Follicular pathway role in chemical warfare simulants percutaneous penetration

Chemical warfare (CW) exposure could be fatal to military and civilians through skin contamination. Our work and others focus on investigating stratum corneum reservoir with less regards to skin appendageal routes including hair follicles. Here, C-14 CW simulants (CWS) with specific activity of 0.1 mCi/ml were tested on abdominal and scalp human cadaver skin using flow-through diffusion system. Quantitative analysis of simulants in skin compartments were performed using scintillation counter. Scalp permeation of dipropylene glycol monomethyl ether (DPGME), diisopropyl methylphosphonate (DIMP) and methyl salicylate (MeS) exceed abdominal skin by 8%, 15%, and 6% (p value < 0.05) of applied dose, respectively. DPGME and DIMP (most hydrophilic) showed earlier permeation peak time (Tmax) through scalp skin at 2 and 4 h, respectively, comparing with 6 h with abdominal skin. The percentage of applied dose of DPGME and DIMP retained in human skin membrane (SC, epidermis, and viable dermis) showed no statistically significant difference between tested abdominal and scalp skin samples (p value >0.05). The percentage of applied dose of MeS in scalp showed higher partitioning in stratum corneum and viable epidermis than abdominal skin (p value <0.05). In conclusion, human scalp showed greater total skin absorption than abdominal skin. This work points to a qualitative importance of high follicular density body regions in percutaneous penetration and suggests that transfollicular pathway might have a significant role in early stage permeation of chemical warfare simulants. However, the difference noticed here between scalp and abdominal skin could be attributed to regional variability in anatomy, physiology, and barrier characteristics.