Substances Included Synonyms

Therapeutic Toxic Class

A)

Specific Substances

A)

1.2.1) MOLECULAR FORMULA
1) F5-Sb

Available Forms Sources

A)

1) Antimony pentafluoride is an oily, moderately viscous, colorless, water soluble, very reactive nonflammable liquid with a sharp or pungent odor.
2) It reacts violently with water, releasing HYDROGEN FLUORIDE and other substances with release of heat (AAR, 1987; (Budavari, 1989; CHRIS , 1993) HSDB, 1993).
3) Antimony pentafluoride is a pentavalent antimony compound which may be less toxic than trivalent antimony compounds (HSDB, 1993).

B)

1) The more critical component for occupational medical monitoring is ANTIMONY. With an atomic weight of 121.76, compared with 19 for fluorine, 0.5 mg/m(3) of antimony from antimony pentafluoride would be associated with only 0.39 mg/m(3) of fluoride. NIOSH has published a Criteria Document for fluorides (NIOSH, 1975).

C)

1) It is used in the fluorination of organic compounds and as a catalyst (EPA, 1985; Sax & Lewis, 1989; Sax & Lewis, 1987) AAR, 1987; (Budavari, 1989; CHRIS , 1993) HSDB, 1993).

Overview

Life Support

A)

Clinical Effects

0.2.1)

A) Antimony pentafluoride is an oily, moderately viscous, colorless, water soluble, very reactive nonflammable liquid with a sharp or pungent odor used in the fluorination of organic compounds and as a catalyst. It reacts violently with water, releasing HYDROGEN FLUORIDE and other substances with release of heat.

1) Inhalation and dermal exposure to antimony pentafluoride has caused cough, wheezing, dyspnea, chest tightness, pulmonary edema, and severe skin burns.
2) Antimony poisoning resembles arsenic poisoning; in ingestions, antimony may cause more severe vomiting. In ingestions, violent vomiting, diarrhea, mucosal irritation, and sloughing of mucosal cells may be seen from the antimony component. Death is due to hypovolemia and shock from the corrosive effects and hypocalcemia, hypomagnesemia, and hyperkalemia and associated cardiac effects.
3) Exposure to antimony salts may result in irritation of skin and mucous membranes.

B) Antimony pentafluoride causes corrosive burns or irritation of the eyes, skin, and mucous membranes. If ingested, vomiting and severe burns of the oral cavity and throat may occur; bloody diarrhea may develop. Systemic absorption by any route can lead to bradycardia, hypotension, coma, seizures, and cardiac arrest.

1) Myocardial injury with decreased contractility and electrical activity and higher excitability, jaundice, dyspnea, weight loss, alopecia, albuminuria, glomerular nephritis, splenic hyperplasia, elevated erythrocyte counts, and decreased leukocyte counts may be seen with chronic antimony exposure.
2) Chronic inhalation exposure can lead to interstitial pneumonitis, lipoid deposits in the pulmonary alveoli, and cardiac and liver damage. Dermatitis, keratitis, conjunctivitis, and nasal septum perforation may occur with chronic exposure to antimony dusts.

C) Antimony pentafluoride releases toxic and irritating fumes of fluoride and antimony when heated to decomposition. It reacts violently with water, releasing HYDROGEN FLUORIDE and other substances with release of heat.

1) Users may REFER to the HYDROGEN FLUORIDE and ANTIMONY managements for MORE INFORMATION.

D) HYDROGEN FLUORIDE TOXICITY -

1) Hydrofluoric acid (HF) is corrosive to skin and mucous membranes. Exposure can result in pneumonitis, eye damage, GI erosion, and severe burns. The severity and rapidity of onset of signs and symptoms depends on the concentration of the acid, duration of exposure and penetrability of the exposed tissue. The pain from burns may be delayed so that the patient does not know he has been burned until some hours later.
2) Dermal exposure to solutions containing greater than 50 percent HF produces immediate burning, erythema and tissue damage whereas exposure to 20 to 50 percent HF results in pain and erythema which may be delayed up to 1 to 8 hours. Exposure to solutions containing less than 20 percent HF results in erythema and pain delayed up to 24 hours after exposure.

E) Systemic fluoride toxicity may result from ingestion, inhalation or extensive dermal burns and cause hypocalcemia, hypomagnesemia, hyperkalemia, pulmonary edema, metabolic acidosis, and death.

0.2.3)

A) Respiratory depression, hypotension, and bradycardia may be seen.

0.2.4)

A) Corneal damage, conjunctivitis, or eye irritation may be seen. Irritation of the nose and throat may follow inhalation. Ingestion can cause caustic injury and burns of the mouth and throat.

0.2.5)

A) Cardiotoxicity with myocardial damage, decreased myocardial contractility, decreased cardiac electrical activity, and increased excitability may be seen.
B) Hypotension and bradycardia may occur. Cardiac arrest may result from hypocalcemia. Thrombophlebitis is common after IV antimony use, but has even been reported when poisoning is by the oral route.

0.2.6)

A) Pneumonitis, hemorrhagic pulmonary edema, airway obstruction from laryngeal edema, coughing, wheezing, and dyspnea may occur. Pulmonary effects may be delayed in onset. Antimony compounds have caused metal fume fever.

0.2.7)

A) Coma and seizures may be seen in acute poisoning with antimony pentafluoride.

0.2.8)

A) Severe vomiting, watery diarrhea (sometimes bloody), nausea, abdominal cramping, and irritation or sloughing of cells from the gastrointestinal mucosa may be seen following ingestion of antimony pentafluoride or other antimony compounds. Gastrointestinal irritation with mucosal inflammation is particularly prevalent in the distal large intestine.
B) Ingestion of antimony pentafluoride may produce severe burns of the oral cavity and throat.
C) Antimony causes a metallic taste.

0.2.9)

A) Jaundice may occur in antimony pentafluoride poisoning.

0.2.10)

A) Glomerular nephritis and albuminuria may be seen in antimony pentafluoride poisoning.

0.2.11)

A) Oral HF ingestion resulted in severe acidosis and death in one case. Metabolic acidosis was described in a 60-year-old male with extensive chemical burns following a splash exposure of 70 percent hydrofluoric acid solution.

0.2.12)

A) Severe hypocalcemia, hyperkalemia, and hypomagnesemia may occur in antimony pentafluoride poisoning.

0.2.13)

A) Experimental animals acutely and fatally poisoned with antimony developed eosinophilia.

0.2.14)

A) Severe dermal burns, sometimes with delayed onset, may occur following direct skin contact. Destruction of tissue proceeds under the toughened coagulated skin so that the ulcers extend deeply, heal slowly and leave a scar. Dermal swelling, redness, or both; blistering; blackish discoloration beneath the fingernail; and pain without dermal changes may occur with onset occurring from 0.5 to 24 hours after exposure to hydrofluoric acid.
B) Alopecia and dry skin may be seen with antimony exposure.

0.2.15)

A) The fluoride ion may cause decalcification and corrosion of bone.

0.2.20)

A) Birth defects were not found in the children of women occupationally exposed to antimony dust. Women exposed occupationally to antimony dust had an excessive prevalence of spontaneous abortions, premature deliveries, and various gynecological disorders.
B) Cases of sexual dysfunction have been mentioned among male workers exposed to antimony.

0.2.21)

A) At the time of this review, no studies were found on the possible carcinogenic activity of antimony pentafluoride in humans.
B) Occupational exposure to ANTIMONY has been linked with an increased risk for lung cancer (Friberg et al, 1986).
C) FLUORIDE is a possible human carcinogen, and has induced osteosarcomas in experimental animals.
D) Refer to ANTIMONY and FLUORIDE Medical Managements for additional information that may be relevant to this agent.

Laboratory Monitoring

A)

B)

C)

D)

E)

F)

G)

H)

I)

J)

Treatment Overview

0.4.2)

A) MANAGEMENT OF MILD TO MODERATE TOXICITY

1) Rule out corrosive GI tract injury with GI consult and endoscopy. Evaluate for and correct hypocalcemia, hypomagnesemia.

B) MANAGEMENT OF SEVERE TOXICITY

1) Systemic toxicity with severe hypocalcemia, hypomagnesemia, acidosis and ventricular dysrhythmia can develop after ingestion or rectal instillation of small amounts, after inhalation, or after dermal exposure to large surface areas or high concentration products. Begin appropriate respiratory and hemodynamic support for critically ill patients. The mainstays of therapy are aggressive correction of hypocalcemia, treatment of hypomagnesemia and avoidance of acidosis. Give empiric calcium. Maintain serum calcium levels in high-normal range. Give appropriate analgesia. If sudden death is avoided in the first 24 hours, prognosis is good; although recovery may be prolonged. Treat patients with dysrhythmias or hypotension with calcium chloride (via central line or large bore catheter) and sodium bicarbonate 1 to 2 mEq/kg IV to serum pH of 7.5. In cases of cardiac arrest, give calcium chloride 3 to 5 g IV bolus and sodium bicarbonate 1 to 2 mEq/kg IV to serum pH of 7.5, vasopressors and defibrillation in addition to advanced cardiac life support measures.
2) INGESTION: Large amounts of oral calcium and/or IV calcium chloride immediately. Administer sufficient intravenous calcium to maintain serum calcium levels at high-normal. Patients also may require magnesium supplementation. Animal models suggest that acidemia may worsen prognosis.

C) DECONTAMINATION

1) PREHOSPITAL: For ingestions, immediately give a substance containing calcium (milk, calcium carbonate antacids) or magnesium (magnesium containing antacids or laxatives). No activated charcoal. Do NOT induce emesis.
2) HOSPITAL: No activated charcoal. If very recent ingestion of large volume, aspirate with soft nasogastric tube. Administer oral calcium or magnesium solutions (ie, antacids, laxatives).

D) AIRWAY MANAGEMENT

1) Perform early in patients with severe intoxication after ingestion or inhalation.

E) ANTIDOTE

1) Calcium in high doses (calcium gluconate or chloride) binds the fluoride atoms to avert tissue injury and systemic fluorosis.

F) HYPOCALCEMIA

1) Administer calcium empirically to any patient with a potentially severe exposure while awaiting laboratory results. Monitor serum calcium. Repeat calcium replenishment as needed to maintain calcium concentrations in the high-normal range. CALCIUM CHLORIDE: ADULT DOSE: 1 g (10 mL of 10% solution) IV infused over 5 minutes; may repeat after 10 minutes. PEDIATRIC DOSE: 10 to 25 mg/kg (0.1 to 0.25 mL/kg) per dose up to a maximum single dose of 5 mL (500 mg) IV infused over 5 minutes; may repeat after 10 minutes. Treat patients with dysrhythmias or hypotension with calcium chloride and sodium bicarbonate 1 to 2 mEq/kg IV to a serum pH of 7.5.

