AUTHOR AND EDITOR INFORMATION

Section 1 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• WORKUP
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

INTRODUCTION

Section 2 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• WORKUP
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Background

Chloropicrin is a soil fumigant used for its broad biocidal and fungicidal properties, primarily in high-value crops such as strawberries, peppers, onions, tobacco, flowers, tomatoes, and nursery crops. John Stenhouse, a Scottish chemist and inventor, synthesized chloropicrin in 1848. Because chloropicrin is toxic by all routes of entry, it has the potential for widespread destruction as a chemical warfare agent.

Properties, stability, and reactivity

Chloropicrin is a colorless–to–light green oily liquid with an intense and penetrating odor. Even though chloropicrin is not flammable, it is a significant explosion hazard if involved in a fire. Bulk containers of this liquid are shock sensitive and can detonate. Chloropicrin is an irritant to all body surfaces. This liquid decomposes in the environment. Photochemical reactions with chloropicrin produce phosgene; other decomposition products include nitrogen oxides and chlorine compounds. 

Chloropicrin photodegrades, with a half-life of 20 days. It is known to undergo violent reactions with aniline, 3-bromopropyne, sodium hydroxide/alcohol solutions, sodium methoxide, and propargyl bromide. Hazardous polymerization does not occur with chloropicrin.

Detection

The odor is a distinctive warning property of this liquid compound.

Symptoms According to Concentrations

*Concentrations expressed in parts of material per million parts of air or water.

Pathophysiology

Inhalation

Overexposure leads to irritation of the nose and throat. Chloropicrin is a lacrimator. Exposure to vapors leads to coughing, labored breathing, sore throat, dizziness, bluish skin, vomiting, and in some instances, chemical pneumonitis and pulmonary edema.

Contact with skin or eyes

Contact with chloropicrin can lead to chemical burns or dermatitis manifested by red, cracked, irritated skin. The extent of skin injury depends on the concentration and duration of exposure. Contact with the eyes can cause pain, redness, and tearing. Prolonged eye exposure to chloropicrin can cause blindness. Entrance through damaged skin causes similar symptoms as those seen in overexposure through inhalation.

Ingestion

If ingested, chloropicrin can cause burns to the mouth, throat, and esophagus. Other symptoms are similar to those of overexposure through inhalation. Ingestion of large quantities of chloropicrin liquid can be fatal.

Injection

Overexposure to chloropicrin by injection can lead to redness and irritation of surrounding tissues. Other symptoms are similar to those of overexposure through inhalation.

Chronic exposure

Dermatitis may result from repeated exposure to chloropicrin.

Frequency

United States

Chloropicrin is commonly used as a soil fumigant for agricultural pest control. Human exposures have occurred in the United States, usually in residential areas in close proximity to agricultural areas. The most recently reported large-scale exposure occurred in Kern County, California, in 2003. One hundred sixty-five people developed symptoms as a result of off-site drift of chloropicrin from a nearby agricultural site. Peak concentrations of chloropicrin were estimated to exceed 1 part per million. Nearly all (99%) of those exposed experienced eye pain, burning, or lacrimation. Fifty-one percent experienced respiratory symptoms including cough, dyspnea, or upper respiratory irritation. Nearly half (47%) complained of gastrointestinal complaints such as nausea, vomiting, abdominal pain or diarrhea, and 25% complained of headache.¹

Mortality/Morbidity

Fatal chloropicrin exposures have been reported. An intentional ingestion of 100 mL of chloropicrin sodium solution resulted in death from metabolic acidosis and acute heart failure approximately 7 hours after ingestion.² Homicidal intoxication has also been reported, in which an 18-year-old female died approximately 4 hours after being sprayed with a liquid that was later determined to be chloropicrin. Postmortem examination demonstrated severe pulmonary edema.³

Elevations of creatine phosphokinase levels have been described in the setting of chloropicrin exposure and may represent some degree of rhabdomyolysis.⁴

Chloropicrin may cause methemoglobinemia.⁵

CLINICAL

Section 3 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• WORKUP
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

History

Clinicians should attempt to elicit an accurate history to involve the setting of exposure. This may occur as an occupational exposure, as an intentional and unintentional industrial release, or as a terrorist attack.

Physical

Physical manifestations depend on the route of exposure.

