Significance of Xenobiotic Metabolism for Bioaccumulation Kinetics of Organic Chemicals in Gammarus pulex

Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Dübendorf, Switzerland.
Environmental Science & Technology (Impact Factor: 5.33). 02/2012; 46(6):3498-508. DOI: 10.1021/es204611h
Source: PubMed

ABSTRACT Bioaccumulation and biotransformation are key toxicokinetic processes that modify toxicity of chemicals and sensitivity of organisms. Bioaccumulation kinetics vary greatly among organisms and chemicals; thus, we investigated the influence of biotransformation kinetics on bioaccumulation in a model aquatic invertebrate using fifteen (14)C-labeled organic xenobiotics from diverse chemical classes and physicochemical properties (1,2,3-trichlorobenzene, imidacloprid, 4,6-dinitro-o-cresol, ethylacrylate, malathion, chlorpyrifos, aldicarb, carbofuran, carbaryl, 2,4-dichlorophenol, 2,4,5-trichlorophenol, pentachlorophenol, 4-nitrobenzyl-chloride, 2,4-dichloroaniline, and sea-nine (4,5-dichloro-2-octyl-3-isothiazolone)). We detected and identified metabolites using HPLC with UV and radio-detection as well as high resolution mass spectrometry (LTQ-Orbitrap). Kinetics of uptake, biotransformation, and elimination of parent compounds and metabolites were modeled with a first-order one-compartment model. Bioaccumulation factors were calculated for parent compounds and metabolite enrichment factors for metabolites. Out of 19 detected metabolites, we identified seven by standards or accurate mass measurements and two via pathway analysis and analogies to other compounds. 1,2,3-Trichlorobenzene, imidacloprid, and 4,6-dinitro-o-cresol were not biotransformed. Dietary uptake contributed little to overall uptake. Differentiation between parent and metabolites increased accuracy of bioaccumulation parameters compared to total (14)C measurements. Biotransformation dominated toxicokinetics and strongly affected internal concentrations of parent compounds and metabolites. Many metabolites reached higher internal concentrations than their parents, characterized by large metabolite enrichment factors.

