Substances Included Synonyms

Therapeutic Toxic Class

A)

Specific Substances

1) 1,2-Dibromoethane
2) 1,2-Ethylene dibromide
3) Alpha,beta-dibromoethane
4) Dibromoethane
5) EDB
6) Ethane, 1,2-dibromo-
7) Ethylene bromide
8) Glycol bromide
9) Glycol dibromide
10) syn-Dibromoethane
11) Molecular formula: C2-H4-Br2
12) CAS 106-93-4
13) EDB (ETHYLENE DIBROMIDE)

1.2.1) MOLECULAR FORMULA
1) C2H4Br2

Available Forms Sources

A)

1) Ethylene bromide is a colorless heavy liquid or a solid. It has a mildly sweet or chloroform odor (HSDB , 2002).

B)

1) It is manufactured from ethylene and bromine; it is also made from acetylene and hydrobromic acid (HSDB , 2002).

C)

1) Ethylene dibromide is used as an antiknock additive in gasoline and as a soil/grain fumigant (Ashford, 1994). This compound is also used as an agricultural fumigant and industrial chemical. However, most agricultural uses have been banned in the United States since 1984 (Lewis, 1998). Ethylene dibromide is used as a scavenger for lead in gasoline, as a grain fumigant, as a general solvent, and as a fumigant for tree crops. It is also used for waterproofing preparations, and in the synthesis of dyes, pharmaceuticals, and other brominated compounds (ACGIH, 1991; Hathaway et al, 1996; Lewis, 1993).
2) This compound is used as a fumigant for ground pest control and as a constituent of ethyl gasoline. It may also be used in gauge fluids, fire extinguishers, in waterproofing preparations, and may be used as a solvent for celluloid, fats, oils, and waxes (Sittig, 1991). Ethylene dibromide is made from ethylene and bromine and can also be made from acetylene and hydrogen bromide (HBr) (Budavari, 1996).
3) Emulsifiable ethylene dibromide weighs 18.1 lbs/gallon (AAR, 1996).
4) Ethylene dibromide was banned from use for grain products and as a soil fumigant in the US in 1984 (Press Release, 1984).
5) Due to its low flammability in air, ethylene dibromide has been used as a fire extinguishing agent (Clayton & Clayton, 1994).

Overview

Life Support

A)

Clinical Effects

0.2.1)

A) Ethylene dibromide is toxic following ingestion, inhalation, and dermal contact. Rapid effects following ingestion are similar to those following inhalation of concentrated vapors and can include altered gastrointestinal motility, nausea, vomiting, dizziness, drowsiness, agitation, decreased urine output or anuria, chest pain, cough, and respiratory distress. Severe ingestions have resulted in acute hepatic and renal failure, metabolic acidosis and coagulopathy.

1) Unconsciousness and coma have occurred after brief inhalation exposure to vapors in confined spaces. Eye, mucous membrane, and respiratory tract irritation with pneumonia and delayed pulmonary edema can result from vapor inhalation.

B) Renal and hepatic damage or failure have resulted from ingestion and inhalation exposures in humans, and are suspected to occur following other routes of exposure, based on experimental animal studies. Cardiac arrest, and/or multiorgan failure have occurred in fatal cases and may result secondarily from hepatic necrosis, massive fluid losses, and/or electrolyte imbalance. Respiratory arrest can occur. Hypoglycemia, acidosis, and hematologic abnormalities have also been reported.
C) Liquid ethylene dibromide is an eye, mucous membrane, and skin irritant. Brief skin contact will cause erythema and discomfort. Blistering can result if the skin is not rapidly decontaminated. Chemical burns/blisters can occur following prolonged dermal exposure, especially if the site of contact is covered in a fashion which inhibits vaporization. Ethylene dibromide can be absorbed through the skin to produce systemic effects.
D) One study has shown adverse effects on the sperm of workers exposed to ethylene dibromide. Oral administration of ethylene bromide has been associated with testicular atrophy, abnormal sperm, and decreased sperm production in experimental animals.
E) Irritating bromide fumes can be released if ethylene dibromide is heated to decomposition.

0.2.3)

A) Severe exposures may result in rapid and labored respirations, rapid, thready pulse, and/or hypotension.

0.2.4)

A) Exposure to high vapor concentrations produces a burning sensation of the eyes, nose, and throat and causes coughing; however, irritation is not a sufficient warning sign to prevent toxic exposure. The odor of ethylene bromide also is not considered a good warning sign. The lowest concentration detectable is 10 ppm.

0.2.5)

A) Dysrhythmias and fatal cardiac arrest have occurred within hours to 5 days after inhalation of high vapor concentrations or ethylene dibromide ingestion. Severe fluid loss, hepatotoxicity, acidosis, renal failure, and/or other adverse effects were contributing factors.

0.2.6)

A) Exposure to high vapor concentrations can produce mucous membrane and respiratory tract irritation. Severe exposures may result in pneumonitis, pulmonary congestion and edema, and ARDS. Pulmonary edema occurred 3 days after ethylene dibromide ingestion in one fatal human poisoning.

0.2.7)

A) Ethylene dibromide is a mild central nervous system (CNS) depressant. Drowsiness has occurred following ingestion and inhalation. Inhalation of vapors in a confined oxygen-deficient space has caused rapid loss of consciousness, coma, and death. CNS depression has occurred in laboratory animals exposed by inhalation or dermal contact.

0.2.8)

A) Abdominal pain, nausea, vomiting, and diarrhea have been reported following ethylene dibromide ingestion. The vomitus may have a strong chemical odor.

0.2.9)

A) The liver is often affected in ethylene dibromide poisoning. Significant liver damage has resulted from vapor inhalation and ingestion (humans) and vapor inhalation (laboratory animals).

0.2.10)

A) The kidney is often affected in ethylene dibromide poisoning. Significant renal damage has resulted from vapor inhalation and ingestion (humans) and vapor inhalation (laboratory animals).

0.2.11)

A) Metabolic acidosis may occur.

0.2.12)

A) Hypercalcemia, hyperphosphatemia, and hyperkalemia have been reported in patients with renal failure.

0.2.13)

A) Coagulation abnormalities occurred in one fatal ingestion case. Leukocytosis can occur within several days of exposure.

0.2.14)

A) Brief dermal contact with ethylene dibromide can produce pain, edema, and erythema. Failure to remove ethylene dibromide from the skin can cause blisters.

1) Significant irritation with intense pain, edema, erythema, blistering, and sloughing is more likely to occur with repeated or prolonged dermal exposures, particularly if the site of contact is covered with an occlusive material which impedes evaporation of the chemical from the skin surface.

B) Experimental animal studies have shown that ethylene dibromide can be absorbed through intact or abraded skin.

0.2.16)

A) Hypoglycemia and histopathologic evidence of adrenal damage were found in one case of ethylene dibromide ingestion.

0.2.20)

A) Human studies are limited. No significant malformations have been found in the offspring of female laboratory animals exposed to ethylene dibromide concentrations that were not maternally toxic.

1) Concentrations that produce maternal toxicity and mortality have been associated with an increase in fetal mortality, reduced fetal body weight, and/or delayed skeletal development in rats and mice. These fetal effects may be due to altered maternal health rather than a direct effect of ethylene dibromide on the fetus.

B) Oral, inhalation, subcutaneous, and intraperitoneal administration of ethylene bromide has been associated with testicular atrophy, abnormal sperm, decreased sperm production, and/or decreased fertility in male bulls, rabbits, and rats. A dominant lethal test in mice was negative.

Laboratory Monitoring

A)

B)

C)

Treatment Overview

0.4.2)

A) EMESIS: Ipecac-induced emesis is not recommended because of the potential for CNS depression.
B) MUCOSAL DECONTAMINATION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. The exact ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting. Patients should not be forced to drink after ingestion of an acid, nor should they be allowed to drink larger volumes since this may induce vomiting, and thereby re-exposure of the injured tissues to the corrosive acid. Dilution may only be helpful if performed in the first seconds to minutes after ingestion.
C) GASTRIC DECONTAMINATION: Ipecac contraindicated. Activated charcoal is not recommended as it may interfere with endoscopy and will not reduce injury to GI mucosa. Consider insertion of a small, flexible nasogastric or orogastric tube to suction gastric contents after recent large ingestion of a strong acid; the risk of further mucosal injury or iatrogenic esophageal perforation must be weighed against potential benefits of removing any remaining acid from the stomach.
D) DILUTION CONTRAINDICATIONS: Do not attempt to administer oral fluids to individuals who are unconscious or have rapidly progressing CNS depression. Rinse the lips and outer oral area of these individuals with water.
E) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
F) Orotracheal or nasotracheal intubation should be performed for airway management of the unconscious patient.
G) HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (ADULT: begin infusion at 0.5 to 1 mcg/min; CHILD: begin infusion at 0.1 mcg/kg/min); titrate to desired response.
H) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
I) Administer sodium bicarbonate as needed for severe (pH < 7.1) acidosis. Follow standard algorithms for control of arrhythmias. Administer IV glucose to control hypoglycemia.

