AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Toxaphene and related organochlorine compounds (eg, endrin, dieldrin, aldrin, endosulfan, chlordane, heptachlor, dichlorodiphenyltrichloroethane [DDT], lindane, chlordecone) have been manufactured since the 1940s for use as pesticides. They are prepared commercially as dusts, sprays, and wettable powders and are used alone or in combination with other pesticides (eg, organophosphorous compounds) for use on cotton and food crops. Their use between the 1940s and 1970s revolutionized modern agriculture, allowing a massive increase in crop output. DDT was also used in public health measures for control of typhus and eradication of malaria in the United States. They are not safe for household application. Organochlorines persist in the environment long after their initial use.

Toxaphene (ie, chlorinated camphene, camphechlor) is a complex mixture of chlorinated derivatives of camphene (ie, polychlorinated 10-carbon cyclic compounds), which are obtained by isomerization of alpha-pinene, a byproduct of turpentine distillation. A major toxic component identified is heptachlorobornane. Toxaphene is identified as CAS#8001-35-2 and by its United Nations Department of Transportation number, UN#2761.

Toxaphene is a tasteless, pleasant-smelling mixture that is fat soluble, possessing low molecular weight and low volatility. It is amber to yellow in color and waxy in consistency; it has an odor similar to turpentine. Toxaphene is not very biodegradable (ie, slow biotransformation and degradation); it persists in the environment and accumulates in biological systems (eg, food chain of fish, poultry, cattle).

Pathophysiology

Toxaphene is absorbed through intact skin, by inhalation, and by ingestion. Because toxaphene is slowly biodegradable and highly lipid-soluble, it accumulates with repetitive exposures and duration of toxicity may be prolonged. Toxaphene acts as a neurotoxin by interfering with transmission of nerve impulses, especially in the brain, resulting in CNS stimulation.

Toxaphene lowers the normal neural excitation threshold with stimulation of sensory and motor nerve fibers and the motor cortex. Toxaphene alters movement of sodium (Na⁺) and potassium (K⁺) across neuronal membranes and adversely effects membrane-related enzymatic reactions. This may antagonize GABA-mediated inhibition in the CNS.

Toxaphene can also induce hepatic enzyme induction (cytochrome P-450 mixed function oxidases), increasing metabolism of therapeutic drugs and reducing their efficacy.

Frequency

United States

Acute poisoning and fatality caused by organochlorine exposure is rare. DDT was banned by the US Environmental Protection Agency (EPA) in 1972. The EPA and manufacturers of organochlorine pesticides agreed to halt sales of organochlorine pesticides in 1987 after a partial ban in 1976. All use of toxaphene was banned in 1990. Despite a ban on sales, organochlorines may still be found in storage in the United States; thus, exposure is still possible. Toxaphene can be transported in the air at long distances and can persist in air, soil, and water for years.

The 1998 annual report of the American Association of Poison Control Centers' Toxic Exposure Surveillance System documented 2782 exposures to chlorinated hydrocarbon pesticides, with 1144 occurring in children younger than 6 years.¹ Although 22 major adverse outcomes were reported, no deaths were noted.

International

Widespread use of organochlorine insecticides has been banned in North America and Europe. In contrast, these chemicals are used extensively in many developing nations.

Mortality/Morbidity

Toxic doses widely vary. The fatal dose in humans is unknown; data from nonfatal cases suggest that a dose of approximately 10 mg/kg can cause convulsions. An oral median lethal dose (LD50) is higher than 50 mg/kg in animal studies.

The estimated approximate minimum lethal dose for humans is 2-7 g.

Race

No scientific data indicate that outcomes of exposure to organochlorine pesticides depend on race.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Obtaining a thorough history is essential to the diagnosis of toxaphene poisoning. At a minimum, the history should include the following:

• Prior medical and psychiatry history
• Nonprescription drugs used
• Natural or herbal preparations used
• Allergies to medications
• Patient activity for that day of exposure
• Occupational history, including farming, field work, and chemical or pesticide manufacturing, handling, or application
• Pest control use
• Location in relation to industrial facilities or waste sites
• Hobbies (eg, gardening)

If possible, obtaining the product in its original container is important. Review the label and contact the poison control center. Save the sample for possible testing and identification. Usually, testing has to be performed at an outside laboratory and has no immediate clinical impact on the patient's treatment.

