Toxicokinetics and toxicodynamics of chlorpyrifos is altered in embryos of Japanese medaka exposed to oil sands process‐affected water: evidence for inhibition of P‐glycoprotein

Abstract

Oil sands process-affected water (OSPW) is generated during extraction of bitumen in the surface mining oil sands industry in Alberta, Canada. Studies were performed in vitro by use of Caco-2 cells, and in vivo with larvae of Japanese medaka (Oryzias latipes) to determine if organic compounds from the aqueous phase of OSPW inhibit ATP binding cassette protein ABCB1 (permeability-glycoprotein, P-gp). Neutral and basic fractions of OSPW inhibited activity of P-gp in Caco-2 cells by 1.9- and 2.0-fold, respectively, while the acidic fraction had the least effect. The organophosphate pesticides chlorpyrifos (a substrate of P-gp) and malathion (not a substrate of P-gp), were used as model chemicals to investigate inhibition of P-gp in larvae. Co-exposure to chlorpyrifos and an extract of OSPW containing basic and neutral compounds reduced survival of larvae to 26.5% compared to survival of larvae exposed only to chlorpyrifos, which was 93.7%. However, co-exposure to malathion and the extract of OSPW did not cause acute lethality compared to exposure only to malathion. Accumulation and bioconcentration of chlorpyrifos, but not malathion, was greater in larvae co-exposed with the extract of OSPW. The terminal elimination half-life of chlorpyrifos in larvae exposed to chlorpyrifos in freshwater was 5 days compared with 11.3 days in larvae exposed to chlorpyrifos in OSPW. Results suggest that in non-acute exposures, basic and neutral organic compounds in the water-soluble fraction of OSPW inhibit activity of P-gp, which suggests that OSPW has the potential to cause adverse effects by chemosensitization. Copyright © 2016 John Wiley & Sons, Ltd.

A Light Touch: Solar Photocatalysis Detoxifies Oil Sands Process-Affected Waters Prior to Significant Treatment of Naphthenic Acids

“…Naphthenic sulfoxides are water-soluble , but, importantly, nonionized at OSPW pH; ionization is known to limit the bioaccumulation and toxicity of NAs. ,,, Indeed, OS + NAFCs reportedly have among the highest partition coefficients ( K ow ) of all OSPW organics, ,, and are readily solvent extracted at the alkaline pH of OSPW; ,, by contrast, many NAs poorly partition as naphthenate ions. ,, Nonionic petroleum substances (e.g., hydrocarbons, PAHs, alkylphenols) are known to be up to orders of magnitude more potently toxic than NAs; ,,,, thus, it may not be unreasonable to expect naphthenic sulfoxides to be significant toxicants. Although the above results could be partially described through baseline hydrocarbon toxicity, other possible MoAs were not ruled out: e.g., NAFCs have been shown to be uncouplers of oxidative phosphorylation, an MoA with fish EC 50 s (∼0.1–1 mmol/kg) comparable to those inferred for OS + NAFCs herein; sulfoxide NAFCs may also act to magnify the effects of other toxicants through chemosensitization. ,, …”

“…Although the above results could be partially described through baseline hydrocarbon toxicity, other possible MoAs were not ruled out: e.g., NAFCs have been shown to be uncouplers of oxidative phosphorylation, 146 an MoA with fish EC 50 s (∼0.1−1 mmol/kg 88 ) comparable to those inferred for OS + NAFCs herein; sulfoxide NAFCs may also act to magnify the effects of other toxicants through chemosensitization. 110,147,148 2) and as predicted by the dose−response models (of Figure 3). Insets: pie (donut) plots of all AEO MS measured in the initial raw OSPWs (t 0 , measurably toxic) and at the first treated sample (t 1 , no measured toxicity), colored according to the PBM-predicted LC 50 (mmol/L) of each NAFC detected�the model predicted that toxic NAFCs constituted a minority of the AEO MS and that their relative abundance declined due to treatment.…”

“…Although the above results could be partially described through baseline hydrocarbon toxicity, other possible MoAs were not ruled out: e.g., NAFCs have been shown to be uncouplers of oxidative phosphorylation, 146 an MoA with fish EC 50 s (∼0.1–1 mmol/kg 88 ) comparable to those inferred for OS + NAFCs herein; sulfoxide NAFCs may also act to magnify the effects of other toxicants through chemosensitization. 110 , 147 , 148 …”

Effects of Agricultural Pesticides in Aquafeeds on Wild Fish Feeding on Leftover Pellets Near Fish Farms

“…The exact mechanism behind the CPM-induced energy stress is not known, but it is interesting to speculate that part of the increased demand for ATP is linked to activation of the P-glycoprotein pump (cellular efflux transporter ABCB1 in mammals, ABCB4 in fish) in order to transport chemical conjugates across cell membranes. The ATP-dependent efflux pump P-glycoprotein has been implicated in the stress response to CPF (Bain and LeBlanc, 1996) and helps protect cells from the effects of a variety of xenobiotics (Fischer et al, 2013; Alharbi et al, 2017). Energy stress might also be linked to perturbations of hepatic fat metabolism, as CPF in mice has been shown to block 21 different metabolic serine hydrolases after in vivo exposure (Medina-Cleghorn et al, 2014).…”

Microbial Eukaryotes in Oil Sands Environments: Heterotrophs in the Spotlight

“…Additionally, Gilbert et al [55] showed that heterotrophic grazers such as ciliates may act as biological dispersants of hydrocarbons, contributing to the bioremediation of hydrocarbon contamination by dispersing the lipid droplets that can cut off oxygen to the water column and also prove lethal to macrofauna and flora. Tailings waste has also been applied in vitro to multicellular organisms, including HeLa cells and fish embryos [56,57,58]. These experiments have shown profound local toxicity to these multicellular tissues and organisms, which implies that macrofauna such as fish and plants would struggle to survive in the environmentally challenging conditions of tailings, fresh process water, and early-stage reclamation environments, though the toxicity of end-pit lake waters would certainly decrease over time due to dilution and reclamation processes.…”