Safety of medicinal comfrey cream preparations (Symphytum officinale s.l.): The pyrrolizidine alkaloid lycopsamine is poorly absorbed through human skin

• Published in: Regulatory toxicology and pharmacology 2020-12, Vol.118, p.104784, Article 104784
• Main Authors: Kuchta, Kenny, Schmidt, Mathias
• Format: Article
• Language: English
• Subjects: Comfrey; Lycopsamine; Pyrrolizidine alkaloids; Symphytum × uplandicum Nyman; Transcutaneous absorption
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2020.104784

European Union guidelines indiscriminately discuss a permitted daily exposure (PDE) for pyrrolizidine alkaloids (PA) of up to 0.007 μg/kg body weight for oral and for topical exposure to herbal medicinal products. In this study, lycopsamine served as a model substance for measuring the extent of skin permeation of PAs following the application of a spiked comfrey cream (Symphytum officinale s.l.) to abdominal skin from human donors in Franz diffusion cells. PAs could be excluded in the non-spiked cream with a limit of detection of 8 μg/kg. Only small amounts of the applied quantity of lycopsamine had migrated through the skin sample into the receptor cell side of the diffusion cell after 24 h. In five of six diffusion cells, there was no detectable lycopsamine within the skin and only 0.6 ± 0.4% of the applied dose in the receptor fluid. The theoretical skin penetration of 4.9% of the applied quantity of lycopsamine largely resulted from the worst case approach of assuming the presence of at least a quantity corresponding to the limit of detection – the true penetration is probably considerably lower. Even with the worst-case calculation, the currently discussed guidelines on PA overestimate the risk related to topical preparations. [Display omitted] •Comfrey (Symphytum officinale s.l.) may contain potentially toxic pyrrolizidine alkaloids (PA).•Medicinal comfrey (Symphytum x uplandicum Nyman) does not contain PA (limit of detection 8 μg/kg).•The PA lycopsamine (typical for the gender of comfrey) is poorly absorbed through human skin.•Regulatory limits calculated for systemic exposure are not applicable to topical preparations.•The low bioavailability of lycopsamine contributes to the safety of comfrey herb cream.