Volatile Nitrite Research Articles

A 10-year retrospective review of exposures to volatile nitrites reported to the Victorian Poisons Information Centre

Introduction Volatile nitrites, such as amyl nitrite, are used recreationally to enhance sexual experience and provide a feeling of euphoria. They are associated with severe adverse reactions including methaemoglobinaemia and maculopathy. The aim of this study was to explore the epidemiology and clinical effects of volatile nitrite exposures reported to the Victorian Poisons Information Centre in Australia over a 10-year period. Methods This was a retrospective, observational study of poison centre call records. Data were extracted for all exposures to volatile nitrites reported from 2013 to 2022. Results There were 132 calls about volatile nitrites, representing 122 exposures, with a more than five-fold increase in the annual number of exposures (from five in 2013 to 26 in 2022). Ingestion (49.2%) and inhalation (27.9%) were the most common routes of exposure. Seventy-six (62.3%) patients reported one or more symptoms related to volatile nitrite exposure. The most common symptoms were light-headedness/dizziness (20.5%), oro-mucosal irritation (15.6%), ocular irritation (14.8%), nasal irritation (12.3%), and nausea/vomiting (9.8%). Less common, but potentially serious, adverse effects included methaemoglobinaemia (4.1%), hypoxia (1.6%) and hypotension (0.8%). Symptom severity was usually classified as minor (70/76, 92.1%) at the time of the poisons centre call. Fifty-four (44.3%) patients were either in the hospital when the poisons centre was contacted or were referred to the hospital by the poisons centre. Discussion The increase in reported volatile nitrite exposures observed in this study aligns with epidemiological data showing an increase in volatile nitrite usage in Australia. The findings about the nature of exposures and symptoms experienced can be used to inform harm reduction and education efforts for community members and health professionals. Conclusions Exposures to volatile nitrites reported to an Australian poisons centre increased between 2013 and 2022. More than 40% of exposures resulted in a hospital presentation. Methaemoglobinaemia was reported in 4.1% of cases.

Determination of Volatile and Non-Volatile Nitrite Products in Sausages

This diploma thesis deals with the issue of nitrite products in sausages by gas chromatography. These products may have carcinogenic or mutagenic properties. In this thesis, method for determination of 4-cyanophenol and N-nitrosoproline in sausages by gas chromatography with mass spectrometric detection was developed. A solution of formic acid in acetonitrile was used for analyte extraction. Prior to analysis, analytes must be derivatized by N,O-bis-(trimethylsilyl)-trifluoracetamide. The developed method was applied to real sausages samples. The standard addition method is used for the quantification of analytes.

Characterization of the physicochemical Properties, bacterial community and non-volatile profiles of fermented Yu jiangsuan by Weissella cibaria and Lactobacillus plantarum

Yu jiangsuan (YJS) is a unique traditional fermented condiment in China. Physicochemical, bacterial communities, and non-volatile properties were examined in inoculation Autochthonous Weissella cibaria and Lactobacillus plantarum. The results indicated that inoculation samples did well in shortening fermentation time; amino acid nitrogen (AN) and TCA-soluble peptide contents of fermented YJS were 10.8% and 17.4% higher than those of naturally fermented YJS, respectively. However, its total volatile base nitrogen (TVB-N), thiobarbituric acid (TBARS), and nitrite were only 74.3%, 87.2% and 83.6% of those of naturally fermented YJS. In addition, the dominant bacterial genera were Lactobacillus, Weissella and Pectobacterium, whose contributions were 41.2%, 20.3% and 5.5%, respectively. Moreover, 26 significantly differential metabolites were identified, and involved in 10 metabolic pathways. The decomposition of substrates and the formation of differential metabolites in YJS were primarily centered on the TCA cycle and the metabolism of carbohydrates. Therefore, this study is conducive to discovering the bacterial community structure and metabolite composition of probiotic inoculated YJS fermentation, as well as the potential value of core functional bacteria genera in controlling YJS production in industry.

