Nitrous Acid

Exists only in solution; Light blue liquid; [Merck Index]

Solid

In water, it changes quickly into nitric oxide and nitric acid. Forms stable, water-soluble nitrites with Li, Na, K, Ca, Sr, Ba, Ag. Does not form salts with weak polyvalent cations like Al or Be. Forms stable esters with alcohols.

Stable only in solution

Nitrous acid decomposes into nitric oxide and nitric acid. It can also react as either an oxidizing or reducing agent.

Known only in solution (pale blue in color)

Danger

H300 (50%): Fatal if swallowed [Danger Acute toxicity, oral]

P260, P264, P264+P265, P270, P273, P280, P301+P316, P301+P330+P331, P302+P361+P354, P304+P340, P305+P354+P338, P316, P317, P321, P330, P363, P391, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 2 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reacts violenty with /phosphine/ and /phosphorus trichloride/. Reactions with 1-amino-5-nitrophenol, ammonium decahydroborate(2-), hydrazine (product is hydrogen azide); may give explosive products. Incompatibilities with anilines (e.g., 4-bromoaniline, 2-chloroaniline, 3-chloroaniline, 2-nitroaniline, 3-nitroaniline, 4-nitroaniline, aniline), semicarbazone, silver nitrate.

CSL00201

1,5-Diamino-1H-tetrazole + Carbonimidic dihydrazide, hydrochloride + 5-Azido-2H-tetrazole + Nitrous acid + Ethanol

"We recently had an unanticipated explosion resulting in the injury of two chemists. The workers were repeating a recently published preparation of 1,5-diamino-1H-tetrazole by the aqueous diazotization of diaminoguanidine hydrochloride using a single equivalent of nitrous acid (Inorg. Chem. 2005, 44, 4237). After neutralization (pH 8) and evaporation, the desired product is extracted from the inorganic salts with hot ethanol. The ethanol is then evaporated and the resulting solid recrystallized from water. The preparation states that the product is pure after the ethanol extraction. Unfortunately, we have found that the ethanol extracts not only the desired product but also a very sensitive side product, 5-azidotetrazole. This side product is produced by either double diazotization of diaminoguanidine or possibly by diazotization of the desired product through the intermediate 1H-tetrazolo[1,5-d]tetrazole. If this procedure is repeated, it is imperative that the ethanol extract not be taken to dryness." (reprint of full text)

Explosive

Not Available

10.1021/cen-v083n030.p005

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.

0.16 [ppm]

24 [ppm]

92 [ppm]

Methemoglobinemia can be treated with supplemental oxygen and methylene blue 1% solution administered intravenously slowly over five minutes followed by IV flush with normal saline. Methylene blue restores the iron in hemoglobin to its normal (reduced) oxygen-carrying state. (L1613)

The Ames/Salmonella assay was used to determine the effect of nitrous acid on the mutagenicity of solvent refined coal (SRC) distillates and distillate fractions. The SRC materials consisted of the higher-molecular-weight, high-boiling distillates, the process solvent (PS) and heavy distillate (HD), and also included the basic tar and neutral tar chemical fractions derived from these 2 distillates. Nitrosation products of each of the SRC materials were less mutagenic than the distillates of distillate fractions from which they were derived (untreated materials); in most cases they were less than 10% as mutagenic as that observed in the starting materials. The mutagenicity of the SRC materials after nitrous acid treatment was direct-acting, whereas all mutagenicity associated with the untreated SRC materials was indirect and required metabolic activation for expression in the Ames assay system.

... The ability of monomeric and dimeric flavanols to scavenge reactive nitrogen species derived from nitrous acid /is demonstrated/. Both epicatechin and dimer B2 (epicatechin dimer) inhibited nitrous acid-induced formation of 3-nitrotyrosine and the formation of the carcinogenic N-nitrosamine, N-nitrosodimethylamine. The reaction of monomeric and dimeric epicatechin with nitrous acid led to the formation of mono- and di-nitroso flavanols, whereas the reaction with hesperetin resulted primarily in the formation of nitrated products. Although, epicatechin was transferred across the jejunum of the small intestine yielding metabolites, its nitroso form was not absorbed. Dimer B2 but not epicatechin monomer inhibited the proliferation of, and triggered apoptosis in, Caco-2 cells. The latter was accompanied by caspase-3 activation and reductions in Akt phosphorylation, suggesting activation of apoptosis via inhibition of prosurvival signaling. Furthermore, the dinitroso derivative of dimer B2, and to a lesser extent the dinitroso-epicatechin, also induced significant toxic effects in Caco-2 cells. The inhibitory effects on cellular proliferation were paralleled by early inhibition of ERK 1/2 phosphorylation and later reductions in cyclin D1 levels, indicating modulation of cell cycle regulation in Caco-2 cells. These effects highlight multiple routes in which dietary derived flavanols may exert beneficial effects in the gastrointestinal tract.

