Percutaneous penetration and metabolism of 2-butoxyethanol

Abstract

2-Butoxyethanol (2-BE) is widely used as an industrial solvent, which may result in human dermal exposure within the workplace. This study compares in vivo and in vitro skin absorption of 2-BE using similar application regimes and determines the potential of skin to metabolise this chemical prior to entering the systemic blood circulation. Following topical application of undiluted [1-14C] 2-BE to occluded rat skin in vivo, 28% of the dose was absorbed after 24 h. The major routes of excretion included the urine (19%), expiration as carbon dioxide (6%) and faeces (0.4%) whilst little of the dose remained in the carcass (1.3%). Free 2-BE (0.5%), butoxyacetic acid (8%), glucuronide conjugate (3%), sulphate conjugates (0.7%) and ethylene glycol (0.6%) were detected in urine. Permeation rates of 2-BE through unoccluded rat dermatomed skin (16%) were greater than rat whole skin (8%) whilst absorption through human dermatomed skin (4%) was lower than the rat. Absorption of undiluted 2-BE through occluded rat dermatomed skin in vitro (18%) most accurately predicted absorption through rat skin in vivo. However, 2-BE absorption (23%) was enhanced by application in methanol. Distribution analysis and microautoradiography demonstrated the lack of 2-BE accumulation within the skin in vitro or in vivo. This was reflected in the absence of first pass metabolism of 2-BE during percutaneous penetration through viable human or rat skin in vitro or rat skin in vivo, despite rat skin cytosol having the potential to metabolise 2-BE. In conclusion, the in vitro system provided a reasonable estimate of dermal absorption in vivo for the rat. Therefore, by extrapolation of the comparative in vitro data for human and rat skin in vitro, dermal absorption of 2-BE in man was about one-fifth of that in the rat. However, the rapid penetration through skin in vitro prevented local metabolism and systemic exposure after skin contact with 2-BE in vivo was likely to be to the parent compound. Thus, in vitro skin systems can be used to model dermal absorption of volatile glycol ethers, to predict how much compound enters the circulation and allows the toxicologist to evaluate the body burden of a chemical and potential systemic toxicity.

The influence of water mixtures on the dermal absorption of glycol ethers

“…Jakasa et al 2004 also investigated the absorption of aqueous solutions of glycol ethers in man compared to studies with human skin in vitro. The ability of in vitro studies to predict in vivo absorption of neat butoxyethanol and ethoxyethanol and butoxyethanol or ethoxyethanol in methanol in the rat has been demonstrated (Lockley et al 2002(Lockley et al , 2004. The aim of this study is to use in vitro methods to determine factors that influence the absorption of ethoxyethanol and butoxyethanol water mixtures through human and rat skin compared to a polydimethylsiloxane membrane.…”

Effect of Skin Metabolism on Dermal Delivery of Testosterone: Qualitative Assessment using a New Short-Term Skin Model

“…These enzymes are able to metabolize xenobiotics which are in contact with skin [4]. These metabolic processes can play an important role in the fate of topically applied substances and therefore modulate their systemic bioavailability [5,6]. The ability of the skin to activate or detoxify xenobiotics has been extensively demonstrated in in vitro studies [7].…”

Influence of Human Skin Specimens Consisting of Different Skin Layers on the Result of in vitro Permeation Experiments

“…The employment of FTS results in an unacceptably long lag time which is easily explained by the thickness of the barrier. As a consequence, degradation of the barrier or drug molecules may influence the diffusion process [26] . Preservation of the system could also result in different absorption rates and hence should be avoided [27] .…”