G) HYPOMAGNESEMIA

1) Correct known and suspected hypomagnesemia with intravenous magnesium sulfate. DOSE: ADULT: 1 to 2 g diluted in 250 mL D5W or NS infused IV, may be repeated as necessary. PEDIATRIC: 25 to 50 mg/kg IV infusion over 30 to 60 minutes; repeat dose as necessary; max 2 g/dose. Monitor serum magnesium. Repeat as needed.

H) CARDIAC ARREST

1) Advanced cardiac life support measures. Give calcium chloride 3 to 5 g IV bolus and sodium bicarbonate 1 to 2 mEq/kg IV to a serum pH of 7.5, vasopressors and defibrillation.

I) ENHANCED ELIMINATION

1) Fluoride is removed by dialysis, but patients with severe toxicity will likely be hemodynamically unstable.

J) Observe and evaluate patient for oral and GI burns. Consider NG suction if less than 90 minutes since ingestion.
K) Endoscopy is recommended after ingestion of high concentration (greater than 20%) products, intentional ingestions of large amounts, or in patients with drooling, stridor, abdominal pain, or repeated vomiting.

0.4.3)

A) MANAGEMENT OF MILD TO MODERATE TOXICITY

1) Supportive care, nebulized bronchodilators, and give calcium gluconate nebulizer treatments.

B) MANAGEMENT OF SEVERE TOXICITY

1) Calcium gluconate 2.5 to 5% nebulizer treatments. Nebulized beta agonists for bronchospasm, humidified oxygen. Intravenous calcium if systemic toxicity or hypocalcemia develop.

C) DECONTAMINATION

1) PREHOSPITAL: Remove from inhalation source and administer oxygen.
2) HOSPITAL: Administer 100% humidified supplemental oxygen with assisted ventilation as required. Exposed skin and eyes should be copiously washed with water. Mild inhalational symptoms may be treated with 2.5% calcium gluconate nebulization

0.4.4)

A) Irrigate promptly with crystalloid solution. Carefully evaluate for eye damage; exposure to dilute solutions may result in delayed signs and symptoms of ocular damage. The patient should be evaluated by an ophthalmologist following appropriate decontamination.

0.4.5)

A) OVERVIEW

1) MANAGEMENT OF MILD TO MODERATE TOXICITY

a) Thoroughly irrigate skin immediately after exposure. Patients with early decontamination do well. Patients with pain should be treated with topical calcium therapy. TOPICAL: Treat with calcium gluconate or carbonate gel (1 g calcium gluconate in 40 g (about 40 mL) water-soluble lubricant = 2.5% gel; alternative is 10 10-g tablets crushed to fine powder + 20 mL water-soluble lubricant mixed into a slurry; apply thin coat to burn, then place hand in glove containing 10 mL slurry for 4 hours). SUBCUTANEOUS: Inject 0.5 mL/cm(2) with 10% calcium gluconate for topical treatment failures (not commonly used).
b) Do not use calcium chloride for bier block procedures. Calcium chloride is irritating to the tissues and may cause injury.

2) MANAGEMENT OF SEVERE TOXICITY

a) Patients with pain not responding to topical calcium can be treated with regional venous or arterial perfusion. These methods are particularly effective for fluoride exposures involving the digits. BIER BLOCK: Inject IV 10 to 40 mL calcium gluconate in 50 mL normal saline for 20 minutes. ARTERIAL: 10 to 20 mL of 10% calcium gluconate in 50 mL D5W. Infuse over 4 hours via radial or brachial artery. The arterial catheter may be placed in normal position (not inverted).
b) Do not use calcium chloride for bier block procedures. Calcium chloride is irritating to the tissues and may cause injury.

3) DECONTAMINATION

a) PREHOSPITAL: For dermal exposure, remove clothing and irrigate skin thoroughly with water.
b) HOSPITAL: Irrigate exposed skin. Remove all exposed clothing and jewelry taking necessary precautions to prevent secondary exposure to health care providers. Irrigate exposed areas promptly with copious amounts of water for at least 30 minutes.

Range Of Toxicity

A)

B)

C)

Clinical Effects

Summary Of Exposure

A)

1) Inhalation and dermal exposure to antimony pentafluoride has caused cough, wheezing, dyspnea, chest tightness, pulmonary edema, and severe skin burns.
2) Antimony poisoning resembles arsenic poisoning; in ingestions, antimony may cause more severe vomiting. In ingestions, violent vomiting, diarrhea, mucosal irritation, and sloughing of mucosal cells may be seen from the antimony component. Death is due to hypovolemia and shock from the corrosive effects and hypocalcemia, hypomagnesemia, and hyperkalemia and associated cardiac effects.
3) Exposure to antimony salts may result in irritation of skin and mucous membranes.

B)

1) Myocardial injury with decreased contractility and electrical activity and higher excitability, jaundice, dyspnea, weight loss, alopecia, albuminuria, glomerular nephritis, splenic hyperplasia, elevated erythrocyte counts, and decreased leukocyte counts may be seen with chronic antimony exposure.
2) Chronic inhalation exposure can lead to interstitial pneumonitis, lipoid deposits in the pulmonary alveoli, and cardiac and liver damage. Dermatitis, keratitis, conjunctivitis, and nasal septum perforation may occur with chronic exposure to antimony dusts.

C)

1) Users may REFER to the HYDROGEN FLUORIDE and ANTIMONY managements for MORE INFORMATION.

D)

1) Hydrofluoric acid (HF) is corrosive to skin and mucous membranes. Exposure can result in pneumonitis, eye damage, GI erosion, and severe burns. The severity and rapidity of onset of signs and symptoms depends on the concentration of the acid, duration of exposure and penetrability of the exposed tissue. The pain from burns may be delayed so that the patient does not know he has been burned until some hours later.
2) Dermal exposure to solutions containing greater than 50 percent HF produces immediate burning, erythema and tissue damage whereas exposure to 20 to 50 percent HF results in pain and erythema which may be delayed up to 1 to 8 hours. Exposure to solutions containing less than 20 percent HF results in erythema and pain delayed up to 24 hours after exposure.

E)

Vital Signs

3.3.1)

A) Respiratory depression, hypotension, and bradycardia may be seen.

3.3.4)

A) HYPOTENSION may be seen in cases of acute poisoning (EPA, 1985; CHRIS, 2004).

3.3.5)

A) BRADYCARDIA may be seen in cases of acute poisoning (EPA, 1985; CHRIS, 2004).

Heent

3.4.1)

A) Corneal damage, conjunctivitis, or eye irritation may be seen. Irritation of the nose and throat may follow inhalation. Ingestion can cause caustic injury and burns of the mouth and throat.

3.4.3)

A) CORNEAL DAMAGE - Eye exposure to HF can cause severe ocular damage. Delayed corneal injury has been reported 4 days postexposure (Hatai et al, 1986). Animal studies have shown mild conjunctivitis after exposure to 0.5 percent, severe conjunctivitis lasting 65 days after exposure to 8 percent, and immediate corneal necrosis after exposure to 20 percent solutions (McCulley et al, 1983).
B) CONJUNCTIVITIS - may be seen after exposure to antimony salts (Friberg, 1979).
C) IRRITATION - Severe eye irritation or corneal burns may follow eye exposure to antimony pentafluoride (EPA, 1985; CHRIS, 2004; HSDB, 2004; Sittig, 1991).

3.4.5)

A) IRRITATION - Mucous membrane irritation may result from inhalation of HF or antimony pentafluoride fumes (Friberg, 1979).
B) NASAL PERFORATION - has been reported from occupational antimony exposure (McCallum, 1989; Raffle et al, 1994).

3.4.6)

A) CORROSIVE BURNS - Antimony pentafluoride is highly corrosive and contact with the oral cavity may cause severe burns (Pohanish, 2002).
B) PHARYNGITIS - as well as laryngitis may be seen after exposure to antimony vapor (Friberg, 1979).
C) IRRITATION - Antimony pentafluoride may cause irritation of the mucosa of the nose and throat (EPA, 1985; CHRIS, 2004; HSDB, 2004).

Cardiovascular

3.5.1)

A) Cardiotoxicity with myocardial damage, decreased myocardial contractility, decreased cardiac electrical activity, and increased excitability may be seen.
B) Hypotension and bradycardia may occur. Cardiac arrest may result from hypocalcemia. Thrombophlebitis is common after IV antimony use, but has even been reported when poisoning is by the oral route.

3.5.2)

A) CARDIOMYOPATHY

1) Histologic myocardial damage has been described in systemic toxicity from ingestion and dermal exposure of HF (Greendyke & Hodge, 1964; Mayer & Gross, 1985).

B) HYPOTENSIVE EPISODE

1) Hypotension and bradycardia may be seen in poisonings with antimony pentafluoride (CHRIS, 2004).

C) CARDIAC ARREST

1) Cardiac arrest may result from hypocalcemia after HF systemic absorption from burns (Manoguerra & Neuman, 1986; Mullett et al, 1987; Tepperman, 1980). Cardiac arrest may occur with antimony pentafluoride poisoning (EPA, 1985).

D) CONDUCTION DISORDER OF THE HEART

1) SUMMARY: Should systemic fluoride poisoning occur following absorption of antimony pentafluoride, cardiac dysrhythmias secondary to hypocalcemia or hyperkalemia can occur(Heifetz & Horowitz, 1986; Clancy, 2002).
2) Prolongation of the QT interval (hypocalcemia) may be an ECG finding(Clancy, 2002).
3) Hyperkalemia resulting in peaked T waves on the ECG may also be present(Clancy, 2002). Dysrhythmias consistent with hyperkalemia have been reported in systemic fluoride poisoning (McIvor et al, 1987; Baltazar et al, 1980).
4) CASE REPORT: Dysrhythmias consistent with hyperkalemia (ie, marked peaking of T-waves) were reported in a fatal fluoride overdose. The patient developed refractory ventricular fibrillation (Baltazar et al, 1980).

E) HEART FAILURE

1) Myocardial failure was the cause of death in experimental animals acutely and fatally poisoned with antimony (Bradley & Fredrick, 1941).

