Production Of N-nitrosodimethylamine Research Articles

Analysis of Ranitidine-Associated N-Nitrosodimethylamine Production Under Simulated Physiologic Conditions

N-nitrosodimethylamine (NDMA), a probable human carcinogen, was recently detected in ranitidine products,1 prompting widespread regulatory recalls.2 Ranitidine is a histamine2-receptor antagonist that inhibits gastric acid secretion and bears a molecular structure that putatively supports NDMA production under suitable reactive and storage conditions.3 We sought to further characterize conditions of NDMA production under simulated physiologic gastric states.

Effects of pre-ozonation on the cell characteristics and N-nitrosodimethylamine formation at three growth phases of Microcystis aeruginosa.

Pre-oxidation in water treatment is considered an effective method to enhance the removal of algal cells and their exuded organic matters. However, pre-oxidation also alters the characteristics of algae and consequently influences disinfection processes. The existing studies mainly focused on the stationary growth phase, but little is known for the exponential and declined phases. The objectives of this study were to examine the effects of pre-ozonation on the integrity of algal cells, the release of algal organic matters, and the formation of disinfection by-products like N-nitrosodimethylamine (NDMA) from Microcystis aeruginosa (M. aeruginosa) at three growth phases. The results demonstrated that pre-ozonation was efficient to inactivate M. aeruginosa cells. The severity of M. aeruginosa cell damage increased as the ozone dosage increased from 0.5 to 2.0mg/L. The damage of cell membranes resulted in the release of intracellular organic matters. Excitation-emission matrix spectra (EEMS) analysis indicated that ozone mainly reacted with soluble microbial products (SMP). With the increase of ozone concentration, although the trend of NDMA formation was similar for all three growth phases, more production of NDMA by algal cells was observed at the declined phase. In the post-disinfection process, chloramine showed the potential as a more suitable disinfectant than chlorination after pre-ozonation to minimize the NDMA formation. Therefore, appropriate pre-ozonation is beneficial to reduce the NDMA formation from exponential algae, while has no significant change during both stationary and declined phases.

Nitrosation of Dimethylamine with Dinitrogen Trioxide

A two-step procedure for preparing N-nitrosodimethylamine by direct nitrosation of aqueous solutions of dialkylamines with dinitrogen dioxide was suggested. The first step involves preparation of dialkylammonium nitrite, and in the second step, on heating to 70–90°С in a weakly acidic solution, it transforms into N-nitrosodialkylamine. The yield of N-nitrosodialkylamines is 95–98% based on the converted dialkylamine. A low-waste process for N-nitrosodimethylamine production was developed.

Effect of ozonation on minocycline degradation and N-Nitrosodimethylamine formation

ABSTRACTThe objective of this study was to assess reactivity of Minocycline (MNC) towards ozone and determine the effects of ozone dose, pH value, and water matrix on MNC degradation as well as to characterize N-Nitrosodimethylamine (NDMA) formation from MNC ozonation. The MNC initial concentration of the solution was set in the range of 2–20 mg/L to investigate NDMA formation during MNC ozonation. Four ozone doses (22.5, 37.2, 58.0, and 74.4 mg/min) were tested to study the effect of ozone dose. For the evaluation of effects of pH value, pH was adjusted from 5 to 9 in the presence of phosphate buffer. MNC ozonation experiments were also conducted in natural water to assess the influence of water matirx. The influence of the typical component of natural water was also investigated with the addition of HA and NaHCO3 solution. Results indicated that ozone was effective in MNC removal. Consequently, NDMA and dimethylamine (DMA) were generated from MNC oxidation. Increasing pH value enhanced MNC removal but led to greater NDMA generation. Water matrices, such as HCO3− and humic acid, affected MNC degradation. Conversely, more NDMA accumulated due to the inhibition of NDMA oxidation by oxidant consumption. Though ⋅OH can enhance MNC degradation, ozone molecules were heavily involved in NDMA production. Seven transformation products were identified. However, only DMA and the unidentified tertiary amine containing DMA group contributed to NDMA formation.

N-nitrosodimethylamine (NDMA) formation during ozonation of wastewater and water treatment polymers.

