Saturday, 26 September 2015

Risk assessment on the use of herbal medicinal products containing pyrrolizidine alkaloids

Risk assessment on the use of herbal medicinal products containing pyrrolizidine alkaloids


We compare the regulations of PA exposure for foodstuff and herbals.
We compare the PA burden originating from food and herbals.
We offer a possibility to calculate the PA exposure by the administration of herbals.


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.


  • pyrrolizidine alkaloids; 
  • risk assessment; 
  • herbals; 
  • margin of exposure; 
  • herbal medicinal products; 
  • safety; 
  • carcinogenicity; 
  • mutagenicity


  • ANZFA, The Australia New Zealand Food Authority; 
  • BfR, Federal Institute for Risk Assessment; 
  • BMDL10, benchmark dose lower confidence limit 10%; 
  • COC, Committee on Carcinogenicity of Chemicals in Food, Consumer Products and the Environment;
  • COT, Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment; 
  • EFSA, European Food Safety Authority; 
  • FDA, U.S. Food and Drug Administration; 
  • IARC, International Agency for Research on Cancer; 
  • MOE, Margin of Exposure; 
  • NOAEL, No-observed-adverse-effect-level; 
  • PA, pyrrolizidine alkaloids; 
  • p.o.,oral; 
  • SOS, sinusoidal obstruction syndrome; 
  • VOD, veno-occlusive disease; 
  • WHO,World Health Organization

Corresponding author. ACA-pharma concept GmbH, Deutscher Platz 5, 04103 Leipzig, Germany. Tel.: +49 341 33 733 360; fax: +49 341 33 733 369.