0.4.3)

A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
B) MONITOR VITAL SIGNS, ECG, and urine output.
C) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
D) ATROPINE: ADULT DOSE: BRADYCARDIA: BOLUS: 0.5 mg IV may repeat every 3 to 5 min. Maximum: 3 mg. PEDIATRIC DOSE: 0.02 mg/kg IV/IO (0.04 to 0.06 mg/kg ET). Repeat once, if needed. Minimum dose: 0.1 mg. Maximum single dose: Child: 0.5 mg; Adolescent: 1 mg. Maximum total dose: Child: 1 mg; Adolescent: 2 mg.

0.4.4)

A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.

0.4.5)

A) OVERVIEW

1) Immediately remove contaminated jewelry, clothing, and footwear. Failure to promptly and thoroughly decontaminate the skin may result in blistering and systemic effects. Ethylene bromide can penetrate ordinary rubber gloves. Blistered areas should be managed as burns. A physician should examine the exposed area if irritation or pain persists after the area is washed.
2) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
3) Treat minor chemical burns with conventional methods (debridement, antibiotics, dressings, and tetanus prophylaxis). Consult a clinician experienced in burn therapy for extensive burns or large-surface area burns.

Range Of Toxicity

A)

B)

1) Most cases of toxic exposure have resulted from inhalation of ethylene dibromide vapors for 20 to 45 minutes in poorly ventilated confined spaces. Ethylene dibromide vapor concentrations in two deaths were believed to range from 15 to 41 ppm. Dermal exposure may have contributed to the adverse effects documented in two human cases of lethal ethylene dibromide inhalation.

C)

1) Fatality has resulted from ingestion of 1 mL by an adult female with a history of ethanol abuse and from ingestion of an estimated 15 mL by a male teenager.

D)

1) Dermal or ocular contact with ethylene dibromide liquid or vapors produces local effects, such as, irritation and blistering (skin). Little data are available concerning the systemic effects of ethylene dibromide absorbed through human skin or eyes. Experimental animal studies have shown that ethylene dibromide liquid produces adverse systemic effects following absorption through intact or abraded skin.

Clinical Effects

Summary Of Exposure

A)

1) Unconsciousness and coma have occurred after brief inhalation exposure to vapors in confined spaces. Eye, mucous membrane, and respiratory tract irritation with pneumonia and delayed pulmonary edema can result from vapor inhalation.

B)

C)

D)

E)

Vital Signs

3.3.1)

A) Severe exposures may result in rapid and labored respirations, rapid, thready pulse, and/or hypotension.

3.3.2)

A) WITH POISONING/EXPOSURE

1) Respiratory distress and tachypnea have occurred following vapor inhalation (Nouchi, 1984) and ingestion of ethylene dibromide (Olmstead, 1960). Dyspnea has developed 3 days after ingestion; pulmonary edema was present (Yodaiken & Babcock, 1973).

3.3.3)

A) WITH POISONING/EXPOSURE

1) Although hypothermia has been reported in laboratory animals exposed dermally to ethylene dibromide (Rowe et al, 1952), temperature has been normal in humans following inhalation or ingestion (Olmstead, 1960; Nouchi, 1984).

3.3.4)

A) WITH POISONING/EXPOSURE

1) Hypotension and shock have been reported in fatal cases of ethylene dibromide ingestion and inhalation (Olmstead, 1960; Yodaiken & Babcock, 1973; Nouchi, 1984).

3.3.5)

A) WITH POISONING/EXPOSURE

1) Slow or rapid pulse may be present in acute inhalation or oral exposures (Olmstead, 1960; Letz et al, 1984; Nouchi, 1984; Singh et al, 2007).

Heent

3.4.1)

A) Exposure to high vapor concentrations produces a burning sensation of the eyes, nose, and throat and causes coughing; however, irritation is not a sufficient warning sign to prevent toxic exposure. The odor of ethylene bromide also is not considered a good warning sign. The lowest concentration detectable is 10 ppm.

3.4.3)

A) WITH POISONING/EXPOSURE

1) High vapor concentrations cause eye discomfort (Letz et al, 1984; Hathaway et al, 1996) but corneal opacification in humans has not been reported even in lethal exposures (Grant & Schuman, 1993). An eye splash may cause mild irritation; injury may result if the chemical is not promptly removed from the eyes or skin (Hayes & Laws, 1991).
2) Corneal clouding developed in dogs exposed for up to 90 minutes to vapor concentrations of 1 to 5 cubic centimeters of ethylene dibromide in 1000 L of air (Grant & Schuman, 1993).
3) A drop of undiluted ethylene dibromide applied to the rabbit eye caused pain, conjunctival irritation that cleared within 48 hours, and transient damage to the corneal epithelium (Rowe et al, 1952). A 10% solution of ethylene dibromide in propylene glycol tested in the rabbit eye caused a more severe response than undiluted ethylene dibromide, with moderate to severe corneal injury, which healed without scarring within 12 days.
4) Bilateral subconjunctival hemorrhages were reported in a teenager following an EDB ingestion. The patient developed cardiac arrest and died (Aneja et al, 1988).

3.4.6)

A) WITH POISONING/EXPOSURE

1) A burning sensation of the throat has been reported following significant exposure to ethylene dibromide (Letz et al, 1984).

Cardiovascular

3.5.1)

A) Dysrhythmias and fatal cardiac arrest have occurred within hours to 5 days after inhalation of high vapor concentrations or ethylene dibromide ingestion. Severe fluid loss, hepatotoxicity, acidosis, renal failure, and/or other adverse effects were contributing factors.

3.5.2)

A) CONDUCTION DISORDER OF THE HEART

1) WITH POISONING/EXPOSURE

a) Inhalation of high concentrations of EDC may result in death from ventricular fibrillation (Hathaway et al, 1996). Right bundle branch block, atrioventricular block, supraventricular tachycardia, and fatal asystole have occurred 12 hours to 5 days after ethylene dibromide vapor inhalation (Letz et al, 1984; Nouchi, 1984) or ingestion (Yodaiken & Babcock, 1973).

1) These cases were complicated by development of hypocalcemia, pulmonary edema, hepatotoxicity, severe metabolic acidosis, progressive renal failure, significant central nervous system depression, and/or hematologic derangements prior to cardiac arrest.

b) CASE REPORT: Aneja et al (1988) reported a fatality following ingestion of 3 ampules of unknown volume containing EDB. The patient developed shock, refractory to vasopressors, and an abnormal ECG on the second day, which included sinus tachycardia, wide QRS complexes, and a terminally slow ventricular rhythm with elevated ST segment. Cardiac arrest followed (Aneja et al, 1988).
c) ECG may reveal evidence of hyperkalemia (peaked T waves, QRS widening) in patients with renal failure (Prakash et al, 1999).

B) MYOCARDITIS

1) WITH POISONING/EXPOSURE

a) Reesal et al (1985) proposed that two ethylene dibromide related fatalities were due to myocarditis associated with infection by Clostridium sordellii, Clostridium septicum, or related species (Reesal et al, 1985).

C) HYPOTENSIVE EPISODE

1) WITH POISONING/EXPOSURE

a) CASE REPORT: Shock secondary to massive hepatic necrosis and gastrointestinal fluid loss occurred in an adult following ingestion of 1 mL of ethylene dibromide (Olmstead, 1960). Vital signs prior to death included a thready, weak pulse of 140 bpm, clear respirations of 48 per minute, blood pressure of 98/72 mm Hg, and temperature of 98.6 degrees C.
b) CASE REPORT: Refractory hypotension, unresponsive to vasopressors, was reported in a 16-year-old girl following ingestion of 2 ampules of unknown volume containing EDB. ECG revealed sinus tachycardia. She had a cardiac arrest and developed acute renal failure within 3 days of the ingestion (Aneja et al, 1988). This same author reported two other cases of refractory hypotension following EDB ingestions.

D) CARDIAC ENZYMES ABNORMAL

1) WITH POISONING/EXPOSURE

a) Lactic dehydrogenase, creatinine phosphokinase, and creatinine phosphokinase isoenzyme values may be elevated (Yodaiken & Babcock, 1973; Nouchi, 1984).

E) PULSE RATE FINDING

1) WITH POISONING/EXPOSURE

a) CASE SERIES: In a series of 64 intentional ethylene dibromide ingestions, 38 of the cases expired. Of these 38 cases, 24 patients had a pulse rate greater than 100 bpm at the time of admission. Pulse rate greater than 100 bpm was a statistically significant prognostic factor (p = 0.0004199) (Singh et al, 2007).

3.5.3)

A) ANIMAL STUDIES

1) CARDIAC ARREST

a) Death due to cardiac arrest or respiratory arrest occurred in laboratory rats within 24 hours of inhalation of high vapor concentrations (Rowe et al, 1952).

Respiratory

3.6.1)

A) Exposure to high vapor concentrations can produce mucous membrane and respiratory tract irritation. Severe exposures may result in pneumonitis, pulmonary congestion and edema, and ARDS. Pulmonary edema occurred 3 days after ethylene dibromide ingestion in one fatal human poisoning.

