Terpene Toxicity

Updated: Apr 29, 2023
Author: John Said Kashani, DO; Chief Editor: Asim Tarabar, MD 

Overview

Practice Essentials

Terpenes are natural products derived from plants that have medicinal properties and biological activity. Terpenes may be found in cleaning products, rubefacients, aromatherapy, and various topical preparations. Terpenes may exist as hydrocarbons or have oxygen-containing compounds such as ketone or aldehyde groups (terpenoids).

The basic structure of terpenes is repeating isoprene units (C5H8)n, and they are grouped according to the number of repeating isoprene units. Monoterpenes contain 2 isoprene units; examples include cantharidin, menthol, pinene, and camphor.[1] Diterpenes contain 4 isoprene units; examples include phytol, vitamin A1,[2] and paclitaxel (Taxol).

The best-known terpene compounds are camphor oil and turpentine.[3] The antineoplastic agent paclitaxel is a terpene derived from yew plant bark.[4] The terpene thujone is found in a variety of plants, including arborvitae (Thuja), sage (Salvia officinalis ), and wormood (Artemisia absinthium). Diviner's sage (Salvia divinorum), which contains the hallucinogenic terpene salvinorin A, was originally used in shamanic ceremonies of the Mazatec Indians of Mexico but became popular internationally as a recreational drug, with attendant adverse effects.[5]

Absinthe is a liquor whose ingredients include the flowers and leaves of wormwood, which provide thujone and help give absinthe its green color. Absinthe was very popular in France from the 19th to the early 20th century, and it has been thought to be responsible for enhancing the creativity of many famous artists, including Edouard Manet, Vincent Van Gogh, and Henri de Toulouse-Lautrec.[6] Absinthe also gained a reputation as a dangerously addictive psychoactive drug, and was banned in many countries for most of the 20th century.[7]   However, chemical analysis of absinthe samples from the early 1900s found that thujone levels were so low that psychoactive effects from it were unlikely.[8]

Pathophysiology

Terpenes are local irritants and thus are capable of causing GI signs and symptoms. CNS manifestations may range from an altered mental status to seizures to coma. Aspiration is a particular concern and can result in long-term complications or fatality.

Absorption begins in the oral cavity and is rapid, as evidenced by the early onset of toxicity in significant ingestions. Terpenes are metabolized through cytochrome P450 and are excreted as conjugated metabolites by the kidney.

Etiology

Most terpene exposures are the result of an unintentional ingestion.

Some subcultures of society continue to use turpentine as an antihelminthic, purgative, and general elixir of good health. This practice may produce the potentially disastrous situation where the product is available and considered to be innocuous.

Exposure to topical products that contain camphor can cause serious toxicity in young chlidren.[9] Camphorated oil often is supplied in small bottles that closely resemble castor oil. The bottles may be kept on pharmacy or grocery store shelves next to each other so that an individual with vision impairment may easily choose the incorrect preparation.

A case report described camphor toxicity in a 35-year-old Cambodian man with diarrhea, vomiting, and altered mental status. He was described as having parallel and symmetric ecchymotic streaks on his back as a result of "coining". In this case, toxicity occurred by the application of camphor to the skin prior to coining. Toxicity occurred presumably by transcutaneous absorption.[10]

Epidemiology

According to the 2021 Annual Report of the American Association of Poison Control National Poison Data System, 3710 single exposures to disinfectants containing pine oil, 7572 single exposures to camphor, and 197 single exposures to turpentine were reported. Two deaths were reported among all of the above exposures.[11]

Males overrepresent cases associated with terpenes. Most exposures are in children and are unintentional.

Prognosis

Morbidity and mortality[12]  associated with exposure to terpenes is largely related to the degree of CNS depression and if aspiration occurs. Despite the toxicity of these agents, morbidity is extremely low. Mortality is rare. Most patients make full recoveries without sequelae. Aspiration of hydrocarbons may result in serious complications requiring long-term follow-up.

Patient Education

Preventive education is essential. Information regarding proper storage of chemicals is important.

All families of victims should be given the telephone number of the local or regional poison control center.

 

Presentation

History

Elicit the exact substance that the patient was exposed to, and the time of exposure. The concentration of terpene in the substance should be noted.[13]

Toxicity may first present as nausea and vomiting. In severe ingestions, seizures have been reported; they are often single and self-limited.[14, 15]

Physical Examination

Respiratory manifestations from aspiration may occur early. A careful examination of the chest and lungs is essential. Central nervous system depression may occur early after the ingestion of a concentrated product or large ingestion.

Seizures may occur early in exposure and tend to be single and self-limited.

Cardiac arrhythmias have been reported; however, vital signs are usually normal.

 

DDx

 

Workup

Laboratory Studies

Order a complete blood count: An elevated white count is nonspecific and does not necessarily imply a superinfection. Thrombocytopenia has been associated with terpene exposure.

Pulse oximetry may be a useful screening tool.

Pregnancy testing is warranted in women of childbearing age because terpenes may act as abortifacients.

Imaging Studies

Evidence of aspiration tends to occur early, usually within 6 hours. Asymptomatic pneumonitis usually is not clinically important; therefore, chest radiography in an asymptomatic patient is not recommended.

As in all patients with altered mental status, consider obtaining a CT scan of the head or MRI for CNS imaging.

 

Treatment

Prehospital Care

Induction of emesis is contraindicated because of the risk of aspiration. Terpenes are not adsorbed by charcoal. It is best to not administer anything by mouth. Careful attention should be paid to the patient's airway.

Treatment guidelines on management of camphor exposure are available from the American Association of Poison Control Centers.[16]

Emergency Department Care

If the patient is asymptomatic, no immediate intervention is warranted. Supportive measures may be all that is needed. Seizures should be managed with benzodiazepines. Gastric emptying is not recommended.

Consultations

Pulmonary consultation may be required if aspiration has occurred. Consider consultation with a poison control center or medical toxicologist. Psychiatric consultation is necessary in cases with deliberate exposure. Counseling may be indicated in exposures as a result of folk remedies.

Prevention

All household products, medications, and chemicals should be safely stored away in their original packages. Medications should never be taken or applied to the skin without first reading the label carefully.

Camphor is found in many essential oils.  It freely crosses the placenta and at high doses may cause damage to fetal organs including the liver, kidney and brain.  Women should avoid using products containing camphor during pregnancy and while breastfeeding.[17]

Long-Term Monitoring

Long-term follow-up care is necessary if pneumonitis develops.

 

Medication

Medication Summary

No specific antidote is indicated. Management is symptomatic and supportive. Benzodiazepines may be used if seizures occur. Gastric decontamination is typically not recommended unless another toxic substance is co-ingested.

Benzodiazepines

Class Summary

Prevent seizure recurrence and terminate clinical and electrical seizure activity.

Lorazepam (Ativan)

Useful to treat seizures and induce sedation. Sedative hypnotic with short onset of effects and relatively long half-life.

By increasing the action of GABA, a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation. Monitor carefully for respiratory depression.

Diazepam (Valium)

Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA. Third-line agent for agitation or seizures because of shorter duration of anticonvulsive effects and accumulation of active metabolites that may prolong sedation. Individualize dosage cautiously to avoid adverse effects. Monitor carefully for respiratory depression.

Midazolam (Versed)

Used as alternative in termination of refractory status epilepticus. Because water soluble, takes approximately 3 times longer than diazepam to peak EEG effects. Thus, clinician must wait 2-3 min to fully evaluate sedative effects before initiating procedure or repeating dose. Has twice the affinity for benzodiazepine receptors than diazepam. May be administered IM if unable to obtain vascular access.

Monitor carefully for respiratory depression.