Lavandula angustifolia

Lavandula angustifolia also known as English lavender, common lavender or French lavender, Lavandula vera or Lavandula officinalis, is an essential-oil-bearing aromatic shrub in the Lamiaceae family (the mint family). Lavender is native to countries in the Mediterranean region, including France, Spain, and Italy through northern and eastern Africa and Middle Eastern countries to southwest Asia and southeast India ¹. Lavandula angustifolia pleasant aroma combined with its purported health benefits make lavender essential oil a popular choice for aromatherapy and a common ingredient in cosmetics, flavors, and fragrances. The name lavender comes from the Latin verb “lavare,” meaning “to wash.” In ancient Rome, lavender was used as a bath additive. Lavender is used to flavor foods and beverages and as a fragrance ingredient in soaps and cosmetics. Lavandula angustifolia is promoted as a dietary supplement for anxiety, depression, digestive symptoms, and other conditions. It is also promoted for topical use (application to the skin) and use in aromatherapy. Among the many traditional uses for the lavender plant, those commonly cited are the purported sedative and anti-inflammatory properties ². These traditional uses have been substantiated through recent studies ³, ⁴, ⁵. Lavender essential oil has also been shown to have a positive effect on anxiety and depression in humans and in animal models ⁶, ⁷, ⁸, ⁹.

Lavenders belong to the Labiatae (Lamiaceae) family of plants. Most commercially marketed lavender essential oils are obtained from cultivars of two Lavandula species, Lavandula angustifolia and Lavandula latifolia, as well as from lavender hybrids, commonly known as lavandins ¹⁰. Other lavender species, such as Lavandula stoechas and Lavandula dentata, have also been used in folk medicinal practices for their anti-spasmolytic properties ¹¹. The name lavender comes from the Latin verb “lavare,” meaning “to wash.” In ancient Rome, lavender was used as a bath additive. Lavender and its essential oil have been used since centuries due to antiseptic, anti-inflammatory, antioxidant, antibacterial, antifungal, antiviral, antidepressive, sedative, immune-stimulating, and even anticancer effects ¹². In today’s folk and complementary medicine, lavender essential oil is applied also for the treatment of conditions such as anxiety, restlessness, insomnia and depression. Administration routes include absorption via the respiratory tract (aromatherapy) or oral ingestion ¹³. Lavender oil has a strong bactericidal effect on many strains of bacteria (e.g., Staphylococcus aureus, Enterococcus faecalis), accompanied by a weak fungicidal activity (e.g., Botrytis cinereal, Aspergillus fumigatus) ¹⁴.

Lavender oil is distilled from the flowers and the top growth of narrow-leaved lavender ¹⁵. The calyx of Lavandula angustifolia is the main site of essential oil accumulation (yield 1.3%), the corolla had the next highest yield (0.1%), followed by the leaf (0.05%) ¹⁶. The whole flowering top, composed of corolla, calyx, stem, and leaf, had a yield of 0.7%. The medicinal raw material comes mainly from the flowers, with the essential oil obtained about 3%. The quality and composition of lavender essential oil depend on the origin, growing conditions, variety, and other factors. Lavender oil can contain more than 100 different components. Mainly, these are terpenoid compounds (monoterpenes, triterpenes, sesquiterpenes) as well as phenolic compounds (flavonoids, phenolic acids, coumarin, tannins). The main components of the essential oil should be linalool (20–45%) and its acetate (25–46%). The percentage of other ingredients falls usually within the following ranges: limonene (<1.0%), eucalyptol (<2.5%), camphor (<1.2%), terpinen-4-ol (0.1–6.0%), lavandulol (>0.1%), lavandulyl acetate (>0.2%), and α-terpineol (<2.0) ¹⁷.

Studies have been done on the use of lavender for a variety of conditions, but there hasn’t been enough high-quality research to allow definite conclusions to be reached about its effectiveness. Although there is evidence-based information on the pharmaceutical efficacy of lavender oil for the treatment of anxiety-related disturbances ¹⁸, its therapeutic significance was little appreciated for a long time, due to the lack of larger clinical trials, but also due to methodological problems in constituent identification and standardization of such complex multicomponent preparations. Studies of a lavender oil product that is taken orally (by mouth) have suggested it might be beneficial for anxiety, but because of limitations of the research, including the small size of the studies, no definite conclusions can be reached about its effectiveness. It’s also uncertain whether lavender oil used as aromatherapy is helpful for anxiety or other conditions.

