The percutaneous absorption of the plasticizer and fragrance chemical diethyl phthalate (DEP) has been evaluated in vitro in flow-through diffusion cells using shaved full-thickness skin from male Fischer 344 rats and human breast skin. Neat DEP (16.3-20.6 mg/cm(2)) was applied to the epidermal surface of the skin, which was then either left uncovered (unoccluded) or covered (occluded) with a teflon cap 2.9 cm above the skin surface. The absorption of DEP through rat skin and into the receptor fluid was relatively extensive reaching 35.9 +/- 2.9% (mean +/- SD, n = 4) of the applied dose over 72 hr when the skin was occluded and 38.4 +/- 2.5% (mean +/- SD, n = 3) when the skin was unoccluded. Absorption of DEP through human skin was significantly less (P < 0.05) than through rat skin reaching 3.9 +/- 1.2% (mean +/- SD, n = 4) of the applied dose over 72 hr when the skin was occluded and 4.8 +/- 0.7% (mean +/- SD, n = 3) when the skin was unoccluded. Occlusion of the skin did not significantly alter the percutaneous absorption of DEP through rat or human skin. There was a four-fold variation in absorption between skin samples taken from human donors, ranging from 1.6 +/- 1.2% (mean +/- SD, n = 3) to 8.7 +/- 3.9% (mean +/- SD, n = 6) at 72 hr. This inter-individual variation was greater than the variation between animals, which ranged from 26.4 +/- 3.3% (mean +/- SD, n = 4) to 38.9 +/- 0.6% (mean +/- SD, n = 5). This information may be of significance for the safety evaluation of DEP for occupational and consumer use. Although human in vivo data are lacking, the percutaneous absorption of DEP through rat skin in vitro compares well with rat in vivo data from the literature, which supports the use of this technique as a model for in vivo absorption.