Understanding the kinetics of biophysical processes that yield potentially

The skin appendages, and in particular the hair follicle, constitute transport pathways through which chemicals may access the network of blood vessels surrounding the appendages as well as penetrate to the viable tissues bypassing the SC (Fig. 1). The follicular pathway is a potential route for lipophilic chemicals able to easily partition into the sebum-filled infundibulum [70], [71] and [72]. From there, toxicant LY2109761 might cross the relatively permeable boundary of the hair follicle [73] and/or penetrate into the deeper hair follicle. A study comparing blood flow, skin temperature and redness on the forehead, the forearm and the calf of volunteers found the highest baseline levels on the forehead [74]. Application of the vasodilator benzyl nicotinate to each site yielded an increase in each parameter, with the fastest increase, but also the fastest decrease, on the forehead. This study illustrates the potential impact of hair follicles (vellus hairs on the forehead) to both permeation and systemic uptake. The efficacy of follicular transport to the systemic circulation also likely depends on the hair follicle cycle [70] and whether follicular protein transporters [75] would affect transport into the deep follicle. The hair follicle, the hair shaft cuticle and the sebaceous gland are potential reservoir sites [13], [76] and [77].