Tea tree oil: contact allergy and chemical composition.

In this article, contact allergy to, and the chemical composition of, tea tree oil (TTO) are reviewed. This essential oil is a popular remedy for many skin diseases, and may be used as neat oil or be present in cosmetics, topical pharmaceuticals and household products. Of all essential oils, TTO has caused most (published) allergic reactions since the first cases were reported in 1991. In routine testing, prevalences of positive patch test reactions have ranged from 0.1% to 3.5%. Nearly 100 allergic patients have been described in case reports and case series. The major constituents of commercial TTO are terpinen-4-ol, γ-terpinene, 1,8-cineole, α-terpinene, α-terpineol, p-cymene, and α-pinene. Fresh TTO is a weak to moderate sensitizer, but oxidation increases its allergenic potency. The major sensitizers appear to be ascaridole, terpinolene, α-terpinene, 1,2,4-trihydroxymenthane, α-phellandrene, and limonene. The clinical picture of allergic contact dermatitis caused by TTO depends on the products used. Most reactions are caused by the application of pure oil; cosmetics are the culprits in a minority of cases. Patch testing may be performed with 5% oxidized TTO. Co-reactivity to turpentine oil is frequent, and there is an overrepresentation of reactions to fragrance mix I, Myroxylon pereirae, colophonium, and other essential oils.

Contact allergy to essential oils cannot always be predicted from allergy to fragrance markers in the baseline series.

BACKGROUND: Essential oils are fragrance substances that are labelled on cosmetic products by their INCI names, potentially confusing consumers. OBJECTIVES: To establish whether contact allergy to essential oils might be missed if not specifically tested for. METHODS: We tested 471 patients with 14 essential oils and 2104 patients with Melaleuca alternifolia oil between January 2008 and June 2014. All patients were tested with fragrance mix I, fragrance mix II, hydroxyisohexyl 3-cyclohexene carboxaldehyde, and Myroxylon pereirae. Three hundred and twenty-six patients were tested with hydroperoxides of limonene and linalool. RESULTS: Thirty-four patients had a +/++/+++ reaction to at least one essential oil. Eleven had no reaction to any of the six marker fragrance substances. Thus, 4 of 11 positive reactions to M. alternifolia oil, 2 of 7 reactions to Cymbopogon flexuosus oil, 1 of 5 reactions to Cananga odorata oil, 3 of 4 reactions to Santalum album oil and 2 of 3 reactions to Mentha piperita oil would have been missed without individual testing. CONCLUSION: A small number of patients who are allergic to essential oils could be missed if these are not specifically tested. Labelling by INCI names means that exposure may not be obvious. Careful inspection of so-called 'natural' products and targeted testing is recommended.

Preventive effect of American ginseng against premature ovarian failure in a rat model.

Preclinical Research Premature ovarian failure (POF) is defined by the WHO as the loss of physiological ovarian function before the age of 40. The effect of American ginseng and its underlying mechanisms in preventing and treating premature ovarian failure (POF) was studied in female Sprague-Dawley rats where POF was induced by ip administration of 4-vinylcyclohexene diepoxide (VCD). Rat behavior, serum hormone levels, ovarian and uterine size, pathological features, and ovarian tissue expression of genes associated with POF were assessed in controls, untreated POF model rats, and POF model rats treated with low- (1.125 g/kg), medium- (2.25 g/kg), and high-dose (4.5 g/kg) American ginseng. Compared with untreated POF model rats, those treated with medium- and high-dose American ginseng had more stable behavior and better coat appearance as well as serum hormone levels closer to those in control rats. Moreover, treatment with medium- or high-dose American ginseng increased ovarian and uterine size. Hematoxylin and eosin-staining revealed mature follicles and endometrium with an alternating concave/convex surface structure with visible capillaries and glands in ginseng- treated POF rats. PLA2G4A expression was positively correlated with POF, while the expression levels of PAPPA, STC2, CCL2, and NELL1 were negatively correlated with POF. Our study showed that American ginseng may effectively prevent POF and alleviate POF symptoms by regulating serum hormone levels and altering the expression levels of genes related to POF in ovarian tissue.

The fate of dermally applied [14C]d-limonene in rats and humans.

The fate of dermally applied [(14)C]d-limonene was evaluated in humans and Long-Evans rats. In rats, 5 mg/kg body weight of [(14)C]d-limonene applied dermally to the shaved back under occlusion, resulted in the absorption of approximately 12% of the dose. The absorbed d-limonene was completely metabolized and excreted rapidly, primarily from the urine (80%) with a small fraction (20%) excreted in the feces. There was no long-term retention of the test material in body tissues. In humans, following dermal application of 12 mg of [(14)C]d-limonene in ethanol (1 mL) to the back under nonocclusive conditions (for 1 h after application to allow the material to dry, thereafter under occlusion), only 0.16% of the dose was absorbed and the radioactivity was recovered from the urine. Radioactivity in human feces was below the limit of detection. These results indicate that under conditions of simulated use of fragrances and cosmetics, d-limonene has a low potential for dermal absorption and tissue accumulation, and the d-limonene that is absorbed is rapidly excreted in the urine. Based upon these findings and the knowledge that d-limonene possesses a low-systemic toxicity profile, it is reasonable to conclude that dermal exposure to d-limonene from fragrance and cosmetic applications is highly unlikely to result in any clinically significant human toxicity.

D-Limonene: safety and clinical applications.

D-limonene is one of the most common terpenes in nature. It is a major constituent in several citrus oils (orange, lemon, mandarin, lime, and grapefruit). D-limonene is listed in the Code of Federal Regulations as generally recognized as safe (GRAS) for a flavoring agent and can be found in common food items such as fruit juices, soft drinks, baked goods, ice cream, and pudding. D-limonene is considered to have fairly low toxicity. It has been tested for carcinogenicity in mice and rats. Although initial results showed d-limonene increased the incidence of renal tubular tumors in male rats, female rats and mice in both genders showed no evidence of any tumor. Subsequent studies have determined how these tumors occur and established that d-limonene does not pose a mutagenic, carcinogenic, or nephrotoxic risk to humans. In humans, d-limonene has demonstrated low toxicity after single and repeated dosing for up to one year. Being a solvent of cholesterol, d-limonene has been used clinically to dissolve cholesterol-containing gallstones. Because of its gastric acid neutralizing effect and its support of normal peristalsis, it has also been used for relief of heartburn and gastroesophageal reflux (GERD). D-limonene has well-established chemopreventive activity against many types of cancer. Evidence from a phase I clinical trial demonstrated a partial response in a patient with breast cancer and stable disease for more than six months in three patients with colorectal cancer.