Under the Federal Pesticide Act of 1962, the package label must contain certain information regarding product classification and toxicity, which is based on animal oral LD50 studies.

The following are classifications for the toxic categories:

• Danger - High toxicity
• Warning - Moderate toxicity
• Caution - Low toxicity
• No signal word - Safe

Physical

Perform a carefully directed physical examination and look for clues (eg, odor, injuries, neurological findings), which can help in determining type of exposure, underlying medical condition, or concomitant trauma. Look for signs of a toxidrome. In patients with agricultural or occupational exposure, concomitant organophosphorus or carbamate poisoning is common.

Repeated assessments of the ABCs and all vital signs are of extreme importance for proper treatment of patients with acute poisoning.

• Generally, onset of symptoms is characteristically abrupt and is mainly caused by CNS stimulation and lowering of the seizure threshold.
• • Patients with significant exposure usually develop nausea and vomiting, followed by confusion, tremors, coma, seizures, and respiratory depression. Fatality usually occurs within 4-8 hours because of respiratory failure and the sequelae of metabolic acidosis secondary to prolonged seizure activity.
  • The first manifestation of toxicity may be a seizure without any prodromal signs or symptoms. Generalized convulsions should suggest severe exposure.
  • Seizures often develop within 1-2 hours when ingested on an empty stomach and as late as 5-6 hours on a full stomach. Strong external stimuli and reflex hyperexcitability may precipitate muscle fasciculations and tonic spasms, which may evolve into seizures.
  • In addition, the myocardium could become oversensitized to dysrhythmogenic effects of endogenous catecholamines. Cyanosis has been reported to appear before convulsions at least once.
• Possible acute clinical findings that may be encountered include the following:
• • Mild dermal irritation (in dermal exposure)
  • Anorexia, nausea, and vomiting
  • Paresthesia of the tongue, lips, and face
  • Behavioral changes (eg, confusion, restlessness, apprehension, irritability)
  • Movement disorders (eg, involuntary movements, tremor, dystaxia)
  • Convulsions and status epilepticus
  • Hypersusceptibility to stimuli, hyperreflexia, and sustained ankle clonus
  • Coma (cerebral edema noted postmortem)
  • Respiratory failure (aspiration pneumonitis, prolonged seizures)
  • Liver cell necrosis (secondary to toxic metabolites)
  • Hyperthermia (from protracted muscle fasciculations, clonic movements, and agitation or prolonged seizure activity)
• Patients with long-term occupational exposure to organochlorine pesticides may develop various nonspecific symptoms, including headaches, nausea, fatigue, muscle twitching, and visual disturbances. In addition, chronic exposure to these agents may be associated with the development of blood dyscrasias, including aplastic anemia and leukemia in humans (inconclusive).
• • Some epidemiologic evidence suggests that organochlorines may be carcinogenic in humans. The EPA classifies these agents as probable human carcinogens.
  • Results of epidemiologic studies have been inconsistent.
  • Toxaphene interferes directly or indirectly with fertility and reproduction in rodents (testicular degeneration and endocrine changes). Toxaphene is teratogenic in mice and rats at doses that result in overt maternal toxicity. Also, tumors arise in the liver (eg, hepatomas) and renal tubules of chronically exposed animals.

Causes

• Acute exposure (unintentional or intentional)
• Chronic low-grade exposure

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Camphor toxicity
Lindane toxicity
Picrotoxin toxicity
Sodium monofluoroacetate (SMFA) toxicity
Strychnine toxicity
Hypoxemia
Idiopathic epilepsy

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Glucose (bedside fingerstick) testing
• ABG testing (pH and ventilation status) in patients with respiratory distress or evidence of acidosis
• Serum electrolytes testing
• Renal profile
• Liver function tests (LFTs)
• CBC count
• Urinalysis (indirect check for myoglobinuria)
• Creatinine kinase (CK) testing
• Urine or serum pregnancy test if indicated
• Plasma and RBC cholinesterase testing in cases in which organophosphorous compound coexposure may have occurred or if offending toxicant has not been determined and the patient presents with signs or symptoms consistent with cholinergic toxidrome

Imaging Studies

• Abdominal radiography may be indicated in ingestion because chlorinated pesticides are usually radiopaque. Negative radiography findings do not rule out significant exposure.
• Chest radiography may be indicated to rule out aspiration.
• CT scanning of the head may be indicated to rule out intracranial pathology (eg, masses, focal edema, traumatic or nontraumatic intracerebral bleeds). In severe exposures to toxaphene, diffuse cerebral edema has been reported.