F) THROMBOPHLEBITIS

1) Thrombophlebitis is common after IV antimony use, but has even been reported when poisoning is by the oral route (Lauwers et al, 1990).

Respiratory

3.6.1)

A) Pneumonitis, hemorrhagic pulmonary edema, airway obstruction from laryngeal edema, coughing, wheezing, and dyspnea may occur. Pulmonary effects may be delayed in onset. Antimony compounds have caused metal fume fever.

3.6.2)

A) PNEUMONITIS

1) Following HF inhalation, severe chemical pneumonitis may occur. Death due to severe pulmonary lesions occurred 3 hours after sustaining an HF inhalation and dermal injury (Chela et al, 1989).

B) ACUTE LUNG INJURY

1) Hemorrhagic pulmonary edema has been observed after significant HF inhalations, ingestions, and dermal exposures (Kleinfeld, 1965; Mayer & Guelich, 1963; Watson et al, 1973; Manoguerra & Neuman, 1986; Chan et al, 1987).

C) RESPIRATORY OBSTRUCTION

1) Airway obstruction may occur after HF ingestion or inhalation secondary to laryngeal edema.

D) TRACHEOBRONCHITIS

1) Several days after an HF dermal exposure, tracheobronchitis was described in one case (Braun et al, 1984).

E) COUGH

1) Various antimony dusts can cause pulmonary irritation and cough. The extent of damage is often due to the elements bound to the antimony. Metallic antimony and the oxides are less irritating than are the halide salts (Friberg, 1979).

F) METAL FEVER

1) Antimony compounds have caused metal fume fever (Finkel, 1983).

Neurologic

3.7.1)

A) Coma and seizures may be seen in acute poisoning with antimony pentafluoride.

3.7.2)

A) COMA

1) Coma may be seen in acute poisoning with antimony pentafluoride (Sittig, 1991).

B) SEIZURE

1) Seizures may be seen in acute poisoning with antimony pentafluoride (Sittig, 1991).

Gastrointestinal

3.8.1)

A) Severe vomiting, watery diarrhea (sometimes bloody), nausea, abdominal cramping, and irritation or sloughing of cells from the gastrointestinal mucosa may be seen following ingestion of antimony pentafluoride or other antimony compounds. Gastrointestinal irritation with mucosal inflammation is particularly prevalent in the distal large intestine.
B) Ingestion of antimony pentafluoride may produce severe burns of the oral cavity and throat.
C) Antimony causes a metallic taste.

3.8.2)

A) NAUSEA, VOMITING AND DIARRHEA

1) Severe vomiting, watery diarrhea, nausea, abdominal cramping, and irritation or sloughing of cells from the gastrointestinal mucosa may be seen following ingestion of antimony pentafluoride or other antimony compounds (Lauwers et al, 1990).
2) Vomiting is a constant symptom of antimony poisoning by any route of entry. Gastrointestinal irritation with mucosal inflammation is particularly prevalent in the distal large intestine (IRPTC, 1984).
3) In older drinking vessels, antimony may have been used to bind enamel to metal. Acid drinks may dissolve the antimony and cause nausea, vomiting and diarrhea (Werrin, 1963).

B) CHEMICAL BURN

1) Ingestion of antimony pentafluoride may produce severe burns of the oral cavity and throat (EPA, 1985).

C) GASTRIC HEMORRHAGE

1) Hemorrhagic gastritis invariably occurs in significant HF ingestions (Kleinfeld, 1965; Menchel & Dunn, 1984; Manoguerra & Neuman, 1986).

D) TASTE SENSE ALTERED

1) Antimony causes a metallic taste (Harbison, 1998; Raffle et al, 1994).

E) DIARRHEA

1) Diarrhea may be seen after antimony exposure (Harbison, 1998; Raffle et al, 1994).
2) Bloody diarrhea may be seen following ingestion of antimony pentafluoride (EPA, 1985; Pohanish, 2002).

F) INFLAMMATORY DISEASE OF MUCOUS MEMBRANE

1) Sores in the mouth and sore throat may be seen after antimony exposure, which helps differentiate antimony from lead poisoning (Finkel, 1983).

Hepatic

3.9.1)

A) Jaundice may occur in antimony pentafluoride poisoning.

3.9.2)

A) JAUNDICE

1) Jaundice may occur in antimony pentafluoride poisoning (Zenz, 1994).

Genitourinary

3.10.1)

A) Glomerular nephritis and albuminuria may be seen in antimony pentafluoride poisoning.

Acid-Base

3.11.1)

A) Oral HF ingestion resulted in severe acidosis and death in one case. Metabolic acidosis was described in a 60-year-old male with extensive chemical burns following a splash exposure of 70 percent hydrofluoric acid solution.

3.11.2)

A) ACIDOSIS

1) Oral HF ingestion resulted in severe acidosis and death in one case (Manoguerra & Neuman, 1986). Metabolic acidosis was described in a 60-year-old male with extensive chemical burns following a splash exposure of 70 percent hydrofluoric acid solution (Chan et al, 1987).

Hematologic

3.13.1)

A) Experimental animals acutely and fatally poisoned with antimony developed eosinophilia.

3.13.2)

A) EOSINOPHIL COUNT RAISED

1) Experimental animals acutely and fatally poisoned with antimony developed eosinophilia (Bradley & Fredrick, 1941).

Dermatologic

3.14.1)

A) Severe dermal burns, sometimes with delayed onset, may occur following direct skin contact. Destruction of tissue proceeds under the toughened coagulated skin so that the ulcers extend deeply, heal slowly and leave a scar. Dermal swelling, redness, or both; blistering; blackish discoloration beneath the fingernail; and pain without dermal changes may occur with onset occurring from 0.5 to 24 hours after exposure to hydrofluoric acid.
B) Alopecia and dry skin may be seen with antimony exposure.

3.14.2)

A) CHEMICAL BURN

1) Antimony pentafluoride is highly corrosive. HF is corrosive to skin and mucous membranes (Dibbell et al, 1970; Iverson et al, 1971). The severity of the burn and onset of symptoms depends on the concentration of HF, duration of exposure and penetrability of the exposed tissue (Iverson et al, 1971). Destruction of tissue proceeds under the toughened coagulated skin so that the ulcers extend deeply, heal slowly and leave a scar.
2) In a study of 14 patients with hydrofluoric acid burns of the hand, 2 patients developed permanent impairment that was associated with a delay in diagnosis and appropriate treatment. All patients were treated with immediate flushing with water for 15 minutes, CALCIUM GLUCONATE gel 2.5 percent massaged into burned skin for at least 30 minutes, and subcutaneous injections of 10 percent calcium gluconate into the affected area if pain persisted (Anderson & Anderson, 1988).
3) In a retrospective review, 219 patients exposed to dilute (6 to 11 percent) hydrofluoric acid reported symptoms of dermal swelling, redness, or both (55 percent); blistering (5 percent); blackish discoloration beneath the fingernail (5 percent); and pain without dermal changes (27 percent). Onset of symptoms reported occurred from 0.5 to 24 hours after exposure (El Saadi et al, 1989).

B) ALOPECIA

1) Experimental animals acutely and fatally poisoned with antimony developed hair loss (Bradley & Fredrick, 1941).

C) DRY SKIN

1) Dry skin with a scaly appearance was seen in experimental animals acutely and fatally poisoned with antimony (Bradley & Fredrick, 1941).

Musculoskeletal

3.15.1)

A) The fluoride ion may cause decalcification and corrosion of bone.

3.15.2)

A) ASEPTIC NECROSIS OF BONE

1) The fluoride ion may cause decalcification and corrosion of bone (Dibbell et al, 1970).

Reproductive

3.20.1)

A) Birth defects were not found in the children of women occupationally exposed to antimony dust. Women exposed occupationally to antimony dust had an excessive prevalence of spontaneous abortions, premature deliveries, and various gynecological disorders.
B) Cases of sexual dysfunction have been mentioned among male workers exposed to antimony.

3.20.2)

A) LACK OF EFFECT

1) Birth defects were not found in the children of women occupationally exposed to antimony dust (Schardein, 2000).

3.20.3)

A) ABORTION

1) Women exposed occupationally to antimony dust had an excessive prevalence of spontaneous abortions, premature deliveries, and various gynecological disorders (Schardein, 2000; Harbison, 1998).

B) FERTILITY DECREASED FEMALE

1) Female antimony workers showed an increased incidence of gynecologic diseases (IRPTC, 1984). Female rats have their reproductive function altered by antimony exposure (IRPTC, 1984).

a) Most of the data concerning reproductive effects of antimony have been published in the Russian literature.

C) MENSTRUAL DISORDER

1) Increased incidence of menstrual cycle disturbances has been reported among workers exposed to antimony aerosols (Harbison, 1998).

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS7783-70-2 (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) Not Listed

3.21.2)

A) At the time of this review, no studies were found on the possible carcinogenic activity of antimony pentafluoride in humans.
B) Occupational exposure to ANTIMONY has been linked with an increased risk for lung cancer (Friberg et al, 1986).
C) FLUORIDE is a possible human carcinogen, and has induced osteosarcomas in experimental animals.
D) Refer to ANTIMONY and FLUORIDE Medical Managements for additional information that may be relevant to this agent.

Genotoxicity

A)

B)

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) Continuous repeated exposure to HF vapor greater than 3 ppm in air can result in excessive deposition of fluoride in the body, resulting in chronic fluorosis, which is detectable by measuring blood or urine fluoride levels.
B) Obtain serum electrolytes including serial calcium, potassium, and magnesium levels in symptomatic patients. Obtain serial ECGs looking for signs of hypocalcemia (prolonged QTc interval) and hyperkalemia (peaked T waves). Institute continuous cardiac monitoring.
C) If respiratory tract irritation is present, monitor arterial blood gases and chest x-ray.
D) Whole blood concentrations of antimony in unexposed subjects are usually less than 3 mcg/L.
E) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count and liver and kidney function tests is suggested for patients with significant exposure.
F) In chronically exposed antimony workers with pulmonary changes, urine antimony levels ranged from 0.4 to 0.7 milligrams/Liter. Urine levels up to 5.0 mg/L have been noted in some occupationally-exposed individuals.
G) Urine assay may be used to assess clinical symptoms. Levels of 1 mg/L or greater may indicate a potentially harmful antimony exposure. A normal subject may have a level of 0.8 mcg/L.
H) This agent may cause nephrotoxicity. Monitor renal function tests and urinalysis in patients with significant exposure.
I) If respiratory tract irritation is present, it may be useful to monitor pulmonary function tests.
J) If respiratory tract irritation is present, monitor chest x-ray.

