Ammonia solutions (containing more than 35% but not more than 50% ammonia) appears as a clear colorless liquid consisting of ammonia dissolved in water. Corrosive to tissue and metals. Although ammonia is lighter than air, the vapors from a leak will initially hug the ground. Long term exposure to low concentrations or short term exposure to high concentrations may result in adverse health conditions from inhalation. Prolonged exposure of containers to fire or heat may result in their violent rupturing and rocketing.
颜色/状态：
Colorless gas
气味：
Sharp, cloying, repellent
蒸汽密度：
0.6 (EPA, 1998) (Relative to Air)
蒸汽压力：
Vapor pressure: 1 Pa at -139 °C, 10 Pa at -127 °C, 100 Pa at -112 °C; 1 kPa at -94.5 °C (solids); 10 kPa at -71.3 °C, 100 kPa at -33.6 °C (liquid)
亨利常数：
Henry's Law constant = 1.61X10-5 atm cu-m/mole at 25 °C
Healthy hepatocytes detoxify ammonia where hepatic glutaminase, glutamine synthetase and the urea cycle enzymes act as major enzymes for ammonia metabolism. Ammonia is converted to urea in the liver and other tissues. Glutaminase and glutamine synthetase catalyze the condensation of ammonia with glutamate to glutamine, which is a common nontoxic carrier of ammonia. In case of hepatic dysfunction or impairment, detoxification capacity decreases and may cause severe pathologies from hyperammonemia, such as hepatic encephalopathy.
Human adults produce around 1000 mmol of ammonia daily. Some is reutilized in biosynthesis. The remainder is waste and neurotoxic. Eventually most is excreted in urine as urea, together with ammonia used as a buffer. In extrahepatic tissues, ammonia is incorporated into nontoxic glutamine and released into blood. Large amounts are metabolized by the kidneys and small intestine. In the intestine, this yields ammonia, which is sequestered in portal blood and transported to the liver for ureagenesis, and citrulline, which is converted to arginine by the kidneys. The amazing developments in NMR imaging and spectroscopy and molecular biology have confirmed concepts derived from early studies in animals and cell cultures. The processes involved are exquisitely tuned. When they are faulty, ammonia accumulates. Severe acute hyperammonemia causes a rapidly progressive, often fatal, encephalopathy with brain edema. Chronic milder hyperammonemia causes a neuropsychiatric illness. Survivors of severe neonatal hyperammonemia have structural brain damage. Proposed explanations for brain edema are an increase in astrocyte osmolality, generally attributed to glutamine accumulation, and cytotoxic oxidative/nitrosative damage. However, ammonia neurotoxicity is multifactorial, with disturbances also in neurotransmitters, energy production, anaplerosis, cerebral blood flow, potassium, and sodium. Around 90% of hyperammonemic patients have liver disease. Inherited defects are rare. They are being recognized increasingly in adults. Deficiencies of urea cycle enzymes, citrin, and pyruvate carboxylase demonstrate the roles of isolated pathways in ammonia metabolism. Phenylbutyrate is used routinely to treat inherited urea cycle disorders, and its use for hepatic encephalopathy is under investigation. /Hyperammonemia/
The inhibitory effects of ammonia on two different degradation pathways of methanogenic acetate were evaluated using a pure culture (Methanosaeta thermophila strain PT) and defined co-culture (Methanothermobacter thermautotrophicus strain TM and Thermacetogenium phaeum strain PB), which represented aceticlastic and syntrophic methanogenesis, respectively. Growth experiments with high concentrations of ammonia clearly demonstrated that sensitivity to ammonia stress was markedly higher in M. thermophila PT than in the syntrophic co-culture. M. thermophila PT also exhibited higher sensitivity to high pH stress, which indicated that an inability to maintain pH homeostasis is an underlying cause of ammonia inhibition. Methanogenesis was inhibited in the resting cells of M. thermophila PT with moderate concentrations of ammonia, suggesting that the inhibition of enzymes involved in methanogenesis may be one of the major factors responsible for ammonia toxicity. Transcriptomic analysis revealed a broad range of disturbances in M. thermophila PT cells under ammonia stress conditions, including protein denaturation, oxidative stress, and intracellular cation imbalances. The results of the present study clearly demonstrated that syntrophic acetate degradation dominated over aceticlastic methanogenesis under ammonia stress conditions, which is consistent with the findings of previous studies on complex microbial community systems. Our results also imply that the co-existence of multiple metabolic pathways and their different sensitivities to stress factors confer resiliency on methanogenic processes.
