ARSENIC TRIOXIDE

Arsenic trioxide is used for induction of remission and consolidation in patients with acute promyelocytic leukemia (APL) with the presence of the t (15;17) translocation or PML/RAR-alpha gene expression, who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy (Prod Info TRISENOX(R) IV injection, 2010).

OTHER USES

Arsenic trioxide is the most important commercial arsenic compound (Clayton & Clayton, 1994). It is the primary material used to produce all arsenical compounds, and is used as an intermediate for insecticides, herbicides, and fungicides, as a wood preservative, as a decoloring and refining agent in the manufacture of glass, in pharmaceutical preparations, pigments, and in sheep and cattle dip for preserving hides, as a textile mordant, and to purify synthetic gases (EPA, 1985; Lewis, 1993; Budavari, 1996; Morgan, 1989).
About 85% of the pesticidal use of arsenic trioxide has been in liquid preparations intended to kill mice and rats (EPA, 1988). The remaining 15% has been used to kill moles, pocket gophers, and ants (EPA, 1988). However, many arsenic-containing pesticides have been banned in the US (Clayton & Clayton, 1994). For many years, arsenical pesticides were the most common cause of fatal poisoning in the US (Hayes & Laws, 1991).

FORMS

THERAPEUTIC USE

Arsenic trioxide injection is available as 10 mg/10 mL (1 mg/mL) sterile, clear, colorless solution in 10 mL glass, single-use ampules (Prod Info TRISENOX(R) IV injection, 2010).

SOURCES

OTHER USES

Arsenic trioxide is obtained as a byproduct in the smelting of copper and lead concentrates (HSDB, 2006).
In the United States, arsenic trioxide is mainly found in smelting of copper sulfide ores; the highest exposures are usually to roaster workers (HSDB, 2006). Arsenic trioxide in a solubilized form becomes sodium arsenite, which is more toxic than in the unsolubilized form.

-CLINICAL EFFECTS

GENERAL CLINICAL EFFECTS

USES: Arsenic trioxide is used for induction of remission and consolidation in patients with acute promyelocytic leukemia (APL). Arsenic trioxide is the primary material used to produce all arsenical compounds, and is used as an intermediate for insecticides, herbicides, and fungicides, as a wood preservative, a decoloring and refining agent in the manufacture of glass, and a textile mordant. It is also used in pharmaceutical preparations, pigments, and in sheep and cattle dip for preserving hides.

PHARMACOLOGY: The precise mechanism of action of arsenic trioxide in acute promyelocytic leukemia (APL) remains to be clearly defined. However, in vitro studies indicated that morphological changes and DNA fragmentation characteristic of apoptosis occur in NB4 human promyelocytic leukemia cells following arsenic trioxide administration. Selective apoptosis of APL cells mediated by activation of cysteine-proteases (caspases) may be involved. Additionally, arsenic trioxide induces damage and degradation of the fusion protein PML/RAR-alpha.

TOXICOLOGY: Trivalent arsenic (As3+) disrupts oxidative phosphorylation, leading to free radical formation via inhibition of pyruvate dehydrogenase, which subsequently decreases gluconeogenesis due to lack of acetyl-CoA. Chronically, arsenic may cause DNA damage, mutation in the p-53 suppressor gene, and inhibition of DNA repair mechanisms leading to cancer.

EPIDEMIOLOGY: INTRAVENOUS ROUTE: Overdose is rare. OTHER ROUTES: Toxicity from arsenic is uncommon and major effects are rare.

WITH POISONING/EXPOSURE

INTRAVENOUS ROUTE

Data is limited. Seizures, muscle weakness, confusion may occur; other effects are similar to exposure by other routes (see below).

OTHER ROUTES

ACUTE OVERDOSE: Arsenic compounds are mainly absorbed through the gastrointestinal tract, but some absorption may occur through intact skin or inhalation. Acute arsenic ingestion generally produces signs and symptoms within 30 minutes but symptoms may be delayed for several hours if ingested with food. Many arsenic compounds are severe irritants of the skin, eye, and mucous membranes; some may be corrosive. Contact produces local hyperemia, followed by vesicular or pustular eruptions. Trivalent compounds are particularly caustic. Acute inhalation exposures have resulted in irritation of the upper respiratory tract.
MILD TO MODERATE TOXICITY: Gastrointestinal symptoms occur rapidly after acute ingestion. Initial signs and symptoms include burning lips, throat constriction, and dysphagia. Excruciating abdominal pain, severe nausea, vomiting, and profuse "rice water-like" diarrhea that may lead to hypovolemia follows these symptoms. In addition, hypovolemia from capillary leakage (third-spacing of fluids) is a common early effect. QTc prolongation may occur. Muscle cramps, facial edema, bronchitis, dyspnea, chest pain, dehydration, intense thirst, and fluid-electrolyte disturbances are also common following significant exposures. A garlic-like odor of the breath and feces may also develop. Subacute toxicity can produce neuropathies, both motor and sensory, and can progress to a Guillain-Barre like syndrome.
SEVERE TOXICITY: Hypotension and tachycardia are common early signs of severe poisoning. Hypotension may be resistant to fluid resuscitation and multi-organ failure may ensue. Fever and tachypnea may occur. These patients can develop ventricular dysrhythmias including torsade de pointes. Encephalopathy, seizures and coma have been reported. Acute renal failure, hemolytic anemia, rhabdomyolysis, and hepatitis may occur several days after ingestion.
CHRONIC TOXICITY: Inhalation is the most common route of exposure in arsenic workers. The sequence of chronic poisoning involves weakness, anorexia, hepatomegaly, jaundice, and gastrointestinal complaints, followed by conjunctivitis, irritation of the upper respiratory tract, hyperpigmentation, and eczematoid and allergic dermatitis. A hoarse voice and chronic upper respiratory septum is a common result after prolonged inhalation of white arsenic dust or fume. Peripheral nervous system symptoms may include numbness, burning, and tingling of the hands and feet; pain; paresthesias; tenderness; muscle fasciculations; gross tremors; ataxia; discoloration; and mental confusion. Muscular weakness, limb tenderness and difficulty walking may follow. The final phase consists of peripheral sensory neuropathy of the hands and feet. Associated motor neuropathy may occur as well. Certain arsenic compounds are known human carcinogens. Chronic exposure in either occupational settings or by drinking contaminated groundwater can cause poisoning and carries an increased risk of skin, lung, bladder, and possibly liver cancers.

