Dermal absorption and disposition of musk ambrette, musk ketone and musk xylene in rats

Abstract Dermal doses of carbon-14 labelled musk ambrette (MA), musk ketone (MK) or musk xylene (MX) to male Sprague–Dawley CD rats were applied at a nominal dose level of 0.5 mg/kg (11 μg/cm 2 of skin) and excess material removed at 6 h. Means of about 40, 31 and 19% of the applied doses of MA, MK and MX, respectively, were absorbed. Most of the absorbed material was excreted within 5 days with only 1–2% of the applied dose remaining in the animal at this time. Tissue concentrations of radiolabel were similar for all three compounds with peak concentrations occurring at 6–8 h. In general, fat and liver contained the highest concentrations at around 0.2 μg nitromusk equivalents/g but concentrations in fat declined fairly rapidly to around 0.005 μg equiv./g at 120 h. Most of the absorbed dose was eliminated in bile mainly in the form of polar conjugated metabolites. Structural characterisation of the major aglycones for MA and MX indicated that they were hydroxylated analogues formed by oxidation of the ring methyl. Repeated daily dosing for 14 days resulted in little bioaccumulation for musk xylene and accumulation of about three-fold for musk ketone.