Recently, spatial-temporal/metabolic mathematical models have been established that allow the simulation of metabolic processes in tissues. We applied these models to decipher ammonia detoxification mechanisms in the liver. An integrated metabolic-spatial-temporal model was used to generate hypotheses of ammonia metabolism. Predicted mechanisms were validated using time-resolved analyses of nitrogen metabolism, activity analyses, immunostaining and gene expression after induction of liver damage in mice. Moreover, blood from the portal vein, liver vein and mixed venous blood was analyzed in a time dependent manner. Modeling revealed an underestimation of ammonia consumption after liver damage when only the currently established mechanisms of ammonia detoxification were simulated. By iterative cycles of modeling and experiments, the reductive amidation of alpha-ketoglutarate (alpha-KG) via glutamate dehydrogenase (GDH) was identified as the lacking component. GDH is released from damaged hepatocytes into the blood where it consumes ammonia to generate glutamate, thereby providing systemic protection against hyperammonemia. This mechanism was exploited therapeutically in a mouse model of hyperammonemia by injecting GDH together with optimized doses of cofactors. Intravenous injection of GDH (720 U/kg), alpha-KG (280 mg/kg) and NADPH (180 mg/kg) reduced the elevated blood ammonia concentrations (>200 uM) to levels close to normal within only 15 min. If successfully translated to patients the GDH-based therapy might provide a less aggressive therapeutic alternative for patients with severe hyperammonemia. /Hyperammonemia/
The rodent liver eliminates toxic ammonia. In mammals, three enzymes (or enzyme systems) are involved in this process: glutaminase, glutamine synthetase and the urea cycle enzymes, represented by carbamoyl phosphate synthetase. The distribution of these enzymes for optimal ammonia detoxification was determined by numerical optimization. This in silico approach predicted that the enzymes have to be zonated in order to achieve maximal removal of toxic ammonia and minimal changes in glutamine concentration. Using 13 compartments, representing hepatocytes, the following predictions were generated: glutamine synthetase is active only within a narrow pericentral zone. Glutaminase and carbamoyl phosphate synthetase are located in the periportal zone in a non-homogeneous distribution. This correlates well with the paradoxical observation that in a first step glutamine-bound ammonia is released (by glutaminase) although one of the functions of the liver is detoxification by ammonia fixation. The in silico approach correctly predicted the in vivo enzyme distributions also for non-physiological conditions (e.g. starvation) and during regeneration after tetrachloromethane (CCl4) intoxication. Metabolite concentrations of glutamine, ammonia and urea in each compartment, representing individual hepatocytes, were predicted. Finally, a sensitivity analysis showed a striking robustness of the results. These bioinformatics predictions were validated experimentally by immunohistochemistry and are supported by the literature. In summary, optimization approaches like the one applied can provide valuable explanations and high-quality predictions for in vivo enzyme and metabolite distributions in tissues and can reveal unknown metabolic functions.
IDENTIFICATION AND USE: Ammonia is a colorless gas or liquid. Ammonia is used in the production of ammonium sulfate and ammonium nitrate for fertilizers; and in the manufacture of nitric acid, soda, synthetic urea, synthetic fibers, dyes, and plastics. Ammonia, or dissociated ammonia, is used in such metal treating operations as nitriding, carbo-nitriding, bright annealing, furnace brazing, sintering, sodium hydride descaling, atomic hydrogen welding, and other applications where protective atmospheres are required. The petroleum industry utilizes anhydrous ammonia in neutralizing the acid constituents of crude oil and in protecting equipment such as bubble plate towers, heat exchangers, condensers, and storage tanks from corrosion. It is also used as medication. Ammonia in an aqueous environment exists in equilibrium between ionized ammonium cation and the non-ionized ammonia. This equilibrium can be affected by buffers, pH, temperature, and salinity. Thus, in many cases it is not possible to assign the associated toxicity to the ionized or non-ionized form of the ammonia-nitrogen. HUMAN EXPOSURE AND TOXICITY: Studies using low levels of ammonia show that inhaled ammonia is temporarily dissolved in the mucus of the upper respiratory tract, and then a high percentage of it is released back into the expired air. Following exposure to 500 ppm ammonia for 10-27 min, healthy male subjects eliminated 70-80% of the inspired ammonia by this route. Short term exposure: eye or skin contact with ammonia can cause irritation, burns, frostbite (anhydrous), and permanent damage. Irritates the respiratory tract causing coughing, wheezing, and shortness of breath. Higher exposure can cause pulmonary edema, a medical emergency, that can be delayed for several hours and is life-threatening. Exposure can cause headache, loss of sense of smell, nausea, and vomiting. Inhalation: nose and throat irritation have been reported at 72 ppm after 5 min exposure. Exposures of 500 ppm for 30 min have caused upper respiratory irritation, tearing, increased pulse rate, and blood pressure. Death has been reported after an exposure to 10,000 ppm for an unknown duration. Skin: Solutions of 2% ammonia can cause burns and blisters after 15 min of exposure. These burns may be slow to heal. Anhydrous ammonia may cause skin to