Toxicology and Poisoning Phosphine and Phosphide Phosphine Phosphide (PH(3)) CAS 7803-51-2; UN 2199 Also:Aluminum Phosphide (CAS 20859-73-8, ' UN 1397) and Zinc Phosphide (CAS 1314-84-7; UN 1714) Synonyms of phosphine include hydrogen phosphide, phosphorus hydride, phosphorous trihydride, and phosphorated hydrogen. Victims exposed to phosphine gas only do not pose a significant risk of secondary contamination; however, victims exposed to solid phosphides may present such a risk. Metallic phosphides on clothes, skin, or hair, or in vomitus can react with water or moisture to generate phosphine gas. Phosphine is a respiratory irritant and can cause CNS depression and cardiovascular failure. Most phosphine exposures occur by inhalation of the gas or ingestion of metallic phosphides. Description -- Industrial phosphine is a colorless, flammable, and toxic gas with an odor of garlic or decaying fish. It can ignite spontaneously on contact with air. The gas is shipped as a liquefied, compressed gas. Aluminum phosphide (Celphos, Phostoxin, Quick Phos) and zinc phosphide (ZNP-Field Rat Powder) are solids that are used as a grain fumigant and rodenticide, respectively. Zinc phosphide is often mixed with bait foods such as cornmeal; if not placed judiciously, it can be a danger to pets and children. When phosphides are ingested or exposed to moisture, they release phosphine. Phosphine gas also may be released when acid contacts metal shavings. Routes of Exposure -- Inhalation - Inhalation is the major route of phosphine toxicity. Odor is not an adequate indicator of phosphine's presence and may not provide reliable warning of dangerous concentrations. In cases of acute exposure, however, the odor of phosphine will probably be detected. Phosphine is heavier than air and may cause asphyxiation in enclosed, poorly ventilated, or low-lying areas. Skin/Eye Contact - Phosphine produces no adverse effects on the skin or eyes, and contact does not result in systemic toxicity. Contact with liquified or compressed phosphine may result in frostbite injury. Ingestion - Ingestion of phosphine is unlikely, but ingestion of metallic phosphides can produce phosphine intoxication when the solid phosphide contacts the acidic gastric milieu. Properties -- Description: Colorless gas; odor of garlic or decaying fish Warning properties: Inadequate; nonirritating and garlic-like or fishy odor at 1 to 3 ppm OSHA PEL (permissible exposure limit) = 0.3 degrees ppm (averaged over an 8-hour workshift) OSHA STEL (short term exposure limit) = 1 ppm (.15-minute sample) NIOSH IDLH (immediately dangerous to life or health) = 200 ppm Molecular weight = 34.0 Melting Point = -209 degrees F (-134 degrees C) Boiling point (760 mm Hg) = -126 degrees F (- 87.7 degrees C) Vapor pressure (67.1 degrees F) = >760 mm Hg Gas density = 1.17 (air = 1) Slightly water-soluble Extremely flammable and explosive; may ignite spontaneously on contact with air. Sources/Uses -- Phosphine is produced by reacting water or acid with metallic phosphides. It may be produced during the generation of acetylene gas. Phosphine is used in the semiconductor industry to introduce phosphorus into silicon crystals as an intentional impurity. It also is used as a fumigant and a polymerization initiator. Health Effects Phosphine is cytotoxic and causes profound changes in multiple organs with high oxygen demand--brain, kidneys, heart, and liver. Signs and symptoms of phosphine poisoning typically represent various stages of cardiovascular collapse. Acute Exposure -- Mechanism of Injury. Phosphine interferes with enzymes and protein synthesis, primarily in the myocardial mitochondria and pulmonary cells. In the myocardium, these changes produce cation permeability disturbances, which give rise to transmembrane potentials that ultimately result in peripheral vascular collapse and cardiac arrest. The majority of deaths are cardiovascular in origin and occur within the first 12 to 24 hours after exposure. If the patient survives the initial 24 hours, the ECG returns to normal, indicating that myocardial damage is reversible. Phosphine's direct cytotoxicity to pulmonary cells can result in pulmonary edema and pneumonitis. The liver and kidneys also are affected. Neurologic - Phosphine is a CNS depressant. Initial effects may include headache, restlessness, vertigo, paresthesias, ataxia, intention tremor, diplopia, and stupor. Severe exposure can cause seizures and coma. Respiratory - Toxicity that occurs after inhalation is characterized by chest tightness, cough, and dyspnea. Severe exposure can cause pulmonary edema, which may have a delayed onset of 72 hours or more after exposure. Pulmonary symptoms also can result from ingestion of metallic phosphides (e.g., aluminum or zinc phosphide). Cardiovascular - Cardiovascular manifestations include toxic myocarditis, which may result in valve damage, myocardial ischemia, congestive heart failure, dysrhythmias, or cardiac arrest. Phosphine's effect on the small peripheral vessels causes a profound decrease in systemic vascular resistance. These vascular changes may lead to marked hypotension that may be poorly responsive to pressor agents. Gastrointestinal - Gastrointestinal symptoms are usually the first to manifest after an exposure. Symptoms may include nausea, vomiting, abdominal pain, and