Arsenic Trioxide 

### Arsenic Trioxide (As O ) 2 3 

### CAS 1327-53-3; UN 1561 Synonym s include arsenic oxide, arsenious acid, arsenious oxide, arsenious trioxide, arsenous aci d anhydride, crude arsenic, arsenolite, and white arsenic.

• Persons whose clothing or skin is contaminated with arsenic trioxide can secondarily contaminate rescuers by direct contact or through release of inhalable dust.

• Arsenic trioxide is an odorless, tasteless, white or transparent nonflammable solid.

• Arsenic trioxide is readily absorbed if inhaled or ingested, but only slowly absorbed through the skin. Toxicity usually results from ingestion.


### Description Ther e are many forms of arsenic, but this medical Management Guideline focuses specifically on ar senic trioxide (As O ), one of 2 3 the most toxic and prevalent forms. Arsenic trioxide is a whit e or transparent solid in the form of glassy, shapeless lumps or a crystalline powde r that resembles sugar. It has no odor or taste. It forms readily when elemental metal lic arsenic is heated to high tem peratures or burned. When arsenic trioxide is burned, i t releases toxic fumes and arsine gas which is highly toxic. 

### Routes of Exposure
Inhalation Arsen ic trioxide dust is readily absorbed from the lungs, bu t inhaled quantities are usually in sufficient to cause acute systemic toxic ity. Arsenic trioxide has no odor. Thus, odor provides n o warning of hazardous airborne concentrations. Skin/Eye Contact Direct contact with arsenic trioxide dust can cause localized skin irritation, but sy stemic absorption through the skin is negligible. Ski n contact is unlikely to cause systemic effects unless th e dermal barrier is compromis ed. Arsenic trioxide dust is irritating to the eyes. Ingestion Ingestio n is the most important route of acute exposure o f arsenic trioxide. Ingested arsenic trioxide is q uickly absorbed and can be extremely hazardous. Significant tis sue and organ damage and death may result. Mo st acute intoxications are from suicidal or homicidal ingestion.

ATSDR • General Information 1Arsenic Trioxide 

### Sources/Uses

Standards and Guidelines

Physical Properties Arsenic is ubiquitous in the natural environmen t. Arsenic trioxide is one of the arsenites (inor ganic forms of arsenic in the trivalent state [A s 3+ ]), found in nature and is produced mainly from by

pro ducts of copper smelting. It is no longer commerciall y manufactured in t he United States, but is imported primarily for use in manufacturing other arsenic compounds used as woo d prese rvatives, insecticides, and herbicides. It is also used i n meta llurgical processes, and in the manufacturing of glass an d ceramics. Arsenic compounds were formerly used medicinally in humans (e.g., Fowler’s solution), but these uses have largel y been abandoned. Inorganic arseni c compounds, however, can be found in some homeopathic and folk remedies.

3 OSHA PEL (permissible exposure limit) = 10 μg/m (averaged over an 8-hour workshift) for inorganic arsenic compounds. NIOSH IDLH (im mediately dangerous to life or health) = 5 mg 3 As/m (for all inorganic arsenic compounds).
Descri ption: white or transparent solid in the form of glassy , shapeless lumps or a crystalline powder that resembles sugar. Warning properties : inadequate; odorless and tasteless; airborne arse nic trioxide may produce a burning sensation to the nose , mouth, and eyes and cause coughing, shortness of breath , headache, sore throat, and dizziness. Molecular weight: 197.84 daltons Boiling point (760 mm Hg): 869 E F (465 E C) Sublimes at 379 E F (193 E C) Melting point : 594 E F (312 E C) Vapor pressure : 66.1 mm Hg at 594 E F (312 E C) Density (solid): 3.74 (water = 1.00) Water solubility : Low solubility in water (37 g/L at 20 E C , 115 g/L at 100 E C); slightly soluble in alcohol; soluble in dilute HCl solutions. Flammability : not flammable, but emits highly toxic arsine gas and oxides of arsenic fumes when burned.

2 General Information • ATSDRArsenic Trioxide 

### Incompatibilities Fl ammable reactions can occur in the presence of stron g oxidizers. If arsenic trioxide is exposed to hydrogen gas or to the combination of acid (acid fu mes) or water and active metals, the reaction can form toxic arsine gas (see Medical Managemen t Guideline for Arsine)

.

ATSDR • General Information 3Arsenic Trioxide

4 General Information • ATSDRArsenic Trioxide 

### Health Effects

• Toxic effects of arsenic trioxide usually result from ingestion. Small amounts of arsenic trioxide can lead to multiple organ damage and death. Acute signs and symptoms include nausea, vomiting, diarrhea, gastrointestinal hemorrhage, cerebral edema, tachycardia, dysrhythmias, and hypovolemic shock. Symptoms are dose dependent and can be delayed.

