Chemical and Physical Properties

Cedarwood oils can be extracted from several members of the Cupressaceae family, which encompasses true cedars, junipers, and cypresses. The three most prevalent cedarwood oil products in the United States are Virginia cedarwood oil (Juniperus virginiana), Texas cedarwood oil (Juniperus mexicana or Juniperus ashei), and Western red cedar (Thuja plicata).¹ Western red cedar is the least commonly used of the three.^2,3

The most common components of cedarwood oils are sesquiterpene hydrocarbons and include cedrol, α-cedrene, cedrenol, cedral, cuparene, thujopsene, and widdrol, though the relative percentages can differ depending on the origin of the cedar trees.^4-8 The International Organization for Standardization set the following minimum and maximum standards for the components that make up the chromatographic profile of cedarwood oil (from Juniperus virginiana): α-cedrene (20% to 35%), β-cedrene (4% to 8%), thujopsene (10% to 25%), cuparene (1.5% to 7%), cedrol (16% to 25%), and widdrol (2% to 5%).⁹

Cedarwood oil is a colorless to pale brown viscous liquid with a cedarwood odor and bitter taste.^6,7 It is insoluble in water but soluble in ethanol or ether¹⁰ and may solidify at room temperature.⁶

Production, Use, and Human Exposure

Virginia cedarwood oil is extracted from Juniperus virginiana trees by steam distillation.⁶ Cedarwood oil of unspecified origin is used commonly in fragrance formulations, and production for this purpose exceeds 100,000 pounds per year.^6,11 Several cedarwood oil components can be isolated and acetylated for use in fragrances. Of the chemical components that make up cedarwood oil, cedrene, thujopsene, and cedrol are commonly isolated and often acetylated in the production of fragrance materials such as cedryl acetate and cedryl methylether.⁶ These extracts can be found in many cosmetic products (i.e., perfumes, lotions) that may be applied to most parts of the body and may come into contact with the ocular and nasal mucosae. Frequent application of these products on a daily basis leads to long-term chronic exposure. The cosmetics industry no longer reports concentration of use values to the United States Food and Drug Administration.¹² However, data submitted to the FDA indicated that the maximum use concentration ranges from the 1984 product formulation data for Juniper Extract and Juniper Tar in cosmetics were 0.1% to 1%, and 1% to 5%, respectively.¹³ Limited or no toxicity was found in rats and rabbits following dermal application of either Western juniper oil (0.5%, 5%, or 50%) or Port-Orford cedar extract (0.5%, 5%, or 50%) when tested using a local lymph node assay and an acute dermal irritation study.¹⁴

As a pesticide, cedarwood oil is used as an insect repellent in sunscreens, pet collars, and for horses.¹⁵ The potential use of cedarwood oil as a topical mosquito repellent was explored, but found to be ineffective against multiple mosquito species.^16,17 However, it was found to be effective with an average knock-down range of 20% to 80% when applied directly to mosquitoes, cockroaches, and houseflies.¹⁸ Virginia cedarwood oil was also found to be effective as a barrier repellent to red imported fire ants and black-legged tick nymphs.¹⁹ Additionally, it is used in blocks and as a liquid spray for repelling moths and mildew from clothing and fabrics.^8,15 In vitro, Japanese cedarwood oils have been found to have anti-fungal properties against Trichophyton rubrum through the inhibition of DNA polymerase.²⁰

Historically, in ancient Rome and in early America, cedarwood oil was taken orally to induce abortion.^21,22,10 Data on current human use of cedarwood oil as an abortifacient are minimal. However, exposure to the bark, leaves, and berries of western juniper trees (Juniperus occidentalis) has been shown to induce abortions in late-term cattle in Oregon.²³

Based on the 1981 to 1983 National Occupational Exposure Survey, cedarwood oil was used in 7,990 facilities, and 117,858 employees were exposed to cedarwood oil.²⁴ From this NIOSH report, the scope of occupational facilities in which cedarwood oil is used is large and includes industrial settings, medical fields, and esthetics and beauty care.

Regulatory Status

Cedarwood oil alcohols and terpenes are listed as synthetic flavoring substances and adjuvants that are permitted by the United States Food and Drug Administration²⁵ for direct addition to food for human consumption. Cedarwood oil was registered as a pesticide in the United States in 1960.⁸ Currently, cedarwood oil is listed as a minimum risk pesticide and exempted from the Federal Insecticide, Fungicide, and Rodenticide Act regulations.²⁶ Cedarwood oil is listed in the Toxic Substances Control Act Inventory.²⁷ However, no limits on recommended or permissible exposures are available.

Absorption, Distribution, Metabolism, and Excretion

There are very limited data in the literature on the disposition of cedarwood oil and its components. Following gavage administration of 25 (males only), 50 (females only), or 100 mg/kg α-cedrene to male and female Sprague Dawley rats, the chemical was absorbed slowly with a T_max between 2.8 and 4.4 hours.^28,29 The values estimated for absolute bioavailability were 42% (males, 25 mg/kg), 49% (females, 50 mg/kg), 71% (female, 100 mg/kg), or 85% (male, 100 mg/kg). Tissue distribution was investigated only in female rats, and α-cedrene was extensively distributed to tissues with tissue:plasma ratios greater than 1 for all tissues with lipid showing the highest tissue:plasma ratio. Plasma elimination half-life was between 2 and 5.9 hours depending on the study.^28,29 In females, C_max and AUC values increased proportionally to the dose.²⁹ There were no sex- or dose-related differences in the disposition of α-cedrene. The urinary excretion of unmetabolized α-cedrene following gavage administration was equal to or less than 0.017%.

Toxicity

Reproductive and Developmental Toxicity

Oral exposure of pregnant Sprague Dawley rats to the cedarwood oil derivative acetyl cedrene at concentrations of 25, 50, or 100 mg/kg per day on gestation days 7 to 17 resulted in no significant fetal effects and minor maternal effects such as decreased body weight gains and feed consumption; the no-observed-adverse-effect levels were 50 and 100 mg/kg per day for the dams and fetuses, respectively.³⁵ In a separate study, β-thujaplicin (another cedarwood oil derivative) was orally administered to pregnant ICR mice on gestation day 9; evaluation of the fetuses on gestation day 18 found that the chemical induced several malformations at doses of 560 mg/kg or greater, including cleft lip, cleft palate, and facial dysmorphism.³⁶

Carcinogenicity

No information on the carcinogenicity of cedarwood oil in experimental animals or humans was found in a review of the literature.

Genetic Toxicity

No information on the genotoxicity of cedarwood oil was found in the literature.

Study Rationale

Cedarwood oil was nominated for study by the National Cancer Institute based on widespread and increasing human exposure to the substance and a lack of toxicology data. Due to the frequent use of cedarwood oil as a fragrance material and a pesticide, the dermal route of administration was selected for these studies because it is the most common route of exposure in humans.