Toxicology
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The duration of action of the cyanide antidotes sodium thiosulphate and hydroxocobalamin was investigated in guinea-pigs after prophylactic administration before a long-term infusion of NaCN. The parameter for the diminution of the antidote action was the point of time at which the concentration of HCN in the exhaled air of the animals exceeded 100 nmol/kg per min. The time taken to reach this threshold level in the control animals was 12 min. ⋯ Additionally we found a plasma half-life of sodium thiosulphate in guinea-pigs of 26 min. This value corresponds approximately to the plasma half-life of sodium thiosulphate in humans given in the literature. Because of the large injection volume necessary, sodium thiosulphate is not suitable for prophylactic use in man.
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We have documented visual and auditory neurotoxicity in 42 of 89 patients with transfusion-dependent anemia who were receiving iron chelation therapy with subcutaneous deferoxamine (DFO). Of the affected groups, 13 presented with visual loss or deafness or both, and ophthalmologic, audiologic, and visual evoked potential studies (VEPs) uncovered abnormalities in 29 more. Four patients with visual loss had optic neuropathy with a marked decrease in acuity and loss of color vision. ⋯ Significantly lower doses of DFO were being taken by patients without abnormalities than by those with visual symptoms, abnormal audiograms, or prolonged VEPs (P less than 0.001, less than 0.006, and less than 0.04, respectively). The data implicate high-dose DFO as a central factor in the pathogenesis of the neurotoxicity. Our serial studies provide the basis for effective yet safe DFO administration for patients who require the agent.
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Fire creates a complex toxic environment involving flame, heat, oxygen depletion, smoke, and toxic gases. The nature of that environment is dependent upon not only the materials present but on the fire event, that is, the fire scenario. Materials have different toxic gas profiles under different conditions; therefore, toxic fire gas generation is not intrinsic to any one material. ⋯ All fire parameters are interrelated, that is, they are not independent variables. Thus, predicting the toxicity of burning materials is a problem without a comprehensive solution. Measures have been taken, however, to reduce the number of fires and to reduce fire severity.
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Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese-containing compound which is used as an additive in unleaded gasoline. One neurotoxic effect of MMT in mice is seizure activity. In this study, seizures were observed in mice treated with MMT in propylene glycol or corn oil. ⋯ However, MMT inhibited the binding of t-[3H]t-butylbicycloorthobenzoate [3H]-TBOB (a ligand for the GABA-A-receptor linked chloride channel) in mouse brain membranes with an IC50 value of 22.8 microM. The data suggest that MMT (organic manganese) or a closely related metabolite and not elemental manganese itself is responsible for the seizure activity observed. The seizure activity may be the result of an inhibitory effect of MMT at the GABA-A receptor linked chloride channel.
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This study evaluates a major metabolite of misonidazole, desmethylmisonidazole, for its potential to induce peripheral nerve damage using the lysosomal enzyme correlates of neuropathological change, namely beta-glucuronidase and beta-galactosidase. The results showed that desmethylmisonidazole like misonidazole had a similar potential for inducing peripheral nerve damage as measured biochemically, but the dosing regimen had to be maintained for 10 consecutive days as opposed to the 7 days required for misonidazole.