Jianchao Liu

Occurrence, bioaccumulation and risk assessment of lipophilic pharmaceutically active compounds in the downstream rivers of sewage treatment plants

The occurrence, bioaccumulation and risk assessment of lipophilic pharmaceutically active compounds (LPhACs), such as antibiotics (roxithromycin, erythromycin and ketoconazole), anti-inflammatories (ibuprofen and diclofenac), β-blockers (propranolol), antiepileptics (carbamazepine) and steroid hormones (17α-ethinylestradiol), were investigated in the downstream rivers of sewage treatment plants in Nanjing, China. The results indicate that these LPhACs were widely detected in the surface water and fish samples, with the mean concentrations of the total LPhACs (ΣLPhACs) being in the range of 15.4 and 384.5 ng/L and 3.0 and 128.4 ng/g (wet weight), respectively. The bioaccumulation of the ΣLPhACs in wild fish tissues was generally in the order the liver>brain>gill>muscle. Among the target LPhACs, however, an interspecies difference in tissue distribution was evident for erythromycin. The bioaccumulation factors of LPhACs in the liver and brain, the two major targeted storage sites for toxicants, exhibited an obvious negative correlation with the aquatic concentrations (P<0.05). Finally, risk quotients posed by pharmaceuticals were assessed by comprehensive and comparative methods for different aquatic organisms (algae, daphnids and fish). The overall relative order of susceptibility was estimated to be algae>daphnids>fish. However, the results indicate that diclofenac, ibuprofen and 17α-ethinylestradiol each posed chronic risks for high trophic level organisms (fish). In all of the risk assessments, erythromycin was found to be the most harmful for the most sensitive algae group. In this work, however, the total BAF and toxicological interactions of pharmaceuticals were not performed due to the lack of metabolite information and combined toxicity data, which represents a major hindrance to the effective risk assessment of pharmaceuticals.

Occurrence, bioaccumulation, and trophic magnification of pharmaceutically active compounds in Taihu Lake, China.

The occurrence, bioaccumulation, and trophic magnification of pharmaceutically active compounds, (PhACs) including antibiotics (roxithromycin and erythromycin), non-steroidal anti-inflammatory drugs (ibuprofen and diclofenac), a non-selective β-adrenoceptor blocker (propranolol), an antiepileptic drug (carbamazepine), and steroid estrogens (17β-estradiol and 17α-ethynylestradiol), were investigated in Taihu Lake, China. All eight PhACs were widely detected in surface water and sediment samples with maximal concentrations in the range of 8.74-118 ng L(-1) and 0.78-42.5 ng g(-1) dry weight (dw), respectively. The investigated organisms in the natural freshwater food web in Taihu Lake included phytoplankton, zooplankton, zoobenthos, and fish, and the maximal concentrations of target compounds in these biota samples ranged from 0.65 to 132 ng g(-1) dw. Bioaccumulation factors (BAFs) for all target PhACs were lower than 1000 L kg(-1), suggesting their low bioaccumulation potential in aquatic organisms from Taihu Lake. Trophic magnification factors (TMFs) were estimated at 1.11 for roxithromycin, 0.31 for propranolol, and 1.06 for diclofenac, indicating none of these PhACs underwent trophic magnification in this freshwater food web.

An integrated assessment of estrogenic contamination and feminization risk in fish in Taihu Lake, China

An integrated approach, combining biological and chemical methods, was used to assess potential exposure to exogenous estrogens and their possible interference with the endocrine system of male goldfish (Carassius auratus) in Taihu Lake. A suite of biomarkers in caged fish after in situ exposure for 28 days, coupled with six selected exogenous estrogens in water, were determined at eight biomonitoring stations. The compounds estrone, 17β-estradiol (E2), estriol, 17α-ethinylestradiol (EE2), bisphenol-A and diethylstilbestrol were detected in most of the samples and the concentrations of total estradiol equivalent (EEQ) ranged between 5.69 and 17.8 ng/L. E2 and EE2 were thought to be the major causal agents responsible for the estrogenic activities. Elevated serum vitellogenin and E2, gonadal DNA damage and reduced gonadosomatic index were observed in fish collected from most stations. The integrated biomarker response (IBR) index showed good agreement with the observed total EEQ levels in water, and feminization risk in fish may be present in northern Taihu Lake, especially in Meiliang Bay and Zhushan Bay.