3.6.2)

A) IRRITATION SYMPTOM

1) WITH POISONING/EXPOSURE

a) Limited human data supplemented by experimental animal data indicate that inhalation of concentrated ethylene dibromide vapors produces respiratory irritation with potential development of respiratory arrest, pneumonia, and/or pulmonary edema (Torkelson, 1994).

B) ACUTE LUNG INJURY

1) WITH POISONING/EXPOSURE

a) Pulmonary effects of concentrated vapor exposures to EDB include pneumonitis, pulmonary congestion and edema, and ARDS (Mehrotra et al, 2001).
b) CASE REPORT: Pulmonary edema was present after successful cardiac resuscitation of a 15-year-old patient who had ingested 15 mL of ethylene dibromide 3 days prior to cardiac arrest (Yodaiken & Babcock, 1973). The boy had vomited after ingestion, but there was no reported evidence of aspiration pneumonitis. Dyspnea and oliguria were present prior to cardiac arrest and development of pulmonary edema. Peritoneal dialysis was performed, and pulmonary edema resolved within 36 hours.

C) TACHYPNEA

1) WITH POISONING/EXPOSURE

a) Tachypnea (Olmstead, 1960) and significant respiratory distress (Nouchi, 1984) despite clear lung sounds have been reported in fatal cases of ethylene dibromide ingestion and inhalation. One worker developed respiratory distress 24 hours after inhalation of vapors in a confined space (Nouchi, 1984).

3.6.3)

A) ANIMAL STUDIES

1) APNEA

a) High vapor concentrations produced death due to respiratory arrest or cardiac failure within 24 hours of exposure in laboratory rats (Rowe et al, 1952).

2) PULMONARY EDEMA

a) Exposure of laboratory rats to ethylene dibromide vapor concentrations ranging from 200 to 10,000 ppm for up to 16 hours produced pulmonary edema, pneumonia, and death; exposure for up to 16 hours to 100 ppm was not lethal (Rowe et al, 1952).

3) PNEUMONIA

a) Death due to pneumonia has resulted from single exposures of laboratory rats to vapor concentrations ranging from 100 to 10,000 ppm and from repeated 7 hour exposures to 50 ppm for up to 63 times in 91 days. An increase in fatal upper respiratory tract infections was also found with long-term low dose exposure (Rowe et al, 1952).

Neurologic

3.7.1)

A) Ethylene dibromide is a mild central nervous system (CNS) depressant. Drowsiness has occurred following ingestion and inhalation. Inhalation of vapors in a confined oxygen-deficient space has caused rapid loss of consciousness, coma, and death. CNS depression has occurred in laboratory animals exposed by inhalation or dermal contact.

3.7.2)

A) CENTRAL NERVOUS SYSTEM DEFICIT

1) WITH POISONING/EXPOSURE

a) Ethylene dibromide has weak anesthetic properties, but can produce CNS depression (Torkelson, 1994; Aneja et al, 1988). Accidental use of 22 grams of ethylene dibromide as an anesthetic failed to produce desirable anesthesia, but did cause death (Marmetschke, 1910; Letz et al, 1984). Headache, nausea, anorexia, dizziness, and drowsiness have been reported following vapor inhalation (Finkel, 1983; Nouchi, 1984) and ingestion (Olmstead, 1960; Yodaiken & Babcock, 1973; Aneja et al, 1988; Singh et al, 2007).
b) Ingestions of ethylene dibromide have resulted in metabolic encephalopathy secondary to renal and hepatic insufficiency (Prakash et al, 1999).

B) COMA

1) WITH POISONING/EXPOSURE

a) Brief exposure to ethylene dibromide vapors in confined spaces has caused loss of consciousness within 5 minutes of exposure and coma in two cases. Coma has occurred with only 45 minutes of vapor exposure in one case (Letz et al, 1984), but was delayed for 24 hours after 30 minutes of vapor exposure in another (Nouchi, 1984). Death occurred within 12 hours or 4 days following exposure, respectively, in these two cases.
b) CASE SERIES: Drowsiness, altered mental status, and coma occurred in 28.3% of patients (n=53) following intentional ethylene dibromide ingestions (Pahwa et al, 2013).

C) PSYCHOMOTOR AGITATION

1) WITH POISONING/EXPOSURE

a) Agitation and delirium have been reported in fatal cases of ethylene dibromide inhalation (Letz et al, 1984; Nouchi, 1984) and ingestion (Olmstead, 1960).

3.7.3)

A) ANIMAL STUDIES

1) CNS DEPRESSION

a) Appreciable CNS depression occurred in laboratory animals exposed to very high vapor concentrations. Intense CNS depression occurred in rabbits following application of 0.21, 0.30, 0.65, or 1.1 gram/kg of ethylene dibromide dermally for 24 hours with an occlusive dressing at the application site (Rowe et al, 1952).

Gastrointestinal

3.8.1)

A) Abdominal pain, nausea, vomiting, and diarrhea have been reported following ethylene dibromide ingestion. The vomitus may have a strong chemical odor.

3.8.2)

A) GASTROENTERITIS

1) WITH POISONING/EXPOSURE

a) Nausea, vomiting, abdominal pain, and profuse watery diarrhea have been reported following inhalation exposure (Letz et al, 1984; Nouchi, 1984) and ingestion (Olmstead, 1960; Yodaiken & Babcock, 1973; Aneja et al, 1988; Singh et al, 2000; Mehrotra et al, 2001). Recurrent vomiting is common following ingestions, with onset usually occurring within 15 to 60 minutes (Mehrotra et al, 2001).
b) CASE REPORT: Abdominal pain, nausea, vomiting, and watery diarrhea of 2 day's duration occurred in an adult 48 hours after ingesting 2 Fumisoil capsules, a total dose of 1 mL of ethylene dibromide (Olmstead, 1960). The woman died 54 hours after ingestion in a state of profound shock linked to excessive gastrointestinal tract fluid loss and hepatic necrosis.
c) CASE REPORT: The onset of vomiting was 2 hours following ingestion of 15 mL of ethylene dibromide in another fatal case(Yodaiken & Babcock, 1973). Severe headache and lethargy were also present, suggesting that vomiting may be due to CNS depression and gastric irritation.
d) The vomitus may have a strong chemical odor (Letz et al, 1984).
e) CASE SERIES: In a series of 64 intentional ethylene bromide ingestions, nausea and vomiting were the most common symptoms. Abdominal pain and diarrhea were also common symptoms, occurring in 25% and 12.5% of cases, respectively (Singh et al, 2007).
f) CASE SERIES: Of 58 patients with intentional ethylene dibromide ingestions, nausea and vomiting were the most common presenting symptoms. Abdominal pain was also frequently reported in approximately 80% of the patients (Pahwa et al, 2013).

B) GASTRIC ULCER

1) WITH POISONING/EXPOSURE

a) Erosion or ulceration of the gastrointestinal tract may occur following ingestion of EDB (Saraswat et al, 1986).

Hepatic

3.9.1)

A) The liver is often affected in ethylene dibromide poisoning. Significant liver damage has resulted from vapor inhalation and ingestion (humans) and vapor inhalation (laboratory animals).

3.9.2)

A) LIVER DAMAGE

1) WITH POISONING/EXPOSURE

a) Elevated liver enzymes, jaundice, palpable liver, abdominal pain, abnormally high bilirubin levels, elevated serum ammonia, and histopathologic evidence of centrilobular necrosis and other injury have been documented in fatal cases of ethylene dibromide ingestion and inhalation (Marmetschke, 1910) reviewed in (Letz et al, 1984; Olmstead, 1960; Yodaiken & Babcock, 1973; Letz et al, 1984; Nouchi, 1984).
b) Non-fatal cases have been reported following EDB ingestions with rapid onset (within 4 days) of jaundice, abnormal serum liver enzymes levels and hepatic-like illness without evidence of acute liver failure (Mehrotra et al, 2001).
c) CASE REPORT: A later toxic effect is liver necrosis. Massive liver necrosis was observed at postmortem exam of a 23-year-old woman following ingestion of one ampule of EDB (Saraswat et al, 1986).
d) CASE SERIES: Jaundice and elevated liver enzymes occurred in 39.6% of patients (n=53) approximately 48 hours following intentional ethylene dibromide ingestions. Serum transaminase concentrations (SGPT) were significantly higher (p=0.008) in patients who had ingested more than one ethylene dibromide ampule (1628 +/- 3158 units/L) compared to patients who had ingested one ampule or less (717 +/- 1506 units/L) (Pahwa et al, 2013).

B) HEPATIC FAILURE

1) WITH POISONING/EXPOSURE

a) Hepatic failure has been reported following significant exposure to ethylene dibromide (Singh et al, 2000; Letz et al, 1984; Olmstead, 1960).
b) CASE REPORT: Thirty-six hours following an ingestion of 3 mL of ethylene dibromide, a 16-year-old boy developed jaundice and anuria. Coagulopathy and elevated hepatic enzyme levels were reported. Liver dysfunction progressed to hepatic encephalopathy. The patient was administered hemodialysis, due to acute renal failure, and supportive care. His liver function returned to normal 20 days after hospitalization (Singh et al, 2000).
c) CASE SERIES: In a series of 64 intentional ethylene dibromide ingestions, hepatotoxicity, manifesting as jaundice, elevated liver enzymes, increased prothrombin time and bleeding time, was reported in 28 (43.7%) patients. Twenty of the 38 patients who expired (52.5%) had both renal and hepatic failure; four of the 38 patients who expired (10.5%) demonstrated hepatic failure only (Singh et al, 2007).

