Pennyroyal oil has caused deaths in adults and children; even tea has caused serious poisonings in children.
[LFODKM ] Letter Key
Latin Name
(Hedeoma pulegioides L. Pers.); European pennyroyal (Mentha pulegium L.)
Family
Labiatae
Other Common Names
Tick-weed, stinking balm
Description
Part used: leaf
Known Active Constituents
Pulegone and other ketones (L-menthone, D-isomenthone, piperitone) and terpene hydrocarbons. Pulegone levels are highest in the spring (55 mg/g foliage and 3.8 mg/g stem) (1).
Mechanism/Pharmacokinetics
- Pulegone is oxidized by the cytochrome P450 system to the hepatotoxic metabolite menthofuran and possibly other hepatotoxic metabolites. Menthofuran damages hepatic and pulmonary cells; pulegone augments the damage by depleting glutathione (which conjugates many toxins) and thus allowing the buildup of menthofuran (2). Reactive metabolites formed by pulegone apparently form covalent adducts with glutathione (3).
- Menthofuran is metabolized to (R)-2-hydroxymenthofuran. Glutathione-S-transferase catalyzes the tautomerization of 2-hydroxymenthofuran to mintlactone and isomintlactone (4).
- In rats, 150 mg/kg intraperitoneally resulted in peak pulegone levels of 13.5 ± 3.0 µg/mL at 15 minutes with a terminal half-life of 1 hour. Menthofuran levels also peaked at 1 hour at 7.0 ± 1.2 µg/mL and had a terminal half-life of about 2 hours (3). In rats, 300 mg/kg i.p. caused hepatocellular damage with necrosis; menthofuran serum level of 250 ng/mL is hepatotoxic in rats (2).
- Little is available on pharmacokinetics in humans. Serum samples collected 26 hours after a death from pennyroyal poisoning revealed pulegone levels of 18 ng/mL and menthofuran levels of 1 ng /mL, but it is unknown whether cellular shifts may have occurred postmortem. In the case of a 20-month-old toddler who had ingested an unknown amount of pennyroyal oil, 10-hour menthofuran serum levels were 40 ng/mL; no pulegone was detected (3). An 8-week-old Hispanic boy given a mint tea containing pulegone had a menthofuran level of 10 ng/mL 3 days after admission; after 24 hours of N-acetylcysteine (NAC) the level decreased to 2 ng/mL (2). A 6-month-old Hispanic boy given a pulegone-containing mint tea (2) had pulegone levels of 25 ng/mL and menthofuran levels of 41 ng/mL.
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[CAO ] Letter Key
Clinical Trials
No clinical trials identified.
Animal/In Vitro
No information identified.
Other Claimed Benefits/Actions
- Abortifacient
- Fibroids
- Cramps
- Colds
- Liver and gallbladder ailments
- Gout
- Fainting
- Flatulence
- Insect repellant (topical)
[Outline]
[ADPT ] Letter Key
Adverse Reactions
- Pennyroyal oil poisoning
- All severe poisonings in adults have involved pennyroyal oil; however, in infants, fatalities have been reported even with pennyroyal tea. A review identified four fatal cases of pennyroyal oil poisoning in adults reported since 1897 (3). In the most recent case, reported in 1996, a 24-year-old woman with an ectopic pregnancy tried to induce abortion with a pennyroyal alcohol extract and black cohosh extract for 2 weeks, increasing her intake of both herbs shortly before developing abdominal cramps, chills, vomiting and syncope, sustaining a cardiopulmonary arrest 7.5 hours after ingestion. She was resuscitated but developed hemodynamic shock and disseminated intravascular coagulation; an exploratory laparotomy revealed a hemorrhagic ectopic pregnancy with evidence of superinfection; she died after life support was withdrawn 46 hours after ingestion. Autopsy revealed centrilobular hepatic necrosis and degenerative changes in the proximal tubules of the kidney. Bleeding from the ectopic pregnancy and possible sepsis may well have contributed to this death. A letter in response to this report noted that septic shock could also cause hepatic necrosis (5).
- A fatal case of pennyroyal oil poisoning was reported in 1978 in an 18-year-old woman who ingested up to 30 mL pennyroyal oil (about 24 g); she experienced abdominal cramps, nausea, hematemesis, and altered mental status and later developed kidney failure, hepatic necrosis, and disseminated intravascular coagulation. Autopsy showed enlarged pale kidneys and centrilobular hepatic necrosis. In 1955, a case was reported of a 24-year-old woman who ingested two bottles of pennyroyal oil (unknown volume and preparation); an abortion resulted but she later developed malaise, nausea, vomiting, diarrhea, abdominal pain, oliguria, and acute renal failure; she died 14 days after ingestion. Proximal tubule degeneration and slight hepatic centrilobular cloudy swelling were noted. In a case report from 1897, a 23 year old ingested 15 mL pennyroyal oil, developed vomiting and gastritis, and died 8 days after ingestion (3).
- Nine other case reports of moderate to severe outcomes (all involving coma or seizures) were identified. Eight involved pennyroyal oil; this includes three cases involving essence of pennyroyal, which is pennyroyal oil in alcohol (1:7). One case involved pennyroyal tablets. All recovered without sequelae.