4.1.2)

A) BLOOD/SERUM CHEMISTRY

1) Continuous repeated exposure to HF vapor greater than 3 ppm in air can result in excessive deposition of fluoride in the body, resulting in chronic fluorosis, which is detectable by measuring blood fluoride levels.
2) Obtain serum electrolytes including serial calcium, potassium, and magnesium levels in symptomatic patients.
3) Serum concentration of antimony in normal subjects is 3 mcg/L or less (Friberg, 1979). Whole blood antimony concentrations in unexposed individuals are generally less than 10 mcg/L(Baselt, 2000).
4) If systemic fluorosis is likely and hypocalcemia is apprent, monitor coagulation studies.
5) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count and liver and kidney function tests is suggested for patients with significant exposure.
6) This agent may cause nephrotoxicity. Monitor renal function tests and urinalysis in patients with significant exposure.

4.1.3)

A) URINARY LEVELS

1) Urine levels up to 5.0 mg/L have been noted in some occupationally-exposed individuals (Baselt & Cravey, 1989; Baselt, 1988).

a) In unexposed individuals, urine antimony levels are generally lower than 0.001 mg/L (Baselt & Cravey, 1989; Baselt, 1988).

2) Urine assay may be used to assess clinical symptoms. Levels of 1 mg/L or greater may indicate a potentially harmful antimony exposure (Elkins, 1959). A normal subject may have a level of 0.8 mcg/L (Friberg, 1979).

4.1.4)

A) OTHER

1) ECG

a) Obtain serial ECGs looking for signs of hypocalcemia (prolonged QTc interval) and hyperkalemia (peaked T waves). Institute continuous cardiac monitoring.

2) MONITORING

a) If respiratory tract irritation is present, monitor arterial blood gases and chest x-ray.

3) PULMONARY FUNCTION TESTS

a) If respiratory tract irritation is present, it may be useful to monitor pulmonary function tests.

Radiographic Studies

A)

1) If respiratory tract irritation is present, monitor chest x-ray.

Treatment

Life Support

A)

Patient Disposition

6.3.1)

6.3.1.1) ADMISSION CRITERIA/ORAL

A) Patients with a history of significant exposures or with significant symptomatology should be admitted to an intensive care unit and observed with continuous ECG monitoring for a minimum of 24 to 48 hours (Caravati, 1988).

Monitoring

A)

B)

C)

D)

E)

F)

G)

H)

I)

J)

Oral Exposure

6.5.1)

A) PREHOSPITAL: For DERMAL exposure, remove clothing and irrigate skin thoroughly with water. Remove from INHALATION source and administer oxygen. Irrigate EYES with copious saline or water. For INGESTION, immediately give a substance containing calcium (milk, calcium carbonate antacids) or magnesium (magnesium containing antacids or laxatives). No activated charcoal. Do NOT induce emesis.

6.5.2)

A) SUMMARY

1) FLUORIDE BINDING - Attempt immediate administration of a fluoride binding substance which includes milk (one-half to one glassful), chewable calcium carbonate tablets, or milk of magnesia. Avoid large amounts of liquid, since this may induce vomiting.
2) The precise amount of oral calcium required is unknown. One protocol for oral decontamination used 2400 mg of elemental calcium every two hours until hospital admission (Browne, 1982). This is equivalent to 12 TUMS(R) tablets (contain 200 milligrams each), 11 ROLAIDS CALCIUM RICH(R) tablets (contain 220 milligrams each), or 8 TUMS EXTRA STRENGTH(R) tablets (contain 300 milligrams each) per dose. Milk contains approximately 300 milligrams elemental calcium per 8 ounces.

B) EMESIS/NOT RECOMMENDED

1) Do not induce vomiting.

C) NASOGASTRIC SUCTION

1) Consider careful nasogastric suction or lavage with a small (18 Fr) soft tube for patients with significant ingestions who present within 90 minutes of exposure and have not spontaneously vomited. CALCIUM GLUCONATE 10 percent may be added to the lavage fluid.
2) Brushite (calcium phosphate, dibasic, dihydrate) suspension is superior in inactivating hydrofluoric acid when compared to apatite (calcium orthophosphate, basic) suspension, calcium gluconate solution, or skim milk in an in vitro model of acute fluoride poisoning (Larsen & Jensen, 1991).

a) Hydrofluoric acid containing test solutions were prepared by dissolving sodium fluoride in hydrochloric acid to produce three solutions, each with a pH of 4.5 (solution I), 4.0 (solution II), or 2.1 (solution III).
b) The solutions provide a source of calcium that reacts with hydrofluoric acid producing calcium fluoride.
c) The table below illustrates the percentage of fluoride removed by calcium fluoride formation in vitro.

SOLUTION
CALCIUMSOURCE	I		II		III
CALCIUMSOURCE	pH	%F	pH	%F	pH	%F
Brushite 0.16 g/mL	7.2	88	7.0	99	2.4	90
Brushite 0.16 g/mL	7.2	75	6.5	64	2.1	56
Apatite 0.58 g/mL	7.4	34	7.0	38	3.4	100
Apatite 0.058 g/mL	7.4	30	6.6	25	2.1	84
Calcium gluconate0.24 g/mL	4.8	87	3.6	60	2.2	9
Skim Milk 0.1 g/mL	7.1	46	6.9	33	4.5	8.3

d) Additional in vitro studies are needed to confirm the safety and efficacy of these agents for gastric lavage in human fluoride poisoning.

6.5.3)

A) SELECTIVE DECONTAMINATION OF THE DIGESTIVE TRACT

1) FLUORIDE BINDING - Attempt immediate administration of a fluoride binding substance which includes milk (one-half to one glassful), chewable calcium carbonate tablets, or milk of magnesia. Avoid large amounts of liquid, since this may induce vomiting.
2) The precise amount of oral calcium required is unknown. One protocol for oral decontamination used 2400 mg of elemental calcium every two hours until hospital admission (Browne, 1982). This is equivalent to 12 TUMS(R) tablets (contain 200 milligrams each), 11 ROLAIDS CALCIUM RICH(R) tablets (contain 220 milligrams each), or 8 TUMS EXTRA STRENGTH(R) tablets (contain 300 milligrams each) per dose. Milk contains approximately 300 milligrams elemental calcium per 8 ounces.
3) ANIMAL STUDY - In one animal study, it was determined that oral decontamination with calcium chloride or magnesium sulfate does not improve survival following hydrofluoric acid ingestion (Delgado & Heard, 2002).

B) HYPOCALCEMIA

1) Hypocalcemia in the absence of clinical tetany may occur following oral ingestion or dermal exposure (Tepperman, 1980). Check patient for a positive Trousseau's or Chvostek's sign.
2) CALCIUM CHLORIDE

a) ADULT DOSE: 1 g (10 mL of 10% solution) IV infused over 5 minutes; may repeat after 10 minutes (Jones & Flanagan, 2004; Saxena, 1989; Anon, 2000).
b) PEDIATRIC DOSE: 10 to 25 mg/kg (0.1 to 0.25 mL/kg) per dose up to a maximum single dose of 5 mL (500 mg) IV infused over 5 minutes; may repeat after 10 minutes (Jones & Flanagan, 2004; Barkin, 1986; Anon, 2000).
c) CALCIUM FOR INJECTION is available as three salts; calcium chloride, calcium gluconate, and calcium gluceptate.
d) While the other salts may be used, calcium chloride is the preferred salt for resuscitation since it directly delivers ionized calcium, whereas the other salts must be hepatically metabolized to release ionized calcium (Chameides, 1988). However, other studies have suggested that hepatic metabolism may not be required for calcium gluconate (Martin et al, 1990).
e) Calcium chloride is very irritating, and is ideally given via a central venous catheter. It may cause hypotension and bradycardia. Calcium salts are incompatible with bicarbonate (Chameides, 1988; Saxena, 1989; Anon, 2000).

3) Monitor ECG continuously and at least hourly serial total or ionized calcium, magnesium, potassium levels during therapy. Suspect hypocalcemia and/or hypomagnesemia when QTc interval is prolonged.
4) Treat aggressively with intravenous calcium in the presence of any ECG or clinical signs of hypocalcemia while serum calcium levels are pending.

C) HYPOMAGNESEMIA

1) Hypomagnesemia may develop following oral ingestion or dermal exposure and has been associated with QTc prolongation and ventricular dysrhythmias.
2) MAGNESIUM SULFATE DOSE

a) ADULT: 1 to 2 g diluted in 250 mL D5W or NS and infused IV, may be repeated as necessary.
b) PEDIATRIC: 25 to 50 mg/kg IV infusion over 30 to 60 minutes; repeat dose as necessary; max 2 g/dose (Kleinman et al, 2010; Manrique et al, 2010; Haque & Saleem, 2009).

3) Serial evaluation of the patient's knee jerk reflex is the most important and reliable guide to magnesium treatment. Serum magnesium levels are not a reliable indicator for what is a "therapeutic level". Patient should be monitored with ECG continuously.

D) HYPERKALEMIA

1) Patients should be monitored for laboratory and/or ECG evidence of hyperkalemia after ingestion of HF.

a) ECG changes include peaked T waves in the precordial leads, prolongation of the PR interval and QRS duration, progressive flattening of the P wave, merging of the QRS complex with the T wave to produce a continuous sine wave appearance, and ventricular fibrillation or asystole (Martin et al, 1986; Smith et al, 1985) Williams, 1986).
b) ECG manifestations of hyperkalemia and/or a serum potassium concentration of 7.5 milliequivalents/liter or greater indicates a medical emergency and requires aggressive therapy and continuous cardiac monitoring.
c) Fluoride-induced hyperkalemia, once developed, may be irreversible. Therapeutic intervention to prevent development of elevated serum potassium is essential. Note: the beta-adrenergic receptor and the calcium channel do NOT appear to have major roles in fluoride-induced hyperkalemia. Early aggressive therapy with glucose, insulin and/or sodium bicarbonate prior to the development of hyperkalemia was ineffective in dog studies; however, quinidine was shown effective in preventing the K+ efflux from cells and preventing cardiotoxicity in fluoride-toxic dogs. Therapeutic doses of other antidysrhythmics, such as lidocaine, were not effective. Propranolol worsened fluoride-induced cardiotoxicity (Cummings & McIvor, 1988; McIvor & Cummings, 1987).
d) In an in-vitro model of human erythrocytes, the potassium channel blockers, amiodarone and quinidine, attenuated fluoride-induced hyperkalemia. The authors recommended further in-vivo studies to determine whether amiodarone can enhance survival in fluoride poisoning (Su et al, 2003).
e) Death is usually the result of delayed sudden cardiovascular collapse with ventricular fibrillation triggered by electrolyte imbalances (hypocalcemia, hypomagnesemia, hyperkalemia). If sudden death is avoided in the first 24 hours, prognosis is good, although recovery may be prolonged. In dog studies, increase in serum potassium levels began at approximately 2 hours post-exposure and began to rise exponentially at 6 hours post-exposure. Maintain normal or alkalotic pH. Cation exchange resins or dialysis may be the only effective means in which to reverse fluoride-induced hyperkalemia (Cummings & McIvor, 1988; McIvor & Cummings, 1987; McIvor et al, 1987).