3.9.3)

A) ANIMAL STUDIES

1) HEPATOCELLULAR DAMAGE

a) Increased liver weight, slight to significant centrilobular fatty degeneration, and hepatic necrosis were found upon postmortem examination of rats, rabbits, guinea pigs, and monkeys acutely exposed to high concentrations of ethylene dibromide vapors (100 ppm to 10,000 ppm), or repeatedly exposed up to more than 100 times, 7 hours per exposure, to vapor concentrations of 50 ppm (Rowe et al, 1952). Some animals of each species did not have hepatotoxicity despite a very high number of repeated exposures.
b) Hepatic fatty degeneration and necrosis following exposure of rats to ethylene dibromide vapors have also been reported (McCollister et al, 1956).

Genitourinary

3.10.1)

A) The kidney is often affected in ethylene dibromide poisoning. Significant renal damage has resulted from vapor inhalation and ingestion (humans) and vapor inhalation (laboratory animals).

3.10.2)

A) RENAL FAILURE SYNDROME

1) WITH POISONING/EXPOSURE

a) Renal insufficiency and progressive renal failure have been reported in fatal cases of ethylene dibromide ingestion and inhalation (Yodaiken & Babcock, 1973; Letz et al, 1984; Nouchi, 1984). Acute renal failure has been reported in non-fatal cases (Mehrotra et al, 2001; Singh et al, 2000; Prakash et al, 1999).

1) Oliguria, dark urine, anuria, and elevated blood urea nitrogen, creatinine, inorganic phosphate, and urinary sodium were present in one case. Hypovolemia and cardiovascular complications were contributing factors. Peritoneal and hemodialysis were instituted with mixed results.

b) CASE SERIES: In a series of 64 intentional ethylene dibromide ingestions, nephrotoxicity, manifesting as hematuria, albuminuria, uremia and oliguria, was reported in 32 (50%) patients. Twenty of the 38 patients who expired (52.5%) had both renal and hepatic failure; four of the 38 patients who expired (10.5%) demonstrated renal failure only (Singh et al, 2007).
c) CASE REPORT: A 16-year-old girl died within 3 days of ingesting 2 ampules of EDB. The day following the ingestion she developed acute renal failure with anuria, resistant to symptomatic therapy. The patient died of circulatory failure and cardiac arrest (Aneja et al, 1988).
d) CASE REPORT: Prakash et al (1999) reported a non-fatal case of anuric acute renal failure resulting from an ingestion of a 3 mL solution containing 6480 mg ethylene dibromide. On hospital admission, BUN of 150 mg/dL and serum creatinine of 6.9 mg/dL were observed. Following supportive therapy and hemodialysis, the 20-year-old patient recovered (Prakash et al, 1999).
e) CASE REPORT: Following the ingestion of ethylene dibromide (3 mL), anuria and jaundice were reported within 36 hours in a 16-year-old boy. Jaundice progressed to acute hepatic failure with encephalopathy. The patient was also diagnosed with acute renal failure (urea 166 mg/dL; creatinine 9 mg/dL; total proteins 5 gm/dL with albumin at 2.8 gm/dL; albuminuria). The patient was started on alternate day hemodialysis. Renal and hepatic function returned to normal by the 20th hospital day (Singh et al, 2000).
f) CASE REPORT: Postmortem examination revealed parenchymal degeneration of the kidneys in one fatality involving accidental use of 22 grams of ethylene dibromide as an anesthetic (Marmetschke, 1910; Letz et al, 1984).
g) CASE SERIES: Nephrotoxicity, characterized by hematuria, proteinuria, azotemia, and oliguria, was reported in 26.4% of patients (n=53) approximately 48 hours after intentional ethylene dibromide ingestions (Pahwa et al, 2013).

B) ACUTE TUBULAR NECROSIS

1) WITH POISONING/EXPOSURE

a) Acute tubular necrosis may occur following ethylene dibromide ingestion (Saraswat et al, 1986). Postmortem examination in cases of inhalational and oral exposure have found tubular necrosis (Olmstead, 1960; Nouchi, 1984).

3.10.3)

A) ANIMAL STUDIES

1) RENAL FAILURE

a) Interstitial congestion, edema, and slight cloudy swelling of the renal tubular epithelium were found postmortem in rats exposed once to high ethylene dibromide vapor concentrations (Rowe et al, 1952). Vapor exposures which produced 50% mortality in rats also produced severe degeneration of the renal tubular epithelium (McCollister et al, 1956).

2) TESTIS DISORDER

a) Animals exposed to toxic amounts of EDB developed testicular atrophy and sterility. Prolonged exposure to 4 mg/kg/day every other day resulted in decreased sperm quality and amount. No effects on humans have been reported from occupational exposure. If permissible exposure levels are kept at a minimum, it is not considered a hazard in the workplace (AMA, 1985).

Acid-Base

3.11.1)

A) Metabolic acidosis may occur.

3.11.2)

A) ACIDOSIS

1) WITH POISONING/EXPOSURE

a) Metabolic acidosis has been reported following ingestions (Singh et al, 2000) and vapor exposures (Letz et al, 1984). Prolonged exposures, or exposure to higher concentrations, may result in intractable metabolic acidosis (Mehrotra et al, 2001).
b) CASE REPORT: Metabolic acidosis (pH of 7.06 and 7.18) developed in two workers exposed to vapors in a confined space (Letz et al, 1984). Vomiting, diarrhea, and renal and circulatory impairment were present.

Hematologic

3.13.1)

A) Coagulation abnormalities occurred in one fatal ingestion case. Leukocytosis can occur within several days of exposure.

3.13.2)

A) BLOOD COAGULATION DISORDER

1) WITH POISONING/EXPOSURE

a) Coagulopathy with hemorrhage, decreased platelets, prolonged prothrombin time, decreased fibrinogen, and deficiency of clotting factors may occur following significant exposures to ethylene dibromide (Singh et al, 2000).
b) CASE REPORT: Hemorrhage, ecchymoses, prolonged partial thromboplastin time (PTT) of 68 seconds, low hematocrit (24%), decreased fibrinogen (100 mg/dL), and significant deficiency of all clotting factors, except for factor VII, developed 3 to 4 days after a 14-year-old patient drank approximately 15 mL of ethylene dibromide (Yodaiken & Babcock, 1973).
c) CASE SERIES: Prolonged prothrombin time was reported in 30.2% of patients (n=53) following intentional ethylene dibromide ingestions (Pahwa et al, 2013).

B) LEUKOCYTOSIS

1) WITH POISONING/EXPOSURE

a) Significantly increased white blood cell count has been reported several days following ethylene dibromide ingestion or inhalation (Yodaiken & Babcock, 1973; Letz et al, 1984; Nouchi, 1984).

Dermatologic

3.14.1)

A) Brief dermal contact with ethylene dibromide can produce pain, edema, and erythema. Failure to remove ethylene dibromide from the skin can cause blisters.

1) Significant irritation with intense pain, edema, erythema, blistering, and sloughing is more likely to occur with repeated or prolonged dermal exposures, particularly if the site of contact is covered with an occlusive material which impedes evaporation of the chemical from the skin surface.

B) Experimental animal studies have shown that ethylene dibromide can be absorbed through intact or abraded skin.

3.14.2)

A) CHEMICAL BURN

1) WITH POISONING/EXPOSURE

a) A review of 16 cases of accidental exposure found that mild irritation of the skin occurred following liquid splashes; rapid decontamination prevented injury. Chemical burns occurred if ethylene dibromide was not rapidly removed from the skin (Hayes & Laws, 1991).
b) The inflammation and blistering can be delayed for 15 to 20 hours.
c) EDB readily penetrates clothing, including leather (Zwaveling et al, 1987).

B) ERUPTION

1) WITH POISONING/EXPOSURE

a) Forest workers exposed to EDB treated wood developed an itchy rash which improved after treatment with steroids (NIOSH, 1983).

C) CYANOSIS

1) WITH POISONING/EXPOSURE

a) Cyanosis has been reported in toxic ethylene dibromide exposures (Letz et al, 1984).

3.14.3)

A) ANIMAL STUDIES

1) IRRITATION

a) Erythema and exfoliation developed following application of a 1% solution of ethylene dibromide in butylcarbitol acetate, 10 times over 14 days to a rabbit's ear (Rowe et al, 1952).

1) Administration of this same solution 10 times over 14 days to the shaved abdomen with occlusive dressings produced erythema and edema followed by necrosis and exfoliation of the skin surface. Application of 0.21 to 1.1 grams/kg of ethylene dibromide produced systemic toxicity and moderate to severe dermal erythema, edema, and necrosis.

