[A case of occupational contact dermatitis due to hydroxylamine].

A 36-year-old man, working in a chemical industry, had a generalized pruritic eruption. A forty-eight hour patch test revealed positivity for 1% hydroxylamine. Prevention of exposure to this chemical resulted in a dramatic improvement of the symptoms. Based on these findings, we diagnosed this case as occupational contact dermatitis due to hydroxylamine. There has been few case reports of contact dermatitis due to hydroxylamine. Histopathological examination revealed a marked spongiosis and a spongiotic bulla formation in the epidermis and follicular infundibulum, suggesting an allergic reaction.

Comparison of the in vitro cytotoxicity of hydroxylamine metabolites of sulfamethoxazole and dapsone.

The differential incidence of adverse drug reactions (ADR) between trimethoprim-sulfamethoxazole and dapsone might be explained, in part, by differences in the inherent toxicity of the hydroxylamine metabolites of sulfamethoxazole and dapsone. To test this hypothesis, the in vitro cytotoxicities of sulfamethoxazole hydroxylamine, dapsone hydroxylamine, and monoacetyldapsone hydroxylamine were compared using peripheral blood mononuclear cells (PBMC) from healthy volunteers. After 3 hr of exposure to hydroxylamine metabolites, PBMC were washed thoroughly to remove residual hydroxylamine, and viability was assessed 16 hr later by determination of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) conversion. A concentration-dependent toxicity was observed with each hydroxylamine metabolite. While dapsone hydroxylamine and monoacetyldapsone hydroxylamine were not significantly different, both showed significantly greater cytotoxic potency than sulfamethoxazole hydroxylamine (P < 0.05). This differential potency was not a function of differential stability in aqueous medium and was maintained over time. The effects of red blood cells (RBC), impermeable RBC "ghosts," and RBC lysate on hydroxylamine-induced cytotoxicity were determined using a two-compartment dialysis system. Amelioration of hydroxylamine-dependent cytotoxicity occurred when RBC were included in PBMC incubations. This apparent detoxifying effect was markedly greater using RBC lysate in comparison with impermeable "ghosts" (P < 0.05). No difference in detoxification was observed between sulfamethoxazole hydroxylamine and monoacetyldapsone hydroxylamine. Differences in the inherent cytotoxicity of their hydroxylamine metabolites do not appear to explain the differential incidence of ADR between trimethoprim-sulfamethoxazole and dapsone.

Hydroxylamine treatment increases glutathione-protein and protein-protein binding in human erythrocytes.

Hydroxylamine is a direct-acting hematotoxic agent leading to hemolytic anemia in animals and man. The effect of hydroxylamine on the morphology, sulfhydryl status and membrane skeletal proteins of human erythrocytes were studied. Loss of reduced glutathione (GSH) from the red blood cells was directly proportional to the hydroxylamine concentration used. This loss of GSH was larger than the sum of the increase in the amounts of extracellular glutathione and intracellular oxidized glutathione (GSSG). The extracellular glutathione is mainly present as GSSG, which is in agreement with the fact that only GSSG is exported from the erythrocytes by membrane bound ATPases. Lack of GSSG export was not limited by decreased ATP levels in the erythrocytes and we concluded that the GSH that disappeared did not become available as intracellular GSSG. After reduction of the erythrocyte incubates the lost GSH was almost completely recovered indicating that the lost GSH is present in the cell as protein-glutathione mixed disulfides. Glutathione thus stored within the cell can be quickly recovered by combined thioltransferase and glutathione reductase activity when conditions become more favorable again. SDS-polyacrylamide gel electrophoresis of membrane ghosts from human red cells revealed changes in skeletal proteins with a smearing of bands 1, 2 and 3 to the higher molecular weight end of the gel and the appearance of new monomeric and dimeric hemoglobin bands at about 16 and 30 kD. The observed alterations are probably a consequence of disulfide bridge formation between cellular proteins (mainly hemoglobin) and skeletal proteins as well as between hemoglobin monomers. Exposure of hydroxylamine to erythrocytes caused severe Heinz body formation but the outside morphology of the cells was only marginally altered. The described changes in sulfhydryl status of the red blood cells are likely to play a major role in the premature splenic sequestration of hydroxylamine-damaged erythrocytes.