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Environmental Science & Technology Nov 2023Krypton chloride (KrCl*) excimer ultraviolet (UV) light may provide advantages for contaminant degradation compared to conventional low-pressure (LP) UV. Direct and...
Krypton chloride (KrCl*) excimer ultraviolet (UV) light may provide advantages for contaminant degradation compared to conventional low-pressure (LP) UV. Direct and indirect photolysis as well as UV/hydrogen peroxide-driven advanced oxidation (AOP) of two chemical contaminants were investigated in laboratory grade water (LGW) and treated secondary effluent (SE) for LPUV and filtered KrCl* excimer lamps emitting at 254 and 222 nm, respectively. Carbamazepine (CBZ) and -nitrosodimethylamine (NDMA) were chosen because of their unique molar absorption coefficient profiles, quantum yields (QYs) at 254 nm, and reaction rate constants with hydroxyl radical. Quantum yields and molar absorption coefficients at 222 nm for both CBZ and NDMA were determined, with measured molar absorption coefficients of 26 422 and 8170 M cm, respectively, and QYs of 1.95 × 10 and 6.68 × 10 mol Einstein, respectively. The 222 nm irradiation of CBZ in SE improved degradation compared to that in LGW, likely through promotion of in situ radical formation. AOP conditions improved degradation of CBZ in LGW for both UV LP and KrCl* sources but did not improve NDMA decay. In SE, photolysis of CBZ resulted in decay similar to that of AOP, likely due to the in situ generation of radicals. Overall, the KrCl* 222 nm source significantly improves contaminant degradation compared to that of 254 nm LPUV.
Topics: Dimethylnitrosamine; Water Pollutants, Chemical; Oxidation-Reduction; Carbamazepine; Ultraviolet Rays; Photolysis; Hydrogen Peroxide; Water Purification
PubMed: 37186817
DOI: 10.1021/acs.est.3c00703 -
The Science of the Total Environment Jun 2024The drugs and personal care products in water sources are potential threats to the ecological environment and drinking water quality. In recent years, the presence of... (Review)
Review
The drugs and personal care products in water sources are potential threats to the ecological environment and drinking water quality. In recent years, the presence of PPCPs has been detected in multiple drinking water sources in China. PPCPs are usually stable and resistant to degradation in aquatic environments. During chlorination, chloramination, and ozonation disinfection processes, PPCPs can act as precursor substances to generate N-nitrosodimethylamine (NDMA) which is the most widely detected nitrosamine byproduct in drinking water. This review provides a comprehensive overview of the impact of PPCPs in China's water environment on the generation of NDMA during disinfection processes to better understand the correlation between PPCPs and NDMA generation. Chloramine is the most likely to form NDMA with different disinfection methods, so chloramine disinfection may be the main pathway for NDMA generation. Activated carbon adsorption and UV photolysis are widely used in the removal of NDMA and its precursor PPCPs, and biological treatment is found to be a low-cost and high removal rate method for controlling the generation of NDMA. However, there are still certain regional limitations in the investigation and research on PPCPs, and other nitrosamine by-products such as NMEA, NDEA and NDBA should also be studied to investigate the formation mechanism and removal methods.
Topics: China; Disinfection; Water Purification; Water Pollutants, Chemical; Dimethylnitrosamine; Drinking Water; Disinfectants
PubMed: 38657805
DOI: 10.1016/j.scitotenv.2024.172498 -
Nigerian Journal of Physiological... Dec 2023Dimethyl nitrosamine (DMN), a potent hepatotoxin, exerts carcinogenic effects and induces hepatic necrosis in experimental animals via CYP2E1 metabolic activation, and...