Acute hemolytic anemia in a 34-year-old man after inhalation of a volatile nitrite "popper" product.

Acute hemolytic anemia in a 34-year-old man after inhalation of a volatile nitrite "popper" product.

Influence of plant protein‐dietary fiber composite gel and Lactiplantibacillus plantarum XC‐3 on quality characteristics of Chinese dry fermented sausage

To explore the reuse of brewer's grains and develop novel Chinese fermented sausage with healthy characteristics, the influences of the addition of plant protein-dietary fiber composite gel and Lactiplantibacillus plantarum XC-3 on Chinese dry fermented sausages were studied. The results showed that the addition of Lactiplantibacillus plantarum XC-3 reduced the pH, water activity, total volatile base nitrogen, residual nitrite, and thiobarbituric acid of fermented sausages while increasing the hardness, springiness, chewiness, and total volatile flavor substances of the fermented sausages (p < 0.05). In all, 69 volatile flavor substances were identified in the fermented sausages. The addition of plant protein-dietary fiber composite gel resulted in a significant increase in the acids and esters content of fermented sausages (p < 0.05), but the increase in gel addition resulted in a decrease in the total content of volatile flavor substances in fermented sausages (p < 0.05) (still much higher than in the fermented sausage without gel addition). Novelty impact statement The addition of plant protein-dietary fiber gel and inoculation with Lactiplantibacillus plantarum XC-3 effectively reduced harmful carcinogens in fermented sausages while promoting the production of flavor substances and adding some new ones. The novel fermented sausage developed in this study is delicious and healthy, which provides theoretical support for the development of healthy foods in the meat processing industry.

Poppers maculopathy as an effect of drug poisoning. A clinical case

In recent years, the range of combined narcotic drugs has widened. New chemical modifications have emerged, including so-called designer drugs, whose action on the body and in particular on the state of vision is increasingly difficult to determine. While the problem of drug abuse is growing drastically, timely detection of a possible toxic damage to the eye induced by drugs and reliable diagnosis differentiating such damage from other etiologies becomes a topical practical issue. The paper presents a clinical case of poppers maculopathy (poppers being a slang name of aromatic volatile alkyl nitrite compounds). Ophthalmological manifestations and differential diagnostic criteria of the damage are described. The mechanisms of action and possible treatment methods are discussed.

Volatile N-nitrosamine, residual nitrite, and ascorbic acid levels in sausages during storage

Introduction. The increasing global consumption of processed meat products has led to certain concerns. For instance, processed meat products are known to contain carcinogen precursor compounds, thus creating the risk of chronic diseases. The present study was performed to estimate the food safety status of processed meat products available in Iran and evaluate the related effective factors.&#x0D; Study objects and methods. 140 samples of seven most popular commercial types of cooked sausages were obtained from four major meat factories (A, B, C and D) in 140 samples were collected from seven most popular commercial types of cooked sausages as follows: beef salami 90%, chicken salami 90%, dry cured sausage 70%, dry cured salami 60%, beef sausages 55%, chicken sausages 55% and Frankfurt sausage 40% (n = 5) from four major meat factories (A, B, C and D) in Tehran. The samples were screened for residual nitrite, ascorbic acid, and nitrosamine contents on days 0, 7, 14, 21, and 28. The results indicated that products from meat factory B had lower residual nitrite content in the samples with high content of meat. Beef salami (90% of meat) and Frankfurt sausage (40% of meat) contained the lowest and highest amounts of residual nitrite on day 0 – 73.99 and 177.42 mg of nitrite per 1 kg of meat, respectively.&#x0D; Results and discussion. Beef salami contained 90% of meat, chicken salami – 90%, dry cured sausage –70%, dry cured salami – 60%, beef sausages – 55%, chicken sausages – 55%, and Frankfurt sausage – 40% (n = 5). Nitrite reduction rates in sausages with a smaller diameter, e.g. Frankfurt sausage, were significantly lower (P &lt; 0.05), compared to salami samples. The difference can be explained by the shorter cooking time. Nitrosamine formation increased during refrigerated storage; however, it was not significant in all samples. During refrigerated storage, nitrosamine formation depended on the level of added nitrite, the amount of residual nitrite, ascorbic acid, pH, and cooking temperature. Ascorbic acid content decreased significantly (P &lt; 0.05) during refrigerated storage.&#x0D; Conclusion. The findings demonstrate significant correlation between the meat content, cooking time, nitrite content, and nitrosamine formation.

