Human skin absorption of bis-2-(chloroethyl)sulphide (sulphur mustard) in vitro

Abstract

The purpose of this study was to measure the absorption and intra-epidermal fate of S-35-radiolabelled sulphur mustard ((SM)-S-35) in human breast skin in vitro. Skin (full-thickness or heat-separated epidermis) was placed into static diffusion cells and was exposed to droplets of liquid (SM)-S-35 or saturated (SM)-S-35 vapour. Amounts of (SM)-S-35 penetrating the skin were measured from which skin absorption rates were calculated. Unbound radiolabel was washed from the surface, extracted from the skin and analysed to determine the identity of the radiolabelled species in order to measure the extent of hydrolysis of sulphur mustard. Penetration rates of liquid (SM)-S-35 measured in vitro (71-294 mug cm(-2) h(-1)) were in agreement with those measured previously in vivo using human volunteers (60-240 mug cm(-2) h(-1)), Rates of liquid (SM)-S-35 Skin absorption under occluded, infinite dose conditions were highest through heat-separated epidermal membranes (294 +/- 58 mug cm(-2) h(-1)) and lowest through full-thickness skin (71 +/- 14 mug cm(-2) h(-1)). Fluxes of saturated (SM)-S-35 vapour (110 +/- 75 mug cm(-2) h(-1)) through heat-separated membranes were similar to those previously measured through human forearm skin in vivo (162 mug cm(-2) h(-1)), Although hydrolysis of 35SM did occur, both on the surface and within the skin, it accounted for only a small percentage of the total applied dose (<2.7 +/- 1.2%). The difference in total amount of liquid 35SM penetrated between occluded and unoccluded conditions in. vitro (79 +/- 14%) was similar to that lost as vapour from unoccluded skin in vivo (80%), A substantial reservoir of (SM)-S-35 (14-36% of the applied dose) was measured within heat-separated epidermal membranes for up to 24h which may have significant implications for the management of personnel exposed to sulphur mustard. (C) Crown copyright 2000. Reproduced with the permission of Her Majesty's Stationery Office. Published by John Wiley & Sons.