Emerging disinfection byproducts 3-bromine carbazole induces cardiac developmental toxicity via aryl hydrocarbon receptor activation in zebrafish larvae.

3-bromine carbazole (3-BCZ) represents a group of emerging aromatic disinfection byproducts (DBP) detected in drinking water; however, limited information is available regarding its potential cardiotoxicity. To assess its impacts, zebrafish embryos were exposed to 0, 0.06, 0.14, 0.29, 0.58, 1.44 or 2.88 mg/L of 3-BCZ for 120 h post fertilization (hpf). Our results revealed that ≥1.44 mg/L 3-BCZ exposure induced a higher incidence of heart malformation and an elevated pericardial area in zebrafish larvae; it also decreased the number of cardiac muscle cells and thins the walls of the ventricle and atrium while increasing cardiac output and impeding cardiac looping. Furthermore, 3-BCZ exposure also exhibited significant effects on the transcriptional levels of genes related to both cardiac development (nkx2.5, vmhc, gata4, tbx5, tbx2b, bmp4, bmp10, and bmp2b) and cardiac function (cacna1ab, cacna1da, atp2a1l, atp1b2b, atp1a3b, and tnnc1a). Notably, N-acetyl-L-cysteine, a reactive oxygen species scavenger, may alleviate the failure of cardiac looping induced by 3-BCZ but not the associated cardiac dysfunction or malformation; conversely, the aryl hydrocarbon receptor agonist CH131229 can completely eliminate the cardiotoxicity caused by 3-BCZ. This study provides new evidence for potential risks associated with ingesting 3-BCZ as well as revealing underlying mechanisms responsible for its cardiotoxic effects on zebrafish embryos.

Analysis of synthetic cannabinoids in wastewater of major cities in China.

Synthetic cannabinoids (SCs) could pose serious health risks to its users. It is necessary to monitor its community consumption. Wastewater-based epidemiology is a potentially useful approach in this regard. However, limited research has been conducted to investigate the occurrence of SCs in wastewater. In this study, liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was optimized to analyze 8 SCs and metabolites (in total 16 analytes) in wastewater. The limit of quantification for this method for certain analytes in wastewater was as low as 0.03 ng L-1. The validated method was used to examine the stability of the analytes under different conditions and to examine their occurrence in wastewater collected from 31 major cities across China. The overwhelming majority of the analytes were stable within 24 h, even at room temperature. However, 5-fluoro MDMB-PICA and MDMB-4en-PINACA butanoic acid metabolite showed significant degradation within 120 days even when stored at -20 °C or -80 °C. At least one cannabinoid or their metabolite was detected in 21 cities. In the city with the highest detection rate, at least one synthetic cannabinoid or metabolite was detected in 95% of samples of the city. MDMB-4en-PINACA butanoic acid metabolite had the highest detection frequency (in 13.4% of the samples). These results indicated that SCs were used in a significant number of Chinese cities. A few parent drugs (MDMB-4en-PINACA, ADB-BUTINACA, 5-fluoro MDMB-PICA, 4-fluoro MDMB-BUTINACA) were detected in a small fraction of wastewater samples, possibly due to release from manufacturing of these cannabinoids or illegal addition of electronic cigarettes.

Monitoring consumption of methadone and heroin in major Chinese cities by wastewater-based epidemiology.

BACKGROUND: Methadone maintenance treatment (MMT) services have been used in China for treatment of heroin dependence. But no study has been conducted to assess the appropriateness of MMT distribution and the potential abuse of methadone in China. This study aims to do that through a nationwide estimation of methadone consumption in China via wastewater-based epidemiology and subsequently compare it with MMT data and level of heroin abuse. METHODS: Wastewater samples were collected from 53 wastewater treatment plants in 27 major cities that cover all geographic regions of China. Methadone and pure heroin consumptions were estimated based on influent concentrations of methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), morphine and codeine. RESULTS: Drug residues were detected in most samples. The ratio of EDDP/methadone was around 2 in influents and methadone and EDDP loads were strongly correlated, indicating that they originated from human consumption. Both influent methadone and EDDP loads in Southwest and Northwest China were significantly higher than those in other regions. The highest estimated consumptions of methadone and heroin in China were 22.0 ±â€¯2.1 mg/1000 in./d and 263.9 ±â€¯115.9 mg/1000 in./d, respectively. There was a significant positive correlation between methadone and heroin consumptions. CONCLUSIONS: Consumption of methadone in China was primarily from MMT services. The use of methadone and heroin displayed a clear geographical pattern: it is higher in the western inland regions than in the eastern regions. This study has shown that the distribution of MMT services is reflective of the level of heroin abuse in different regions of China.

Estimating heroin abuse in major Chinese cities through wastewater-based epidemiology.

Heroin consumption in major cities across China was estimated for the first time via wastewater-based epidemiology. Influent and effluent wastewater samples were collected from 49 wastewater treatment plants (WWTPs) in 24 major cities that cover all the geographic regions of the country. Concentrations of morphine, 6-acetylmorphine, and codeine were measured. Near complete removal of morphine by wastewater treatment processes was observed, whereas removal rates of codeine were slightly lower. Morphine loads were much higher than codeine loads at most WWTPs in China, a trend opposite to that in many European countries. In addition, morphine and codeine loads were strongly correlated at most WWTPs, indicating morphine and codeine in wastewater were predominantly from the same source, street heroin. At WWTPs in Guangzhou and Shenzhen, codeine loads were considerably higher than morphine loads, consistent with previous reports of codeine abuse (e.g., as cough syrup) among middle and high school students in Guangdong province. Heroin consumption was derived based on morphine loads and taking into account therapeutic use of morphine and codeine, as well as contribution of codeine and acetylcodeine in street heroin. Highest heroin consumption was observed in northwestern and southwestern China. The average heroin consumption of the sampled cities was 64.6±78.7mg/1000inh/d. The nation-wide average heroin consumption was much lower than that of methamphetamine, consistent with seizure data and numbers of registered heroin and methamphetamine users in China.