• Skin - Evidence of chemical burns or dermatitis manifested by red, cracked, irritated, or bluish skin
• Eyes - Pain, redness, and tearing
• Respiratory - Coughing, labored breathing, rales, and rhonchi

DIFFERENTIALS

Section 4 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• WORKUP
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

WORKUP

Section 5 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• WORKUP
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Lab Studies

Laboratory testing should be dictated by clinical presentation and condition of the patient. The provider may consider addition of creatine kinase (CK) and blood gas with co-oximetry. Chloropicrin may be detected by gas chromatography/mass spectrometry (GC/MS). 

TREATMENT

Section 6 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• WORKUP
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Prehospital Care

• General considerations
• • The rescuer's protective equipment should be Level A (eg, triple gloves [polyethylene gloves and nitrile gloves over latex gloves], fully encapsulating chemical resistant suit and boots, hard hat, self-contained breathing apparatus).
  • Standard organic vapor filters used with gas masks or air-purifying respirators do not remove chloropicrin effectively.
• Skin exposure
• • Immediately begin decontamination with running water. Flush for a minimum of 15 minutes.
  • Remove contaminated clothing, taking care not to contaminate eyes further.
• Eye exposure
• • If possible, open victim's eyes while under gentle running water. Use sufficient force to open the eyelids. The victim must "roll" the eyes.
  • Flush for a minimum of 15 minutes.
• Inhalation
• • Remove the victim to fresh air.
  • Provide assisted ventilation as needed to support pulmonary function.
  • Cover or remove gross contamination to avoid exposure to rescuers.
• Ingestion
• • Do not induce vomiting.
  • Rinse mouth immediately with water.
  • Have the victim drink milk, egg whites, or large quantities of water if available.

Emergency Department Care

• Skin exposure: If not completed in the field, continue decontamination with running water for at least 15 minutes.
• Eye exposure: If not completed in the field, continue flushing for at least 15 minutes.
• Inhalation
• • Continue assisted ventilation and initiate artificial ventilation as needed to support pulmonary function.
  • In severe respiratory compromise, ventilatory support is mandatory. If a PaO₂ cannot be maintained greater than 60 mm Hg with a fraction of inspired oxygen (FIO₂) less than or equal to 0.6, then add positive end-expiratory pressure in attempts to open previously closed alveoli.
  • For methemoglobinemia greater than 10-20%, consider administration of methylene blue 1-2 mg/kg as 1% solution intravenously over 5 minutes, followed by a 15-30 mL flush.⁵
• Ingestion 
• • Contact poison control for the most current information.
  • Do not induce vomiting.
  • Administer large quantities of water.
  • Do not give diluents to a patient who is convulsing, unconscious, or unable to swallow.

MEDICATION

Section 7 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• WORKUP
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Albuterol and aminophylline may be beneficial in cases involving signs of bronchoconstriction. Use supplemental humidified oxygen in cases of respiratory compromise.

In severe respiratory compromise, ventilatory support is mandatory. If a PaO₂ cannot be maintained greater than 60 mm Hg with a fraction of inspired oxygen (FIO₂) less than or equal to 0.6, then add positive end-expiratory pressure in attempts to open previously closed alveoli. No specific drug therapy is available for chloropicrin toxicity.

For methemoglobinemia greater than 10-20%, consider the use of methylene blue.⁵

Drug Category: Sympathomimetic (adrenergic) agents

These agents relieve reversible bronchospasm by relaxing smooth muscles of the bronchi.

Drug Category: Respiratory smooth muscle relaxant

Aminophylline relieves bronchospasm through smooth muscle relaxation of respiratory tract, thereby increasing flow rates and vital capacity.

Drug Category: Antidotes

This agent is used to reduce methemoglobin.

FOLLOW-UP

Section 8 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• WORKUP
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Further Inpatient Care

• Signs of pulmonary edema may not be evident early after exposure. Observation for 24-48 hours for progression or worsening of symptoms is recommended.⁵

Patient Education

• For excellent patient education resources, visit eMedicine's Bioterrorism and Warfare Center. Also, see eMedicine's patient education articles Chemical Warfare and Personal Protective Equipment.