Effect of Weissella cibaria co-inoculation on the quality of Sichuan Pickle fermented by Lactobacillus plantarum

The effect of Weissella cibaria co-inoculation on the quality of Sichuan Pickle (SCP) fermented by Lactobacillus plantarum was evaluated. The fresh cowpea and seasoning ingredients were sterilized firstly by 70% (v/v) edible alcohol solution, and then respectively fermented with W. cibaria or L. plantarum or their mixed inoculums in brine containing 6.0% salt for 7 days at 25 °C. The cell growth, pH, non-volatile organic acids, volatile flavor compounds, residual nitrite and biogenic amines were monitored during fermentation. Compared to mono-inoculation of L. plantarum, co-inoculation accelerated cell proliferation, pH decrease and production of non-volatile organic acids in initial fermentation, and also significantly promoted the formation of volatile flavor compounds in types and contents during fermentation, especially for the aroma-active and key volatile compounds, thus improved the overall sensory quality of SCP. Furthermore, the co-inoculation decreased the concentration of nitrite and biogenic amines by 5–12% and 6–12%, respectively. Therefore, co-inoculating W. cibaria has improved the food quality of SCP fermented by mono-inoculation of L. plantarum.

Effects of inoculating autochthonous starter cultures on N-nitrosodimethylamine and its precursors formation during fermentation of Chinese traditional fermented fish

This study investigated the effects of Lactobacillus plantarum 120, Saccharomyces cerevisiae 2018 and Staphylococcus xylosus 135 inoculation on N-nitrosodimethylamine (NDMA) and its precursors formation, and on microbiological characteristics of Chinese traditional fermented fish products (CTFPs). The results indicated that three strains could directly degrade NDMA in culture broth, and the highest degradation rate was observed in L. plantarum 120. The lactic acid bacteria counts in samples inoculated with L. plantarum 120 and mixed starter cultures were significantly (P < 0.05) higher than the others during the initial and middle fermentation stages (≤3 weeks). The final contents of total volatile base nitrogen, trimethylamine, dimethylamine, nitrite and NDMA in inoculated samples were significantly (P < 0.05) lower than those in spontaneous fermentation samples. According to these results, the inoculation with autochthonous starter cultures was a promising method to inhibit the NDMA and its precursors accumulation in CTFPs during fermentation process.

Poppers: legal highs with questionable contents? A case series of poppers maculopathy

BackgroundPoppers are volatile alkyl nitrite compounds that are inhaled to enhance sexual experience and for their psychoactive effects. A less well-known side effect is foveal maculopathy, which has emerged following...

Irradiated Chinese Rugao ham: Changes in volatile N-nitrosamine, biogenic amine and residual nitrite during ripening and post-ripening

N-nitrosamines, biogenic amines and residual nitrite are harmful substances and often present in cured meat. The effects of gamma-irradiation (γ-irradiation) on these chemicals in dry-cured Chinese Rugao ham during ripening and post-ripening were investigated. Rugao hams were irradiated at a dose of 5 kGy before ripening and were then ripened in an aging loft. Although γ-irradiation degraded tyramine, putrescine and spermine, on the other hand, it promoted the formation of spermidine, phenylethylamine, cadaverine and tryptamine. Residual nitrite was significantly reduced by γ-irradiation. N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA) and N-nitrosopyrrolidine (NPYR) were found in Chinese Rugao ham during ripening and post-ripening but could be degraded with γ-irradiation. The results suggest that γ-irradiation may be a potential decontamination measure for certain chemical compounds found in dry-cured meat.

