Dermal absorption and metabolism of [14C]-C12 alkyl benzoate in Finsolv TN in human skin in vitro.

Abstract

C12 alkyl benzoate is present in the commercial emollient cosmetic ingredient C12-15 alkyl benzoate (Finsolv TN). Finsolv TN is a mixture of linear and branched esters of benzoic acid and aliphatic alcohols where linear C12 alkyl benzoate is a representative homolog with the shortest alkyl C-chain and lowest molecular weight. A preliminary non-GLP in vitro skin penetration study which monitored dermal bioavailability of all C12-15 alkyl benzoate constituents using GC-MS was carried out which demonstrated C12 alkyl benzoate could be considered a worst-case representative constituent to determine dermal absorption of the overall substance. Subsequently, [14C]-C12 alkyl benzoate was mixed into Finsolv TN, and applied, neat (10 µl/cm2), to dermatomed human skin mounted in a flow-through diffusion cell system. Receptor fluid was collected up to 24 h postdose and the skin was decontaminated at 8 h postdose. The absorbed dose, dermal delivery, potentially absorbable dose and dermally absorbed value of [14C]-C12 alkyl benzoate were 0.41%, 0.97%, 2.20%, and 2.97%, respectively. Metabolism during absorption was assessed in skin from the same donors, with no C12 alkyl benzoate detected in the receptor fluid, although the primary metabolite, [14C]-benzoic acid (>93%), was detected. A phenyl acetate esterase assay confirmed the presence of esterase activity in the donor skins used. Therefore, this study confirmed that dermal exposure of C12-15 alkyl benzoate (Finsolv TN) results in an absorbed dose of 2.97% completely metabolized to benzoic acid and aliphatic alcohol(s) in human skin. These findings indicate that a more in-depth investigation and assessment of toxicokinetic behavior (specifically for occupational exposures via the skin) provide opportunities to develop exposure-led strategies to avoid unnecessary animal testing allowing registrants to fulfill obligations to adhere to the "last resort" principle under REACH.