2) CALCIUM CHLORIDE

a) Intravenous calcium has no effect on circulating potassium levels, but it antagonizes cardiac toxicity in patients demonstrating cardiac signs and/or symptoms of hyperkalemia.
b) ADULT DOSE: 1 g (10 mL of 10% solution) IV infused over 5 minutes; may repeat after 10 minutes (Jones & Flanagan, 2004; Saxena, 1989; Anon, 2000).
c) PEDIATRIC DOSE: 10 to 25 mg/kg (0.1 to 0.25 mL/kg) per dose up to a maximum single dose of 5 mL (500 mg) IV infused over 5 minutes; may repeat after 10 minutes (Jones & Flanagan, 2004; Barkin, 1986; Anon, 2000).
d) CALCIUM FOR INJECTION is available as three salts; calcium chloride, calcium gluconate, and calcium gluceptate.
e) While the other salts may be used, calcium chloride is the preferred salt for resuscitation since it directly delivers ionized calcium, whereas the other salts must be hepatically metabolized to release ionized calcium (Chameides, 1988). However, other studies have suggested that hepatic metabolism may not be required for calcium gluconate (Martin et al, 1990).
f) Calcium chloride is very irritating, and is ideally given via a central venous catheter. It may cause hypotension and bradycardia. Calcium salts are incompatible with bicarbonate (Chameides, 1988; Saxena, 1989; Anon, 2000).

3) SODIUM BICARBONATE

a) Administer intravenous sodium bicarbonate to shift potassium intracellularly. Expect 0.5 to 1 milliequivalent/liter reduction in serum potassium for each 0.1 unit rise in blood pH.
b) A standard syringe contains 50 milliliters of 8.4% solution, 1 milliequivalent/milliliter, 50 milliequivalents/syringe.
c) ADULT DOSE - 50 milliliters (50 milliequivalents) intravenously over 5 minutes, repeated at 20 to 30 minute intervals.
d) PEDIATRIC DOSE - 1 to 2 milliliters/kilogram/dose (1 to 2 milliequivalents/kilogram/dose) intravenously every 2 to 4 hours or as required by pH (Barkin, 1986). The onset is 15 minutes, the duration of action 1 to 2 hours (Ellenhorn & Barceloux, 1997).

4) INSULIN/DEXTROSE

a) Enhances intracellular potassium shift.
b) ADULT DOSE - Administer 25 grams of dextrose (250 milliliters of a 10% solution) intravenously over 30 minutes, and then continue the infusion at a slower rate.
c) Ten units of regular insulin are given subcutaneously or added to the infusion.
d) ALTERNATIVELY, 50 milliliters of a 50% dextrose solution with 5 to 10 units of regular insulin may be administered intravenously over 5 minutes.
e) Typically, this regimen will lower serum potassium by 1 to 2 milliequivalents/liter within 30 to 60 minutes with the decrease lasting for several hours.
f) PEDIATRIC DOSE - 0.5 to 1 gram/kilogram/dose followed by 1 unit of regular insulin intravenously for every 4 grams of glucose infused; may repeat every 10 to 30 minutes (Barkin, 1986).
g) HYPEROSMOLARITY - It must be remembered that 50 percent dextrose, and even 25% dextrose, are very hyperosmolar and may be sclerosing to peripheral veins (Chameides, 1988); administration of hypertonic solutions via central lines is preferred, if possible.

E) VENTRICULAR ARRHYTHMIA

1) Evaluate for and treat hypocalcemia, hypomagnesemia and hyperkalemia. Because amiodarone has potassium channel blocking effects, it may be the preferred antidysrhythmic in the setting of hydrofluoric acid poisoning.
2) AMIODARONE

a) AMIODARONE/INDICATIONS

1) Effective for the control of hemodynamically stable monomorphic ventricular tachycardia. Also recommended for pulseless ventricular tachycardia or ventricular fibrillation in cardiac arrest unresponsive to CPR, defibrillation and vasopressor therapy (Link et al, 2015; Neumar et al, 2010). It should be used with caution when the ingestion involves agents known to cause QTc prolongation, such as fluoroquinolones, macrolide antibiotics or azoles, and when ECG reveals QT prolongation suspected to be secondary to overdose (Prod Info Cordarone(R) oral tablets, 2015).

b) AMIODARONE/ADULT DOSE

1) For ventricular fibrillation or pulseless VT unresponsive to CPR, defibrillation, and a vasopressor therapy give an initial dose of 300 mg IV followed by 1 dose of 150 mg IV. For stable ventricular tachycardias: Infuse 150 milligrams over 10 minutes, and repeat if necessary. Follow by a 1 milligram/minute infusion for 6 hours, then a 0.5 milligram/minute. Maximum total dose over 24 hours is 2.2 grams (Neumar et al, 2010).

c) AMIODARONE/PEDIATRIC DOSE

1) Infuse 5 milligrams/kilogram as a bolus for pulseless ventricular tachycardia or ventricular fibrillation; may repeat twice up to 15 mg/kg. Infuse 5 milligrams/kilogram over 20 to 60 minutes for perfusing tachycardias. Maximum single dose is 300 mg. Routine use with other drugs that prolong the QT interval is NOT recommended (Kleinman et al, 2010).

d) ADVERSE EFFECTS

1) Hypotension and bradycardia are the most common adverse effects (Neumar et al, 2010).

F) BURN

1) Patient should be observed and evaluated for evidence of oral and gastrointestinal burns after deliberate ingestions or ingestion of high concentration products. While gastrointestinal burns may occur after ingestion they are generally NOT an immediate life threat.

G) ENDOSCOPIC PROCEDURE

1) Endoscopy is recommended after ingestion of high concentration (greater than 20%) products, deliberate ingestion of large amounts of low or high concentration products, or in patients manifesting drooling, stridor, abdominal pain, or repeated vomiting. There is little published information regarding the use of endoscopy and the therapy of mucosal burns after ingestion of hydrofluoric acid.

H) ACIDOSIS

1) METABOLIC ACIDOSIS: Treat severe metabolic acidosis (pH less than 7.1) with sodium bicarbonate, 1 to 2 mEq/kg is a reasonable starting dose(Kraut & Madias, 2010). Monitor serum electrolytes and arterial or venous blood gases to guide further therapy.

Inhalation Exposure

6.7.1)

A) 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.
B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
C) 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.

6.7.2)

A) OXYGEN

1) Administer 100 percent humidified oxygen to patients with abnormal respiratory signs or symptoms.

B) 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).

C) CALCIUM

1) Administration of nebulized CALCIUM GLUCONATE 2.5 percent has been recommended (Trevino et al, 2001; Trevino et al, 1983).
2) CASE SERIES - Lee et al (1992) report the use of calcium gluconate nebulization in 13 workers exposed to 150 to 200 parts per million HF gas for 2 minutes. Patients were treated quickly after exposure, and only minor upper respiratory tract irritation was noted. All patients tolerated the treatment without adverse effects. None developed delayed pulmonary edema or any permanent sequelae.
3) CASE REPORT - Following a one minute exposure to fumes from an anhydrous HF spill in an enclosed area, a male worker experienced immediate upper airway irritation and dyspnea. Three nebulized calcium gluconate treatments were immediately administered with resolution of respiratory complaints. The authors suggested this treatment may have prevented pulmonary injury (Boyer et al, 2000).
4) CASE SERIES - After 5 workers were exposed to inhalational HF fumes, they presented to the ED 4 hours later. Burning of the mouth and tongue were reported in 3 of the patients and one complained of nausea and abdominal cramps. All patients were administered a 2.5% calcium gluconate nebulized treatment. All symptoms resolved by the end of the treatment. The authors recommend calcium gluconate nebulization therapy for mild symptoms of HF inhalation (Trevino et al, 2001).

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

Eye Exposure

6.8.1)

A) Irrigate promptly with crystalloid solution (lactated ringer's or normal saline). Carefully evaluate for eye damage; exposure to dilute solutions may result in delayed signs and symptoms of ocular damage (Caravati, 1988). The patient should be evaluated by an ophthalmologist following appropriate decontamination.

6.8.2)

A) IRRIGATION

1) SUMMARY - Similar to treatment of skin exposure, calcium gluconate solution and benzethonium chloride (benzethonium hydrochloride) have been suggested for treatment of eye exposure. In addition, single irrigation with isotonic sodium chloride or magnesium chloride has been suggested (with repeated irrigation an increase in the frequency of corneal ulceration was reported in rabbit eyes) (Grant & Schuman, 1993).
2) Based on animal studies, immediate SINGLE 30 minutes irrigation with one liter of water, isotonic sodium chloride or magnesium chloride may provide the most beneficial therapy for ocular exposure to 0.25 M/L or greater of HF. However, multiple irrigations increased the corneal ulceration rate from 6 to 40 percent (McCulley et al, 1983) 1990). Other animal studies suggest that irrigation with 1 percent calcium gluconate solution did not have any significant advantage over saline irrigation and topical treatment only following ocular exposure to 2 percent HF (Beiran et al, 1986).
3) Monitor eye fluid pH with litmus paper and continue irrigation until ocular pH is in the normal range. The patient should be evaluated by an ophthalmologist following appropriate decontamination (Grant, 1986).
4) Equivocal results have been reported after immediate copious washing of the eyes, followed by application of ice packs until arrival at a health care facility, then irrigation with 1 percent calcium gluconate for 5 to 10 minutes, and instillation of 1 percent calcium gluconate drops every 2 to 3 hours for 2 to 3 days (Trevino et al, 1983).
5) Bentur et al (1993) report the case of 33-year-old man who splashed 49 percent HF into his eye. Treatment consisted of immediate flushing with water by the patient followed by further flushing with water for 10 minutes at the worksite and with 1 liter of normal saline 50 minutes later in the emergency department.

a) Examination at that time revealed chemotic and hyperemic conjunctiva and sloughing of nearly all of the corneal epithelium. The patient was treated with 1 percent calcium gluconate drops (3 drops every 3 hours for 2 days), topical cycloplegia and antibiotics and a mild pressure patch. The epithelial defect healed over the next 4 days and eye exam was normal at 3 months.

