Carbon monoxide methylene chloride metabolized

Available data suggest that there are two pathways by which methylene chloride is metabolized. One utilizes the mixed function oxidase enzymes and produces carbon monoxide, while the other pathway involves glutathione transferase and produces carbon dioxide. The mixed function oxidase pathway seems to be the preferred pathway for methylene chloride metabolism following inhalation exposures. In addition to carbon monoxide and carbon dioxide, methylene chloride is also metabolized to a lesser extent to formaldehyde and formic acid. 

Methylene chloride metabolizes in body to carbon monoxide, which forms carboxy-hemoglobin in blood. The concentration of the latter is related to the vapor concentration and the duration of exposure. 

In addition to tobacco smokers, individuals who have had previous exposure to materials containing methylene chloride, such as degreasers, solvents, paint removers, and furniture strippers, are at greater risk because of an existing body burden of carbon monoxide. Approximately one-fourth to one-third of inhaled methylene chloride vapor is metabolized in the liver to carbon monoxide. In addition, methylene chloride is readily stored in body tissue. This stored material is released over time and results in elevated levels of carbon monoxide for extended periods, in some cases more than twice as long as compared with direct carbon monoxide inhalation. 

These are formed much less commonly than electrophiles. An example is cyanide (CN-), which can be produced by metabolism of acrylonitrile, or of the drug sodium nitroprusside. Carbon monoxide is another example, which can be produced by metabolism of methylene chloride. 

Figure 7.65 Metabolism of methylene chloride to carbon monoxide.

Some of the solvent wiU be metabolized in the liver, and one product of the metabolism is the poisonous gas carbon monoxide. There have been cases of severe carbon monoxide poisoning due to prolonged exposure to methylene chloride. Someone exposed to the solvent for two to three hours may achieve a level of 15 per cent carbon monoxide in the blood, which would cause only mild effects in a healthy individual but possibly more severe problems in someone with heart or lung disease. 

Human subjects exposed by inhalation to 500 ppm or greater for 1 or 2 h experienced elevated carbox-yhemoglobin concentrations indicating that methylene chloride was metabolized to carbon monoxide by the mixed function oxidase pathway. Metabolism of methylene chloride in animals is similar to that in humans. Animal data on metabolism indicate that the process is similar for both inhalation and oral exposures. 

Methyl chloride, methylene dichloride. Colourless liquid, bp 40-41°C. Industrial solvent and paint remover. Fumigant. Rapidly metabolized to carbon monoxide produces carboxy-Hb. Irritant to eyes and skin blistering on prolonged contact. Anaesthetic effects on CNS coma, death. 

Methylene chloride Rat LDjo 1.6gJkg (oral) Hitman LDLo 357mg/kg (oral) narcotic effect Siispected carcinogen and mutagen Damage to hver and kidneys Metabolized to carbon monoxide Nervous system disorders Skin irritation Therapeutic category Pharmaceutical aid (solvent) ... 

Methylene Chloride (MC) is primarily an inhalation hazard. The principal acute hazardous effects are the depressant action on the central nervous system, possible cardiac toxicity and possible liver toxicity. The range of CNS effects are from decreased eye/hand coordination and decreased performance in vigilance tasks to narcosis and even death of individuals exposed at very high doses. Cardiac toxicity is due to the metabolism of MC to carbon monoxide, and the effects of carbon monoxide on heart... 

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