**2. Primary routes of systemic absorption of essential oils**

Essential oils have a significant lipophilicity due to a high content of monoterpenes, being capable of easily passing through several biological barriers. Thus, a systemic absorption of specific chemical constituents is possible after oral, cutaneous or pulmonary administration of essential oils with beneficial therapeutic effects but also with toxicological implications [6].

After an oral administration of EOs, the systemic absorption of several molecules present in their chemical composition could be significant. A study in rats showed that after oral administration of radio-labeled trans-anethole, over 90% of the substance was absorbed from the digestive tract into the bloodstream, being subsequently metabolized and excreted in feces and urine [7]. Recently, a study from 2018 showed that an immediate release formulation with geraniol orally administered in Sprague-Dawley rats showed an absolute bioavailability of 92%, thus showing an increased systemic absorption [8]. In humans, the absorption of 1,8-cineole from the digestive tract was clearly demonstrated in a study which used enteric coated capsules with a mixture of three terpenoids: limonene, 1,8-cineole and α-pinene [9].

The contact of essential oils with the skin, frequently encountered in aromatherapy massage, could also lead to a systemic absorption of the chemical constituents, depending on the contact time, size of exposed skin surface and concentration of the compound. Essential oils and their volatile constituents can penetrate the skin barrier and facilitate the absorption of other topically applied drugs by inducing a conformational modification of intercellular proteins in the corneal layer and by increasing the drug partitioning [10]. Transdermal absorption was demonstrated for several monoterpenes like α-pinene, camphor or limonene, other structurally related compounds being also capable of passing the skin barrier and generating systemic effects [6].

The volatility of essential oils makes them ideal for pulmonary administration, suitable in the treatment of respiratory diseases. Nevertheless, a fraction of the inhaled compounds could be rapidly absorbed at alveolar level and through airway mucosa, with the apparition of plasmatic concentrations and possible systemic effects. The pulmonary absorption was confirmed for α-pinene, camphor and menthol, the rate of absorption depending on the nature and concentration of inhaled volatile substances and local physiological factors like breathing mechanics [6].