WITH THERAPEUTIC USE

INTRAVENOUS ROUTE: COMMON (greater than 20%): Nausea, vomiting, diarrhea, constipation, abdominal pain, fatigue, fever, edema, rigors, chest pain, injection site pain, sore throat, hypokalemia, hypomagnesemia, hyperglycemia, elevated liver enzymes, headache, insomnia, paresthesia, dizziness, cough, dyspnea, epistaxis, hypoxia, pleural effusion, dermatitis, pruritus, ecchymosis, tachycardia, hypotension, sinusitis, arthralgia, myalgia, bone pain, leukocytosis, anemia, anxiety. OTHER ADVERSE EFFECTS: Palmar keratosis, rashes, hyperkalemia, hypocalcemia, nausea, vomiting, diarrhea, anorexia, abdominal pain, thrombocytopenia, neutropenia, neutropenia, noncirrhotic portal hypertension, hypersensitivity reaction, tremor, peripheral neuropathy, seizure, coma, and acidosis.
Patients receiving arsenic trioxide may develop QT interval prolongation, complete atrioventricular block, premature ventricular contractions (PVCs), ventricular tachycardia, and a potentially fatal torsade de pointes ventricular dysrhythmia.
Retinoic acid syndrome (retinoic-acid-Acute Promyelocytic Leukemia, RA-APL, or APL differentiation syndrome), a serious adverse effect, may also occur. It is characterized by fever, skin rash, lower leg edema, weight gain, dyspnea, pulmonary infiltrates, and pleural or pericardial effusions, with or without leukocytosis and death.

POTENTIAL HEALTH HAZARDS - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 151 (ERG, 2004)

Highly toxic, may be fatal if inhaled, swallowed or absorbed through skin.
Avoid any skin contact.
Effects of contact or inhalation may be delayed.
Fire may produce irritating, corrosive and/or toxic gases.
Runoff from fire control or dilution water may be corrosive and/or toxic and cause pollution.

ACUTE CLINICAL EFFECTS

WITH POISONING/EXPOSURE

TOXICITY: Arsenic trioxide is highly poisonous. The potency of arsenic trioxide in acute exposures is a combination of several factors: whether it is dry or in solution, the purity, and the coarseness of grind of the solid form (Hayes & Laws, 1991). As much as 80% of ingested arsenic trioxide may be absorbed (Mahieu et al, 1981).
TARGET ORGANS: The primary target organs initially are the gastrointestinal tract, heart, brain, and kidneys. Eventually, the skin, bone marrow, and peripheral nervous system may be significantly damaged (Finkel, 1983; Morgan, 1989; Sittig, 1985; HSDB, 2006).
ONSET: Acute arsenic ingestion generally produces symptoms within 30 to 60 minutes, but symptom onset may be delayed for several hours if ingested with food (Morgan, 1989; Sittig, 1985).
SIGNS AND SYMPTOMS: Hypovolemia from capillary leaking ("third spacing" of fluids) is a common early sign. The following effects have been reported: a sensation of burning, dryness, and constriction of the oral and nasal cavities, a metallic or garlic taste and garlic-like odor of the breath, vomiting, abdominal pain, dysphagia, profuse watery (rice-water-like) and sometimes bloody diarrhea, dehydration, intense thirst, fluid-electrolyte disturbances, hemolysis, pancytopenia, anemia (HSDB, 2006; Hathaway et al, 1991; Morgan, 1989; Sittig, 1985; Finkel, 1983; EPA, 1988; Kjeldsberg & Ward, 1972; Kyle & Pease, 1965). Cardiac dysrhythmias may occur, but these may be secondary to electrolyte imbalance (Peterson & Rumack, 1977; Goldsmith, 1980; St Peter et al, 1970; Sittig, 1985). Severe hypotension and metabolic acidosis were seen in a case of arsenic trioxide ingestion (Levin-Scherz et al, 1987).
MEE'S LINES, transverse white lines in the nails, may be seen after acute exposure. Mee's lines commonly take 5 weeks to appear above the cuticle and advance 1 mm per week afterwards, allowing an approximation of the time of acute exposure (Heyman et al, 1956).
CNS EFFECTS:

ENCEPHALOPATHY: Permanent encephalopathy may ensue from acute exposure to arsenic compounds. The encephalopathy can result in atrophy of the cortex one to six months after exposure (Fincher & Koerker, 1987). This can cause loss of many higher functions.
PERIPHERAL NEUROPATHY: Peripheral neuropathy of both the sensory and motor type can appear in a similar pattern regardless of the route of exposure to arsenic compounds (Finkel, 1983). It commonly begins one to 3 weeks later (Le Quesne & McLeod, 1977; Heyman et al, 1956), usually as paresthesias of the soles of the feet, then the hands, progressing proximally over the next few days (Heyman et al, 1956). Severe muscle weakness and wasting then develops (distal more so than proximal), causing disability (Donofrio et al, 1987; Le Quesne & McLeod, 1977; Heyman et al, 1956). It may initially be confused with Guillain-Barre' syndrome (Donofrio et al, 1987).
Physical findings of arsenic neuropathy usually include prominently decreased sensation to touch, pinprick, and temperature, frequently in a stocking and glove distribution (Heyman et al, 1956). Loss of vibration sense is also common. Wrist drop, foot drop, and fasciculations may also occur with arsenic poisoning (Heyman et al, 1956).

CASE REPORTS: Ingestion of 9 to 14 mg was sufficient to produce signs of arsenic poisoning in a 16-month-old child (Watson et al, 1981).
FATAL CASES -

As little as 70 to 200 mg of arsenic trioxide ingested acutely by an adult may be lethal (Baselt & Cravey, 1989; Baselt, 1988; HSDB, 2006).
Ingestion of 2 grams of arsenic trioxide in a suicide attempt was fatal despite chelation therapy, intensive supportive care, and hemodialysis (Levin-Scherz et al, 1987).
Severe hypotension and metabolic acidosis were seen in a worker who died within a few hours after being buried under crude arsenic trioxide for 1 to 2 minutes at a copper smelting facility (Gerhardsson et al, 1988).

ANIMAL STUDIES: In experimental animal studies, arsenic trioxide caused edema of the eyelid and corneal injury and opacity in rabbits (Grant, 1986).
TOXICOLOGY: Arsenic inhibits enzymes required for cellular respiration, and has the effect of depleting cellular energy stores, leading to cellular death (Schoolmeester & White, 1980).
TREATMENT: Of six analogues of dimercaptosuccinic acid (DMSA) evaluated for efficacy in treating mice poisoned with arsenic trioxide, none were superior to DMSA for reducing either lethality or arsenic concentrations in tissues (Kreppel et al, 1993).

CHRONIC CLINICAL EFFECTS

TOXICITY: Workers chronically exposed to arsenic by inhalation and dermal contact have developed a hoarse voice, nasal irritation, possible perforation of the nasal septum, irritation of eyes, skin, and mucous membranes, alopecia, enlarged livers, and rarely, cirrhosis of the liver (ACGIH, 1991; Finkel, 1983; Sittig, 1985; Hathaway et al, 1991; Clayton & Clayton, 1994).