Dimethyl nitrosamine (DMN), a potent hepatotoxin, exerts carcinogenic effects and induces hepatic necrosis in experimental animals via CYP2E1 metabolic activation, and generation of reactive oxygen species (ROS). Protocatechuic acid (PCA), a plant-based simple phenolic compound and potent antioxidant, has been shown to affect the development of neoplasia in the rat liver and inhibit the initiation or progression phases of most cancers. In this study, the modulatory effects of PCA on DMN-induced hepatotoxicity, oxidative stress, inflammation, and selected phase I xenobiotic metabolizing enzymes were investigated in male Wistar rats. This study assessed biomarkers of hepatic injury (alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and gamma- glutamyl transferase); oxidative stress (hydrogen peroxide concentration, lipid peroxidation, and reduced glutathione levels); measured activities of antioxidant enzymes (catalase, sodium dismutase, glutathione peroxidase, glutathione S-transferase); and inflammation (Tumor necrosis factor (TNF)-α, interleukin-1-Beta (IL-1β) and iNOS). The results of our investigation demonstrated that pretreatment with PCA at 50 and 100 mg/kg body weight p.o. reduced DMN (20 mg/kg bw) i.p. mediated hepatic injury, oxidative stress, and inflammation in a dose-dependent manner. In addition, the activities of phase I metabolizing enzymes were significantly induced except for aminopyrine-N-demethylase in the DMN-treated rats when compared with the DMN alone control group. This induction was also reversed by pre-treatment with PCA. The result of this study suggests that PCA is hepatoprotective against DMN-induced hepatic damage by its ability to suppress oxidative stress, inflammation, and modulate the activities of the selected phase I drug metabolizing enzymes. Thus, PCA may prove useful in combating DMN-induced hepatic damage.
Topics: Animals; Oxidative Stress; Rats, Wistar; Hydroxybenzoates; Male; Liver; Rats; Inflammation; Dimethylnitrosamine; Antioxidants; Chemical and Drug Induced Liver Injury
PubMed: 38696681
DOI: 10.54548/njps.v38i2.4 -
The Science of the Total Environment Sep 2023The discharge of substantial amounts of N-nitrosamines-contained wastewater into receiving rivers can significantly deteriorate water quality, as these carcinogenic...
The discharge of substantial amounts of N-nitrosamines-contained wastewater into receiving rivers can significantly deteriorate water quality, as these carcinogenic compounds can be easily transported into groundwater and drinking water systems. This study investigated the distribution of eight species of N-nitrosamines in river water, groundwater, and tap water located in the center of the Pearl River Delta (PRD), China. The results showed that three major N-nitrosamines, including N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), and N-nitrosodibutylamine (NDBA), with concentrations of up to 64 ng/L, were observed in river water, groundwater, and tap water, whereas the other compounds occurred sporadically. In river water and groundwater, high concentrations of NDMA, NDEA, N-nitrosomorpholine (NMOR), and NDBA were found in industrial and residential lands as compared to agricultural lands owing to the influence of various human activities. The primary sources of N-nitrosamines in river water were industrial and domestic wastewater, and the infiltration of river water was responsible for the high levels of N-nitrosamines in groundwater. Among the target N-nitrosamines, NDEA and NMOR with long biodegradation half-lives (>4 days) and low LogK values (<1) displayed the highest potential for groundwater. N-nitrosamines in groundwater and tap water pose significant potential cancer risks to residents, especially children, and juveniles, with lifetime cancer risks of over 10, necessitating advanced water treatments for drinking water and critical controls on primary industrial discharge in urban areas.
Topics: Child; Humans; Rivers; Wastewater; Drinking Water; Nitrosamines; Dimethylnitrosamine; Diethylnitrosamine; China
PubMed: 37201810
DOI: 10.1016/j.scitotenv.2023.164251 -
Journal of Hazardous Materials Aug 2023The carcinogenic nitrogenous disinfection by-product, N-nitrosodimethylamine (NDMA), is challenging to adsorb due to its high polarity and solubility. Our previous...