One of the drawbacks in interpreting results of lavender oil treatments in human subjects is the lack of standardization in reporting dosage ¹⁰. In many studies, the precise dosage is reported as percent of oil in solvent for transdermal studies, or as percent of air in a closed chamber in olfactory studies. Furthermore, many studies report essential oil dosages in vague terms, while some lack a discussion of dosage altogether, which limits the implications of such studies ¹⁰. In addition, many studies often lack explicit reporting of the use of Good Clinical Practice or a suitable alternative standard, and authors should be encouraged to report adherence to clinical standards.

Human pharmacokinetic data are lacking for many lavender essential oil metabolites ¹⁹. However, one study in humans showed that transdermal applications of lavender oil resulted in the accumulation of monoterpenoids linalool and linalyl acetate in subjects’ blood samples ²⁰. Another common lavender monoterpenoid, 1,8-cineole, was shown to be rapidly absorbed by a human subject via inhalation, with detectible quantities within 5 minutes and peak quantities at ∼ 18 minutes of inhalation, followed by a 104.6-minute elimination half-life ²¹. In mice, a direct correlation was observed between inhalation of linalool and blood plasma linalool levels ²². Kohlert et al ²³ found that there is little risk in accumulation of these compounds as they likely have a short half-life (hours) in the human body and are quickly eliminated. It was concluded that most of lavender essential oil constituents are metabolized into carbon dioxide by the body or excreted in conjugated form by the kidneys, with a small fraction of inhaled terpenoids released from the lungs during exhalation ²³.

Figure 1. Lavender

Footnote: Portions of Lavandula angustifolia used: (A) corolla, (B) calyx, (C) leaf, (D) flowering top.

[Source ¹⁶ ]

Lavender oil benefits

Lavender essential oils have long been considered to be natural remedies for various ailments. Lavender essential oils possess potent calming and sedative effects, making them popular in aroma-therapeutic practices. There are few reports suggesting beneficial effects of inhalation of lavender oil on pain ²⁴, allergic airway inflammation of asthma ²⁵, anxiety disorder ²⁶, quality of sleep ²⁷ and dementia ²⁸. Besides these expected effects, the influence of topical application of lavender oil on wound healing ²⁹. Furthermore, some studies have shown that several constituents of lavender essential oil possess anticancer and antimutagenic properties. A multitude of clinical studies have quantified the potential of lavender essential oils in altering the behavior of patients suffering from dementia. Inhalation of lavender oils alone was shown to decrease agitation in dementia patients ³⁰. In combination with massage therapy, exposure to lavender aromatics was shown to significantly decrease excessive motor behavior in subjects diagnosed with dementia ³¹. Over the course of a four-week study, dementia patients showed significant decreases in cognitive impairment after dermal applications (e.g., skin cream) containing lavender oil ³². While these results support the hypothesis that absorption of lavender essential oils through the nose and skin may assist in promoting mental health, studies involving dementia patients often have many methodological constraints inherent in their experimental design which inhibit cogent interpretations of experimental conclusions. For instance, as Holmes and Ballard ³³ report that the signature fragrances of lavender often compromise double-blind studies, that expectation of lavender exposure influences test subjects’ responses to treatment, and that patients with severe dementia have likely lost an acute sense of smell. These limitations, in addition to other clinical phenomena such as the Hawthorne effect, are all factors that compromise many studies ³³. Lavender oil has been studied in special populations like newborn children, children with autistic behavior, psychogeriatric patients and hospitalized patients with positive outcomes. However the study populations are small and might be too diverse.

