The continuous influx of opioid compounds into aquatic environments has become an increasing and persistent concern, due to their extensive use. This is especially alarming as wastewater treatment plants (WWTPs) are unable to completely remove them. Despite the reported health concerns, the occurrence of opioid compounds in the environment has not received much attention. The present study investigates the occurrence of 19 opioids in four WWTPs and their respective receiving water bodies. All wastewater samples revealed opioids at concentration ranging from ng/L to μg/L with most influents having higher concentrations than effluents. WWTPs appeared to perform poorly (p > 0.05 between influents and effluents), and were unable to remove some opioids including Methadone (−27.3%) from the Leeuwkuil WWTP, Codeine (−21.7%) and Thebaine (−3.77%) from the Sandspruit WWTP, and Hydrocodone (−1.06%) from the Meyerton WWTP, respectively. Samples collected from the Leeuwkuil WWTP were the most contaminated, with eighteen out of nineteen opioid analogues exceeding 1 μg/L. Upstream surface water contained less opioids (most < LOQ) than downstream (p < 0.05), with Hydrocodone, Oxycodone, Hydromorphone, Fentanyl, Ketamine and Dihydrocodeine not detected. The occurrence of high concentrations of opioid analogues in downstream surface water (298 ng/L −10.8 μg/L for Klip River, 4.49 ng/L −13.1 μg/L for Vaal River, 70.5 ng/L −10.0 μg/L for Soutspruit River and 8.0 ng/L – 2.43 μg/L for Sun Spruit River) was directly linked to their mass loads in the respective wastewater effluent samples.

The occurrence of 8 drugs of abuse and metabolites in the influent and effluent of the 3 Wastewater Treatment Plants (WWTP) that treat wastewater from Valencia was studied in 2011, 2012 and 2013. Target drugs except 6-monoacetylmorphine (6-ACMOR) were detected in 100% of the influents. The WWTPs eliminate cocaine (COC), amphetamine (AMP), methamphetamine (MAMP) and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH). Benzoylecgonine (BECG) was also efficiently eliminated (93–98%), whereas 3,4-methylenedioxymethamphetamine (MDMA) presented removal rates of 32–57% and ketamine (KET) was not eliminated. The most consumed illicit drugs, according to the estimated concentrations of each compound in the studied WWTPs, were cannabis and COC followed by KET, AMP, MAMP, MDMA and heroin. Environmental risk assessment was evaluated by calculating Risk Quotient (RQ). MDMA and KET could pose a medium risk and low risk, respectively, to the aquatic organisms. Although short-term environmental risk is not worrisome, long-term effects cannot be known exactly.

With increasing problems of drug abuse worldwide, aquatic ecosystems are contaminated by human pharmaceuticals from the discharge of hospital or municipal effluent. However, ecotoxicity data and related toxic mechanism for neuroactive controlled or illicit drugs are still lacking, so assessing the associated hazardous risk is difficult. This study aims to investigate the behavioral changes, oxidative stress, gene expression and neurotoxic or apoptosis effect(s) in larvae of medaka fish (Oryzias latipes) with environmentally relevant exposures of ketamine (KET) solutions for 1–14 days. KET exposure at an environmentally relevant concentration (0.004 μM) to 40 μM conferred specific patterns in larval swimming behavior during 24 h. At 14 days, such exposure induced dose- and/or time-dependent alteration on reactive oxygen species induction, the activity of antioxidants catalase and superoxide dismutase, glutathione S-transferase and malondialdehyde contents in fish bodies. KET-induced oxidative stress disrupted the expression of acetylcholinesterase and p53-regulated apoptosis pathways and increased caspase expression in medaka larvae. The toxic responses of medaka larvae, in terms of chemical effects, were qualitatively analogous to those of zebrafish and mammals. Our results implicate a toxicological impact of waterborne KET on fish development and human health, for potential ecological risks of directly releasing neuroactive drugs-containing wastewater into the aquatic environment.

Illicit drugs have been recognized as a group of emerging contaminants. In this work, occurrence of common illicit drugs and their metabolites in Chinese surface waters was examined by collecting samples from 49 lakes and 4 major rivers across the country. Among the drugs examined, methamphetamine and ketamine were detected with highest frequencies and concentration levels, consistent with the fact that these are primary drugs of abuse in China. Detection frequencies and concentrations of other drugs were much lower than in European lakes and rivers reported in the literature. In most Chinese surface waters methamphetamine and ketamine were detected at concentrations of several ng L−1 or less, but in some southern lakes and rivers, these two drugs were detected at much higher concentrations (up to several tens ng L−1). Greater occurrence of methamphetamine and ketamine in southern surface waters was attributed to greater abuse and more clandestine production of the two drugs in southern China.