Musculoskeletal

3.15.2)

A) NECROSIS

1) WITH POISONING/EXPOSURE

a) Skeletal muscle necrosis has been reported following significant exposure to ethylene dibromide (Letz et al, 1984). Elevated creatine phosphokinase may be present, possibly due to myocardial or skeletal muscle damage (Nouchi, 1984).

Endocrine

3.16.1)

A) Hypoglycemia and histopathologic evidence of adrenal damage were found in one case of ethylene dibromide ingestion.

3.16.2)

A) HYPOGLYCEMIA

1) WITH POISONING/EXPOSURE

a) CASE REPORT: Blood glucose levels of 40 mg/dL decreasing to 12 mg/dL developed 2 and 3 days after an adolescent drank 15 mL of ethylene dibromide (Yodaiken & Babcock, 1973). Hypoglycemia was attributed to massive hepatic necrosis and possibly adrenocortical necrosis. Autopsy revealed adrenal gland congestion, focal degenerative cell damage, and degenerative cytoplasmic changes in the zona fasciculata, zona glomerulosa, and zona reticularis.
b) CASE SERIES: Three workers exposed to EDB via inhalation and dermal routes developed hypoglycemia which may have been secondary to liver injury. Hypoglycemia lasted several days, despite a high carbohydrate diet (Wirtschafter & Schwartz, 1939).
c) CASE SERIES: In a series of 64 intentional ethylene dibromide ingestions, hypoglycemia was observed in 24 patients (37.5%)(Singh et al, 2007).

Reproductive

3.20.1)

A) Human studies are limited. No significant malformations have been found in the offspring of female laboratory animals exposed to ethylene dibromide concentrations that were not maternally toxic.

1) Concentrations that produce maternal toxicity and mortality have been associated with an increase in fetal mortality, reduced fetal body weight, and/or delayed skeletal development in rats and mice. These fetal effects may be due to altered maternal health rather than a direct effect of ethylene dibromide on the fetus.

B) Oral, inhalation, subcutaneous, and intraperitoneal administration of ethylene bromide has been associated with testicular atrophy, abnormal sperm, decreased sperm production, and/or decreased fertility in male bulls, rabbits, and rats. A dominant lethal test in mice was negative.

3.20.2)

A) ANIMAL STUDIES

1) EDB was not teratogenic in mice or rats (Minor, 1978; Short et al, 1978; Short et al, 1979), where some skeletal defects were attributed to maternal malnourishment (Short et al, 1978). Adverse effects were only found at exposure levels that were maternally toxic or lethal (20, 38 or 89 ppm) (Short et al, 1978). Some fetal abnormalities were seen with exposure to 31.6 ppm in mice and rats (HSDB , 2002). EDB was fetotoxic, affected male and female fertility, and produced smaller litter sizes in rats and mice with inhalation exposure (RTECS , 2002). Other studies have shown no effects. Injection of 55 mg/kg into rats from 1 to 15 days of pregnancy caused maternal toxicity, but no teratogenicity (RTECS , 2002).
2) No teratogenic effects were observed in offspring of male rabbits exposed to ethylene dibromide doses that caused sperm abnormalities (Williams et al, 1991).

3.20.3)

A) ANIMAL STUDIES

1) EMBRYOTOXICITY

a) Ethylene dibromide vapor exposure at levels that produced maternal toxicity caused reduced number of implants, embryotoxicity (increased resorptions), and decreased fetal weights in mice and rats (Short et al, 1978).

3.20.5)

A) HUMANS

1) There was slightly lower fertility in the WIVES of men exposed to airborne levels of less than 5 ppm of EDB, but this was attributed to increased prevalence of vasectomies in the husbands (Wong, 1979).

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS106-93-4 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) IARC Classification

a) Listed as: Ethylene dibromide
b) Carcinogen Rating: 2A

1) The agent (mixture) is probably carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans. This category is used when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals. In some cases, an agent (mixture) may be classified in this category when there is inadequate evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals and strong evidence that the carcinogenesis is mediated by a mechanism that also operates in humans. Exceptionally, an agent, mixture or exposure circumstance may be classified in this category solely on the basis of limited evidence of carcinogenicity in humans.

3.21.3)

A) NEOPLASM

1) The death incidence and cause of death among workers exposed to ethylene dibromide and other chemicals in two factories prior to 1977 have been determined in a small study involving 161 workers (Ott et al, 1980). Fewer than expected deaths from malignant neoplasms were reported in one factory (2 observed versus 3.6 expected); whereas, 5 versus 2.2 expected deaths due to malignant neoplasms were reported for the other factory. This incidence was not statistically significant.
2) Studies of men exposed to EDB in two factories showed a slight increase in deaths due to cancer over those expected (IARC, 1987).

B) LACK OF EFFECT

1) Other studies (Clayton & Clayton, 1994; Sweeney et al, 1986) reviewed by the International Agency for Research on Cancer (1987) found no statistically significant excess of cancer at any site among over 2500 workers exposed ethylene dibromide and other chemicals, but an excess of lymphoma among grain workers in the USA who may have been exposed to ethylene dibromide and other chemicals.
2) The existing human data are ranked as insufficient (IARC, 1987). Limitations of some studies include small cohort size, lack of complete exposure data, and exposure to potentially toxic and/or carcinogenic chemicals in addition to ethylene dibromide.

3.21.4)

A) CARCINOMA

1) ETHYLENE DIBROMIDE - NIOSH (1981) has noted that the combination of ethylene dibromide and disulfiram has shown to be carcinogenic and teratogenic in laboratory animals. NIOSH is concerned about individuals on disulfiram who are exposed to ethylene dibromide at work.
2) EDB has caused cancer in laboratory animals in many species and by several routes of exposure (RTECS; (Clayton & Clayton, 1994). A NTP carcinogenicity bioassay found it to cause tumors in rats and mice (Anon, 1978) Anon, 1982) at levels of 10 to 40 ppm (p 15). The IARC found EDB to be carcinogenic in mice and rats with inhalation and ingestion exposure, and carcinogenic in mice by dermal absorption (IARC, 1987).
3) Dermal application of ethylene dibromide has produced skin carcinomas and lung tumors in mice; chronic exposure by inhalation to 10 or 40 ppm increased tumors at many sites in rats and mice (Hathaway et al, 1996). Squamous cell carcinomas of the forestomach were produced in rats and mice given ethylene dibromide by gavage for about a year, with total doses of about 13 grams/kg (mice) and 11 grams/kg (rats) (ACGIH, 1991). Oral administration also produced alveolar/bronchiolar lung tumors in mice, liver carcinomas and hemangiosarcomas in rats, and esophageal papillomas in mice (IARC, 1987).

Genotoxicity

A)

B)

C)

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) Monitor arterial blood gases, pulse oximetry, CBC, serum electrolytes, liver and renal function tests, blood glucose, urinalysis, and serum calcium, phosphorus, and magnesium levels. Anion and osmolal gap determinations may be useful.
B) Electrocardiogram, cardiac enzyme determination, chest radiograph, and/or coagulation studies may be required if there are signs and symptoms of cardiac, hematologic, or pulmonary effects. Toxicology screening may be performed to rule out other causative agents if there is uncertainty about the exposure.
C) Serum bromide levels have been elevated in fatal poisonings but are not considered clinically useful.

4.1.2)

A) BLOOD/SERUM CHEMISTRY

1) Monitor CBC, arterial blood gases, pulse oximetry, serum electrolytes, blood urea nitrogen (BUN), creatinine, blood glucose, serum aminotransferases (ALT, AST, ALP), and serum calcium, phosphorus, and magnesium levels. Clotting studies, creatinine phosphokinase (CPK), and lactate dehydrogenase (LDH) determination may be required. Toxicology screening may be performed to rule out other causative agents if there is uncertainty about the exposure.

B) TOXICITY

1) Serum bromide ion monitoring is generally considered to be of limited clinical value (Torkelson, 1994).

4.1.3)

A) URINALYSIS

1) Monitor renal output and urinalysis.

B) URINARY LEVELS

1) Bromide may be found in the urine following exposure to ethylene dibromide (Hayes, 1982), but measurement is not valuable in making treatment decisions.

4.1.4)

A) OTHER

1) TISSUE

a) Bromide may be found in the tissues following exposure to ethylene dibromide (Letz et al, 1984).

Radiographic Studies

A)

1) Chest x-ray is advisable in cases of significant inhalation exposure, if aspiration or pulmonary edema is suspected, or if there is other evidence of impending respiratory distress and/or hypoxia.

Treatment

Life Support

A)

Patient Disposition

6.3.1)

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) Carefully observe patients with ingestion exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.

Monitoring

A)

B)

C)

Oral Exposure

6.5.1)

A) Prevent exposure of rescuers and other individuals - refer to PREVENTION OF CONTAMINATION.
B) EMESIS/NOT RECOMMENDED

1) Ingestion of these compounds may result in burns of the oropharynx. Emesis is NOT recommended. Rinse the victim's mouth. If spontaneous vomiting is occurring, assist the victim to adopt a position that will maintain an open airway and prevent aspiration. Leaning forward or placing on the left side may be useful.

C) ACTIVATED CHARCOAL

1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION

a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).

1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).

2) CHARCOAL DOSE

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).

