Substances Included Synonyms

Therapeutic Toxic Class

A)

B)

C)

Specific Substances

1) Antimony White
2) Antimony Oxide
3) Antimony Peroxide
4) Molecular Formula: Sb2O3
5) CAS 1309-64-4
6) NYCOL A 1510LP
7) NYCOL A 1530

1.2.1) MOLECULAR FORMULA
1) O3-Sb2

Available Forms Sources

A)

1) Antimony trioxide exists as odorless, white crystals, cubes or powder: It exists in the vapor phase as Sb4O6 (Budavari, 1996) Lewis, 1996; (Sax & Lewis, 1987).

B)

1) Antimony trioxide is obtained by heating concentrated antimony ore (primarily antimony trisulfide) and recondensing the fumes (Groth et al, 1986). It can also be produced by air oxidation of molten antimony metal (ACGIH, 1986).
2) Antimony trioxide is often contaminated with arsenic. Air levels of arsenic at factory sites showed levels to range from 1 to 20 mcg/m(3) and averaged 5.6 mcg/m(3). However, it has been concluded that arsenic exists in antimony trioxide in a physically and toxicologically inert form (ACGIH, 1991).

C)

1) Antimony trioxide is used as a flame retardant in plastics (especially PVC), textiles and other materials (Rathjen, 1980). It is used in the manufacture of tartar emetic; as paint pigment; in enamels and glasses; as mordant; in flame-proofing of textiles, canvas, paper, and plastics (chiefly polyvinyl chloride); as ceramic opacifier; as a catalyst; as an intermediate; and in staining iron and copper (Harbison, 1998; Budavari, 1996; Sax & Lewis, 1987).

Overview

Life Support

A)

Clinical Effects

0.2.1)

A) The primary toxicity of antimony trioxide is pulmonary and gastrointestinal. Myocardial, liver, and kidney damage as well as mucous membrane irritation may be seen.
B) Following a massive ingestion, coma and seizures may occur.

0.2.3)

A) Slow pulse and low blood pressure may occur following inhalation.

0.2.4)

A) Conjunctivitis was reported due to exposure to antimony trioxide dust. Metallic taste and laryngitis may occur following acute inhalation.

0.2.5)

A) Chronic inhalation in humans may result in heart disease due to effects on heart muscle.
B) Myocardial damage was seen in animals chronically exposed to antimony trioxide.

0.2.6)

A) Interstitial fibrosis and pneumoconiosis have been seen after exposure to dust of antimony trioxide. Emphysema and upper airway inflammation may also occur following chronic exposure.

0.2.8)

A) Ingestions may result in nausea, vomiting and often bloody diarrhea.

0.2.9)

A) Fatty degeneration of the liver was seen in most animals exposed to chronic daily inhalations.

0.2.13)

A) Anemia as well as decreased white count and polymorphonuclear leucocytes reduction were seen in animals exposed to chronic daily inhalations.

0.2.14)

A) Antimony Spots is a rash consisting of papules and pustules surrounding sweat and sebaceous glands. They are primarily found on forearms, thighs and areas where clothing is tight.

0.2.21)

A) Some animal studies indicate that long term exposure to antimony trioxide is carcinogenic. Data on its carcinogenicity are conflicting and this is still being investigated.

Laboratory Monitoring

A)

B)

C)

Treatment Overview

0.4.2)

A) 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.
B) Treatment is mainly symptomatic and supportive.
C) Chelators such as BAL and unithiol have been used to decrease serum antimony levels, but experience with these in antimony trioxide poisoning is very limited.
D) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 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) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 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).

1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.

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.

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) 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).

Range Of Toxicity

A)

B)

C)

Clinical Effects

Summary Of Exposure

A)

B)

Vital Signs

3.3.1)

A) Slow pulse and low blood pressure may occur following inhalation.

3.3.2)

A) Shortness of breath and shallow breathing have been reported following acute inhalation exposures (HSDB , 2001) Prod Info Antimony Trioxide, 1997).

3.3.4)

A) Following acute inhalation exposures, lowered blood pressure may occur (HSDB , 2001).

3.3.5)

A) Decreased pulse may be noted following acute inhalation exposures (HSDB , 2001).

Heent

3.4.1)

A) Conjunctivitis was reported due to exposure to antimony trioxide dust. Metallic taste and laryngitis may occur following acute inhalation.

3.4.3)

A) CONJUNCTIVITIS was reported due to exposure to antimony trioxide dust (Dernehl et al, 1945). Contact with eyes is expected to result in lacrimation, irritation and conjunctivitis (HSDB , 2001) Prod Info Antimony Trioxide, 1997).
B) Dose-related cataracts were produced in rats exposed by inhalation at concentrations up to 4.5 mg/m(3) for 12 months (Newton et al, 1994). This effect has not been seen in exposed humans.

