Evaluation of the mutagenicity of β‐myrcene in mammalian cells in vitro

Abstract

The genotoxicity of the terpene beta-myrcene was evaluated in mammalian cells in vitro. Myrcene is the major constituent of oil of bay and hop which are used in the manufacture of alcoholic beverages. Myrcene is also present in lemon grass (Cymbopogon citratus), a plant widely used in Brazilian folk medicine. Recently, it was shown that myrcene is a very potent analgesic substance and might be an alternative to the already available analgesic drugs. Myrcene was tested up to 1,000 micrograms/ml (limit of solubility) in the presence and absence of S9-mix and did not induce chromosome aberrations and sister chromatid exchanges (SCEs) in human lymphocytes in vitro. Neither the mitotic index nor the proliferation index was influenced by the myrcene treatment. Myrcene did not cause increased mutation frequencies at the hprt-locus in V79-cells. Tests with and without S9-mix revealed negative results. There was no indication for induced cytotoxicity. However, myrcene reduced the SCE-inducing effect of cyclophosphamide in human lymphocytes in a dose dependent manner and also reduced the toxic and mutagenic effect of cyclophosphamide in V79-cells. Under the same test conditions, SCE induction by ethyl methanesulfonate (EMS) and benzo [a]pyrene (BP) was not significantly influenced by simultaneous myrcene treatment. The in vitro results show that myrcene is not mutagenic in mammalian cells, but has antimutagenic properties. The possibility that myrcene exerts its antimutagenic activity by inhibiting certain forms of the cytochrome P-450 isoenzymes required for activation of premutagens and precarcinogenes is discussed.

Scientific Opinion on Flavouring Group Evaluation 78, Revision 1 (FGE.78Rev1): Consideration of aliphatic and alicyclic and aromatic hydrocarbons evaluated by JECFA (63rd meeting) structurally related to aliphatic and aromatic hydrocarbons evaluated by EF

“…Chinese hamster ovary cells 10-100 μg/ml -S9; 50-500 μg/ml +S9 Negative c (Anderson et al, 1990;NTP, 1990e (Kauderer et al, 1991) Sister chromatid exchange Human lymphocytes 100-1 000 μg/ml Negative c (Kauderer et al, 1991) Sister chromatid exchange…”

“…Human lymphocytes 100-1 000 μg/ml Negative c (Kauderer et al, 1991) (Jagannath, 1984a) EFSA Journal 2011; 9(6):2178 (Connor et al, 1985) Reverse mutation S. typhimurium TA98, TA100, TA1535, TA1537, TA1538…”

“…Myrcene also did not induce SCE or chromosomal aberrations in human lymphocytes, with and without metabolic activation, at concentrations of up to 1000 µg/ml (Kauderer et al, 1991), nor did it induce SCE in hepatic tumour cells, at concentrations of up to 500 µg/ml, although a slight, reproducible but not dose-dependent increase was noted (Röscheisen et al, 1991). EFSA Journal 2011; 9(6):2178…”

“…With and without metabolic activation, myrcene .008] did not induce gene mutations at the hypoxanthine guanine phosphoribosyl transferase (Hprt) locus in Chinese hamster V79 cells, at concentrations of up to 1000 µg/ml (Kauderer et al, 1991), nor did it induce SCE in these cells at concentrations up to 500 µg/ml (Röscheisen et al, 1991). Myrcene also did not induce SCE or chromosomal aberrations in human lymphocytes, with and without metabolic activation, at concentrations of up to 1000 µg/ml (Kauderer et al, 1991), nor did it induce SCE in hepatic tumour cells, at concentrations of up to 500 µg/ml, although a slight, reproducible but not dose-dependent increase was noted (Röscheisen et al, 1991).…”

Study of the effects of ß-myrcene on rat fertility and general reproductive performance

“…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).…”