ArticlePDF Available

Abstract and Figures

Menthol is a monocyclic terpene alcohol, which is present naturally in peppermint and can be synthesized artificially as well. Generally, it is considered as very safe and has wide usage in medicine and food. There are case reports of toxicity due to excessive consumption of menthol, but a fatal intoxication has never been reported in the medical literature. We present a case of fatal menthol intoxication in a worker, who accidently got exposed when he was working in a peppermint factory. Emergency physicians must keep in mind this extremely rare manifestation of menthol poisoning. All necessary precaution should be taken to reduce its intake or exposure, as it has no specific antidote. Early recognition and supportive treatment of this poisoning is the key for a successful outcome.
Content may be subject to copyright.
© 2016 International Journal of Applied and Basic Medical Research | Published by Wolters Kluwer - Medknow 137
A fatal case of menthol poisoning
Akshay Kumar, Upendra Baitha, Praveen Aggarwal, Nayer Jamshed
Department of Emergency Medicine, All India Institute of Medical Sciences, New Delhi, India
Menthol is a monocyclic terpene alcohol, which is present naturally in peppermint and can be synthesized articially as well.
Generally, it is considered as very safe and has wide usage in medicine and food. There are case reports of toxicity due to
excessive consumption of menthol, but a fatal intoxication has never been reported in the medical literature. We present a
case of fatal menthol intoxication in a worker, who accidently got exposed when he was working in a peppermint factory.
Emergency physicians must keep in mind this extremely rare manifestation of menthol poisoning. All necessary precaution
should be taken to reduce its intake or exposure, as it has no specic antidote. Early recognition and supportive treatment
of this poisoning is the key for a successful outcome.
Key words: Hematuria, menthol, peppermint, renal dysfunction, seizure
Submission: 01‑06‑2015 Accepted: 22‑11‑2015
Address for correspondence: Dr. Nayer Jamshed,
Department of Emergency Medicine, All India Institute of
Medical Sciences, Aurobindo Marg, New Delhi ‑ 110 029, India.
Menthol is a monocyclic terpene alcohol having 3
asymmetric carbon atoms in the cyclo‑hexane ring.
Naturally, it is present in peppermint but can also be
obtained synthetically. It is widely used as cooking oils,
candies, mouth fresheners, cigarette, and desserts. It
has also been effectively used as herbal and alternative
medicine in common cold, flu, and as a digestive aid. It has
a cooling, analgesic, and muscle‑relaxing effect through
transient receptor potential cation channel subfamily
M member 8, kappa, and voltage‑gated sodium channel
receptors, respectively.[1] Menthol is generally considered
safe and its toxic effect has rarely been reported in the
literature. We here report for the 1st time a case of fatal
menthol toxicity after acute exposure.
C R
A twenty‑one‑year‑old farmer living in a village of Uttar
Pradesh, India, was brought to our emergency department
in unconscious state. The history suggested that 4 days ago,
he was asked to clean a tank in a peppermint factory. He
got down inside the tank and soon after the inhalation of
toxic fumes, he was found in unconscious state. It took
an hour to bring him out from the tank. He remained
unconscious and then developed recurrent convulsions
and intermittent hematuria. The recurrent seizure activity
was controlled with intravenous midazolam followed by
intravenous levetiracetam. Supportive treatment such
as nasogastric lavage and intravenous uids were also
given. The patient was then referred to our Tertiary Care
Center, where we received the patient in the emergency
department with stable vitals, pulse 90/min, blood pressure
130/70 mm of Hg, respiratory rate 16/min, and Glasgow
coma scale (GCS) of E3V2M3. On the further history and
clinical examination, there was no upper or lower limb
weakness, or myoclonic jerks. Pupils were normal in size
Case Report
Access this article online
Quick Response Code:
10.4103/2229-516X.179015 How to cite this article: Kumar A, Baitha U, Aggarwal P, Jamshed N. A
fatal case of menthol poisoning. Int J App Basic Med Res 2016;6:137-9.
