In vitro and In vivo percutaneous absorption of 14C-octamethylcyclotetrasiloxane (14C-D4) and 14C-decamethylcyclopentasiloxane (14C-D5)

Abstract Octamethylcyclotetrasiloxane (D 4 ) and decamethylcyclopentasiloxane (D 5 ) are cyclic siloxanes used as chemical intermediates with some applications in consumer products. The in vitro percutaneous absorption of 14 C-D 4 and 14 C-D 5 was studied in flow-through diffusion cells. Single doses were applied neat and in antiperspirant formulations to dermatomed human skin for 24 h. The majority of applied D 4 and D 5 (∼90%) volatilized before being absorbed. Only 0.5% of applied D 4 was absorbed while the absorption of D 5 (0.04%) was one order of magnitude lower. The largest percentage (>90%) of the absorbed D 4 and D 5 was found in the skin. The fate of D 4 and D 5 absorbed in the skin was studied in rat in vivo . A single dose of 14 C-D 4 (10, 4.8 and 2 mg/cm 2 ) and 14 C-D 5 (10 mg/cm 2 ) was topically applied inside a dosing chamber attached to the dorsal area. Rats were housed in metabolism cages up to 24 h to enable collection of urine, feces, expired/escaped volatiles. The majority of applied D 4 or D 5 had volatilized from the skin surface. Less than 1.0% of the applied D 4 and only 0.2% of applied D 5 was absorbed with approximately 60% of absorbed D 4 and 30% of absorbed D 5 reaching systemic compartments. The amount absorbed into the skin decreased with time showing that residual D 4 and D 5 diffused back to the skin surface and continued to evaporate. Overall, a low tendency to pass through the skin into systemic compartments was demonstrated for both D 4 (⩽0.5% of applied dose) and D 5 (