Methemoglobin formation, effect

Test Species/Strain/Sex/Number Adult male Sprague-Dawley rats, 5/exposure group Exposure Route/Concentrations/Durations 0-150 ppm for 8 h Effects Concentration (ppm) Methemoglobin Formation (%)a... 

Calabrese, E.J., J.A. Garreffi, and E.J. Stanek. 1992. The effects of joint exposures to environmental oxidants on methemoglobin formation copper/nitrate and copper/chlorite. Jour. Environ. Sci. Health 27A 629-642. 

Sun et al. (1995) reported that the nitric oxide generator, isosorbide dinitrate, is an effective cyanide antidote in mice. They showed that the mechanism does not involve methemoglobin formation and suggested that nitric oxide might antagonize the respiratory depressant effects of cyanide. Other more efficient nitric oxide generators may be very useful cyanide antidotes. 

The major effects observed in animals after exposure to 1,3-DNB are methemoglobin formation and testicular damage at doses that are higher than 1 mg/kg. Both effects are common to other nitroaromatic compounds. The biochemical changes that occur in the blood, primarily methemoglobin formation, lead to oxygen deprivation in the tissues, and then to cyanosis and neurotoxicity. 

One of the earliest effects of 1,3-DNB exposure is induction of methemoglobin formation. The level of methemoglobin in the blood can be used as an indicator of exposure to 1,3-DNB. 

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... 

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. 

After the initial therapy of methemoglobin inducers, the cyanide has to be converted to thiocyanate which is eliminated in urine. This enzymatic detoxification of cyanide is facilitated by a sulfur donor like sodium thiosulfate. The mechanism of this reaction was discussed earlier under elimination of cyanide. High tissue oxygen markedly potentiates the effects of this reaction. In cases where methemoglobin formation is not desirable, sodium thiosulfate together with oxygen alone is sufficient. The utility of... 

For example, levels for odor detection in humans, mild sensory irritation, asymptomatic or nonsensory effects, such as methemoglobin formation (22%) and altered pulmonary function (transient changes in clinically insignificant pulmonary functions of a susceptible individual), have been used as AEGL-1 endpoints. 

Ciccoli and coworkers have shown that incubation of rat erythrocytes with hydroxy lated metabolites of aniline, dapsone (39) and the corresponding hydroxylamines brings about enhanced release of iron and methemoglobin formation. This did not occur with parent compounds. That xenobiotics are effective only after biotransformation to metabolites in vivo is supported by acute intoxication of rats with aniline or 39 and marked increase in the erythrocyte content of free iron and of methemoglobin144. The potent toxicity of aniline-derived aminophenylnorharman in the liver of the gpt delta transgenic mouse has been demonstrated145,146. 

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