Comparative haemolytic activity of bis(phenylmethyl) disulphide, bis(phenylethyl) disulphide and bis(phenylpropyl)...

Thiols and disulphides make an important contribution to the organoleptic characteristics of foodstuffs, and many such compounds are approved for use as food flavours. Some thiols and disulphides are haemolytic agents in vivo. The haemolysis is caused by oxidative damage to erythrocytes initiated by "active oxygen" species formed during redox cycling between the thiol and disulphide. In all cases so far examined, the haemolytic activity of a thiol or disulphide in vivo is correlated with its ability to cause oxidative damage to red cells in vitro. In the present study, the in vitro and in vivo effects of three aryl-alkyl disulphides have been compared. Bis(phenylmethyl) and bis(phenylpropyl) disulphide induced no oxidative damage in vitro, and, as expected, caused no haemolysis in rats. In contrast, bis(phenylethyl) disulphide, while causing little or no oxidative damage in vitro, was a potent haemolytic agent in vivo. It is suggested that this effect is due to dehydrogenation of the ethyl disulphide to the ethenyl derivative in vivo. Bis(phenylethenyl) disulphide was found to cause extensive oxidative damage to red cells in vitro and severe haemolytic anaemia in rats. The results of this study show that the in vivo toxicity of thiols and disulphides cannot always be predicted on the basis of their effects in vitro.