Methemoglobinemia Caused by Volatile Nitrites

We report two cases of severe methemoglobinemia caused by accidental oral ingestion of volatile nitrites. Amyl nitrite, isobutyl nitrite, and other volatile nitrites are used as aromas and video head cleaners. However, they are also inhaled and abused to achieve arousal and mood-enhancement. Case 1 was a 26-year-old female who accidentally drank one 10 ml bottle of the inhaled stimulant “KIX®”, the primary ingredient of which is amyl nitrite and experienced dizziness, vomiting, and prominent systemic cyanosis. Arterial blood gas analysis demonstrated a Met-hemoglobin value of 58.3 percent. One hour after intravenous administration of 1.0 mg/kg methylene blue, Met-hemoglobin had decreased to 17.4 percent, and cyanosis had also disappeared. Case 2 was a 45-year-old male who accidentally drank a 9 ml bottle of the inhaled stimulant “RUSH®”, the primary ingredient of which is isobutyl nitrite. After 30 minutes, the subject experienced vomiting, loss of consciousness, prominent systemic cyanosis, and urinary and fecal incontinence. Arterial blood gas analysis demonstrated a Met-hemoglobin value of 54.7 percent. One hour after intravenous administration of 1.0 mg/kg methylene blue, Met-hemoglobin had decreased to 3.8 percent, and cyanosis had also disappeared. Intravenous administration of methylene blue was effective against methemoglobinemia caused by volatile nitrite poisoning. In severe methemoglobinemia, the proportion of oxygenated hemoglobin is reduced and exposes tissues to a hypoxic state in the first hour after treatment, even if oxygen partial pressure by arterial blood gas is high. In the interest of rapid treatment, we believe that pharmacies at emergency treatment facilities should prepare aqueous solutions of methylene blue in advance.

Intragastric volatile N-nitrosamines, nitrite, pH, and Helicobacter pylori during long-term treatment with omeprazole

Background & Aims: This study evaluated the effect of long-term gastric acid suppressive therapy with omeprazole on intragastric levels of carcinogenic N-nitrosamines and related parameters. Methods: Forty-five patients on long-term omeprazole medication (mean, 35 months) and 13 healthy subjects without medication participated. Volatile N-nitrosamines were determined in gastric juice and urine. Intragastric pH, nitrite, nitrate, and H. pylori status were determined. DNA isolated from gastric biopsy specimens was analyzed for precarcinogenic alkyl-DNA adducts. Results: The intragastric pH in patients was significantly higher compared with controls (P = 0.0001). Gastric nitrite levels in patients were nonsignificantly higher. There was no difference in total levels of intragastric volatile N-nitrosamines between patients and controls, however, urinary N-nitrosodimethylamine excretion was higher in patients (P = 0.001). On omeprazole, Helicobacter pylori–positive vs.–negative patients had a nonsignificantly higher intragastric nitrite level and higher urinary N-nitrosodimethylamine excretion. No alkyl-DNA adducts could be detected in gastric epithelium. Conclusions: Increased intragastric pH caused by long-term treatment with omeprazole does not result in increased intragastric levels of nitrite and volatile N-nitrosamines. The significantly higher urinary N-nitrosamine excretion implies the risk of increased endogenous formation of N-nitrosamines during long-term omeprazole treatment. This risk may be higher in H. pylori–positive patients.GASTROENTEROLOGY 2001;121:517-525

Recreational drugs and sexual behavior in the Chicago MACS/CCS cohort of homosexually active men

