Toxicity of Selected Monoterpenes and Essential Oils Rich in These Compounds

Abstract

Monoterpenes make up the largest group of plant secondary metabolites. They can be found in numerous plants, among others, the Lamiaceae family. The compounds demonstrate antioxidative, antibacterial, sedative and anti-inflammatory activity, hence, they are often employed in medicine and pharmaceuticals. Additionally, their fragrant character is often made use of, notably in the food and cosmetic industries. Nevertheless, long-lasting studies have revealed their toxic properties. This fact has led to a detailed analysis of the compounds towards their side effects on the human organism. Although most are safe for human food and medical applications, there are monoterpene compounds that, in certain amounts or under particular circumstances (e.g., pregnancy), can cause serious disorders. The presented review characterises in vitro and in vivo, the toxic character of selected monoterpenes (α-terpinene, camphor, citral, limonene, pulegone, thujone), as well as that of their original plant sources and their essential oils. The selected monoterpenes reveal various toxic properties among which are embryotoxic, neurotoxic, allergenic and genotoxic. It is also known that the essential oils of popular plants can also reveal toxic characteristics that many people are unaware of.

Keywords: abortifacient; genotoxicity; monoterpenes; neurotoxicity; plant secondary metabolites; teratogenicity; toxicity.

Figure 1

Monoterpene synthesis via IPP and DMAPP pathway based on the MEP pathway of IPP and DMAPP synthesis. The MEP pathway is built-upon pyruvate and glyceraldehyde 3-phosphate (G3P) condensation by thiamine diphosphate enzyme 1-deoxy-ᴅ-xylulose-5-phosphate synthase (DXS) to form 1-deoxy-d-xylulose 5-phosphate (DXP). The latter is reduced by 1-deoxy-ᴅ-xylulose-5-phosphate reductoisomerase (DXR) to form MEP. In the next step, MEP is catalysed by 2-C-methyl-ᴅ-erythritol 4-phosphate cytidylyltransferase (MCT) to generate 4-(cytidine 5′-diphospho)-2-C-methyl-d-erythritol (CD-ME). After phosphorylation, cyclisation and ring opening, CD-ME is converted into 1-hydroxy-2-methyl-2-butenyl 4-diphosphate (HMBPP) under the catalysis of 4-diphosphocytidyl-2-C-methyl-d-erythritol kinase (CMK), 2-C-methyl-d-erythritol 2,4-cyclodiphosphate synthase (MDS) and 4-hydroxy-3-methylbut-2-enyldiphosphate synthase (HDS), respectively. The IPP and DMAPP derived from the MEP pathway are directly generated from HMBPP by 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (HDR)—which is different from the MVA pathway [9].

Figure 2

Structures of selected terpenes and their derivatives.

Figure 3

Metabolism of pulegone. The most important metabolites are emboldened.