diarrhea. Hepatic - Typically, hepatic injury does not manifest until 48 to 72 hours after exposure. Findings include jaundice, hepatomegaly, and elevated serum transaminases. Hyperbilirubinemia was reported in adult patients with acute aluminum phosphide poisoning. Renal - Microhematuria, proteinuria, and acute renal failure can occur. Potential Sequelae Although most survivors of acute phosphine exposure show no permanent disabilities, ischemic damage to the brain and heart have been reported in at least one case. Subacute poisoning re suiting from exposure of a few days was reported to cause reactive airways dysfunction syndrome (RADS) 18 months later. Chronic Exposure -- Cardiac, hepatic, and renal dysfunction may occur from chronic exposure to phosphine. Carcinogenicity No studies have been done to determine if phosphine is carcinogenic. Reproductive and Developmental Effects - In the absence of maternal toxicity, phosphine is unlikely to be a developmental hazard. Prehospital Management Victims exposed to phosphine gas only do not pose a significant risk of secondary contamination to personnel outside the Hot Zone. However, patients exposed to solid phosphides, which react with moisture to produce phosphine, can pose such a risk if phosphides are on clothes, skin, or in hair. Phosphine is a multisystem toxicant that can cause pulmonary irritation, CNS depression, and cardiovascular collapse. There is no antidote for phosphine poisoning; treatment consists of supportive measures. Hot Zone - Note. Rescuers should be trained and appropriately attired before entering the Hot Zone. If the proper equipment is not available, or if rescuers have not been trained to use it, call for assistance from a local or regional hazmat team or other properly equipped response organization. Rescuer Protection - Rescuers in the Hot Zone should wear self-contained breathing apparatus (SCBA). Chemical-protective clothing and gloves are not required. ABCs - Quickly ensure a patent airway. Stabilize the cervical spine with a collar if trauma is suspected. Administer supplemental oxygen and assist ventilation with a bag-valve-mask device if necessary. Brush powder from the skin, hair, and clothes of victims before leaving the Hot Zone. Victim Removal - If victims can walk, lead them out of the Hot Zone to the Decontamination Zone. If victims are unable to walk, remove them on a backboard or gurney. If there is no other means of transport, carefully carry or drag the victims to safety. Decontamination Zone -- Note. Victims with exposure to only phosphine gas do not need decontamination. They may be transferred immediately to the Support Zone. Victims exposed to metallic phosphides will require decontamination; see Basic Decontamination on the following page. Rescuer Protection - Rescuers in the Decontamination Zone should wear self-contained breathing apparatus (SCBA). Chemical-protective clothing and gloves are not required. If the proper equipment is not available, or if rescuers have not been trained to use it, call for assistance from a local or regional hazmat team or other properly equipped response organization. ABCs - Quickly ensure a patent airway. Stabilize the cervical spine with a collar if trauma is suspected. Administer supplemental oxygen and assist ventilation with a bag-valve-mask device if necessary. Monitor cardiac function. Decontamination - Brush all visible particles from clothes, skin, and, hair. Remove and double-bag contaminated clothing while flushing exposed skin with water. Patients who are able and cooperative may assist with their own decontamination. Thoroughly flush exposed skin and hair with plain water for at least 5 minutes. If phosphides have been ingested, administer activated charcoal. Phosphides will release phosphine in the stomach; therefore, watch for signs similar to those produced by phosphine inhalation. Transfer to Support Zone - As soon as basic decontamination is completed, move the patient to the Support Zone. Support Zone -- Note. Be certain that patients exposed to metallic phosphides have undergone basic decontamination (see Decontamination Zone). Patients who have been exposed to gas only or who have undergone proper decontamination pose no serious risk of causing secondary contamination. Support Zone personnel require no specialized protective gear in such cases. ABCs - Quickly ensure a patent airway. Stabilize the cervical spine with a collar if trauma is suspected. Administer supplemental oxygen and assist ventilation with a bag-valve-mask device if necessary. Establish intravenous access in all seriously symptomatic patients and attach a cardiac monitor. Monitor cardiac function. Advanced Treatment - Intubate the trachea if indicated (as in cases of respiratory compromise). When endotracheal intubation cannot be performed due to airway obstruction, perform cricothyroidotomy if equipped and trained to do so. Treat bronchospasm with aerosolized bronchodilators. Treat coma, seizures, and ventricular dysrhythmias according to ALS protocol. If massive exposure is suspected or if the patient is hypotensive, infuse intravenous saline or lactated Ringer's solution (adult dose: 500 to 1000 mL). If phosphides have been ingested, administer activated charcoal. Phosphides will release phosphine in the stomach; therefore, watch