This is an open access article distributed under the terms of the Creative
Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows
others to remix, tweak, and build upon the work non-commercially, as long as the
author is credited and the new creations are licensed under the identical terms.
For reprints contact:
[Downloaded free from on Wednesday, September 28, 2016, IP:]
Kumar, et al.: Fatal menthol poisoning
International Journal of Applied and Basic Medical Research, Apr-Jun 2016, Vol 6, Issue 2
and were reactive to light, and there was no neck rigidity. The
patient had an increased muscle tone in all 4 limbs, and the
deep tendon reexes were exaggerated. There was no history
of substance abuse, smoking, alcohol intake, and medications.
The patient’s past medical history was also noncontributory.
His blood results showed hemoglobin 13.1 g/L, total leukocyte
count 10,400/µL, platelet 180,000/µL, blood urea 44 mg/dL,
serum creatinine 2.8 mg/dL, Na 146 mEq/L, K 3.9 mEq/L, blood
sugar 119 mg/dL, serum glutamic oxaloacetic transaminase
148 U/L, serum glutamic pyruvic transaminase 86U/L,
and bilirubin 1.1 mg/dL. Chest radiograph [Figure 1] and
electrocardiogram [Figure 2], cerebrospinal uid examination
were within normal limits. Urine microscopy showed several
red blood cells/high power eld. Urine culture was sterile.
Urine toxicology screen was positive for benzodiazepine,
probably secondary to intravenous midazolam, which was
given to control the seizures. His arterial blood gas showed
pH 7.49, PaO2 68 mmHg, PCO2 59.1 mmHg, and HCO3 30
mEq/L with carboxyhemoglobin level of 1.4%. Noncontrast
computed tomography brain showed loss of gray‑white matter
differentiation and evidence of cerebral edema [Figure 3].
The patient remained in a coma due to low GCS patient
was intubated to protect his airways. He was continued on
levetiracetam, but sodium valproate and midazolam infusion
was added to control the seizures. The patient remained
unconscious with poorly controlled recurrent seizures.
During his hospital stay, he developed ventilator associated
pneumonia, sepsis with shock, and acute renal dysfunction.
Broad spectrum antibiotics, intravenous uids, nor‑adrenaline,
and dopamine were added along with other supportive
measures. Unfortunately, the patient expired after 10 days
of hospitalization.
Peppermint oil is a herbal extract from essential oils
of peppermint leaves, which is widely grown in the
state of Uttar Pradesh in India. Menthol is the principal
ingredient of peppermint. The United States Food and Drug
Administration and the Flavoring Extract Manufacturer’s
Association generally consider menthol, a safe substance
and its toxicities are rarely been reported in the
literature. Ingestion of pure menthol can be dangerous
and its over dosage is possible with excess consumption
of menthol‑containing products. Orally, the lethal dose
has been estimated as 50–150 mg/kg.[2] Several adverse
effects of peppermint oil have been reported that include
dermatitis, cheilitis, mouth ulceration, abdominal pain,
nausea, vomiting, bradycardia, and tremor. Chronic exposure
to menthol ingestion has been reported in the USA and is
associated with cutaneous, gastrointestinal, and neurological
manifestations.[3] A high dose of peppermint oil ingestion
was also reported where the patient presented in transient
shock, hematuria, renal, and respiratory failure.[4] Renal
dysfunction is common probably because of interstitial
nephritis. An excessive amount of menthol is also reported
to have caused agitation, dizziness, ataxia, hallucination,
convulsion, and coma.[5] There is no specific antidote
Figure 1: Normal chest radiograph of the patient
Figure 2: Normal 12 lead electrocardiograph of the patient
Figure 3: Noncontrast computed tomography brain showed loss of gray-white
matter differentiation and evidence of cerebral edema
[Downloaded free from on Wednesday, September 28, 2016, IP:]
Kumar, et al.: Fatal menthol poisoning
International Journal of Applied and Basic Medical Research, Apr-Jun 2016, Vol 6, Issue 2 139
available for menthol poisoning. The management includes
gastrointestinal decontamination, oral activated charcoal
along with other supportive measures. Complications
such as seizure, respiratory failure, renal dysfunction, and
shock should be managed accordingly. Prognosis in menthol
poisoning depends on the dose of ingestion, duration
of exposure, and how quickly the medical treatment is
provided to the patient.