The carcinogenic nitrogenous disinfection by-product, N-nitrosodimethylamine (NDMA), is challenging to adsorb due to its high polarity and solubility. Our previous research demonstrated that the adsorptive removal of NDMA can be improved using surface-modified activated carbon (AC800). The current study evaluated the efficacy of AC800 in removing NDMA in a continuous-flow column over 75 days, using both granular activated carbon (GAC) and biologically activated carbon (BAC) columns. The AC800 GAC column demonstrated extended breakthrough and exhaustion times of 10 days and 22 days, respectively, compared to the conventional GAC column at 4 days and 10.5 days. The surface modification effect persisted for 25 days before the removal trends became indistinguishable. The AC800 BAC column outperformed the conventional BAC column with a longer breakthrough time of 11.3 days compared to 7.4 days. BAC columns consistently showed greater NDMA removal, emphasizing the role of biodegradation in NDMA removal on carbon. The higher NDMA removal in the inoculated columns was attributed to increased microbial diversity and the dominance of six specific genera, Methylobacterium, Phyllobacterium, Curvibacter, Acidovorax, Variovorax, and Rhodoferax. This study provides new insights into using modified activated carbon as GAC and BAC media in a real-world continuous-flow setup.
Topics: Biodegradation, Environmental; Charcoal; Dimethylnitrosamine; Water Pollutants, Chemical; Water Purification
PubMed: 37172385
DOI: 10.1016/j.jhazmat.2023.131518 -
Antioxidants (Basel, Switzerland) Aug 2023Liver fibrosis, defined by the aberrant accumulation of extracellular matrix proteins in liver tissue due to chronic inflammation, represents a pressing global health...
Liver fibrosis, defined by the aberrant accumulation of extracellular matrix proteins in liver tissue due to chronic inflammation, represents a pressing global health issue. In this study, we investigated the transcriptomic signatures of three independent liver fibrosis models induced by bile duct ligation, carbon tetrachloride, and dimethylnitrosamine (DMN) to unravel the pathological mechanisms underlying hepatic fibrosis. We observed significant changes in gene expression linked to key characteristics of liver fibrosis, with a distinctive correlation to the burn-wound-healing pathway. Building on these transcriptomic insights, we further probed the p53 signaling pathways within the DMN-induced rat liver fibrosis model, utilizing western blot analysis. We observed a pronounced elevation in p53 protein levels and heightened ratios of BAX/BCL2, cleaved/pro-CASPASE-3, and cleaved/full length-PARP in the livers of DMN-exposed rats. Furthermore, we discovered that orally administering oligonol-a polyphenol, derived from lychee, with anti-oxidative properties-effectively countered the overexpressions of pivotal apoptotic genes within these fibrotic models. In conclusion, our findings offer an in-depth understanding of the molecular alterations contributing to liver fibrosis, spotlighting the essential role of the apoptosis pathway tied to the burn-wound-healing process. Most importantly, our research proposes that regulating this pathway, specifically the balance of apoptosis, could serve as a potential therapeutic approach for treating liver fibrosis.
PubMed: 37627582
DOI: 10.3390/antiox12081588 -
Environmental Science and Pollution... Nov 2023Exposure to cadmium has been related to liver and kidney diseases such as polycystic and nephrotic syndrome. It is still unclear how cadmium contributes to these...
