Nitrocompounds are characterized by the linkage C–NO2. They include the mononitroparaffins, polynitroparaffins, nitro-olefins, and the alkyl nitrites and nitrates.
The mononitroparaffins below are obtained by direct nitration of the appropriate paraffins in the vapour phase and are used chiefly as solvents for cellulose esters, other resins, and for oils, fats, waxes and dyes. Among the special groups of mononitroparaffins are the chloronitroparaffins.
Uses
The aliphatic nitrocompounds are used as solvents, explosives, rocket propellants, fumigants and gasoline additives. Several are found in the rubber, textile, and paint and varnish industries.
Pentaerythritol tetranitrate, ethylene glycol dinitrate (EGDN), tetranitromethane, nitroglycerin and 2-nitropropane are ingredients in explosives. Ethylene glycol dinitrate is a high explosive, but it also has the property of lowering the freezing point of nitroglycerin. In most countries with a temperate-to-cold climate, dynamite is made from a mixture of nitroglycerin and EGDN. Nitroglycerin is used in high explosives and in the production of dynamite and other explosives; however, it has gradually been replaced by ammonium nitrate in this application. In addition, nitroglycerin is used to combat fires in oil wells. Nitroglycerine is also used in medicine as a vasodilator in coronary artery spasm.
Nitroglycerin, 2-nitropropane, tetranitromethane and nitromethane serve as rocket propellants. 1-Nitropropane and 2-nitropropane are solvents and gasoline additives, and tetranitromethane is a diesel fuel booster. 2-Nitropropane finds use as a smoke depressant in diesel fuel and as a component of racing-car fuels and paint and varnish removers.
Chloropicrin is a rodenticide and a chemical warfare agent, while nitromethane and nitroethane are utilized as propellants in the military. Nitrilotriacetic acid has numerous uses in water treatment, textiles, rubber, and the pulp and paper industries. It also functions as a boiler feedwater additive and a chelating agent in the cleaning and separation of metals.
The chlorinated nitroparaffins are used most frequently as solvents and intermediates in the chemical and synthetic rubber industries. They have found use as pesticides, especially fumigants, fungicides and mosquito ovicides.
Nitro-olefins may be produced by dehydration of the nitro-alcohols or by immediate addition of nitrogen oxides to olefins. They have no broad industrial use.
Alkyl nitrites are produced by the action of nitrites on alcohols in the presence of dilute sulphuric acid, and also with the mononitroparaffins by the reaction of alkyl halides and nitrites. The major use of alkyl nitrites has been in industrial and military explosives, although these substances are also used in organic synthesis and as therapeutic agents (vasodilators) in medicine. They undergo hydrolysis easily with the release of nitrous acid, as well as exchange reactions when dissolved in alcohols. Alkyl nitrates are formed by the interaction of alcohols and nitric acid. Ethyl nitrate and to some extent methyl nitrate are used in organic synthesis as nitrating agents for aromatic compounds. Methyl nitrate is also used as a rocket fuel.
Hazards
Effects may be produced from absorption by any route (i.e., inhalation, ingestion, skin absorption). Irritation may occur as a result of skin contact. Often the most important industrial hazard is inhalation of vapours, since the vapour pressures are often sufficiently high to produce considerable vapour levels in the workplace. When exposed to high temperatures, flames or impact, certain aliphatic nitro-compounds constitute a fire and explosion hazard. Spontaneous exothermic chemical reactions may also take place. Symptoms of exposure can include mucosal irritation, nausea, vomiting, headaches, shortness of breath (dyspnea) and dizziness. Chronic exposure to these substances can increase the risk of carcinogenicity (in animals), ischemic heart disease and sudden death.
