GLUTARALDEHYDE - SPECIES COMPARISONS OF IN-VITRO SKIN PENETRATION

It has been reported that the major portion of the applied dose was re covered from skin at the application site in previously conducted in v ivo rat and rabbit pharmacokinetic studies with C-14-labeled glutarald ehyde. To investigate this finding further, and to compare penetration of glutaraldehyde through human skin with absorption data for animal skin preparations, the potential for in vitro skin penetration of [1,5 -C-14]glutaraldehyde (Cas #111-30-8) was evaluated with samples of exc ised skin from Fischer 344 rats, CD-1 mice, Hartley guinea pigs, New Z ealand White rabbits, and humans (women undergoing reconstructive mamm oplasty). A flow-through skin penetration chamber design was used and the aqueous glutaraldehyde concentrations of 0.75% and 7.5% used in pr evious in vivo rat and rabbit percutaneous study were applied. The in vitro results indicated that glutaraldehyde did not penetrate human or animal skin to any substantial degree following application of either a 0.75% or a 7.5% aqueous solution. Averages of less than 0.5% of the applied radioactivity for the 0.75% solution and 0.7% of the applied dose for the 7.5% solution were recovered in the effluents for all ani mal species (range of 0.05 [female rat] to 1.55 [female rabbits] for t he 7.5% solution). For human female skin, the recovery was approximate ly 0.2% in effluents for both applied glutaraldehyde concentrations. U nder these in vitro experimental conditions, glutaraldehyde did not pe netrate human breast skin to any of the dose binding to the skin durin g uptake. Thus, these results are consistent with previous reports and suggest that only a minimal amount of glutaraldehyde may be available for systemic uptake and distribution following cutaneous exposure. Ba sed on these findings, it was concluded that the potential for absorpt ion may be less for humans than for common laboratory test species.