• Dermal contact and inhalation of airborne arsenic trioxide can cause localized irritation and usually does not result in systemic effects.



### Acute Exposure The toxic effects caused by acute exposure to arsenic trioxid e are d ue in large part to its ability to bind to cellular protein s containing sulfhydryl groups. This inhibits the production o f energy needed to maintain tissue functions, and results in a decrease in glutathione, which is necessary for the metaboli c deto xification of arsenic. The primary target organs are th e ga strointestinal tract, heart, brain and kidney. Eventually th e skin, bone marrow and peripheral nervous system are als o affecte d. Arsenic trioxide has direct toxic effects on endothelial cells, increasing the permeability of small blood vessels. Childre n do not always respond to chemicals in the same wa y that adults do. Different protocols for managing their care may be needed. This medical management guide focuses specifically on arsenic trioxid e (an arsenite), which is one of the most toxic forms o f arsenic

. As little as 1 to 2.5 mg/kg of arsenic trioxide is a potentially fatal dose. Toxi city from natural sources of arsenic is rare except from drinking highly contaminated groundwater or fr om breathing highly contaminated air (e.g., from burning o f arse nic-containing coal indoors without adequate ventilation)

. Other inorganic forms of arsenic called arsenates are in th e 5+ pentavalent state (As ) and are several times less toxic than the arsenites. Eleme ntal arsenic has a gray metal-like appearance, is insolubl e in water or body fluids, and is not considere d poisonous. Organic arsenic, also known as fish or seawee d arsenic (arsenocholine, arsenobetaine , or arsenosugars) is mostly found in seafood such as bivalves, bottom-feeding fish, an d seaweed and has a lower toxicity. Gastrointestinal Ini tial symptoms occurring within 30 minutes to several hour s inclu de burning of the lips, pharyngeal constriction, sever e abdominal pain and nausea. A metal lic or garlic taste and intense

ATSDR • Health Effects 5Arsenic Trioxide

CNS

Peripheral Neurologic

Cardiovascular

Respiratory

Musculoskeletal

Renal thirst also occur. Inflammation and necrosis of the mucosa and submuco sa can lead to bloody or “rice water” diarrhea , vomiting, and gastrointestinal perforat ion and bleeding. Bleeding and/ or fluid loss can result in electrolyte abnormalities, shock , and death. Encephalopathy (cerebral edema), headache, lethargy, delirium, hall ucinations, seizures, or coma can occur. Cerebral lesion s consisting of multipl e, symmetrical foci of hemorrhagic necrosis occur in the gray and white matter.
Per ipheral neuropathy resembling Guillain-Barré syndrom e (ascending flaccid paralysis) is common acutely or subacutely

. Sensory symptoms predominate ea rly, with patients complaining of “pins and needles” or electrical shock like pains in the lower ex tremities. This may be followed by numbness and moto r weakness. Increased capillary per meability (third-spacing and vasodilation) ca n result in hypovolemic shock. Sinus tachycardia can be a n early sign of poisoning. Polymorphous ventricular tachycardia, ventr icular fibrillation, and congestive heart failure can occur

. Elec trocardiographic findings can include, prolongation of th e QT interval, ST depression, and flattened T waves. Pulmonary edema, acute respir atory distress syndrome (ARDS), and res piratory failure due to weakness of the respirator y muscl es can occur following ingestion. Coughing, chest pain , dyspnea, and general i rritation of the upper respiratory tract can occur following inhalation. Exposu re to certain chemicals can lead to Reactive Airwa y Dy sfunction Syndrome (RADS), a chemically- or irritant

induced type of asthma. Children may be more vuln erable because of relatively increased minut e ventilation per kg and failure to evacuate an are a promptly when exposed. Myalgia, weakness, muscular atrophy and rhabdomyolysis ca n occur. Initia l glomerular damage leading to proteinuria is commo n following high arsenic exposure. Tubular necrosis an d deg eneration, oliguria with proteinuria, hematuria and acut e renal failure are also frequently observed.

