eMedicine Specialties > Emergency Medicine > Toxicology

Toxicity, Terpene

John Said Kashani, DO, Assistant Medical Director of the New Jersey Poison ad Information Education System; Assistant Professor, Department of Preventive Medicine and Community Health, Assistant Professor, Department of Pediatrics, New Jersey Medical School, University of Medicine and Dentistry of New Jersey
Steven Marcus, MD, Professor, Department of Preventive Medicine and Community Health, Associate Professor, Department of Pediatrics, New Jersey Medical School, University of Medicine and Dentistry of New Jersey; Executive and Medical Director, New Jersey Poison Information and Education System; Consulting Staff, Departments of Pediatrics and Internal Medicine, University Hospital, University of Medicine and Dentistry of New Jersey; Consulting Staff, Department of Pediatrics, Newark Beth Israel Medical Center

Updated: Nov 10, 2009

Introduction

Background

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. Diterpenes contain 4 isoprene units; examples include phytol, vitamin A1¹ , and paclitaxel (Taxol).

The best-known compounds in this group are camphor oil and turpentine. The antineoplastic agent paclitaxel is a terpene derived from yew plant bark. An oil derived from the Saliva officinalis tree, thujone, has recently become popular because of its hallucinogenic qualities, and it is quickly becoming a drug of abuse.²

Absinthe, a green liquor containing thujone, 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.

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 fatalities and long-term complications.

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.

Frequency

United States

According to the 2007 Annual Report of the American Association of Poison Control National Poison Data System, 3895 single exposures to disinfectants containing pine oil, 9639 single exposures to camphor, and 510 single exposures to turpentine were reported.³ No deaths were reported with exposure to pine oil, camphor, or turpentine.³

Mortality/Morbidity

Morbidity and mortality⁴ 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.

Sex

Males overrepresent cases associated with terpenes.

Age

Most exposures are the result of unintentional exposures in childhood.

Clinical

History

• Elicit the exact substance⁵ that the patient was exposed to, and the concentration of terpene should be noted.
• Toxicity may first present with GI symptoms of nausea and vomiting.
• In severe ingestions, seizures have been reported;⁶ they are often single and self-limited.

Physical

• Respiratory symptoms from aspiration may occur early.
• A careful examination of the chest and lungs is essential. CNS depression may occur early in 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.

Causes

• Most 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.
• 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 male with diarrhea, vomiting, and altered mental status. He was described as having parallel and symmetric ecchymotic streaks on his back as a result "coining". In this case, toxicity occurred by the application of camphor to the skin prior to coining. Toxicity occurred presumably by transcutaneous absorption.

Differential Diagnoses

Other Problems to Be Considered

Airway obstruction

Workup

Laboratory Studies

• 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

• Chest radiography
  • 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.
• CNS imaging
  • 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.⁷

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.

Medication

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

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.

Dosing

Adult

2 mg IV/IM titrate to effect; some patients may require larger doses

Pediatric

0.05 mg/kg IV/IM

Interactions

Effects potentiated by phenothiazines, narcotics, barbiturates, MAOIs, and other antidepressants

Contraindications

Documented hypersensitivity; preexisting CNS depression, hypotension, and narrow-angle glaucoma

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, or Parkinson disease; monitor 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.

Dosing

Adult

5-10 mg IV q10-15min until symptoms resolve; not to exceed 30 mg

Pediatric

30 days to 5 years: 0.2-0.5 mg IV (slowly) q2-5min until symptoms resolve; not to exceed 5 mg
>5 years: 1 mg IV (slowly) q2-5min until symptoms resolve; not to exceed 10 mg

Interactions

Effects potentiated by phenothiazines, narcotics, barbiturates, MAOIs, and other antidepressants

Contraindications

Documented hypersensitivity; acute narrow-angle glaucoma

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution with other CNS depressants, low albumin levels, or hepatic disease (may increase toxicity); monitor for respiratory depression with high or repeated doses

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.

