title: Thujone and thujone-containing herbal medicinal and botanical products: toxicological assessment.
abstract: Thujone, a major component of the notoriously famous absinthe drink, is neurotoxic, although the current view rather downgrades its risk to humans. In animal studies, thujone inhibits the gamma-aminobutyric acid A (GABA(A)) receptor causing excitation and convulsions in a dose-dependent manner, although there are uncertainties about the doses required in humans. Toxicity of thujone has been extensively studied. Neurotoxicity is the principal toxic outcome in acute and chronic studies. There is some equivocal evidence of carcinogenicity in rats. Metabolism of thujone has been elucidated both in vitro and in vivo in several species and in vitro in human liver preparations. CYP2A6 is the principal metabolic enzyme, followed by CYP3A4 and, to a lesser extent, CYP2B6. CYP-associated metabolism may give rise to some potential pharmacogenetic and metabolic interaction consequences. Although the data base for determining exposure limits is of variable usefulness, the best estimates for allowable daily intakes via herbal preparations and diet are of the order of 3-7 mg/day. There are still important gaps in the knowledge required to assess thujone toxicity, the most important ones being human dose-concentration-effect relationships including the elucidation of bioavailability, and the actual toxicological consequences of potential pharmacogenetic variations and environmental factors.
authors.affiliation: Department of Pharmacology and Toxicology, Institute of Biomedicine, University of Oulu, FIN-90014 Oulu, Finland. olavi.pelkonen@oulu.fi
authors.forename: Olavi
authors.initials: O
authors.lastname: Pelkonen
authors.forename: Khaled
authors.initials: K
authors.lastname: Abass
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Wiesner
mesh_terms: D000818:Animals; D000081008:Bicyclic Monoterpenes; D004305:Dose-Response Relationship, Drug; D058787:GABA-A Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D006801:Humans; D039821:Monoterpenes / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D020258:Neurotoxicity Syndromes / Q000209:etiology; D010597:Pharmacogenetics; D028321:Plant Preparations / Q000009:adverse effects* / Q000737:chemistry; D051381:Rats; D018570:Risk Assessment; D013045:Species Specificity; D023382:Toxicity Tests, Acute; D036401:Toxicity Tests, Chronic
chemical_list: D000081008:Bicyclic Monoterpenes; D058787:GABA-A Receptor Antagonists; D039821:Monoterpenes; D028321:Plant Preparations; C005790:beta-thujone