Organochlorine Pesticide Toxicity

Updated: Dec 29, 2015
  • Author: Matthew L Wong, MD, MPH; Chief Editor: Asim Tarabar, MD  more...
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Overview

Practice Essentials

Chlorinated hydrocarbon (organochlorine) pesticides, solvents, and fumigants are largely banned in North America and Europe, but are used extensively in many developing nations. In addition, these chemicals may still be found in storage in the United States; thus, exposure remains possible.

Signs and symptoms

CNS excitation and depression, typically abrupt in onset, are the primary clinical effects of acute organochlorine toxicity; therefore, patients may present with any of the following:

  • Initial euphoria with auditory or visual hallucinations and perceptual disturbances
  • Seizures
  • Agitation, lethargy, or unconsciousness

Other symptoms include the following:

  • Pulmonary - Cough, shortness of breath
  • Dermatologic - Skin rash
  • Gastrointestinal - Nausea, vomiting, diarrhea, and abdominal pain
  • Nervous system - Headache, dizziness, or paresthesias of the face, tongue, and extremities

Ingestion produces the following manifestations:

  • Nausea and vomiting
  • Confusion, tremor, myoclonus, coma, and seizures
  • Respiratory depression or failure
  • Unusual odor - Toxaphene may have a turpentine-like odor; endosulfan may have a sulfurous odor

Skin absorption or inhalation produces the following manifestations:

  • Ear, nose, and throat irritation
  • Blurred vision
  • Cough
  • Acute lung injury
  • Dermatitis

Long-term occupational exposure to organochlorine pesticides may result in 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).

Other manifestations of chronic exposure are as follows:

  • Anorexia
  • Hepatotoxicity
  • Renal toxicity
  • CNS disturbances
  • Skin irritation

See Presentation for more detail.

Diagnosis

The history of exposure is the most important piece of information. Laboratory studies may include the following:

  • Rapid bedside glucose finger-stick test
  • Electrolytes
  • Renal panel
  • Liver function tests
  • Creatine phosphokinase (CPK)
  • Lactate
  • Arterial or venous blood gas
  • Urinalysis
  • Urine pregnancy testing in women of childbearing age
  • Electrocardiography
  • Screening serum and urinary toxicology panels, particularly acetaminophen and salicylate levels if intentional exposure is suspected
  • Chlorinated hydrocarbon levels (can be measured, but not clinically helpful nor routinely available)

Possible abnormal findings by organ system are as follows:

  • Pulmonary - Increased A-a gradient, hypoxemia (see the A-a Gradient calculator)
  • Cardiovascular - Sinus tachycardia or bradycardia, QTc prolongation, nonspecific ST-segment changes
  • Gastrointestinal - Transaminitis and hyperbilirubinemia
  • Hematologic - Leukocytosis and prolonged activated partial thromboplastin time (aPTT)
  • Renal - Acidemia, azotemia, creatinine elevation, hyperkalemia

See Workup for more detail.

Supportive care and observation for signs of end-organ damage (eg, CNS, heart, lung, liver) are the mainstays of therapy. No specific antidotes are available for organochlorine poisoning.

Decontamination may be indicated to prevent continued absorption, as well as exposure of health care personnel. For dermal decontamination, remove clothing and wash skin with soap and water. This is best performed in the field.

Observe patients with an apparent nonsignificant and nontoxic exposure in the ED for 6-8 hours. If any signs or symptoms of toxicity develop during that time, admit the patient to the hospital. Intensive care unit admission is indicated for patients with significant exposure or with signs and symptoms of intoxication.

Repeated assessments of the patient’s ABCs and vital signs are of extreme importance in cases of acute poisoning. In particular, airway protection must be assured.

Regardless of the route of exposure, consider multiple-dose activated charcoal (MDAC) because it may enhance fecal elimination by interrupting the biliary-enterohepatic and enteroenteric recirculation of the toxin. Cholestyramine may be used to bind these highly lipophilic agents.

See Treatment and Medication for more detail.

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Background

Chlorinated hydrocarbon (organochlorine) insecticides, solvents, and fumigants are widely used around the world. This class of chemicals comprises a variety of compounds containing carbon, hydrogen, and chlorine.

