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Pygmy rabbits (Brachylagus idahoensis) are one of only three vertebrates that subsist virtually exclusively on sagebrush (Artemisia spp.), which contains high levels of monoterpenes that can be toxic. We examined the mechanisms used by specialist pygmy rabbits to eliminate 1,8-cineole, a monoterpene of sagebrush, and compared them with those of cottontail rabbits (Sylvilagus nuttalli), a generalist herbivore. Rabbits were offered food pellets with increasing concentrations of cineole, and we measured voluntary intake and excretion of cineole metabolites in feces and urine. We expected pygmy rabbits to consume more, but excrete cineole more rapidly by using less-energetically expensive methods of detoxification than cottontails. Pygmy rabbits consumed 3-5 times more cineole than cottontails relative to their metabolic body mass, and excreted up to 2 times more cineole metabolites in their urine than did cottontails. Urinary metabolites excreted by pygmy rabbits were 20 % more highly-oxidized and 6 times less-conjugated than those of cottontails. Twenty percent of all cineole metabolites recovered from pygmy rabbits were in feces, whereas cottontails did not excrete fecal metabolites. When compared to other mammals that consume cineole, pygmy rabbits voluntarily consumed more, and excreted more cineole metabolites in feces, but they excreted less oxidized and more conjugated cineole metabolites in urine. Pygmy rabbits seem to have a greater capacity to minimize systemic exposure to cineole than do cottontails, and other cineole-consumers, by minimizing absorption and maximizing detoxification of ingested cineole. However, mechanisms that lower systemic exposure to cineole may come with a higher energetic cost in pygmy rabbits than in other mammalian herbivores.

Eucalyptus leaf-eating marsupials such as the brushtail possum (Trichosurus vulpecula) ingest large amounts of terpenes, especially 1,8-cineole (cineole)--the major component of many eucalyptus oils. Brushtail possums were acclimated to a non-Eucalyptus diet with increasing concentrations of cineole (0.5-4.0% wet weight) added over 18 d. We measured food and cineole consumption and urinary metabolites of cineole. Food intake decreased with cineole content, indicating that it was constrained by the maximum tolerable intake of cineole that was 3.8 +/- 0.2 g kg(-1) or 5.2 +/- 0.3 g kg(-0.75) (mean +/- SE, N = 6). The pattern of metabolites was similar at all cineole intakes (56% hydroxycineolic acids, 27% cineolic acids, 13% hydroxycineoles, and 4% dihydroxycineoles). In another experiment, possums maintained on artificial diet were abruptly presented with 4% cineole for 5 d. Food intake fell by 45 +/- 6% (mean +/- SE, N = 6) and mean cineole intake was 2.9 +/- 0.3 g kg(-1). There was evidence of induction of secondary oxidative pathways, as hydroxycineoles were the major metabolites (48% total) on the first day, but rapidly dropped to 15% on subsequent days as the acid metabolites increased. These findings indicate that ingestion of cineole is not constrained by selective saturation of individual enzymes involved in its multiple pathways of oxidation, but rather the total detoxification capacity appears to limit feeding on a cineole diet.

We investigated effects of two plant secondary metabolites (PSMs), cineole and gallic acid, on the nightly feeding behavior of the common brushtail possum (Trichosurus vulpecula), a generalist folivore. We tested whether possums altered their feeding behavior in response to increasing levels of cineole, a dietary terpene. Possums were fed artificial diets containing three levels of cineole: zero (basal diet), medium (6.8% of total dry matter, DM), and high (15.3% DM). In another experiment, we introduced gallic acid, a dietary phenolic, into the diets. Possums were offered a Choice PSM diet (cineole and gallic acid diets simultaneously) or a No-Choice PSM diet (containing either cineole or gallic acid). Detoxification products of cineole and gallic acid were examined in urine to determine that different detoxification pathways were utilized in the elimination of each compound. With increasing cineole levels, possums ate less, had smaller feeding bouts, and had a lower rate of intake, but did not extend their total nightly feeding time. Possums offered the Choice PSM diet, compared with the No-Choice diets, ate more, had larger feeding bouts, and tended to increase their rate of intake. Results from the urinary analysis indicated that gallic acid and cineole were not involved in competing detoxification pathways in brushtail possums. There was also a significant sex effect: females ate more overall, ate more per feeding bout, and ate at a higher rate than males. These results indicate that PSMs not only constrain overall intake, but that possums alter their feeding behavior in response to them. Altered feeding patterns may reduce the negative influence of PSMs on intake.