Nitrite causes the autocatalytic oxidation of oxyhemoglobin to hydrogen peroxide and methemoglobin. This elevation of methemoglobin levels is a condition known as methemoglobinemia, and is characterized by tissue hypoxia, as methemoglobin cannot bind oxygen. (A2450, L1613)

/PLANTS/ An open top chamber experiment was carried out ... to examine the effect of nitrous acid (HONO) gas on the physiological status of Scots pine saplings (Pinus sylvestris). Four-year-old pine trees were exposed to two different levels of HONO gas (at ca. 2.5 ppb and 5.0 ppb) and a control (filtered air) from early evening to early morning (18:00-6:00), in duplicate open top chambers. Significant decreases in the ratios of chlorophylls a to b, an increase in the carbon to nitrogen (C/N) ratio, and a reduction of maximum yield of PS II (F(v)/F(m)) in pine needles were also observed after the 2 months' fumigation. Cation contents of pine needles were also decreased by the fumigation with HONO gas. The results could be explained by the harmful effects of OH radicals, generated from photolysis of HONO gas, and/or aqueous phase HONO (NO(2)(-)/HONO), on the photosynthetic capacity of pine needles.

Nitrite poisoning causes methemoglobinemia. Symptoms include cyanosis, cardiac dysrhythmias and circulatory failure, and progressive central nervous system (CNS) effects. CNS effects can range from mild dizziness and lethargy to coma and convulsions. (L1137)

/HUMAN EXPOSURE STUDIES/ Nitrous acid, a component of photochemical smog and a common indoor air pollutant, may reach levels of 100 ppb where gas stoves and unvented portable kerosene heaters are used. Nitrous acid is a primary product of combustion and may also be a secondary product by reaction of nitrogen dioxide with water. ... To assess the respiratory effects of nitrous acid exposure alone, ... a double-blinded crossover chamber exposure study /was conducted/ with 11 mildly asthmatic adult subjects. Each underwent 3-hr exposures to 650 ppb nitrous acid and to filtered room air with three 20-min periods of moderate cycle exercise. Symptoms, respiratory parameters during exercise, and spirometry after exercise were measured. A statistically significant decrease in forced vital capacity was seen on days when subjects were exposed to nitrous acid. This effect was most marked at 25 min and 85 min after exposure began. Aggregate respiratory and mucous membrane symptoms were also significantly higher with nitrous acid. ... This concentration and duration of exposure to nitrous acid alters lung mechanics slightly, does not induce significant airflow obstruction, and produces mild irritant symptoms in asthmatics.

/EPIDEMIOLOGY STUDIES/ Exposure to nitrous acid, which is a primary product of combustion, and is also formed when nitrogen dioxide (NO2) reacts with water, may play an important role in respiratory health. We estimate the independent effects of exposure to nitrogen dioxide and nitrous acid on respiratory symptoms during the first year of life. METHODS: Nitrogen dioxide and nitrous acid concentrations were measured once (1996-1998) in the homes of 768 infants who were at risk for developing asthma. Infants were living in southern New England. The frequency of respiratory symptoms in these children was recorded during the first year of life. RESULTS: Infants living in homes with an NO2 concentration exceeding 17.4 ppb (highest quartile) had a higher frequency of days with wheeze (rate ratio = 2.2; 95% confidence interval = 1.4-3.4), persistent cough (1.8; 1.2-2.7), and shortness of breath (3.1; 1.8-5.6) when compared with infants in homes that had NO2 concentrations lower than 5.1 ppb (lowest quartile), controlling for nitrous acid concentration. Nitrous acid exposure was not independently associated with respiratory symptoms. CONCLUSIONS: Among infants at risk for developing asthma, the frequency of reported respiratory symptoms in the first year of life was associated with levels of NO2 not currently considered to be harmful.