The purported aroma-therapeutic properties of lavender in healthy individuals have remained as the most controversial application of lavender essential oil. Proponents of lavender aromatherapy could cite studies like Dunn et al. ³⁴ which showed that the use of Lavandula angustifolia essential oil in aroma-therapeutic practices reduced anxiety in intensive care unit patients. Conversely, Howard and Hughes ³⁵ found that expectancy bias limits the objective study of the efficacy of lavender oils in aroma-therapeutic practices. Such studies often lack adequate placebos and objective measurement of physiological responses ³⁵. Researchers who study the therapeutic properties of lavender have recently used measurable physiological response parameters, such as electroencephalography (EEG) and coronary flow velocity reserves, in attempts to objectively quantify the effects of such treatments. Fernandez et al. ³⁶ showed that infants of depressed mothers had increased left frontal EEG asymmetry (a characteristic response to positive stimuli) after they were exposed to lavender odors. In another study using EEG, Diego et al. ³⁷ found that individuals who received lavender odors during aromatherapy showed increased alpha power in their EEG readings, which is a signature indicator of increased drowsiness. Shiina et al. ³⁸ showed that lavender in aromatherapy resulted in significant increases in test subjects’ coronary flow velocity reserves, in addition to a decrease in serum cortisol levels, which is indicative of improvement of coronary vessel function and decreased stress, respectively. Taken together, these reports suggest that while there are some potentially positive effects of lavender essential oils in such therapies, interpreting the results of such experiments is often problematic due to the many inherent methodological difficulties.

Table 1. Clinical experiments using lavender oil constituents

Test subjects	Number of volunteers	Compound	Dosage	Delivery	Method of assessment	Outcome	Reference
Elderly hospitalized for acute care	31	Lavender oil	“One drop” on “a pillow”	Olfactory	Observation	Enhanced sleep	39
Healthy infants	30	Lavender oil	Data not shown/aromatic bath oil	Olfactory, transdermal	Observation, salivary cortisol levels	Enhanced sleep, decreased stress	40
Healthy adults	31	Lavender oil	Aromatic exposure in 2 minute intervals	Olfactory	Polysomnographic recording	Enhanced sleep	41
Healthy adult dental patients	343	Lavender oil	5 Drops of oil in 10 mL diffused by candle	Olfactory	Modified dental anxiety scale, state trait anxiety inventory	Decreased anxiety	42
Healthy adults	12 and 24	R-(−)- and S-(+)-linalool	20 µL of various oil dilutions (between 0.003–30 % of air)	Olfactory	Survey, electroencephalographic activity	Increased favorable impressions	43
Healthy adults	24	R-(−)- and S-(+)-linalool	2.7 mg/m3 (R-(−) linalool) and 9.8 mg/m3 (S-(+)-linalool) of air in room	Olfactory	Autonomic and endocrine system parameters including salivary cortisol levels	Decreased anxiety	44
Dermatitis patients	1511	Linalool, myrcene, and caryophellene, and oxidation products	0.5–3.9 % of oxidized terpenoids, 20 % non-oxidized linalool in petrolatum	Transdermal patch test	Observation of skin irritation	Contact allergy to terpenoid oxidation products	45
Dermatitis patients	1511	Linalool, oxidized linalool	2–11 % Petrolatum (0.80–4.4 mg/cm2)	Transdermal patch test	Observation according to the International Contact Dermatitis Research Group guidelines	Contact allergy to oxidized linalool	46
Elderly hospitalized for dementia	21	Lavender oil	Data not shown	Olfactory, transdermal	Observation of motor behaviours	Decreased agitation	30
Elderly hospitalized for dementia	15	Lavender oil	2 % of air	Olfactory	Pittsburgh agitation scale	Decreased agitation	31
Elderly hospitalized for dementia	36	Lavender oil	3.5 % of aqueous solution	Transdermal	Mini-mental state examination	Increased cognition	32
Elderly hospitalized in ICU shortterm	122	Lavender oil	1.0 % of aqueous solution	Olfactory, transdermal	Behavioral observation, blood pressure, heart rate, breath rate	Increased sedation	34
Healthy adult females	96	Lavender oil	Cotton wood soaked with three drops of oil in a jar	Olfactory	Galvanic skin response	Increased relaxation	35
Healthy infants	45	Lavender oil	10 % v/v	Olfactory	Electroencephalographic activity	Increased positive affect	36
Healthy adults	40	Lavender oil	10 % v/v	Olfactory	Electroencephalographic activity	Increased positive mood, sedation	37
Healthy adult males	30	Lavender oil	“Four oil drops diluted with 20 mL hot water”	Olfactory	Coronary flow velocity reserve	Increased relaxation, coronary circulation	38
Adult male	1	Lavender oil	2 % in peanut oil	Transdermal	Gas chromatography analysis of blood	Rapid accumulation (peak 20 minutes) and expulsion (90 minutes) of linalool/linalyl acetate	20
Healthy adults	4	1,8-Cineole	Air passing over four mL for 20 minutes	Olfactory	Gas chromatography analysis of blood	Accumulation (peak ∼ 18 minutes) and expulsion half-life (104.6 minutes) of 1,8 cineole	21