6 Health Effects • ATSDRArsenic Trioxide Hepatic

Dermal

Ocular
Potential Sequelae



### Chronic Exposure

Carcinogenicity Hepatocellular injury after acute exposure to inorganic arsenicals is unco mmon, but fatty infiltration of the liver, central necrosis, an d cirrhosis may occur. Hepatitis may also develop due t o alter ed intrahepatic heme metabolism, increased synthesis o f bilirubin, and altered interhepatocyte protein transport.
Fl ushing, diaphoresis, edema (especially periorbital) , hype rkeratosis, and brawny desquamation or exfoliativ e dermatitis can occur. Conjunctivitis, photophobia, and dimnes s of vision, diplopia, and lacrimation can occur. If the immediate ef fects of acute arsenic poisoning are survived, a variety of delayed eff ects, including peripheral neuropathy and bo ne marrow suppression (anemia, leukopenia, pancytopenia) , may d evelop. New or persistent encephalopathy, dysrhythmias, and nail changes (Mee’s lines) can also occur. Periphera l neuro pathy involves sensory and motor neurons in a stocking

glove distribution. Initially painful dysesthesias (i.e., “pins an d needles” or an electric shock-like sensation) are prominent. Early treatment with the chelator dimercaprol, also known as BA L (British AntiLewisite), may not eliminate the risk of delaye d effects. Survival of the acute phas e of arsenic poisoning is highly dependent on the dose received and the timing and extent o f tre atment. Recovery from subsequent peripheral neuropathy i s usually only partial and may require months to years.
Chro nic exposure is characterized by malaise, periphera l sen sorimotor neuropathy, anemia, jaundice, gastrointestina l comp laints, and characteristic skin lesions includin g hyp erkeratosis (small corn-like elevations) an d hyperpigmentation. Hyperkeratosi s usually appears on the palms or soles. Pigmentation changes and hyperkeratosis can take 3 to 7 ye ars to appear. Chronic inhalation can also lead t o co njunctivitis, irritation of the throat and respiratory tract, an d perfora tion of the nasal septum. Chronic exposure can caus e all ergic contact dermatitis. Chronic exposure may be mor e ser ious for children because of their potential longer latenc y period. The Department of Health and Human Services (DHHS), th e Inter national Agency for Research on Cancer (IARC), th e Envir onmental Protection Agency (EPA), and the Nationa l Toxicology Program (NTP) have classified arsenic as a huma n carcinogen based on sufficient evidence from human data

. Arsenic trioxide causes skin and lung cancer, and may caus e

ATSDR • Health Effects 7Arsenic Trioxide inte rnal cancers such as liver, bladder, kidney, colon, an d prostate cancers. Reproductive and Developmental Effects A r senic ions released from arsenic trioxide within the body can cross the placenta and affect the developing fetus; arsenic is also excreted in breast milk. Experimental animal studies support an association between high ingested arsenic dose and fetal toxicity. Arsenic trioxide is not included in Reproductive an d Developmental Toxicants , a 1991 report published by th e General Accounting Office (GAO) that lists 30 chemicals o f co ncern because of widely acknowledged reproductive an d developmental consequences. Special consideration regarding the exposure of pregnant women may be warranted, since arsenic trioxide has been shown to b e mutagenic and clastogenic, and is suspected of being teratogenic; thus, medical counseling is recommended for the acutel y exposed pregnant woman.

8 Health Effects • ATSDRArsenic Trioxide 

### Prehospital Management

• Exposed persons whose skin or clothing is contaminated with arsenic trioxide can contaminate rescuers by direct contact or through release of inhalable dust.

• There is no serious risk of secondary contamination after clothing is removed and the skin is washed.

• Arsenic trioxide is irritating to the skin, eyes, and respiratory tract. Systemic effects can occur from all routes of exposure and may include severe gastrointestinal injury, life-threatening shock, and nerve damage.

• There is no specific antidote for arsenic trioxide. Prehospital treatment consists of supportive care and gastric decontamination. Chelation therapy is strongly recommended.



### Hot Zone Res cuers should be trained and appropriately attired befor e entering the Hot Zone. If the proper equipment is not available, or if the rescuers have not been trained in its use, call fo r assistance from a local or regional HAZMAT team or othe r properly equipped response organization.
Rescuer Protection Arsenic tr ioxide dust is readily absorbed through inhalation and can irritate the respiratory tract. Although it is poorly absorbed dermally, skin contact should be avoided because arsenic trioxide can irritate the skin.
Re spiratory Protection : Positive-pressure, self-containe d breat hing apparatus (SCBA) is recommended in respons e situations that involve exposure to potentially unsafe levels o f arse nic trioxide or combustion products (arsine and arseni c trioxide fumes).
S k in Protection : Chemical-protective clothing is recommended whe n contact with arsenic trioxide is expected because ski n irritation might occur. ABC Reminders Quickl y access for a patent airway, ensure adequate respiration and pulse. If trauma is suspected, manually maintain cervica l immobilization and apply a cervical collar and a backboard when feas ible. Apply direct pressure to stop any heavy bleeding

. Maintain adequate circulation. Victim Removal If v ictims can walk, lead them out of the Hot Zone to th e Decontami nation Zone. Victims who are unable to walk should

