Experimental exposure of rat skin to methyl bromide: a toxicokinetic and histopathological study

Methyl bromide was experimentally exposed to a 12 cm2 area of the back skin of Wistar rats for 30 s, and for 1, 3, and 5 min, and time courses of both changes in plasma bromide concentration and of histopathological changes were examined. To measure bromide ion, a head space gas chromatography was used. The concentration of plasma bromide ion showed a sharp increase immediately after the exposure in all exposed groups, reaching a peak level after 1 h, then decreased rapidly. The ion level gradually decreased after 72 h to 1 week, and returned to a normal level after 4 to 8 weeks. Calculating from a regressive curve, the biological half lives of plasma bromide ion were 5.0 days to 6.5 days. Histopathologically, the impairments to the epidermal cells, fibroblasts and blood vessels were observed in the early phase. These cellular changes could be due to the direct cytotoxicity of the compound. In the next phase, newly infiltrating cells showed degeneration and necrosis. Subsequently, an impairment of the collagen bundles was observed. Our experiments suggested an immediate permeation and rapid metabolization of methyl bromide in the skin and a multistep formation of the skin damage induced by the compound. These processes of methyl bromide-induced skin damage are quite different from chemical skin injuries caused by the representative causative agents such as alkaline and acid.