Methyl bromide, a potent alkylating agent, is an odorless, colorless, extremely toxic gas used as a fumigant in soil, perishable foods, cargo containers, and buildings. It is also used in the chemical industry. Fields or buildings to be fumigated are evacuated and covered with a giant tarp, and the gas is introduced. After 12–24 hours, the tarp is removed, and the area is ventilated and then tested for residual methyl bromide before reoccupation. Methyl bromide is a major source of ozone-destroying bromine in the stratosphere, and most production and use were scheduled to be phased out by 2005 in developed countries and by 2015 in developing countries; however, it is still being used in the United States owing to EPA critical use exemptions.
Mechanism of toxicity
Methyl bromide is a potent, nonspecific alkylating agent with a special affinity for sulfhydryl and amino groups. Limited data indicate that toxicity is the result of direct alkylation of cellular components (eg, glutathione, proteins, or DNA) or formation of toxic metabolites from methylated glutathione. Animal data clearly indicate that its toxicity does not result from the bromide ion.
Pharmacokinetics. Inhaled methyl bromide is distributed rapidly to all tissues and metabolized. In sublethal animal studies, approximately 50% is eliminated as exhaled carbon dioxide, 25% is excreted in urine and feces, and 25% is bound to tissues as a methyl group. The elimination half-life of the bromide ion is 9–15 days.
Toxic dose. Methyl bromide is threefold heavier than air, may accumulate in low-lying areas, and may seep via piping or conduits from fumigated buildings into adjacent structures. It may condense to a liquid at cold temperatures (3.6°C [38.5°F]), then vaporize when temperatures rise. Methyl bromide gas lacks warning properties, so the lacrimator chloropicrin (2%) usually is added. However, chloropicrin has a different vapor pressure and may dissipate at a different rate, limiting its warning properties.
Inhalation is the most important route of exposure. The ACGIH-recommended workplace exposure limit (TLV-TWA) in air is 1 ppm (3.9 mg/m3) as an 8-hour time-weighted average. Toxic effects generally are seen at levels of 200 ppm, and the air level considered immediately dangerous to life or health (IDLH) is 250 ppm. NIOSH considers methyl bromide a potential occupational carcinogen.
Skin irritation and absorption may occur, causing burns and systemic toxicity. Methyl bromide may penetrate clothing and some protective gear. Retained gas in clothing and rubber boots can be a source of prolonged dermal exposure.
Acute irritant effects on the eyes, mucous membranes, and upper respiratory tract are attributed to the added lacrimator chloropicrin. (Lethal exposures can occur without warning if chloropicrin has not been added.) Moderate skin exposure can result in dermatitis and, in severe cases, chemical burns.
Acute systemic effects usually are delayed by 2–24 hours. Initial toxicity may include malaise, visual disturbances, headache, nausea, vomiting, and tremor, which may advance to intractable seizures and coma. Death may be caused by fulminant respiratory failure with noncardiogenic pulmonary edema or ...