ATSDR • Prehospital Management 9Arsenic Trioxide



### Decontamination Zone

Rescuer Protection

ABC Reminders

Basic Decontamination be removed on backboards or gurneys. If these are not available, carefully carry or drag victims to safety.
Cons ider appropriate management of chemically contaminate d children, anticipate separation anxiety if a child is separated from a parent or other adult.
All victi ms exposed to arsenic trioxide require decontamination (see Basic Decontamination, below).
If

exp osure levels are determined to be safe, decontaminatio n may be conducted by personnel wearing a lower level o f protection than that required i n the Hot Zone (described above). Quickl y access for a patent airway, ensure adequate respiration and pulse. Maintain adequate circulation. If trauma is suspected, man ually maintain cervical immobilization and apply a cervica l co llar and a backboard when feasible. Administer supplemental oxygen as required. Assist ventilation with a bag-valve-mas k devic e if necessary. Apply direct pressure to control an y bleeding. Victims who are able may assist with their o wn decontamination. Remove and do uble-bag contaminated clothing and all personal belongings. Wash exposed skin and hair with mild soap and wate r (preferably under a shower). Rinse thoroughly with water. Use caution to avoid hypoth ermia when decontaminating children or the elderly. Use blankets or warmers when appropriate. Flush exposed or irritated eyes with plain water or saline for at least 15 minutes . Remove contact lenses if easily removabl e without additional trauma to the eye. If pain or injury is evident, continue irrigation while transferring the victim to the Suppor t Zone.
In cases of ingestion, do not induce emesis . Aggressiv e decontamination with gastric lavage is recommended withi n 1 hour of ingestion of a life-threatening amount of poison. The eff ectiveness of activated charcoal in binding arsenic trioxide is quest ionable, but administration of a charcoal slurry i s recommended pending further evaluat ion in cases of ingestion of unknown quantities (at 1 gm/kg , usual adult dose 60–90 g, child dose 25–50 g). A soda can and straw may be of assistance when offering charcoal to a child.

10 Prehospital Management • ATSDRArsenic Trioxide

Transfer to Support Zone


### Support Zone

ABC Reminders

Additional Decontamination

Advanced Treatment Cons ider appropriate management of chemically contaminate d chil dren at the exposure site. Also, provide reassurance to th e ch ild during decontamination, especially if separation from a parent occurs. If possible, seek assistance f rom a child separation expert. As soo n as basic decontamination is complete, move the victim to the Support Zone.
Be certai n that victims have been decontaminated properly (see Decontamination Zone, above). Victims who have undergon e dec ontamination pose no serious risk of secondar y conta mination to rescuers. In such cases, Support Zon e personnel require no specialized protective gear. Quickl y access for a patent airway, ensure adequate respiration and pulse. If trauma is suspected, manually maintain cervica l immobilization and apply a cervical collar and a backboard when feas ible. Administer supplemental oxygen as required. Assis t ventilation with a b ag-valve-mask device, if necessary. Maintain adequ ate circulation. Apply direct pressure to control an y bleeding. Establish intravenous access, if necessary. Place on a cardiac monitor.
If

ev idence of shock or hypotension is observed begin flui d administration. For adults, bolus 1,000 mL/hour if bloo d pres sure is under 80 mm Hg; if systolic pressure is over 90 mm Hg, a n infusion rate of 150 to 200 mL/hour is sufficient. Fo r childr en with compromised perfusion administer a 20 mL/k g bolus of normal saline over 10 to 20 minutes, then infuse at 2 to 3 mL/kg/hour.
Con tinue irrigating exposed skin and eyes, as appropriate. I n cases of ingestion, do not induce emesis . Aggressiv e decontamination with gastric lavage is recommended withi n 1 hour of ingestion of a life-threatening amount of poison. The eff ectiveness of activated charcoal in binding arsenic trioxide is quest ionable, but administration of a charcoal slurry i s recommended pending further evaluat ion in cases of ingestion of unknown quantities (at 1 gm/kg , usual adult dose 60–90 g, child dose 25–50 g). A soda can and straw may be of assistance when offering charcoal to a child. In cases of respiratory compromise secure ai rway and respiration via endotracheal intubation. If not possible, perfor m cricothyroidotomy if equipped and trained to do so.