/ALTERNATIVE and IN VITRO TESTS/ Cultured fibroblasts from normal persons or persons afflicted by xeroderma pigmentosum were used as hosts for adenovirus 2 infection. With xeroderma cells as hosts, nitrous acid-treated virus showed less plaque-forming ability than when normal cells were used, indicating that DNA damaged by nitrous acid is at least partly repaired by normal human cells.

/OTHER TOXICITY INFORMATION/ ... Residual nicotine from tobacco smoke sorbed to indoor surfaces reacts with ambient nitrous acid (HONO) to form carcinogenic tobacco-specific nitrosamines (TSNAs). Substantial levels of TSNAs were measured on surfaces inside a smoker's vehicle. Laboratory experiments using cellulose as a model indoor material yielded a > 10-fold increase of surface-bound TSNAs when sorbed secondhand smoke was exposed to 60 ppbv HONO for 3 hours. In both cases we identified 1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal, a TSNA absent in freshly emitted tobacco smoke, as the major product. The potent carcinogens 4-(methylnitrosamino)-1-(3-pyridinyl)-1-butanone and N-nitroso nornicotine were also detected. Time-course measurements revealed fast TSNA formation, with up to 0.4% conversion of nicotine. Given the rapid sorption and persistence of high levels of nicotine on indoor surfaces-including clothing and human skin-this recently identified process represents an unappreciated health hazard through dermal exposure, dust inhalation, and ingestion. These findings raise concerns about exposures to the tobacco smoke residue that has been recently dubbed "thirdhand smoke."

/GENOTOXICITY/ Deoxyinosine occurs in DNA by spontaneous deamination of adenine or by incorporation of dITP during replication. Hypoxanthine residues (HX) are mutagenic and give rise to A-T-->G-C transition. They are substrates for the Escherichia coli product of the alkA gene, the 3-methyl-adenine-DNA glycosylase II (ALK A protein). In mammalian cells and in yeast, HX is excised by the counterpart of ALK A protein, the ANPG or the MAG proteins respectively. ... In vivo the contribution of the alkA gene to counteract the lethal and/or mutagenic effects of HX residues induced by nitrous acid treatment /was examined/. Using an E.coli strain allowing the detection of A-T-->G-C transition, /it was shown/ that the alkA mutant has a slightly increased spontaneous rate of mutation and about the same sensitivity when treated with HNO2 as compared with the wild-type strain. Using the E.coli alkA mutant carrying a multicopy plasmid expressing the ALK A protein or the ANPG protein, ... barely ... any effect of HNO2 treatment on sensitivity and mutation rate of the bacteria /was observed/. In contrast, the same experiment performed with a uvrA- strain, deficient in nucleotide excision repair (NER), shows that this mutant is extremely sensitive to HNO2 treatment. Furthermore, the sensitivity and the spontaneous mutation rate observed in the double mutant alkA- uvrA- are almost identical to those of the uvrA- mutant. Hence, NER has the major role in vivo for the repair of lethal and mutagenic lesions induced by HNO2.

/GENOTOXICITY/ Nitrous acid (NA) is often presumed to cause base substitutions in organisms with double-stranded DNA as a direct consequence of oxidative deamination of adenine and of cytosine residues. Here ... evidence indicating that other mechanisms are involved in the case of NA-induced G/C-->A/T transition mutations /is summarized/. ...Several models /are presented/ for pathways of NA mutagenesis that may account for our experimental results and overlapping data noted in the literature. One model proposes that the base substitution mutations observed are due to DNA alkylation damage mediated via nitrosation of polyamines and/or other ubiquitous cellular molecules. Other models assume that predisposing lesions, such as G-to-G cross-links, are first formed. The cross-links are pictured as leading to perturbations in DNA structure that allow subsequent opportunity for NA-induced deaminations of cytosine residues in their immediate vicinity. The deaminations preferentially result in G/C-->A/T transition mutations at sites highly dependent on adjoining base sequence context (i.e., in NA "mutational hotspots"). A final model proposes that NA-induced G/C-->A/T transition mutations arise mainly from oxidative deamination of guanosine residues and not from deamination of cytosine residues in duplex DNA.

