DIGITOXIN

Editor's Note: This material is not listed in the Emergency Response Guidebook. Based on the material's physical and chemical properties, toxicity, or chemical group, a guide has been assigned. For additional technical information, contact one of the emergency response telephone numbers listed under Public Safety Measures.

MOLECULAR FORMULA

C41-H64-O13

ERG GUIDE NUMBER

151-SUBSTANCES - TOXIC (NON-COMBUSTIBLE)

SYNONYM REFERENCE

(RTECS , 1990; Budavari, 1989; HSDB , 1990)

USES/FORMS/SOURCES

USES

Much is known about the clinical effects of both acute and chronic exposure because of the widespread use of digitalis, and more recently, digitoxin as a drug for treatment of low output congestive heart failure and management of cardiac arrhythmias in humans, including atrial flutter, atrial fibrillation, and paroxysmal atrial tachycardia (PAT) (HSDB , 1993).

FORMS

Digitoxin is a cardiac glycoside drug. It occurs as small, rectangular plates or as a white or pale buff microcrystalline powder (HSDB , 1993). It is soluble in amyl alcohol, pyridine, and acetone, is slightly soluble in petroleum ether, ether, chloroform, alcohol, and ethyl acetate, and is soluble to the extent of 10 ppm in water at 20 degrees C (HSDB , 1993).
Digitoxin is metabolized to DIGOXIN, which is 1000 times more active (Baselt & Cravey, 1989). Its pharmacologic activity is similar to that of OUABAIN. The mode of action of all cardiac glycosides is binding and inhibition of the sodium-potassium ATPase in the cellular membrane and subsequent interference with cellular ion transport (Hastreiter et al, 1988).
Digitoxin is a SUPER-TOXIC SUBSTANCE, with an estimated lethal dose being only a few milligrams.
All of the following clinical effects may not have been documented specifically for digitoxin. They are a compilation of effects of CARDIAC GLYCOSIDES. It is assumed that any or all of these effects could occur with digitoxin ingestion, because all these substances have an identical mode of action by inhibition of sodium-potassium ATPase. Effects which have been documented specifically for digitoxin are indicated. The pharmacology of digitalis glycosides has been extensively reviewed (Bigger, 1985; Bhatia & Smith, 1987; Hastreiter et al, 1988).

SOURCES

Digitoxin is the most active cardiac glycoside obtained from the dried whole leaf of Digitalis purpurea (foxglove) (Sax & Lewis, 1987). The commercial drug in the US is either the pure compound, or a mixture of the active cardiac glycosides from the plant (Budavari, 1989). Pure digitoxin is 1000 times more potent than the powdered Digitalis leaf on a weight basis (HSDB , 1993).

-CLINICAL EFFECTS

GENERAL CLINICAL EFFECTS

WITH POISONING/EXPOSURE

Digitoxin is a cardiac glycoside which is metabolized to DIGOXIN in acute exposures. Both chronic and acute digitoxin poisoning may result in vomiting, bradycardia, varying degrees of AV block, atrial and ventricular arrhythmias, and mental status changes. The onset and peak manifestations of cardiac toxicity following acute digoxin poisoning may be 30 minutes and between 3 to 12 hours respectively.