ATSDR • Prehospital Management 11Arsenic Trioxide

Transport to Medical Facility



### Multi-Casualty Triage Treat patients who have bronchospasm with aerosolize d bro nchodilators. The use of bronchial sensitizing agents i n si tuations of multiple chemical exposures may pose additiona l ris ks. Also consider the health of the myocardium befor e ch oosing which type of bronchodilator should be administered. Cardiac sensitizing agent s may be appropriate; however, the use of cardiac se nsitizing agents after exposure to certain chemicals may pose enhanced risk o f cardiac arrhythmias (especially in the elder ly). Arsenic trioxide poisoning is not known to pos e additional risk during the use of bronchial or cardiac sensitizing agents. Consider racemic epinephrine aerosol for children who develop stridor. Dose 0.25–0.75 mL of 2.25% racemic epinephrin e so lution in 2.5 cc water, repeat every 20 minutes as neede d cautioning for myocardial variability.
Pa tients who are comatose, hypotensive, or have seizures o r cardiac dysrhythmias should be treated according to advance d life support (ALS) protocols. If massive exposure is suspected or if the patient is hypotensive, infu se intravenous saline or lactated Ringer’s solution. Fo r adults, bolus 1,000 mL/hour if blood pressure is under 80 m m Hg; if systolic pressure is over 90 mm Hg, an infusion rate o f 150 to 200 mL/hour is sufficient. For childr en with compromised perfusion adm inister a 20 mL/kg bolus of normal saline over 10 to 20 minutes, then infuse at 2 to 3 mL/kg/hour.
On ly decontaminated patients or patients not requirin g decon tamination should be transported to a medical facility

. “Body bags” are not recommended. Rep ort to the base station and the receiving medical facility the cond ition of the patient, treatment given, and estimated time of arrival at the medical facility.
If the patient has ingested arsenic trioxide, prepare th e amb ulance in case the patient vomits toxic material or ha s di arrhea. Have ready several towels and open plastic bags t o quickly clean up and isolate vomitus.
Consult with the base station physician or the regional poiso n control center for advice regarding triage of multiple victims.

12 Prehospital Management • ATSDRArsenic Trioxide Patien ts with evidence of significant exposure and all patient s who have ingested arsenic trioxide should be transported to a medical facility for evaluation. Asy mptomatic patients who have not had direct exposure t o arsenic trioxide may be discharged from the scene, after thei r names, addresses, and telephone numbers are recorded. Thes e patie nts should be advised to seek medical care promptly i f symptoms develop (see Patient Information Sheet below).

ATSDR • Prehospital Management 13Arsenic Trioxide

14 Prehospital Management • ATSDRArsenic Trioxide 

### Emergency Department Management

• Patients whose skin or clothing is contaminated with arsenic trioxide can contaminate rescuers by direct contact or through release of inhalable dust.

• Patients do not pose a serious risk of secondary contamination after their clothing is removed and their skin is washed.

• Arsenic trioxide is irritating to the skin, eyes, and respiratory tract. Systemic effectscan occur from all routes of exposure and may include gastrointestinal injury, lifethreatening shock, and nerve damage.

• There is no specific antidote for arsenic trioxide. Treatment consists of supportive care and gastric decontamination. Chelation therapy is strongly recommended.


### Decontamination Area Previously decontaminated patients may be transferred directly to the Critical Care Area. Others require decontamination a s de scribed below. Because arsenic trioxide can irritate the skin , thu s increasing the probability of dermal absorption, chemical

protective clothing is recommended when contact with arseni c trioxide is expected.
Be awar e that use of protective equipment by the provider may ca use fear in children, resulting in decreased compliance wit h further management efforts.
Because of their relatively larger surface area:weight ratio , children are more vulnerable to toxicants absorbed through the skin. Also, emergency room personnel shoul d examine children’s mo uths because of the frequency of hand-to-mouth activit y among children. ABC Reminders Evalu ate and support the airway, breathing, and circulation

. Secure airway and respiration via endotracheal intubation. If not po ssible, perform cricothyroidotomy if equipped and trained to do so.
Treat patients who have bronchospasm with aerosolize d bro nchodilators. The use of bronchial sensitizing agents i n si tuations of multiple chemical exposures may pose additiona l ris ks. Also consider the health of the myocardium befor e ch oosing which type of bronchodilator should be administered. Cardiac sensitizing agent s may be appropriate; however, the use of cardiac se nsitizing agents after exposure to certain chemicals may pose enhanced risk o f cardiac arrhythmias (especially in the elder ly). Arsenic trioxide poisoning is not known to pos e
ATSDR • Emergency Department Management 15Arsenic Trioxide

