Baynes, R.E., G. L. Qiao, J.D. Brooks, N.A. Monteiro-Riviere and J.E. Riviere. Percutaneous Absorption and Toxicity of the Benzidine Dye Direct Red 28 in a Mechanistically Defined Chemical Mixture Using Isolated Perfused Porcine Skin Flap. The Toxicologist 1995. 15:325.

sodium lauryl sulfate - 00151-21-3; methyl nicotinate - 00093-60-7; stannous chloride - 10025-69-1

Humans are more likely to be exposed to chemical mixtures than to a single chemical at hazardous waste sites. Mechanistically defined chemicals (MDCM) can potentially consist of a marker chemical and 1 to 4 other chemicals, each of which can have different mechanistic actions on dermal penetration and absorption of the marker chemical. Sixteen mixtures, consisting of a marker chemical (direct red 28, DR28), and solvent (acetone or dimethyl sulfoxide, DMSO), a surfactant (0 or 10% sodium lauryl sulfate, SLS), a vasodilator (0 or 180 ug methyl nicotinate, MNA), and a reducing agent (0 or 2% stannous chloride, SnCl₂) were selected. Isolated perfused porcine skin flaps (IPPSF) were utilized. For each of the 16 skin flaps, 50 ug/cm² DR28 was topically applied. Perfusate samples were collected for 8 hrs and skin biopsies were obtained for histology. Preliminary data suggest that little or no DR28 or its carcinogenic benzidine metabolites were absorbed. Light microscopic evaluations depicted minor alterations (inter- and/or intracytoplasmic edema) with DR28 mixtures containing SLS and/or DMSO. Use of an MDCM experimental design will identify if additive, synergistic, or inhibitory interaction occur.