1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

b) ADVERSE EFFECTS/CONTRAINDICATIONS

1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).

D) DILUTION

1) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).

E) Move the victim out of the contaminated area and to fresh air. If the victim is not responsive, activate the emergency response system. If the victim is not breathing but has a pulse, administer artificial respiration. If the victim is pulseless, administer CPR. If the victim has difficulty in breathing, administer humidified oxygen, if available.
F) DERMAL/EYE: Remove contaminated clothing, jewelry, and shoes. Immediately wash contaminated skin, hair, and under the nails with soap and copious amounts of water. Flush contaminated eyes with running water for at least 15 minutes. Prompt removal of contaminated items and dermal/eye decontamination is of extreme importance in order to prevent severe local and systemic effects. After decontamination, lightly cover skin burns with dry sterile dressings. Contaminated items should be isolated in sealed containers, away from light, heat, active metals, and liquid ammonia.
G) Keep the victim quiet and maintain normal body temperature. Observe for delayed effects. Central nervous system depression, respiratory distress, and cardiac disturbances may develop and necessitate resuscitation efforts or continued support to prevent aspiration.

6.5.2)

A) EMESIS/NOT RECOMMENDED

1) EMESIS: Ipecac-induced emesis is not recommended because of the potential for CNS depression.

B) DILUTION

1) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).
2) DILUTION CONTRAINDICATIONS: Do not attempt to administer oral fluids to individuals who are unconscious or have rapidly progressing CNS depression. Rinse the lips and outer oral area of these individuals with water.

C) ACTIVATED CHARCOAL

1) Activated charcoal (Bronstein & Currance, 1994), or activated charcoal and cathartics which are not oil based (Morgan, 1993), have been recommended as methods by which to prevent absorption of ingested ethylene dibromide. There is insufficient information concerning the benefits and risks of using activated charcoal in actual cases of ethylene dibromide ingestion by humans.
2) CHARCOAL ADMINISTRATION

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

3) CHARCOAL DOSE

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).

1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

b) ADVERSE EFFECTS/CONTRAINDICATIONS

1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).

6.5.3)

A) AIRWAY MANAGEMENT

1) Although not reported, edema of the pharyngeal area may occur in cases of ingestion. Carefully monitor for the development of laryngeal edema, airway constriction, or respiratory distress. Supplemental oxygen, endotracheal intubation, and/or assisted ventilation with positive-end-expiratory pressure (PEEP) or continuous-positive-airway pressure (CPAP) may be needed.

B) FLUID/ELECTROLYTE BALANCE REGULATION

1) Avoid a net positive fluid balance.

C) MONITORING OF PATIENT

1) Respiratory and cardiovascular function should be followed carefully. Onset of symptoms may be delayed and sudden in onset.
2) Monitor ECG for potential cardiac arrhythmias.
3) Monitor liver and kidney function following significant exposure.

D) ACUTE LUNG INJURY

1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).

a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)

3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).

E) GENERAL TREATMENT

1) Treatment should include recommendations listed in the INHALATION EXPOSURE section when appropriate.

Inhalation Exposure

6.7.1)

A) Rescuers should avoid breathing vapors or mists and should wear appropriate protective gloves, boots, goggles, and respiratory protective equipment. Refer to PREVENTION OF CONTAMINATION section of this document.
B) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
C) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
D) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.
E) Cases of inhalation exposure have also involved dermal contact (Letz et al, 1984). Evaluate victim for dermal and clothing exposure to liquid ethylene dibromide and follow recommendations listed under DERMAL EXPOSURE DECONTAMINATION.

6.7.2)

A) MONITORING OF PATIENT

1) Monitor urine for albumin and cells and keep accurate account of fluid electrolyte balance to prevent fluid overload in the event of acute tubular necrosis. Monitor SGOT, SGPT, LDH, and bilirubin to assess degree of liver injury. Obtain a baseline CBC.

B) HYPOTENSIVE EPISODE

1) SUMMARY

a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

2) DOPAMINE

a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).

3) NOREPINEPHRINE

a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
b) DOSE

1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).

C) BRADYCARDIA

1) ATROPINE/DOSE

a) ADULT BRADYCARDIA: BOLUS: Give 0.5 milligram IV, repeat every 3 to 5 minutes, if bradycardia persists. Maximum: 3 milligrams (0.04 milligram/kilogram) intravenously is a fully vagolytic dose in most adults. Doses less than 0.5 milligram may cause paradoxical bradycardia in adults (Neumar et al, 2010).
b) PEDIATRIC DOSE: As premedication for emergency intubation in specific situations (eg, giving succinylchoine to facilitate intubation), give 0.02 milligram/kilogram intravenously or intraosseously (0.04 to 0.06 mg/kg via endotracheal tube followed by several positive pressure breaths) repeat once, if needed (de Caen et al, 2015; Kleinman et al, 2010). MAXIMUM SINGLE DOSE: Children: 0.5 milligram; adolescent: 1 mg.

1) There is no minimum dose (de Caen et al, 2015).
2) MAXIMUM TOTAL DOSE: Children: 1 milligram; adolescents: 2 milligrams (Kleinman et al, 2010).

D) CONDUCTION DISORDER OF THE HEART

1) VENTRICULAR DYSRHYTHMIAS SUMMARY

a) Obtain an ECG, institute continuous cardiac monitoring and administer oxygen. Evaluate for hypoxia, acidosis, and electrolyte disorders (particularly hypokalemia, hypocalcemia, and hypomagnesemia). Lidocaine and amiodarone are generally first line agents for stable monomorphic ventricular tachycardia, particularly in patients with underlying impaired cardiac function. Amiodarone should be used with caution if a substance that prolongs the QT interval and/or causes torsades de pointes is involved in the overdose. Unstable rhythms require immediate cardioversion.

E) ACUTE LUNG INJURY

1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).

a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)

3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).

F) ACIDOSIS

1) Administer sodium bicarbonate as needed to control acidosis, and IV glucose as needed to control hypoglycemia.

G) SEIZURE

1) Seizures have been reported following toxic inhalational exposures to methyl bromide, a related agent, and may be expected to occur with toxic acute inhalations of ethylene dibromide.
2) SUMMARY

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

3) DIAZEPAM

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

4) NO INTRAVENOUS ACCESS

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

5) LORAZEPAM

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).

6) PHENOBARBITAL

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

7) OTHER AGENTS

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).

8) RECURRING SEIZURES

a) If seizures are not controlled by the above measures, patients will require endotracheal intubation, mechanical ventilation, continuous EEG monitoring, a continuous infusion of an anticonvulsant, and may require neuromuscular paralysis and vasopressor support. Consider continuous infusions of the following agents:

1) MIDAZOLAM: ADULT DOSE: An initial dose of 0.2 mg/kg slow bolus, at an infusion rate of 2 mg/minute; maintenance doses of 0.05 to 2 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: 0.1 to 0.3 mg/kg followed by a continuous infusion starting at 1 mcg/kg/minute, titrated upwards every 5 minutes as needed (Loddenkemper & Goodkin, 2011).
2) PROPOFOL: ADULT DOSE: Start at 20 mcg/kg/min with 1 to 2 mg/kg loading dose; maintenance doses of 30 to 200 mcg/kg/minute continuous infusion dosing, titrated to EEG; caution with high doses greater than 80 mcg/kg/minute in adults for extended periods of time (ie, longer than 48 hours) (Brophy et al, 2012); PEDIATRIC DOSE: IV loading dose of up to 2 mg/kg; maintenance doses of 2 to 5 mg/kg/hour may be used in older adolescents; avoid doses of 5 mg/kg/hour over prolonged periods because of propofol infusion syndrome (Loddenkemper & Goodkin, 2011); caution with high doses greater than 65 mcg/kg/min in children for extended periods of time; contraindicated in small children (Brophy et al, 2012).
3) PENTOBARBITAL: ADULT DOSE: A loading dose of 5 to 15 mg/kg at an infusion rate of 50 mg/minute or lower; may administer additional 5 to 10 mg/kg. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: A loading dose of 3 to 15 mg/kg followed by a maintenance dose of 1 to 5 mg/kg/hour (Loddenkemper & Goodkin, 2011).
4) THIOPENTAL: ADULT DOSE: 2 to 7 mg/kg, at an infusion rate of 50 mg/minute or lower. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusing dosing, titrated to EEG (Brophy et al, 2012)

b) Endotracheal intubation, mechanical ventilation, and vasopressors will be required (Brophy et al, 2012) and consultation with a neurologist is strongly advised.
c) Neuromuscular paralysis (eg, rocuronium bromide, a short-acting nondepolarizing agent) may be required to avoid hyperthermia, severe acidosis, and rhabdomyolysis. If rhabdomyolysis is possible, avoid succinylcholine chloride, because of the risk of hyperkalemic-induced cardiac dysrhythmias. Continuous EEG monitoring is mandatory if neuromuscular paralysis is used (Manno, 2003).

H) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

6.8.1)

A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

6.8.2)

A) GENERAL TREATMENT

1) Patients with significant signs and symptoms of ocular injury require prolonged initial irrigation and prompt referral to an ophthalmologist.
2) Treatment should include recommendations listed in the INHALATION EXPOSURE section when appropriate.