Basic Decontamination



### Critical Care Area

ABC Reminders

Inhalation Exposure additional risk during the use of bronchial or cardiac sensitizing agents. Consider racemic epinephrine aerosol for children who develop stridor. Dose 0.25–0.75 mL of 2.25% racemic epinephrin e so lution in 2.5 cc water, repeat every 20 minutes as neede d cautioning for myocardial variability.
Pa tients who are comatose, hypotensive, or have seizures o r car diac dysrhythmias should be treated in the conventiona l manner. Patients who are able an d cooperative may assist with their own decontamination. Remove and double-bag conta minated clothing and all personal belongings. Wash exposed skin and hair with mild soap and wate r (preferably under a shower). Rinse thoroughly with water. Flush exposed or irritated eyes with plain water or saline for at least 15 minutes . Remove contact lenses if present and easil y removable without additional trauma to th e eye. If ocular pain or injury is evident, continue ir rigation while transferring the victim to the Critical Care Area . In case s of ingestion, do not induce emesis . Consider gastri c lavage for recent l arge ingestion. (More information is provided in Ingestion Exposure under Critical Care Area below). Be certain that appropriate decontaminat ion has been carried out (see Decontamination Area above). Evaluate and support the airw ay, breathing, and circulation as in ABC Re minders above. Children may be more vulnerable t o corros ive agents than adults because of the relatively smalle r diame ter of their airways. Establish intravenous access i n symptomatic patients. Continuously monitor cardiac rhythm.
Pa tients who are comatose, hypotensive, or have seizures o r car diac dysrhythmias should be treated in the conventiona l manner. Admi nister supplemental oxygen by mask to patients who have resp iratory complaints. For serious exposure, respiratory trac t irritation can progress to pulmonary edema, maintain adequate oxy genation and provide mechanical support if needed. Trea t patients who have bronchospasm with aerosolize d

16 Emergency Department Management • ATSDRArsenic Trioxide

Skin Exposure
Eye Exposure

Ingestion Exposure bro nchodilators. The use of bronchial sensitizing agents i n si tuations of multiple chemical exposures may pose additiona l ris ks. Also consider the health of the myocardium befor e ch oosing which type of bronchodilator should be administered. Dopamine or norepinephrine may be appropriate in management of

s hock; however, the use of cardiac sensitizing agents afte r exposure to certain chemicals may pose enhanced risk of cardiac arrhythmias (especially in the elderly). Ar senic trioxide poisoning is not kn own to pose additional risk during the use of bronchial or cardiac sensitizing agents. Consider racemic epinephrine aerosol for children who develop stridor. Dose 0.25–0.75 mL of 2.25% racemic epinephrin e so lution in 2.5 cc water, repeat every 20 minutes as neede d cautioning for myocardial variability.
De rmal exposure to arsenic trioxide may cause skin irritation

. Treat symptomatically.
Ensur e that adequate eye irrigation has been completed. Tes t visual acuity. Examine the eyes for corneal damage and trea t appropriately. Consult an ophtha lmologist for patients who have apparent or suspected corneal injury. Flu id repletion should begin as soon as possible in severe acute poisoning. Central venous or pulmonary wedge pressur e mo nitoring can be useful in managing severe exposures wher e hypotension is a risk.
Do not induce emesis . In case of recent ingestion (less tha n 1 hour), and if spontaneous emesis has not occurred, conside r performing gastric lavage to prevent further a bsorption. Insert an orogastri c tube and begin lavage with water or normal saline as soon as possible. Continue lavage until the return is clear

. Activ ated charcoal may not bind significant amounts but i s recommended (at 1 gm/kg, u sual adult dose 60–90 g, child dose 25–50 g). Arsenic is radiopaque and an abdominal radiograph should b e obtaine d in cases of ingestion. If opacities compatible wit h arse nic are noted on the radiograph, consider whole bowe l irrigation (e.g., with a polyethylene glycol [PEG-3350 ] electrolyte lavage solution). Conside r alkalization of urine (pH 7.5) to protect kidney fro m dep osition of red cell breakdown products. Assure adequat e renal function before administering sodium bicarbonate.

ATSDR • Emergency Department Management 17Arsenic Trioxide Antidotes and Other Treatments Chelation thera py curtails the distribution of arsenic in the body and reduces the body burden. The decision to chelate for a patient should be made only by professionals experienced in the use of chelation, preferably in consultation with a regiona l poison control center or a medical toxicologist. Patients with a clear history of exposure to arsenic with significant GI and/o r cardiovascular symptoms may require chelation befor e labor atory confirmation. As time increases after exposure , chelation therapy beco mes less effective in reducing the severity of poisoning and in reduci ng the risks of serious delayed effects. Do not chelate asympt omatic patients without the guidance of a 24-hour urinary arsenic level.
In acutely ill patients, the agent most frequently recommende d is dimercaprol, also known as BAL (British AntiLewisite). The standard d osage regimen is 3 to 5 mg/kg IM every 4–6 hour s until the 24-hour urinary arsenic level falls below 50 μg/L, unless an orally admi nistered chelating agent (e.g., DMSA, see below) is substituted. This regimen may be adjusted depending upon the severity of the exposure and the symptoms. Contraindications to BAL include preexisting renal disease, pregnancy (except in life-threatening circumstances) an d conc urrent use of medicinal iron (BAL and iron togethe r form a complex that is very toxic). An increased risk for hemolysis should also be considered when ad ministering BAL to patients with glucose-6-phosphat e dehydrogenase deficiency; arsenic tri oxide is itself an inhibitor of G-6-PD. Chelation therapy should be continued until the 24-hour urinary arseni c level falls below 50 μg/L. Alkalization of the urin e stabilizes the dimercaprol-me tal complex and has been proposed to protect the kidneys during chelation therapy. If any degree of acute renal insufficiency devel ops during chelation, hemodialysis sh ould be considered to remove the dimercaprol-arseni c complex

