Nitrous oxide toxicity

Goldhirsch Gelber RD, Tattersall MNH, Rudenstam C-M, Cavalli F. Methotrexate/nitrous-oxide toxic interaction in perioperative chemotherapy for early breast cancer. Lancet i 9ZT) ii, 151. 

Danger Cylinders that may contain nitrous oxide, toxic, or flammable gases should not be subjected to an odor (sniff) test. 

There appear also to be toxic effects. In animals, nitrous oxide has been shown to inactivate methionine synthetase which prevents the conversion of deoxyuridine to thymidine and thus has the potential for inducing megaloblastic anemia, leukopenia, and teratogenicity (44—46). A variety of epidemiologic surveys suggest positive correlations between exposure to nitrous oxide and spontaneous abortion in dental assistants (47). 

Many gases dissolve in fats and make good propellants. However, most are flammable or toxic, or they react with the fats. Other possible propellants, such as the propane used in hairsprays or in Freon, also cause intoxication when they dissolve in the fats around nerve cells. These substances are not used, since their flammability, safety, cost, or taste makes them less desirable than nitrous oxide for spray cans of whipping cream. 

Garrido, J.M., Moreno, J., Mendez-Pamptn, R., and Lema, J.M., Nitrous oxide production under toxic conditions in a denitrifying anoxic filter, Water Res., 32, 2550-2552, 1998. 

The conventional selective reduction of NOx for car passengers still competes but the efficient SCR with ammonia on V205/Ti02 for stationary sources is not available for mobile sources due to the toxicity of vanadium and its lower intrinsic activity than that of noble metals, which may imply higher amount of active phase for compensation. As illustrated in Figure 10.9, such a solution does not seem relevant because a subsequent increase in vanadium enhances the formation of undesirable nitrous oxide at low temperature. Presently, various attempts for the replacement of vanadium did not succeed regarding the complete conversion of NO into N2 at low temperature. Suarez et al. [87] who investigated the reduction of NO with NH3 on CuO-supported monolithic catalysts... 

The first use of supercritical fluid extraction (SFE) as an extraction technique was reported by Zosel [379]. Since then there have been many reports on the use of SFE to extract PCBs, phenols, PAHs, and other organic compounds from particulate matter, soils and sediments [362, 363, 380-389]. The attraction of SFE as an extraction technique is directly related to the unique properties of the supercritical fluid [390]. Supercritical fluids, which have been used, have low viscosities, high diffusion coefficients, and low flammabilities, which are all clearly superior to the organic solvents normally used. Carbon dioxide (C02, [362,363]) is the most common supercritical fluid used for SFE, since it is inexpensive and has a low critical temperature (31.3 °C) and pressure (72.2 bar). Other less commonly used fluids include nitrous oxide (N20), ammonia, fluoro-form, methane, pentane, methanol, ethanol, sulfur hexafluoride (SF6), and dichlorofluoromethane [362, 363, 391]. Most of these fluids are clearly less attractive as solvents in terms of toxicity or as environmentally benign chemicals. Commercial SFE systems are available, but some workers have also made inexpensive modular systems [390]. 

Until recent times, the only toxicological hazards attributable to nitrous oxide were those common to asphyxiants, with death or permanent brain injury occurring only under conditions of hypoxia. A number of untoward and toxic effects have now been associated with exposure. One of the earliest findings was that patients given 50% nitrous oxide and 50% oxygen for prolonged periods, to induce continuous sedation, developed bone marrow depression and granuloqn openia. The bone marrow usually returned to normal within a matter of days once the nitrous oxide was removed, but several deaths from aplastic anemia have been recorded. ... 

Central nervous system toxicity from either social abuse of nitrous oxide or extremely heavy occupational exposure has been characterized by symptoms of numbness, paresthesias, impairment of equilibrium, and difficulty in concentration. In severe cases, the patient becomes incontinent, impotent, and unable to walk. Neurological signs include ataxic gait, muscle weakness, impaired sensation, and diminished reflexes. 

The possible carcinogenicity of nitrous oxide has been studied in dentists and chairside assistants with occupational exposures. No effect was observed in male dentists, but a 2.4-fold increase in cancer of the cervix in heavily exposed female assistants was reported. Other epidemiological reports of workers exposed to waste anesthetic gases have been negative. Carcinogenic bioassays in animals have yielded negative results. Nitrous oxide was not geno-toxic in a variety of assays. ... 

Usually various anesthetic agents are combined to increase efficacy and at the same time decrease toxicity and shorten the time to recovery. For example induction of anesthesia is obtained with an intravenous agent with a rapid onset of action like thiopentone and then anesthesia is maintained with a nitrous oxide/oxygen mixture in combination with halothane or a comparable volatile anesthetic. 

Halogenated hydrocarbon inhalation anesthetics may increase intracranial and CSF pressure. Cardiovascular effects include decreased myocardial contractility and stroke volume leading to lower arterial blood pressure. Malignant hyperthermia may occur with all inhalation anesthetics except nitrous oxide but has most commonly been seen with halothane. Especially halothane but probably also the other halogenated hydrocarbons have the potential for acute or chronic hepatic toxicity. Halothane has been almost completely replaced in modern anesthesia practice by newer agents. 

The metabolism of enflurane and sevoflurane results in the formation of fluoride ion. However, in contrast to the rarely used volatile anesthetic methoxyflurane, renal fluoride levels do not reach toxic levels under normal circumstances. In addition, sevoflurane is degraded by contact with the carbon dioxide absorbent in anesthesia machines, yielding a vinyl ether called "compound A," which can cause renal damage if high concentrations are absorbed. (See Do We Really Need Another Inhaled Anesthetic ) Seventy percent of the absorbed methoxyflurane is metabolized by the liver, and the released fluoride ions can produce nephrotoxicity. In terms of the extent of hepatic metabolism, the rank order for the inhaled anesthetics is methoxyflurane > halothane > enflurane > sevoflurane > isoflurane > desflurane > nitrous oxide (Table 25-2). Nitrous oxide is not metabolized by human tissues. However, bacteria in the gastrointestinal tract may be able to break down the nitrous oxide molecule. 

The exact mechanism of action of most volatile substances remains unknown. Altered function of ionotropic receptors and ion channels throughout the central nervous system has been demonstrated for a few. Nitrous oxide, for example, binds to NMDA receptors and fuel additives enhance GABAa receptor function. Most inhalants produce euphoria increased excitability of the VTA has been documented for toluene and may underlie its addiction risk. Other substances, such as amyl nitrite ("poppers"), primarily produce smooth muscle relaxation and enhance erection, but are not addictive. With chronic exposure to the aromatic hydrocarbons (eg, benzene, toluene), toxic effects can be observed in many organs, including white matter lesions in the central nervous system. Management of overdose remains supportive. 

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