3.4.5)

A) Nosebleeds may occur following large exposures. Inhalation may result in loss of smell and rhinitis. Nasal septal perforation may be noted (HSDB , 2001).

3.4.6)

A) Metallic taste, laryngitis and bronchitis have been reported following inhalation exposures (HSDB , 2001).

Cardiovascular

3.5.1)

A) Chronic inhalation in humans may result in heart disease due to effects on heart muscle.
B) Myocardial damage was seen in animals chronically exposed to antimony trioxide.

3.5.2)

A) CARDIOVASCULAR FINDING

1) Although rare, it is possible that chronic inhalation of antimony trioxide may result in heart disease due to effects on the heart muscle (Prod Info Antimony Trioxide, 1997).

3.5.3)

A) ANIMAL STUDIES

1) CARDIOMYOPATHY

a) Myocardial damage and changes in coronary blood supply were noted in studies on animals who chronically inhaled air containing antimony trioxide (IRPTC, 1984).

Respiratory

3.6.1)

A) Interstitial fibrosis and pneumoconiosis have been seen after exposure to dust of antimony trioxide. Emphysema and upper airway inflammation may also occur following chronic exposure.

3.6.2)

A) PNEUMOCONIOSIS

1) Antimoniosis is a pneumoconiosis seen after exposure to airborne dust of antimony trioxide. It is characterized by numerous small opacities of the pinhead type found in the middle and lower lung fields. No massive lung fibrosis is noted (HSDB , 2001).

a) Lung changes develop after a minimum of 10 years of exposure (HSDB , 2001; Potkonjak & Pavlovich, 1983). Diffuse pneumosclerosis has been reported in human workers who averaged 11.0 years of exposure (IRPTC, 1984).

B) INJURY OF UPPER RESPIRATORY TRACT

1) Acute inhalation may result in dyspnea and upper and lower respiratory tract inflammation, including pneumonitis (HSDB , 2001). Inhalation of fumes may result in metal fume fever (Prod Info Antimony Trioxide, 1997).

3.6.3)

A) ANIMAL STUDIES

1) PULMONARY FIBROSIS

a) Interstitial fibrosis has been seen in several studies done on rats exposed chronically to between 45 to 125 mg of Sb2O3/m(3) air for up to 14.5 months (Groth et al, 1986) Gross et al, 1955 a & b).

2) PNEUMONIA

a) An interstitial pneumonia was seen in animals chronically exposed to 190 mg/m(3). Rats exposed to 1700 mg of antimony trioxide/m(3) for 1 hour/day for 2 months over 1 year did not produce chronic pneumonitis and this compound was thought to be relatively inert (Stokinger, 1981).

Neurologic

3.7.2)

A) SEIZURE

1) Massive ingestion may result in coma and seizures, possibly followed by death (HSDB , 2001) Prod Info Antimony Trioxide, 1997).

Gastrointestinal

3.8.1)

A) Ingestions may result in nausea, vomiting and often bloody diarrhea.

3.8.2)

A) GASTROENTERITIS

1) Should antimony trioxide be ingested, nausea or vomiting and diarrhea would be expected (Harbison, 1998) Prod Info Antimony Trioxide, 1997; (IRPTC, 1984). Bloody diarrhea may occur (HSDB , 2001).
2) Following the ingestion of lemonade contaminated with antimony trioxide, 56 out of 70 people were hospitalized with burning abdominal pain, colic, nausea and vomiting; recovery occurred within 3 hours for most of the victims (HSDB , 2001).

3.8.3)

A) ANIMAL STUDIES

1) SPLEEN DISORDER

a) Hypertrophy of splenic follicles was seen in animals exposed to chronic daily concentrations of 45 mg/m(3) (Dernehl et al, 1945).

Hepatic

3.9.1)

A) Fatty degeneration of the liver was seen in most animals exposed to chronic daily inhalations.

3.9.3)

A) ANIMAL STUDIES

1) LIVER FATTY

a) Fatty degeneration of the liver was seen in most animals exposed to chronic daily inhalation of 45 mg/m(3) of antimony trioxide (Dernehl et al, 1945).

Hematologic

3.13.1)

A) Anemia as well as decreased white count and polymorphonuclear leucocytes reduction were seen in animals exposed to chronic daily inhalations.

3.13.3)

A) ANIMAL STUDIES

1) LEUKOPENIA

a) Eosinopenia as well as a decrease in white blood count and polymorphonuclear leucocytes were seen in animals exposed to chronic daily levels of 45 mg/m(3) (Dernehl et al, 1945).

2) ANEMIA

a) Animals dusted chronically with antimony trioxide (57 +/- 9 mg/m(3)) had decreased numbers of erythrocytes and amount of hemoglobin (IRPTC, 1984).