Above, we presented a rare case of hypoxic brain injury,
hematuria, and acute renal failure secondary to recurrent
seizure activity after acute and heavy exposure to menthol,
which ultimately proved fatal.
Menthol is widely used and is considered very safe.
Prolonged and heavy exposure of menthol can cause severe
intoxication and even death. All necessary precaution should
be taken to reduce its intake or exposure. Early recognition
and treatment of this poisoning is key for the successful
Financial support and sponsorship
Conicts of interest
There are no conicts of interest.
1. Gaudioso C, Hao J, Martin‑Eauclaire MF, Gabriac M, Delmas P. Menthol
pain relief through cumulative inactivation of voltage‑gated sodium
channels. Pain 2012;153:473‑84.
2. Gosselin RE, Hodge HC, Smith RP, Gleason MN. Clinical Toxicology of
Commercial Products. 4th ed. Baltimore: Williams and Wilkins; 1976.
p. II‑168.
3. Baibars M, Eng S, Shaheen K, Alraiyes AH, Alraies MC. Menthol toxicity:
An unusual cause of coma. Case Rep Med 2012;2012:187039.
4. Nath SS, Pandey C, Roy D. A near fatal case of high dose peppermint
oil ingestion‑lessons learnt. Indian J Anaesth 2012;56:582‑4.
5. Opdyke DL. Monographs on fragrance raw materials. Food Cosmet
Toxicol 1976;14:307‑38.
[Downloaded free from on Wednesday, September 28, 2016, IP:]
... These findings reveal the low potential of menthol to cause toxicity in humans. However, some cases of menthol poisoning has been reported due to the excessive consumption of menthol (50-150 mg/kg), which eventually led to coma and fatal intoxication [127,128]. In addition to menthol, some other MEO compounds, such as menthone, menthofuran, and pulegone also showed toxic effects in certain conditions, which can cause hepatotoxicity, nephrotoxicity, carcinogenicity, or mutagenicity in animal tests at high concentrations [124,129]. ...
Mint essential oil (MEO) is an outstanding antibacterial and antioxidant agent, that can be considered as a promising natural preservative, flavor, insecticide, coolant, and herbal medicine. However, the low solubility and volatility of MEO limits its extensive applications. In order to utilize MEO in different products, it is essential to develop treatments that can overcome these limitations. More recently, encapsulation technology has been developed as a promising method to overcome the shortcomings of MEO. In which, sensitive compounds such as essential oils (EOs) are entrapped in a carrier to produce micro or nanoparticles with increased stability against environmental conditions. Additionally, encapsulation of EOs makes transportation and handling easier, reduces their volatility, controls their release and consequently improves the efficiency of these bioactive compounds and extends their industrial applications. Several encapsulation techniques, such as emulsification, coacervation, ionic gelation, inclusion complexation, spray drying, electrospinning, melt dispersion, melt homogenization, and so on, have been emerged to improve the stability of MEO. These encapsulated MEOs can be also used in a variety of food, bioagricultural, pharmaceutical, and health care products with excellent performance. Therefore, this review aims to summarize the physicochemical and functional properties of MEO, recent advances in encapsulation techniques for MEO, and the application of micro/nanocapsulated MEO in different products.
... Levomenthol's stereoisomer, menthol, has also been reported to alleviate hyperglycemia and improve glucose homeostasis in STZ-Nicotinamide-induced rats by modulating the activity of the enzymes involved in glucose metabolism (Muruganathan et al., 2017). However, due to the toxicity associated with menthol (Kumar et al., 2016), we used the core structure of levomenthol-cyclohexane-as a scaffold for the identification of novel DPP4Is. Cyclohexane is a nonheterocyclic ring whose derivatives are explored in drug discovery to generate different compounds with diverse biological activities (Rodr ıguez et al., 2012;Shoaib et al., 2019). ...