. Side effects of BAL administered at 2.5 mg/kg ar e most ly pain at the injection site. At an intramuscular dose o f 5 mg/kg, the effects can include hypertension, nausea, vomiting, headache, lacrimation, rhinorrhea, salivation, and diaphoresis. Oral agents such as 2,3-demercaptosuccinic acid (DMSA o r Succimer®) or D-penicillamine have b een used as alternatives to BAL. DMSA is approved for the treatment of pediatric lea d poisoning in the United States; it also has been used successfully to chelate arsenic in humans, and is being further evaluated for

18 Emergency Department Management • ATSDRArsenic Trioxide

Laboratory Tests



### Disposition and Follow-up

Delayed Effects this use. Water-soluble chelating agents like DMSA are les s toxic than BAL and are often substituted when the patient’ s condition improves. DMSA might also be preferable for patients with renal insuffici ency, but GI motility is a prerequisite, as well as GI decontamination (to prevent incr eased arsenic absorption). The use of D-penicillamine as an oral chelating agent i s cont roversial. It has been used successfully in children, bu t should be avoided in penicillin allergic patients. Routine laboratory studies for serio usly exposed patients include CBC, serum electrolytes, u rinalysis and liver enzyme and kidney functi on tests. Chest radiographs and pulse oximetry (or AB G measurements) are recommended for patients who hav e respi ratory symptoms. An abdominal radiograph can detec t radiopaque ingested ar senic. Additionally, 24-hour urine arsenic levels are useful for monitoring symptomatic patients. A chelated or non-chelated level above 100 μg is usually considere d abnorma l. Normal total urinary arsenic levels are less than 5 0 μg/L in the absence of recent consumption of seafood tha t contains organic forms of arsenic (i.e., fish arsenic). A high blood arsenic level (norm al being less than 7 μg/100 mL) might confirm a diagnosis of poisoning. However, arsenic moves quickly out of the bloodstream (its i nitial half-life in blood is 1 to 2 hours) and a normal value does not exclude poisoning. If the blood arsenic level is normal, but the 24-hour urinary arseni c ex cretion is elevated, and there is a compatible clinica l presentation, the diagnosis can still be made.
Note: If the patient has eaten sea food containing organic arsenic (fish arsenic) within the past 48 hours, total urinary arsenic might be significantly elevated (urinary arsenic of up to 1,700 μg/L has be en measured following a large shellfish meal). Som e labor atories can speciate arsenic into the nontoxic organi c arsenics found in seafood and the toxic inorganic forms , although results are often not quickly available. Hospitalize patients who have ingested a significant amount o f ar senic trioxide, those who have had significant inhalatio n exposure, and those who require chelation therapy. Delayed effects can occur after an acute arsenic exposure tha t result ed in significant acute effects. Delayed effects includ e per ipheral neuropathy, bone marrow suppression (anemia , leukopenia, pancytopenia), encephalophathy, cardiomyopathy , and dermatologic lesions. Although timely chelation therap y

ATSDR • Emergency Department Management 19Arsenic Trioxide reduce s the occurrence of delayed effects, follow-up shoul d include particular attention to these organ systems. Patient Release Asymptomatic patients who have minimal exposure, norma l initial examinations, and no signs o f toxicity after 6 to 8 hours of observation may be discharged with instructions to seek medical att ention promptly if symptoms develop (see the Arseni c Trioxide—Patient Information Sheet below). Follow-up Obtain the name of the patient’s primary care physician so that th e hospital can send a copy of the ED visit to the patient’ s doctor. Patien ts who remain asymptomatic after exposure require n o fo llow-up. Discharged patients who had relatively minor o r transient symptoms following an ingestion exposure shoul d initi ate a 24-hour urine collection for arsenic measurement

. Follow-up should include evaluation of urinary arsenic levels , and co nsultation with the regional poison center regardin g outpatient chelation. For severely exposed patients wit h significant symptoms of acute poisoning, follow-up evaluation of neur ologic, circulatory, renal, pulmonary, hematologic, an d hepatic function should be arranged. Patients who have corneal lesions should be reexamined within 24 hours. 