/GENOTOXICITY/ The rate of nitrous acid deamination of labeled cytosine residues in native Escherichia coli deoxyribonucleic acid was monitored in vitro by release of acid-soluble counts after treatment with uracil deoxyribonucleic acid glycosylase. The reaction exhibited a lag and was not stimulate by several agents previously shown to enhance base substitution mutagenesis during nitrous acid treatment of duplex deoxyribonucleic acid. We conclude that a significant proportion of nitrous acid induced mutagenic lesions are novel lesions and not cytosine deaminations.

/GENOTOXICITY/ Purified native Hemophilus influenzae DNA is relatively insusceptible to nitrous acid (NA) mutagenesis in vitro, but is readily mutated following denaturation. NA mutagenicity for duplex DNA is significantly increased in the presence of various alcohols, glycols, phenols or primary amines. Phenol-extracted DNA contains dissociable contaminants of low molecular weight that enhance NA mutagenesis. Enhancement of NA mutagenesis by phenol and by spermine is due to the formation of unstable molecular species. We propose that reactive organic nitroso compounds are formed which then serve as delivery vehicles to promote mutagenicity of native DNA, perhaps via transnitrosation reactions. Similar reactions probably occur in vivo to promote NA-induced base substitution (but not frameshift) mutations in Salmonella typhimurium and in Escherichia coli.

For more Non-Human Toxicity Excerpts (Complete) data for Nitrous acid (16 total), please visit the HSDB record page.

Cyanide has a high affinity for the oxidized form of iron (Fe3+) such as that found in cytochrome oxidase a3. Cyanide binds to and inhibits cytochrome oxidase a3, preventing oxidative phophorylation from occuring. The resultant lack of ATP cannot support normal cellular processes, particularly in the brain. Compensatory increases in anaerobic respiration result in rising levels of lactic acid and subsequent acidosis. Nitrite primarily acts by oxidizing hemoglobin to methemoglobin. The now oxidized Fe3+ in methemoglobin also binds cyanide with high affinity and accepts cyanide from cytochrome a3. This leaves cytochrome a3 free to resume its function in oxidative phosphorylation. The slow dissociation of cyanide from methemoglobin allows hepatic enzymes such as rhodanese to detoxify the compound without further systemic toxicity occuring. Methemoglobin is reduced back to hemoglobin by methemoglobin reductase allowing the affected blood cells to resume normal functioning. The reduction of nitrite by hemoglobin results in the formation of nitric oxide. Nitric oxide acts as a powerful vasodilator, producing vascular smooth muscle relaxation through activation of soluble guanylate cyclase and the subsequent cyclic guanylyl triphosphate mediated signalling cascade.

The effect of nitrous acid (NA) on viability, integrity of cellular DNA and on membrane transport were studied in 5 strains of Escherichia coli. Stationary phase cells, grown on mineral salts medium, were exposed to NA. The viability of strains decreased in the following order: W3110 wild-type greater than WP2 wild-type, WP2 uvrA greater than NG30 recA greater than P3478 polA. Alterations were found in the DNA sedimentation profile in alkaline sucrose gradient. Disturbance of DNA synthesis was measured by 3H-labelled thymidine ([3H]Thd) incorporation. No degradation of DNA was found after NA treatment. Low doses of NA caused significant inhibition of leucine and glucose transport into whole cells. The results are interpreted in terms of the multi-target action of NA causing the death of cells.

Exposure of alpha 1-proteinase inhibitor (alpha 1-PI) to nitrous acid resulted in a complete inactivation of either of its elastase or trypsin inhibitors activities. Amino acid analyses of the nitrous acid treated inhibitor revealed only losses of one tryphanyl and three lysyl residues. Reductive methylation of alpha 1-PI offered no protection against loss of activity by nitrous acid. Since no further loss of lysyl residues was observed upon exposure of fully active reductively methylated alpha 1-PI to nitrous acid, modification of one tryptophanyl residue appears to be responsible for the inhibitor's sensitivity to nitrous acid. Absorption spectral studies of the nitrous acid treated alpha 1-PI indicated that the tryptophanyl residue was modified to its N-nitroso derivative.