This study provides a first estimate of the sources, distribution, and risk presented by emerging organic contaminants (EOCs) in coastal waters off southwestern Taiwan. Ten illicit drugs, seven nonsteroidal anti-inflammatory drugs (NSAIDs), five antibiotics, two blood lipid regulators, two antiepileptic drugs, two UV filters, caffeine, atenolol, and omeprazole were analyzed by solid-phase extraction and liquid chromatography coupled to tandem mass spectrometry (SPE–LC–MS/MS). Thirteen EOCs were detected in coastal waters, including four NSAIDs (acetaminophen, ibuprofen, ketoprofen, and codeine), three antibiotics (ampicillin, erythromycin, and cefalexin), three illicit drugs (ketamine, pseudoephedrine, and MDMA), caffeine, carbamazepine, and gemfibrozil. The median concentrations for the 13 EOCs ranged from 1.47ng/L to 156ng/L. Spatial variation in concentration of the 13 EOCs suggests discharge into coastal waters via ocean outfall pipes and rivers. Codeine and ampicillin have significant pollution risk quotients (RQ>1), indicating potentially high risk to aquatic organisms in coastal waters.

Illicit drug use has long been a key issue of international concern, and the true situation is unknown to the relevant authorities. To develop a profile of comprehensive consumption patterns of illicit drugs in China, data from 34 wastewater treatment plants in 25 cities were collected to analyze four classes of drugs, including amphetamine-type stimulants, opioids, ketamine, and cocaine. They were identified and quantified in samples using methods based on gas chromatography coupled to mass spectrometry. According to the wastewater-based epidemiology (WBE) approach, an analysis of the consumption pattern was performed regarding per inhabitant consumption based on the revised metabolic rate. The consumption quantity of illicit drug and precursor was divided into four categories based on statistical difference analyses: methamphetamine and ephedrine (precursor) were the predominant drugs in the first category, followed by ketamine and heroin in the second category, methcathinone and 3,4-methylenedioxymethamphetamine (MDMA) in the third category, and cocaine and methadone in the fourth category. There were distinctive spatial patterns: heroin and cocaine consumption was higher in Southern China than in Northern China, heroin consumption was higher in Western China than in Eastern China, and the consumption of each drug differed across seven regions of China, especially with ephedrine and methcathinone consumption higher in North China; heroin consumption higher in Southwest, Central, and Northwest China; and ketamine and MDMA consumption higher in East, South, and Central China. Compared with findings in previous studies, there were temporal patterns, in which ketamine consumption presented a downward trend but heroin remained stable. Based on correlation analyses, there were the polydrug abuse patterns between heroin and cocaine, methcathinone and ketamine, and cocaine and MDMA. In general, this study based on WBE provides a comprehensive evaluation of drug consumption in China.

BACKGROUND, AIM AND SCOPE: The Pego-Oliva Marsh is the second most important wetland in the Valencian Community (Spain). It is included in the RAMSAR agreement and represents one key point for migratory birds. Emerging contaminants from the human pressure, such as pharmaceuticals, illicit drugs and personal care product, are not included in the list of priority contaminants of the Water Framework Directive yet, and are neither monitored nor controlled. However, pollution of emerging contaminants can threaten the environment and even human health. In order to understand the status of the emerging contamination and recommend future rationalization of countermeasures, the occurrence of illicit drugs was investigated. MATERIAL AND METHODS: Samples were collected at 23 sites from the main irrigation channels and the marsh. Illicit drugs were extracted using solid phase extraction and determined by liquid chromatography tandem mass spectrometry. The method detection limits ranged from 0.01 to 1.54 ng l−1 and the recoveries from 57% to 120%. RESULTS AND DISCUSSION: 3,4-Methylenedioxymethamphetamine, ketamine, morphine, benzoylecgonine, cocaine, methadone, 6-acetylmorphine and nor-9-carboxy-tetrahydrocannabinol were detected. The mean concentrations were 0.62, 21.33, 1.30, 1.92, 2.25, 0.32, 0.04 and 0.07 ng l−1, respectively. The highest concentrations were in the north of Pego-Oliva Marsh. CONCLUSIONS: The pollution status by illicit drugs of the Pego-Oliva Marsh has been established. However, contamination levels in all the area of the natural park were low compared with those reported in other superficial waters.

