Dermal absorption and disposition of musk ambrette, musk ketone and musk xylene in human subjects.

Musk ambrette, musk ketone and musk xylene have a long history of use as fragrance ingredients, although musk ambrette is no longer used in fragrances. As part of the review of the safety of these uses, it is important to consider the systemic exposure that results from these uses. Since the primary route of exposure to fragrances is on the skin, dermal doses of carbon-14 labelled musk ambrette, musk ketone and musk xylene were applied to the backs (100 cm2) of healthy human volunteers (two to three subjects) at a nominal dose level of 10-20 microg/cm2 and excess material removed at 6 h. Means of 2.0% musk ambrette, 0.5% musk ketone and 0.3% musk xylene were absorbed based on the amounts excreted in urine and faeces during 5 days. Most of the material was excreted in the urine with less than 10% of the amount excreted being found in faeces. No radioactivity was detected in any plasma sample, consistent with low absorption, and no radioactivity was detected (<0.02% dose) in skin strips taken at 120 h. Analysis of urine samples indicated that all three compounds were excreted mainly as single glucuronide conjugates. The aglycones were chromatographically different, but of similar polarity, to the major rat metabolites excreted in bile also as glucuronides.