**5.1 Skin irritation**

*Essential Oils - Bioactive Compounds, New Perspectives and Applications*

70 kg, difficult to reach in normal circumstances [12, 13].

systemic, could develop in specific circumstances [12].

**4. Acute intoxication with essential oils**

essential oils is possible [13].

supportive treatment was given [17].

**5. Dermatological toxicity of essential oils**

avoid confusion.

necessary precautions for their use [12].

Potential toxic effects of some essential oils and their components were tested on laboratory animals, usually rodents. Acute toxicity was evaluated by LD50 test (median lethal dose) in rats, which revealed that most essential oils have a LD50 of 1–20 g/kg, indicating a low toxicity. In humans, some essential oils like lemon oil have an LD50 of above 5 g/kg. Thus, the lethal dose would be 350 g for an adult of

A few notable exceptions are EOs from *Boldo* leaf, *Chenopodium*, *Mentha pulegium* (pennyroyal), *Satureja hortensis* (savory) and *Thuja* who presented an LD50 between 0.1 and 1 g/kg in rats, signaling a significant toxicity which recommends

Essential oils are susceptible to oxidative degradation, some of the resulting molecules like oxidation products of limonene being potential skin sensitizers [14]. Therefore, a proper storage of essential oils is necessary to conserve their effectiveness and reduce the risk of adverse reactions. Essential oils should be stored in a refrigerator or in a cool, dark place in tightly sealed recipients (brown bottles). Although most essential oils received the GRAS (generally recognized as safe) status, granted by Flavor and Extract Manufacturers Association (FEMA), it should be pointed out that they were evaluated as flavors with a very low concentration in the tested products. For a concentrated essential oil, certain toxic effects, local or

Acute intoxication (poisoning) with essential oils almost invariably results from an oral ingestion of large quantities of undiluted oil, usually accidental. The intoxicated person may present polypnea, convulsions, nausea and vomiting or even death in rare cases. Tea tree oil and the oils of wintergreen, clove, cinnamon and eucalyptus are responsible for most cases, although acute intoxication with other

In the US, 966 intoxication cases due to tea tree oil ingestion were recorded in 2006, most subjects being represented by children up to 6 years old [13]. In Australia, a recent study identified 1387 cases of essential oil poisoning between 2014 and 2018 [15]. The exposures were accidental or due to a confusion between liquid cough medicines and essential oils. In young children, oral ingestion of 0.6–5 mL of pure eucalyptus oil is sufficient to cause severe symptoms, a fatal case being reported after the ingestion of 30 mL of the oil by an 8-month-old infant [16]. In acute intoxication, infants and young children are particularly at risk due to their reduced body weight combined with

Essential oil poisoning was reported also in dogs and cats treated topically with tea tree oil used in large doses for dermatological conditions. The animals presented depression, weakness, motor incoordination and tremors but they recovered after

In order to reduce acute intoxication risk, it is recommended that essential oils are kept in child proof recipients, with droppers, separated from oral medication, to

In aromatherapy, essential oils, usually diluted in a carrier oil, are applied directly to the skin. The most important dermatological adverse reactions that may

occur include irritation, sensitization and photosensitization [18, 19].

the immaturity of enzymatic systems capable of metabolizing essential oils.

**44**

Cutaneous irritation is the biological response of the skin to a variety of external stimuli that can induce skin inflammation. The main pathological mechanisms of irritancy include skin barrier disruption, induction of a cytokine cascade and involvement of the oxidative stress network [20]. Primary irritation (contact dermatitis) occurs rapidly the first time an essential oil is used, manifesting as a red wheal or burn and is more likely to occur when essential oils contain large amounts of compounds like phenol, carvacrol and thymol (oregano, savory or thyme), phenolic ethers like eugenol and anethole (clove) or aromatic aldehydes like cinnamaldehyde (cinnamon) (**Figure 2**). Skin reaction is usually limited to the area where the essential oil is applied [21].

The plants whose essential oils are potentially irritant to the skin are listed in **Table 2**. Considering all these aspects, it is recommended that a patch test should be performed before using these oils.