Nitroparaffins
Nitroparaffins have a depressive effect on the central nervous system and also cause lesions in the liver and kidneys. The polynitroparaffins are considerably more toxic than the mononitroparaffins. Industrial exposure to 30 ppm of nitropropane (a mononitroparaffin) caused symptoms such as headache, nausea, vomiting and diarrhoea. No signs were observed at concentrations of 10 to 20 ppm. In workers, the observed effects of tetranitromethane (a polynitroparaffin) included irritation of the respiratory system, dyspnoea, dizziness and, with repeated exposures, anaemia, cyanosis and bradycardia. The carcinogenic potential is discussed below. Under ordinary conditions, nitromethane (a mononitroparaffin) is relatively stable, but it can be detonated by impact or by heat. The damage caused by two separate tank car explosions of nitromethane was very considerable, and, as a result of these experiences, nitromethane is now stored and transported in drums rather than in bulk. Inhalation of nitromethane produces mild irritation and toxicity before narcosis occurs; liver damage can result from repeated exposure. It should be handled under conditions of good ventilation, preferably local exhaust ventilation; personal protective equipment should be worn.
Although nitroethane is less explosive than nitromethane, this substance could explode under appropriate conditions of contamination and confinement, and safe handling methods are necessary. It is a moderate respiratory tract irritant, but no serious industrial injury has been recorded. Well-ventilated conditions should be provided.
Nitro-olefins
Nitro-olefins are considered highly toxic because of the vigorous local irritation that is caused by coming into contact with the liquids or with vapours in concentrations as low as 0.1 to 1 ppm (e.g., nitrobutene, nitrohexene, nitrononene), and to the rapid absorption of these compounds by any route. The toxic effects appear immediately after exposure and include hyperexcitability, convulsions, tachycardia, hyperpnoea, depression, ataxia, cyanosis and asphyxia. Pathologic changes are most pronounced in the lungs, regardless of the route of absorption.
Alkyl nitrites and nitrates
Alkyl nitrites are considered toxic because of their effect on the formation of nitrite ions, which are strong oxidizing agents. The alkyl nitrates and nitrites may cause methaemoglobin formation in the blood. When heated, they may decompose, releasing nitrogen oxides, which are highly toxic. In high concentrations alkyl nitrites are narcotic. Alkyl nitrates are highly toxic and in large doses may cause dizziness, abdominal cramps, vomiting, bloody diarrhoea, weakness, convulsions and collapse. Small, repeated doses may lead to weakness, general depression, headache and mental disorders.
Chloropicrin vapours are highly irritating to the eyes, causing intense lacrimation, and to the skin and respiratory tract. Chloropicrin causes nausea, vomiting, colic and diarrhoea if it enters the stomach.
Data on the effects of chloropicrin are derived mainly from First World War experience with chemical warfare agents. It is a pulmonary irritant with a toxicity greater than chlorine but less than phosgene. Military data indicate that exposure to 4 ppm for a few seconds is sufficient to render a person unfit for action, and 15 ppm for 60 seconds causes marked bronchial or pulmonary lesions. It causes injury particularly to the small and medium bronchi, and oedema is frequently the cause of death. Because of its reaction with sulphydryl groups, it interferes with oxygen transport and can produce weak and irregular heartbeats, recurrent asthmatic attacks and anaemia. A concentration of around 1 ppm causes severe lacrimation and provides good warning of exposure; at higher concentrations, skin irritation is evident. Ingestion may occur due to the swallowing of saliva containing dissolved chloropicrin and produce vomiting and diarrhoea. Chloropicrin is non-combustible; however, when heated it can detonate and can also be shock detonated above a critical volume.
Ethylene glycol dinitrate (EGDN). When ethylene glycol dinitrate was first introduced into the dynamite industry, the only changes noticed were similar to those affecting workers exposed to nitroglycerin—headache, sweating, face redness, arterial hypotension, heart palpitations and dizziness especially at the beginning of work, on Monday mornings and after an absence. EGDN, which is absorbed through the respiratory tract and the skin, has indeed a significant acute hypotensive action. When cases of sudden death started to occur amongst workers in the explosives industry, no one immediately suspected the occupational origin of these accidents until, in 1952, Symansky attributed numerous cases of fatality already observed by the manufacturers of dynamite in the United States, the United Kingdom and the Federal Republic of Germany to chronic EGDN poisoning. Other cases were then observed, or at least suspected, in a number of countries, such as Japan, Italy, Norway and Canada.
