The comparative toxicity of a reduced, crude comfrey (Symphytum officinale) alkaloid extract and the pure, comfrey-derived pyrrolizidine alkaloids, lycopsamine and intermedine in chicks (Gallus gallus domesticus)

Authors: BROWN, AMMON - Environmental Laboratory, Us Army Engineer Research And Development Center, Waterways Experiment St; Stegelmeier, Bryan; Colegate, Steven; Gardner, Dale; Panter, Kip; Knoppel, Edward; HALL, JEFFERY - Utah State University

Submitted to: Journal of Applied Toxicology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/2/2015
Publication Date: 5/1/2016
Publication URL: http://handle.nal.usda.gov/10113/62999
Citation: Brown, A.W., Stegelmeier, B.L., Colegate, S.M., Gardner, D.R., Panter, K.E., Knoppel, E.L., Hall, J.O. 2016. The comparative toxicity of a reduced, crude comfrey (Symphytum officinale) alkaloid extract and the pure, comfrey-derived pyrrolizidine alkaloids, lycopsamine and intermedine in chicks (Gallus gallus domesticus). Journal of Applied Toxicology. 36:716-725.

Interpretive Summary: Comfrey (Symphytum officinale), a commonly used herb, contains toxins that damage liver and lung and they can alter nucleic acid and can cause cancer. Consequently, regulatory agencies and international health organizations have recommended comfrey be used for external use only. However, in many locations comfrey continues to be ingested as a heral infusion or as a leafy vegetable. The objective of this work was to compare the toxicity of a crude, reduced comfrey alkaloid extract to purified lycopsamine and intermedine that are major constituents of S. officinale. Male, California White chicks were orally exposed to daily doses of 0.04, 0.13, 0.26, 0.52, and 1.04 mmol lycopsamine, intermedine or comfrey extract kg-1 bodyweight for 7 days. After another 10 days chicks were euthanized. Based on clinical, serum biochemical, and histopathological analysis the comfrey extract was more toxic than lycopsamine and intermedine. This work suggests there is a synergist action of the combined alkaloid or that other minor alkaloids are highly toxic. As comfrey toxicity has been based on the toxicity of its purified compounds, these estimates probably underestimate the potential toxicity of comfrey.

Technical Abstract: Comfrey (Symphytum officinale), a commonly used herb, contains dehydropyrrolizidine alkaloids (DHPAs) that, as a group of bioactive metabolites, are potentially hepatotoxic, pneumotoxic, genotoxic and carcinogenic. Consequently, regulatory agencies and international health organizations have recommended comfrey be used for external use only. However, in many locations comfrey continues to be ingested as a tisane or as a leafy vegetable. The objective of this work was to compare the toxicity of a crude, reduced comfrey alkaloid extract to purified lycopsamine and intermedine that are major constituents of S. officinale. Male, California White chicks were orally exposed to daily doses of 0.04, 0.13, 0.26, 0.52, and 1.04 mmol lycopsamine, intermedine or comfrey extract kg-1 bodyweight for 7 days. After another 10 days chicks were euthanized. Based on clinical, serum biochemical, and histopathological analysis the comfrey extract was more toxic than lycopsamine and intermedine. This work suggests a synergy and/or a more potent toxicity of other minor alkaloids in the comfrey extract that may result in safety recommendations, based on purified compounds, underestimating the potential toxicity of comfrey.