Uptake of two zwitterionic surfactants into human skin in vivo

To evaluate the potential risk associated with dermal exposure to nitrogen-containing amphiphiles commonly found in household and personal-care products, the uptake of N,N-dimethyl-N-dodecylglycine (dodecylbetaine, C12BET) and N,N-dimethyl-N-hexadecylglycine (hexadecylbetaine, C16BET) into human skin in vivo has been measured. The 14C-radiolabeled chemicals were applied in aqueous solution (C12BET concentrations 16, 100, and 800 mM; C16BET concentrations 0.14, 1.0, and 5.4 mM) to the dorsal upper arms of male volunteers for 30 min. At the end of this exposure period, the remaining applied solution was removed, the skin surface was thoroughly washed, and the stratum corneum at the administration site was removed by repeated tape-stripping. Dermal uptake was assessed (i) by direct measurement of the radioactivity recovered on the tape-strips, and (ii) from a predictive relationship previously derived from other research using a similar protocol. As expected, agreement between the two approaches was reasonable (generally within a factor of 3-4); the predictive relationship attempts to account for penetrant which cannot be recovered by the tape-stripping process, and anticipates, therefore, greater chemical exposure to the body than that expected on the basis of the tape-strip associated material alone. A positive control, using the previously studied penetrant, caffeine, demonstrated that the experimental procedure was conducted appropriately. Absorption of the betaines into human skin was significant (for C12BET, uptake was 28-160 nmol/cm2; that for C16BET was 2.3-19.5 nmol/cm2) and was primarily localized (as was caffeine) in the outer layers of the stratum corneum. In parallel experiments, in which unlabeled betaines were applied for 30 min, instead of tape-stripping, skin barrier function (measured by transepidermal water loss) was assessed. No betaine-induced effects on the stratum corneum were observed (in contrast to the sometimes large perturbations seen in vitro following considerably longer exposure times). Overall, the results indicated that the use of these betaines in personal care products, when intended for limited use and rinse-off application, gives no reason for safety concerns.