Comparison of toxicity of selected mustard agents by percutaneous and subcutaneous routes

Comparative toxicity of nitrogen mustards (HN-1, HN-2 and HN-3) and sulphur mustard was carried out in mice. Based on LD50, the toxicity pattern was HN-2 < HN-1 < HN-3 < sulphur mustard by percutaneous route whereas, by subcutaneous route the toxicity pattern was sulphur mustard < HN-3 < HN-2 < HN-1. Single dose of 1 LD50 of nitrogen mustards and sulphur mustard was administered percutaneously and various oxidative stress parameters were also evaluated. The weight loss was more in HN-2 on day 3 and in sulphur mustard on day 7. There was a drastic fall of WBC count on day 3 in all groups with a recovery in nitrogen mustard groups on day 7. The RBC count and haemoglobin content showed a significant increase on day 7 in sulphur mustard group. The plasma enzymes (ALT, AST and ALP) showed an increase in all groups on day 3 and day 7. The hepatic GSH and GSSG contents were reduced and MDA content increased in all groups, with a further change in sulphur mustard on 7 day. Extensive DNA fragmentation was observed in all the nitrogen mustard groups compared to sulphur mustard group, on day 3. However, on the day 7 the DNA fragmentation was same in all groups. This study showed that the nitrogen mustards and sulphur mustard were extremely toxic by percutaneous route and caused oxidative stress. Sulphur mustard was more toxic by the percutaneous route and the effects were delayed and progressive.