Dermal permeation of 2-hydroxypropyl acrylate, a model water-miscible compound: Effects of concentration, thermodynamic activity and skin hydration
Graphical abstract
Introduction
2-Hydroxypropyl acrylate (HPA, Table 1) is a monomer that is used primarily in thermosetting resins for surface coatings, adhesives, and textiles. HPA and water are miscible in all proportions at room temperature. Other chemicals with similarly high aqueous solubility display unusual skin permeation behavior. For example, the dermal permeation of 2-butoxyethanol (BE) in aqueous solutions has been a matter of debate based on the observation that steady-state dermal flux (JSS) of BE is a strongly non-linear function of BE concentration (Johanson and Fernstrom, 1988, Traynor et al., 2007). Three distinct regions of behavior have been noted. At low concentrations, JSS increases with increasing BE concentration. At intermediate concentrations, JSS remains relatively constant, while at high concentrations, JSS decreases with BE concentration to such an extent that flux from neat BE is about the same as from a 10 wt.% solution.
Bunge et al. (2012) have summarized these observations on BE and presented a reasonable explanation. They pointed out that the general driving force for permeation is thermodynamic activity, not concentration (Higuchi, 1960). Additionally, the thermodynamically appropriate metric for concentration is mole fraction and not volume fraction or weight fraction, which are typically used. For ideal solutions, thermodynamic activity is a linear function of mole fraction, but not, in general, of volume or weight fraction. Thus, for an ideal solution that does not alter the membrane barrier, JSS is a linear function of the mole fraction of the chemical. BE-water forms a non-ideal solution. Therefore, the thermodynamic activity in aqueous BE solutions must be known in order to make informative observations on BE flux. Bunge et al. (2012) showed that activity-normalized BE fluxes are constant up to a weight fraction of about 0.8. For higher concentrations, a sharp drop in the activity-normalized flux corresponds to a sharp decrease in the thermodynamic activity of water in the solutions. Bunge et al. (2012) reasoned that BE steady-state fluxes can therefore be explained by the effects of BE-water solutions on skin hydration status. While the data support this hypothesis, no direct evidence was provided linking BE exposure and skin hydration.
Human skin permeability measurements for HPA are, to our knowledge, lacking in the peer reviewed literature. Dermal exposure to HPA may occur during its manufacture, transportation and industrial use. Dedicated systems designed to handle HPA during loading and unloading procedures limit the risk of exposure to spills or leaks during transportation (SIDS, 2004). Nevertheless, moderate systemic toxicity of this chemical, which is also known to be a severe skin irritant, warrants the study of its dermal absorption potential. Therefore one goal of the present study was to provide these data for dermal risk assessment purposes.
HPA is not used in aqueous solutions in the industrial setting, but the miscibility of this chemical in water presented an opportunity to investigate its skin permeation in a manner comparable with the well-studied water miscible chemical BE. Steady-state fluxes and lag times of HPA in both heat separated human epidermal membranes and silicone rubber membranes were undertaken over the full range of HPA-H2O concentrations. Thermodynamic activities of HPA and H2O in aqueous solutions of HPA were measured to gain knowledge of the driving force for permeation and to gain insight into the effect of H2O activity on skin permeation. A further set of permeation experiments was designed such that HPA thermodynamic activity could be held constant, while H2O activity was varied from about 0.8 to 1. Finally, water uptake into desiccated human stratum corneum was measured following incubation in aqueous HPA solutions. Results presented here offer incontrovertible evidence that stratum corneum becomes dehydrated with increasing HPA concentrations, and that this dehydration substantially increases the barrier property of the skin to this chemical.
Section snippets
Materials
Fresh full thickness human skin samples from Caucasian female (age range: 32–62 y) nonmalignant mammoplasties were obtained on the day of surgery from the West Virginia University Tissue Bank. Skin was submersed in 60 °C buffer for 60 s. Epidermis was teased from underlying tissue with cotton swabs, floated onto buffer + 10% glycerol, and stored frozen (−85 °C) until use. Medical grade silicone rubber sheeting (thickness: 0.020 in. and 0.040 in.) was purchased from Bioplexus.
Commercial grade HPA (CAS:
HPA permeation
Fig. 1 displays representative HPA absorption curves for HEM (top) and SRM (bottom), from which steady-state fluxes and lag times were derived. For HEM, displayed are the means and SD's for 3 discs taken from one skin donor, for ϕHPA = 0.25 and 1.00. For SRM, the means and SD's for 3 membranes are displayed. The solid lines represent best-fit regression curves to the diffusion equation (Eq. (6)), with resulting JSS's and τ’s. Correlation coefficients (r2) of the regression for all HEM and SRM
Summary and conclusions
The permeability behavior from neat and aqueous HPA solutions through human epidermis and silicone membranes has been described. For SRM, the observed dependence of JSS on HPA concentration is expected based on the non-ideal nature of aqueous HPA solutions: JSS is a linear function of aHPA (Fig. 5). For HEM on the other hand, JSS increases with HPA thermodynamic activity up to aHPA ∼ 0.35 (Fig. 6). As aHPA increases further, JSS decreases. We have provided direct evidence of the effect of
Disclaimer
The findings and conclusions in this report have not been formally disseminated by the National Institute for Occupational Safety and Health (NIOSH) and should not be construed to represent any agency determination or policy.
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