Disposition of fragrance ingredient [¹⁴C]1-(1,2,3,4,5,6,7,8-octahydro-2,3,8,8-tetramethyl-2-naphthalenyl)ethanone in male Fisher rats following oral administration and dermal application

Abstract

1. Disposition of 1-(1,2,3,4,5,6,7,8-octahydro-2,3,8,8-tetramethyl-2-naphthalenyl)ethanone (β-OTNE), a fragrance ingredient in variety of consumer products, was investigated following a single oral (20 mg/kg) or a dermal (55 or 550 mg/kg) dose of [¹⁴C]β-OTNE to male Fisher rats.

2. Following oral administration, 28% and 39% of the dose was recovered in urine and feces, respectively, 48 h following administration. About 73% of a 20 mg/kg dose was excreted in bile within 48 h post-administration supporting significant oral absorption of [¹⁴C]β-OTNE.

3. Following dermal application to a covered site, absorption of [¹⁴C]β-OTNE 96 h following application was low (ca. 14%) and dose-independent. When the dose site was uncovered, the absorption increased to ca. 33% (55 mg/kg) and ca. 72% (550 mg/kg).

4. [¹⁴C]β-OTNE was distributed to tissues following both routes of exposure with the highest radioactive equivalents found in bladder, liver, kidney, adipose and pancreas.

5. Elimination of [¹⁴C]β-OTNE equivalents in blood and tissues was slow following both oral and dermal application suggesting potential for accumulation following multiple exposure.

• 1-(1,2,3,4,5,6,7,8-Octahydro-2,3,8,8-tetramethyl-2-naphthalenyl)ethanone
• biliary excretion
• dermal absorption
• enterohepatic recirculation
• fragrance ingredient
• oral absorption

Acknowledgements

The authors are grateful to Drs. Matt Stout and Mike DeVito for their review of this manuscript. This work was performed by RTI International (RTP, NC) for the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, U.S. Department of Health and Human Services, under contract No. N01-ES-25482.