Lavender oil for sleep

One of the most common uses of lavender oils is in the enhancement of sleep. It has been demonstrated that lavender aromatics can improve sleep in the elderly ³⁹ and infants ⁴⁰. Furthermore, exposure to lavender odors during sleep results in increased duration of deep slow-wave stage sleep ⁴¹. A therapeutic effect that is closely related to sleep is anxiety reduction, and many studies have evaluated the anxiolytic potential of lavender essential oil (see below). Tasev et al. ⁴⁷ related the sedative and relaxant effect of lavender oils with its effect on the central nervous system delivered via the olfactory system, and Tisserand ⁴⁸ suggested that Lavandula angustifolia odors have a similar action to benzodiazepines in effecting gamma-aminobutyric acid (GABA) neurotransmission. A study on dental patients who were exposed to lavender scents showed significantly reduced anticipatory anxiety ⁴². Many of the anxiolytic effects of lavender have been linked to the activity of linalool ⁴³ and Hoferl et al. ⁴⁴ demonstrated that linalool fragrances alone reversed the psychological parameters produced by stress.

A placebo-controlled, double-blind, crossover, randomized trial compared an essential oil (choice of lavender, peppermint, or chamomile) with a pleasant-smelling placebo (rose water) administered by diffuser overnight for 3 weeks in 50 adult patients with newly diagnosed acute myeloid leukemia (AML) who were hospitalized for administration of intensive chemotherapy ⁴⁹. Most patients reported poor quality sleep on the Pittsburgh Sleep Quality Index (PSQI) at baseline, with a mean score of 12.7. During the aromatherapy week, the mean PSQI score decreased to 9.7, but returned to a near-baseline score of 12.4 during the washout week ⁴⁹. The difference in mean PSQI score and mean placebo score was statistically significant. Aromatherapy also reduced the weekly average Edmonton Symptom Assessment Scale–Revised (ESASr) score by 6.06 points, which was statistically significant ⁴⁹. All subscales demonstrated a reduction in Edmonton Symptom Assessment Scale–Revised (ESASr) score with six symptom score changes showing a statistically significant benefit from aromatherapy:

• Tiredness
• Drowsiness
• Lack of appetite
• Depression
• Anxiety
• Well-being

Another randomized controlled trial examined the effects of aromatherapy massage and massage alone in 42 patients with advanced cancer over a 4-week period ⁵⁰. Patients were randomly assigned to receive weekly massages with or without aromatherapy; the treatment group (aromatherapy group) received massages with lavender essential oil (Lavandula angustifolia Miller) and an inert carrier oil, and the control group (massage group) received either an inert carrier oil alone or no intervention. No significant long-term benefits of aromatherapy or massage in pain control, quality of life, or anxiety were reported, but sleep scores (as measured by the Verran and Snyder-Halpern sleep scale) improved significantly in both groups. A statistically significant reduction in depression scores was also reported (as measured by the HADS) in the massage-only group ⁵⁰.

