The aromatic nitrocompounds are a group of organic chemicals headed by nitrobenzene (C6H5NO2) and derived from benzene and its homologues (toluene and xylene), naphthalene and anthracene by replacement of one or more hydrogen atoms by a nitro- group (NO2). The nitro- group may be replaced along with halogen and certain alkyl radicals at almost any position in the ring.
Nitrocompounds of major industrial importance include nitrobenzene, the mono- and dinitrotoluenes, trinitrotoluene (TNT), tetryl, the mononitrochlorobenzenes, nitroanilines, nitrochlorotoluenes, nitronaphthalene, dinitrophenol, picric acid (trinitrophenol) and dinitrocresol. Sufficient experience has been documented on these compounds to provide an outline of their toxic properties and the exposure control measures required to prevent injury to humans.
A much larger number of compounds in this group is accounted for by those derivatives which in no single case have been manufactured in sufficient quantities to allow complete hazard evaluation; these derivatives include the dinitrochlorobenzenes, dichloronitrobenzenes, nitroxylenes, nitrotoluidines, nitrochloroanilines, nitroanisoles, nitrophenetoles and nitroanisidines.
Uses
Aromatic nitrocompounds have few direct uses other than in the formulation of explosives or as solvents. The major consumption involves reduction to aniline derivatives used in the manufacture of dyes, pigments, insecticides, textiles (heat-resistant polyamide-”Nomex”), plastics, resins, elastomers (polyurethane), pharmaceuticals, plant-growth regulators, fuel additives, and rubber accelerators and antioxidants.
The dinitrotoluenes are used in organic syntheses, dyes, explosives, and as propellant additives. Nitrotoluenes are employed in the manufacture of dyes, explosives, toluidines, and nitrobenzoic acids. They are also used in some detergent formulations, flotation agents, and in the tyre industry. Nitrotoluenes are employed in the synthesis of sunscreening agents and in the production of gasoline inhibitors. 2,4,6-Trinitrotoluene is a military and industrial explosive. Nitrobenzene is utilized in the manufacture of aniline. It acts as a solvent for cellulose ethers and as an ingredient in metal, floor and shoe polishes, and soaps. Nitrobenzene is also used for refining lubricating oils and in the production of isocyanates, pesticides, rubber chemicals and pharmaceuticals.
In the leather industry, m-nitrophenol is a fungicide and p-nitrophenol is a chemical intermediate for leather preservatives. 2,4-Dinitrophenol is useful in the manufacture of photographic developers and serves as a wood preservative and an insecticide. 2-Nitro-p-phenylenediamine and 4-amino-2-nitrophenol are components of permanent hair dye products and fur dyes.
p-Nitrosodiphenylamine acts as an accelerator for rubber vulcanization and as a polymerization inhibitor during the manufacture of vinyl monomers. Picric acid has numerous uses in the leather, textile and glass industries. It is found in explosives, dyes, germicides, fungicides, electric batteries, and in rocket fuel. Picric acid is also used for etching copper and as a chemical intermediate. Tetryl is employed as an intermediary detonating agent for other less sensitive high explosives and as a booster charge for military devices.
Hazards
Health
The most prominent acute health hazard of the aromatic nitro- compounds is cyanosis, and the chronic manifestation is anaemia. The fat-soluble nitrocompounds are very rapidly absorbed through the intact skin. A certain amount is excreted unchanged through the kidneys, but the major portion is reduced to cyanogenic nitroso and hydroxylamine derivatives, which in turn are degraded to the ortho- and para-aminophenol analogues and excreted in the urine. Three out of four cases of cyanosis will exhibit the classical blue or ashen-grey appearance, but only one-third of the victims will complain of anoxia symptoms (headache, fatigue, nausea, vertigo, chest pain, numbness, abdominal pain, aching, palpitation, aphonia, nervousness, air hunger and irrational behaviour). Blood and urine analyses are required for confirmation. Heinz bodies may be detected in the red cells. Methaemoglobinemia is discussed in more detail elsewhere in this Encyclopaedia.