Other Tests

• Generally, toxaphene whole blood levels document exposure, but these levels do not correlate well with the degree of toxicity.
• No specific method is available for detection of the hundreds or thousands of compounds in toxaphene-derived residues.
• If necessary, gas chromatographic analytical studies of serum, adipose tissue, urine, and breast milk can be considered for documentation of exposure.
• For occupational purposes, performing adipose tissue biopsy testing for estimating total body burden of an exposed population is possible. This has no application in acute treatment of the exposed patient.
• For the emergency department clinician, the above studies are unlikely to be of any acute clinical value because the likelihood of a rapid test result is small. However, obtaining samples for these examinations may be valuable for the extended-term evaluation and treatment of the patient.
• Electrocardiography may be indicated.

Procedures

• In a postmortem forensic examination, brain analytical studies are warranted because severity of toxicity correlates with CNS concentration of these insecticides. Therefore, when a patient's death possibly is caused by acute or chronic pesticide exposure, alert the coroner so that appropriate safety issues may be addressed. This action is especially important in occupationally related cases.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prehospital Care

• Establish the ABCs. Protect the airway at all times. Do not induce emesis because the patient may have a sudden change in mental status and could aspirate gastric contents.
• Avoid strong external stimuli to the patient, which may precipitate convulsions.
• Remove the patient from source of exposure and prevent contamination of others.
• Consider skin decontamination by washing with soap and water and removing clothing (place in plastic bags) as early as possible; it is performed best in the field.
• With massive exposure or multiple victims, contact a hazardous materials (HAZMAT) team for assistance.
• Initiate cooling measures (eg, wetting, fanning, ice bath) if the patient is hyperthermic.

Emergency Department Care

• Early (preventive) and aggressive supportive measurements are required for a good outcome. No specific antidote is available for toxaphene poisoning.
• Continue ABCs. Consider early and gentle rapid sequence intubation with prophylactic use of a benzodiazepine to control agitation and theoretically reduce possibility of seizures.
• • Seizures may begin without any prodromal signs or symptoms.
  • If paralyzed, EEG monitoring is warranted.
• If ingested, do not induce emesis. Carefully perform orogastric lavage with suction, especially for recent liquid ingestion. Always secure the airway well before executing lavage.
• • GI decontamination with aqueous-based oral activated charcoal (AC) is indicated to limit drug absorption from the GI tract.
  • Never use oral oil-based cathartics because they may facilitate absorption of toxaphene.
  • Avoid sorbitol-based AC because it may induce vomiting.
• Regardless of the route of exposure, consider multiple dose activated charcoal (MDAC) because it may enhance fecal elimination of toxaphene by interrupting its biliary-enterohepatic and enteroenteric recirculation.
• • Induced diuresis, hemodialysis, and hemoperfusion have not been shown to be effective enhanced elimination techniques.
  • In contrast, cholestyramine resin is a selective oral binding agent that has been successfully used to enhance fecal elimination of chlorinated hydrocarbons by interrupting the biliary-enterohepatic and enteroenteric recirculation.
• Dysrhythmias may occur because of increased myocardial sensitization to catecholamines induced by chlorinated hydrocarbon.
• • If at all possible, avoid use of epinephrine and other sympathomimetic drugs possessing beta1-agonist properties to avoid increased risk of developing ventricular dysrhythmias.
  • Use of beta-blockers is reported to control ventricular dysrhythmias because of sensitized myocardium.
  • If the patient is hypotensive and unresponsive to fluids, intravenous administration of a pure alpha-adrenergic agonist agent (eg, phenylephrine) is the therapy of choice.
• Because of a theoretical benefit from using N-acetylcysteine (NAC) if liver abnormalities or necrosis is suspected in the patient (elevated serum levels of liver enzymes), administration of the drug is suggested to prevent irreversible hepatic injury. Favorable outcomes following use of NAC have been reported in cases of carbon tetrachloride and chloroform poisonings (not proven).
• • Suspected mechanism of hepatic injury appears similar to that of acetaminophen and empiric use of NAC may be justified, especially in significant poisoning.
  • Generally, the only significant adverse event associated with oral use of NAC is pulmonary aspiration (although one case of an anaphylactoid reaction to oral NAC has been reported); therefore, ensure proper protection of the airway.
• Aggressive cooling measures may be required if the patient presents with or develops hyperthermia.

