In Vitro Skin Penetration of Ethylene Glycol Using Excised Skin from Mice and Humans

Abstract

AbstractEthylene glycol (EG; CAS No. 107-21-1) has a wide variety of industrial uses, but its most common consumer use is as an antifreeze and a deicing fluid. Therefore, skin contact is considered the most common exposure route for people. Because of this, EG was evaluated for its skin penetration characteristics using an established in vitro technique. Full-thickness skin preparations from female CD-I mice and female human abdominal skin were used. Skin preparations were placed in a dynamic, flow-through design skin penetration apparatus. [14C]EG was applied undiluted or as a 50% (w/w) aqueous solution (antifreeze use concentration) at a target dosage of 22–28 mg EG/cm2 of skin surface in an "infinite dose" manner. The time course of 14C penetration was measured for 6 h. The lag times before steady-state rates of penetration were attained were three times longer for human skin (∼3 h) than that for mouse skin (∼ 1 h). For mouse skin, the steady-state rate of penetration for undiluted EG (0.52 mg/cm2/h) was approximately twice that of the 50% aqueous EG solution (0.22 mg/cm2/h), while the permeability constants (kp) were about the same (∼4.5 × 10−4 cm/h). For human skin, the steady-state rate of penetration for undiluted EG (0.013 mg/cm2/h) was again approximately twice that of the 50% aqueous EG solution (0.007 mg/cm2/h), while the permeability constants (kp) were again approximately the same (∼0.1 × 10 4 cm/h). Therefore, the total absorbed dose of EG would be half for cutaneous exposure to 50% water solutions of EG than for similar cutaneous exposure to un-diluated EG for both mice and humans. When these results are compared between species, the steady-state rates of penetration and kp values of both the undiluted EG and the 50% aqueous solution of EG were 30–40 times less for human skin than those for mouse skin. In previous studies, EG has been shown to cause maternal and developmental toxicity after repeated oral and, to a lesser extent, repeated inhalation exposures, but not after repeated dermal applications. Therefore, because the permeability of EG through human skin is significantly less than that through mouse skin, it is highly unlikely that EG would be toxic to humans if exposure was by the dermal route.