Since initial reports emerged of an association between recreational drug use and high-risk sexual behaviors in gay men, there has been interest in studying this relationship for its relevance to behavioral interventions. Reported here are the longitudinal patterns of alcohol and recreational drug use in the Chicago Multicenter AIDS Cohort Study (MACS)/Coping and Change Study (CCS) of gay men. A pattern of decreasing drug use over 6 years was observed that paralleled a decline in high-risk sexual behavior (i.e., unprotected anal intercourse). In contrast, alcohol consumption tended to be more stable over time, and to show no relationship to sexual behavior change. Men who combined volatile nitrite (popper) use with other recreational drugs were at highest risk both behaviorally and in terms of human immunodeficiency virus-1 (HIV) seroconversion throughout the study. Popper use also was associated independently with lapse from safer sexual behaviors (failure to use a condom during receptive anal sex). Use of other recreational substances showed no relationship to sexual behavior change patterns, and stopping popper use was unrelated to improvement in safer sexual behavior. When popper use and lapse from safer sex were reanalyzed, controlling for primary relationship status, popper use was associated with failure to use condoms during receptive anal sex among nonmonogamous men only. These findings suggest an association between popper use and high-risk sexual behavior among members of the Chicago MACS/CCS cohort that has relevance to HIV prevention intervention efforts.

Effect of Vitamin C on Endogenous Formation of N-Nitrosamines in Ureterosigmoidostomy Patients

The bacterially catalyzed formation of nitrosamines in the rectosigmoid is a favorite theroy for the increased risk of colon carcinomas following ureterosigmoidostomy. The urine/feces mixtures of 20 ureterosigmoidostomy patients were analyzed for nitrate, nitrite, volatile and nonvolatile nitrosamines prior to, and after, oral administration of vitamin C, a known nitrosation inhibitor. Following a 4-week period of daily ingestion of 2 g vitamin C (1 g in children) there was a slight, but not significant, decrease of volatile and nonvolatile nitrosamines and nitrite, as well as a nonsignificant increase in nitrate in the urine/feces of these patients. No correlation between the vitamin C concentration in serum or urine/feces mixture and the nitrosamine excretion was observed. These results suggest that the administration of vitamin C is not a suitable method for prophylaxis of endogenous nitrosation in ureterosigmoidostomy patients. Clinical and experimental findings implicate that factors other than nitrosamines play an important role in colon carcinogenesis of patients with ureterosigmoidostomies or other forms of urinary diversions using the small or large bowel.

Increased urinary nitrosamine excretion in paraplegic patients

An increased risk of bladder cancer is a recognized complication in spine-injured patients undergoing long-term urethral catheterization to preserve renal function. Aerobic cultures from 28 of 30 paraplegic patients showed complex bacterial flora containing nitrate-reducing organisms (Escherichia coli, Proteus and Klebsiella spp.). Urine samples from 29 paraplegic patients were also found to contain volatile nitrosamines. Mean N-nitrosamine excretion levels were 0.65 +/- 0.69 micrograms/day N-nitrosodimethylamine, 0.25 +/- 0.44 micrograms/day N-nitrosopiperidine and 0.39 +/- 0.50 micrograms/day N-nitrosopyrrolidine. A mean urinary nitrite excretion of 10.4 +/- 13.2 mg/day was found in 24 out of 30 paraplegic patients. In the sterile urine of control volunteers (medical staff attending the paraplegic patients and in-patients from other wards of the hospital), no urinary excretion of volatile N-nitrosamines and nitrite was found. The results clearly demonstrate a bacterially mediated in vivo formation of N-nitroso compounds in the urinary tracts of paraplegic patients which may be an important etiological risk factor for bladder cancer in this patient group.

Amyl Nitrite Alters Human in Vitro Immune Function

Effects on the human immune system of volatile nitrite inhalation were studied in 18 male volunteers. While nitrite inhalation decreased the absolute number of CD3+ T lymphocytes during the period of inhalation, cell numbers returned to pre-treatment levels within one week after cessation of the drug. Nitrite inhalation did not alter the percentage of CD3+, CD4+, CD8+ or CD19+ lymphocytes. Natural killer (NK) cell activity against K562 target cells was depressed by nitrite administration but returned to pre-inhalation or greater levels after nitrite discontinuation. Cell proliferation following cell activation by PHA, ConA and PWM was unaffected by amyl nitrite inhalation. We conclude that in humans inhalation of volatile nitrites causes cycles of modest immunosuppression, particularly in NK activity, followed by gradual recovery when the drug is not inhaled for several days.