Following a period of exposure which often varies between 6 and 10 years, workers exposed to mixtures of nitroglycerin and EGDN may complain of sudden pain in the chest, resembling that of angina pectoris, and/or die suddenly, usually between 30 and 64 hours after termination of exposure, either during sleep or following the first physical efforts of the day after arriving at work. Death is generally so sudden that it is usually not possible to assess the victims carefully during the attack.
Emergency treatment with coronary dilators and, in particular, nitroglycerin has proved ineffective. In most cases, autopsy proved negative or it did not appear that coronary and myocardial lesions were more prevalent or extensive than in the general population. In general, electrocardiograms have also proved deceptive. From the clinical point of view, observers have noted systolic hypotension, which is more marked during working hours, accompanied by increased diastolic pressure, sometimes with modest signs of hyperexcitability of the pyramidal system; less frequently there have been signs of acrocyanosis—together with some changes in vasomotor reaction. Peripheral paraesthesia, particularly at night, has been reported, and this may be attributed to arteriolar spasms and/or to peripheral neuropathy. Skin sensitization has also been reported.
Nitroglycerin. Nitroglycerin is a highly explosive substance which is very sensitive to mechanical shock; it is also readily detonated by heat or spontaneous chemical reaction. In commercial explosives, its sensitivity is reduced by the addition of an absorbent such as woodpulp and chemicals such as ethylene glycol dinitrate and ammonium nitrate. In the form of straight or ammonia dynamite, the substance presents only a moderate explosion hazard.
Nitroglycerin may be absorbed into the body by ingestion, inhalation or through intact skin. It causes arterial dilation, increased heart rate, and reduced blood and pulse pressure. Cases of sudden death have been reported amongst explosives workers in contact with nitroglycerin; however, death has usually been attributed to the action of the ethylene glycol dinitrate mixed with nitroglycerin in the manufacture of dynamite.
Most workers rapidly adapt to the hypotensive action of nitroglycerin, but discontinuation of exposure (even for a few days, such as at the weekend) may interrupt this adaptation, and some workers may even be subject to a period of nausea when resuming work on Monday mornings; some workers never adapt and have to be removed from exposure after a trial period of 2 to 3 weeks. Prolonged exposure to nitroglycerin may result in neurological disorders, and ingestion of large amounts usually causes fatal collapse.
The initial symptoms of exposure are headache, dullness and reduced blood pressure; these may be followed by nausea, vomiting with consequent fatigue and weight loss, cyanosis and central nervous disorders that may be as intense as acute mania. In cases of severe poisoning, confusion, pugnaciousness, hallucinations and maniacal manifestations have been observed. Alcoholic beverages may precipitate poisoning and increase its severity. In chronic poisoning, there are digestive troubles, tremors and neuralgia.
Nitroglycerin may produce moderate irritation at the site of application; eruptions of the palms and interdigital spaces, and ulcers under the nails have been observed in workers handling nitroglycerin.
Chlorinated nitroparaffins. When exposed to heat or flame, chlorinated nitroparaffins are easily decomposed into dangerous fumes such as phosgene and nitrogen oxides. These highly toxic fumes may result in the irritation of mucous membranes and pulmonary damage with varying degrees of acute oedema and death. However, no information about accidental exposures of humans has been reported.
The toxicity of some of the substances has not been clearly elucidated. In general, however, experimental exposures to high concentrations produced damage not only to the respiratory system but also possibly to the liver, kidneys and cardiovascular system. In addition, ingestion has caused congestion of the gastrointestinal tract, and skin irritation resulted from contact with large amounts. No significant reports about chronic local or systemic cases of poisoning in industrial workers have been recorded.
The chlorinated nitroparaffins include chloronitromethane, dichloronitromethane, 1-chloro-1-nitroethane, 1,1-dichloro-1-nitro-ethane, 1-chloro-1-nitropropane, 1-chloro-2-nitropropane, 2-chloro-1-nitropropane and 2-chloro-2-nitropropane.