Full-text available
Dipeptidyl peptidase-4 (DPP4) inhibitors are a potent therapeutic treatment for type 2 diabetes mellitus (T2DM). There is a family of compounds used as DPP4 inhibitors (DPP4Is) called gliptins. They bind tightly to DPP4 to form an inactive protein-ligand complex. However, there remains a need to identify novel DPP4Is that are more efficacious and safer due to the increasing prevalence of T2DM and the undesirable side effects of gliptins. To identify potential DPP4Is, we screened over 1800 novel compounds in a comparative study with gliptins. We performed dual-factor molecular docking to assess the binding affinity of the compounds to DPP4 and found four compounds with a higher binding affinity to DPP4 than currently used gliptins. The newly identified compounds interacted with the dyad glutamate (GLU205 and GLU206) and tyrosine (TYR662 and TYR666) residues in DPP4's active site. We performed molecular dynamics simulations to determine the stability of the protein-ligand complexes formed by the compounds and DPP4. Furthermore, we examined the toxicity and pharmacological profile of the compounds. The compounds are drug-like, easy to synthesize, and relatively less toxic than gliptins. Collectively, our results suggest that the novel compounds are potential DPP4Is and should be considered for further studies to develop novel antidiabetics.Communicated by Ramaswamy H. Sarma.
... One patient improved after hospitalization (Nath et al., 2012). However, the other patient experienced recurrent convulsions and intermittent hematuria and died after 10 days of persistent coma under hospital care (Kumar et al., 2016). Pharmacokinetic studies in humans have revealed that L-menthol (100-mg capsules) has an area under the curve of 1,214 μmol/L·min/L and a plasma half-life of 56 ± 8 min (range: 45-74 min). ...
Full-text available
Menthol, a widely used natural, active compound, has recently been shown to have anticancer activity. Moreover, it has been found to have a promising future in the treatment of various solid tumors. Therefore, using literature from PubMed, EMBASE, Web of Science, Ovid, ScienceDirect, and China National Knowledge Infrastructure databases, the present study reviewed the anticancer activity of menthol and the underlying mechanism. Menthol has a good safety profile and exerts its anticancer activity via multiple pathways and targets. As a result, it has gained popularity for significantly inhibiting different types of cancer cells by various mechanisms such as induction of apoptosis, cell cycle arrest, disruption of tubulin polymerization, and inhibition of tumor angiogenesis. Owing to the excellent anticancer activity menthol has demonstrated, further research is warranted for developing it as a novel anticancer agent. However, there are limitations and gaps in the current research on menthol, and its antitumor mechanism has not been completely elucidated. It is expected that more basic experimental and clinical studies focusing on menthol and its derivatives will eventually help in its clinical application as a novel anticancer agent.
... The mechanisms underpinning toxicity appear to be hepatotoxicity 101 or nephrotoxicity 76 . Toxicity may still prove fatal when exposure is indirect and of a limited duration i.e. inhalation of peppermint fumes for ~60 min 82 . It should be noted that serious or fatal cases used doses beyond the recognised upper tolerable limit and in environments 3 of 18 that may have also facilitated a negative outcome e.g. ...
Full-text available
Mint and to a lesser extent menthol have been used since antiquity for medicinal purposes. Key components of mint and menthol use such as composition and intake, safety and traditional uses are discussed prior to a review of clinical and human performance outcomes in the areas of digestive and respiratory health; antibacterial and anti-fungal properties, nocioception, migraine and headache and emerging evidence regarding COVID 19. Evidence suggests benefit for patients with irritable bowel syndrome and related digestive issues, with analgesic and respiratory effects also noted. Perceptual characteristics relating to thermal comfort and sensation, taste sensitivity and alertness are also considered; these effects are predominantly driven by stimulation of transient receptor potential melastatin 8 (TRPM8) activity resulting in sensations of cooling and freshness, with lesser influence on thirst. Finally, sport performance is considered as a domain that may further elucidate some of the aforementioned underpinning outcomes due to its systemic and dynamic nature, especially when performed in hot environmental conditions.