Exposure to cadmium has been related to liver and kidney diseases such as polycystic and nephrotic syndrome. It is still unclear how cadmium contributes to these diseases. It is believed that the induction of oxidative stress resulting from the inhibition of antioxidant enzyme activities and changes in drug-metabolizing enzymes in the liver could explain the role of cadmium in the development of different diseases in the kidney and probably other organs. Changes in oxidative stress markers, antioxidant enzymes, and drug-metabolizing enzyme activities were assessed in the liver of male rats exposed to cadmium chloride. Additionally, the protective effects of silymarin and garlic extract against cadmium toxicosis were evaluated. Rats were randomly divided into eight groups as follows, groups 1, 2, 3, 4, and 5, received orally saline, CdCl (1 mg/kg), garlic extract [800 mg/kg], silymarin (25 mg/kg) and silymarin plus garlic extract respectively for 28 consecutive days. Rats in groups 6, 7, and 8 were pretreated with the same doses of garlic, silymarin, and garlic plus silymarin, respectively for two hours before cadmium administration. The Western immunoblotting technique was used to investigate the protein expression of cytochrome P450 isozymes. Spectrophotometric methods were used to assess the activity of both antioxidant- and drug-metabolizing enzymes. Free radical levels [measured as thiobarbituric acid reactive substances (TBARS)], catalase, superoxide dismutase, and glutathione peroxidase activities increased whereas the levels of glutathione and the activities of glutathione S-transferase, glutathione reductase, and glutamyl transferase, cytochrome P450, aryl hydrocarbon dehydrogenase (AHH), dimethylnitrosamine-N-demethylase I (DMN-dI), 7-ethoxycoumarine-O-deethylase (ECOD), cytochrome b and NADPH-Cytochrome-c-reductase enzyme activities decreased after cadmium treatment. Furthermore, Western immunoblotting data revealed that glutathione peroxidase protein expression increased following cadmium exposure, but cytochrome P450 2E1 and 3A4 expressions were downregulated. However, pretreatment of rats with silymarin or garlic extract or both before cadmium administration was found to restore the protein expression of cytochrome P450 2E1 and 3A4, the level of free radicals, antioxidant enzymes, drug-metabolizing enzyme activities to their normal levels. Similarly, histological studies revealed that silymarin and/or garlic extract reduced the liver damage caused by cadmium. Silymarin and/or garlic extract reduced the adverse effects of cadmium on the activity of both drug-metabolizing and antioxidant enzymes activity. These antioxidants could be provided to those who work in cadmium-based sectors to help them cope with the adverse effects of cadmium on their kidneys. In addition, Inhibiting drug-metabolizing enzyme activity should be considered when administering therapeutic medications to persons exposed to cadmium because most therapeutic drugs and many endogenous substances are largely metabolized by these enzymes.
Topics: Male; Rats; Animals; Antioxidants; Cytochrome P-450 CYP2E1; Silymarin; Garlic; Cadmium; Pharmaceutical Preparations; Cytochrome P-450 Enzyme System; Oxidative Stress; Glutathione; Liver; Plant Extracts; Glutathione Peroxidase
PubMed: 37831250
DOI: 10.1007/s11356-023-30197-1 -
Archives of Toxicology Mar 2024N-nitrosodimethylamine (NDMA) is classified as a human carcinogen and could be produced by both natural and industrial processes. Although its toxicity and...
N-nitrosodimethylamine (NDMA) is classified as a human carcinogen and could be produced by both natural and industrial processes. Although its toxicity and histopathology have been well-studied in animal species, there is insufficient data on the blood and tissue exposures that can be correlated with the toxicity of NDMA. The purpose of this study was to evaluate gender-specific pharmacokinetics/toxicokinetics (PKs/TKs), tissue distribution, and excretion after the oral administration of three different doses of NDMA in rats using a physiologically-based pharmacokinetic (PBPK) model. The major target tissues for developing the PBPK model and evaluating dose metrics of NDMA included blood, gastrointestinal (GI) tract, liver, kidney, lung, heart, and brain. The predictive performance of the model was validated using sensitivity analysis, (average) fold error, and visual inspection of observations versus predictions. Then, a Monte Carlo simulation was performed to describe the magnitudes of inter-individual variability and uncertainty of the single model predictions. The developed PBPK model was applied for the exposure simulation of daily oral NDMA to estimate blood concentration ranges affecting health effects following acute-duration (≤ 14 days), intermediate-duration (15-364 days), and chronic-duration (≥ 365 days) intakes. The results of the study could be used as a scientific basis for interpreting the correlation between in vivo exposures and toxicological effects of NDMA.
