CROSS-ADAPTATION BY STRUCTURAL ANALOGS 373 (59.8% of original estimates for the 10:1 E:Z mixture [Figure 3, Table I] 71.0% of original estimates for the 10:1 Z:E mixture [Figure 4, Table II]). Exposure to the Z-isomer of EE3M2H affected the perception of the 10:1 Z:E 3M2H mixture, as intensity estimates for this mixture were reduced to 67.0% of initial esti- mates via cross-adaptation by the Z-isomer (Figure 4, Table II). However, no persistence of this cross-adaptation was noted following removal of the adapting Z-isomer estimates of the 10:1 Z:E mixture during the recovery period were 92.1% of the initial estimates (Figure 4, Table II). Estimates for the 10:1 E:Z 3M2H mixture decreased following exposure to the Z-isomer, although the reduction was not significant at thep .01 level set for comparisons (reduction to 72.1% of initial estimates Figure 3, Table I). This gradual pattern of reduction continued even following removal of the adapting odorant estimates for the 10:1 E:Z 3M2H mixture during the recovery period following exposure to the Z-isomer were significantly different from initial estimates (66.9% of baseline estimates Figure 3, Table I). DISCUSSION Significant cross-adaptation was noted between structurally similar, perceptually differ- ent odorants: isomeric mixtures of sweaty-smelling 3M2H and each of its purified, fruity-smelling ethyl ester isomers. The ethyl ester E-isomer was singularly more effec- tive in cross-adapting both 3M2H mixtures than was the Z-isomer. Thus, greater cross-adaptation was seen following exposure to the ethyl ester E-isomer in both the 10:1 E:Z and 10:1 Z:E acid mixtures. This occurred even though the ethyl ester E-isomer shared more structural similarity with the 10:1 E:Z acid mixtures, while the 10:1 Z:E acid mixture shared greater similarity with the ethyl ester Z-isomer. Although exposure to the Z-isomer significantly decreased intensity estimates for the 10:1 Z:E mixture, it was less effective in reducing the perception of the 10:1 E:Z mixture. Our previous study demonstrated, via molecular modeling, that the differences in acids and their esters were principally in their lipid solubility and size (10). In that earlier study, we postulated that the greater lipid solubility of the esters allowed them to have greater access to the olfactory receptors than the acids, therefore accounting for the asymmetric cross-adaptation. The differential ability of the E- and Z-ethyl ester isomers to produce cross-adaptation may be explained by an overlapping set of receptor fields that intersect with each other within the olfactory epithelium. Those receptors prefer- entially responding to the Z-ethyl ester isomer are postulated to be smaller in number, occupying less space, and overlapping with those responding to the E-isomer. Conse- quently, EE3M2H arriving at the olfactory epithelium would preferentially occupy receptors used by both the 10:1 Z:E or 10:1 E:Z-3M2H. The results of the olfactory threshold measures for each of the isomers were surprising since, as discussed above, the ethyl ester Z-isomer possesses a lower olfactory threshold than the ethyl ester E-isomer (Z vs E, 3.051 x 10-6% vs 4.11 x 10-5%). This is the opposite of what is seen for the 3M2H isomers. For the acids, the E-3M2H olfactory threshold is lower than that of the Z-3M2H (17,18). The results presented here suggest novel strategies for both personal and living space (room) deodorancy. Use of the EE3M2H as part of a deodorant/antiperspirant fragrance

374 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS may add considerable efficacy to the fragrance by blocking the perception of a major component in the mixture of axillary odors (19). Further, lockerroom odors are also thought to be a mixture of axillary and other body odors, such as those from the feet and the genital area, which also contain volatile organic acids as important contributing malodors (20-22). Consequently, the data provided here suggest a general strategy for identifying compounds that can be used to reduce the perception of malodors. This strategy could consist of identifying the principle volatile constituents and synthesizing (or purchasing) a structurally similar, albeit pleasant smelling, compound. For odors whose principle notes consist of organic acids, the ethyl esters we have discussed here, as well as the ethyl esters of the higher and lower homologues of 3M2H described in our previous study (10), provide ideal candidates for use in cross-adaptation paradigms to suppress the perception of volatile C4-C1• organic acids. Acids with these carbon chain lengths are generally found to be associated with both body odors and bacterially mediated odors (23). ACKNOWLEDGMENTS The present research was supported by NRSA grant DC00080 to J.D.P., NIH grant DC00298 to C.J.W. and NIH grant DC-01072 to G.P., and by institutional support to E.V.A. REFERENCES (1) T. Engen, The Perception of Odors (Academic Press, New York, 1982). (2) R. W. Moncrieff, Olfactory adaptation and odour likeness, J. Physiol., 133, 301-316 (1956). (3) J. D. Pierce, Jr., C.J. Wysocki, and E. V. Aronov, Mutual cross-adaptation of the volatile steroid androstenone and a non-steroid perceptual analog, Chem. Senses, 18, 245-256 (1993). (4) J. Todrank, C.J. Wysocki, and G. K. Beauchamp, The effects of adaptation on the perception of similar and dissimilar odors, Chem. Senses, 16, 467-482 (1991). (5) W. S. Cain and E. H. Polak, Olfactory adaptation as an aspect of odor similarity, Chem. Senses, 17, 481-491 (1992). (6) W. S. Cain, Odor intensity after self-adaptation and cross-adaptation, Percept. Psychophys., 7, 271-275 (1970). (7) W. S. Cain and T. Engen, "Olfactory Adaptation and the Scaling of Odor Intensity," in Olfaction and Taste, C. Pfaffman, Ed. (Rockefeller University Press, New York, 1969), pp. 127-141. (8) T. Engen and C. O. Lindstrom, Cross-adaptation to the aliphatic alcohols, Amer. J. Psychol., 76, 96-102 (1963). (9) J. D. Pierce, Jr., C.J. Wysocki, E. V. Aronov, J. B. Webb, and R. M. Boden, The role of perceptual and structural similarity on cross-adaptation, Chem. Senses, 21, 223-237 (1996). (10) J. D. Pierce, Jr., X.-N., Zeng, E. V. Aronov, G. Preti, and C. J. Wysocki, Cross-adaptation of sweaty- smelling 3-methyl-2-hexenoic acid by a structurally-similar, pleasant-smelling odorant, Chem. Senses, 20, 401-411 (1995). (11) X-N. Zeng, J. J. Leyden, H. J. Lawley, K. Sawano, I. Nohara, and G. Preti, Analysis of characteristic odors from human male axillae, J. Chem. Ecol., 17, 1469-1492 (1991). (12) X-N. Zeng, J. J. Leyden, J. G. Brand, A. I. Spielman, K. J. McGinley, and G. Preti, An investigation of human apocrine gland secretion for axillary odor precursors,J. Chem. EcoL, 18, 1039-1055 (1992). (13) W. B. Cutler, G. Preti, A. Krieger, G. R. Huggins, C. R. Garcia, and H. J. Lawley, Human axillary secretions influence women's menstrual cycles: The role of donor extract from men, Horm. Behav., 20, 463-473 (1986). (14) G. Preti, W. B. Cutler, C. R. Garcia, G. R. Huggins, and H.J. Lawley, Human axillary secretions