Tissue distribution, bioconcentration, metabolism, and effects of erythromycin in crucian carp (Carassius auratus)

In this study, the tissue distribution, bioconcentration, metabolism and biological effects of the macrolide antibiotic erythromycin (ERY) were investigated in fish using crucian carp (Carassius auratus) as a model. Crucian carp were exposed to various concentrations of ERY (4, 20, and 100 μg/L) for 28 days. The UPLC/MS/MS analysis of both water and tissue provided the bioconcentration of ERY and its metabolites in the fish body. The results from tissue samples showed that a maximum tissue concentration occurred in the muscle and that the bioconcentration factor (BCF) of 72.2 was lower than the theoretical BCF of 90.4 calculated from the octanol-water coefficient of ERY. A significant portion of the absorbed ERY was metabolized via demethylation and dehydration and observed in the form of descladinose in fish. In addition, the relevant biomarkers, including acetylcholinesterase in the brain, as well as 7-ethoxyresorufin O-deethylase and superoxide dismutase in the liver, changed significantly during 28 days of exposure (P<0.05). These results clearly indicated that ERY accumulated in fish and that similar metabolites as those observed in mammals were produced, resulting in the biochemical disturbance of biological systems.

Potential environmental implications of emerging organic contaminants in Taihu Lake, China: Comparison of two ecotoxicological assessment approaches

In this study, the hazard quotient (HQ) and a novel enhanced integrated biomarker response (EIBR) were applied to indirectly/directly estimate the ecotoxicological risk of emerging organic contaminants in Taihu Lake. Nine out of sixteen target compounds were detected in most sampling points at comparable concentrations (1.58-206.95 ng/L). Simultaneously, changes in multi-biomarkers were measured in caged fish for 28 days. The 0HQ results preliminarily indicated that most water areas were at significant risk for adverse effects to aquatic organisms (HQ>10). The prioritisation was then ranked and 17α-ethinylestradiol, diethylstilbestrol and 17β-estradiol were regarded as the greatest hazards. The EIBR, covering multi-biomarkers and their weighting, was applied to field study, and Zhushan Bay was suggested as the most stressful place, followed by Meiliang Bay. The HQ showed significant positive linear correlation with the EIBR (r=0.848, P<0.001), suggesting mutual consistency between the two approaches based on laboratory and field study in ecotoxicological risk assessment.

Biological fate and effects of propranolol in an experimental aquatic food chain

The aim of this study was to evaluate the trophic transfer of the β-blocker propranolol (PRP) in an experimental aquatic food chain involving the green algae Scenedesmus obliquus, the water flea Daphnia magna and the crucian carp Carassius auratus, as well as the metabolism and effects of PRP in the liver of crucian carp. After a 48 h PRP aqueous exposure for algae, with a subsequent 48 h dietary exposure for daphnia and an 8d dietary exposure for crucian carp, PRP was observed in each trophic level, despite significant bioaccumulation did not occur in daphnia and crucian carp. A portion of the absorbed PRP was metabolized by the crucian carp to N-desisopropylated propranolol, propranolol glucuronic acid, monohydroxylated propranolol, hydroxypropranolol glucuronide and dihydroxypropranolol glucuronide, which were similar to those in mammals. In addition, multiple biomarkers in the liver of crucian carp (7-ethoxyresorufin O-deethylase, EROD; 7-benzyloxyresorufin O-dealkylation, BROD; superoxide dismutase, SOD and malondialdehyde, MDA) were measured. BROD and MDA were not significantly affected by PRP, while EROD and SOD did change significantly during the 8d dietary exposure. This work indicated that the trophic transfer of PRP, resulting in biochemical perturbations of fish biological systems, should be a concern for the assessment of the environmental risks to aquatic food chains.

