METHYLISOCYANATE 1 X 500MG NEAT

Methyl isocyanate (MIC) is an organic compound with the molecular formula CH3NCO. MIC is an extremely toxic, colorless, highly flammable liquid that evaporates quickly when exposed to the air and has a sharp, strong odor. It is hazardous to human health, and was involved in the Bhopal disaster in December 1984, which resulted in the deaths of more than 2250 individuals, with another 50 000 incapacitated, and about 100 000 treated in area hospitals.

Methyl isocyanate is a colorless liquid. Sharp odor which is a lachrymator (causes tears) and has poor warning properties: IDLH 5 3 ppm; odor threshold 5 2.1 ppm.

Methyl isocyanate is used as a chemical intermediate for the production of carbamate insecticides and herbicides. Occupational exposure to methyl isocyanate may occur in those workers who use insecticides and herbicides produced from methyl isocyanate.

colourless liquid

Clear, colorless, very flammable, posionous liquid with a sharp, unpleasant, penetrating odor. Odor threshold concentration is 2.1 ppm (quoted, Amoore and Hautala, 1983).

Methyl isocyanate is used primarily in making pesticides and herbicides such as carbaryland aldicarb. It is also used to a lesserextent to produce plastics and polyurethanefoams. Methyl isocyanate was attributed tothe deaths of more than 3000 people inBhopal, India, in a very tragic industrial accident during the 1980s.

Production of polyurethane foams and plastics; chemical intermediate

In organic synthesis; in manufacture of carbamate pesticides.

ChEBI: The isocyanate that is methane modified by a single isocyanato substituent.

Methyl isocyanate is reacted with 1-naphthol to produce the carbamate insecticide carbaryl and with α-methylthioisobutyrladoxime in the industrial synthesis of aldicarb.

Highly flammable. Reacts exothermically with water to produce carbon dioxide, methylamine, dimethylurea and/or trimethylbiuret. Heat of reaction causes evolution of the vapors of the isocyanate. Reaction is relatively slow below 20°C but becomes violent at more elevated temperatures or in the presence of acids and bases.

Airborne vapors of METHYLISOCYANATE 1 X 500MG NEAT are explosive when exposed to heat, flame or sparks. Vapor may ignite on contact with strong oxidizing agents. Emits toxic fumes of nitriles and oxides of nitrogen when heated to decomposition [Lewis, 3rd ed., 1993, p. 860]. Caused the death of thousands in 1984 in Bhopal, India when released accidentally as a vapor following an exothermic reaction caused by contamination with water [Chem. Eng. News, 1985, 63(6), p. 27]. Reacts rapidly with acids and bases (including amines). May polymerize in contact with iron, tin, copper and certain other catalysts such as triphenylarsenic oxide, triethyl phosphine and tributyltin oxide. Polymerizes at elevated temperatures. Attacks some plastics, rubbers, and coatings [NTP].

Flammable, dangerous fire risk. Toxic byskin absorption and a strong eye and upper respira-tory tract irritant.

METHYLISOCYANATE 1 X 500MG NEAT is a skin irritant and can cause permanent eye damage. A concentration of 2 ppm has been reported toxic in humans. METHYLISOCYANATE 1 X 500MG NEAT attacks the respiratory system, eyes and skin. It can injure the lungs and bronchial airways, cause permanent eye damage, and death. Death has been attributed to various forms of respiratory distress.