MISCELLANEOUS

Section 9 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• WORKUP
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Medical/Legal Pitfalls

• Because chloropicrin is toxic by all routes, failure to recognize exposure may result in long-term disability or death.
• Failure to educate users of chloropicrin in the danger of its use and importance of proper protective equipment can result in unnecessary morbidity or mortality from routine use.

Special Concerns

• Chloropicrin as a chemical weapon of war
• • Chloropicrin is toxic by all routes of entry, especially by inhalation and ingestion.
  • Short overexposures may cause fatal lung damage.
  • Although not flammable, chloropicrin presents a significant explosion hazard if involved in a fire.
  • Bulk containers are shock sensitive and can detonate.
  • Standard organic vapor filters used with gas masks or air-purifying respirators do not remove chloropicrin effectively.
  • In 1887, while the Germans apparently were considering using lacrimators for military purposes, the French began a chemical warfare program. The French developed a tear gas grenade containing ethyl bromoacetate and proposed artillery shells filled with chloropicrin. In addition, the US War Department's Chemical Warfare Service (CWS) produced chloropicrin-filled artillery shells at the Edgewood Arsenal in Aberdeen, Maryland, as part of the war effort during World War I.

ACKNOWLEDGMENTS

Section 10 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• WORKUP
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, Joanne Williams, MD, to the development and writing of this article.

MULTIMEDIA

Section 11 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• WORKUP
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Media file 1:  Chemical structure of chloropicrin.
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Media type:  Graph

Media file 2:  Level A suit (DuPont Tychem 10,000).
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Media type:  Photo

Media file 3:  Chemical Terrorism Agents and Syndromes. Signs and symptoms. Chart courtesy of North Carolina Statewide Program for Infection Control and Epidemiology (SPICE), copyright University of North Carolina at Chapel Hill, www.unc.edu/depts/spice/chemical.html.
	View Full Size Image
Media type:  Image

REFERENCES

Section 12 of 12

• Authors and Editors
• Introduction
• Clinical
• Differentials
• WORKUP
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

1. O'Malley MA, Edmiston S, Richmond D, Ibarra M, Barry T, Smith M, et al. Illness associated with drift of chloropicrin soil fumigant into a residential area--Kern County, California, 2003. MMWR Morb Mortal Wkly Rep. Aug 20 2004;53(32):740-2. [Medline]. [Full Text].
2. Honda H, Kawashima T, Kaku N, Kawasaki K. [A case of fatal chloropicrine poisoning induced by ingestion]. Chudoku Kenkyu. Oct 2002;15(4):381-4. [Medline].
3. Gonmori K, Muto H, Yamamoto T, Takahashi K. A case of homicidal intoxication by chloropicrin. Am J Forensic Med Pathol. Jun 1987;8(2):135-8. [Medline].
4. Prudhomme JC, Bhatia R, Nutik JM, Shusterman DJ. Chest wall pain and possible rhabdomyolysis after chloropicrin exposure. A case series. J Occup Environ Med. Jan 1999;41(1):17-22. [Medline].
5. Material Safety Data Sheet - Lacrythor Fumigation Warning Agent. Revised October 2006. Material Safety Data Sheet. Available at http://forthor.com/labels/chloropicrin/pic_MSDS.pdf. Accessed January 1, 2008.
6. Goldman LR, Mengle D, Epstein DM, Fredson D, Kelly K, Jackson RJ. Acute symptoms in persons residing near a field treated with the soil fumigants methyl bromide and chloropicrin. West J Med. Jul 1987;147(1):95-8. [Medline].
7. Harber LF. The Poisonous Cloud: Chemical Warfare in the First World War. 1986:15-40.
8. HoltraChem Manufacturing Company, LLC. Material Safety Data Sheet, Chloropicrin. July 30, 1996; revised February 28, 2000.
9. McEvoy GK, Litvak K, Welsh, Jr. OH. AHFS 96 Drug Information. 1996;861-864, 2654-2657.
10. Smart JK. History of chemical and biological warfare fact sheets. In: Special Study 50; US Army Chemical and Biologic Defense Command. 1996.
11. Tintinalli JE. Emergency medicine. JAMA. Jun 19 1996;275(23):1804-5. [Medline].
12. Wilhelm SN, Sheipier K, Lawrence H. Environmental fate of chloropicrin. In: Fumigants: Environmental Fate, Exposure, and Analysis. 1996.

Article Last Updated: Feb 13, 2008