Behavioral and biochemical responses in freshwater fish Carassius auratus exposed to sertraline

Sertraline is one of the most commonly prescribed selective serotonin reuptake inhibitors and is frequently detected in the aquatic environment. However, knowledge regarding relationships among molecular or biochemical endpoints involved in modes of action (MOAs) of sertraline and ecologically important behavioral responses of fish is insufficient. The present study aimed to investigate the bioconcentration and possible adverse outcomes pathways (AOPs) in crucian carp (Carassius auratus) exposed to various concentrations of sertraline (4.36, 21.3 and 116 μg L(-1)) for 7 d. Bioconcentration factor values were in the range of 19.5-626 in liver, 6.94-285 in brain, 4.01-146 in gill and 0.625-43.1 in muscle during the entire period of exposure. Liver superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities and brain acetylcholinesterase (AChE) activity were selected as biochemical endpoints associated with MOAs. Swimming activity, shoaling, feeding rate and food consumption were determined to assess behavioral responses. Fish plasma levels of sertraline exceeding human therapeutic doses were also predicted from external exposure concentrations. Significant enhancements in CAT, GPx, AChE and swimming activities and decreases in shoaling tendency, feeding rate and food consumption were observed when fish plasma levels exceeded human therapeutic thresholds. Shoaling, feeding rate and food consumption were correlated with the activities of SOD, CAT and GST. A significant positive correlation between swimming activity and AChE activity was also observed. As such, our study provides important AOPs linking biochemical responses with ultimate ecologically relevant behavioral endpoints.

Uptake, depuration, and bioconcentration of two pharmaceuticals, roxithromycin and propranolol, in Daphnia magna.

The objective of the present study was to investigate the uptake, depuration, and bioconcentration of two pharmaceuticals, roxithromycin (ROX) and propranolol (PRP), in Daphnia magna via aqueous exposure. Additionally, dietary and pH effects on the bioconcentration of two pharmaceuticals in daphnia were studied. During the 24-h uptake phase followed by the 24-h depuration phase, the uptake rate constants (k(u)) of ROX for daphnia were 9.21 and 2.77 L kg(-1) h(-1), corresponding to the exposure concentrations of 5 and 100 μg L(-1), respectively; For PRP at the nominal concentrations of 5 and 100 μg L(-1), k(u) were 2.29 and 0.99 L kg(-1) h(-1), respectively. The depuration rate constants (k(d)) of ROX in daphnia, at the exposure concentrations of 5 and 100 μg L(-1), were 0.0985 and 0.207 h(-1), respectively; while those of PRP were 0.0276 and 0.0539 h(-1) for the nominal concentrations of 5 and 100 μg L(-1), respectively. With the decreasing exposure concentrations, the bioconcentration factors (BCFs) in daphnia ranged from 13.4 to 93.5 L kg(-1) for ROX, and 18.4 to 83.0 L kg(-1) for PRP, revealing the considerable accumulation potential of these two pharmaceuticals. Moreover, after 6h exposure, the body burdens of ROX and PRP in dead daphnia were 4.98-6.14 and 7.42-12.9 times higher than those in living daphnia, respectively, implying that body surface sorption dominates the bioconcentration of the two pharmaceuticals in daphnia. In addition, the presence of algal food in the media could significantly elevate the kd values for both ROX and PRP, thereby restraining their bioconcentration in daphnia. A pH-dependent bioconcentration study revealed that the bioconcentration of the two pharmaceuticals in daphnia increased with increasing pH levels, which ranged from 7 to 9. Finally, a model was developed to estimate the relationships between pH and the BCFs of the two pharmaceuticals in zooplankton. The predicted values based on this model were highly consistent with wildlife monitoring data, implying that this model will be useful in identifying the bioaccumulation risks that pharmaceuticals pose to zooplankton.