Consultations

• In all cases, seek consultation with the regional poison control center and a medical toxicologist (certified through the American Board of Medical Toxicology or the American Board of Emergency Medicine).

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Drug Category: Antidote, adsorbents

These agents are empirically used to minimize systemic absorption of the toxin and are only beneficial if administered within 1-2 h of ingestion.

Drug Category: Bile acid sequestrants

Theoretically, cholestyramine enhances rate of fecal excretion of stored toxin. This may be true because toxaphene and other related chlorinated hydrocarbons are normally recirculated through the biliary-enterohepatic and enteroenteric system.

Binding resin binds secreted insecticide and metabolites, reducing reabsorption and retaining the bound agent in the lumen of the intestinal tract. Also, by binding bile salts and, therefore, reducing formation of emulsions, binding resin minimizes uptake of these highly lipid-soluble agents.

Drug Category: Beta-adrenergic blockers

Ventricular dysrhythmias may respond to beta-adrenergic blockade therapy. In contrast, if mixed adrenergic stimulation is highly suspected acutely, do not use beta-blockers because of the possibility of developing deleterious unopposed alpha-adrenergic stimulation.

This category of drugs has the potential to suppress ventricular ectopy due to ischemia or excess catecholamines. In the setting of myocardial ischemia, beta-blockers have antiarrhythmic properties and reduce myocardial oxygen demand secondary to elevations in heart rate and inotropy.

Consider an alpha-agonist, such as phenylephrine, for the treatment of hypotension that does not respond to fluid replacement.

Drug Category: Vasopressors

These agents decrease portal circulation pressure by diminishing blood flow due to vasoconstriction. The major indication for these agents is variceal bleeding.

Drug Category: Benzodiazepines and other sedatives

These agents are used to treat acute seizure activity.

Drug Category: Other Anticonvulsants

These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Hospitalization in ICU is indicated for patients with significant exposure or with signs and symptoms of intoxication. Observation for signs of end-organ damage (eg, CNS, heart, lung, liver) and supportive care are mainstays of therapy.
• Obtain a psychiatric evaluation, if warranted.
• Explore possibility of child, elderly person, or vulnerable adult abuse or neglect.

Further Outpatient Care

• Observe patients with an apparent nonsignificant and nontoxic exposure in the emergency department for 6-8 hours before discharge from the hospital. If any signs or symptoms of toxicity develop within that period of observation, admit the patient to the hospital.
• If warranted and before discharge, facilitate psychiatric evaluation and exploration of abuse and neglect possibilities.
• Arrange follow-up care before discharge so that the patient may be monitored for possible long-term sequelae.

Deterrence/Prevention

• Alert public health authorities in cases of occupational exposure to assist in prevention of further exposures in a potentially unsafe work environment.

Prognosis

• With adequate decontamination and supportive care, patients generally recover from acute exposure to their previous functional level. Studies have suggested, but not proven, a long-term risk of cancer and neurodegenerative diseases.² However, these risks are more attributable to chronic exposure.

Patient Education

• Refer patients and their families to public health authorities for education regarding use, storage, and proper disposal of pesticides.
• Educate patients about proper medical discharge instructions regarding acute and potential chronic signs and symptoms that are observed in toxaphene and organochlorine toxicity.
• Teach patients and their families about the hazards of pesticide use.
• For unknown pesticide exposures, information is available at the Extension Toxicology Network (EXTOX-NET). The National Pesticide Information Center is available 9:30 am to 7:30 pm EST at 1-800-858-7378.
• For excellent patient education resources, visit eMedicine's Poisoning Center and Poisoning - First Aid and Emergency Center. Also, see eMedicine's patient education articles Poisoning, Activated Charcoal, and Poison Proofing Your Home.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Exposure may be caused by a work-related incident. Legally, the physician may be required to file a report to the state or local health department. Even if not legally required, reporting the exposure to prevent further cases from occurring may be wise. Because organochlorines are banned by the EPA, any use of these compounds is illegal.
• Do not forget that other persons still may be at risk of intoxication. Medically evaluate all of these persons as soon as possible.
• If the patient is medically cleared to return home, provide clear proper medical discharge instructions and arrange proper medical follow-up care.
• Teach the patient and family about the hazards of pesticide use. Furthermore, do not forget to document instruction in the medical record.

