Methemoglobin/methemoglobinemia

Inhalation is the chief route of worker exposure. Comparative data from acute or subchronic inhalation exposures with rats (98) indicate that nitromethane and nitroethane are the least toxic of the nitroparaffins by this route and do not induce methemoglobin formation. The nitropropanes are less well tolerated 2-nitropropane is more toxic than 1-nitropropane and is more likely to cause methemoglobinemia. 

In methemoglobinemia, the heme iron is ferric rather than ferrous. Methemoglobin thus can neither bind nor transport Oj. Normally, the enzyme methemoglobin... 

Methemoglobinemia Intake of excess oxidants (various chemicals and drugs) Genetic deficiency in the NADH-dependent methemoglobin reductase system (MIM 250800) Inheritance of HbM (MIM 141800)... 

Except for cyanosis of the mucous membranes, dogs failed to show any signs of methemoglobinemia at methemoglobin concentrations of less than about 60%. At levels of 60-70% the predominant signs were salivation, ataxia and vomiting. Ataxia and vomiting occurred at 71-80% and loss of consciousness occurred at 81-90% (Bodansky 1951). 

The study by Kim and Carlson (1986) determined that a concentration of 150 ppm for 8 h resulted in 41% methemoglobinemia. No report of clinical signs was included by these authors. According to Bodansky (1951), dogs failed to show any clinical signs at methemoglobin concentrations of less than about 60%. 

Bodansky, O. 1951. Methemoglobinemia and methemoglobin producing compounds. Pharmacol. Rev. 3 144-196. 

The role of deacetylation in methemoglobinemia induced by acetanilide (4.101) and phenacetin (4.107) has been demonstrated. Indeed, concomitant i.p. administration of BNPP considerably reduced the hematotoxicity of these compounds [87]. Recent studies have shown that /V-hydroxyphenetidine (4.144), a metabolite of deacetylated phenacetin, is responsible for hemolysis and methemoglobin formation [88]. 

Intravenous injection of an 18.4 mg/kg dose of 1,2-diphenylhydrazine di(l not cause methemoglobinemia in rats, although methemoglobin was formed by an equimolar dose of aniline (Pfordte 1973) Information On methemoglobinemia in animals following treatment with... 

The primary effect of 1,3-DNB absorbed into blood is the formation of methemoglobin. For a detailed discussion on the mechanism of methemoglobinemia induction please see Section 2.3.5. 

Methemoglobinemia is a primary biomarker of effect for 1,3-DNB and 1,3,5-TNB. Well-established and reliable methods exist for monitoring methemoglobin formation using a complete blood count (Ishihara et al. 1976). However, methemoglobinemia is not a specific effect of 1,3-DNB and 1,3,5-TNB other chemicals also cause methemoglobin formation. Other effects of exposure to... 

Few reports of industrial experience are available from which to form an accurate appraisal of its health hazards it is said to be less potent than aniline as a cause of methemoglobin, but more of a central nervous system depressant. The effects of methemoglobinemia are cyanosis (especially of the lips, nose, and earlobes), weakness, dizziness, and severe headache. ... 

The onset of symptoms of methemoglobinemia is insidious and may be delayed for up to 4 hours headache is commonly the first symptom and may become quite intense as the severity of methemoglobinemia progresses. Cyanosis occurs when the methemoglobin concentration is 15% or more blueness in the lips, the nose, and the earlobes is usually recognized by fellow workers. ... 

In a fatal human exposure, a worker engaged in emptying metal gas cylinders of methyl mercaptan was found comatose at the work site he developed expiratory wheezes, elevated blood pressure, tachycardia, and marked rigidity of extremities. Methemoglobinemia and severe hemolytic anemia developed with hematuria and proteinuria but were brief in duration deep coma persisted until death due to pulmonary embolus 28 days after exposure. It was determined that the individual was deficient in erythrocyte glucose-6-phosphate dehydrogenase, which was the likely cause of the hemolysis and formation of methemoglobin. 

Thirteen-week inhalation exposure to ONCB in mice at doses ranging from 1.1 to 18 ppm caused hyperplasia of the forestomach, hepatocellular necrosis, secondary effects of methemoglobin formation on the spleen, liver, and bone marrow, and, at the highest dose, death. Rats similarly exposed had hyperplasia of the nasal cavity and, at the lowest dose tested, methemoglobinemia. 

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