These compounds can be highly toxic, and the overwhelming majority have been universally banned because of their unacceptably slow degradation and subsequent bioaccumulation and toxicity. [1] Among the more notable examples is dichlorodiphenyltrichloroethane (DDT). The synthesis of DDT by the Swiss chemist Paul Müller in the late 1930s, and the subsequent demonstration of its effectiveness as an insecticide, won Müller the 1948 Nobel Prize in Physiology or Medicine, [2] but DDT was banned in the United States in 1972. [3]

The toxicity of these agents varies according to their molecular size, volatility, and effects on the central nervous system (CNS). In general, they cause either CNS depression or stimulation, depending upon the agent and dose. [4]

These compounds can be separated into 5 groups, as follows:

  • DDT and analogues (eg, dicofol, methoxychlor)
  • Hexachlorocyclohexane (ie, benzene hexachloride) and isomers (eg, lindane, gamma-hexachlorocyclohexane)
  • Cyclodienes (eg, endosulfan, chlordane, heptachlor, aldrin, dieldrin, endrin, isobenzan)
  • Chlordecone, kelevan, and mirex
  • Toxaphene

Toxaphene (ie, chlorinated camphene, camphechlor) is a complex mixture of chlorinated derivatives of camphene (ie, polychlorinated 10-carbon cyclic compounds) that 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).

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Pathophysiology

Organochlorines are well absorbed orally and by inhalation. Transdermal absorption is variable. For example, DDT is poorly absorbed transdermally, whereas cyclodienes have significant transdermal absorption rates. [5] Cyclodienes have high absorption levels when taken orally as in the case of food contamination with these pesticides. [6] Lindane is known to be absorbed after topical application, but oral ingestions are not rare. [7] Young age, malnourishment, and frequent exposure increases the risk for toxicity. [8]

Organic chlorines are strongly lipid soluble and sequester in body tissues with high lipid content, such as the brain and liver. Consequently, blood levels tend to be much lower than fatty tissue levels. [5] The lipophilic tendency of organochlorines accounts for prolonged systemic effects in overdose. The half-life of DDT has been measured in months or years, whereas other organic chlorines are metabolized faster; for example, lindane has a half-life of 21 hours. [9]

Mechanism of toxicity

Toxicity in humans is largely due to stimulation of the CNS. Cyclodienes (eg, endosulfan), hexachlorocyclohexanes (such as lindane), and toxaphene predominately are gamma aminobenzoic acid (GABA) antagonists and inhibit calcium ion influx, but also may inhibit calcium and magnesium adenosine triphosphatase (ATPase). The resulting accumulation of calcium ions at neuronal endplates causes sustained release of excitatory neurotransmitters. [10, 11]

DDT affects potassium and voltage-dependent sodium channels. These changes can result in agitation, confusion, and seizures. Cardiac effects have been attributed to sensitization of the myocardium to circulating catecholamines.

Some of the more volatile organochlorines can be inhaled while in vapor form or swallowed while in liquid form. Inhalation of toxic vapors or aspiration of liquid after ingestion may lead to atelectasis, bronchospasm, hypoxia, and a chemical pneumonitis. In severe cases, this can lead to acute lung injury, hemorrhage, and necrosis of lung tissue. In liquid form, they are easily absorbed through the skin and GI tract.

Highly toxic organochlorines include:

  • Aldrin
  • Dieldrin [12]
  • Endrin [13]
  • Endosulfan [14, 15]

Moderately toxic organochlorines include:

  • Chlordane
  • DDT
  • Heptachlor
  • Kepone
  • Lindane
  • Mirex
  • Toxaphene
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Epidemiology

United States statistics

Organochlorine pesticides are now only rarely used in the developed world, and domestic poisonings have become correspondingly rare. Lindane is still used as a second-line topical prescription treatment for head lice and scabies. Adults are most likely to have serious intentional poisonings, and children are most likely to have unintentional poisonings.

The 2014 Annual Report of the American Association of Poison Control Centers' National Poison Data System lists pesticide exposure as the ninth most common substance involved in human exposures in the United States. [16] In 2014, 82,459 cases of pesticide exposure were reported. However, none of these were due to organochlorine pesticides. [16]

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.

International statistics

Although widespread use of organochlorine insecticides has been banned in North America and Europe, these chemicals are used extensively in many developing nations. An estimated 3 million cases of severe pesticide poisoning and 220,000 deaths occur each year worldwide. Organochlorine poisoning accounts for only a small fraction of pesticide poisoning, but the incidence varies from 1.8% of all poisonings in South Korea to 13.3% in some parts of India. [17, 18] A study of contamination in the Brazilian population showed adverse effects on hematopoietic tissue and the liver. [19]

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Prognosis

The prognosis in patients exposed to organochlorine compounds depends on the amount and type of exposure. Pulmonary fibrosis can occur after significant aspiration. Acute respiratory distress syndrome (ARDS) may develop.

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.

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. [20] However, these risks are more attributable to chronic exposure.

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.

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Patient Education

Refer patients and their families to public health authorities for education regarding the 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. Document this education.

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.

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 Eastern Standard Time at 1-800-858-7378.

For patient education resources, see the Poisoning Center and Poisoning - First Aid and Emergency Center, as well as Poisoning, Activated Charcoal, and Poison Proofing Your Home.

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