Effects of organic solvent vehicles on the viability and morphology of isolated perfused porcine skin

Abstract

Although many organic solvents are known tio be cutaneous irritants, they are commonly utilized as vehicles in percutaneous absorption and toxicity studies. The isolated perfused porcine skin flap (IPPSF) is an alternative animal model that has been used to study percutaneous absoprtion and cutaneous toxicity. The purpose of this study was to evaluate the effect of five organic solvents (ethanol, acetone, dimethyl sulfoxide (DMSO), toluene, and cyclohexane) on biochemical viability parameters, vascular response, and epidermal morphology of the OPPSF. Cumulative glucose utilization (CGU), the ratio of lactate production/glucose utilization (L/CGU ratio),a nd the leakage of lactate dehydrogenase (LDH) were used as biochemical indicators of alterations in glucose metabolism and flap viability. Only ethanol resulted in a statistically sigficantly decrease in the average rate of CGU over the perfusion. All of the solvent treatments resulted in slight in LDH release versus the control. Vascular resistance (VR) was measured to examine the response of the cutaneous vasculature to these solvents,a nd most treatments resulted in a decreased VR in the terminal phases of perfusion. Ethanol was the only solvent to cause an apparent increase in terminal VR. Light micriscopy demonstrated a modelrate increase in intracellular edema in the DMSO, toluene, and acetone flaps. Ultrastructural evaluation showed focal bledding of the nuclear envelope amd vesiculation of the rough endoplasmic reticulum in cells of the stratum basale and styratum spinosum layers with DMSO treatment. The IPPSF allowed the evaluation of subtle biochemical, vascular, and morphological changes associated with non-occlusive topical exposure to these organic solvents. These findings support the necessity of documenting vehicle efefcts which might mask or other wise alter subtle,but potentially important, compound-specific responses.