A randomized controlled trial of lavender, tea tree oil, or no-treatment control in adult patients who received outpatient chemotherapy with paclitaxel reported that trait anxiety and sleep quality improved with lavender, and that tea tree oil led to the highest change in sleep quality ⁵¹. However, changes in anxiety were observed only on the trait anxiety scores, not on the state anxiety scores, which may reflect short term changes associated with an aromatherapy intervention. In addition, there were no significant differences in sleep scores between the two aromatherapy groups and the controls, which the study was designed to detect ⁵¹.

Lavender oil for anxiety

Anxiety is one of the uprising psychiatric disorders of the last decades and lavender administration has been traditionally suggested as a possible treatment ⁵². Although some studies of lavender preparations for anxiety have shown some anxiolytic properties ⁵³, ⁵⁴, ⁷, ⁹, in general, many of these studies have been of poor methodological quality. This has led researchers to study the administration of lavender-based products to treat anxiety, but clear evidence to support its use in clinical practice lacks to date. In fact, the Committee on Herbal Medicinal Products of the European Medicines Agency (European equivalent to the FDA) adopted a final monograph on the essential oil obtained from Lavandula angustifolia Miller as a “traditional” herbal medicinal product with the following therapeutic indications: “relief of mild symptoms of mental stress and exhaustion, sleep aid” ⁵⁵. A 2019 systematic review and meta-analysis ⁵⁴ of a qualitative synthesis of data including 65 randomized controlled trials (7,993 participants) and 25 non-randomized studies (1,200 participants), and a quantitative synthesis of data involving 37 randomized controlled trials (3,964 participants) found that overall, oral administration of lavender essential oil was effective for anxiety, whereas for inhalation there was only an indication of an effect of reasonable size, due to the heterogeneity of available studies. Lavender essential oil administered through massage appeared to be effective, but available studies were not sufficient to determine whether the benefit was due to a specific effect of lavender ⁵⁴. A 2018 randomized controlled trial ⁵⁶ examined the effects of lavender oil aromatherapy on anxiety and sleep quality in 70 patients undergoing chemotherapy and found a significant improvement in anxiety in the lavender group. A 2017 meta-analysis of five studies ⁵⁷ involving 1,165 participants with anxiety diagnoses found lavender oil “Silexan” to be significantly superior to placebo in ameliorating anxiety symptoms independently of diagnosis. The study also found a tendency for greater clinical effect when analyzing separately generalized anxiety disorder patients in comparison with all other diagnosis ⁵⁷.

Lavender oil for skin and scars

Although previous studies suggested a beneficial effect of lavender oil on wound healing, the detailed mechanisms of the effect have not been fully elucidated ⁵⁸. A previous randomized control trial conducted on 120 women demonstrated that treatment with lavender oil significantly reduced pain after episiotomy and redness of incision sites as compared to control ⁵⁹. More recently, another randomized clinical trial for episiotomy demonstrated the similar results; significant reduction of redness, edema, ecchymosis, discharge and approximation (REEDA) score and visual analogue scale score for pain, as compared to control ⁵⁸. Both clinical trials suggest beneficial effect of lavender oil on wound healing. Also, it was reported that topical treatment with lavender oil on aphthous ulceration showed a significant ulcer size reduction as compared to control in both an animal experiment and a clinical study ⁶⁰. Moreover, there is a report evaluating the mechanism of effect of lavender oil on cutaneous wound healing in an animal experiment ²⁹. This paper demonstrated that wound closure progressed more rapidly with topical application of lavender oil as compared to the control, accompanied by increased expression of platelet-derived growth factor-A (PDGF-A) and epidermal growth factor (EGF), which are growth factors playing important roles in wound healing process such as tissue remodeling and re-epithelialization ²⁹. As PDGF-A is known to induce the secretion of matrix metalloproteinases (MMPs) from fibroblasts, this study suggests that lavender oil may accelerate wound closure through a rapid decrease in granulation tissue induced by PDGF and progression of re-epithelialization induced by EGF. This was the only study to refer and suggest molecular mechanisms of the effect of lavender oil on wound healing ⁶¹.

