Methemoglobin

G. L. Coppoc and S. J. Leger, "Effect of Nitrogen Triduoride on Plasma Concentrations of Lactate, Methemoglobin, and Selected Enzymes," ApriWune 1968, SAM-TR-70-42 (AD 711044), School of Aerospace Medicine, Brooks Air Eorce Base, Texas, July 1970. 

Health nd Safety Factors. The mononitrochlorobenzenes are toxic substances which may be absorbed through the skin and lungs giving rise to methemoglobin. Their toxicity is about the same as or greater than that of nitrobenzene. The para isomer is less toxic than the ortho isomer, and the maximum allowable concentration that has been adopted for -nitrochlorobenzene is 1 mg/m (0.1 ppm) (6). The mononitrochlorobenzenes are moderate fire hazards when exposed to heat or flame. They ate classified by the ICC as Class-B poisons. The same handling precautions should be used for these compounds as are used for nitrobenzene. 

Health and Safety Factors. The toxic effects of the mononitrotoluenes are similar to but less pronounced than those described for nitrobenzene. The maximum allowable concentration for the mononitrotoluenes is 2 ppm (11 mg/m ) (6). Mononitrotoluenes are low grade methemoglobin formers (4) and may be absorbed through the skin and respiratory tract. The toxicity of alkyl nitrobenzenes decreases with an increasing... 

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. 

The automated method differs from the ICSH method chiefly in that oxidation and ligation of heme iron occur after the hemes have been released from globin. Therefore, ferricyanide and cyanide need not diffuse into the hemoglobin and methemoglobin, respectively. Because diffusion is rate-limiting in this reaction sequence, the overall reaction time is reduced from approximately three minutes for the manual method to 3 —15 seconds for the automated method. Reaction sequences in the Coulter S + II and the Technicon H 1 and H 2 are similar. Moreover, similar reactions are used in the other Coulter systems and in the TOA and Unipath instmments. 

METHEMOGLOBIN INDUCERS Methemoglobin in blood During or end of shift 1.5% of haemoglobin B, Ns,... 

FIGURE 15.29 The arrangement of snbnnits in horse methemoglobin, the first hemoglobin whose strnctnre was determined by X-ray diffraction. The iron atoms on metHb are in the oxidized, ferric (Fe ) state. (Irving Gets)... 

The oxides of nitrogen are somewhat sol in w, reacting with it in the presence of oxygen to form nitric and nitrous acids. This is the action that takes place deep in the respiratory system. The acids formed are irritants, causing congestion of the throat and bronchi, and edema of the lungs. The acids are neutralized by the alkalies present in the tissues, with the formation of nitrates and nitrites. The latter may cause some arterial dilation, fall in blood press, headache and dizziness, and there may be some formation of methemoglobin. However, the nitrite effect is of secondary importance... 

Other investigations performed with AOS include estimations of haemolytic concentrations [147,148], effect on methemoglobin concentration [156], and in vitro estimation of immunological potential [157]. None of these investigations gave any reason to suspect a toxic hazard of AOS. 

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)... 

The iron of Hb must be maintained in the ferrous state ferric iron is reduced to the ferrous state by the action of an NADH-dependent methemoglobin reductase system involving cytochrome reductase and cytochrome b. ... 

Kanner, J. and Harel, S. (1985). Initiation of membranal lipid peroxidation by activated metmyoglobin and methemoglobin. Arch. Biochem. Biophys. 237, 314-321. 

The purpose of sodium nitrite (or amyl nitrite in the absence of IV access) is to produce methemoglobin, which binds cyanide with greater affinity than mitochondrial cytochromes. In the presence of decreased oxygen carrying capacity, as in combined exposures to cyanide and carbon monoxide (e.g., some fires), sodium nitrite can be detrimental and should be avoided. 

Cooximetry cannot be used to follow initial response, because methylene blue is detected as methemoglobin... 

Duration depends on dapsone half-life ( 20-30 h but prolonged with cimetidine use) and methemoglobin levels... 

Blood transfusions may be indicated with methemoglobin levels >50% and evidence of tissue hypoxia... 

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