In vitro and in vivo assessment of the irritation potential of different spin traps in human skin

No clinical data are available on the acute cutaneous toxicity of spin traps which are frequently used in combination with the electron paramagnetic resonance (EPR) technique for detection of free radicals and reactive oxygen/nitrogen species. The purpose of this study was to evaluate the acute dermatotoxicity of the following spin traps in human skin: C-phenyl-N-tert.-butyl nitrone (PBN, C-(4-pyridinyl-N-oxide)-N-tert.-butylnitrone (POBN), 5,5-dimethyl-1-pyrroline-N-oxide(DMPO), 5 diethoxyphosphoryl-5-methyl-1-pyrroline-N-oxide (DEPMPO), diethyldithiocarbamate (DDC) and N-methyl-D-glucamine dithiocarbamate (MGD). The corrosivity of the test substances was first assessed in human skin in vitro by measurement of transcutaneous electrical resistance (TER). In this assay all spin traps were non-corrosive at 500 mM concentration. Subsequently cutaneous irritation of the spin traps was determined at different concentrations (50, 250 and 500 mM) in human skill according to a routine four h human patch test in comparison to the standardized irritant sodium laurylsulfate (SLS, 20%). The response was evaluated clinically as well as by a biophysical method analyzing transepidermal water loss (TEWL). PEN and DEPMPO caused a transient and weak; inflammatory reaction at 500 mM in four of 17 and in two of 17 volunteers, respectively. DMPO. POBN, DDC, MGID, and the iron complexes of DDC and MGD were clinically non-irritant at all concentrations tested and no delayed-acute inflammatory reactions were observed. However, the TEWL values were significantly increased by all spin traps except DMPO at 500 mM. indicating disturbed epidermal barrier function. We conclude that the spill traps investigated have a low potential to cause acute skin toxicity and may be used safely for in vivo EPR studies in human skin. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.