Cyanogenic potential is profoundly altered by both the nature and position of substituent groups in the benzene ring. In addition to cyanogenic potential, the nitrochlorobenzenes as a class are also skin irritants. The dinitrochlorobenzenes produce sensitivity dermatitis in most people even after slight contact. Dichloronitrobenzenes possess intermediate toxicity.
The long-term chronic effects are more insidious and can be detected only from well-documented medical records. Bimonthly blood analyses will disclose the onset of anaemia over several years even in the absence of detectable cyanosis or significantly elevated urinary excretion.
2,4-Dinitrotoluene affects the drug-metabolizing enzymes in liver microsomes, and it has been shown to be a hepatocarcinogen in the rat. No data are available as regards its carcinogenic potential to humans.
1- and 2-Nitronaphthylamine were isolated as urinary metabolites of 1- and 2-nitronaphthalene, respectively, in the rat. This has important implications for possible carcinogencity of the nitronapthalenes.
Dinitrophenol (DNP) is an acute poison disrupting cellular metabolism in all tissues by disturbing the essential process of oxidative phosphorylation. If not fatal, the effects are rapidly and completely reversible. Exposure may occur by the inhalation of the vapour, dusts or sprays of solutions of DNP. It penetrates the intact skin but, as it is a brilliant yellow dye, skin contamination is readily recognized. Systemic poisoning has occurred during both production and use. DNP solid is explosive, and accidents have also occurred during production and use. Care must be exercised when handling it.
Poisoning results first in excessive sweating, a feeling of warmth with weakness and fatigue. In severe cases, there is rapid respiration and tachycardia even at rest, and there may be a rise in body temperature. Death, if it occurs, is sudden, and rigor mortis ensues almost immediately. DNP exerts its toxic effects by a general disturbance of cell metabolism resulting in a need to consume excessive amounts of oxygen in order to synthesize the essential adenine nucleotide required for cell survival in the brain, heart and muscles. If heat production is greater than heat loss, fatal hyperthermia may result. The effects are most severe in hot workplaces.
DNP is readily reduced to the much less toxic, but not innocuous, aminophenol, which is excreted in the urine in this form. Since DNP is rapidly metabolized and excreted and since poisoning does not lead to structural changes in tissues, chronic or cumulative effects from small doses absorbed over long periods do not occur. Poisoning may be confirmed by finding DNP or aminophenol in the urine by Derrien’s test. Methaemoglobinemia does not develop.
Dinitrobenzene is a potent chemical with multisystemic effects (minimally affecting the central nervous system (CNS), blood, liver, cardiovascular system and eyes). It can cause severe anaemia and is a methaemoglinemia inducer.
Nitrobenzene may be absorbed into the body through the respiratory system or the skin (e.g., from shoes dyed black with a dye containing nitrobenzene, or from contamination of clothing worn by workers employed on nitrobenzene production). The outstanding toxic effect of nitrobenzene is its capacity for causing methaemoglobinemia. The onset is insidious, and cyanosis appears only when the methaemoglobin level in the blood reaches 15% or more. At a later stage, hypotension, headache, nausea, vertigo, numbness of the limbs, severe general weakness and cortical disturbances may occur if methaemoglobinemia is severe. Nitrobenzene is also a central nervous poison, causing in some cases, excitement and tremors followed by severe depression, unconsciousness and coma. Examination of the urine of exposed persons reveals the presence of nitro- and aminophenols, the amounts of which run parallel with the level of methaemoglobinemia. Repeated exposure may be followed by liver impairment up to yellow atrophy, haemolitic icterus and anaemia of varying degrees, with the presence of Heinz bodies in the red cells. Nitrobenzene may also produce dermatitis due to primary irritation or sensitization.