Recreational drug use and sexual behavior change in a cohort of homosexual men

The relationship between use of recreational drugs and high-risk (HIV-transmitting) homosexual behavior was examined in the Multicenter AIDS Cohort Study (MACS) population. Among the 3916 men who completed both the baseline (1984) and first 6-month follow-up evaluations and were sexually active during the 6 months prior to enrollment, self-reported use of each of 10 classes of recreational drugs in conjunction with sexual activity was analyzed for both cross-sectional and prospective relationships with pattern of sexual behavior using a four-level sexual risk behavior index. At baseline, the proportion of men in the highest risk category (unprotected anal exposures with multiple partners) increased from 36 to 85% when men not using any drugs to men using three or more drugs plus volatile nitrites were examined. In multivariate logistical analyses, volatile nitrite use was significantly associated with failure to maintain or attain lower sexual risk levels after controlling for the effects of age, educational level and numbers of high-risk partners. These results suggest that volatile nitrite use may play an important role in the association between recreational drug use and high-risk sexual behavior among homosexual/bisexual men.

Toxicity, immunosuppressive effects and carcinogenic potential of volatile nitrites: possible relationship to Kaposi's sarcoma.

Volatile nitrite in the form of amyl nitrite was used for 100 years for the treatment of angina pectoris. In spite of recognized toxicity, its use in this form was considered safe. During the 1960s prescriptions were not required for purchase of amyl nitrite (called poppers) and its use for recreational purposes became popular. With reinstatement of the prescription requirement in 1969, non-medicinal, street-variety volatile nitrites were made commercially available in the form of mixtures of impure butyl and isobutyl nitrite; some of these preparations also included amyl nitrite. These products have been found to be profoundly immunosuppressive for human lymphocytes in vitro, and their by-products when metabolized into N-nitroso compounds have been known to be highly carcinogenic in many animal species. Recreational use of inhaled volatile nitrites is prevalent among male homosexuals and the compounds have been suspected as possible cofactors in Kaposi's sarcoma associated with the Acquired Immune Deficiency Syndrome (AIDS). This association could be explained by nitrite-induced vasodilation of rectal mucosal vessels providing a port of entry for a transmissible agent, by direct immunosuppression of the host allowing expression of a potentially oncogenic virus by co-carcinogenic effects of by-products by themselves or in conjunction with other putative cofactors such as cytomegalovirus. Nitrites should continue to be considered as a possible cofactor in the etiology of Kaposi's Sarcoma among male homosexuals and possibly those with other manifestations of AIDS.

Effect of Silage Extract on Voluntary Intake, Rumen Fluid Constituents, and Rumen Motility

The effects of intraruminal infusion of juice expressed from second cutting untreated (Silage) and formaldehyde-formic acid treated (Formal) alfalfa silage were investigated in two fistulated wethers. Infusion of 2.25 liters Silage juice coincident with the morning feeding depressed voluntary intake of hay for 1.5 to 9h and caused distortion in rumen motility. Formal juice had intermediate effects and water no effect. With infusions of Silage juice, maximum ruminal fluid volatile fatty acids (982 mg/100ml), lactate (1105 mg/100ml), and osmolality (551 mOsm/kg) were higher than previously associated with intake depression. However, synthetic juice with volatile fatty acids, lactate, soluble carbohydrate, pH, osmolality, ammonia, nitrite, and nitrate identical to the Silage juice accounted for only a maximum of 40% of its intake depressing effect when similarly infused. Other factors, such as amines, may have contributed to the depressing effects of the Silage juice on intake.