National Toxicology Program

TR-557
Toxicology and Carcinogenesis Studies of β-Myrcene (CAS No. 123-35-3) in F344/N Rats and B6C3F1 Mice (Gavage studies)

PLEASE NOTE: The following abstract has been extracted from the DRAFT technical report to be reviewed by the National Toxicology Program Board of Scientific Counselors Technical Reports Review Subcommittee on February 25, 2009 (see the meeting page). When this report becomes final the entire report will be available in pdf format on the NTP website.

Draft Abstract

β-Myrcene, an acyclic unsubstituted monoterpene, and the essential oils which contain it are used as intermediates in the production of terpene alcohols (geraniol, nerol, and linalool), which, in turn, serve as intermediates in the production of aroma and flavor chemicals; thus, β-myrcene is used widely in cosmetics, soaps, and detergents and as a flavoring additive in food and beverages. β-Myrcene is also the major constituent of hop and bay oils, which are used in the manufacture of alcoholic beverages. β-Myrcene was nominated for study by the National Institute of Environmental Health Sciences based on its high production volume, high level of human exposure, and structural relationship to d-limonene, which induced neoplasms in the kidneys of male rats in association with hyaline droplet nephropathy (NTP, 1990). Male and female F344/N rats and B6C3F1 mice were administered β-myrcene (greater than 90% pure) by gavage for 3 months or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes.

3-MONTH STUDY IN RATS

Groups of 10 male and 10 female rats were administered 0, 0.25, 0.5, 1, 2, or 4 g β:-myrcene/kg body weight in corn oil by gavage, 5 days per week for 14 weeks. Additional groups of 10 male and 10 female special study rats were administered the same doses for 22 days. All core study rats in the 4 g/kg groups died during the first week of the study except one male that died on day 11. One to three rats in the 1 and 2 g/kg groups and one 0.5 g/kg male died by week 9 of the study. One 2 g/kg female died during the last week of the study. Except for lesion incidence data in groups administered 2 g/kg or less, data from rats that died early were excluded from the analysis and summary tables. Mean body weights were significantly decreased in the 0.5, 1, and 2 g/kg groups. Special study rats in the 4 g/kg groups died by the end of the first week. Dose-related clinical findings in animals that died early included thinness, lethargy, abnormal breathing, and ruffled fur. Right kidney and liver weights of dosed males and females were generally significantly greater than those of the vehicle controls.

In special study rats evaluated on day 23, the incidences and severities of chronic progressive nephropathy (CPN) and renal tubule necrosis were increased in 2 g/kg males. At the end of the 3-month study, the incidences of renal tubule necrosis were significantly increased in all dosed groups of males and females.

At 3 months, the incidences of olfactory epithelium degeneration in 2 g/kg males and females were significantly increased, and the severities were increased. The incidences of chronic inflammation in 1 and 2 g/kg males and females were significantly increased. All 2 g/kg males and females had splenic atrophy. In the mesenteric lymph node, s...