CNS: Smelter workers exposed to arsenic trioxide may also have a higher incidence of subclinical or clinical peripheral neuropathies (Feldman et al, 1979).

ENDOCRINE: There is evidence that cumulative arsenic exposure of greater than 15 ppm-year increased the prevalence of Diabetes mellitus by an odds ratio of 10 in a population living in an area with endemically high arsenic levels in groundwater (Lai et al, 1994).

GASTROINTESTINAL: Nausea and vomiting are infrequent complaints among arsenic workers (Clayton & Clayton, 1994).

HEENT: Eye irritation, photophobia, dimness of vision, diplopia, and lacrimation may occur with arsenic trioxide exposure (Heyman et al, 1956; Grant, 1986).

HEMATOLOGY: Aplastic anemia has also been described after chronic arsenic exposure (Kjeldsberg & Ward, 1972).

HEPATIC: Noncirrhotic portal hypertension developed in a patient who had taken Fowler's solution (1 percent arsenic trioxide) for four years (Robertson & Low-Beer, 1983).

SKIN: Skin disorders after chronic ingestion have included: melanosis, depigmentation, keratosis, and hyperkeratosis (Das D et al, 1995; Lerda, 1994).

Painful ulceration of the wrist and scrotal skin, lips, and nostrils may develop with arsenic dust exposure (Finkel, 1983; Sittig, 1985).

OCCUPATIONAL EXPOSURE: Exposure to arsenic trioxide during glassmaking (and presumably in other occupations) can result in subacute arsenic poisoning (Ide & Bullough, 1988).

TOLERANCE: Tolerance to arsenic can occur with repeated exposure in humans, dogs, rats, rabbits, and rats (Hayes & Laws, 1991).

-FIRST AID

FIRST AID AND PREHOSPITAL TREATMENT

PREHOSPITAL: Remove the contaminated clothing and wash the patient thoroughly.

-MEDICAL TREATMENT

LIFE SUPPORT

Support respiratory and cardiovascular function.

SUMMARY

FIRST AID - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 151 (ERG, 2004)

Move victim to fresh air.
Call 911 or emergency medical service.
Give artificial respiration if victim is not breathing.
Do not use mouth-to-mouth method if victim ingested or inhaled the substance;give artificial respiration with the aid of a pocket mask equipped with a one-way valve or other proper respiratory medical device.
Administer oxygen if breathing is difficult.
Remove and isolate contaminated clothing and shoes.
In case of contact with substance, immediately flush skin or eyes with running water for at least 20 minutes.
For minor skin contact, avoid spreading material on unaffected skin.
Keep victim warm and quiet.
Effects of exposure (inhalation, ingestion or skin contact) to substance may be delayed.
Ensure that medical personnel are aware of the material(s) involved and take precautions to protect themselves.

FIRST AID

FIRST AID

The following first aid measures are suggested (National Institute for Occupational Safety and Health, 2007; OSHA, 2000):

EYE EXPOSURE: Immediately wash the eyes with large amounts of water, occasionally lifting the lower and upper lids. Get medical attention immediately. Primary eye protection (spectacles or goggles), as defined by the Occupational Safety and Health Administration (OSHA), should be used when working with this chemical. Face shields should only be worn over primary eye protection.

Contact lens use is not recommended when working with this chemical. If contact lenses are worn, then appropriate eye and face protection devices must be used. OSHA emphasizes that dusty and/or chemical environments may represent an additional hazard to contact lens wearers.

DERMAL EXPOSURE: Immediately wash the contaminated skin with soap and water. If this chemical penetrates the clothing, immediately remove the clothing, wash the skin with soap and water, and get medical attention promptly.
INHALATION EXPOSURE: Move the exposed person to fresh air at once. If breathing has stopped, perform artificial respiration. Keep the affected person warm and at rest. Get medical attention as soon as possible.
ORAL EXPOSURE: If this chemical has been swallowed, get medical attention immediately.
TARGET ORGANS: Liver, kidneys, skin, lungs and lymphatic system [lung and lymphatic cancer] .

GENERAL

Patients with acute arsenic poisoning usually die from hypovolemic shock secondary to vomiting and diarrhea, gastrointestinal tract bleeding, and 'third spacing' of fluids. Fluid replacement is a mainstay of initial treatment.
Another threat to life is cardiac toxicity resulting in arrhythmias or cardiogenic shock. Advanced cardiac support may be required after massive acute arsenic poisoning.

INHALATION EXPOSURE

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.

DERMAL EXPOSURE

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).

EYE EXPOSURE

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.

ORAL EXPOSURE

Activated charcoal does not bind arsenic well.

-RANGE OF TOXICITY

MINIMUM LETHAL EXPOSURE

Potentially fatal doses of arsenic trioxide have been listed as 70 to 180 mg or 1 to 2.5 mg/kg (HSDB, 2006).

ORAL: An oral dose of 120 mg of arsenic trioxide may be fatal (Finkel, 1983). Ingestion of 2 grams of arsenic trioxide in a suicide attempt was fatal despite chelation therapy, intensive supportive care, and hemodialysis (Levin-Scherz et al, 1987).

A worker who was buried under crude arsenic trioxide for 1 to 2 minutes died within a few hours of the exposure, despite intensive treatment (Gerhardsson et al, 1988).

Arsenic trioxide in a solubilized form becomes sodium arsenite, which is more toxic than in an unsolubilized form. One source reported that 200 mg of arsenic trioxide ingested acutely by an adult may be lethal (Baselt & Cravey, 1989; Baselt, 1988).

MAXIMUM TOLERATED EXPOSURE

ADULTS

More than 50% of a group of 74 patients who took an antihistaminic herbal preparation (3.3 mg of arsenic trioxide daily) developed a sensorimotor peripheral neuropathy (HSDB , 1991).
A 43-year-old man survived after ingesting 54 g of arsenic trioxide in a suicide attempt, 200 times the lethal dose (Duenas-Laita et al, 2005).
A 23-year-old man intentionally ingested 1040 mg of arsenic trioxide. Clinical manifestations included severe weakness, brown watery diarrhea, vomiting, and unquenchable thirst, followed by constricted visual fields, hepatic dysfunction, dermatitis, and peripheral neuropathy. He was treated with fluid resuscitation and BAL. All of the patient's symptoms, including his visual impairment, resolved over the next 3 weeks and he was discharged without sequelae (Kamijo et al, 1998).
A 33-year-old woman survived ingestion of 1850 mg of arsenic trioxide following treatment with 2,3 propanesulphonate (DMPS) and hemodialysis (Kruszewska et al, 1996).
CASE SERIES: Vomiting was reported in 6 children following ingestion of all or part of an ant bait gel bar containing 0.46% arsenic trioxide (estimated total dose ranging from 5 to 45 mg). One of the children (a 20-month-old girl) also experienced several episodes of diarrhea. Initial urine arsenic concentrations ranged from 1,858 to 13,981 mcg/L. All 6 children recovered following chelation therapy with succimer (Yarris et al, 2008).
A 77-year-old man developed nausea, vomiting, renal impairment, and anemia after ingesting 4 g of arsenic trioxide in a suicide attempt. With supportive care, including chelation therapy with dimercaprol (BAL), the patient gradually recovered (Yilmaz et al, 2009).
A 67-year-old woman who was treated for persistent psoriasis with Fowler's solution over a 15 year period (estimated at 25 g of arsenic trioxide in all) developed noncirrhotic hepatic fibrosis as a result of the chronic arsenic poisoning (Piontek et al, 1989).

