title: Risk assessment on the use of herbal medicinal products containing pyrrolizidine alkaloids.
abstract: Pyrrolizidine alkaloids (PA) are common plantal toxins directed against insect herbivores. Unsaturated PAs are known to be hepatotoxic. Many of the PAs are in addition mutagenic and some may possibly be carcinogenic for humans. The risk of an exposure to PAs associated with their occurrence in herbal medicinal products and in foodstuff is under current discussion. The present risk assessment for herbal medicinal products containing PAs is based on a margin of safety derivation for foodstuff indicating that a life-long exposure to maximally 0.007 μg/kg bw/day is not expected to be associated with safety concerns. This approach offers a possibility to estimate the potential risk of PA-containing herbal medicinal products irrespective of the route of administration. It assumes PA levels in the final herbal medicinal product below 0.01 ppm and considers for dermal administration a 100% skin penetration of the PAs reflecting a worst-case scenario. As a result, the calculated margins of safety show a potential exposure using herbal medicinal products 70-, 45.5-, and 19.3-fold lower on a one-day base and 608-, 396-, and 168- fold lower on a one-year base for adults, children aged 12 years, and children aged 4 years, respectively, than the thresholds considered acceptable for foodstuff.
authors.affiliation: ACA-pharma Concept GmbH, Deutscher Platz 5, 04103, Leipzig, Germany; Rudolf-Boehm-Institute of Pharmacology and Toxicology and PGS Toxikologie und Umweltschutz, University of Leipzig, Leipzig, Germany. Electronic address: aca24@aca-pharma.de.
authors.forename: Clemens
authors.initials: C
authors.lastname: Allgaier
authors.affiliation: ACA-pharma Concept GmbH, Deutscher Platz 5, 04103, Leipzig, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Franz
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D004781:Environmental Exposure / Q000009:adverse effects / Q000592:standards; D005260:Female; D005502:Food / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008517:Phytotherapy / Q000009:adverse effects* / Q000592:standards; D010946:Plants, Medicinal / Q000009:adverse effects*; D011763:Pyrrolizidine Alkaloids / Q000009:adverse effects*; D018570:Risk Assessment / Q000379:methods
chemical_list: D011763:Pyrrolizidine Alkaloids
keywords: Carcinogenicity; Herbal medicinal products; Herbals; Margin of exposure; Mutagenicity; Pyrrolizidine alkaloids; Risk assessment; Safety