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

Authors :
Mathias Schmidt
Kenny Kuchta
Source :
Regulatory toxicology and pharmacology : RTP. 118
Publication Year :
2020

Abstract

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.

Details

ISSN :
10960295
Volume :
118
Database :
OpenAIRE
Journal :
Regulatory toxicology and pharmacology : RTP
Accession number :
edsair.doi.dedup.....771ce03bb1f72f3a8315a0221a601a4f