PEDIATRIC

Acute ingestion of 9 to 14 mg of arsenic trioxide by a 16-month-old child produced classic GI signs and symptoms of arsenic poisoning (Watson et al, 1981).

Carcinogenicity Ratings for CAS1327-53-3 :

ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
EPA (U.S. Environmental Protection Agency, 2011): Not Listed
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): 1 ; Listed as: Arsenic trioxide

1 : The agent (mixture) is carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans. This category is used when there is sufficient evidence of carcinogenicity in humans. Exceptionally, an agent (mixture) may be placed in this category when evidence of carcinogenicity in humans is less than sufficient but there is sufficient evidence of carcinogenicity in experimental animals and strong evidence in exposed humans that the agent (mixture) acts through a relevant mechanism of carcinogenicity.

NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
MAK (DFG, 2002): Category 1 ; Listed as: Arsenic and inorganic arsenic compounds: Arsenic trioxide

Category 1 : Substances that cause cancer in man and can be assumed to make a significant contribution to cancer risk. Epidemiological studies provide adequate evidence of a positive correlation between the exposure of humans and the occurence of cancer. Limited epidemiological data can be substantiated by evidence that the substance causes cancer by a mode of action that is relevant to man.

NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

TOXICITY AND RISK ASSESSMENT VALUES

EPA IRIS

EPA Risk Assessment Values for CAS1327-53-3 (U.S. Environmental Protection Agency, 2011):

Not Listed

TOXICITY VALUES

LD50- (INTRAVENOUS)MOUSE:
- 10,700 mcg/kg (RTECS, 2006)
LD50- (ORAL)MOUSE:
- 20 mg/kg (RTECS, 2006)
LD50- (SUBCUTANEOUS)MOUSE:
- 9800 mcg/kg (RTECS, 2006)
LD50- (INTRAPERITONEAL)RAT:
- 871 mg/kg (RTECS, 2006)
LD50- (ORAL)RAT:
- 10 mg/kg (RTECS, 2006)
LDLo- (ORAL)CATTLE:
- 30 mg/kg (RTECS, 2006)
LDLo- (SUBCUTANEOUS)CHICKEN:
- 13 mg/kg (RTECS, 2006)
LDLo- (ORAL)DOG:
- 10 mg/kg (RTECS, 2006)
LDLo- (ORAL)HUMAN:
- 1429 mcg/kg (RTECS, 2006)
LDLo- (INTRAVENOUS)RABBIT:
- 10,560 mcg/kg (RTECS, 2006)
LDLo- (ORAL)RABBIT:
- 4 mg/kg (RTECS, 2006)
LDLo- (SUBCUTANEOUS)RABBIT:
- 7 mg/kg (RTECS, 2006)
LDLo- (SUBCUTANEOUS)RAT:
- 8 mg/kg (RTECS, 2006)

-STANDARDS AND LABELS

WORKPLACE STANDARDS

ACGIH TLV Values for CAS1327-53-3 (American Conference of Governmental Industrial Hygienists, 2010):

Not Listed

AIHA WEEL Values for CAS1327-53-3 (AIHA, 2006):

Not Listed

NIOSH REL and IDLH Values for CAS1327-53-3 (National Institute for Occupational Safety and Health, 2007):

Not Listed

OSHA PEL Values for CAS1327-53-3 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

Not Listed

OSHA List of Highly Hazardous Chemicals, Toxics, and Reactives for CAS1327-53-3 (U.S. Occupational Safety and Health Administration, 2010):

Not Listed

ENVIRONMENTAL STANDARDS

EPA CERCLA, Hazardous Substances and Reportable Quantities for CAS1327-53-3 (U.S. Environmental Protection Agency, 2010):

Listed as: Arsenic oxide As2O3
Final Reportable Quantity, in pounds (kilograms):

1 (0.454)

Additional Information:
Listed as: Arsenic trioxide
Final Reportable Quantity, in pounds (kilograms):

1 (0.454)

Additional Information:

EPA CERCLA, Hazardous Substances and Reportable Quantities, Radionuclides for CAS1327-53-3 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA RCRA Hazardous Waste Number for CAS1327-53-3 (U.S. Environmental Protection Agency, 2010b):

Listed as: Arsenic oxide As2 O3
P or U series number: P012
Footnote:
Listed as: Arsenic trioxide
P or U series number: P012
Footnote:
Editor's Note: The D, F, and K series waste numbers and Appendix VIII to Part 261 -- Hazardous Constituents were not included. Please refer to 40 CFR Part 261.

EPA SARA Title III, Extremely Hazardous Substance List for CAS1327-53-3 (U.S. Environmental Protection Agency, 2010):

Listed as: Arsenous Oxide
Reportable Quantity, in pounds: 1

Only the statutory or final RQ is shown. For more information, see 40 CFR table 302.4.

Threshold Planning Quantity, in pounds:

100/10,000
Amount necessary to be covered by this standard. See 40 CFR 355.30.

Note(s): d

d: Revised TPQ based on new or re-evaluated toxicity data, April 22, 1987.

EPA SARA Title III, Community Right-to-Know for CAS1327-53-3 (40 CFR 372.65, 2006; 40 CFR 372.28, 2006):

Not Listed

DOT List of Marine Pollutants for CAS1327-53-3 (49 CFR 172.101 - App. B, 2005):

Not Listed

EPA TSCA Inventory for CAS1327-53-3 (EPA, 2005):

Listed as: Arsenic oxide (As2O3)

SHIPPING REGULATIONS

SURFACE

DOT -- Table of Hazardous Materials and Special Provisions for UN/NA Number 1561 (49 CFR 172.101, 2005):

Hazardous materials descriptions and proper shipping name: Arsenic trioxide

Symbol(s): Not Listed
Hazard class or Division: 6.1

6.1: Poisonous materials. See 49 CFR section 173.132 for definitions.

