Oxidative Hemoglobin Breakdown Induced by a Rubber Additive

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Abstract
An antioxidant commonly present in black rubber, N-isopropyl N''-phenyl-p-phenylenediamine (IPPD) caused very rapid oxidation and denaturation of purified Hb. In the [human] red cells, the reaction resulted in the formation of Heinz bodies, a decrease in reduced glutathione concentration and stimulation of the hexose monophosphate shunt. IPPD appears to have the potential to induce hemolysis in glucose-6-phosphate dehydrogenase deficiency. It would be expected to be more potent than most redox reagents of this type. It does not require further metabolism to be reactive, and its reactivity is similar to that of phenylhydrazine; however, since both IPPD and its oxidized form can oxidize hemoglobin it can act catalytically, and at low concentrations is much more effective than phenylhydrazine. Oxidation of blood stored in contact with rubber seals containing IPPD has been observed. Prolonged contact of susceptible individuals either with rubber containing IPPD or to IPPD itself during rubber manufacture could perhaps result in hemolysis.