B) EXPERIMENTAL THERAPY

1) ANIMAL STUDIES: Various eye treatments were tried on animals to determine the most effective method to bind the fluoride ion.

a) Subconjunctival injection of calcium gluconate is too toxic to the eye.
b) Injections of isotonic CaCl2, or mixtures of the most common divalent cations of the cornea cause further injury.
c) Topical ointments of magnesium or magnesium sulfate, irrigation with 0.2 percent hyamine (0.2 percent benzenethonium chloride) or 0.05 percent Zephiran and isotonic CaCl2 were all toxic to the eye.

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

Dermal Exposure

6.9.1)

A) DERMAL DECONTAMINATION

1) Remove all exposed clothing and jewelry taking necessary precautions to prevent secondary exposure to health care providers (i.e., wear protective clothing, gloves, etc). Irrigate all exposed areas promptly with copious amounts of water or crystalloid solution (lactated ringer's or normal saline) for at least 30 minutes. Carefully evaluate for eye damage; exposure to dilute solutions may result in delayed signs and symptoms of ocular damage. The patient should be evaluated by an ophthalmologist following appropriate decontamination.

6.9.2)

A) SKIN FINDING

1) DERMAL DECONTAMINATION

a) Exposure to dilute solutions (6% to 11%) hydrofluoric acid is best treated by immediately washing all exposed areas with copious amounts of water or crystalloid solution (lactated ringer's or normal saline) for at least 30 minutes while removing all potentially contaminated clothing and jewelry. Take necessary precautions to prevent secondary exposure to health care providers. Carefully evaluate for ocular damage when dermal exposure involves the face.
b) Exposure to dilute HF solutions may result in delayed signs and symptoms of ocular damage. If ocular exposure has occurred, the patient should be evaluated by an ophthalmologist after appropriate decontamination. Calcium gluconate or calcium carbonate gel applied topically to the affected area has been associated with relief of pain at the site of exposure. Systemic toxicity or severe tissue damage is unlikely to occur with small surface area exposures to dilute solutions. Aggressive therapy with calcium gluconate infiltration or calcium gluconate arterial perfusion are not likely to be necessary and may increase tissue damage.

2) DERMAL ABSORPTION

a) Dermal exposure to HF can produce hypocalcemia, hypomagnesemia, hyperkalemia, cardiac dysrhythmias, and death (Tepperman, 1980; Proctor et al, 1988; Yamaura et al, 1997).

B) HYPERKALEMIA

1) Fluoride-induced hyperkalemia, once developed, may be irreversible. Therapeutic intervention to prevent development of elevated serum potassium is essential. Note: the beta-adrenergic receptor and the calcium channel do NOT appear to have major roles in fluoride-induced hyperkalemia. Early aggressive therapy with glucose, insulin and/or sodium bicarbonate prior to the development of hyperkalemia was ineffective in dog studies; however, quinidine was shown effective in preventing the K+ efflux from cells and preventing cardiotoxicity in fluoride-toxic dogs. Therapeutic doses of other antidysrhythmics, such as lidocaine, were not effective. Propranolol worsened fluoride-induced cardiotoxicity (Cummings & McIvor, 1988; McIvor & Cummings, 1987).
2) Death is usually the result of delayed sudden cardiovascular collapse with ventricular fibrillation triggered by electrolyte abnormalities (hypocalcemia, hypomagnesemia, hyperkalemia). If sudden death is avoided in the first 24 hours, prognosis is good, although recovery may be prolonged. In dog studies, increase in serum potassium levels began at approximately 2 hours postexposure and began to rise exponentially at 6 hours postexposure. Maintain normal or alkalotic pH. Cation exchange resins or dialysis may be the only effective means in which to reverse fluoride-induced hyperkalemia (Cummings & McIvor, 1988; McIvor & Cummings, 1987; McIvor, 1988).

C) HYPOCALCEMIA

1) Hypocalcemia in the absence of clinical tetany may occur following dermal exposure (Tepperman, 1980). Check patient for a positive Trousseau's or Chvostek's sign.
2) MANAGEMENT OF MILD TO MODERATE TOXICITY

a) Thoroughly irrigate skin immediately after exposure. Patients with early decontamination do well. Patients with pain should be treated with topical calcium therapy. TOPICAL - Treat with calcium gluconate or carbonate gel (1 g calcium gluconate in 40 g (about 40 mL) water-soluble lubricant = 2.5% gel; alternative is 10 10-g tablets crushed to fine powder + 20 mL water-soluble lubricant mixed into a slurry; apply thin coat to burn, then place hand in glove containing 10 mL slurry for 4 hours). SUBCUTANEOUS - Inject 0.5 mL/cm(2) with 10% calcium gluconate for topical treatment failures (not commonly used).
b) Do not use calcium chloride for bier block procedures. Calcium chloride is irritating to the tissues and may cause injury.

3) MANAGEMENT OF SEVERE TOXICITY

a) Patients with pain not responding to topical calcium can be treated with regional venous or arterial perfusion. These methods are particularly effective for HF exposures involving the digits. BIER BLOCK - Inject IV 10 to 40 mL calcium gluconate in 50 mL normal saline for 20 minutes. ARTERIAL - 10 to 20 mL of 10% calcium gluconate in 50 mL D5W. Infuse over 4 hours via radial or brachial artery. The arterial catheter may be placed in normal position (not inverted).
b) Do not use calcium chloride for bier block procedures. Calcium chloride is irritating to the tissues and may cause injury.

4) Monitor ECG continuously and at least hourly serial total or ionized calcium, magnesium, potassium levels during therapy. Suspect hypocalcemia and/or hypomagnesemia when QTc interval is prolonged.
5) Treat aggressively with intravenous calcium in the presence of any ECG or clinical signs of hypocalcemia while serum calcium levels are pending.

D) HYPOMAGNESEMIA

1) Hypomagnesemia may develop after dermal exposure or ingestion and has been associated with QTc prolongation, ventricular dysrhythmias and death.
2) MAGNESIUM SULFATE DOSE

a) ADULT: 1 to 2 g diluted in 250 mL D5W or NS and infused IV, may be repeated as necessary.
b) PEDIATRIC: 25 to 50 mg/kg IV infusion over 30 to 60 minutes; repeat dose as necessary; max 2 g/dose (Kleinman et al, 2010; Manrique et al, 2010; Haque & Saleem, 2009)

3) Serial evaluation of the patient's knee jerk reflex is the most important and reliable guide to magnesium treatment. Serum magnesium levels are not a reliable indicator for what is a "therapeutic level". Patient should be monitored with ECG continuously.

E) VENTRICULAR ARRHYTHMIA

1) Evaluate for and treat hypocalcemia, hypomagnesemia and hyperkalemia. Because amiodarone has potassium channel blocking effects, it may be the preferred antidysrhythmic in the setting of hydrofluoric acid poisoning.
2) AMIODARONE

a) AMIODARONE/INDICATIONS

1) Effective for the control of hemodynamically stable monomorphic ventricular tachycardia. Also recommended for pulseless ventricular tachycardia or ventricular fibrillation in cardiac arrest unresponsive to CPR, defibrillation and vasopressor therapy (Link et al, 2015; Neumar et al, 2010). It should be used with caution when the ingestion involves agents known to cause QTc prolongation, such as fluoroquinolones, macrolide antibiotics or azoles, and when ECG reveals QT prolongation suspected to be secondary to overdose (Prod Info Cordarone(R) oral tablets, 2015).

b) AMIODARONE/ADULT DOSE

1) For ventricular fibrillation or pulseless VT unresponsive to CPR, defibrillation, and a vasopressor therapy give an initial dose of 300 mg IV followed by 1 dose of 150 mg IV. For stable ventricular tachycardias: Infuse 150 milligrams over 10 minutes, and repeat if necessary. Follow by a 1 milligram/minute infusion for 6 hours, then a 0.5 milligram/minute. Maximum total dose over 24 hours is 2.2 grams (Neumar et al, 2010).

c) AMIODARONE/PEDIATRIC DOSE

1) Infuse 5 milligrams/kilogram as a bolus for pulseless ventricular tachycardia or ventricular fibrillation; may repeat twice up to 15 mg/kg. Infuse 5 milligrams/kilogram over 20 to 60 minutes for perfusing tachycardias. Maximum single dose is 300 mg. Routine use with other drugs that prolong the QT interval is NOT recommended (Kleinman et al, 2010).

d) ADVERSE EFFECTS

1) Hypotension and bradycardia are the most common adverse effects (Neumar et al, 2010).

F) DRUG THERAPY

1) CALCIUM GEL

a) SUMMARY

1) Various topical calcium preparations have been used anecdotally for treatment of exposure to HF solutions of less than 20 percent. Concentrations of calcium gluconate or calcium carbonate range from 2.5 to 33 percent. There are no studies comparing relative efficacy among different concentrations of gel.
2) The less viscous gel form may be more practical for application to large surface areas, while the concentrated slurry may be more appropriate for smaller areas such as hands or fingers. Topical application of a 2.5% calcium gluconate gel is easier to perform and less painful than infiltration (Brown, 1974; Trevino et al, 1983; El Saadi et al, 1989; Asvesti et al, 1997). Murao (1989) demonstrated in rats dermally exposed to 20% hydrofluoric acid, that irrigation of the affected skin with running water for 10 minutes followed by application of 2.5% calcium gluconate jelly was an effective therapy for reducing fluoride concentrations in urine and tissues surrounding the injured region.
3) TECHNIQUE

a) After copious irrigation with water, the gel is typically massaged into the affected area until the pain has subsided for 15 minutes. It must have access to the burn, so cloth or thick necrotic coagulum should be removed. The earlier the initiation of this therapy after exposure, the more rapid the resolution of symptoms may occur (El Saadi et al, 1989).
b) For hand and/or finger burns, a thin layer of 32.5 percent calcium carbonate slurry was applied directly to the burned area, and 10 milliliters were placed in a surgical glove into which the affected hand was placed. Patients moved or massaged the hand periodically and the glove was changed at 4 hours and again at 8 hours if pain persisted (Chick & Borah, 1990).