Topics: Rats; Humans; Animals; Dimethylnitrosamine; Carcinogens; Tissue Distribution; Lung; Liver; Models, Biological
PubMed: 38127128
DOI: 10.1007/s00204-023-03652-8 -
The American Journal of Managed Care Apr 2024Generic medications represent 90% of prescriptions in the US market and provide a tremendous financial benefit for patients. Recently, multiple generic drugs have been...
OBJECTIVES
Generic medications represent 90% of prescriptions in the US market and provide a tremendous financial benefit for patients. Recently, multiple generic drugs have been recalled due to the presence of carcinogens, predominantly N-nitrosodimethylamine (NDMA), including an extensive recall of extended-release (ER) metformin products in 2020.
STUDY DESIGN
Primary pharmaceutical quality testing and database analysis.
METHODS
We tested marketed metformin immediate-release (IR) and ER tablets from a wide sample of generic manufacturers for the presence of carcinogenic impurities NDMA and N,N-dimethylformamide (DMF). We examined the association of level of impurity with drug price and the impact of the 2020 FDA recalls on unit price and prescription fill rate.
RESULTS
Postrecall NDMA levels were significantly lower in metformin ER samples (standardized mean difference = -2.0; P = .01); however, we found continued presence of carcinogens above the FDA threshold in 2 of 30 IR samples (6.67%). Overall, the presence of contaminant levels was not significantly associated with price for either IR (NDMA: R2 = 0.142; P = .981; DMF: R2 = 0.382; P = .436) or ER (NDMA: R2 = 0.124; P = .142; DMF: R2 = 0.199; P = .073) samples. Despite recalls, metformin ER prescription fills increased by 8.9% while unit price decreased by 19.61% (P < .05).
CONCLUSIONS
Recalls of metformin ER medications were effective in lowering NDMA levels below the FDA threshold; however, some samples of generic metformin still contained carcinogens even after FDA-announced recalls. The absence of any correlation with price indicates that potentially safer products are available on the market for the same price as poorer-quality products.
Topics: Humans; Metformin; Drugs, Generic; Prescriptions; Dimethylnitrosamine; Carcinogens
PubMed: 38603530
DOI: 10.37765/ajmc.2024.89450 -
Journal of the Science of Food and... Nov 2023Dried and salt-fermented fish products are important sources of N-nitrosodimethylamine (NDMA) exposure for human. As a potent carcinogen, NDMA was frequently detected in...
BACKGROUND
Dried and salt-fermented fish products are important sources of N-nitrosodimethylamine (NDMA) exposure for human. As a potent carcinogen, NDMA was frequently detected in roasted Alaska pollock fillet products (RPFs), which is among the most common fish products in China. Until now, the occurrence and development of NDMA and its precursors (nitrites, nitrates and dimethylamine) in RPFs during processing and storage were not well elucidated, and safety evaluation of this fish product is also urgently needed.
RESULTS
The presence of precursors in the raw material was verified and significant increase of nitrates and nitrites during processing was observed. NDMA was found generated during pre-drying (3.7 μg kg dry basis) and roasting (14.6 μg kg dry basis) process. Continuous increase in NDMA content can also be found during storage, especially at higher storage temperature. The 95th percentile of Monte Carlo simulated cancer risk (3.73 × 10 ) surpassed the WHO threshold (1.00 × 10 ) and sensitivity analysis implies the risk was mainly attributable to NDMA level in RPFs.
CONCLUSION
The occurrence of NDMA in RFPs was mainly a result of endogenous factors originating in Alaska pollock during processing and storage rather than exogenous contamination, and temperature played a pivotal role. The preliminary risk assessment results suggest that long-term consumption of RPFs would impose potential health risks for consumers. © 2023 Society of Chemical Industry.
Topics: Animals; Humans; Dimethylnitrosamine; Nitrites; Alaska; Neoplasms; Nitrates
PubMed: 37317902
DOI: 10.1002/jsfa.12786