B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

6.9.1)

A) DERMAL DECONTAMINATION

1) Some authors suggest that the order of washing exposed skin following dermal decontamination should include rinsing first with COLD water, next wash thoroughly with a mild nongermicidal soap in WARM water, then repeat with HOT water. It is speculated that using cold water first may limit further dermal absorption of EDB (Jacobs, 1985).
2) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. Rescue personnel and bystanders should avoid direct contact with contaminated skin, clothing, or other objects (Burgess et al, 1999). Since contaminated leather items cannot be decontaminated, they should be discarded (Simpson & Schuman, 2002).

6.9.2)

A) BURN

1) APPLICATION

a) These recommendations apply to patients with MINOR chemical burns (FIRST DEGREE; SECOND DEGREE: less than 15% body surface area in adults; less than 10% body surface area in children; THIRD DEGREE: less than 2% body surface area). Consultation with a clinician experienced in burn therapy or a burn unit should be obtained if larger area or more severe burns are present. Neutralizing agents should NOT be used.

2) DEBRIDEMENT

a) After initial flushing with large volumes of water to remove any residual chemical material, clean wounds with a mild disinfectant soap and water.
b) DEVITALIZED SKIN: Loose, nonviable tissue should be removed by gentle cleansing with surgical soap or formal skin debridement (Moylan, 1980; Haynes, 1981). Intravenous analgesia may be required (Roberts, 1988).
c) BLISTERS: Removal and debridement of closed blisters is controversial. Current consensus is that intact blisters prevent pain and dehydration, promote healing, and allow motion; therefore, blisters should be left intact until they rupture spontaneously or healing is well underway, unless they are extremely large or inhibit motion (Roberts, 1988; Carvajal & Stewart, 1987).

3) TREATMENT

a) TOPICAL ANTIBIOTICS: Prophylactic topical antibiotic therapy with silver sulfadiazine is recommended for all burns except superficial partial thickness (first-degree) burns (Roberts, 1988). For first-degree burns bacitracin may be used, but effectiveness is not documented (Roberts, 1988).
b) SYSTEMIC ANTIBIOTICS: Systemic antibiotics are generally not indicated unless infection is present or the burn involves the hands, feet, or perineum.
c) WOUND DRESSING:

1) Depending on the site and area, the burn may be treated open (face, ears, or perineum) or covered with sterile nonstick porous gauze. The gauze dressing should be fluffy and thick enough to absorb all drainage.
2) Alternatively, a petrolatum fine-mesh gauze dressing may be used alone on partial-thickness burns.

d) DRESSING CHANGES:

1) Daily dressing changes are indicated if a burn cream is used; changes every 3 to 4 days are adequate with a dry dressing.
2) If dressing changes are to be done at home, the patient or caregiver should be instructed in proper techniques and given sufficient dressings and other necessary supplies.

e) Analgesics such as acetaminophen with codeine may be used for pain relief if needed.

4) TETANUS PROPHYLAXIS

a) The patient's tetanus immunization status should be determined. Tetanus toxoid 0.5 milliliter intramuscularly or other indicated tetanus prophylaxis should be administered if required.

B) SKIN ABSORPTION

1) Some chemicals can produce systemic poisoning by absorption through intact skin. Carefully observe patients with dermal exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.

C) GENERAL TREATMENT

1) Treatment should include recommendations listed in the INHALATION EXPOSURE section when appropriate.

D) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

A)

1) It is suspected that ethylene dibromide (EDB) may be highly protein bound; therefore, therapeutic plasma exchange may have a beneficial effect as a method of enhanced elimination in cases of EDB poisoning (Pahwa et al, 2013).

a) A retrospective review was conducted, involving 58 cases of EDB poisoning that presented to tertiary care hospitals in India, from 2007 to 2012. Of the 58 cases, 47 were identified as having received therapeutic plasma exchange (TPE). In addition to TPE, all patients received gastric lavage, activated charcoal, and symptomatic and supportive care, including IV fluids, antiemetics, antacids, and proton pump inhibitors. Of the 47 patients given TPE, 39 patients survived, with a significant increase in the survival rate when patients were given TPE 24 hours or less following EDB ingestion as compared to patients given TPE more than 24 hours following EDB ingestion (36 vs 3, p=0.0108). Of the 8 patients who did not survive, 4 patients had ingested more than 3 EDB 3-mL ampules and had died despite TPE treatment within 24 hours following ingestion; however, there was a 100% survival rate in patients who had received TPE within 12 hours following ingestion regardless of the amount of EDB that was ingested, indicating the utility and significant mortality reduction when TPE is performed early in cases of EDB poisoning (Pahwa et al, 2013).

Abstracts

Range Of Toxicity

Summary

A)

B)

1) Most cases of toxic exposure have resulted from inhalation of ethylene dibromide vapors for 20 to 45 minutes in poorly ventilated confined spaces. Ethylene dibromide vapor concentrations in two deaths were believed to range from 15 to 41 ppm. Dermal exposure may have contributed to the adverse effects documented in two human cases of lethal ethylene dibromide inhalation.

C)

1) Fatality has resulted from ingestion of 1 mL by an adult female with a history of ethanol abuse and from ingestion of an estimated 15 mL by a male teenager.

D)

1) Dermal or ocular contact with ethylene dibromide liquid or vapors produces local effects, such as, irritation and blistering (skin). Little data are available concerning the systemic effects of ethylene dibromide absorbed through human skin or eyes. Experimental animal studies have shown that ethylene dibromide liquid produces adverse systemic effects following absorption through intact or abraded skin.

Minimum Lethal Exposure

A)

1) INHALATION

a) GENERAL - The low vapor pressure of ethylene dibromide and increased care in its use appear to limit the number of human cases of toxic inhalational exposures in the workplace (Torkelson, 1994). Use of ethylene dibromide in confined spaces without appropriate protective equipment is potentially hazardous.
b) One worker exposed in a tank for 20 to 45 minutes to a 0.1% to 0.3% solution of ethylene dibromide was intermittently comatose. Death ensued 12 hours later. A co-worker attempted to rescue the first individual and was in the tank for 20 to 30 minutes. He died 64 hours later (Letz et al, 1984).

1) Extensive dermal exposure to the liquid in the tank also occurred. No respiratory or dermal protection was used by either individual. Key effects included coma, metabolic acidosis, acute renal and hepatic failure, and necrosis of skeletal muscle and other organs, as determined postmortem.
2) Evaluation of the liquid contained in the tank and air concentrations of vapors was done two hours after the accident. The tank contained approximately 7.5 centimeters of liquid, comprised of 0.1% to 0.3% of ethylene dibromide, as well as, traces of dichloropropene, dichloropropane, and high concentrations of nitrates and phosphates.
3) The only airborne toxicant detected by gas chromatography was ethylene dibromide, with a range of 15 to 41 ppm. The oxygen level in the tank was 21%. The air was sampled 20 hours after the accident. It is not known if there was any attempt to ventilate the tank during rescue procedures.

c) Another worker exposed for 30 minutes to high airborne ethylene dibromide concentrations in a confined space became comatose approximately 24 hours after exposure and died within 4 days (Nouchi, 1984). Dermal exposure to liquid ethylene dibromide may have contributed to the dose absorbed and the toxic effects.
d) Marmetschke (1910) and reviewed by Letz et al (1984) reported a death resulting from the accidental use of 22 grams of ethylene dibromide as an anesthetic, administered in a gauze mask. Anesthesia did not occur and the patient died from uterine hemorrhage 44 hours after exposure. Post mortem examination showed fatty degeneration of the myocardium and liver, as well as parenchymal degeneration of the kidneys (Marmetschke, 1910).

2) INGESTION

a) A woman with a history of ethanol abuse died 54 hours after ingesting two Fumisoil capsules which contained a total of 1.0 mL of ethylene dibromide (Olmstead, 1960). Death was due to profound shock, linked to excessive gastrointestinal tract fluid loss and hepatic necrosis.
b) Estimated ingestion of 15 mL of ethylene dibromide was fatal to a male teenager (Yodaiken & Babcock, 1973). Key effects included hypoglycemia, renal and hepatic failure, hematologic disturbances, pulmonary edema, and cardiac arrest.
c) In 6 cases of poisoning following ingestion of one ampule of ethylene dibromide, 2 died (Saraswat et al, 1986).
d) In a case series of 64 intentional ethylene dibromide ingestions, the smallest amount ingested was 1/2 ampule (1.5 mL). Ten (15.62%) of the cases ingested this amount of ethylene dibromide, and 2 (20%) of these cases expired. Overall mortality was 46.15% and 100% with ingestions of 1 ampule and greater than or equal to 1.5 ampules, respectively (Singh et al, 2007).

3) DERMAL

a) Dose-response data concerning toxic effects of dermal exposure in humans are not available. Fatalities have occurred in experimental animals exposed dermally to ethylene dibromide (Rowe et al, 1952).

Maximum Tolerated Exposure

A)

1) The maximum tolerated human exposure to this agent has not been delineated.