4) COMMERCIAL PRODUCTS AVAILABLE

a) A commercial gel, "H-F Antidote Gel" is available from Moore & Company, Ltd. Rippleside Commercial Estate, Renwick Rd, Barking, Essex, IG11 05D, England. Also, a 2.5 percent by weight calcium gluconate gel and jelly are available OTC in 25 gram tubes from Pharmascience Inc., Montreal, Quebec (514-340-1114), sold under the name "H-F Antidote Gel".
b) EXTEMPORANEOUS PREPARATION

1) CALCIUM GLUCONATE POWDER (METHOD 1) - Add 3.5 grams of calcium gluconate USP to a 5 ounce tube of water-soluble surgical lubricant, such as K-Y Jelly(R). Other soluble calcium salts (such as calcium lactate) may theoretically be substituted for the gluconate salt, but no data exist on use of these salts. Calcium chloride is NOT recommended due to its potential for irritation. IF CALCIUM GLUCONATE POWDER IS NOT AVAILABLE, PREPARE GEL FROM CALCIUM CARBONATE TABLETS AS DIRECTED UNDER METHOD 3.
2) CALCIUM GLUCONATE POWDER (METHOD 2) - Dissolve 2.5 grams calcium gluconate in 91.25 milliliters of water, heating the water if necessary. Let cool to room temperature. Add 0.25 gram chlorhexidine gluconate and stir. Make a slurry in a separate container of hydroxyethyl cellulose 2 grams and isopropyl alcohol 4 milliliters, and stir. Add slurry to calcium solution, stirring vigorously until a thick gel has formed. Leave overnight before packing (EAPCC, 1987).
3) CALCIUM CARBONATE TABLETS (METHOD 3) - A 32.5 percent slurry used for treatment of hand or finger burns can be prepared by triturating ten (10 grain) tablets into a fine powder and adding to 20 milliliters of a water-soluble lubricant gel, such as K-Y Jelly(R) (Chick & Borah, 1990). Another method is to gradually add the calcium carbonate powder to K-Y Jelly(R) until a spreadable gel is produced.
4) CALCIUM GLUCONATE SOLUTION (METHOD 4) - A gel consisting of equal parts of dimethyl sulfoxide and a 10 percent calcium gluconate solution for injection was shown to enhance percutaneous calcium ion absorption in rat skin (Zachary et al, 1986). Cornstarch, methyl cellulose, or other inert thickeners, may be added in order to produce a spreadable gel.
5) Higher concentrations of calcium gluconate solutions (up to 33 percent) may be used for more serious burns.
6) HEXAFLUORINE

a) A newer compound, Hexafluorine, was developed in France for decontamination of HF eye and skin exposures. In a rat study, a 50% HF solution was applied to the shaved backs of rats via a soaked filter paper. After 30 sec, the animals were either rinsed with 500 mL Hexafluorine over a 3 min period, or rinsed with water followed by calcium gluconate 2.5% gel, or rinsed with water only, or given no treatment. A consistent trend toward poorer results with Hexafluorine was observed (Hojer et al, 2002).
b) EFFICACY

1) CASE SERIES - A calcium carbonate 32.5 percent slurry was effective in relieving pain within 4 to 6 hours in 8 of 9 patients with hydrofluoric acid hand or finger burns. It was unsuccessful in one patient who did not present until 24 hours after exposure (Chick & Borah, 1990).
2) ANIMAL STUDY - In a rat model, animals treated with calcium gluconate gel developed a less serious burn than animals treated with benzalkonium chloride, A & D ointment, aloe gel, or magnesium ointment (Bracken et al, 1985).
3) ANIMAL STUDY - In a rabbit model, calcium gluconate gel was the most effective in preventing severe skin damage. Aluminum and magnesium hydroxide tablets, crushed and mixed with a water-soluble lubricant gel, was also somewhat effective. Magnesium gluconate was no better than control vehicle (Burkhart et al, 1992; Burkhart et al, 1994).
4) CALCIUM CHLORIDE IS NOT RECOMMENDED BASED ON ITS POTENTIAL FOR IRRITATION.
5) INTRAVENOUS CALCIUM/MAGNESIUM PERFUSION

a) Regional intravenous infusion of calcium gluconate, using a technique similar to the Bier block, is a therapeutic option if HF burns of forearm, hand, or digits as adjunct to topical therapy or if topical therapy is unsatisfactory (Graundins et al, 1997; Ryan et al, 1997; Henry & Hla, 1992; Isbister, 2000).
b) An intravenous cannula is inserted into a vein in the dorsum of the affected hand. The superficial veins of the extremity are exsanguinated by raising the arm for about 5 minutes. This can also be accomplished by application of an Esmarch bandage. When exsanguination is complete the sphygmomanometer cuff is inflated to just above the systolic blood pressure to prevent the arm refilling with blood. The arm is then lowered or the Esmarch bandage removed. Ten to 20 milliliters of 10 percent calcium gluconate solution diluted to 30 to 40 mL with 0.9 percent saline solution is infused. Ischemia is maintained for 25 to 30 minutes; the blood pressure cuff is then sequentially released over 5 minutes.
c) Intravenous therapy is considered successful if there is absence of pain and tenderness during the hour following treatment. Intraarterial calcium infusion should be considered in cases in which pain or tenderness persists at exposure sites.
d) ANIMAL STUDY: Williams et al (1994) compared intravenous magnesium sulfate treatment with intradermal calcium gluconate treatment in HF-burned rats.
e) Rats treated with magnesium sulfate (80 milligrams/kilogram) experienced fewer severe burns (1 of 11 surviving rats; 1 died) than controls (4 of 8 surviving rats; 5 died) or those treated with intradermal calcium (7 of 9 surviving rats; 1 died).
f) Intravenous magnesium sulfate (0.2 milliequivalent bolus over 2 minutes, followed by 0.2 milliequivalents per kilogram per hour for 4 hours) diminished burn scars and lessening healing time in rabbits with HF burns (Cox & Osgood, 1994). Calcium gluconate infiltration (0.5 ml of 10 percent solution) was as effective in diminishing burn scars and healing time in this model.
g) ARTERIAL CALCIUM PERFUSION

1) Intraarterial calcium infusion for digital HF burn is also a therapeutic option and should be considered if regional intravenous calcium gluconate is ineffective. This method should be used on severe distal extremity burns by those physicians who are comfortable with the technique and have experience in the treatment of HF burns (Isbister, 2000).
2) Several studies have evaluated arterial perfusion of 10 to 20 percent calcium salt (CALCIUM GLUCONATE or CALCIUM CHLORIDE) solutions to treat distal upper extremity HF burns (Kohnlein & Achinger, 1982; Velvart, 1983; Vance et al, 1986; Siegel & Heard, 1992). Intra-arterial infusion should be continued until pain does not recur (Tournoud et al, 1999). In general, pain relief was obtained and wound healing required 2 to 4 weeks.
3) A long catheter is inserted percutaneously into the radial artery using standard aseptic technique. Intraarterial catheter placement is confirmed by pressure transducer and oscilloscope. If the burn involves only the thumb, index, or long fingers, the catheter is advanced only a few centimeters proximally in preparation for digital subtraction arteriography. If the burn involves the ring or small fingers, the catheter is advanced proximally into the brachial artery because access to the ulnar circulation is necessary.
4) Following satisfactory placement of the arterial line, digital subtraction arteriography is performed to identify the origin of vascular supply to digits involved. Once the tip of the catheter is in the desired location, a dilute preparation of calcium salts (10 mL of a 10% solution mixed in 40 to 50 mL 5% dextrose) is infused with a pump apparatus into the catheter over 4 hours. Generally, calcium gluconate is used, although calcium chloride may be used in a similar manner. The patient should be observed closely during the infusion period for progression of symptoms and potential complications of the procedure, such as alterations of distal vascular supply.
5) Following the 4 hour infusion, the arterial line is maintained in place in the usual manner while the patient undergoes an observation period. If typical HF pain returns within 4 hours, a second calcium infusion is repeated. This cycle is repeated until the patient is pain free 4 hours following completion of the calcium infusion.
6) EFFICACY - The efficacy of this method is difficult to determine since adequate controls were absent in all reports. This technique avoids the painful injections and nail removal required with infiltration therapy. It is able to deliver more calcium ions to the injured tissue. It has not been proven to give superior results to the infiltration technique, however, and requires an invasive vascular procedure, an infusion pump, and hospital admission.
7) COMPLICATIONS associated with intraarterial calcium infusion, include transient ulnar nerve palsy (believed due to the armboard used for infusion), and median nerve palsy from to hematomas from multiple arterial punctures (Siegal & Heard, 1992).
8) Continued tissue destruction and associated pain (due to penetration of free fluoride ion into affected tissue) may be minimized by subcutaneous administration of CALCIUM GLUCONATE to form an insoluble (inactive) fluoride salt (Blunt, 1964). This procedure is NOT recommended for digital areas (fingers or toes) unless the physician is experienced with the technique, due to potential for tissue injury from increased pressure.
9) CALCIUM CHLORIDE should NOT be used because it is irritating and may cause tissue injury.
10) INDICATIONS - Local infiltration with CALCIUM GLUCONATE may be considered if (1) HF exposure results in immediate tissue damage or (2) erythema and pain persist following adequate irrigation (NOTE: Pain and erythema may be delayed up to 24 hours post exposure depending on the concentration of HF).
11) Infiltrate each square centimeter of the affected (painful) dermis and subcutaneous tissue with about 0.5 milliliter of 10% CALCIUM GLUCONATE using a 30 gauge needle. Repeat as needed to control pain (Matsuno, 1996).
12) CAUTION - Avoid administering large volumes of subcutaneous CALCIUM GLUCONATE, as this will result in decreased tissue perfusion and potential necrosis. Exposure of subungual tissue to concentrated hydrofluoric acid often necessitates removal of the nail in order to adequately decontaminate the nailbed and relieve pain (Mayer & Guenlich,1963; Wetherhold & Shepherd, 1965; Dibbell et al, 1970).
13) IONTOPHORETIC CALCIUM

a) ANIMAL STUDY - Following experimental 50% HF burns to the nude backs of rats, one group of rats was treated with iontophoresis of calcium chloride with constant voltage at 1.5V and electric current at 20-30 microamps at first, then increased to 100-120 microamps within 5 minutes; total treatment, 30 minutes. Burn areas of this group were reduced significantly when compared to untreated rats, rats treated with calcium gluconate jelly and rats treated with intradermal and subcutaneous calcium gluconate injections. Transdermal transport of calcium appeared to be enhanced in stripped skins by iontophoresis. No adverse effects were observed in normal skins. Limitations of iontophoretic treatment include number of lesions that can be treated simultaneously and size of the lesion (patches are small and unable to cover large areas). Use of iontophoretic delivery of calcium in humans is currently not recommended (Yamashita et al, 2001).
b) MAGNESIUM

