eMedicine Specialties > Emergency Medicine > Toxicology

Toxicity, Toxaphene and Organochlorine

Author: Girish Sethuraman, MD, MPH, Clinical Assistant Instructor, Staff Physician, Department of Emergency Medicine, Kings County Hospital, Downstate Medical Center
Coauthor(s): Christopher I Doty, MD, FAAEM, Assistant Professor of Emergency Medicine, Residency Program Director, Department of Emergency Medicine, Kings County Hospital Center, State University of New York Downstate Medical Center
Contributor Information and Disclosures

Updated: Jun 10, 2008

Introduction

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

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

• Search for CME/CE on This Topic »

• Toxicity, Lidocaine (Emergency Medicine)
• Chloroquine/Hydroxychloroquine Toxicity (Ophthalmology)
• Toxicity, Mercury (Emergency Medicine)
• Toxicity, Fluoride (Emergency Medicine)

• Poisoning - First Aid and Emergency Center
• Poisoning Center
• Poisoning Overview
• Poisoning Causes
• Poisoning Symptoms
• Poisoning Treatment
• Poison Proofing Your Home Introduction

• Serotonin Toxicity, ECG Abnormalities Seen With Escitalopram Overdose
• Dietary Supplement May Protect Against Acetaminophen-Induced Liver Toxicity
• "Substantial" Toxicity With Peginterferon Use: FDA Staff

• Tenofovir-associated Renal and Bone Toxicity
• EGFR-Targeted Therapies in Lung Cancer: Predictors of Response and Toxicity
• Role of Pharmacogenetics as Predictive Biomarkers of Response and/or Toxicity in the Treatment of Colorectal Cancer