To illustrate, bioaccumulation of antidepressants in whole-body preparations may be less predictive of adverse effects than the knowledge that they bioaccumulate in the pharmaceuticals' target tissuethe central nervous system (Schultz et al 2011;Arnnok et al 2017). Similarly, Zhao et al (2017) reported bioconcentration for several pharmaceuticals to be highest in the liver and the brain and lower in muscle tissues. An understanding of pharmaceutical bioaccumulation across size classes of organisms displaying ontogenetic feeding shifts is lacking (Haddad et al 2017).…”

Bioaccumulation, Biotransformation, and Multicompartmental Toxicokinetic Model of Antibiotics in Sea Cucumber (Apostichopus japonicus)

“…27,56,57 Sulfamethoxazole was intermittently detected in the tissues with low concentrations in TG-10 (7.1−57.2 μg•kg −1 ), which are close to those in TG-1 (13.2−41.5 μg•kg −1 ), indicating limited uptake of sulfamethoxazole by the juveniles. Zhao et al 58 also observed restricted uptake of sulfamethoxazole in bluegill sunfish (Lepomis macrochirus) exposed to environmentally relevant concentrations. The phenomenon can be due to the predominant presence of the compound as an anionic Environmental Science & Technology pubs.acs.org/est Article species (>99%, pK a = 5.7) 59 in the seawater (pH = 8.1 in the current study) because ionic species were reported to have a slower rate to cross membranes than the corresponding neutral molecule.…”

Evaluation of the effect of carbamazepine on the concentration of vitellogenin in Pseudoplatystoma magdaleniatum

“…This could also affect the livelihoods of people dedicated to selling fish such as catfish, since endocrine disruption could affect the reproductive capacity of fish (Shioda and Wakabayashi, 2000), and therefore decrease fish production. The risk to the health of the human population posed by compounds of this nature, such as carbamazepine (CMZ), is aggravated by its bioaccumulation in aquatic and terrestrial organisms (Vernouillet et al, 2010), which has been reported mainly in fish (Daughton and Brooks, 2011;Du, et al, 2014;Zhao, et al, 2017).…”