for signs similar to those produced by phosphine inhalation. Transport to a Medical Facility - Report to the base station and the receiving medical facility the condition of the patient, treatment given, and estimated time of arrival at the medical facility. If a patient has ingested a metallic phosphide, prepare the ambulance for possible vomiting of toxic material. Have ready several towels and opened plastic bags to quickly clean up and isolate vomitus. Multi-Casualty Triage -- Note. If possible, consult with the base station physician or regional poison control center for advice regarding triage of multiple victims. Inhalation Exposure - Because it is difficult to determine at the scene which patients have had the most serious inhalation exposure and because some systemic symptoms may be delayed for up to 72 hours after exposure, it is prudent to refer all patients with a potentially significant exposure to a medical facility. Those who by history have had a massive exposure and those who experienced a garlic or fish-like odor should be evaluated first. Ingestion Exposure - All patients who have ingested phosphides should be transported to a medical facility without delay. Emergency Department Management Victims exposed to only phosphine gas do not pose a significant risk of secondary contamination to personnel outside the Hot Zone. However, solid phosphides, which react with moisture to produce phosphine, may present a secondary contamination risk if they are present on clothes, skin, or in hair. Phosphine is a multisystem toxicant that causes acute pulmonary irritation, CNS depression, and cardiovascular collapse. Fatal outcomes after the initial 24 hours are usually due to hepatic or renal failure. There is no antidote for phosphine poisoning. Treatment consists of supportive measures. Decontamination Area - Note. Patients exposed to only phosphine do not need decontamination. They may be transferred immediately to the Critical Care Area. Other patients will require decontamination as described below. ABCs - Evaluate and support airway, breathing, and circulation. Watch for signs of airway compromise. Monitor cardiac rhythm. Basic Decontamination - Brush powder from the skin, hair, and clothes of victims who have been exposed to solid phosphides. Remove and double-bag the patient's clothing while flushing the skin and hair with copious water (preferably under a shower). Critical Care Area -- Note. Be certain that patients exposed to solid phosphides have been decontaminated as described above. Decontamination is unnecessary for patients exposed only to phosphine gas. ABCs - Evaluate and support airway, breathing, and circulation. Watch for signs of airway compromise. Monitor cardiac rhythm. Hypotension may develop and may be poorly responsive to pressor agents. Treat seizures and coma in the conventional manner. Patients with significant and persistent signs of CNS depression should be evaluated for the presence of intercurrent disorders (such as trauma, hypoglycemia, or drug intoxication). Inhalation Exposure - Symptomatic patients should receive supplemental oxygen for dyspnea and should be observed for at least 72 hours with repeated chest examinations and other appropriate studies. Follow-up as clinically indicated. Ingestion Exposure - Remove phosphides from the stomach as soon as possible since most phosphides release phosphine gas on contact with water or acids. Administer activated charcoal. A mineral oil cathartic ( 1 CO mL) is recommended rather than a saline cathartic.Watch for signs and symptoms similar to those produced by inhalation exposure, treat accordingly. Antidotes and Other Treatments - There is no antidote for phosphine toxicity. Hemodialysis was used successfully for one patient with massive renal failure from phosphine exposure. The effectiveness of exchange transfusions is questionable. The value of steroids has not been proven in phosphine-exposed patients who develop acute pulmonary symptoms. Laboratory Tests - Establish baseline for pulmonary function (ABGs, chest radiography), renal function (BUN, creatinine, urinalysis) and liver function (AST, ALT, bilirubin); monitor as required. Serial myocardial enzyme levels also may be helpful. Phosphine is metabolized to phosphite and hypophosphite, which are excreted in the urine. Although analysis for these metabolites i s not clinically useful in an emergency setting, urine samples can be collected and frozen for future analysis, particularly if questions on the nature or extent of exposure are likely. Disposition and Follow-up -- Note. Decisions to admit or discharge a patient should be based on exposure history, physical examination, and test results. Delayed Effects - Because onset of pulmonary edema and liver damage may be delayed for 72 hours or more after exposure, all patients with a history of significant exposure should be admitted and observed carefully. In cases of severe exposure, survival for 4 days usually predicts full recovery. Patient Release - Asymptomatic patients with normal initial examinations, minimal exposure, and no signs of toxicity after observation for 4 to 6 hours may be discharged with instructions to return to the ED if symptoms of toxicity develop (see the reverse side of Patient Information Sheet--Phosphine). Follow-up - Patients exposed to