title: Percutaneous absorption of 4,4'-methylene-bis(2-chloroaniline) and 4,4'-methylenedianiline through rat and human skin in vitro.
abstract: The percutaneous absorption of 4'4'-methylene-bis(2-chloroaniline) (MbOCA) and 4,4'-methylenedianiline (MDA) has been investigated after topical application to full-thickness skin from male Fischer 344 rats and humans in flow-through diffusion cells, on four separate occasions. After application of MbOCA (13.4-62.5 mug/cm(2) in ethanol) to unoccluded skin, the extent of absorption into the receptor fluid at 72 hr was poor, reaching 1.3 +/- 0.6% and 2.4 +/- 1.4% (mean +/- SD, n = 10-12) of the applied dose, for rat and human skin, respectively. When the skin was occluded with a teflon cap, the absorption of MbOCA at 72 hr was not statistically significantly different through rat or human skin. After application of MDA (17.7-40.6 mug/cm(2) in ethanol) to unoccluded skin, the absorption into the receptor fluid at 72 hr was more extensive than for MbOCA, reaching 6.1 +/- 2.0% and 13.0 +/- 4.3% (mean +/- SD, n = 10-12) of the applied dose for rat and human skin, respectively. When the skin was occluded, the absorption of MDA at 72 hr was significantly enhanced (P<0.05), reaching 13.3 +/- 4.0% and 32.9 +/- 9.0% (mean +/- SD, n = 14-16), for rat and human skin, respectively. At the end of each experiment, considerable residual material remained within the skin for MbOCA (about 31-66%) and MDA (about 23-58%). The total recovery of radioactivity for all experiments was generally >/=90%. These data indicate that significant amounts of MbOCA and MDA are absorbed into rat and human skin in vitro although diffusion through the tissue into the receptor fluid is relatively low. If these in vitro observations are representative of events occurring under conditions of human exposure in vivo, they may have implications for the risk assessment of the chemicals for occupational use.
authors: Department of Pharmacology and Toxicology, St Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London W2 1PG, UK.
authors: S A
authors: SA
authors: Hotchkiss
authors: P
authors: P
authors: Hewitt
authors: J
authors: J
authors: Caldwell