Nitrous acid is a mutagenic agent. It can induce interstrand cross-links in duplex DNA, preferentially at d(CpG) steps: two guanines on opposite strands are linked via a single shared exocyclic imino group. Recent synthetic advances have led to the production of large quantities of such structurally homogenous cross-linked duplex DNA. Here ... the high resolution solution structure of the cross-linked dodecamer [d(GCATCCGGATGC)]2 (the cross-linked guanines are underlined), determined by 2D NMR spectroscopy, distance geometry, restrained molecular dynamics and iterative NOE refinement /is presented/. The cross-linked guanines form a nearly planar covalently linked 'G:G base pair' with only minor propeller twisting, while the cytidine bases of their normal base pairing partners have been flipped out of the helix and adopt well defined extrahelical positions in the minor groove. On the 5'-side of the cross-link, the minor groove is widened to accommodate these extrahelical bases, and the major groove becomes quite narrow at the cross-link. The cross-linked 'G:G base pair' is well stacked on the spatially adjacent C:G base pairs, particularly on the 3'-side guanines. In addition to providing the first structure of a nitrous acid cross-link in DNA, these studies could be of major importance to the understanding of the mechanisms of nitrous acid cross-linking and mutagenicity, as well as the mechanisms responsible for its repair in intracellular environments...

Reduced by deoxyhemoglobin to form nitric oxide. Nitrite is also reduced to nitric oxide and further reduced to ammonia by gut bacteria. Nitrite can be oxidized to nitrate by oxyhemoglobin.

The reactions of nitrogen dioxide with cyclohexene have been studied as a model for the reactions that occur between nitrogen dioxide in smoggy air and unsaturated fatty acids in pulmonary lipids. As predicted from earlier studies at high nitrogen dioxide concentrations, this gas reacts with cyclohexene predominantly by addition to the double bond at nitrogen dioxide concentrations of 1 percent (10,000 parts per million) to 40 percent in nitrogen; in the presence of air or oxygen, this reaction initiates the autoxidation of the alkene. However, at concentrations below 100 parts per million in nitrogen, nitrogen dioxide reacts with cyclohexene almost exclusively by abstraction of allylic hydrogen; this unexpected reaction also initiates the autoxidation of the alkene in the presence of oxygen or air, but it leads to the production of nitrous acid rather than of a product containing a nitro group attached to a carbon atom. The nitrous acid can react with amines to produce nitrosamines. Moreover, the nitrite ion produced by the hydrogen abstraction mechanism would be expected to diffuse throughout the body, unlike nitrated lipids that would be confined to the pulmonary cavity. These findings have been confirmed with methyl oleate, linoleate, and linolenate; some of the kinetic features of the nitrogen dioxide-initiated autoxidation of these unsaturated fatty acids have been studied. .

Nitrites and their metabolites are excreted in the urine. (L1137)

Reactive nitrogen species derived from nitric oxide are potent oxidants formed during inflammation that can oxidize membrane and lipoprotein lipids in vivo. ... Several of these species react with unsaturated fatty acid to yield nitrated oxidation products. ... Reaction of HPODE, but not linoleate, with nitrous acid (HONO) or isobutyl nitrite (BuiONO) yielded a product at m/z 340, or 341 upon reacting with [15N]HONO. MS/MS analysis gave an NO2- fragment, and 15N NMR indicated that the product contained a nitro (RNO2) functional group, suggesting that the product was nitroepoxylinoleic acid [L(O)NO2]. This species could form via homolytic dissociation of LOONO to LO* and *NO2 and rearrangement of LO* to an epoxyallylic radical L(O)* followed by recombination of L(O)* with *NO2. Since unsaturated lipids of membranes and lipoproteins are critical targets of reactive oxygen and nitrogen species, these pathways lend insight into mechanisms for the formation of novel nitrogen-containing lipid products in vivo and provide synthetic strategies for further structural and functional studies.

Formed as a product of combustion and when nitrogen dioxide reacts with water; Used to make diazotizing compounds and as a source of nitric oxide; [HSDB]

Formation of diazotizing compounds by reaction with primary aromatic amines, source of nitric oxide

Nitrous acid is used in chemical synthesis. (L1615)

Formed by the action of strong acids on inorganic nitrites.

Nitrous acid is not an article of commerce owing to its inherent instability. Sodium nitrite serves as the primary industrial source for nitrous acid in organic syntheses, for instance in the diatozation and nitrosation of aromatic amines. Under controlled conditions of acidification, the nitrous acid generated can react before excessive decomposition occurs.

Nitrous acid: ACTIVE

... also formed when nitrogen dioxide (NO2) reacts with water