Repeated administration of chlorpyrifos (CPF), an organophosphate pesticide, can increase the risk of oral cytotoxicity. The current study was designed to assess the mechanism by which CPF mediates its cytotoxic effect on lingual mucosa of rats. Twenty-four male Wistar rats were used in the present study and divided into three groups: group I: healthy rats (negative control), group II: rats treated with CPF 1/40 LD50 (3.375 mg/kg, orally/daily) for 28 days, group III: rats treated with CPF 1/10 LD50 (13.5 mg/kg, orally/daily) for 28 days. At the end of the experiment, all rats were sacrificed by cervical dislocation under ketamine anesthesia. Tongue samples were dissected out at their base for detection of heme oxygenase-1 (HO-1) and nuclear erythroid 2-related factor 2 (Nrf-2) by western blotting and histopathological and electron microscopic studies. Immunostaining was used to determine cleaved caspase 3 and the nuclear factor kappa B (NF-κB) localization. Structural and ultrastructural examination of treated lingual mucosa with CPF demonstrated degenerative changes that involved both the dorsal and ventral surfaces of the tongue as well as the lingual glands. CPF-treated rats demonstrated a significant increase in the levels of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor (TNF-α) in addition to a significant dose-dependent activation of NF-κB and cleaved caspase 3. Furthermore, CPF activated HO-1 and Nrf-2 pathway in a dose-dependent manner. In conclusion, this data suggests that the CPF-induced cytotoxicity may be explained by NF-κB activated inflammatory cascade. In addition, CPF triggers an adaptive activation of Nrf-2/HO-1 pathway.

Ketamine is an anesthetic and analgesic drug widely used in clinical anesthesia. To ensure the safety of anesthesia, it is necessary to study its side effects. Pregnancy is a key period for the development and growth of offspring. During this period, the proliferation and differentiation of brain cells and the synaptic formation are easily affected by external stimuli. Therefore, the aim of this study was to evaluate the effect of ketamine. Ketamine anesthesia was administered to rats in the second trimester of pregnancy, and two behavioral tests were performed, including contextual and cued fear conditioning test (CFC) and Morris water maze (MWM). At the end of the behavioral test, Nissl and Golgi staining were used to detect the dendrite density of hippocampal neurons to reveal the effect of maternal ketamine anesthesia on the hippocampus of offspring. Key proteins and their downstream transcription factors in Wnt/β-catenin signaling pathway from the embryonic development to the adulthood were studied. Our results showed that rats receiving maternal ketamine suffered from nerve injury. The density of hippocampal nerves and dendritic spine changed. Some genes related to Wnt/β-catenin pathway and Tcf/Lef were downregulated. In conclusion, maternal anesthesia with ketamine in the second trimester of pregnancy can lead to cognitive memory impairment and neurotoxicity in the hippocampus of offspring through Wnt/ β-catenin signaling pathway.

Illicit drugs and their metabolites have recently been recognized as an emerging group of contaminants due to their potential ecotoxicological impact in aquatic ecosystems. To date, information on the occurrence of these compounds in the aquatic environment of China remains limited. In this study, we collected surface water samples from 36 rivers in north China that discharge into the Bohai Sea and north Yellow Sea and measured the concentrations of amphetamine-like compounds, ketamines, cocainics, and opioids. The occurrence and spatial patterns of these substances show significant differences between the rivers and regions. Two designer drugs, methamphetamine (METH) and ketamine (KET), were the most abundant compounds detected in the entire set of samples (detection frequency of 92 and 69 %). The concentrations of METH and KET ranged from <0.1 to 42.0 ng L⁻¹ (mean = 4.53 ng L⁻¹) and <0.05 to 4.50 ng L⁻¹ (mean = 0.49 ng L⁻¹), respectively. The high detection frequencies of METH and KET are consistent with the fact that they are the main illicit drugs consumed in China. The high concentrations of these illicit drugs and their metabolites were found in areas that have a high population density. The riverine input of total illicit drugs into the Bohai Sea and north Yellow Sea was estimated to be in the range of 684 to 1160 kg per year.