Picric acid and derivatives. Picric acid derivatives of industrial importance are the metallic picrates (iron, nickel, barium, chromium, lead and potassium) and the salts of ammonia and guanidine. Some of the metallic salts (barium, lead or potassium) have been used as constituents of detonating and boosting mixtures in bombs, mines and shells. Toxic effects may result from skin contact or inhalation or ingestion of the dust of picric acid or its salts. Skin contact may also produce skin disease. A number of its metallic salts are also dangerous fire and explosion hazards.
Following ingestion of a few grams of picric acid, which has an intensely bitter taste, acute gastroenteritis, toxic hepatitis, nephritis, haematuria and other urinary symptoms may occur. The skin and conjunctivae become yellow, mostly due to the acid but partly due to jaundice. Yellow vision may develop. Death, if it follows, is due to renal lesions and anuria. Rarely, jaundice and coma with convulsions precede death. Headache and vertigo with nausea and vomiting and skin rashes occur after absorption from the body surface.
In industry, particularly in the manufacture of explosives, the main health problem has been the occurrence of skin disease, and systemic poisoning is rare. It has been reported that picric acid is a distinct skin irritant in the solid form, but in aqueous solution it irritates only hypersensitive skin; it causes sensitization dermatitis similar to that produced by ammonium picrate. The face is usually involved, especially around the mouth and sides of the nose. There are oedema, papules, vesicles and finally desquamation. Hardening occurs as with tetryl and trinitrotoluene. Workers handling picric acid or its salts have the skin and hair dyed a yellowish colour.
Experimental animals severely exposed to ammonium picrate dust for periods up to 12 months revealed lesions that suggested definite injury to certain tissues. Dust of picric acid may cause not only irritation of the skin but also of the nasal mucosa. The inhalation of high concentrations of dust has caused temporary unconsciousness followed by weakness, myalgia, anuria and later polyuria. The effects of picric acid on the eyes include irritation, corneal injury, strange visual effects (e.g., yellow appearance of objects) and yellow colouring of the tissues.
Picric acid and its flammable and explosive derivatives should be stored in small quantities in a cool, ventilated area away from acute fire hazards and powerful oxidizing materials and, preferably, in an isolated or detached building.
Tetryl. The explosion hazards encountered in the production of tetryl are basically the same as those for other products of the explosives industry, although tetryl, being relatively stable, cannot be considered among the most hazardous of explosives.
During the manufacture of tetryl, workers may be exposed to nitrogen oxides and acid vapours should leakage occur from the nitration reactors. There can be exposure to appreciable amounts of tetryl dust during booster manufacture and subsequent handling operations, especially in non-automated mixing, weighing, tablet-pressing, dedusting, and in the loading and assembling of explosive devices. The principal manifestations of exposure are irritation of the mucous membranes, staining and discoloration of the skin and hair, dermatitis and, in cases of prolonged, severe exposure, systemic poisoning due to inhalation and skin absorption.
On initial exposure, tetryl produces acute irritation of the nasal and pharyngeal mucous membranes. Within a few days, the hands, face, scalp and hair of exposed workers are stained a yellowish colour. Under severe exposure, the conjunctivae are affected and nearly always bloodshot; palpebral and periorbital oedema is not uncommon. During the first 2 to 3 weeks of exposure, workers may develop a dermatitis in the form of erythema, particularly in the region of the neck, chest, back and the inside surface of the forearms. After a few days the erythema may regress, leaving moderate desquamation. Workers who can continue to work in spite of the dermatitis develop a tolerance for, or become hardened to, tetryl. However, with severe exposure, or in subjects with poor personal hygiene or very fair skin, the dermatitis may spread to other parts of the body and become papular, vesicular and eczematous.
After only 3 to 4 days of exposure to high dust concentrations, workers may complain of headaches followed by periodic nosebleeding. Upper respiratory tract irritation does not frequently extend to the bronchi because, due to their large size, tetryl crystals do not usually reach this far; however, dry cough and bronchial spasms have been observed. Diarrhoea and menstrual disorders may occur occasionally.
Many of the disorders caused by tetryl are to be attributed to the irritant action of the crystals. In some cases, the dermatitis is allergic; in many cases, mechanisms such as local histamine liberation have been suggested.