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Available from: Juliane Hollender, Sep 26, 2015
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    • "For example, (Smith et al. (2010) demonstrated that hepatic metabolism of fluoxetine in trout was limited unless induced by pre-exposure to carbamazepine. In fact, limited information exists on invertebrate metabolism of organic chemicals (Katagi, 2010); however, biotransformation by the invertebrate G. pulex has been to shown to alter internal concentrations of xenobiotics (Ashauer et al., 2012). Clearly, an advanced understanding of biotransformation of pharmaceuticals in fish, invertebrate, plant and periphytic communities is needed to improve bioaccumulation assessments (Boxall et al., 2012). "
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    ABSTRACT: Increasing evidence indicates that pharmaceutical bioaccumulate in fish collected downstream from municipal wastewater effluent discharges. However, studies of pharmaceutical bioaccumulation by other aquatic organisms, including primary producers (e.g., periphyton) and grazers (e.g., snails), are lacking in wadeable streams. Here, we examined environmental occurrence and bioaccumulation of a range of pharmaceuticals and other contaminants of emerging concern in surface water, a common snail (Planorbid sp.) and periphyton from an effluent-dependent stream in central Texas, USA, during a historic drought, because such limited dilution and instream flows may represent worst-case exposure scenarios for aquatic life to pharmaceuticals. Water and tissue samples were liquid-liquid extracted and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization. Target analytes included 21 pharmaceuticals across multiple drug classes and 2 pharmacologically active metabolites. Several pharmaceuticals were detected at up to 4.7μgkg(-1) in periphyton and up to 42μgkg(-1) in Planorbid sp. We then identified limitations of several bioconcentration factor and bioaccumulation factor models, developed for other invertebrates, to assist interpretation of such field results. Observations from the present study suggest that waterborne exposure to pharmaceuticals may be more important than dietary exposure for snails.
    Chemosphere 09/2014; 119C:927-934. DOI:10.1016/j.chemosphere.2014.08.044 · 3.34 Impact Factor
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    • "Lipid corrected based on conc. in food, analysis by GLC D. Mackay et al. out previously (Ashauer et al. 2012), these data were unusable. Uptake of CPY was rapid in Gammarus pulex (Ashauer et al. 2012), with equilibrium reached in less than 1 d. Formation of an unidentified metabolite and CPYO were rapid with rate constants of 3.5 and 0.132 d −1 , respectively. "
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    ABSTRACT: The fate and movement of the organophosphorus insecticide chlorpyrifos (CPY;CAS No.2921-88-2) and its metabolite chlorpyrifos-oxon (CPYO; CASNo.5598-15-2) determine exposures in terrestrial and aquatic environments.Detectable concentrations of the organophosphorus insecticide CPY in air, rain,snow and other environmental media have been measured in North America and other locations at considerable distances from likely agricultural sources, which indicates the potential for long range transport (LRT) in the atmosphere. This issue was addressed by first compiling monitoring results for CPY in all relevant environmental media. As a contribution to the risk assessment of CPY in remote regions, a simple mass balance model was developed to quantify likely concentrations at locations ranging from local sites of application to more remote locationsup to hundreds of km distant. Physical-chemical properties of CPY were reviewed and a set of consistent values for those properties that determine partitioning and reactivity were compiled and evaluated for use in the model. The model quantifies transformation and deposition processes and includes a tentative treatment of dispersion to lesser atmospheric concentrations. The model also addressed formation and fate of CPYO, which is the major transformation product of CPY. The Characteristic Travel Distance (CTD) at which 63% of the original mass of volatilized CPY is degraded or deposited-based on a conservative concentration of •OHradicals of 0.7 x 106 molecules cm-3 and a half-life of 3 h, was estimated to be 62 km. At lesser concentrations of •OH radical, such as occurs at night and at lesser temperatures, the CTD is proportionally greater. By including monitoring data from a variety of media, including air, rain, snow and biota, all monitored concentrations can be converted to the equilibrium criterion of fugacity, thus providing asynoptic assessment of concentrations of CPY and CPYO in multiple media. The calculated fugacities of CPY in air and other media decrease proportionally with increasing distance from sources, which can provide an approximate prediction of downwind concentrations and fugacities in media and can contribute to improved risk assessments for CPY and especially CPYO at locations remote from points of application, but still subject to LRT. The model yielded estimated concentrations that are generally consistent with concentrations measured, which suggests that the canonical fate and transport processes were included in the simulation model. The equations included in the model enable both masses and concentrations of CPY and CPYO to be estimated as a function of distance downwind following application.While the analysis provided here is useful and an improvement over previous estimates of LRT of CPY and CPYO, there is still need for improved estimates of the chemical-physical properties of CPYO.Based on the persistence in water, soils, and sediments, its bioconcentration and biomagnification in organisms, and its potential for long-range transport, CPY and CPYO do not trigger the criteria for classification as a POP under the Stockholm convention or a PB chemical under EC 1107/2009. Nonetheless, CPY is toxic at concentrations less than the trigger for classification as T under EC 11 07 /2009; however,this simple trigger needs to be placed in the context of low risks to non-target organisms close to the areas of use. Overall, CPY and CPYO are judged to not trigger the PBT criteria of EC 1107/2009.
    Reviews of environmental contamination and toxicology 04/2014; 231:35-76. DOI:10.1007/978-3-319-03865-0_3 · 3.74 Impact Factor
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    • "The uptake and bioconcentration of pharmaceuticals in different tissues are often monitored to characterize their potential impacts on exposed organisms (Ashauer et al., 2012). Togunde et al. (2012) found that the unmodified parent compounds or metabolites detected in bile may be used as biomarkers for pharmaceutical uptake by fish exposed to these emerging contaminants in aquatic environments. "
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    ABSTRACT: To investigate the distribution, bioconcentration, metabolism, and biomarker responses of macrolide antibiotic roxithromycin (ROX) in fish, crucian carp (Carassius auratus) were exposed to various concentrations of ROX (4, 20, and 100μgL(-1)) for 20d. The ROX content in different tissues was quantified using UPLC/MS/MS. The liver exhibited the highest ROX concentration followed by the bile, gills, and muscle tissues. After 15d of exposure to different concentrations of ROX, the bioconcentration factors were 2.15-38.0 in the liver, 0.950-20.7 in the bile, 0.0506-19.7 in the gill, and 0.0439-13.8 in the muscle; these results were comparable to the estimated BCF values. The metabolites formed in the bile were identified based on metabolic identification in human bile. Additionally, the biomarkers, including acetylcholinesterase in the brain, as well as 7-ethoxyresorufin O-deethylase and superoxide dismutase in the liver changed significantly after 5, 10, 15, and 20d of exposure (P<0.05). Our results suggest that ROX can accumulate and be metabolized in fish; therefore, interactions between ROX or its metabolites and the biological systems may induce biochemical disturbances in fish.
    Chemosphere 11/2013; 99. DOI:10.1016/j.chemosphere.2013.10.036 · 3.34 Impact Factor
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