Risk assessment of thujone in foods and medicines containing sage and wormwood--evidence for a need of regulatory changes?
Thujone is a natural substance found in plants commonly used in foods and beverages, such as wormwood and sage, as well as in herbal medicines. The current limits for thujone in food products are based on short-term animal studies from the 1960s, which provided evidence for a threshold-based mechanism, yet only allowed for the derivation of preliminary values for acceptable daily intakes (ADI) based on the no-observed effect level (NOEL). While the 2008 European Union Regulation on flavourings deregulated the food use of thujone, the European Medicines Agency introduced limits for the substance in 2009. The present study re-evaluates the available evidence using the benchmark dose (BMD) approach instead of NOEL, and for the first time includes data from a long-term chronic toxicity study of the National Toxicology Program (NTP). The NTP data provide similar results to the previous short-term studies. Using dose-response modelling, a BMD lower confidence limit for a benchmark response of 10% (BMDL10) was calculated as being 11 mg/kg bw/day for clonic seizures in male rats. Based on this, we propose an ADI of 0.11 mg/kg bw/day, which would not be reachable even for consumers of high-levels of thujone-containing foods (including absinthe). While fewer data are available concerning thujone exposure from medicines, we estimate that between 2 and 20 cups of wormwood or sage tea would be required to reach this ADI, and view that the short-term medicinal use of these herbs can also be regarded as safe. In conclusion, the evidence does not point to any need for changes in regulations but confirms the current limits as sufficiently protective for consumers.
Lachenmeier
Dirk W
DW
Chemisches und Veterinäruntersuchungsamt (CVUA) Karlsruhe, Weißenburger Strasse 3, D-76187 Karlsruhe, Germany. Lachenmeier@web.de
Uebelacker
Michael
M
D018646:Absinthe / Q000633:toxicity; D000818:Animals; D019306:Artemisia / Q000633:toxicity*; D000081008:Bicyclic Monoterpenes; D003198:Computer Simulation; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004335:Drug and Narcotic Control; D005062:European Union; D005260:Female; D005502:Food / Q000633:toxicity; D008297:Male; D039821:Monoterpenes / Q000008:administration & dosage / Q000633:toxicity*; D019055:No-Observed-Adverse-Effect Level; D051381:Rats; D018570:Risk Assessment / Q000379:methods; D027543:Salvia officinalis / Q000633:toxicity*; D012640:Seizures / Q000139:chemically induced*; D018675:Toxicity Tests / Q000592:standards*
D000081008:Bicyclic Monoterpenes; D039821:Monoterpenes; C005790:beta-thujone