More recently another study demonstrated that topical application of lavender oil promoted collagen synthesis and differentiation of fibroblasts, accompanied by up-regulation of transforming growth factor-β (TGF-β) ⁶¹. These data suggest that lavender oil has the potential to promote wound healing in the early phase by acceleration of formation of granulation tissue, tissue remodeling by collagen replacement and wound contraction through up-regulation of TGF-β. The beneficial effect of lavender oil on wound healing may raise the possibility of new approaches as complementary treatment besides conventional therapy.

Lavender oil anticancer properties

Many of the studies regarding the anticancer properties of lavender oil constituents have been conducted in vitro (test tubes) using rat, bovine, human, and bacterial cell lines. Such investigations have shown that there are compounds found in trace amounts in lavender oils which have potentially significant anticancer activity ⁶². One such component, the monoterpenoid perillyl alcohol, has been investigated as a potential component of anticancer treatments ⁶³ and has been shown to inhibit angiogenic cell growth and division in vitro ⁶⁴. Subsequent studies into the chemoprevention potential of perillyl alcohol were undertaken in National Cancer Institute-sponsored phase I, II, and III trials for prostate, breast, and colon cancers. Other lavender oil constituents, such as 1,8-cineole ⁶⁵ and terpinen-4-ol ⁶⁶, also display anticancer properties in vitro by inducing apoptosis in tumor cells. Nerolidol, a sesquiterpene found in some lavender essential oils, is also believed to have anticancer potential, as rats fed diets laced with nerolidol showed significantly reduced adenomas and the number of tumors per rat ⁶⁷.

Lavender oil uses

Lavender is used to flavor foods and beverages and as a fragrance ingredient in soaps and cosmetics. Lavender is promoted as a dietary supplement for anxiety, depression, digestive symptoms, and other conditions. It is also promoted for topical use (application to the skin) and use in aromatherapy. Formulations containing lavender oil are used to treat inflammation in the mouth and throat and upper respiratory tract infections. In dermatology, the essential oil preparations help to relieve skin inflammation, psoriasis, or eczema ⁶⁸. Moreover, Lavender oil is a component of ointments used to treat wounds and burns. According to the literature, pure lavender oil was used to treat wounds after burns during World War I ⁶⁸. Due to its antibacterial properties, it causes the purulent states of the skin to subside and it improves the healing rate of the wounds. It should be noted, however, that the direct contact of essential oils with the skin can lead to irritation and allergic reactions ⁶⁹. In aromatherapy, lavender oil acts as a remedy with a potential sedative, sleeping, anxiolytic, and mood-enhancing effect ⁷⁰. In the cosmetic industry, lavender oil is used to produce bath salts, shampoos, skin tonic, cosmetic face masks, and for aromatizing naturally manufactured creams, balsam, or toilet waters ⁷¹. Lavender essential oil may also be used to preserve cosmetic products as an effective alternative for synthetic preservatives such as DMDM hydantoin, which acts as formaldehyde releaser ⁷². Although studies of a lavender oil product that is taken orally (by mouth) have suggested it might be beneficial for anxiety, stress and insomnia, but because of limitations of the research, including the small size of the studies (number of patients per study was too low to establish an effect), no definite conclusions can be reached about its effectiveness. It’s uncertain whether lavender oil used as aromatherapy is helpful for anxiety or other conditions. The European Medicines Agency (European equivalent to the FDA) concluded that, on the basis of its long-standing use, lavender oil can be used for the relief of mild symptoms of mental stress and exhaustion, and to aid sleep ⁵⁵. The European Medicines Agency conclusions on the use of medicines containing lavender oil are based on their ‘traditional use’. This means that, although there is insufficient evidence from clinical trials, the effectiveness of these herbal medicines is plausible and there is evidence that they have been used safely in this way for at least 30 years ⁵⁵. Lavender oil medicines should only be used in adults and children over the age of 12 years ⁵⁵.