Bioconcentration and multi-biomarkers of organic UV filters (BM-DBM and OD-PABA) in crucian carp

Organic UV filters (OUV-Fs) are increasingly used in sunscreens and personal care products. In the present work, the bioconcentration and multi-biomarker effects of butyl methoxydibenzoylmethane (BM-DBM) and ethylhexyl dimethyl p-aminobenzoate (OD-PABA) were investigated in crucian carp (Carassius auratus). The fish were exposed to various concentrations of BM-DBM (3.88, 35.61, 181.85 and 337.15μg/L), OD-PABA (4.66, 53.83, 264.22 and 459.32μg/L) and their mixture (2.31+2.79, 23.69+26.18, 97.37+134.81 and 193.93+246.08μg/L) for 28 days. The maximal concentrations of two OUV-Fs were detected in the fish liver, followed by the brain, kidney, gill and muscle in most cases. The maximal BCF values of OD-PABA calculated in various exposure concentrations were 0.37 - 101.21 in single exposure groups and 0.11 - 31.09 in mixed exposure groups. Acetylcholinesterase (AChE) activity was significantly inhibited by BM-DBM as well as the mixtures at all of the exposure concentrations and by OD-PABA at higher concentrations (≥264.22μg/L) during 28 days of exposure. The maximal inhibition rates of AChE activity reached 64.04% for BM-DBM, 41.05% for OD-PABA and 61.50% for the mixtures at the highest concentration, which indicated that these two OUV-Fs might damage the central nervous system. Concerning oxidative stress status, BM-DBM and the mixtures significantly increased superoxide dismutase (SOD) and glutathione reductase (GR) activities and inhibited catalase (CAT) activity, while OD-PABA caused a significant increase of GR and CAT activities. AChE and GR activities seemed to be more sensitive biomarkers for BM-DBM and OD-PABA.

Investigation of pharmaceutically active compounds in an urban receiving water: Occurrence, fate and environmental risk assessment

Pharmaceutically active compounds (PhACs) recently have been recognized to constitute a health risk for aquatic ecosystems. The major pathways of PhACs to enter the aquatic environment are excretion and discharge of effluents through sewage treatment plants (STPs). The occurrence, bioaccumulation and risk assessment of lipophilic PhACs, including erythromycin, ketoconazole, indomethacin, diclofenac, gemfibrozil, bezafibrate, propranolol, carbamazepine, sertraline and 17α-ethinylestradiol were investigated in a river that receives effluents from STP. The results indicate that the PhACs were extensively existed in fish, sediment, suspended particulate matter (SPM), colloidal phase (5 kDa to 1 µm) and truly dissolved phase (< 5 kDa) water, with total concentration of ten PhACs (Σ10PhACs) of ND-19.6 ng/g, 7.3-11.2 ng/g, 25.3-101.5 ng/g, 10.1-27.7 ng/L and 67.0-107.6 ng/L, respectively. The Σ10PhACs for particulate and water samples collected from STPs outfall site were higher than those collected from upstream and downstream, indicating that the STP is an important PhACs source of river. However, the Σ10PhACs in sediment showed no significant statistical differences in the sampling area, and which was 3.5-9.5 times lower than those in SPM samples. The colloidal phase contributed 2.5-28.5% of erythromycin, 5.8-45.6% of ketoconazole, 8.4-32.2% of indomethacin, 7.0-21.4% of diclofenac, 11.6-36.9% of gemfibrozil, 10.2-45.9% of bezafibrate, 5.9-16.8% of propranolol, 1.9-11.1% of carbamazepine and 1.1-23.8% of sertraline in the aquatic environment. This suggests that aquatic particulates (e.g., colloids and SPM) maybe an important carrier for PhACs in the aquatic system. In general, the Σ10PhACs in the tissues of fish were in order as follows: kidney > brain > liver > gill > muscle. Based on truly dissolved concentrations of PhACs in the water, bioaccumulation factors were between 3.7 and 2727.3 in the fish tissues, sertraline exhibited bioaccumulation potential. In all the risk assessments, erythromycin could cause most harmful adverse health effects for the most sensitive algae group based on the acute and chronic data. In addition, the risk quotient values for diclofenac toward fish were higher than 1. These results indicate that the PhACs pose a potential risk to the aquatic organisms, especially for chronic risk.