j. Cosmet. Sci., 49, 369-376 (November/December 1998) Reduction in the sweaty smell of 3-methyl-2-hexenoic acid by cross-adaptation using its pleasant-smelling methyl esters JOHN D. PIERCE, JR., DAVID H. BLANK, GEORGE PRETI*, and CHARLES J. WYSOCKI, Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104-3308 (J.D.P., D.H.B., G.P., C.J.W.) Department of Dermatology, School of Medicine, University of Pennsylvania (G.P.) and Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania (C.J.W.). Accepted for publication October 15, 1998. Synopsis Magnitude estimates for a 10:1 mixture of (E)- and (_Z)-3-methyl-2-hexenoic acid (3M2H), a principal component of human underarm odor, decreased following adaptation to a mixture of methyl esters of 3M2H (ME3M2H), which possess a pleasant, fruity odor. These results provide further demonstration that struc- turally similar, yet perceptually distinct, odorants may cross-adapt and suggest that the extent of cross- adaptation may be affected by the degree of structural, as well as perceptual, similarity. INTRODUCTION The extent of olfactory cross-adaptation, the decrease in sensitivity to one odorant following exposure to a different odorant, may represent the degree to which odors share common sensory channels (1-4). Thus, by documenting the extent of cross-adaptation among different odorants, inferences about structure-activity relationships and coding in the olfactory system can be drawn. Yet, surprisingly little is known about the determinants of olfactory self- and cross-adaptation. The present report continues our long-term study of the structural features of odorous compounds as they affect cross- adaptation between sweaty-smelling 3-methyl-2-hexenoic acid and its fruity-smelling esters. It is now well established that the occurrence of cross-adaptation typically entails a David H. Blank's current address is Albany Molecular Research, Inc., 21 Corporate Circle, Albany, NY 12203. John D. Pierce, Jr's current address is Department of Psychology, Philadelphia College of Textiles and Science, Philadelphia PA 19144. 369

370 JOURNAL OF COSMETIC SCIENCE degree of similarity, either perceptual or structural, between the tested odorants. There is a good deal of evidence demonstrating that perceptual similarity affects cross- adaptation since perceptually similar odorants, irrespective of structural similarity, cross- adapt (1-5). Conversely, structurally similar odorants, irrespective of perceptual simi- larity, can cross-adapt as well (6-10). One system we have used to study structural similarity and cross-adaptation (10) is an isomeric mixture of (E)- and (Z)-3-methyl-2-hexenoic acid (3M2H). Both isomers are present in axillary sweat of males and females, albeit in different ratios (11,12). The E-isomer of 3M2H is a major component (analytically) in male underarm sweat (11,13). A synthetic mixture of the two isomers was formulated in the 10:1 E:Z ratio found in the male secretions (11,13) and tested for cross-adaptation with three homologous ethyl esters: the ethyl esters of 3-methyl-2-hexenoic acid (EE3M2H), 3-methyl-2-octenoic acid (EE3M20), and 3-methyl-2-pentenoic acid (EE3M2P). The esters, in contrast to the volatile sweaty-smelling organic acids, are pleasant and fruity-smelling. Significant cross-adaptation was observed between 3M2H and its ethyl esters (10) since exposure to EE3M2H resulted in significantly reduced magnitude estimates for the intensity of 3M2H. Cross-adaptation was asymmetric adaptation to 3M2H did not significantly affect the perceived intensity of EE3M2H. Further, there was no significant cross-adaptation between 3M2H and the ethyl esters of the lower (EE3M2P) and higher (EE3M20) molecular weight homologues (10). Similarity ratings between the ethyl esters and 3M2H revealed no significant differences among the ethyl esters in their mean similarity rating to 3M2H i.e., each was rated equally dissimilar to 3M2H (10). Thus, it is unlikely that the differences among the ethyl esters in their efficacy in cross- adapting 3M2H were attributable to perceptual differences. A more likely explanation for the pattern of cross-adaptation observed is the greater structural similarity between EE3M2H and 3M2H as revealed by molecular modeling studies (10). We have recently also established that the E-isomer is singularly more effective in cross-adapting 3M2H than is the Z-isomer (9). The methyl esters of 3M2H (ME3M2H) have a pleasant, fruity odor however, the odor is much weaker than that possessed by the ethyl esters (9,10). In the present work, we sought to determine whether the ME3M2H would be as effective in cross-adapting 3M2H as the ethyl esters. We assessed cross-adaptation between a mixture of methyl esters of 3M2H and a 10:1 E:Z mixture of 3M2H. EXPERIMENTAL SUBJECTS Twelve paid subjects (five males and seven females mean age of 25.3 years) were recruited from among colleagues and the surrounding university community. All sub- jects were first screened for sensitivity to the odorants used in the experiment and paid to participate. STIMULI SYNTHESIS AND PURIFICATION The stimuli used are presented in Figure 1. The 3M2H was synthesized and purified in