Safety and Feasibility of Topical Application of Limonene as a Massage Oil to the Breast

Abstract

Background: Limonene, a major component in citrus oil, has demonstrated anti-cancer effects in preclinical mammary cancer models. However, the effective oral dose translates to a human dose that may not be feasible for chronic dosing. We proposed to evaluate topical application of limonene to the breast as an alternative dosing strategy.

Materials and methods: We conducted a mouse disposition study to determine whether limonene would be bio available in the mammary tissue after topical application. SKH-1 mice received topical or oral administration of limonene in the form of orange oil every day for 4 weeks. Plasma and mammary pads were collected 4 hrs after the final dosing. We also conducted an exploratory clinical study to evaluate the safety and feasibility of topically applied limonene in the form of orange oil to the breast. Healthy women were recruited to apply orange oil containing massage oil to their breasts daily for four weeks. Safety and feasibility were assessed by reported adverse events, clinical labs, and usage compliance. Pre and post-intervention nipple aspirate fluid (NAF) and plasma were collected for limonene concentration determination.

Results: The mouse disposition study showed that topical and oral orange oil administration resulted in similar mammary tissue disposition of limonene with no clinical signs of toxicity. In the clinical study, the topical application of limonene containing massage oil to the breast was found to be safe with high levels of usage compliance for daily application, although NAF and plasma limonene concentrations were not significantly changed after the massage oil application.

Conclusions: Our studies showed that limonene is bio available in mammary tissue after topical orange oil application in mice and this novel route of administration to the breast is safe and feasible in healthy women.

Keywords: Limonene; Safety; Topical Application.

Figure 1

Mammary gland whole mounts (a) untreated control (b) topically applied limonene (c) orally administered limonene demonstrated that limonene did not adversely affect normal mammary gland morphology.

Figure 2

NAF and plasma limonene concentrations at baseline and after 4 weeks of topical application of limonene containing massage oil. Limonene levels in NAF were 95.11 ± 50.02 nM at baseline and were not significantly different post-intervention. Plasma limonene concentrations were 18.60 ± 24.02 nM at baseline and were also not significantly different post-intervention. NAF limonene levels were significantly higher than the time-matched plasma (P < 0.01).