Dosing

Adult

0.01-0.05 mg/kg (usually 0.5-4 mg, up to 10 mg) IV slowly over several min; may repeat q10-15min until adequate response achieved

Pediatric

<32 weeks: 0.5 mcg/kg/min IV infusion
>32 weeks: 1 mcg/kg/min IV infusion
Children: 0.05-0.2 mg/kg IV over 2-3 min, followed by 1-2 mcg/kg/min continuous infusion
Status epilepticus (refractory to standard therapy), >2 months and children: 0.15 mg/kg followed by continuous infusion of 1 mcg/kg/min, titrating dose upward q5min until seizures controlled

Interactions

Sedative effects may be antagonized by theophyllines; narcotics, cimetidine, ethanol, and erythromycin may accentuate sedative effects because of decreased clearance; reduce dose of thiopental by 15% when using together

Contraindications

Documented hypersensitivity; preexisting hypotension, narrow-angle glaucoma, and sensitivity to propylene glycol (diluent)

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in congestive heart failure, pulmonary disease, renal impairment, hepatic failure, neuromuscular disease, hypotension, and patients >60 y; monitor for respiratory depression with high or repeated doses; consider lower dosages organic brain syndrome and patients who may have inhibition of benzodiazepine metabolism and clearance (eg, using nicotine, taking cimetidine)

Follow-up

Further Outpatient Care

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

Deterrence/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.

Complications

• Aspiration of hydrocarbons may result in serious complications requiring long-term follow-up.

Prognosis

• Mortality is rare.
• Most patients make full recoveries without sequelae.

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.

Miscellaneous

Medicolegal Pitfalls

• Missed pulmonary impairment may not be defendable. On the other hand, use of gastric emptying procedures that may result in aspiration pneumonitis also can be a liability problem. Withholding antibiotic or steroid treatment is difficult if an elevated white blood count is found, but it could result in selection of highly resistant microorganisms.

References

1. Lam HS, Chow CM, Poon WT, Lai CK, Chan KC, Yeung WL. Risk of vitamin A toxicity from candy-like chewable vitamin supplements for children. Pediatrics. Aug 2006;118(2):820-4. [Medline].

2. Bucheler R, Gleiter CH, Schwoerer P, Gaertner I. Use of nonprohibited hallucinogenic plants: increasing relevance for public health? A case report and literature review on the consumption of Salvia divinorum (Diviner's Sage). Pharmacopsychiatry. Jan 2005;38(1):1-5. [Medline].

3. Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Heard SE. 2007 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 25th Annual Report. Clin Toxicol (Phila). Dec 2008;46(10):927-1057. [Medline].

4. Soo Hoo GW, Hinds RL, Dinovo E, Renner SW. Fatal large-volume mouthwash ingestion in an adult: a review and the possible role of phenolic compound toxicity. J Intensive Care Med. May-Jun 2003;18(3):150-5. [Medline].

5. Myhre AM, Carlsen MH, Bøhn SK, Wold HL, Laake P, Blomhoff R. Water-miscible, emulsified, and solid forms of retinol supplements are more toxic than oil-based preparations. Am J Clin Nutr. Dec 2003;78(6):1152-9. [Medline].

6. Khine H, Weiss D, Graber N, Hoffman RS, Esteban-Cruciani N, Avner JR. A cluster of children with seizures caused by camphor poisoning. Pediatrics. May 2009;123(5):1269-72. [Medline].

7. [Guideline] Manoguerra AS, Erdman AR, Wax PM, Nelson LS, Caravati EM, Cobaugh DJ. Camphor Poisoning: an evidence-based practice guideline for out-of-hospital management. Clin Toxicol (Phila). 2006;44(4):357-70. [Medline]. [Full Text].

8. Brook MP, McCarron MM, Mueller JA. Pine oil cleaner ingestion. Ann Emerg Med. Apr 1989;18(4):391-5. [Medline].

9. Dalgarno P. Subjective effects of Salvia divinorum. J Psychoactive Drugs. Jun 2007;39(2):143-9. [Medline].

10. Decker WJ, Corby DG, Hilburn RE, Lynch RE. Adsorption of solvents by activated charcoal, polymers, and mineral sorbents. Vet Hum Toxicol. 1981;23(Suppl 1):44-6. [Medline].

11. Gambelunghe C, Melai P. Absinthe: enjoying a new popularity among young people?. Forensic Sci Int. Dec 4 2002;130(2-3):183-6. [Medline].

12. Guillen MD, Manzanos MJ. Extractable components of the aerial parts of Salvia lavandulifolia and composition of the liquid smoke flavoring obtained from them. J Agric Food Chem. Aug 1999;47(8):3016-27. [Medline].