### Reporting If a w ork-related incident has occurred, you may be legall y requi red to file a report; contact your state or local healt h department. Other per sons may still be at risk in the setting where thi s incide ntoccurred. If the incident occurred in the workplace , discus sing it with company personnel may prevent futur e incidents. I f a public health risk exists, notify your state or local health department or other responsible public agency. Whe n appropriate, inform pa tients that they may request an evaluation of their workplace form OSHA or NIOSH. See Appendices III and IV for a list of agencies that may be of assistance.

20 Emergency Department Management • ATSDRArsenic Trioxide 

### Arsenic Trioxide (As O ) 2 3 

### Patient Information Sheet This handout provides information and follow-up instructions for persons who have been exposed to arsenic trioxide. What is arsenic trioxide? Arsenic is a n element found naturally in the environment. There are many arsenic compounds o f c o mmercial importance. One of the most toxic of these is arsenic trioxide. Arsenic trioxide is a white or transparent solid that has no taste or odor and low flammability. Arsenic trioxide is used in th e manufa cture of wood preservatives, as an insecticide and herbicide, in metallurgy, and in glass an d ceramic manufacturing. What immediate health effects can be caused by exposure to arsenic trioxide? Breathing arsenic trioxide can cause nose and throat irritation, but generally, a person cannot inhal e enough to severely harm internal organs. Skin or eye contact can cause irritation.
Intent ional or unintentional swallowing of even a tiny amount of arsenic trioxide can cause sever e vomiting, di arrhea, abdominal cramps, and shock, as well as seizures; coma; damage to the liver , kidneys, nerves, and bone marrow; and death. Can arsenic trioxide poisoning be treated? Wa shing arsenical residues from the skin or eyes usually reduces the irritant effect. If arsenic trioxide is swallowed, measures can be taken to remove it from the body. In severe cases, medicines calle d chelating age nts are given to remove arsenic from the body and eliminate it in the urine. Severel y affected individuals must be hospitalized. In some cases, permanent nerve damage can result even i f chelation therapy is used. Are any future health effects likely to occur? Arseni c trioxide can cause adverse health effects in the liver, kidney, brain, nervous system, or bon e marrow for months or years after a severe poisoning. What tests can be done if a person is exposed to arsenic trioxide? Blood and urine tests for arsenic can be done to co nfirm exposures. In cases of ingestion, arsenic might show up in the intestines or stomach on x-rays. Arsenic levels in urine can be monitored to tell when the arsenic has been eliminated form the body. Monitoring for past or lo ng-term exposure can be carried out by analysis of arsenic levels in hair or nails. Where can more information about arsenic trioxide be found? More information about arsenic trioxide can be obtained fro m your regional poison control center; your state, county, or local health department; the Agency for Toxic Substances and Disease Registr y (ATSDR) ; your doctor; or a clinic in your area that specializes in occupational and environmenta l hea lth. If the exposure happened at work, you may wish to discuss it with your employer, th e Occupat ional Safety and Health Administration (OSHA) or the National Institute for Occupationa l Safety and Health (NIOSH). Ask the person who gave you this form for help in locating these telephone numbers.

ATSDR • Patient Information Sheet 21Arsenic Trioxide 

### Follow-up Instructions Keep this page and take it with you to your next appointment. Follow only the instructions checked below. [ ] Call your doctor or the Emergency Department if you develop any unusual signs or symptoms within the next 24 hours, especially:

• vomiting, abdominal cramps, diarrhea

• severe weakness

• rapid heart rate

• shortness of breath, coughing, or wheezing

• increased pain or discharge from injured eyes [ ] No follow-up appointment is necessary unless you develop any of the symptoms listed above. [ ] Call for an appointment with Dr. in the practice of

. When you call for your appointment, please say that you were treated in the Emergency Department at Hospital by and were advised to be seen again in days. [ ] Return to the Emergency Department/ Clinic on (date) at AM/PM for a follow-up examination. [ ] Do not perform vigorous physical activities for 1 to 2 days. [ ] You may resume everyday activities including driving and operating machinery. [ ] Do not return to work for days. [ ] You may return to work on a limited basis. See instructions below. [ ] Avoid exposure to cigarette smoke for 72 hours; smoke may worsen the condition of your lungs. [ ] Avoid drinking alcoholic beverages for at least 24 hours; alcohol may worsen injury to your stomach or have other effects. [ ] Avoid taking the following medications: [ ] You may continue taking the following medication(s) that your doctor(s) prescribed for you:

[ ] Other instructions:

• Provide the Emergency Department with the name and the number of your primary care physician so that the ED can send him or her a record of your emergency department visit.

• You or your physician can get more information on the chemical by contacting: or , or by checking out the following Internet Web sites: ; . Signature of patient Date Signature of physician Date

22 Patient Information Sheet • ATSDR