Dermatologic

3.14.1)

A) Antimony Spots is a rash consisting of papules and pustules surrounding sweat and sebaceous glands. They are primarily found on forearms, thighs and areas where clothing is tight.

3.14.2)

A) MACULOPAPULAR ERUPTION

1) Antimony trioxide is a contact irritant (HSDB , 2001). Antimony spots have been seen after industrial exposure. These spots are a rash consisting of itchy papules and pustules surrounding sweat and sebaceous glands and are referred to as "antimony measles" (Prod Info Antimony Trioxide, 1997).

a) They are primarily found on forearms, thighs and areas where clothing is tight. It is more common in hot weather (Stokinger, 1981).

Immunologic

3.19.2)

A) IMMUNE SYSTEM FINDING

1) LACK OF EFFECT

a) Antimony trioxide is a contact irritant; patch tests for allergy generally produce no reaction (HSDB , 2001).

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS1309-64-4 (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: Antimony trioxide
b) Carcinogen Rating: 2B

1) The agent (mixture) is possibly carcinogenic to humans. The exposure circumstance entails exposures that are possibly carcinogenic to humans. This category is used for agents, mixtures and exposure circumstances for which there is limited evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals. It may also be used when there is inadequate evidence of carcinogenicity in humans but there is sufficient evidence of carcinogenicity in experimental animals. In some instances, an agent, mixture or exposure circumstance for which there is inadequate evidence of carcinogenicity in humans but limited evidence of carcinogenicity in experimental animals together with supporting evidence from other relevant data may be placed in this group.

3.21.2)

A) Some animal studies indicate that long term exposure to antimony trioxide is carcinogenic. Data on its carcinogenicity are conflicting and this is still being investigated.

3.21.3)

A) LACK OF INFORMATION

1) Data on whether antimony trioxide is a human carcinogen are conflicting and are still being investigated (ACGIH, 1986). Antimony trioxide is a suspected human carcinogen and is carcinogenic in experimental animals (HSDB , 2001; Lewis & Sr, 2000).

B) NEOPLASM

1) In a study done by Groth et al (1986) on rats exposed to antimony trioxide (TWA 45 mg/m(3)) for 7 hours/day, 5 days/week for 52 weeks, 27% of females had lung neoplasms.

a) Male rats did not develop the neoplasms. There was no significant difference in the incidence of other types of cancer between the exposed group and the controlled group.

3.21.4)

A) LACK OF EFFECT

1) LACK OF EFFECT

a) Antimony trioxide was not carcinogenic in Fischer 344 rats exposed to doses as high as 4.5 mg/m(3) for 12 months. Previous studies which reported antimony trioxide to be carcinogenic were carried out at higher lung burdens (Newton et al, 1994).

Genotoxicity

A)

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) A urine assay can be used to confirm diagnosis. Levels of 1.0 mg/L may indicate a potentially harmful antimony exposure.
B) Monitor vital signs and monitor for gastrointestinal effects following acute exposures.
C) Monitor for respiratory effects (dyspnea, upper airway injury) following inhalation exposures.

4.1.2)

A) HEMATOLOGIC

1) Monitor CBC in all significant exposures.

B) BLOOD/SERUM CHEMISTRY

1) Monitor fluid status and serum electrolytes following vomiting and diarrhea after oral exposures.

4.1.3)

A) URINARY LEVELS

1) A urine assay can be used to confirm diagnosis. Levels of 1.0 mg/L may indicate a potentially harmful antimony exposure (Elkins, 1959).

4.1.4)

A) OTHER

1) ECG

a) Obtain an ECG in symptomatic patients.

2) MONITORING

a) Monitor the CNS for signs of seizures or coma following a significant ingestion.

3) PULMONARY FUNCTION TESTS

a) Following acute inhalation exposures with respiratory signs or symptoms, monitor pulse oximetry and/or blood gases and chest radiograph.

Methods

A)

1) A spectrochemical method for analysis of antimony in biologic materials has been published by Kinser et al (1965). It has a lower limit of detection of 50 ppm in 2 mg of ash.

Treatment

Life Support

A)

Monitoring

A)

B)

C)

Oral Exposure

6.5.1)

A) ACTIVATED CHARCOAL

1) There are no reports of activated charcoal being used to adsorb to antimony salts. Since there is little risk in using activated charcoal, we recommend it until further data are available.
2) 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).

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).

6.5.2)

A) ACTIVATED CHARCOAL

1) There are no reports of activated charcoal being used to adsorb to antimony salts. Since there is little risk in using activated charcoal, we recommend it until further data are available.
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) SUPPORT

1) There is no specific treatment other than chelation, which has been recommended by some authors; however there is no good clinical data demonstrating a benefit with chelation. Patients should be treated symptomatically. Monitor for respiratory and CNS effects.