Following severe, prolonged exposure, tetryl causes chronic poisoning with digestive disorders (such as loss of appetite, abdominal pain, vomiting), loss of weight, a chronic hepatitis, central nervous system irritation with insomnia, exaggerated reflexes, and mental excitation. Cases of leucocytosis with occasional slight anaemia have been reported. There have been reports of menstrual disturbances as well. Animal experiments indicate renal tubule damage.
Trinitrotoluene, commonly known as TNT, is also a methaemoglobin inducer. During the First World War it was found that workers who were involved in the manufacture of munitions developed severe liver effects and anaemia, with at least 25% of the approximately 500 cases reported ending in fatalities. Adverse effects were also observed during the Second World War. Presumably conditions have improved so that exposure is far more limited and overt poisoning should then not occur. Menstrual irregularities, urinary tract problems and cataracts have also been reported.
Fire and explosion
Aromatic nitrocompounds are flammable and the di- and trinitroderivatives are explosive under favourable conditions (heat and shock). Pumps operating against a closed discharge valve or plugged line have produced sufficient frictional heat with mononitrotoluene and nitrochlorobenzenes to produce explosions. Other than nitrobenzene, aromatic nitro- compounds should not be heated under alkaline conditions. Dinitro- compounds may form shock-sensitive nitrolium salts, and fires have resulted from heating potassium carbonate in
o-nitrotoluene.
Contact with strong reducing agents such as sodium sulphide, zinc powder, sodium hydrosulphite and metallic hydrides, and strong oxidizing agents such as bichromates, peroxides and chlorates, must be avoided in storage and transit. Those derivatives containing reactive chlorine atoms require special care in storage and transit. Chemical reduction processes must provide for addition of the nitro- compound to the reducing system (acidic iron reduction, alkaline sulphide and so on) in small increments at a rate which avoids overheating or accumulation of excess nitro- compound.
Although hazards inherent in concentrated nitric and sulphuric acids are recognized, caution must be observed in the disposal of spent mixed acid which contains organic components which are highly unstable in storage or on heating. The finished product must be washed thoroughly and neutralized to avoid metallic corrosion and spontaneous decomposition.
Safety and Health Measures
An effective health programme to prevent health impairment due to exposure to aromatic nitro- compounds requires exposure control and medical supervision measures. Job analysis to ensure proper handling procedures, adequate equipment design for both operating and maintenance, and appropriate ventilation with air-pollution control are minimum requirements. Totally enclosed systems are preferred. Where appropriate, air analysis can be helpful; but in general, results have been misleading due to the low vapour pressure of nitrobenzene derivatives and contamination of surfaces where skin contact occurs. However, mist from hot charges, leaking lines, steaming operations, hot drainage ditches and so on, cannot be ignored as sources of gross skin exposure and contamination of the work environment.
The necessary protective measures in ascending order of effectiveness are respiratory protection, job rotation, limitation of exposure time, use of protective clothing and whole-body protection. Respiratory protection has limited application, since skin absorption is the major problem. Protective equipment must be selected carefully to assure impermeability to the chemicals in use.
A high standard of personal hygiene—in particular, a warm shower with plenty of soap and water vigorously applied at the end of the shift—will minimize chronic exposure which deprives the worker of limited tolerance to cyanogenic agents. Because of the suspected carcinogenic potential for humans of 1- and 2-nitronaphthalene, occupational exposure to these compounds should be kept at the lowest possible level.
Where possible, picric acid and its hazardous derivatives should be replaced by substances which are innocuous or less harmful. Where this is not possible, the process should be modified, isolated or enclosed; automatic or mechanical handling techniques, local exhaust ventilation and wet methods should be employed to minimize atmospheric concentrations; and direct contact with the chemicals should be avoided.
Aromatic nitrocompounds tables
Table 1 - Chemical information.
Table 2 - Health hazards.
Table 3 - Physical and chemical hazards.
Table 4 - Physical and chemical properties.