1) Harris et al (1981) evaluated the efficacy of subcutaneous and intradermal injections of magnesium salts (10% acetate and sulfate) in rats dermally exposed to HF. In this study, the magnesium salts effectively minimized the depth and progression of the HF burn but further studies are needed before these salts can be routinely recommended.
2) Burkhart et al (1992) found that magnesium gluconate in water soluble lubricant gel (K-Y Jelly(R)) was less effective than calcium gluconate in preventing deep layer skin damage in HF-exposed rabbit skin.
3) QUATERNARY AMMONIUM SALTS

a) Soaking the burn in a quaternary ammonium compound solution has been recommended (Wetherhold & Shepherd, 1965; Reinhart et al, 1966), and although successful it is uncomfortable to the patient and difficult to use in awkward or large areas.
b) In a porcine model of hydrofluoric acid burns topical application of iced benzalkonium chloride (17%) was more effective than topical calcium gluconate gel (2.5%), calcium gluconate injections (5% or 10%), topical calcium acetate (10%) soaks, or benzethonium chloride soaks in reducing the gross size and severity of skin lesions produced after a 9 minute exposure to 38% hydrofluoric acid (Dunn et al, 1992). Calcium acetate soaks (10%) were most effective in reducing the gross size and severity of lesions produced after 15 minutes exposure to 38 percent hydrofluoric acid.
c) In the same study benzalkonium chloride (17%) soaks, calcium acetate (10%) soaks, calcium gluconate gel (2.5%), and calcium gluconate injection (5%) were all effective in reducing the histologic severity of injury, while benzethonium chloride soaks were less effective and 10% calcium gluconate injection increased the severity of injury (Dunn et al, 1992).
d) IODINE PREPARATIONS

1) ANIMAL STUDY - In an animal study, it was determined that postexposure treatment with an iodine ointment was efficacious upon hydrofluoric acid-induced skin burns. Statistically significant reductions of 76% and 68% in ulceration areas were noted at intervals of 5 and 10 minutes between exposure and treatment; however, a weaker effect was observed at a longer time interval of 15 minutes (a 56% reduction in the ulceration area). It was speculated that the protective effect of iodine may be derived from its ability to inhibit apoptosis or proteinase activity crucial for the evoluation of skin damage. The authors suggested the therapeutic usage of these iodine preparations for hydrofluoric acid-induced skin burns (Wormser et al, 2002).

G) EXCISION

1) SURGICAL THERAPY

a) In patients with extensive skin damage over a small surface area and refractory hypocalcemia, immediate excision of the affected skin may be indicated. Packing the wound with benzalkonium chloride solution until calcium status is stable, followed by split-thickness skin grafting, has been recommended (Buckingham, 1988).
b) In patients without refractory hypocalcemia, immediate excision is not recommended unless necrotic tissue necessitates debridement. A conservative initial approach with local calcium injections has been suggested (Craig, 1964).

H) NAIL DAMAGE

1) FINGERNAIL REMOVAL

a) Exposure of the subungual (nailbed) tissue to HF is particularly painful and difficult to decontaminate. Nail removal is probably not necessary for exposures to concentrations of less than 10%; more concentrated solutions may produce tissue necrosis. The nailplate can be split, lifted, or totally removed in cases of severe exposure to facilitate decontamination and calcium therapy (Roberts et al, 1989). This disfiguring procedure may not be necessary when regional intravenous or intraarterial calcium salt treatment is initiated in a timely manner.

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

Abstracts

Range Of Toxicity

Summary

A)

B)

C)

Minimum Lethal Exposure

A)

1) An estimated lethal oral dose of antimony pentafluoride is between 5 and 50 milligrams/kilogram (EPA, 1985; Sittig, 1991).
2) RATS - chronically given 5 ppm of antimony in the drinking water exhibited decreased longevity; this dose corresponded to 350 mcg/kg/day (HSDB , 1990). When administered intratracheally to rats, antimony pentafluoride caused death at all doses greater than 1.5 mg (Clayton & Clayton, 1981).
3) RATS - given 0.5 - 500 ppm of antimony potassium tartrate in water for 13 weeks demonstrated various biochemical and histopathological changes at doses of 5.0 ppm and above. A NOEL of 0.5 ppm corresponded to an average dose of 60 mcg/kg/day (Poon et al, 1998).

B)

1) As the acute toxicity of antimony pentafluoride is largely due to released hydrofluoric acid, the following data may assist in estimating severity.

a) ORAL INGESTION -

1) Death has occurred after ingestion of 1.5 grams of hydrofluoric acid (Gosselin et al, 1984; HSDB , 1990) (concentration unknown) within 6.5 hours of ingestion. Postmortem findings in this case revealed no gross tissue damage and a liver fluoride level of 165 micrograms/100 gram (Curry, 1962).
2) Oral ingestion of an unknown rust remover resulted in death within 90 minutes. The calcium level upon arrival to the emergency department was 3.1 milligrams/deciliter with a plasma fluoride of 35.2 milligrams/liter. Postmortem findings included hemorrhagic pulmonary edema and gastritis without ulceration (Manoguerra & Neuman, 1986).
3) A 33-year-old man who ingested 3 to 4 ounces of a rust remover (unstated HF concentration) died within 45 to 60 minutes. At autopsy, severe mucosal edema of the stomach and hemorrhage and necrosis of the pancreas were noted. The postmortem blood fluoride level was 56.2 milligrams/liter (Menchel & Dunn, 1984).
4) Oral ingestion of 15 milliliters of a 9 percent solution was reported to cause death (Webster, 1930).

b) DERMAL EXPOSURE -

1) An adult patient who developed 25 percent total body surface area second degree burns after exposure to a 70 percent hydrofluoric acid preparation died in cardiac arrest. Ionized serum calcium level was 1.7 milligrams per deciliter (normal: 4 to 4.8) immediately premortem (El Saadi et al, 1989).
2) Two workers died following a splash exposure of 70 percent hydrofluoric acid while unloading a tanker. Both workers were promptly removed from site of exposure. Clothing was removed and burns were initially treated at the workplace with a cold shower and alcohol was applied to burn areas (Chan et al, 1987).
3) A dermal exposure to 70 percent hydrofluoric acid over a 2.5 percent total body surface area resulted in death. The serum calcium level was 2.2 milligrams/deciliter (Tepperman, 1980).
4) A patient with hydrofluoric acid burns involving 8 percent of his body died from intractable cardiac arrhythmia secondary to the depletion of ionized calcium by fluoride ion (Mullett et al, 1987).

Maximum Tolerated Exposure

A)

1) Hydrogen fluoride gas is potentially corrosive to the skin at 20 ppm. It is an irritant and can be tolerated for only 1 minute at a concentration of 120 ppm (Thienes & Haley, 1972; HSDB , 1990) and 122 ppm (CHEMINFO , 1990).
2) Dermal exposure to solutions containing greater than 50 percent hydrofluoric acid produces immediate burning, erythema and tissue damage whereas exposure to 20 to 50 percent hydrofluoric acid results in pain and erythema which may be delayed up to 1 to 8 hours. Exposure to solutions containing less than 20 percent hydrofluoric acid results in erythema and pain delayed up to 24 hours after exposure (Iverson et al, 1971; Dibbell et al, 1970).
3) Velvart (1983) reported that 7 percent hydrofluoric acid produced symptoms in 1 to several hours, 12 percent acid produced symptoms in under an hour, and 14.5 percent solutions produced symptoms immediately.
4) Two children who developed 3 to 4 percent and 8 to 10 percent total body surface area first degree burns after exposure to a 6 to 11 percent hydrofluoric acid preparation had serial serum calcium levels and cardiac monitoring which remained normal. No systemic toxicity developed from this exposure (El Saadi et al, 1989).
5) Inhalation exposure to hydrogen fluoride at 122 parts per million for 1 minute can cause severe irritation of nose, throat, and respiratory tract. Exposures at 50 parts per million and above for several minutes may be fatal (CHEMINFO , 1990).
6) Rhinitis and nose bleeds were seen in smelter workers exposed to antimony in concentrations of 4.7 to 11.8 milligrams/cubic meter (Renes, 1953).
7) Workers exposed to air having about 3 milligrams of antimony per cubic meter showed urinary values ranging from 0.8 to 9.6 milligrams/liter (Friberg, 1979).

a) WORKPLACE AIR - Concentrations of antimony in the air have ranged from 1 to 10 milligrams/cubic meter. Working zone concentrations have ranged from 4.7 to 10.2 milligrams/cubic meter in smelters (Friberg, 1979).
b) Antimony ore frequently contains arsenic as an impurity, thus complicating the issue.

Workplace Standards

A)

1) Not Listed

B)

1) Not Listed

C)

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
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): Not Listed
4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
5) MAK (DFG, 2002): Not Listed
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

D)

1) Not Listed

Toxicity Information

7.7.1)

A) References: RTECS, 1999 EPA, 1985

Pharmacology Toxicology

Physicochemical

Physical Characteristics

A)

Molecular Weight

A)

Animal Toxicology

References

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FeedBack

ANTIMONY PENTAFLUORIDE

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

Respiratory

Neurologic

Gastrointestinal

Hepatic

Genitourinary

Acid-Base

Hematologic

Dermatologic

Musculoskeletal

Reproductive

Carcinogenicity

Genotoxicity

Monitoring Parameters Levels

Radiographic Studies

Life Support

Patient Disposition

Monitoring

Oral Exposure

Inhalation Exposure

Eye Exposure

Dermal Exposure

Summary

Minimum Lethal Exposure

Maximum Tolerated Exposure

Workplace Standards

Toxicity Information

Physical Characteristics

Molecular Weight

General Bibliography