Identification Number: UN1561
Packing Group: II

II: Packing Group II - indicates the degree of danger presented by the material is medium.

Label(s) required (if not excepted): 6.1

6.1: Poison Inhalation Hazard (inhalation hazard, Zone A or B) or Poison (other than inhalation hazard, Zone A or B; the packing group for a material is indicated in column 5 of the table.).

Special Provisions: IB8, IP2, IP4, T3, TP33

IB8: Authorized IBCs: Metal (11A, 11B, 11N, 21A, 21B, 21N, 31A, 31B and 31N); Rigid plastics (11H1, 11H2, 21H1, 21H2, 31H1 and 31H2); Composite (11HZ1, 11HZ2, 21HZ1, 21HZ2, 31HZ1 and 31HZ2); Fiberboard (11G); Wooden (11C, 11D and 11F); Flexible (13H1, 13H2, 13H3, 13H4, 13H5, 13L1, 13L2, 13L3, 13L4, 13M1 or 13M2).
IP2: When IBCs other than metal or rigid plastics IBCs are used, they must be offered for transportation in a closed freight container or a closed transport vehicle.
IP4: Flexible, fiberboard or wooden IBCs must be sift-proof and water-resistant or be fitted with a sift-proof and water-resistant liner.
T3: Minimum test pressure (bar): 2.65; Minimum shell thickness (in mm-reference steel) (See sxn.178.274(d)): sxn.178.274(d)(2); Pressure-relief requirements (See sxn.178.275(g)): Normal; Bottom opening requirements (See sxn.178.275(d)): sxn.178.275(d)(2).
TP33: The portable tank instruction assigned for this substance applies for granular and powdered solids and for solids which are filled and discharged at temperatures above their melting point which are cooled and transported as a solid mass. Solid substances transported or offered for transport above their melting point are authorized for transportation in portable tanks conforming to the provisions of portable tank instruction T4 for solid substances of packing group III or T7 for solid substances of packing group II, unless a tank with more stringent requirements for minimum shell thickness, maximum allowable working pressure, pressure-relief devices or bottom outlets are assigned in which case the more stringent tank instruction and special provisions shall apply. Filling limits must be in accordance with portable tank special provision TP3. Solids meeting the defnintion of an elevated temperature material must be transported in accordance with the applicable requirements of this subchapter.

Packaging Authorizations (refer to 49 CFR 173.***):

Exceptions: 153
Non-bulk packaging: 212
Bulk packaging: 242

Quantity Limitations:

Passenger aircraft or railcar: 25 kg
Cargo aircraft only: 100 kg

Vessel Stowage Requirements:

Vessel stowage location: A

A: The material may be stowed "on deck" or "under deck" on a cargo vessel and on a passenger vessel.

Vessel stowage other: Not Listed

ICAO International Shipping Name for UN1561 (ICAO, 2002):

Proper Shipping Name: Arsenic trioxide
UN Number: 1561

LABELS

NFPA

NFPA Hazard Ratings for CAS1327-53-3 (NFPA, 2002):

Not Listed

-HANDLING AND STORAGE

STORAGE

CONTAINER

Protect containers against physical damage.

ROOM/CABINET RECOMMENDATIONS

Store in well ventilated area away from food or food products and combustible materials (ITI, 1988).
Store in a cool, dry and well-ventilated location away from acids, halogens, and iron salts (NFPA, 1991).

-PERSONAL PROTECTION

SUMMARY

RECOMMENDED PROTECTIVE CLOTHING - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 151 (ERG, 2004)

Wear positive pressure self-contained breathing apparatus (SCBA).
Wear chemical protective clothing that is specifically recommended by the manufacturer. It may provide little or no thermal protection.
Structural firefighters' protective clothing provides limited protection in fire situations ONLY; it is not effective in spill situations where direct contact with the substance is possible.

Wear a self-contained positive pressure breathing apparatus when working in the vicinity of spills or leaks or when fighting fires (AAR, 1987).

Emergency response teams should wear appropriate personal protective clothing and respiratory protection.

Wear full protective clothing when working in the vicinity of spills or leaks or when fighting fires (AAR, 1987).

RESPIRATORY PROTECTION

Wear a self-contained positive pressure breathing apparatus when working in the vicinity of spills or leaks or when fighting fires (AAR, 1987).

Refer to "Recommendations for respirator selection" in the NIOSH Pocket Guide to Chemical Hazards on TOMES Plus(R) for respirator information.

PROTECTIVE CLOTHING

CHEMICAL PROTECTIVE CLOTHING. Search results for CAS 1327-53-3.

Specific recommendations and test data for this chemical were not found in the available manufacturers' product literature. A complete list of consulted manufacturers and references is presented below.

-PHYSICAL HAZARDS

FIRE HAZARD

SUMMARY

POTENTIAL FIRE OR EXPLOSION HAZARDS - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 151 (ERG, 2004)
- Non-combustible, substance itself does not burn but may decompose upon heating to produce corrosive and/or toxic fumes.
- Containers may explode when heated.
- Runoff may pollute waterways.
Arsenic trioxide is non-combustible, but if involved in a fire may decompose to produce toxic arsenic fumes and gaseous arsine (NFPA, 1991).
Extinguish fire using agent suitable for surrounding fire (AAR, 1987).
Use flooding quantities of water as a spray (AAR, 1987).
Control runoff and isolate discharged material for proper disposal (NFPA, 1991).

FLAMMABILITY CLASSIFICATION

NFPA Flammability Rating for CAS1327-53-3 (NFPA, 2002):

Not Listed

FIRE CONTROL/EXTINGUISHING AGENTS

SMALL FIRE PRECAUTIONS - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 151 (ERG, 2004)

Dry chemical, CO2 or water spray.

LARGE FIRE PRECAUTIONS - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 151 (ERG, 2004)

Water spray, fog or regular foam.
Move containers from fire area if you can do it without risk.
Dike fire control water for later disposal; do not scatter the material.
Use water spray or fog; do not use straight streams.

TANK OR CAR/TRAILER LOAD FIRE PRECAUTIONS - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 151 (ERG, 2004)

Fight fire from maximum distance or use unmanned hose holders or monitor nozzles.
Do not get water inside containers.
Cool containers with flooding quantities of water until well after fire is out.
Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank.
ALWAYS stay away from tanks engulfed in fire.
For massive fire, use unmanned hose holders or monitor nozzles; if this is impossible, withdraw from area and let fire burn.

NFPA Extinguishing Methods for CAS1327-53-3 (NFPA, 2002):

Not Listed

Choose an extinguishing agent suitable for fires in surrounding material (AAR, 1987).

Water may be used in flooding quantities as fog (AAR, 1987).