Methyl isocyanate is a dangerously toxiccompound. Inhalation, oral intake, andabsorption through skin can seriously affectthe lungs, eyes, and skin. The compoundcan exert toxic effects on numerous organsystems. Such systemic effects may beattributed to its ability to traverse cellmembranes and reach distant organs as areversible conjugate with glutathione (Varmaand Guest 1993).
Exposure to its vapor can cause lacrimation, irritation of nose and throat, and respiratory difficulty. In humans, exposure to 2 ppmfor 5 minutes caused irritation and lacrimation, which became unbearable at 20 ppm.Odor was perceived at 4–5 ppm concentration. However, irritation of the nose and throat, occurring to a lesser extent than lacrymation, was evident in humans at 2 ppm(5 minutes exposure). The recovery from lowexposure was fast — all effects disappearedwithin 10–20 minutes.
Methyl isocyanate is a severe acute toxicant. Penetration through the skin causedhemorrhage and edema. Acute symptomsfrom oral intake or absorption through skinwere asthma, chest pain, dyspnea, pulmonaryedema, difficulty in breathing, and death.Direct contact into eyes can damage vision.
LC50 value, inhalation (rats): 6.1 ppm/6 hr
LD50 value, oral (rats): 69 mg/kg
LD50 value, skin (rabbits): 213 mg/kg
In an acute and subacute toxicity studyof inhaled methyl isocyanate in rats, Sethiet al. (1989) observed that the animals hadcongestion in the eyes, lacrimation, nasalsecretion, dyspnea, progressively increasedataxia, and immobility following a singleexposure to 3.52- and 33.32-ppm doses for10 minutes each. The higher concentrationdose produced severe effects. The same clinical signs were observed in subacute toxicity experiments at doses of 0.21–0.35 ppmfor 30 minutes daily for 6 days by inhalation. Uncoordinated movements were alsoobserved during this exposure period, whichindicated that the nervous system was injured.A 2-hour exposure to 65 ppm was lethal torats — the death resulting from pulmonaryedema (Salmon et al. 1985). There was erosion of the corneal epithelium in eyes, whichwas most severe at intermediate levels ofexposure. Congestion of the blood vessels,edematous changes, and cellular reaction persisted several days after a single exposure to3.2 mg/L for 8 minutes (Dutta et al. 1988).The recovery was slow and gradual. Exposureto higher concentrations resulted in necrotizing or corrosive action, lung injury, and deathof all exposed rats.
Acute exposure of mice and rats to sublethal and lethal concentrations for 2 hours produced restlessness, lacrimation, and a reddish discharge from the nose and mouth(Bucher et al. 1987a,b). The lethal concentrations were 20–30 ppm. The deaths occurredwithin 15–18 hours after severe respiratory distress. Males were more prone toearly death than females. Animals exposedto 10 ppm died after 8–10 days. The studyindicated that there was no cyanide in theblood. Thus at these doses methyl isocyanatetoxicity was not due to cyanide. Repeatedinhalation of 3 and 6 ppm for 6 hours/dayfor 4 consecutive days was lethal for ratsand mice, respectively. The respiratory system was the primary site of injury. There waslittle evidence of direct effects on nonrespiratory tissues.
Methyl isocyanate administered subcutaneously in rabbits resulted in a fall in arterial blood pressure and respiratory inhibition(Jeevaratnam et al. 1988). The LD50 valuesfor the pure compound for male and femalemice were 81.9 and 85.3 mg/kg, respectively(Vijayaraghavan and Kaushik 1987). Ratsexhibited greater resistance.
Jeevaratnam and Sriramachari (1994a,1994b) have described and compared the toxicity of methyl isocyanate and its hydrolytic derivatives in rats in acute, subacute andchronic phases. The compound hydrolyzesto methylamine and N,N0-dimethyl urea. Theacute effects from inhalation of methyl isocyanate are necrotizing bronchitis of theentire respiratory tract along with varyingdegrees of confluent congestion, hyperemia,and interstitial and intra-alveolar edema.Subcutaneous administration produced vascular endothelial damage, congestion andsevere interstitial pneumonitis with apparently normal bronchial epithelium. In comparison, the hydrolytic products methylamineand N,N0- dimethyl urea, the latter only tosome extent, caused interstitial pneumonitislesion. The authors suggested the possibleinvolvement of both these hydrolytic products in the subsequent inflammatory responseof methyl isocyanate. The long-term histopathological effects in the lungs of rats from a single exposure to MIC by both the inhalation and subcutaneous routes indicated intraalveolar and interstitial edema that wereprominent only in the inhalation group asagainst the more pronounced inflammatoryresponse from subcutaneous administration.Evolution of lesions appeared to be similarwith progress in time developing into significant interstitial pneumonitis and fibrosis.Methylamine, one of the hydrolytic derivatives of MIC also manifested the sameeffects, however, to a lesser extent than MIC.
In an earlier study, Jeevaratnam et al.(1993) found that the systemic effects weresolely from the MIC, despite of its hydrolyticinstability and there were no effects eitherfrom methylamine or N,N0-dimethylurea.Thus, MIC administered subcutaneously atLD50 dose induced severe hyperglycemia,lactic acidosis and uraemia in rats in contrastto almost no effect from equimolar doses ofits two hydrolytic derivatives
Methyl isocyanate was not mutagenic inthe Salmonella reversion assay but cytotoxicat relatively higher concentrations (Meshramand Rao 1987). McConnell et al. (1987)observed that it was genotoxic in culturedmammalian cells and showed marginal evidence of chromosomal damage in the bonemarrow of mice.