B)

1) INHALATION

a) REPORTED NO OBSERVED EFFECT DOSE - Six hour exposure of workers to 0.75 ppm reportedly produced no symptoms (Perry et al, 1994).
b) CAUTION - There is little information regarding maximum tolerated exposure. Estimates are available (McCollister et al, 1956; Sittig, 1991) Perry et al, 1994). These estimates may be based exclusively on laboratory animal data, may have been estimated prior to documented human fatalities, and may not consider the effects of long term and/or repeated exposures.

2) INGESTION

a) Acute ingestion of a solution containing 6480 mg ethylene dibromide resulted in a non-fatal case of acute renal failure with hyperkalemia and metabolic encephalopathy in a 20-year-old male (Prakash et al, 1999).
b) Acute ingestion of 3 mL of ethylene dibromide (estimated to be greater than 6000 mg) resulted in acute hepatic and renal failure, metabolic acidosis, and coagulopathy in a 16-year-old male (Singh et al, 2000).
c) In a case series of 64 intentional ethylene dibromide ingestions, the maximum amount ingested and associated with survival was 1 ampule (3 mL). Twenty-six (40.62%) of the cases ingested this amount of ethylene dibromide, and 14 (53.85%) of these cases survived (Singh et al, 2007).

Serum Plasma Blood Concentrations

7.5.2)

A) TOXIC CONCENTRATION LEVELS

1) CONCENTRATION LEVEL

a) Serum bromide concentration measured two hours after a 45 minute inhalational exposure was 830 mg/L (Letz et al, 1984). Another individual had a serum bromide concentration of 500 mg/L, 24 hours after exposure to ethylene dibromide vapors for 20 to 30 minutes. Normal serum bromide concentration was reported as less than 4 mg/L.

1) Ethylene dibromide vapor concentrations in the air measured from the tank where the exposures occurred ranged from 15 to 41 ppm. Air sampling was done 20 hours after the accident.

Workplace Standards

A)

1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.

a) Adopted Value

1) Ethylene dibromide

a) TLV:

1) TLV-TWA:
2) TLV-STEL:
3) TLV-Ceiling:

b) Notations and Endnotes:

1) Carcinogenicity Category: A3
2) Codes: Skin
3) Definitions:

a) A3: Confirmed Animal Carcinogen with Unknown Relevance to Humans: The agent is carcinogenic in experimental animals at a relatively high dose, by route(s) of administration, at site(s), of histologic type(s), or by mechanism(s) that may not be relevant to worker exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or levels of exposure.
b) Skin: This refers to the potential significant contribution to the overall exposure by the cutaneous route, including mucous membranes and the eyes, either by contact with vapors or, of likely greater significance, by direct skin contact with the substance. It should be noted that although some materials are capable of causing irritation, dermatitis, and sensitization in workers, these properties are not considered relevant when assigning a skin notation. Rather, data from acute dermal studies and repeated dose dermal studies in animals or humans, along with the ability of the chemical to be absorbed, are integrated in the decision-making toward assignment of the skin designation. Use of the skin designation provides an alert that air sampling would not be sufficient by itself in quantifying exposure from the substance and that measures to prevent significant cutaneous absorption may be warranted. Please see "Definitions and Notations" (in TLV booklet) for full definition.

c) TLV Basis - Critical Effect(s):
d) Molecular Weight: 187.88

1) For gases and vapors, to convert the TLV from ppm to mg/m(3):

a) [(TLV in ppm)(gram molecular weight of substance)]/24.45

2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:

a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance

e) Additional information:

B) NIOSH REL and IDLH Values for CAS106-93-4 (National Institute for Occupational Safety and Health, 2007):

1) Listed as: Ethylene dibromide
2) REL:

a) TWA: 0.045 ppm
b) STEL:
c) Ceiling: 0.13 ppm [15-minute]
d) Carcinogen Listing: (Ca) NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).
e) Skin Designation: Not Listed
f) Note(s): See Appendix A

3) IDLH:

a) IDLH: 100 ppm
b) Note(s): Ca

1) Ca: NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A).

C) Carcinogenicity Ratings for CAS106-93-4 :

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A3 ; Listed as: Ethylene dibromide

a) A3 :Confirmed Animal Carcinogen with Unknown Relevance to Humans: The agent is carcinogenic in experimental animals at a relatively high dose, by route(s) of administration, at site(s), of histologic type(s), or by mechanism(s) that may not be relevant to worker exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or levels of exposure.

2) EPA (U.S. Environmental Protection Agency, 2011): B2 ; Listed as: 1,2-Dibromoethane

a) B2 : Probable human carcinogen - based on sufficient evidence of carcinogenicity in animals.

3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): 2A ; Listed as: Ethylene dibromide

a) 2A : The agent (mixture) is probably carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans. This category is used when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals. In some cases, an agent (mixture) may be classified in this category when there is inadequate evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals and strong evidence that the carcinogenesis is mediated by a mechanism that also operates in humans. Exceptionally, an agent, mixture or exposure circumstance may be classified in this category solely on the basis of limited evidence of carcinogenicity in humans.

4) NIOSH (National Institute for Occupational Safety and Health, 2007): Ca ; Listed as: Ethylene dibromide

a) Ca : NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).

5) MAK (DFG, 2002): Category 2 ; Listed as: 1,2-Dibromoethane

a) Category 2 : Substances that are considered to be carcinogenic for man because sufficient data from long-term animal studies or limited evidence from animal studies substantiated by evidence from epidemiological studies indicate that they can make a significant contribution to cancer risk. Limited data from animal studies can be supported by evidence that the substance causes cancer by a mode of action that is relevant to man and by results of in vitro tests and short-term animal studies.

6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): R ; Listed as: 1,2-Dibromoethane (Ethylene dibromide)

a) R : RAHC = Reasonably anticipated to be a human carcinogen

D) OSHA PEL Values for CAS106-93-4 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

1) Listed as: Ethylene dibromide
2) Table Z-1 for Ethylene dibromide:

a) 8-hour TWA:

1) ppm:

a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.

2) mg/m3:

a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.

3) Ceiling Value:
4) Skin Designation: No
5) Notation(s): Not Listed

3) Table Z-2 for Ethylene dibromide (Z37.31-1970):

a) 8-hour TWA:20 ppm
b) Acceptable Ceiling Concentration: 30 ppm
c) Acceptable Maximum Peak above the Ceiling Concentration for an 8-hour Shift:

1) Concentration: 50 ppm
2) Maximum Duration: 5 minutes

d) Notation(s): Not Listed

Toxicity Information

7.7.1)

A) References: Clayton & Clayton, 1994 HSDB, 1999 ITI, 1995 Lewis, 1996 RTECS, 2002

1) LD50- (INTRAPERITONEAL)MOUSE:

a) 220 mg/kg

2) LD50- (ORAL)MOUSE:

a) 250 mg/kg
b) female, 420 mg/kg

3) LD50- (ORAL)RAT:

a) 108 mg/kg
b) 140 mg/kg
c) 146 mg/kg
d) male, 148 mg/kg
e) female, 117 mg/kg

4) LD50- (SKIN)RAT:

a) 300 mg/kg

5) TCLo- (INHALATION)HUMAN:

a) Man, 88 ppb for 8H -- 5Y prior to mating

6) TCLo- (INHALATION)MOUSE:

a) Female, 32 ppm for 23H -- 6-15D of pregnancy
b) Female, 38 ppm for 23H -- 6-15D of pregnancy
c) Female, 20 ppm for 23H -- 6-15D of pregnancy
d) 40 ppm for 6H/90W-I -- CAR

7) TCLo- (INHALATION)RAT:

a) Female, 66,670 ppb for 4H -- 3-20D of pregnancy
b) Female, 39 ppm for 7H -- 3W prior to mating
c) Female, 80 ppm for 7H -- 3W prior to mating
d) Male, 89 ppm for 7H -- 10W prior to mating
e) Female, 80 ppm for 23H -- 6-15D of pregnancy
f) 10 ppm for 6H; 2Y-I -- CAR

Pharmacology Toxicology

Toxicologic Mechanism

A)

1) The molecular site of ethylene dibromide reaction is N7 of guanine and the major reactive product of this reaction is S-(2-(N7-guanyl)ethyl)glutathione (Fossett et al, 1995; Kim & Guengerich, 1997).

Physicochemical

Physical Characteristics

A)

B)

C)

D)

E)

Molecular Weight

A)

Other

A)

1) 10 ppm (Sittig, 1991)
2) Low: 76.80 mg/m(3) (HSDB , 2002)
3) High: 62.5 mg/m(3) (HSDB , 2002)

Animal Toxicology

References

General Bibliography

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ETHYLENE DIBROMIDE

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Summary Of Exposure

Vital Signs

Heent

Cardiovascular

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Hematologic

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Monitoring Parameters Levels

Radiographic Studies

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Oral Exposure

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Enhanced Elimination

Summary

Minimum Lethal Exposure

Maximum Tolerated Exposure

Serum Plasma Blood Concentrations

Workplace Standards

Toxicity Information

Toxicologic Mechanism

Physical Characteristics

Molecular Weight

Other

General Bibliography