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Association FaEM, “d-Limonene Monograph,” No. 1991, pp. 1-4.

has been cited by the following article:

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

    AUTHORS: Jessica A. Miller, Patricia A. Thompson, Iman A. Hakim, Ana Maria Lopez, Cynthia A. Thomson, Wade Chew, Chiu-Hsieh Hsu, H.-H. Sherry Chow

    KEYWORDS: Limonene; Topical Application; Safety

    JOURNAL NAME: Journal of Cancer Therapy, Vol.3 No.5A, November 1, 2012

    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 bioavailable 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 bioavailable 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.