BIOLOGICAL FATE OF SULFUR MUSTARD (1,1'-THIOBIS(2-CHLOROETHANE)) - UPTAKE, DISTRIBUTION AND RETENTION OF S-35 IN SKIN AND IN BLOOD AFTER CUTANEOUS APPLICATION OF S-35 SULFUR MUSTARD IN RAT AND COMPARISON WITH HUMAN BLOOD INVITRO

1. During the 6-h occluded cutaneous application of S-35-sulphur mustard vapour to rat, most of the dose, approximately 75%, passed through the skin and was systemically-distributed. Up to 25% of the S-35 was retained in the skin, up to 30% was excreted in the urine and 5-8% was present in the blood, by the end of the application. 2. S-35 initially declined rapidly in skin and then more slowly with a half-life of approximately 7.4 days. Some of the early loss was as sulphur mustard vapour from a possible depot of this compound which was larger with increase in dose. There was some apparent continuing uptake from such a depot into the systemic circulation. 3. The decline of S-35 in blood was much slower than that from skin. About one-fifth of the original post-exposure level in the blood still present 6 weeks later. 4. The S-35 in blood was mainly in the red cell contents as reaction products of haemoglobin with sulphur mustard. Its persistence in the systemic circulation, after an initial rapid decline due to its removal from the plasma, reflected the 65 day life span of these cells. Significant levels of S-35 were found in the plasma only for a few days (t1/2 = 2.4 days). 5. Uptake and subsequent distribution of S-35 in rat and human blood in vitro during gradual exposure to S-35-sulphur mustard using a novel method were similar. S-35 in the red cells was associated mainly with the haemoglobin protein, but slightly greater binding with human, rather than with rat, plasma components was indicated.