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

Digitoxin is a SUPER-TOXIC substance. The estimated lethal oral dose for an adult is in the range of a few milligrams. In one study, there was a 17% mortality rate in a group of 179 patients who had absorbed more than 2 mg of digitoxin (Dally et al, 1982). There is a narrow margin of safety between therapeutic and toxic doses (Bhatia & Smith, 1987).
Systemic effects from digitoxin by routes of exposure other than ingestion are not well defined in the literature. However, systemic toxicity may be possible by other routes (Sax & Lewis, 1989).
Nausea and vomiting are early signs of acute cardiac glycoside toxicity, irrespective of the route of exposure (Ekins & Watanabe, 1978; HSDB , 1993). Severity of gastrointestinal symptoms did not correlate with plasma digoxin levels in a group of 412 persons (Holt & Volans, 1977).
Acute poisoning by the cardiac glycosides can cause severe hyperkalemia which may in itself be life-threatening (Smith & Willerson, 1971; Citrin et al, 1972; Hastreiter et al, 1984; Antman & Smith, 1985). The degree of hyperkalemia has correlated with risk of mortality in a series of 91 digitoxin overdose patients (Bismuth et al, 1973).
Hyperkalemia occurs with digitoxin overdose by inhibition of Na+/K+ ATPase activity, and produces abdominal pain, muscle pain and weakness, diarrhea, ECG changes, and cardiac arrhythmias (Bradberry & Vale, 1995).
Acute poisoning may result in sinus bradycardia, varying degrees of heart block, and atrial and ventricular arrhythmias (Smith & Willerson, 1971; Citrin et al, 1973; Reza et al, 1974; Ekins & Watanabe, 1978). Cardiac arrhythmias of every known type have been produced in digitalis poisoning (Rodensky & Wasserman, 1961). Nonparoxysmal nodal tachycardia, atrial tachycardia with AV dissociation and bidirectional ventricular tachycardia are common (Soffer, 1961; Lyon & DeGraff, 1967). Different arrhythmias may be seen in the same patient at different times (Fisch & Knoebel, 1985).
Acute exposure to cardiac glycosides can have various neuropsychiatric effects, including drowsiness, weakness, paresthesias, and headache (Smith & Willerson, 1971; Ekins & Watanabe, 1978). Psychological changes of emotional instability, confusion, aphasia, disorientation and delirium may occur, and occasionally, convulsions (HSDB , 1993).
The onset and peak of cardiac toxicity following acute digitoxin overdose is 1 to 2 hours and 4 to 12 hours, respectively.
In one review, 9 to 66 percent of patients studied for digitalis intoxication displayed only cardiac signs, and up to 47 percent exhibited only symptoms other than those involving the heart. Up to 95 percent of patients experienced visual effects (Lely & van Enter, 1972).

WITH THERAPEUTIC USE

Severe thrombocytopenia was induced by digitoxin (Hess et al, 1983). Acute hemorrhage, a consequence of thrombocytopenia, is common in patients receiving cardiac glycosides (HSDB , 1993).
Digitoxin forms DIGOXIN, which is an order of magnitude more pharmacologically active on a molar basis.

ANIMAL STUDIES - Ouabain affected the contractions of dog hearts; the effects were long-lasting, with a half-time for washout of 7 to 10 hours. There was significant loss of contractile force and development of contracture (Grupp et al, 1985). Ouabain at 1.2 or 2.4 mcM impaired mechanical performance and induced ultrastructural aberrations in isolated rabbit hearts. These effects appeared to be due to excessive uptake of calcium in the left ventricle (Pilati & Paradise, 1984).

CHRONIC CLINICAL EFFECTS

WITH POISONING/EXPOSURE

Other cardiac glycosides produce visual disturbances with chronic exposure. These have not been documented with clinical use of digitoxin (Grant, 1986), but may be possible in massive accidental exposures. Visual effects include photophobia, amblyopia, aberrations of color vision, and scotoma, but generally are only seen in chronic digoxin toxicity. Illusions of flickering or shimmering lights, snow or frost covering objects, and yellow or green appearance of objects have been associated with reduced visual acuity. These effects are thought to be reversible, but the mechanism is unknown (Grant, 1986; HSDB , 1993). Disturbances of color vision are apparently more common with digoxin than with pengitoxin (Muller-Limmeroth & Dimakos, 1966).

WITH THERAPETUIC USE

Formed visual hallucinations, including butterflies, bird houses, and persons, were experienced in two elderly patients receiving digoxin therapy who were otherwise mentally normal; hallucinations resolved when digoxin was withheld initially and then maintained in the therapeutic range (Volpe & Soave, 1979). Recurring "blackouts" and EEG changes were seen in a 72-year-old man with signs of digitalis toxicity (Douglas et al, 1971).
CUMULATIVE TOXICITY is likely with repeated exposure to digitoxin. The half-life is 5 to 7 days in the body, and the heart becomes more sensitive to a lower dose after digitalization (HSDB , 1993). Both of these factors would work in the same direction to produce a lower threshold with chronic exposure.
Clinical experience suggests that the effects of chronic cardiac glycoside toxicity resemble those of acute toxicity, but may be more pronounced. Nausea and vomiting can also occur with chronic exposure to the cardiac glycosides (Ekins & Watanabe, 1978), along with weight loss (Kelton & Scullin, 1978). As with acute exposures, cardiac arrhythmias and thrombocytopenia can occur if doses exceed the safe range (Schneider et al, 1992).
Neuropsychiatric effects of chronic exposure include headache, fatigue, irritability, malaise, lassitude and lethargy, sudden personality changes, confusion, paranoia and psychosis (HSDB , 1993; Miller & Forker, 1974; Carney et al, 1985; Grubb, 1987).
Allergic reactions have occasionally been reported with cardiac glycosides (HSDB , 1993).