COMBUSTION TOXICITY

When heated to decomposition, arsenic trioxide releases highly toxic fumes of oxides of arsenic and gaseous arsine (CHRIS , 1991).
A mixture of arsenic trioxide with excess zinc filings will explode on heating (Bretherick, 1990).
Arsenic trioxide and sodium chlorate form a spontaneously flammable mixture (NFPA, 1990).
- Hydrogen fluoride and arsenic trioxide react with incandescence (NFPA, 1990).
Forms toxic volatile halides in contact with halide acids.
- Forms volatile, highly toxic arsine when reduced in acid solution (HSDB , 1991).
Water solution of arsenicals are in contact with active metals, e.g., arsenic, iron, aluminum, and zinc, highly toxic fumes of arsenic (including arsine) are released (HSDB , 1991).

EXPLOSION HAZARD

When heated to decomposition, arsenic trioxide releases highly toxic fumes of oxides of arsenic and gaseous arsine (CHRIS , 1991).

A mixture of arsenic trioxide with excess zinc filings will explode on heating (Bretherick, 1990).

Arsenic trioxide and sodium chlorate form a spontaneously flammable mixture (NFPA, 1990).

Hydrogen fluoride and arsenic trioxide react with incandescence (NFPA, 1990).

Forms toxic volatile halides in contact with halide acids.

Forms volatile, highly toxic arsine when reduced in acid solution (HSDB , 1991).

Violent reactions occur between arsenic trioxide and (ITI, 1988):

Oxygen difluoride
Fluorine
Chlorine trifluoride

DUST/VAPOR HAZARD

When heated to decomposition, arsenic trioxide releases highly toxic fumes of oxides of arsenic and gaseous arsine (CHRIS , 1991).

Forms toxic volatile halides in contact with halide acids.

Forms volatile, highly toxic arsine when reduced in acid solution (HSDB , 1991).

Water solution of arsenicals are in contact with active metals, e.g., arsenic, iron, aluminum, and zinc, highly toxic fumes of arsenic (including arsine) are released (HSDB , 1991).

REACTIVITY HAZARD

When heated to decomposition, arsenic trioxide releases highly toxic fumes of oxides of arsenic and gaseous arsine (CHRIS , 1991).

A mixture of arsenic trioxide with excess zinc filings will explode on heating (Bretherick, 1990).

Arsenic trioxide and sodium chlorate form a spontaneously flammable mixture.

Hydrogen fluoride and arsenic trioxide react with incandescence (NFPA, 1990).

Forms toxic volatile halides in contact with halide acids.

Forms volatile, highly toxic arsine when reduced in acid solution (HSDB , 1991).

Incompatibilities (Budavari, 1989):

Iron in solution
Tannic acid
Infusion cinchona and other vegetable astringents infusions and decoctions (Budavari, 1989).

Violent reactions occur between arsenic trioxide and (ITI, 1988):

Oxygen difluoride
Fluorine
Chlorine trifluoride

Water solution of arsenicals are in contact with active metals, e.g., arsenic, iron, aluminum, and zinc, highly toxic fumes of arsenic (including arsine) are released (HSDB , 1991).

Corrosive to metals in the presence of moisture (AAR, 1987).

EVACUATION PROCEDURES

SUMMARY

Editor's Note: This material is not listed in the Table of Initial Isolation and Protective Action Distances.

SPILL - PUBLIC SAFETY EVACUATION DISTANCES - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 151 (ERG, 2004)

Increase, in the downwind direction, as necessary, the isolation distance of at least 25 to 50 meters (80 to 160 feet) in all directions.

FIRE - PUBLIC SAFETY EVACUATION DISTANCES - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 151 (ERG, 2004)

If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions.

PUBLIC SAFETY MEASURES - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 151 (ERG, 2004)

CALL Emergency Response Telephone Number on Shipping Paper first. If Shipping Paper not available or no answer, refer to appropriate telephone number:

MEXICO:

SETIQ:

01-800-00-214-00 in the Mexican Republic;
For calls originating in Mexico City and the Metropolitan Area: 5559-1588;
For calls originating elsewhere, call: 011-52-555-559-1588.

CENACOM:

01-800-00-413-00 in the Mexican Republic;
For calls originating in Mexico City and the Metropolitan Area: 5550-1496, 5550-1552, 5550-1485, or 5550-4885;
For calls originating elsewhere, call: 011-52-555-550-1496, or 011-52-555-550-1552; 011-52-555-550-1485, or 011-52-555-550-4885.

ARGENTINA:

CIQUIME:

0-800-222-2933 in the Republic of Argentina;
For calls originating elsewhere, call: +54-11-4613-1100.

BRAZIL:

PRÓ-QUÍMICA:

0-800-118270 (Toll-free in Brazil);
For calls originating elsewhere, call: +55-11-232-1144 (Collect calls are accepted).

COLUMBIA:

CISPROQUIM:

01-800-091-6012 in Colombia;
For calls originating in Bogotá, Colombia, call: 288-6012;
For calls originating elsewhere, call: 011-57-1-288-6012.

CANADA:

CANUTEC:

613-996-6666 (Collect calls are accepted);
*666 cellular (in Canada only).

UNITED STATES:

CHEMTREC®:

1-800-424-9300 (Toll-free in the U.S., Canada, and the U.S. Virgin Islands);
703-527-3887 for calls originating elsewhere (Collect calls are accepted).

CHEM-TEL, INC.:

1-800-255-3924 (Toll-free in the U.S., Canada, and the U.S. Virgin Islands);
813-248-0585 for calls originating elsewhere (Collect calls are accepted).

INFOTRAC:

1-800-535-5053 (Toll-free in the U.S., Canada, and the U.S. Virgin Islands);
352-323-3500 for calls originating elsewhere (Collect calls are accepted).

3E COMPANY:

1-800-451-8346 (Toll-free in the U.S., Canada, and the U.S. Virgin Islands);
760-602-8703 for calls originating elsewhere (Collect calls are accepted).

NATIONAL RESPONSE CENTER (NRC):

1-800-424-8802 - (24 hours) (Toll-free in the U.S., Canada, and the U.S. Virgin Islands);
202-267-2675 for calls in the District of Columbia.

MILITARY SHIPMENTS:

703-697-0218 - Explosives/ammunition incidents (Collect calls are accepted);
1-800-851-8061 - All other dangerous goods incidents.

NATIONWIDE POISON CONTROL CENTER (United States only):

1-800-222-1222 (Toll-free in the U.S.).

For additional details see the section entitled "WHO TO CALL FOR ASSISTANCE" under the ERG Instructions.
As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids.
Keep unauthorized personnel away.
Stay upwind.
Keep out of low areas.

When heated to decomposition, arsenic trioxide releases highly toxic fumes of oxides of arsenic and gaseous arsine (CHRIS , 1991).

