Olfactory Sensitivity and Odor Structure-Activity Relationships for Aliphatic Carboxylic Acids in CD-1 Mice

• Using a conditioning paradigm, the olfactory sensitivity of CD-1 mice for a homologous series of aliphatic n-carboxylic acids(ethanoic acid to n-octanoic acid) and several of their isomeric forms was investigated. With all 14 odorants, the animalssignificantly discriminated concentrations as low as 0.03 ppm (parts per million) from the solvent, and with four odorantsthe best-scoring animals even detected concentrations as low as 3 ppt (parts per trillion). Analysis of odor structure-activityrelationships showed that the correlation between olfactory detection thresholds of the mice for the unbranched carboxylicacids and carbon chain length can best be described as a U-shaped function with the lowest threshold values at n-butanoicacid. A significant positive correlation between olfactory detection thresholds and carbon chain length of the carboxylicacids with their branching next to the functional carboxyl group was found. In contrast, no such correlation was found forcarboxylic acids with their branching at the distal end of the carbon chain relative to the functional carboxyl group. Finally, asignificant correlation was found between olfactory detection thresholds and the position of the branching of the carboxylicacids. Across-species comparisons suggest that mice are more sensitive for short-chained (C2 to C4) aliphatic n-carboxylicacids than other mammalian species, but not for longer-chained ones (C5 to C8). Further comparisons suggest that odorstructure-activity relationships are both substance class- and species-specific.

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