Lavender oil side effects

There were no major concerns over the safety of lavender oil. Only few and mild side effects had been reported in studies with lavender oil, including very rare cases allergic reactions have been reported due to contact with lavender oil. While inhalation of lavender oil and linalool has been shown to impart positive psychopharmacological effects in humans, recent studies have indicated that linalool exposure results in allergenic responses. European legislators have become increasingly aware of the allergenic properties of many common essential oil constituents, and in 2003, the 7th Amendment to the European Cosmetic Directive required that cosmetic products containing any of 26 natural products, including linalool, be labeled as potentially allergenic ⁷³. While linalool itself may have limited allergenic properties, it can auto-oxidize upon air exposure into a hyperoxide species ⁷⁴ which can lead to contact allergy responses in mice ⁷⁵. In a study of 1511 dermatitis patients, auto-oxidized linalool was shown to induce allergenic responses in 1.3 % of those tested, with 1.1 % of patients sensitive to the linalool hyperoxide fraction, using patch tests ⁴⁵. A follow-up study, again involving 1511 dermatitis patients, showed that exposure to oxidized linalool at concentrations of > 6.0 % resulted in allergenic irritation in 5–7 % of test subjects ⁴⁶. Given the allergenic nature of some of the constituents of lavender essential oil and their breakdown products, as well as an increasing awareness of their presence in cosmetics and aromatherapeutic products, future research directed towards understanding the potential allergenic properties of commonly used monoterpenoids, and their breakdown products, is critical to ensure their safe usage.

Coulson and Khan ⁷⁶ described two case reports of mild facial ‘pillow’ dermatitis due to lavender oil allergy. Lavender oil does not seem to be a major sensitizing substance ⁷⁷. A case of allergic reactions have been reported in young students (20 years) ⁷⁸. When an aromatherapy student started massaging the feet of a client with a mixture of Lavandula, Origanum and Juniperus oil, her hands started to tingle and became swollen with redness to her arms and throat area. Shortness of breath occurred within 3 minutes of exposure. The symptoms were reversible upon cleaning the skin of lavender oil ⁷⁸. Another case of contact dermatitis was reported after rubbing the face with hands that were not cleaned from a massage gel, containing 5% benzylamine and lavender fragrance. Redness, followed by acute vesicular dermatitis developed ⁷⁹. Three cases of gynecomastia (swollen male breast tissue) in prepubertal boys were seen after topical application of products that contained lavender and tea tree oils ⁸⁰. The boys were between 4 and 10 years old. Exposure was as a ‘healing balm’ with lavender on the skin, styling gel containing lavender on hair and scalp and the use of lavender-scented soap. Gynecomastia resolved after discontinuing of the therapy. No re-application is mentioned. Nevertheless, causality was accepted between the topical use of the plant species mentioned and the gynecomastia ⁸⁰.

Lavender oil safety and side effects summary ⁸¹:

• Consumption of lavender in the amounts typically used in foods is likely to be safe. Short-term oral use in the amounts tested in studies of lavender for anxiety or other conditions may also be safe.
• The topical use of products containing lavender may cause allergic skin reactions in some people.
• Patients with open wounds, skin problems, high fever, severe infections and severe heart and circulation problems should not have full baths with lavender oil.
• A few cases of swelling of breast tissue (gynecomastia) have been reported in prepubertal boys who used topical products containing lavender. However, it’s unclear whether the lavender was responsible for the breast swelling, a condition that can have many causes.
• Little is known about whether it’s safe to use lavender during pregnancy or while breastfeeding.

Lavender oil toxicity

There is no major concern about human toxicity due to lavender essential oil or lavender flowers.

Acute toxicity

The acute oral LD50 of lavender oil in rats was found to be >5 g/kg body weight. Lethal Dose 50 (LD50) refers to an estimate of the amount of poison that, under control conditions, will be a lethal dose to 50% of a large number of test animals of a particular species. The value is expressed in milligrams of the substance being tested per kilogram of animal body weight (mg/kg). Other authors reported the oral LD50 in male rats as 6.2 ml/kg and in female rats as 5.0 ml/kg; the oral LD50 in male rats as 5 ml/kg and in female rats as 3 ml/kg. Furthermore an oral LD100 in male rats as > 7 ml/kg and in female rats as >6 ml/kg was reported. In an earlier study the acute oral LD50 of lavender oil was determined as 9 g/kg ⁸². Acute oral LD50 values in rodents have been reported as 2.2-3.9 g/kg b.w. for linalool and 5.0-48.8 g/kg for linalyl esters. The dermal LD50 of linalool in rabbits exceeded 5 g/kg. No adverse effects were reported from administration of linalool to female mice via a stomach tube at 94, 188 or 375 mg/kg/day for 5 days ⁸³.

