PENNYROYAL TOXICITY - MEASUREMENT OF TOXIC METABOLITE LEVELS IN 2 CASES AND REVIEW OF THE LITERATURE

Background: Pennyroyal is a widely available herb that has long been u sed as an abortifacient despite its potentially lethal hepatotoxic eff ects. However, quantitative data for pennyroyal constituents and their metabolites in humans have not been previously reported. Objectives: To quantify pennyroyal metabolites in human overdose, to correlate the se findings with clinical variables, and to place these findings in th e context of previously reported cases of pennyroyal toxicity. Design: Clinical case series of pennyroyal ingestions; quantification of penn yroyal metabolites by gas chromatography and mass spectrometry; qualit ative detection of protein-bound adducts of the metabolites of pennyro yal constituents in human liver by Western blot assay; and review of t he literature based on a search of MEDLINE, Index Medicus, and the ref erence citations of all available publications. Results: We report fou r cases of pennyroyal ingestion. One patient died, one received N-acet ylcysteine, and two ingested minimally toxic amounts of pennyroyal and were not treated with N-acetylcysteine. In the fatal case, postmortem examination of a serum sample, which had been obtained 72 hours after the acute ingestion, identified 18 ng of pulegone per mL and 1 ng of menthofuran per mL. In a serum sample from the patient treated with N- acetylcysteine, which had been obtained 10 hours after ingestion, the menthofuran level was 40 ng/mL. Review of 18 previous case reports of pennyroyal ingestion documented moderate to severe toxicity in patient s who had been exposed to at least 10 mL of pennyroyal oil. Conclusion : Pennyroyal continues to be an herbal toxin of public health importan ce. Data on human metabolites may provide new insights into the toxic mechanisms and treatment of pennyroyal poisoning, including the potent ial role of N-acetylcysteine, Better understanding of the toxicity of pennyroyal may also lead to stricter control of and more restricted ac cess to the herb.