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Percutaneous penetration and metabolism of 2-ethoxyethanol

Lookup NU author(s): Professor Faith Williams

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Abstract

Percutaneous absorption and cutaneous metabolism of 2-ethoxyethanol were assessed in vivo and with an in vitro flow-through diffusion system. Topical application of undiluted 14C-ethoxyethanol to occluded rat skin in vivo resulted in 25% of the dose being absorbed after 24 h. The major routes of excretion included the urine (15%), expiration as carbon dioxide (6%), and feces (1.2%), while little of the dose remained in the carcass (1.3%). Free ethoxyethanol, ethoxyacetic acid, and glycine conjugate were detected in urine. Permeation rates of ethoxyethanol through unoccluded rat split skin (20%) were greater than rat whole skin (11%), while absorption through human split skin (8%) was lower than the rat. Absorption of undiluted ethoxyethanol through occluded rat split skin in vitro (22%) most accurately predicted absorption through rat skin in vivo. However, ethoxyethanol absorption (29%) was enhanced by application in methanol. First pass metabolism of ethoxyethanol was not detected during percutaneous penetration through viable human or rat skin in vitro or rat skin in vivo. However, rat skin cytosol had the potential to metabolize ethoxyethanol, suggesting that the rapid penetration through skin in vivo prevented metabolism and that systemic exposure after skin contact with 2-ethoxyethanol is likely to be to the parent compound. In conclusion, the in vitro system provided a reasonable estimate of dermal absorption for the rat in vivo and comparison of human and rat skin in vitro indicated 2-ethoxyethanol absorption in humans is about one-third of that in the rat. © 2002 Elsevier Science (USA).


Publication metadata

Author(s): Williams FM; Lockley DJ; Howes D

Publication type: Article

Publication status: Published

Journal: Toxicology and Applied Pharmacology

Year: 2002

Volume: 180

Issue: 2

Pages: 74-82

ISSN (print): 0041-008X

ISSN (electronic):

Publisher: Academic Press

URL: http://dx.doi.org/10.1006/taap.2002.9373

DOI: 10.1006/taap.2002.9373

PubMed id: 11969374


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