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Hirono et al investigated carcinogenicity by feeding young rats comfrey leaf at 8-33% of their diet or root at 1-8% of the diet for 179 to 600 days. All diet groups showed an increase in liver tumors over controls. Of the liver tumors detected, 96% were benign, but three animals developed hemangionendothelial sarcoma of the liver. All dosing levels in this study were significantly higher than expected human intake at therapeutic levels.
A second feeding study investigating the changes in activity of three liver enzymes found that 21 days of comfrey leaf at 10 and 30% of the diet increased the activity of aminopyrine-N-demethylase, but did not affect the activity of glutathione S-transferase or epoxide hydrolase. This result was also found when the diet included 30% alfalfa. The 30% comfrey group also displayed a significant reduction in weight gain. Liver histology was not done.
Culvenor et al  investigated the chronic liver effects of comfrey PAs administered as a single high dose or as repetitive lower doses in 2 week old nursing rats. This model was chosen for the increased susceptibility to the toxins; therefore, the results may not be indicative of effect on adults. The highest dose given caused peracute death (not liver related). Half this dose caused temporary distress but no observable histological liver damage when the animals were killed and examined 4 weeks later. Administration of 71mg/kg thrice weekly until death due to liver failure at 3 to 4 weeks induced only mild histological liver damage. Lower doses at 17.8 and 8.9 mg/kg thrice weekly for three weeks resulted in reduced liver function. The 17.8mg/kg dosing was continued for 9 weeks and megalocytosis was observed. The two lower dosing regimes may reflect levels that humans could encounter if ingesting comfrey that contains PAs at the extreme upper range of its natural occurrence (8000µg/g root or 2000µg/g leaf). A similar study was conducted by Yeong et al in young adult rats. The dose levels and frequency are summarized in Table 5. All rats showed liver damage that was dose dependent. The lowest dose 50mg/kg is still higher than therapeutic dosing for humans.
© 2004 Dorena Rode       Acknowledgment