B) CHELATION THERAPY

1) BAL, given intramuscularly for 10 days has been recommended as treatment (Moeschlin, 1965).
2) Unithiol (not available in the U.S.) has been used experimentally (IRPTC, 1984; Reynolds, 1982).

a) Unithiol is a dimercaprol derivative.
b) Doses used are 1 milliliter of a 5 percent solution per 10 kilograms of patient's weight 3 to 4 times a day on day 1, 2 to 3 times on day two and 1 to 2 times on day 3 through 7.
c) The drug is given intramuscularly. Children 5 to 10 years old have been given 1/3 to 1/2 of the adult dose (IRPTC, 1984).

C) AIRWAY MANAGEMENT

1) If CNS and respiratory depression occur, ensure airway patency and adequacy of oxygenation and ventilation. Endotracheal intubation, supplemental oxygenation, and assisted ventilation could be required.

D) SEIZURE

1) 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).

2) 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 .

3) 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).

4) 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, 2010; Chin et al, 2008).

5) 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).

6) 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).

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 supplemental oxygen with assisted ventilation as required to patients with respiratory tract irritation.

B) 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).

Dermal Exposure

6.9.1)

A) DERMAL DECONTAMINATION

1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Abstracts

Range Of Toxicity

Summary

A)

B)

C)

Minimum Lethal Exposure

A)

1) The minimum lethal human dose to this agent has not been delineated.

Maximum Tolerated Exposure

A)

1) INHALATION - Exposure to 0.5 to 5 milligrams/cubic meter of dust and fumes in an antimony plant (presumably primarily antimony trioxide) resulted in only radiographic changes without systemic toxicity (McCallum, 1963).
2) INGESTION - Antimony trioxide leached from an enamel container into lemonade, which 70 people drank. Fifty-six of these people became ill with colic, nausea and vomiting, with recovery occurring within about 3 hours. It was estimated that anyone ingesting 300 milliliters of the lemonade would have consumed about 36 milligrams antimony (HSDB , 2001).

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) Antimony trioxide production

a) TLV:

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

b) Notations and Endnotes:

1) Carcinogenicity Category: A2
2) Codes: L
3) Definitions:

a) A2: Suspected Human Carcinogen: Human data are accepted as adequate in quality but are conflicting or insufficient to classify the agent as a confirmed human carcinogen; OR, the agent is carcinogenic in experimental animals at dose(s), by route(s) of exposure, at site(s), of histologic type(s), or by mechanism(s) considered relevant to worker exposure. The A2 is used primarily when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals with relevance to humans.
b) L: Exposure by all routes should be carefully controlled to levels as low as possible.

c) TLV Basis - Critical Effect(s): Lung cancer; pneumoconiosis
d) Molecular Weight: 291.5

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 CAS1309-64-4 (National Institute for Occupational Safety and Health, 2007):

1) Not Listed

C) Carcinogenicity Ratings for CAS1309-64-4 :

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A2 ; Listed as: Antimony trioxide production

a) A2 :Suspected Human Carcinogen: Human data are accepted as adequate in quality but are conflicting or insufficient to classify the agent as a confirmed human carcinogen; OR, the agent is carcinogenic in experimental animals at dose(s), by route(s) of exposure, at site(s), of histologic type(s), or by mechanism(s) considered relevant to worker exposure. The A2 is used primarily when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals with relevance to humans.

2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Antimony trioxide
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): 2B ; Listed as: Antimony trioxide

a) 2B : The agent (mixture) is possibly carcinogenic to humans. The exposure circumstance entails exposures that are possibly carcinogenic to humans. This category is used for agents, mixtures and exposure circumstances for which there is limited evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals. It may also be used when there is inadequate evidence of carcinogenicity in humans but there is sufficient evidence of carcinogenicity in experimental animals. In some instances, an agent, mixture or exposure circumstance for which there is inadequate evidence of carcinogenicity in humans but limited evidence of carcinogenicity in experimental animals together with supporting evidence from other relevant data may be placed in this group.

4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
5) MAK (DFG, 2002): Category 2 ; Listed as: Antimony trioxide

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 ): Not Listed

D) OSHA PEL Values for CAS1309-64-4 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

1) Not Listed

Toxicity Information

7.7.1)

A) References: RTECS, 2001 Lewis, 1996)

1) LD50- (INTRAPERITONEAL)MOUSE:

a) 172 mg/kg

2) LD50- (INTRAPERITONEAL)RAT:

a) 3250 mg/kg

3) LD50- (ORAL)RAT:

a) > 20 g/kg

4) TCLo- (INHALATION)RAT:

a) 4200 mcg/m(3) for 52W-I -- CAR

Pharmacology Toxicology

Toxicologic Mechanism

A)

Physicochemical

Physical Characteristics

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Ph

A)

Molecular Weight

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Other

A)

1) Odorless (CHRIS, 2005).

Animal Toxicology

References

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ANTIMONY TRIOXIDE

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