Effects of Chronic Alcohol Consumption on Dermal Penetration of Pesticides in Rats

Abstract

Topically applied ethanol is a well-known dermal penetration enhancer. The purpose of this work was to determine if ethanol consumption might also increase transdermal penetration. Male rats were fed either an ethanol containing or control diet for 6-8 wk. After the feeding regime was completed, skin was removed and placed in an in vitro diffusion system. The transdermal absorption of four very commonly used herbicides was determined. Penetration through skin from ethanol-fed rats was enhanced when compared to control by a factor of 5.3 for paraquat, 2.4 for atrazine, and 2.2 for 2,4-dichlorophenoxyacetic acid (2,4-D), and reduced by a factor 0.6 for trifluralin. Comparison of physical factors of the herbicides to the penetration enhancement revealed an inverse linear correlation with lipophilicity, as defined by log octanol/water partition coefficient (log Kow) with r2 =.98. These changes were at least partially reversible after 1 wk of abstinence from ethanol. These experiments demonstrate that regular ethanol consumption can alter the properties of the dermal barrier, leading to increased absorption of some chemicals through rat skin. If ethanol consumption has the same effect on human skin it could potentially have adverse health effects on people regularly exposed to agricultural, environmental, and industrial chemicals.

Alcohol and inflammation and immune responses: summary of the 2006 Alcohol and Immunology Research Interest Group (AIRIG) meeting

“…Rhonda Brand, Evanston Northwestern Hospital, summarized her research testing the effect of ethanol consumption on the barrier function of the skin. Rats were provided ethanol either acutely by gavage (Brand et al, 2006) or chronically (up to 12 weeks) using a liquid diet (Brand et al, 2004) and subsequently tested for transdermal penetration of xenobiotics. Both chronic and acute exposure to alcohol resulted in increased penetration of chemicals such as paraquat, N,N-diethyl-m-toluamide (DEET), dimethyl formamide and 2,4-Dichlorophenoxyacetic acid (2,4-D).…”

Mechanisms by which chronic ethanol consumption impairs cutaneous immunity

“…The similar S. aureus-induced injuries in EtOH-fed and control GPX-1 -/mice suggests that oxidative stress in the skin may primarily occur as a result of EtOH metabolism. This result is consistent with the prior studies showing ADH activity and major indicia of ROS damage (i.e., lipid peroxidation and barrier permeability) in EtOHexposed skin (208,289). It will be important to verify the presence of cutaneous ROS in our experimental system; flow cytometric efforts toward this end have been hampered by the strong ROS signals generated during tissue dissociation and incubation with ROS detection reagents.…”

“…Given that ROS and TNFα can positively reinforce their own production, the EtOH-induced elevation in these factors would be expected to increase cellular vulnerability to a highly cytotoxic alcoholics are predisposed to skin disorders that correlate strongly with elevated ROS levels (67,208). In addition, impaired barrier function in the skin of EtOH-fed rodents corresponds with increased ADH activity as well as key molecular footprints of altered redox homeostasis (i.e., increased cutaneous lipid peroxidation) (208,288,289).…”

“…Given that appropriate synthesis and retention of lipids is needed to maintain stratum corneum integrity, it is perhaps unsurprising that the EtOH-induced increase in lipid peroxidation corresponded with a breakdown in the barrier function of the skin. Increases in both trans-epidermal water loss and transdermal absorption of topically applied xenobiotics demonstrate the capacity of chronic EtOH to undermine cutaneous barrier integrity(288,289). When the results fromFigures 24 and 25 are viewed alongside reports from the literature, it appears that while cutaneous oxidative stress is a consequence of chronic EtOH consumption, damaging ROS may arise from pathways mediating EtOH metabolism and not TNFα stimulation (208).…”

Percutaneous absorption of volatile solvents following transient liquid exposures II. Ethanol

“…In this respect its synergistic behavior with water as an enhancer system for transdermal nitroglycerin has been particularly well studied (Berner et al, 1989a,b). In rats even an oral dose of ethanol can increase skin permeability to toxic chemicals (Brand et al, 2004(Brand et al, , 2006. Its "inside-out" kinetics has recently been modeled (Anderson and Hlastala, 2006) in an attempt to understand the operation of new devices that measure the concentration of blood alcohol transdermally.…”