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

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 d ose level of 0.5 mg/kg (11 mu g/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 w ithin 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 c ompounds with peak concentrations occurring at 6-8 h. In general, fat and l iver contained the highest concentrations at around 0.2 mu g nitromusk equi valents/g but concentrations in fat declined fairly rapidly to around 0.005 mu g equiv./g at 120 h. Most of the absorbed dose was eliminated in bile m ainly in the form of polar conjugated metabolites. Structural characterisat ion of the major aglycones for MA and MX indicated that they were hydroxyla ted analogues formed by oxidation of the ring methyl. Repeated daily dosing for 14 days resulted in little bioaccumulation for musk xylene and accumul ation of about three-fold for musk ketone. (C) 1999 Published by Elsevier S cience Ireland Ltd. All rights reserved.