Glutaraldehyde: Species Comparisons of in Vitro Skin Penetration

Abstract

It has been reported that the major portion of the applied dose was recovered from skin at the application site in previously conducted in vivo rat and rabbit pharmacokinetic studies with 14C-labeled glutaraldehyde. 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 [1,5-14C]glutaraldehyde (CAS #111-30-8) was evaluated with samples of excised skin from Fischer 344 rats, CD-1 mice, Hartley guinea pigs, New Zealand White rabbits, and humans (women undergoing reconstructive mammoplasty). A flow-through skin penetration chamber design was used and the aqueous glutaraldehyde concentrations of 0.75% and 7.5% used in the previous 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 animal species (range of 0.05 [female rats] to 1.73 [male mouse] for the 0.75% solution and 0.08 [male rat] to 1.55 [female rabbits] for the 7.5% solution). For human female skin, the recovery was approximately 0.2% in effluents for both applied glutaraldehyde concentrations. Under these in vitro experimental conditions, glutaraldehyde did not penetrate human breast skin to any substantial degree, and this was largely due to a substantial portion of the dose binding to the skin during 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. Based on these findings, it was concluded that the potential for absorption may be less for humans than for common laboratory test species.