... The EOs obtained using the HD method were subjected to quantitative and qualitative analysis via GC-MS and the results are presented in Table 1. Menthol is generally recognized as safe (GRAS), and its toxic effects on humans have rarely been reported [12,13]. Among the analyzed Eos, only the oil from M. × piperita var. ...
Full-text available
Various mint taxa are widely cultivated and are used not only for medicinal purposes but also in cosmetic and industrial applications. The development of new varieties or cultivars of mint generates difficulties in their correct identification and safe use. Volatile organic compounds (VOCs) from the leaves of seven different taxa of the genus Mentha obtained by hydrodistillation (HD) and headspace solid-phase microextraction (HS-SPME) were analyzed using gas chromatography–mass spectrometry (GC-MS). Principal component analysis (PCA) was also performed. Comparative GC-MS analysis of the obtained extracts showed similarity in the major compounds. PCA data allowed the separation of two groups of chemotypes among the analyzed mints, characterized by the abundance of piperitenone oxide and carvone. Two out of seven analyzed taxa were not previously examined for VOC profile, one was examined only for patent application purposes, and six out of seven were investigated for the first time using the HS-SPME technique. The presented analysis provides new data on the abundance and qualitative characterization of VOCs in the studied mint plants and on the safety of their use, related to the possibility of the presence of potentially toxic components. HS-SPME is a valuable method to extend the characterization of the VOC profile obtained by hydrodistillation.
Full-text available
Nature offers us spices, which are a significant part of healthy and nutritious foods. The presence of abundant bioactive compounds in these spices makes them interesting from a scientific and health perspective. Extracts obtained from spice materials possess many health benefits and are rich sources of antioxidants, which suppress reactive oxygen species. Spice Bioactive Compounds: Properties, Applications, and Health Benefits collects such information together in one book, presenting all necessary features related to spices and their properties. Exploring the most recent research related to the extraction, isolation, encapsulation, identification, and characterization of bioactive compounds present in spices, this book also covers the health element of spices and its utilization as a treatment for various disorders. Key Features: Discusses about 14 different spices and their salient features Presents the novel technologies used in the extraction, isolation, and identification of bioactive compounds from spices Explores the utilization of spices for culinary use in food Industries such as the food and pharmaceutical industries have great interest in the use of bioactive compounds for the production of drugs and functional foods. Written by experts in their field, this book will be useful to anyone in either industry, as well as those who have an interest in the use of such bioactive compounds for the production of drugs and functional foods.
Full-text available
Neuropathic pain is defined as pain caused by a lesion or disease of the somatosensory nervous system and affects 7–10% of the worldwide population. Neuropathic pain can be induced by the use of drugs, including taxanes, thus triggering chemotherapy-induced neuropathic pain or as consequence of metabolic disorders such as diabetes. Neuropathic pain is most often a chronic condition, and can be associated with anxiety and depression; thus, it negatively impacts quality of life. Several pharmacologic approaches exist; however, they can lead numerous adverse effects. From this perspective, the use of nutraceuticals and diet supplements can be helpful in relieve neuropathic pain and related symptoms. In this review, we discuss how diet can radically affect peripheral neuropathy, and we focus on the potential approaches to ameliorate this condition, such as the use of numerous nutritional supplements or probiotics.