Subacute toxicity

In a 90-day chronic dermal toxicity study in rats (20 per group), linalool was applied daily at 250, 1000 and 4000 mg/kg body weight. At 250 mg/kg no changes were observed except decreased activity and transient erythema; at 1000 mg/kg weight gain and activity were reduced; at the highest dose level, 11 animals died ⁸³. In a 90-day study, a 1:1 mixture of linalool and citronellol was added to the diet of rats to provide an intake of about 50 mg/kg/day of each substance. A slight retardation of body weight gain was observed in the males, but no effects were evident from histopathology, hematology, clinical chemistry or urine analysis at weeks 6 and 12 ⁸³.

Investigations on rats showed that the acute toxicity of essential oil of lavender, given orally in olive oil, was relatively low, while when given to mice pharmacological tests demonstrated that it had anxiolytic effects and prolonged sleep induced by intraperitoneal pentobarbital Na, though the latter effect was reduced after repeated p.o. administration. Impaired balance, piloerection and hypersalivation sometimes occurred. The authors concluded that, if its chronic toxicity is also low, lavender essential oil might be used instead of more active anxiolytics or tranquilizers for minor conditions ⁸⁴.

Undiluted lavender oil was not irritant when applied to the backs of hairless mice or pigs, but was slightly irritant on intact or abraded rabbit skin under occlusion for 24 hours ⁸⁵. Undiluted linalool caused slight to severe irritation to guinea pigs and rabbits when applied to open or occluded skin; no irritation was observed at 10% dilution. Undiluted linalyl acetate caused slight to severe irritation in guinea pigs and rabbits; at 5% dilution it was slightly irritating to rabbits ⁸³.

Mutagenicity

Linalool and linalyl acetate showed no mutagenic potential in the Ames mutagenicity test, with or without metabolic activation ⁸⁶. In the mouse lymphoma assay, no effects were seen with linalool in the absence of metabolic activation at concentrations up to 300 μg/ml; weak positive effects were observed in the presence of metabolic activation at doses of 200 μg/ml and above ⁸³.

Linalool did not induce chromosomal aberrations when incubated with Chinese hamster fibroblast cells at concentrations up to 0.25 mg/ml ⁸⁶ nor with Chinese hamster ovary cells at concentrations up to approximately 300 μg/ml ⁸³.

No induction of unscheduled DNA synthesis in rat hepatocytes was evident at concentrations of linalool up to 50 μg/ml or linalyl acetate up to 300 μg/ml ⁸³.

Evrandi et al. ⁸⁷ studied the antimutagenic activity of lavender essential oil in the bacterial reverse mutation assay using Salmonella typhimurium TA98 and TA100 strains and in Escherichia coli WP2 uvrA strain, with and without an extrinsic metabolic activation system, without pre-incubation. Lavender essential oil had no mutagenic activity on the two tested Salmonella strains or on E. coli, with or without the metabolic activation system ⁸⁷. Lavender oil exerted strong antimutagenic activity, reducing mutant colonies in the TA98 strain exposed to the direct mutagen 2-nitrofluorene. Antimutagenicity was concentration-dependent: the maximal concentration (0.80 mg/plate) reduced the number of histidine-independent revertant colonies by 66.4%. Lavender oil (0.80 mg/plate) also showed moderate antimutagenicity against the TA98 strain exposed to the direct mutagen 1-nitropyrene.

Rahimifard et al. ⁸⁸ investigated the mutagenic and antimutagenic activities of lavender (and cardamom) oil by reverse mutation assay in the same strains of Salmonella typhimurium with and without S9 (microsomal mutagenesis assay) for 7 dilutions. For lavender oil, the concentration per plate varied from 0.13 to 0.80 mg/plate. No mutagenicity was seen. On the contrary, there was a antimutagenic effect when 0.4 mg lavender essential oil per plate was applied.

References

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