2-Nitropropane (2-NP)
Studies of humans who were accidentally exposed to 2-NP show that brief exposure to high concentrations may be harmful. One report attributes the death of one worker and liver damage in another to high-level exposures to 2-NP that occurred while they painted the inside of a tank. They had used a zinc-epoxy paint diluted with 2-NP and ethylglycol (2-ethoxyethanol). Another report describes the deaths of four men who were working in confined spaces with paint, surface coating, and polyester-based resin products containing 2-NP. All four workers had liver damage and destruction of hepatocytes. The authors attributed the deaths to overexposure to 2-NP but admitted that other solvents might have played a role since 2-NP was not identified by toxicological analysis. Continuing exposure to concentrations of 20 to 45 ppm of 2-NP caused nausea, vomiting, diarrhoea, anorexia and severe headaches in workers in one plant. In another instance toxic hepatitis developed in construction workers applying epoxy resins to the walls of a nuclear power plant. Although the hepatitis was attributed to a known hepatoxin, p,p'-methylenedianiline (4,4'-diaminodiphenylmethane), it could also have resulted from the 2-NP that the men used to wash the epoxy resins from their skin.
Workers may not be able to detect 2-NP by its odour, even in the presence of potentially hazardous concentrations. One report states that humans cannot detect 2-NP at 83 ppm by its odour. Another states that 2-NP cannot be detected by odour until the concentration is about 160 ppm. However, in 1984 one study did report odor detection at 3.1 and 5 ppm.
Carcinogenicity studies. 2-NP is carcinogenic in rats. Studies have shown that exposure to 100 ppm of 2-NP for 18 months (7 hours per day, 5 days per week) resulted in destructive liver changes and hepatocellular carcinoma in some males. Increasing the exposure to 2-NP resulted in increased incidence in liver cancer and more rapid liver damage. In 1979 an epidemiological study of 1,481 workers in a chemical company exposed to 2-NP was reported. The authors conclude that “analysis of these data does not suggest any unusual cancer or other disease mortality pattern among this group of workers”. They appropriately note, however, that “both because the cohort is small and because the period of latency is, for most, relatively short, one cannot conclude from these data that 2-NP is non-carcinogenic in humans”.
There are, in addition, a number of unexplained findings with respect to cancer mortality observed among employees whom the company has classified as not exposed to 2-NP. When the mortality figures for all males, regardless of exposure category, are combined, there were four deaths from lymphatic cancer where only one was expected. Among the total of 147 female employees there were eight deaths from all causes compared to 2.9 expected deaths, and four deaths from cancer compared to 0.8 expected. Finally, the authors report that seven deaths from sarcomas, which is a relatively rare form of malignancy, were observed in the small study cohort. This number seems unusually high. However, it was not possible to generate an expected number of deaths for comparison to determine statistically if the sarcomatous cancers were in excess, because as a category they cannot be broken out in the standard method of reporting and classifying deaths. In short, there is no direct evidence to date that 2-NP is carcinogenic in humans. By 1982 the IARC had concluded that there was “sufficient evidence” for 2-NP as a carcinogen in rats; at the same time the ACGIH classified it as a suspected human carcinogen. Currently it is classified as an A3 carcinogen (carcinogenic in animals).
Safety and Health Measures
The most important methods of technical control to prevent hazards are general or local exhaust ventilation. General ventilation entails dilution of contaminated air with fresh air by fans or blowers in the working environment. Local exhaust ventilation usually means removal of the contaminants from the environments where harmful fumes are generated. The working room concentration should be maintained below the exposure limits by using both of these methods.
If it is not possible to reduce excessive amounts of contaminants in the air by only the ventilation methods, enclosure of a process or segregation of personnel is recommended. Apparatus in which aliphatic nitro-compounds are produced or processed should be of the sealed type. Workers should be provided with respiratory protective equipment and skin protection. Measures against fires and explosions are also necessary. General medical supervision, including periodic medical examination of workers, is also recommended.
Where possible, chloropicrin should be replaced by a less toxic chemical. Where there is a risk of exposure (e.g., in soil fumigation), workers should be adequately protected by wearing suitable chemical eye protection, respiratory protective equipment preferably of the supplied-air type and, in the case of high concentrations, protective clothing to prevent skin exposure. Particular care should be taken during mixing and dilution of chloropicrin; greenhouses in which soil has been treated should be clearly labelled and entry of unprotected persons prevented.