freeze. Eyes: Levels of 70 ppm (gas) have caused eye irritation. If not flushed with water immediately, contact with eye may cause partial or complete blindness. Ingestion: ammonia will cause pain if swallowed and burning of the throat and stomach. May cause vomiting. One teaspoon of 28% aqua ammonia may cause death. Long term exposure: repeated exposure can cause chronic eye, nose, and throat irritation. Repeated lung irritation can result in bronchitis with coughing, shortness of breath, and phlegm. Analysis of blood samples from 22 workers exposed to ammonia in a fertilizer factory and 42 control workers not exposed to ammonia showed increased frequency of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs), increased mitotic index (MI), and increased frequency of CAs and SCEs with increasing length of exposure. ANIMAL STUDIES: Analysis of endogenous ammonia levels in the expired air of rats showed concentrations ranging from 10-353 ppb (mean = 78 ppb) in nose-breathing animals. The quantitative difference between inspired and expired ammonia suggests that small amounts are absorbed across the nasopharyngeal membranes into the systemic circulation. Absorbed ammonia is excreted by the kidneys as urea and urinary ammonium compounds, as urea in feces, and as components of sweat. Toxic levels do not develop as a result of chronic inhalation exposure because the body has multiple effective mechanisms for detoxifying and excreting it. Cardiovascular changes that may be analogous to those observed in humans have been observed in rabbits exposed to high concentrations of ammonia. Bradycardia was seen at 2,500 ppm, and hypertension and cardiac arrhythmias leading to cardiovascular collapse followed acute exposures to concentrations exceeding 5,000 ppm. Pathological correlates for these effects have not been demonstrated. Atrophy of pericardial fat has been observed in mice exposed to 4,000 ppm ammonia. Hepatic effects are usually not seen in animals exposed to ammonia gas. Liver necrosis has been observed following acute lethal exposure of mice to 3,440 ppm ammonia for 1 hour. Levels of 170 ppm of ammonia vapor caused mild changes in the spleens, kidneys, and livers of guinea pigs. Static exposures of cats and rabbits for 1 hr at 7000 mg/cu m resulted in the death of approx 50%. Postmortem exam showed severe effects on the upper respiratory tract. Less severe effects in the lower respiratory tract included damage to bronchioles and alveolar congestion, edema, atelectasis, hemorrhage, emphysema, and fluid. The search for the peripheral toxins responsible for the CNS impairment present in hepatic encephalopathy has shown that the administration of ammonia in normal rats reproduced behavioral and electrophysiological changes similar to those seen in galactosamine induced encephalopathy. No statistically significant differences were noted in ovarian or uterine weights of pigs exposed to about 7 or 35 ppm ammonia for 6 weeks. Female pigs that were continuously exposed to about 35 ppm ammonia from 6 weeks before breeding until day 30 of gestation had no statistically significant differences in age at puberty, number of live fetuses, or fetus-to-corpus luteum ratio compared to pigs exposed to only about 7 ppm. No unexposed controls were included in that study. No statistically significant difference in fetal length was evident at 30 days of gestation in offspring of pig dams that were continuously exposed to about 7 or 35 ppm ammonia from 6 weeks before breeding until day 30 of gestation. The mutagenicity of anhydrous ammonia was investigated in a Ames test in S. typhimurium TA98, TA100, TA1535, TA1537 and TA1538, and in E. coli WP2uvrA. The test method was modified appropriately to investigate a volatile test substance. Studies were performed in duplicate in the presence and absence of an exogenous metabolic activation system. No evidence of mutagenicity was seen under the conditions of this assay. ECOTOXICITY STUDIES: Ammonia is an environmental pollutant that is toxic to all aquatic animals. The major sources for atmospheric NH3 are agricultural activities and animal feedlot operations, followed by biomass burning (including forest fires) and to a lesser extent fossil fuel combustion. Close to its sources, acute exposures to NH3 can result in visible foliar injury on vegetation.
The topical damage caused by ammonia is probably due mainly to its alkaline properties. Its high water solubility allows it to dissolve in moisture on the mucous membranes, skin, and eyes, forming ammonium hydroxide. Ammonium hydroxide causes saponification of cell membrane lipids, resulting in cell disruption and death. Additionally, it extracts water from the cells and initiates an inflammatory response, which further damages the surrounding tissues. Excess circulating levels of ammonia (hyperammonemia) can cause serious neurological effects. This is thought to involve the alteration of glutamate metabolism in the brain and resultant increased activation of NMDA receptors, which causes decreased protein kinase C-mediated phosphorylation of Na+/K+ ATPase, increased activity of Na+/K+ ATPase, and depletion of ATP. Ammonia can chemically interact with an internal thiolester bond of
complement 3 (C3). This causes a conformation change in C3, which activates the alternative complement pathway, causing the release of chemoattractants and the assembly of the membrane attack complex of complement. The altered C3 can also bind directly to phagocyte complement receptors, which causes the release of toxic oxygen species. (L958)
来源:Toxin and Toxin Target Database (T3DB)
毒理性
致癌物分类
对人类无致癌性（未列入国际癌症研究机构IARC清单）。
No indication of carcinogenicity to humans (not listed by IARC).