Downwind evacuation should be considered if this material is involved in a fire or if a large discharge has occurred (AAR, 1987).

AIHA ERPG Values for CAS1327-53-3 (AIHA, 2006):

Not Listed

DOE TEEL Values for CAS1327-53-3 (U.S. Department of Energy, Office of Emergency Management, 2010):

Listed as Arsenic trioxide
TEEL-0 (units = mg/m3): 0.0132
TEEL-1 (units = mg/m3): 0.4
TEEL-2 (units = mg/m3): 3
TEEL-3 (units = mg/m3): 9.1
Definitions:

TEEL-0: The threshold concentration below which most people will experience no adverse health effects.
TEEL-1: The airborne concentration (expressed as ppm [parts per million] or mg/m(3) [milligrams per cubic meter]) of a substance above which it is predicted that the general population, including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic, nonsensory effects. However, these effects are not disabling and are transient and reversible upon cessation of exposure.
TEEL-2: The airborne concentration (expressed as ppm or mg/m(3)) of a substance above which it is predicted that the general population, including susceptible individuals, could experience irreversible or other serious, long-lasting, adverse health effects or an impaired ability to escape.
TEEL-3: The airborne concentration (expressed as ppm or mg/m(3)) of a substance above which it is predicted that the general population, including susceptible individuals, could experience life-threatening adverse health effects or death.

AEGL Values for CAS1327-53-3 (National Research Council, 2010; National Research Council, 2009; National Research Council, 2008; National Research Council, 2007; NRC, 2001; NRC, 2002; NRC, 2003; NRC, 2004; NRC, 2004; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; United States Environmental Protection Agency Office of Pollution Prevention and Toxics, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; 62 FR 58840, 1997; 65 FR 14186, 2000; 65 FR 39264, 2000; 65 FR 77866, 2000; 66 FR 21940, 2001; 67 FR 7164, 2002; 68 FR 42710, 2003; 69 FR 54144, 2004):

Listed as: Arsenic trioxide
Proposed Value:

AEGL-1

10 min exposure:

ppm:
mg/m3: Not recommended because of insufficient data

30 min exposure:

ppm:
mg/m3: Not recommended because of insufficient data

1 hr exposure:

ppm:
mg/m3: Not recommended because of insufficient data

4 hr exposure:

ppm:
mg/m3: Not recommended because of insufficient data

8 hr exposure:

ppm:
mg/m3: Not recommended because of insufficient data

Definitions:

AEGL-1 is the airborne concentration of a substance above which it is predicted that the general population, including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic non-sensory effects. However, the effects are not disabling, are transient, and are reversible upon cessation of exposure.

Listed as: Arsenic trioxide
Proposed Value:

AEGL-2

10 min exposure:

ppm:
mg/m3: 3.7 mg/m(3)

30 min exposure:

ppm:
mg/m3: 3.7 mg/m(3)

1 hr exposure:

ppm:
mg/m3: 3 mg/m(3)

4 hr exposure:

ppm:
mg/m3: 1.9 mg/m(3)

8 hr exposure:

ppm:
mg/m3: 1.2 mg/m(3)

Definitions:

AEGL-2 is the airborne concentration of a substance above which it is predicted that the general population, including susceptible individuals, could experience irreversible or other serious, long-lasting adverse health effects or an impaired ability to escape.

Listed as: Arsenic trioxide
Proposed Value:

AEGL-3

10 min exposure:

ppm:
mg/m3: 11 mg/m(3)

30 min exposure:

ppm:
mg/m3: 11 mg/m(3)

1 hr exposure:

ppm:
mg/m3: 9.1 mg/m(3)

4 hr exposure:

ppm:
mg/m3: 5.7 mg/m(3)

8 hr exposure:

ppm:
mg/m3: 3.7 mg/m(3)

Definitions:

AEGL-3 is the airborne concentration of a substance above which it is predicted that the general population, including susceptible individuals, could experience life-threatening health effects or death.

NIOSH IDLH Values for CAS1327-53-3 (National Institute for Occupational Safety and Health, 2007):

Not Listed

CONTAINMENT/WASTE TREATMENT OPTIONS

SUMMARY

SPILL OR LEAK PRECAUTIONS - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 151 (ERG, 2004)
- Do not touch damaged containers or spilled material unless wearing appropriate protective clothing.
- Stop leak if you can do it without risk.
- Prevent entry into waterways, sewers, basements or confined areas.
- Cover with plastic sheet to prevent spreading.
- Absorb or cover with dry earth, sand or other non-combustible material and transfer to containers.
- DO NOT GET WATER INSIDE CONTAINERS.
RECOMMENDED PROTECTIVE CLOTHING - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 151 (ERG, 2004)
- Wear positive pressure self-contained breathing apparatus (SCBA).
- Wear chemical protective clothing that is specifically recommended by the manufacturer. It may provide little or no thermal protection.
- Structural firefighters' protective clothing provides limited protection in fire situations ONLY; it is not effective in spill situations where direct contact with the substance is possible.
DECONTAMINATION OF SPILLS
- Land Spill:
- Water Spill:
Water spray may be used to reduce or knock down vapors (AAR, 1987).

SMALL LEAK/SPILL

Isolate and ventilate the area. Keep sources of fire away. Wear rubber or neoprene gloves and overshoes and an approved respirator. Get fire-fighting equipment ready. Contain any liquid spill around the edge and absorb with Zorb-All(R), soil, sweeping compound, sawdust, dry sand or similar material. Dispose of absorbed or dry material in disposable containers (EPA, 1975).

-ENVIRONMENTAL HAZARD MANAGEMENT

POLLUTION HAZARD

Arsenic trioxide occurs naturally as the mineral arsenolite (As4O6), and is formed when arsenic-containing ores are roasted. The release of gases and waste waters from ore refineries may result in the environmental release of arsenic trioxide. It may also be released to the environment from other production sites where it is further refined and used (HSDB, 2003).

Potential for accumulation in kidney and neural tissues (OHM/TADS , 1991).

Potential for concentration in food chain is positive; arsenic compounds tend to accumulate in oysters and the molluscan shellfish (OHM/TADS , 1991).

SWEDEN: The background level of arsenic in Swedish lakes was 0.06 to 1.2 mcg/L (Reuther, 1992).