Exposures to methyl isocyanate are extremely toxic to humans. In Bhopal, India, in 1984, accidental exposures to methyl isocyanate caused poisoning and fatal injuries to large numbers of occupational workers as well as the general public, because of a Union Carbide gas leak. The accidental gas leakage resulted in the deaths of more than 2,000 people and adverse health effects in greater than 170,000 survivors. Pulmonary edema was the cause of death in most cases, with many deaths resulting from secondary respiratory infections such as bronchitis and bronchial pneumonia. The acute inhalation exposure to methyl isocyanate in humans caused poisoning with symptoms that include, but are not limited to, respiratory tract irritation, diffi culty breathing, blindness, nausea, gastritis, sweating, fever, chills, and liver and kidney damage. Survivors continued to exhibit damage to the lungs with bronchoalveolar lesions and decreased lung function. The damage to the eyes included loss of vision, loss of visual acuity, and cataracts. There is no report on the chronic/long-term effects of methyl isocyanate in humans or animals. Studies on animals have indicated increased incidence of fetal deaths and decreased fertility, live litter size, fetal body weight, and neonatal survival following inhalation exposure to methyl isocyanate during pregnancy.

Reacts violently with water. Extremely flammable; may be ignited by heat, sparks, or flames. Vapors may travel to a source of ignition and flash back. Container may explode violently in heat of fire. Vapor explosion and poison hazard indoors, outdoors, or in sewers. Runoff to sewer may create fire or explosion hazard. When heated to decomposition, METHYLISOCYANATE 1 X 500MG NEAT emits toxic fumes of nitrogen oxides. Avoid water, acids, alkali, amines, iron, tin, copper, and other catalysts. Avoid heat, flame, oxidizers, water. Hazardous polymerization may occur. METHYLISOCYANATE 1 X 500MG NEAT (MIC) will react with water, or in the presence of catalysts (such as sodium hydroxide, sodium methoxide, triphenylarsine, triethyl phosphine, metallic chlorides) to form either a cyclic trimer (trimethyl isocyanurate) or a gummy, resinous polymer. These reactions are exothermic, producing about 540 Btu per pound of MIC. Heat produced in these reactions may result in pressure build up and rupturing of tanks.

Poison by inhalation, ingestion, and skin contact. Human systemic effects by inhalation: conjunctiva irritation, olfactory and pulmonary changes. An experimental teratogen. Other experimental reproductive effects. Mutation data reported. A severe eye, skin, and mucous membrane irritant and a sensitizer. It can be absorbed through the skin. Exposure to high concentrations of the vapor can cause blindness; lung damage, including edema, permanent fibrosis, emphysema, and bronchitis; and gynecological effects. Most deaths are a result of lung tissue damage. This was the predominant cause of death in the release of MIC in 1984 at Bhopal, India. Effects of cyanide poisoning have been noted but this may be due to impurities. A flammable liquid and a very dangerous fire hazard when exposed to heat, flame, or oxiduers. To fight fire, use spray, foam, CO2, dry chemical. Exothermic reaction with water. When heated to decomposition it emits toxic fumes of NOx and CN-.

Methyl isocyanate is used in carbamates and as chemical intermediate; in the manufacture of a wide variety of pesticides; in the production of polyurethane foams and plastics. A release of this chemical was involved in the world’s largest chemical accident, causing the death of thousands of industrial workers in 1984 in Bhopal, India.

May cause allergic sensitization ofskin and respiratory tract. Subsequent exposure even atextremely low levels may cause asthma attacks. May causechronic lung disease and increased susceptibility to lunginfection. May affect the lungs, causing tissue lesions.Exposure may cause miscarriages among pregnant women.