N-Nitrosodimethylamine (NDMA) formation by ozonation was investigated in the effluents of four different wastewater treatment plants destined for alternative reuse. Very high levels of NDMA formation were observed in wastewaters from treatment plants non operating with biological nitrogen removal. Selected experiments showed that hydroxyl radical did not have a significant role in NDMA formation during ozonation of wastewater. Furthermore, ozonation of three different polymers used for water treatment, including polyDADMAC, anionic polyacrylamide, and cationic polyacrylamide, spiked in wastewater did not increase the NDMA formation. Effluent organic matter (EfOM) likely reduced the availability of ozone in water able to react with polymers and quenched the produced ·OH radicals which limited polymer degradation and subsequent NDMA production. Excellent correlations were observed between NDMA formation, UV absorbance at 254 nm, and total fluorescence reduction. These data provide evidence that UV and fluorescence surrogates could be used for monitoring and/or controlling NDMA formation during ozonation.

N-nitrosodimethylamine formation from ozonation of chlorpheniramine: Influencing factors and transformation mechanism

As a disinfection byproduct, the detection of N-nitrosodimethylamine (NDMA) in aquatic environments across the globe has caused widespread concern due to its potential carcinogenicity. In this study, the possibility of NDMA formation from chlorpheniramine ozonation was investigated. The influencing factors including the initial chlorpheniramine concentration, ozone dose, pH, and water matrix were quantified. Furthermore, the mechanisms for chlorpheniramine transformation and NDMA formation were explored. Our results demonstrate that ozonation is effective in removing chlorpheniramine. Generation of dimethylamine (DMA) and NDMA was observed during chlorpheniramine ozonation. Higher initial chlorpheniramine concentration and ozone dose resulted in higher production of NDMA. Acidic conditions (pH≤5) did not facilitate the production of NDMA. Ozone molecules played a dominant role in chlorpheniramine degradation, and influenced DMA release and NDMA formation. DMA and NDMA generations as well as their degradations were mainly attributed to hydroxyl radicals (OH) produced by ozone decomposition. Water matrix properties such as HCO3− and humic acid affected DMA and NDMA generation due to OH competition. The degradation intermediates of chlorpheniramine were identified, among which only the intermediates with a DMA group were attributable to NDMA formation. A possible pathway for NDMA formation from chlorpheniramine ozonation is proposed.

N-nitrosodimethylamine formation upon ozonation and identification of precursors source in a municipal wastewater treatment plant.

Ozone doses normalized to the dissolved organic carbon concentration were applied to the primary influent, primary effluent, and secondary effluent of a wastewater treatment plant producing water destined for potable reuse. Results showed the most N-Nitrosodimethylamine (NDMA) production from primary effluent, and the recycle streams entering the primary clarifiers were identified as the main source of NDMA precursors. The degradation of aminomethylated polyacrylamide (Mannich) polymer used for sludge treatment was a significant cause of precursor occurrence. A strong correlation between NDMA formation and ammonia concentration was found suggesting an important role of ammonia oxidation on NDMA production. During ozonation tests in DI water using dimethylamine (DMA) as model precursor, the NDMA yield significantly increased in the presence of ammonia and bromide due to the formation of hydroxylamine and brominated nitrogenous oxidants. In addition, NDMA formation during ozonation of dimethylformamide (DMF), the other model precursor used in this study, occurred only in the presence of ammonia, and it was attributable to the oxidation of DMF by hydroxyl radicals. Filtered wastewater samples (0.7 μm) produced more NDMA than unfiltered samples, suggesting that ozone reacted with dissolved precursors and supporting the hypothesis of polymer degradation. Particularly, the total suspended solids content similarly affected NDMA formation and the UV absorbance decrease during ozonation due to the different ozone demand created in filtered and unfiltered samples.

Drinking Water as a Proportion of Total Human Exposure to Volatile N‐Nitrosamines

Some volatile N-nitrosamines, primarily N-nitrosodimethylamine (NDMA), are recognized as products of drinking water treatment at ng/L levels and as known carcinogens. The U.S. EPA has identified the N-nitrosamines as contaminants being considered for regulation as a group under the Safe Drinking Water Act. Nitrosamines are common dietary components, and a major database (over 18,000 drinking water samples) has recently been created under the Unregulated Contaminant Monitoring Rule. A Monte Carlo modeling analysis in 2007 found that drinking water contributed less than 2.8% of ingested NDMA and less than 0.02% of total NDMA exposure when estimated endogenous formation was considered. Our analysis, based upon human blood concentrations, indicates that endogenous NDMA production is larger than expected. The blood-based estimates are within the range that would be calculated from estimates based on daily urinary NDMA excretion and an estimate based on methylated guanine in DNA of lymphocytes from human volunteers. Our analysis of ingested NDMA from food and water based on Monte Carlo modeling with more complete data input shows that drinking water contributes a mean proportion of the lifetime average daily NDMA dose ranging from between 0.0002% and 0.001% for surface water systems using free chlorine or between 0.001% and 0.01% for surface water systems using chloramines. The proportions of average daily dose are higher for infants (zero to six months) than other age cohorts, with the highest mean up to 0.09% (upper 95th percentile of 0.3%).