phosphine should be monitored for late neurologic sequelae and pulmonary dysfunction. Reporting -- If a work-related incident has occurred, you may be legally required to file a report; contact your state or local health department. Other persons may still be at risk in the setting where this incident occurred. If the incident occurred in the workplace, contact the employer or OSHA for assistance in evaluating workplace conditions. An appropriate public agency can be notified ira public health risk exists. If appropriate, inform patients that they may request an evaluation of their workplace from NIOSH. See Appendix III for a list of these and other agencies that may be of assistance. Phosphine and Phosphides Patient Information Sheet This handout provides information and follow-up instructions for persons who may have been exposed to phosphine or phosphides. What is phosphine? What are phosphides? Phosphine is a toxic gas that has no color and smells like garlic or fish. A serious exposure to phosphine could occur, however, even if a person does not smell it. Phosphine is used widely in the semiconductor industry. Certain pesticides containing zinc phosphide or aluminum phosphide can release phosphine when they come in contact with water or acid. The phosphine formed in the stomach when these solid phosphides are swallowed can result in phosphine poisoning. What is the treatment for phosphine poisoning? There is no antidote (remedy) for phosphine poisoning, but its effects can be treated, and most exposed persons get well. Persons who have experienced serious symptoms may need to be hospitalized for 72 hours or more. What immediate health effects may be caused by exposure to phosphine? Exposure to even small amounts of phosphine can cause headache, dizziness, nausea, vomiting, diarrhea, drowsiness, cough, and chest tightness. More serious exposure can cause shock, convulsions, coma, abnormal heart rhythms, and liver and kidney damage. Are any future health effects likely to occur? After a single, small exposure, no delayed or long-term effects are likely to occur. After a severe exposure, symptoms usually begin immediately but might not appear for up to 72 hours or more. The reverse side of this page lists some signs and symptoms to watch for--if any of them occur, seek medical care. Some severely exposed persons have experienced long-term brain, heart, and lung injury. What tests can be done if a person has been exposed to phosphine? There are no specific blood or urine tests for phosphine itself. However, metabolites of phosphine can be measured in urine. Blood, urine, and other tests also may show if there has been any serious effect on the brain, lungs, heart, liver, or kidneys. Testing is not needed in every case. Where can more information about phosphine be found? More information about phosphine and phosphides may be obtained from your regional poison control center, your state, county, or local health department; the Agency for Toxic Substances and Disease Registry (ATSDR); your doctor; or a clinic in your area that specializes in occupational and environmental health. If the exposure happened at work, you may wish to contact the Occupational Safety and Health Administration (OSHA) or the National Institute for Occupational Safety and Health (NIOSH). Ask the person who gave you this form for help in locating these telephone numbers. Phosphine and Phosphides Follow-up Instructions - Follow only the instructions checked below. Pease take this page with you to your next appointment. ( ) Call your doctor or the Emergency Department if you develop any of the following symptoms within the next 24 hours: * cough * difficulty breathing or shortness of breath * wheezing * chest pain * fever * fatigue or flu-like symptoms ( ) No follow-up appointment is necessary unless you develop any of the symptoms described above. ( ) Call for an appointment with Dr. _________ in the practice of_________. When you call for your appointment, please tell the receptionist/nurse that you were treated in the Emergency Department at__________________ Hospital by __________ and were advised to be seen again in __ days. ( ) Return to the Emergency Department/__________Clinic on (date)__________ at____ AM/PM for a follow-up examination. ( ) Do not perform vigorous physical activities for __ days. ( ) You may resume everyday activities including driving and operating machinery. ( ) Do not return to work for __ days. ( ) You may return to work on a limited bais. See instructions below. ( ) Avoid exposure to cigarette smoke for 24 hours since smoke may worsen injury to your lungs. ( ) Avoid drinking alcoholic beverages or taking aspirin for 24 hours since these substances may aggravate injury to your stomach lining or may have other effects. ( ) You may continue taking the following medication(s) that your doctor(s) prescribed for you:____________________________________________________ _______________________________________________________________________ ( ) Other instructions:____________________________________________________ _______________________________________________________________________ Signature of patient _______________________ Date _________________________ Signature of physician _____________________ Date _________________________ Above courtesy of C.D.C.