The systemic exposure to the polycyclic musks, AHTN and HHCB, under conditions of use as fragrance ingredients: evidence of lack of complete absorption from a skin reservoir

Abstract 7-Acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (AHTN) and 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-γ-2-benzopyran (HHCB) are two large volume fragrance ingredients widely used in consumer products. As part of the risk evaluation, the systemic exposures to these materials was determined in rats under occlusion and in humans under simulated conditions of exposure. Ring 14 C-labeled AHTN or HHCB were applied dermally in alcoholic solutions to rats at doses of 4.5 mg/kg and occluded for 6 h. Urine, feces and air were collected for up to 120 h and analyzed for radioactivity. Pairs of rats were sacrificed periodically for analysis of tissues and organs. The total amount absorbed was approximately 19% for AHTN and 14% for HHCB. In both cases, significant amounts diffused into the skin, most of which was further absorbed but a significant amount of which was lost to surface dressing by reverse diffusion and/or desquamation. Ring 14 C-labeled AHTN or HHCB were applied in alcoholic solutions without occlusion to three male volunteers at concentrations approximating that which might be encountered in a typical cologne type product. After a 6-h period, all material was removed from the surface of the skin. Blood, feces and urine were collected over a 5-day period. For both materials, levels in blood and plasma were below limits of detection at all times. Based on excretion, primarily in the urine, the total absorbed dose was approximately 1 and 0.1% for AHTN and HHCB, respectively. However, over the 5-day period, 14.5% of AHTN and 19.5% of HHCB was recovered from the skin in dressings over the site of application indicating that a ‘reservoir’ had formed in the skin but the material in the reservoir was lost, by desquamation and/or by reverse absorption, and not available systemically. A mean of 24% (AHTN) and 22% (HHCB) was shown to evaporate under the conditions of exposure.