Identification of Antiyellowing Agents as Precursors of N-Nitrosodimethylamine Production on Ozonation from Sewage Treatment Plant Influent

In Japan, N-nitrosodimethylamine (NDMA) formation associated with ozonation at a relatively high concentration has been reported only at a small number of water treatment plants (WTPs) in the western part of Japan for which the source water is the Yodo River. In the present study, the formation of relatively high concentrations of NDMA was found upon ozonation of water samples taken from sewage treatment plants (STPs) located upstream of the water intake points of the WTPs in the Yodo River basin. NDMA concentrations before and after ozonation were 16-290 and 14-280 ng/L, respectively. At least some of the STPs investigated receive industrial effluents. At one STP in this area, an extremely high concentration of NDMA (10,000ng/L) was found in one influent water sample after ozonation. To identify potential NDMA precursors upon ozonation in the influent at this STP, the concentrated extracts of the influent were fractionated by high-performance liquid chromatography (HPLC). Ultraperformance liquid chromatography coupled with tandem mass spectrometry (UPLC/MS/MS) identified 4,4'-hexamethylenebis(1,1-dimethylsemicarbazide) (HDMS) and 1,1,1',1'-tetramethyl-4,4'-(methylene-di-p-phenylene)disemicarbazide (TMDS) as precursors of NDMA on ozonation of the influent. Both HDMS and TMDS are used as antiyellowing agents in polyurethane fibers and as light stabilizers in polyamide resins. Their contributions to NDMA production on ozonation of water samples at STPs were up to 17%. The remaining unidentified NDMA precursors may be hydrophilic compounds that were not trapped by the cartridges used for extraction of the water samples. HDMS and TMDS were frequently present in surface waters and STP effluents in the Yodo River basin and were also detected in surface waters from several other areas in Japan.

Breakpoint chlorination and free-chlorine contact time: Implications for drinking water N-nitrosodimethylamine concentrations

North American drinking water utilities are increasingly incorporating alternative disinfectants, such as chloramines, in order to comply with disinfection by-product (DBP) regulations. N-Nitrosodimethylamine (NDMA) is a non-halogenated DBP, associated with chloramination, having a drinking water unit risk two to three orders of magnitude greater than currently regulated halogenated DBPs. We quantified NDMA from two full-scale chloraminating water treatment plants in Alberta between 2003 and 2005 as well as conducted bench-scale chloramination/breakpoint experiments to assess NDMA formation. Distribution system NDMA concentrations varied and tended to increase with increasing distribution residence time. Bench-scale disinfection experiments resulted in peak NDMA production near the theoretical monochloramine maximum in the sub-breakpoint region of the disinfection curve. Breakpoints for the raw and partially treated waters tested ranged from 1.9:1 to 2.4:1 (Cl 2:total NH 3-N, M:M). Bench-scale experiments with free-chlorine contact (2 h) before chloramination resulted in significant reductions in NDMA formation (up to 93%) compared to no free-chlorine contact time. Risk-tradeoff issues involving alternative disinfection methods and unregulated DBPs, such as NDMA, are emerging as a major water quality and public health information gap.

Oxidation of 1,1-dimethylhydrazine (UDMH) in aqueous solution with air and hydrogen peroxide

The degradation of 1,1-dimethylhydrazine (UDMH), a component of some rocket fuels, was investigated using atmospheric oxygen and hydrogen peroxide. The reactions were carried out in the presence and absence of copper catalysis and at varying pH. Reactions were also carried out in the presence of hydrazine, a constituent, along with UDMH, of the rocket fuel Aerozine-50. In the presence of copper, UDMH was degraded by air passed through the solution; the efficiency of degradation increased as the pH increased but the carcinogen N-nitrosodimethylamine (NDMA) was formed at neutral and alkaline pH. Oxidation was not seen in the absence of copper. Production of NDMA occurred even at copper concentrations of < 1 ppm. Oxidation of UDMH with hydrogen peroxide also gave rise to NDMA. When copper was absent degradation of UDMH did not occur at acid pH but when copper was present some degradation occurred at all pH levels investigated. The production of NDMA occurred mostly at neutral and alkaline pH. In general, higher concentrations of hydrogen peroxide and copper favored the production of NDMA. Dimethylamine, methanol, formaldehyde dimethylhydrazone, formaldehyde hydrazone, and tetramethyltetrazene were also produced. The last three compounds were tested and found to be mutagenic.