The prime consideration in the production and use of EGDN is the prevention of explosions; it is consequently necessary to adopt the same safety measures as those employed in the manufacture of nitroglycerin and in the explosives industry as a whole. Considerable progress in this respect has been achieved by remote control (by optical, mechanical or electronic means) of the most dangerous operations (in particular milling) and by the automation of numerous processes such as nitration, mixing, cartridge filling and so on. Arrangements of this type also have the advantage of reducing to a minimum both the number of workers exposed to direct contact with EGDN and the related exposure times.
In cases where workers are still exposed to EGDN, a variety of safety and health measures are necessary. In particular, the concentration of EGDN in the explosives mixture should be reduced depending on the ambient temperature, and—in temperate-climate countries—it should not exceed 20 to 25% EGDN; during the warm season, it may be appropriate to exclude EGDN completely. However, too frequent changes in the EGDN concentration should be avoided in order to prevent an increased frequency of withdrawals. In order to reduce the inhalation hazard, it is necessary to control the atmospheric concentration at the workplace by means of general ventilation and, if necessary, air induction, since local exhaust ventilation may entail an explosion hazard.
Skin absorption may be reduced by the adoption of suitable working methods and the use of protective clothing, including polyethylene hand protection; neoprene, rubber and leather are easily penetrated by nitroglycol and cannot provide adequate protection. The employer should assure that the equipment is washed at least twice per week. Personal hygiene should be encouraged, and workers should shower at the end of each shift. A sulphite indicator soap could detect any residual traces of nitroglycerin/EGDN mixture on the skin; work clothing should be completely separated from personal clothing. Respiratory protective equipment may be necessary under certain circumstances (such as work in confined areas).
During the production of nitroglycerin it is essential to apply the measures needed for handling explosive materials, as discussed elsewhere in the Encyclopaedia. Special attention should be paid to effective control of the nitration process, which involves a highly exothermic reaction. Nitration vessels should be fitted with cooling coils or similar devices, and it must be possible to drown the charge completely in the event of a dangerous situation developing. No exposed glass or metal should be used in the plant, and electrically operated equipment is normally excluded.
Where possible, the process should be fully automated, with remote control and closed-circuit television supervision. Where persons are required to work with nitroglycerin, local exhaust ventilation backed up by good general ventilation should be installed. Each worker should be provided with at least three complete sets of working clothes, including headwear, which should be laundered by the employer. These clothes should be changed at least at the beginning of each shift; on no account should trouser legs or tunic sleeves be turned back, and only approved shoes in good condition should be worn. Nitroglycerin will penetrate thin rubber; consequently, hand protection should be made from nylon or polyethylene with a sweat-absorbent cotton liner.
Where unduly high atmospheric concentrations of nitroglycerin may be suspected, workers should wear respiratory protective equipment, and workers cleaning tally bowls, hall machines and drag belt pits should be equipped with an airline respirator. Under no circumstances should food, beverages or tobacco products be allowed into the workplace, and careful washing is necessary before meals.
2-Nitropropane should be handled in the workplace as a potential human carcinogen.
Medical prevention. This includes a pre-placement examination dealing with the general state of health, the cardiovascular system (electrocardiographic examination at rest and during exercise is essential), neurological system, urine and blood. Persons with systolic pressure higher than 150 or lower than 100 mm Hg or diastolic pressure higher than 90 or lower than 60 mm Hg should not in principle be considered fit for occupational exposure to nitroglycol. It is inadvisable for pregnant women to be exposed. In addition to periodic examinations, examination of workers returning to work after lengthy absence due to illness is necessary. The electrocardiogram should be repeated at least once a year.
All workers suffering from cardiac diseases, hypertension, hepatic disorders, anaemia or neurological disorders, especially of the vasomotor system, should not be exposed to nitroglycerin/EGDN mixtures. It is also advisable to move to other jobs all workers who have been employed for more than 5 to 6 years on dangerous work, and to avoid too frequent a change in the intensity of exposure.
Aliphatic nitrocompounds tables
Table 1 - Chemical information.
Table 2 - Health hazards.
Table 3 - Physical and chemical hazards.
Table 4 - Physical and chemical properties.