Genetic and Related Cellular Effects Studies. Mason et al. found that methyl isocyanate did not induce mutagenic response in the Salmonella assay under test conditions. It was also negative in the Drosophila test for sex-linked recessive lethal mutations; however, it was positive in the cultured CHO cells. Mason et al. found that methyl isocyanate was positive in the mouse lymphoma assay.

Chemical/Physical. Reacts with water forming 1,3-dimethylurea and carbon dioxide. In excess water, the hydrolysis half-life is 9 min. (Castro et al., 1985)

Color Code—Blue: Health Hazard/Poison: Storein a secure poison location. Prior to working with thischemical you should be trained on its proper handling andstorage. Before entering confined space where this chemicalmay be present, check to make sure that an explosive concentration does not exist. Methyl isocyanate must be storedto avoid contact with water, acid, alkali, amines; or iron,tin, copper (or their salts); and certain other catalysts sinceviolent reactions occur. Store in tightly closed containers ina cool, well-ventilated area away from water or heat.Sources of ignition, such as smoking and open flames, areprohibited where methyl isocyanate is handled, used, orstored. Metal containers involving the transfer of 5 gallonsor more of methyl isocyanate should be grounded andbonded. Drums must be quipped with self-closing valves,pressure vacuum bungs, and flame arresters. Use only nonsparking tools and equipment, especially when opening andclosing containers of methyl isocyanate. Wherever methylisocyanate is used, handled, manufactured, or stored, useexplosion-proof electrical equipment and fittings.

UN2480 Methyl isocyanate Hazard class: 6.1; Labels: 6.1-Poison Inhalation Hazard, 3-Flammable liquid, Inhalation Hazard Zone A

Mechanisms of toxicity have still not been clearly elucidated for MIC per se. It is hypothesized that carbamylation of globin and blood proteins may be involved. Histopathologic evaluation of rodents exposed to MIC by inhalation suggest that MIC-induced injury is limited to the respiratory system. Immediate deaths most likely are a result of tissue hypoxia secondary to blockage of airways by cellular debris, mucus, and fluid. Delayed deaths most likely are caused by chronic obstructive and restrictive lung diseases. Persistent respiratory and ocular effects may also be a result of MIC-induced immunologic effects since specific antibodies have been demonstrated in the blood of exposed patients. MIC is highly reactive; therefore, the resulting onset of respiratory effects following acute exposure to MIC can be immediate in some cases. In other exposure scenarios, respiratory injury can evolve over periods of hours or days. Exposure-related deaths sometimes can occur as late as 30 or more days postexposure, due in part to the development of pneumonia. Results from human and animal studies indicate that MIC is a severe irritant to mucous membranes. Ocular irritation was the most pronounced symptom reported in human experimental studies. The most frequently reported symptoms among the exposed population in Bhopal, India, were burning of the eyes, coughing, respiratory distress from pulmonary congestion, watering of the eyes, nausea, vomiting, muscle weakness, and CNS involvement secondary to hypoxia and animal fatalities are which attributed to pulmonary edema.

Highly flammable liquid. Vapors may form explosive mixture with air. Rapid reaction in presence of acid, alkalis, amine; iron, tin, copper, their salts; or their catalysts (such as triphenylarsenic oxide, triethylphosphine, and tributyltin oxide). Exothermic reaction with water, producing carbon dioxide, highly flammable and air-reactive methylamine, dimethylurea and/or trimethyl biuret. The reaction with water is slow @ # 20C, but violent at elevated temperatures and/or in the presence of acids and bases. Elevated temperatures may cause explosive polymerization. This chemical usually contains inhibitors to prevent polymerization. Reacts with water, acids, alcohols, glycols, amines, amides, ammonia, caprolactum, caustics, strong oxidizers. Attacks some plastics, rubber or coatings. Attacks some forms of plastic, rubber and coatings

Consult with environmental regulatory agencies for guidance on acceptable disposal practices. Generators of waste containing this contaminant (≥100 kg/mo) must conform to EPA regulations governing storage, transportation, treatment, and waste disposal. Incineration in the presence of a flammable solvent. A flue gas scrubber is recommended as well.