Abstract
beta-Myrcene (MYR) is a monoterpene found in the oils of a variety of aromatic plants including lemongrass, verbena, hop, bay, and others. MYR and essential oils containing this terpenoid compound are used in cosmetics, household products, and as flavoring food additives. This study was undertaken on investigate the effects of MYR on fertility and general reproductive performance in the rat. MYR (0, 100, 300 and 500 mg/kg) in peanut oil was given by gavage to male Wistar rats (15 per dose group) for 91 days prior to mating and during the mating period, as well as to females (45 per dose group) continuously for 21 days before mating, during mating and pregnancy, and throughout the period of lactation up to postnatal day 21. On day 21 of pregnancy one-third of the females of each group were submitted to cesarean section. Resorption, implantation, as well as dead and live fetuses were counted. All fetuses were examined for external malformations, weighed, and cleared and stained with Alizarin Red S for skeleton evaluation. The remaining dams were allowed to give birth to their offspring. The progeny was examined at birth and subsequently up to postnatal day 21. Mortality, weight gain and physical signs of postnatal development were evaluated. Except for an increase in liver and kidney weights, no other sign of toxicity was noted in male and female rats exposed to MYR. MYR did not affect the mating index (proportion of females impregnated by males) or the pregnancy index (ratio of pregnant to sperm-positive females). No sign of maternal toxicity and no increase in externally visible malformations were observed at any dose level. Only at the highest dose tested (500 mg/kg) did MYR induce an increase in the resorption rate and a higher frequency of fetal skeleton anomalies. No adverse effect of MYR on postnatal weight gain was noted but days of appearance of primary coat, incisor eruption and eye opening were slightly delayed in the exposed offspring. On the basis of the data presented in this paper the no-observed-adverse-effect level (NOAEL) for toxic effects on fertility and general reproductive performance can be set at 300 mg of beta-myrcene/kg body weight by the oral route.
Highlights
Introduction ß-Myrcene (7-methyl-3-methylene-1,6octadiene) (MYR) is an acyclic monoterpene found in a large variety of plants including lemongrass, verbena, hop, bay, and others [1,2]. ß-Myrcene and essential oils containing this terpenoid compound are widely used as a fragrance in cosmetics, as a scent in household products, and as a flavoring additive in food and alcoholic beverages [3]
Since ß-myrcene has proved to be an inducer of hepatic monooxygenases [8], liver enlargement probably resulted from the marked hypertrophy of the endoplasmic reticulum due to the induction of microsomal enzyme synthesis in treated animals [18]
The mechanism underlying the ß-myrcene-induced enlargement of kidneys is still far from being entirely understood. ß-Myrcene was reported to cause a sex-specific hyaline droplet nephropathy in male rats very similar to that produced by dlimonene, a monocyclic monoterpene [19]. d-Limonene-induced hyaline nephropathy was shown to be due to an epoxide metabolite (d-limonene-1,2-oxide) that binds to an α2μ-globulin thereby preventing its lysosomal degradation and leading to an accumulation of this low molecular weight protein in the cytoplasm of the proximal tubule cells [20]
Summary
Introduction ßMyrcene (7-methyl-3-methylene-1,6octadiene) (MYR) is an acyclic monoterpene found in a large variety of plants including lemongrass, verbena, hop, bay, and others [1,2]. ß-Myrcene and essential oils containing this terpenoid compound are widely used as a fragrance in cosmetics, as a scent in household products, and as a flavoring additive in food and alcoholic beverages [3]. It was reported that ßmyrcene is an analgesic substance and the active principle of lemongrass (Cymbopogon citratus Stapf) abafado, an infusion made with the pan covered in order to prevent the loss of volatile constituents [4]. The importance of human exposure to ßmyrcene, the widespread use of plants as well as essential oils containing large amounts of this monoterpene (e.g. lemongrass oil), and the relative paucity of data about its health risks prompted us to perform a rather comprehensive study of its reproductive toxicity. The acute toxicity of ß-myrcene was reported to be low [10] and this monoterpene was shown to have no genotoxic activity in vitro [11] or in vivo [12]. No evidence that ß-myrcene is a teratogenic substance was found [13] and the no-observed-adverse-effect level (NOAEL) for peri- and postnatal developmental toxicity in the rat was set at 0.25 g ß-myrcene/kg body weight [14]
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