13. Lai MW, Klein-Schwartz W, Rodgers GC, Abrams JY, Haber DA, Bronstein AC. 2005 Annual Report of the American Association of Poison Control Centers' national poisoning and exposure database. Clin Toxicol (Phila). 2006;44(6-7):803-932. [Medline].

14. Love JN, Sammon M, Smereck J. Are one or two dangerous? Camphor exposure in toddlers. J Emerg Med. Jul 2004;27(1):49-54. [Medline].

15. Olsen RW. Absinthe and gamma-aminobutyric acid receptors. Proc Natl Acad Sci U S A. Apr 25 2000;97(9):4417-8. [Medline].

16. Ragucci KR, Trangmar PR, Bigby JG, Detar TD. Camphor ingestion in a 10-year-old male. South Med J. Feb 2007;100(2):204-7. [Medline].

17. Rampini SK, Schneemann M, Rentsch K, Bachli EB. Camphor intoxication after cao gio (coin rubbing). JAMA. Jul 3 2002;288(1):45. [Medline].

18. Riordan M, Rylance G, Berry K. Poisoning in children 4: household products, plants, and mushrooms. Arch Dis Child. Nov 2002;87(5):403-6. [Medline].

19. Rodricks A, Satyanarayana M, D'Souza GA, Ramachandran P. Turpentine-induced chemical pneumonitis with broncho-pleural fistula. J Assoc Physicians India. Jul 2003;51:729-30. [Medline].

20. Shannon M, McElroy EA, Liebelt EL. Toxic seizures in children: case scenarios and treatment strategies. Pediatr Emerg Care. Jun 2003;19(3):206-10. [Medline].

21. Wilson CR, Sauer J, Hooser SB. Taxines: a review of the mechanism and toxicity of yew (Taxus spp.) alkaloids. Toxicon. Feb-Mar 2001;39(2-3):175-85. [Medline].

Keywords

terpene toxicity, terpenes, terpenoids, monoterpenes, isoprene unit, diterpenes, terpene exposure, terpene poisoning, cantharidin, menthol, pinene, camphor, phytol, vitamin A1, paclitaxel, Taxol

Contributor Information and Disclosures

Author

John Said Kashani, DO, Assistant Medical Director of the New Jersey Poison ad Information Education System; Assistant Professor, Department of Preventive Medicine and Community Health, Assistant Professor, Department of Pediatrics, New Jersey Medical School, University of Medicine and Dentistry of New Jersey
John Said Kashani, DO is a member of the following medical societies: American College of Emergency Physicians and American College of Medical Toxicology
Disclosure: Nothing to disclose.

Coauthor(s)

Steven Marcus, MD, Professor, Department of Preventive Medicine and Community Health, Associate Professor, Department of Pediatrics, New Jersey Medical School, University of Medicine and Dentistry of New Jersey; Executive and Medical Director, New Jersey Poison Information and Education System; Consulting Staff, Departments of Pediatrics and Internal Medicine, University Hospital, University of Medicine and Dentistry of New Jersey; Consulting Staff, Department of Pediatrics, Newark Beth Israel Medical Center
Steven Marcus, MD is a member of the following medical societies: Academy of Medicine of New Jersey, American Academy of Clinical Toxicology, American Academy of Pediatrics, American College of Emergency Physicians, American College of Medical Toxicology, American Medical Association, and Medical Society of New Jersey
Disclosure: Nothing to disclose.

Medical Editor

Lance W Kreplick, MD, MMM, FAAEM, FACEP, Medical Director of Hyperbaric Medicine, Fawcett Wound Management and Hyperbaric Medicine; Consulting Staff in Occupational Health and Rehabilitation, Company Care Occupational Health Services; President and Chief Executive Officer, QED Medical Solutions, LLC
Lance W Kreplick, MD, MMM, FAAEM, FACEP is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physician Executives
Disclosure: Nothing to disclose.

Pharmacy Editor

John T VanDeVoort, PharmD, Regional Director of Pharmacy, Sacred Heart & St. Joseph's Hospitals
John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists
Disclosure: Nothing to disclose.

Managing Editor

Michael J Burns, MD, Instructor, Department of Emergency Medicine, Harvard University Medical School, Beth Israel Deaconess Medical Center
Michael J Burns, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, American College of Medical Toxicology, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD, Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital
Disclosure: Nothing to disclose.

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