ENVIRONMENTAL FATE AND KINETICS

OTHER

OTHER
- AQUATIC FATE
- TERRESTRIAL FATE
- ATMOSPHERIC FATE

ENVIRONMENTAL TOXICITY

PUBLISHED VALUES (HSDB , 1991)

1. LC50 CHUM SALMON: 8,330 mcg/L/48h
2. LC50 PINK SALMON: 3,787 mcg/L/10 days
3. LC100 PINK SALMON: 7,195 mcg/L/7 days
4. LC50 FATHEAD MINNOW: 109 mg/L/96h
5. HARMFUL FISH FOOD ORGANISM: 2 to 3 mg/L
6. HARMFUL PINK SALMON: 5.3 mg/L/192h
7. HARMFUL BASS: 10 mg/L/240h
8. HARMFUL MUSSELS: 16 mg/L/72 to 384h

BIOACCUMULATION: In a freshwater model ecosystem arsenic, as arsenate, was readily accumulated in plankton at concentrations of about 5 mcg/L. The algal population remains constant if phosphorus is added at the same concentration. Primary production was effected at As concentrations of about 50 mcg/L, although bioaccumulation did not inhabit plant growth. Phosphorus successfully competes for sediment site with arsenic and has the effect of increasing the concentration of toxic arsenic in solution (Reuther, 1992).

-PHYSICAL/CHEMICAL PROPERTIES

MOLECULAR WEIGHT

197.8 g (Prod Info TRISENOX(R) injection, 2005)

DESCRIPTION/PHYSICAL STATE

ARSENIC TRIOXIDE INJECTION - A sterile, nonpyrogenic, preservative-free, clear solution of arsenic trioxide in water for injection using sodium hydroxide and dilute hydrochloride acid to adjust to pH 8 (Prod Info TRISENOX(R) injection, 2005).

OTHER FORMS - Arsenic trioxide is odorless, tasteless, white or transparent, amorphous lumps or crystalline powder (Budavari, 1989).

It occurs in two crystalline modifications (Budavari, 1989): Claudetite (monoclinic crystals); Arsenolite (cubic crystals).

Arsenic trioxide occurs as colorless monoclinic, cubic, or fibrous crystals, or as white or clear amorphous lumps or powder. It is odorless and tasteless. It is sparingly soluble in cold water, soluble in 15 parts boiling water, and soluble in glycerine, dilute hydrochloric acid, or alkali hydroxide. It will corrode metals under moist conditions, and is somewhat more stable at mildly acidic pH. It sublimes upon heating. Exposure to the vapors is therefore a potential hazard (HSDB, 2006; Budavari, 1996; Lewis, 1993).

VAPOR PRESSURE

66.1 mmHg (at 312 degrees C) (HSDB, 2006)

DENSITY

NORMAL TEMPERATURE AND PRESSURE

(25 degrees C; 77 degrees F and 760 mmHg)
Claudetite: 4.15 g/cm(3) (HSDB, 2006)

OTHER TEMPERATURE AND/OR PRESSURE

3.738 g/cm(3) (at 20 degrees C) (HSDB, 2006)
Arsenolite: 3.865 g/cm(3) (at 20 degrees C) (HSDB, 2006)

FREEZING/MELTING POINT

MELTING POINT

Claudetite: 313 degrees C (Budavari, 1989)
Arsenolite: 275 degrees C (Budavari, 1989)

BOILING POINT

465 degrees C (Budavari, 1989)

SOLUBILITY

IN WATER

sparingly and slowly soluble in cold water (Budavari, 1989)
soluble in 15 parts boiling water (Budavari, 1989)
slightly soluble in water (with hydrolysis); 20,000 ppm at 25 degrees C (OHM/TADS , 1991)

IN ORGANIC SOLVENTS

practically insoluble in chloroform, ether, and alcohols (Budavari, 1989)

OTHER

soluble in dilute hydrochloric acid solutions (Budavari, 1989)
soluble in alkali hydroxide solutions (Budavari, 1989)
soluble in carbonate solutions (Budavari, 1989)
soluble in glycerine (Sax & Lewis, 1987)

HENRY'S CONSTANT

1.7x10(-12) atm-m(3)/mol (Ehrenfeld et al, 1986)

-REFERENCES

GENERAL BIBLIOGRAPHY

40 CFR 372.28: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Lower thresholds for chemicals of special concern. National Archives and Records Administration (NARA) and the Government Printing Office (GPO). Washington, DC. Final rules current as of Apr 3, 2006.

40 CFR 372.65: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Chemicals and Chemical Categories to which this part applies. National Archives and Records Association (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Apr 3, 2006.

49 CFR 172.101 - App. B: Department of Transportation - Table of Hazardous Materials, Appendix B: List of Marine Pollutants. National Archives and Records Administration (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Aug 29, 2005.

49 CFR 172.101: Department of Transportation - Table of Hazardous Materials. National Archives and Records Administration (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Aug 11, 2005.

62 FR 58840: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 1997.

65 FR 14186: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.

65 FR 39264: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.

65 FR 77866: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.

66 FR 21940: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2001.

67 FR 7164: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2002.

68 FR 42710: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2003.

69 FR 54144: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2004.

ACGIH: Documentation of the Threshold Limit Values and Biological Exposure Indices, 6th ed, Am Conference of Govt Ind Hyg, Inc, Cincinnati, OH, 1991, pp 85-86.

ACGIH: Documentation of the Threshold Limit Values and Biological Exposure Indicies, 5th ed, Am Conference of Govt Ind Hyg, Inc, Cincinnati, OH, 1986, pp 37-38.

AIHA: 2006 Emergency Response Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook, American Industrial Hygiene Association, Fairfax, VA, 2006.

Addiego JE, Ridgway D, & Bleyer WA: The acute management of intrathecal methotrexate overdose: pharmacologic rationale and guidelines. J Pediatr 1981; 98(5):825-828.

Al-Mahasneh QM & Rodgers GC: An in vitro study of efficacy of activated charcoal as an adsorbent for arsenical salts (Abstract). International Congress on Clinical Toxicology, Poison Control and Analytical Toxicology, LUXTOX 90, Programme and Abstracts (May 2-5) Luxembourg, 1990.

American Conference of Governmental Industrial Hygienists : ACGIH 2010 Threshold Limit Values (TLVs(R)) for Chemical Substances and Physical Agents and Biological Exposure Indices (BEIs(R)), American Conference of Governmental Industrial Hygienists, Cincinnati, OH, 2010.

American Heart Association: 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2005; 112(24 Suppl):IV 1-203. Available from URL: http://circ.ahajournals.org/content/vol112/24_suppl/. As accessed 12/14/2005.

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National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Selenium Hexafluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2006f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ec55&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Silane (Proposed). United States Environmental Protection Agency. Washington, DC. 2006g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d523&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Sodium Cyanide (Proposed). United States Environmental Protection Agency. Washington, DC. 2009h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbb9&disposition=attachment&contentType=pdf. As accessed 2010-08-15.

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National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Strontium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

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ARSENIC TRIOXIDE

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Information to evaluate chemical incidents

Information to evaluate chemical incidents

Information to evaluate chemical incidents