An Investigation Of Effects Of Copper And Zinc Ions As Well As Ethanol And Acetic Acid On NDMA Formation In Simulated Gastric Fluid

N-nitrosamines are a class of compounds with strong carcinogenicity. Epidemiological investigation has showed that the human stomach, esophagus, liver, colon and bladder cancer may be associated with N-nitrosamines. N-nitrosodimethylamine?NDMA?, as the simplest stable molecule in structure among all the nitrosamines, has been demonstrated to be the one of the most carcinogenic nitrosamines. Human exposure to NDMA occurs through two pathways, i.e., exogenous and endogenous routes. Moreover, endogenously formed NDMA has been estimated to account for 60% of total NDMA exposure. Therefore, investigations of the mechanisms and suppression methods of endogenous NDMA formation have attracted considerable research interests.So far, few studies about the effects of heavy metals, i.e., Cu and Zn ions, ethanol and acetic acid on endogenous NDMA formation have been done. Therefore, the objective of this study is to disclose the effects of Cu and Zn ions as well as ethanol and acetic acid on NDMA formation in simulated gastric fluid?SGF?.1. The effects of heavy metal Cu and Zn ions on NDMA formation in SGFThis study was to investigate the effects of heavy metal ions Cu²⁺ and Zn²⁺ on the formation of N-nitrosodimethylamine?NDMA? from dimethylamine?DMA? and nitrite?NO₂^?? in SGF by using gas chromatography-mass spectrometry?GC-MS? and ion chromatography?IC? methods. The results showed that Cu²⁺ and Zn²⁺ both promoted NDMA formation when the concentrations of Cu²⁺ and Zn²⁺ were in the ranges of 50²00 mg/L and 20²00 mg/L, respectively. Interestingly, Cu²⁺ and Zn²⁺ both inhibited NDMA formation when the concentrations were in the ranges of 10⁵0 mg/L and 10²0 mg/L, respectively. It was noteworthy that in very low concentration?1.0 mg/L? of Cu²⁺ and Zn²⁺, which is their guideline value in drinking water, can still enhance NDMA formation with the promotion rates of 16.9% and 13.4%, respectively. Mechanism research indicated that Cu²⁺ and Zn²⁺ can interact with DMA rather than NDMA and NO₂^?, which inferred that the promotion of the NDMA was mainly due to the interaction between the heavy metal ions with DMA to form intermediates M?DMA?x which were more reactive than DMA. This mechanism was consistent with our previous results about the effects of Pb²⁺, Cr²⁺ and Hg²⁺ on NDMA formation in SGF.2. The effects of ethanol and acetic acid on NDMA formation in SGFIn this study, effects of ethanol and acetic acid on NDMA formation with nitrite?NO₂^?? and DMA in SGF were investigated by using GC-MS and IC as well as quantum chemical calculation methods. Experimental results showed that ethanol and acetic acid in the concentrations of 0¹0%?V/V? exhibited inhibitory and promotion effects on NDMA formation, respectively. Moreover, they were both in a dose-dependent manner. Further experimental investigations indicated that ethanol and acetic acid could both interact with NO₂^? rather than NDMA and DMA. Theoretical calculations confirmed the above experimental results and demonstrated that ethanol and acetic acid could both react with nitrite-related nitrosating agents to produce ethyl nitrite?Et ONO? and acetyl nitrite?AcONO?, respectively. Furthermore, the reactivities of EtONO, AcONO and dinitrogen trioxide?N₂O₃? reacting with DMA were found in the order: AcONO > N₂O₃ >> EtONO. This was probably the main reason why there are completely different effects of ethanol and acetic acid on NDMA formation. Based on the above results, two requirements for a potential inhibitor of NOCs formation in SGF should be met,i.e., it should be feasible to react with nitrite-related species in SGF and the product of the above reaction should be unfavorable to nitrosating reactions. Meanwhile, the theoretical results indicated that EtSH is a potential nitrosamine inhibitor, and HBr could promote nitrosamines formation, which are consistent with the experimental results.In addition,the formation mechanisms of N-nitrosodiethanolamine?NDELA? from diethanolamine?DEA? and N₂O₃ in postcombustion carbon capture?PCC? were investigated by using density functional theory?DFT?. The study demonstrated that DEA could react with CO₂ to form intermediate diethanolcarbamic acid?DECA?. Furthermore, the energy barrier of the nitrosation of DECA by N₂O₃ was much higher than that of the nitrosation of DEA by N₂O₃. It inferred that CO₂ exhibited inhibitory effect on NDELA formation by inactivating amines.The results obtained from this study will be not only helpful to better understand the formation mechanisms of N-nitrosamine but also significant in searching for N-nitrosamine inhibitors. This has an important significance in keeping human health and reducing the incidence of cancer.