- Not all ingestions of pennyroyal oil cause serious adverse effects; for example, a 22 year old ingested 10 mL oil and experienced only an hour of dizziness. A 22-month-old 10-kg girl ingested an unknown amount (up to 20 mL) of pennyroyal oil; gastric lavage was done within 30 minutes of ingestion and she was treated with activated charcoal with sorbitol, and oral N-acetylcysteine (every 4 hours for 17 doses); she experienced no sequelae.
- Pennyroyal tea poisoning
- Pennyroyal tea has not resulted in severe poisonings in adults, but babies are more susceptible. A fatal case of poisoning from a pulegone-containing plant (the report does not specify pennyroyal but other plants contain less pulegone) in an infant was reported in 1996 (2). An 8-week-old Hispanic boy was given 120 mL of a homegrown mint tea 14 hours before being admitted to the hospital with respiratory distress, an elevated white blood cell count, metabolic acidosis, hepatitis, and abnormal coagulation studies. Cytomegalovirus infection was documented and was thought to be a contributing factor. Although treated with N-acetylcysteine, multiple organ failure developed and he died 4 days after admission. Autopsy revealed hepatocellular necrosis, edematous hemorrhagic kidneys, bilateral lung consolidation, and diffuse cerebral edema. No pulegone was detected in samples, but levels of menthofuran were 10 ng/mL on day 3 and 2 ng/mL on day 4 (after treatment with NAC).
- Another 6-month-old Hispanic boy had been given 90 mL homegrown mint tea (from the same unspecified plant species as the previous case) three times weekly for 3 months; he was admitted with seizures, fever, cyanosis, elevated white blood cell count, metabolic acidosis, elevated liver function tests, and coagulopathy (2). Serum levels of 25 ng/mL pulegone and 41 ng/mL menthofuran were documented. Increased intracranial pressure resulting from a sinus hemorrhage was diagnosed on the fourth day. After 2 months the baby was discharged with elevated liver function tests nonspecific myopathic changes, and mild carnitine deficiency (2). Neither infant poisoned by pennyroyal tea had viral hepatitis; it is possible that another concurrent viral infection contributed to these adverse outcomes.
- A woman who drank pennyroyal tea to induce menses (1 tsp herb in 1 cup water) reported dizziness, weakness, and a feeling of impending syncope. She was seen in the emergency department within an hour and her symptoms improved spontaneously; she remained asymptomatic 24 hours later. No other details are given.
- A 24-year-old woman drank two cups of pennyroyal tea (2 tsp herb in 1 pint hot water steeped for 5 to 10 minutes) and then prepared another cup 13 hours later, steeping it for 20 minutes. She developed nausea and abdominal cramping; the cramping persisted for 4 days after which menses began. Assuming that this patient was pregnant, this would be a successful abortion.
- Symptoms of severe poisoning
- Fulminant hepatic failure, acute renal failure, coagulopathy, metabolic acidosis, gastrointestinal hemorrhage, pulmonary congestion with consolidation, mental status changes, and seizures. Hypoglycemia in two infants has also been reported (2).
Drug Interactions
None reported. However, any substance with hepatotoxic effects would be expected to amplify toxic effects of pennyroyal.
Pregnancy/Lactation
Pennyroyal is an abortifacient but is too dangerous to use for this purpose.
Animal Toxicity
- In rats given pulegone by gavage, doses of 80 and 160 mg/kg body weight caused atonia, decreased creatinine, lower terminal body weight, and histopathologic changes in the liver and white matter of the cerebellum.
- Topical application of pennyroyal oil to a dog in an effort to repel fleas resulted in vomiting 2 hours later and death within 48 hours (6).
[Outline]
The use of pennyroyal in any form is not recommended. Typical doses are given for information only.
Infusion: made with 1 to 4 g t.i.d.
Liquid extract (1:1, 45% ethanol): 1 to 4 mL t.i.d.
Treatment of Poisoning
Gastric lavage should be done and activated charcoal administered. Pennyroyal oil is rapidly absorbed; ipecac-induced emesis is, thus, less desirable, especially because it increases the risk of aspiration pneumonia.
Ingestions of more than 10 mL should also be treated with NAC (140 mg/kg, then 70 mg/kg every four hours for 24 hours) (see questions and answers). Hepatic function, renal function, and coagulation parameters should be monitored in all patients (3).
Because NAC increases glutathione levels and prevents hepatotoxic effects of acetaminophen (the toxic intermediate of which is detoxified by glutathione), NAC is used empirically to treat pennyroyal poisoning. The half-life of pennyroyal metabolites is only a few hours in animals, and it is possible that NAC is only helpful in the first hours after pennyroyal poisoning (3). NAC does not prevent pulegone-induced hepatocellular damage in animals, but the treatment appears to be helpful in humans and should be used (2).
Q: Why is the effect of pennyroyal oil so variable?
A: Individual susceptibility clearly varies, and a possible factor is individual differences in levels of cytochrome P (CYP) 450 isoenzymes. Inhibitors of CYP 450 lessen pulegone-induced hepatic damage (3). CYP2E, 1CYP1A2, and CYP2C19 oxidize pulegone to menthofuran (7).