Dermal penetration of ethylene glycol through human skin in vitro.
This study was conducted to determine the in vitro dermal absorption of ethylene glycol (EG) through dermatomed human abdominal skin (containing epidermis and dermis), obtained from cadavers within 24 hours of death and kept frozen until processed. Three formulations of EG (neat, 50%, and 10% aqueous solutions) were applied in triplicate to skin samples from 6 donors, and placed in Teflon Bronaugh flow-through diffusion cells. Barrier integrity of each sample was evaluated with (3)H-H(2)O prior to applying EG and only data from samples passing the test were used. A physiological receptor fluid was pumped beneath the skin samples and collected in a fraction collector at predetermined time points through 24 hours. Possible volatilized EG was trapped in a charcoal basket located above each skin sample. Each skin sample was treated with an infinite dose of 500 microL of EG formulation/cm(2). At the end of 24 hours, volatilized EG trapped in the headspace was collected, the unabsorbed dose was removed from the skin and the skin was rinsed, tape stripped, and solubilized along with a rinse of the flow-through cells, and total radioactivity was determined. Only a small fraction (</=1%) of the applied EG was absorbed in 24 hours, of which <0.7% penetrated through the skin and ~0.4% remained in the skin. Recovery (mass balance) of the applied EG was between 93% and 99%, which further validated the observed low dermal penetration of EG. The net penetration of the applied EG over 24 hours was concentration proportional, comprising 2.97 +/- 0.78, 1.75 +/- 0.62, and 0.23 +/- 0.12 mg/cm(2) of the neat, 50%, and 10% formulations, respectively. The steady-state flux of EG was established between 16 and 24 hours. The mean steady-state flux of EG through dermatomed skin was 217, 129, and 15 microg/cm(2)h for the neat, 50%, and 10% aqueous formulations, respectively, consistent with concentration-proportional penetration of EG. The steady-state permeation coefficient (Kp) for EG was low, between 1.5 x 10(-4) and 2.6 x 10(-4) cm/h. These findings demonstrate that EG dermal penetration is expected to be very low and to be slow, indicating very limited systemic or internal dose of EG due to dermal exposure.
Saghir
Shakil A
SA
Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI 48674, USA. ssaghir@dow.com
Bartels
Michael J
MJ
Snellings
William M
WM
D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000388:Air / Q000032:analysis; D000465:Algorithms; D002626:Chemistry, Pharmaceutical; D019855:Ethylene Glycol / Q000032:analysis / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000737:chemistry; D012869:Skin Absorption; D012997:Solvents / Q000032:analysis / Q000493:pharmacokinetics*
D012997:Solvents; D019855:Ethylene Glycol