Menthol is a natural origin organic compound obtained from the peppermint plant whose effects at the embryonic development level are not completely known. In this work, the effects of an acute exposure (96 h) to menthol were evaluated in zebrafish embryos based on the calculated lethal concentration (LC50, 27.5 mg L⁻¹). The results showed a decreased hatching rate and heart rate as well as a notable increase in malformations and mortality. After menthol exposure, an increased production of reactive oxygen species (ROS) accompanied by an increase in the activity of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase and reductase) and a decrease in glutathione-S-transferase and protein carbonyls was detected. At the metabolic level, a decrease in ATPase activity and an increase in lactate dehydrogenase activity were perceived. Furthermore, mitochondrial membrane potential (ΔΨm) was increased after menthol exposure as well as the expression of Nrf2. At the behavioural level, shorter distance, speed, and percentage of active time were observed in menthol-treated larvae. In addition, an increase in the distance to the centre of the well and in the turn angle was observed supporting an anxiety-like behaviour induced by menthol exposure. Furthermore, there was a decrease in dopaminergic neurons and in the activity of the enzyme acetylcholinesterase (AChE) suggesting neurobehavioral impairment. Overall, while further studies are required, menthol compromised the development of zebrafish by mediating early development through the regulation of Nrf2 by mitochondrial ROS production with the consequent teratogenic outcomes.
Full-text available
Peppermint oil is easily available as a constituent of medicines. A near fatal case due to ingestion of toxic dose of oral peppermint oil is being reported. The patient came in a comatosed state and was in shock. She was managed with mechanical ventilation and ionotropes. Her vital parameters reached normal within 8 hours and became conscious by 24 hours. The side effects of peppermint oil are considered to be mild but this case report warns that ingestion of oral toxic doses of peppermint oil could be dangerous.
Full-text available
The US Food and Drug Administration (FDA) consider menthol an effective substance, which help in common cold symptoms and labeled to have low toxicity profile. Direct exposure to high menthol amount has been reported in animal; but no studies have been done to show the effect of menthol on long-term use in humans. Up to our knowledge we are reporting a rare case of chronic exposure to significant amount of menthol associated with cutaneous, gastrointestinal and neurological manifestations.
A compendium of 15 ingredients used in the production of soap, detergent, creams, lotions and perfume. Information includes synonyms, physical properties, occurrence, preparation, concentration in final product, status, biological data and references.
A number of allyl esters are reviewed to include their current status and concise biological data. Each monograph includes supporting references and the following compounds are discussed: allyl butyrate, allyl cinnamate, allyl cyclohexylacetate, allyl heptylate, allyl phenylacetate, calamus oil, methyl ethyl ketone, and vanillin.(Calesnick - Springfield, Pa.)
Menthol is a natural compound of plant origin known to produce cool sensation via the activation of the TRPM8 channel. It is also frequently part of topical analgesic drugs available in a pharmacy, although its mechanism of action is still unknown. Compelling evidence indicates that voltage-gated Na(+) channels are critical for experiencing pain sensation. We tested the hypothesis that menthol may block voltage-gated Na(+) channels in dorsal root ganglion (DRG) neurons. By use of a patch clamp, we evaluated the effects of menthol application on tetrodotoxin (TTX)-resistant Nav1.8 and Nav1.9 channel subtypes in DRG neurons, and on TTX-sensitive Na(+) channels in immortalized DRG neuron-derived F11 cells. The results indicate that menthol inhibits Na(+) channels in a concentration-, voltage-, and frequency-dependent manner. Menthol promoted fast and slow inactivation states, causing use-dependent depression of Na(+) channel activity. In current clamp recordings, menthol inhibited firing at high-frequency stimulation with minimal effects on normal neuronal activity. We found that low concentrations of menthol cause analgesia in mice, relieving pain produced by a Na(+) channel-targeting toxin. We conclude that menthol is a state-selective blocker of Nav1.8, Nav1.9, and TTX-sensitive Na(+) channels, indicating a role for Na(+) channel blockade in the efficacy of menthol as topical analgesic compound.
Clinical Toxicology of Commercial Products. 4 th ed. Baltimore: Williams and Wilkins
  • R E Gosselin
  • H C Hodge
  • R P Smith
  • M N Gleason
Gosselin RE, Hodge HC, Smith RP, Gleason MN. Clinical Toxicology of Commercial Products. 4 th ed. Baltimore: Williams and Wilkins; 1976. p. II-168.
Baltimore: Williams and Wilkins
  • R E Gosselin
  • H C Hodge
  • R P Smith
  • M N Gleason