Special Concerns

• Discuss possible long-term risk of breast cancer with female patients. Organochlorine pesticides and metabolites accumulate in breast tissue and milk.
• An experienced laboratory should analyze breast milk of pregnant or lactating women for toxic organochlorines, associated product contaminants, and their metabolites.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Litovitz TL, Klein-Schwartz W, Caravati EM, Youniss J, Crouch B, Lee S. 1998 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 1999;17(5):435-87. [Medline].
2. Goodman JI, Brusick DJ, Busey WM, et al. Reevaluation of the cancer potency factor of toxaphene: recommendations from a peer review panel. Toxicol Sci. May 2000;55(1):3-16. [Medline].
3. Amdur MO, Doull J, Klaassen CD. Toxic effects of pesticides. In: Casarett and Doull's Toxicology: The Basic Science of Poisons. 4^th ed. Pergamon Press; 1991:573-80.
4. Casida JE, Holmstead RL, Khalifa S, et al. Toxaphene insecticide: a complex biodegradable mixture. Science. Feb 8 1974;183(124):520-1. [Medline].
5. Ellenhorn MJ. Organochlorines. In: Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2^nd ed. Lippincott Williams & Wilkins; 1997:1625-6.
6. Gossel TA, Bricker JD. Organochlorine insecticides. In: Principles of Clinical Toxicology. 3^rd ed. Raven Press; 1994:155-6.
7. Gosselin RE, Smith RP, Hodge HC. Toxaphene. In: Clinical Toxicology of Commercial Products. 5^th ed. Lippincott Williams & Wilkins; 1984:386-7.
8. Hall AH. Chlordane Toxicity. Department of Health and Human Services;1993:1-24.
9. Haun EC, Cueto C Jr. Fatal toxaphene poisoning in a 9-month-old infant. Am J Dis Child. May 1967;113(5):616-9. [Medline].
10. Hayes AW. Chlorinated hydrocarbon insecticides. In: Principles and Methods of Toxicology. Lippincott-Raven Publishers; 1989:138-40.
11. Holland MG. Insecticides: Organic chlorines, pyrethrins/pyrethroids, and DEET. In: Goldfrank L, ed. Goldfrank's Toxicologic Emergencies. 8^th ed. New York, NY: McGraw-Hill; 2006:1523-35.
12. Hooper NK, Ames BN, Saleh MA, Casida JE. Toxaphene, a complex mixture of polychloroterpenes and a major insecticide, is mutagenic. Science. Aug 10 1979;205(4406):591-3. [Medline].
13. Kamel F, Hoppin JA. Association of pesticide exposure with neurologic dysfunction and disease. Environ Health Perspect. Jun 2004;112(9):950-8. [Medline].
14. Maitai CK, Kamau JA, Gacuhi DM, Njoroge S. An outbreak of arsenic and toxaphene poisoning in Kenyan cattle. Vet Rec. Feb 15 1975;96(7):151-2. [Medline].
15. Mount ME, Traffas V, Milleret RJ, Oehme FW. An unusual occurrence of toxaphene poisoning in swine. J Am Vet Med Assoc. Sep 1 1980;177(5):445-7. [Medline].
16. Peavy GM. The use of diazepam and methocarbamol in the treatment of toxaphene poisoning in a Bengal tiger. J Am Vet Med Assoc. Oct 1 1975;167(7):577-8. [Medline].
17. Purdue MP, Hoppin JA, Blair A, Dosemeci M, Alavanja MC. Occupational exposure to organochlorine insecticides and cancer incidence in the Agricultural Health Study. Int J Cancer. Feb 1 2007;120(3):642-9. [Medline].
18. Simpson WM, Schuman SH. Recognition and management of acute pesticide poisoning. Am Fam Physician. Apr 15 2002;65(8):1599-604. [Medline].
19. Turkington C. Chlorinated hydrocarbon pesticides - toxaphene. In: Poisons and Antidotes. NY: Facts on File;1994:67-8, 289-90.
20. U.S. Department of Health and Human Services, Public Health Service, Agency of Toxic Substances and Disease Registry. Toxicological Profile of Toxaphene. 1996.
21. Whitson RS, Crowder LA. Ion movements in the nervous system of the American cockroach, Periplaneta americana (L.), influenced by toxaphene. J Environ Sci Health. 1979;14(5):545-62. [Medline].

Article Last Updated: Jun 10, 2008