-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

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

CAUTION

Warning Digitoxin is a SUPER-TOXIC substance, ingestion of a few milligrams may be fatal.

POSSIBLE DELAYED TOXICITY

Significant toxic effects can develop from overdoses of digitoxin after one to two hours in the absence of clinical symptoms. Take immediate measures to prevent absorption of digitoxin from the gastrointestinal tract.

SPONTANEOUS EMESIS

Nausea and vomiting can occur from any route of exposure.

EMESIS/NOT RECOMMENDED

Emesis is not recommended for cardiac glycoside ingestion. Activated charcoal should be given to patients who can protect their airway and are not actively vomiting.
PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION

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

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

ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
Patients who have ingested any amount of cardiac glycosides should be admitted to a hospital and carefully observed and treated in a controlled setting until all signs and symptoms have resolved.

MONITORING

Patients who have ingested any amount of cardiac glycosides should be admitted to a hospital and carefully observed and treated in a controlled setting until all signs and symptoms have resolved.
Continuous cardiac monitoring and frequent monitoring of serum potassium and digitoxin levels are indicated. Fab fragments should be given in patients with signs of toxicity, a known large ingestion, or hyperkalemia. If Fab fragments are not readily available, hyperkalemia may be treated with insulin, glucose, and sodium bicarbonate.

-RANGE OF TOXICITY

MINIMUM LETHAL EXPOSURE

GENERAL/SUMMARY

Digitoxin is a SUPER-TOXIC substance, with a lethal dose for an adult being in the range of a few milligrams. In one study, there was a 17% mortality rate in a group of 179 patients who had absorbed more than 2 mg of digitoxin (Dally et al, 1982).
There is insufficient information in the literature to determine the minimum lethal dose of digitoxin. This is because the purity and activity of different preparations may vary, because some individuals may already be receiving a therapeutic dose, and because of interindividual variability.
Published values (RTECS , 1990)

LDLo (Unreported) MAN - 44 mcg/kg
LDLo (IV) RABBIT - 1 mg/kg
LDLo (IV) GUINEA PIG - 310 mcg/kg
LDLo (INTRADUODENAL) GUINEA PIG - 7250 mcg/kg
LDLo (INTRADUODENAL) GUINEA PIG - 3 mg/kg
LDLo (IV) DOG - 500 mcg/kg
LDLo (IV) CAT - 180 mcg/kg
LDLo (Unreported) CAT - 325 mg/kg
LDLo (INTRADUODENAL) CAT - 315 mcg/kg
LDLo (INTRAARTERIAL) CAT - 440 mcg/kg
LDLo (IV) PIG - 400 mcg/kg
LDLo (INTRADUODENAL) PIG - 550 mcg/kg
LDLo (IV) PIGEON - 443 mcg/kg
LDLo (PARENTERAL) PIGEON - 600 mcg/kg
LDLo (PARENTERAL) FROG - 1 mg/kg

MAXIMUM TOLERATED EXPOSURE

GENERAL/SUMMARY

Digitoxin is a SUPER-TOXIC substance, and a few milligrams may be fatal. Toxicity may appear at varying exposures for each individual, as a function of age, presence of heart or kidney disease, imbalances in electrolytes, and possibly other factors (HSDB , 1990).

The lowest published toxic oral dose for an infant is 150 mcg/kg (RTECS , 1990).

Carcinogenicity Ratings for CAS71-63-6 :

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): Not Listed
NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
MAK (DFG, 2002): Not Listed
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 CAS71-63-6 (U.S. Environmental Protection Agency, 2011):

Not Listed

TOXICITY VALUES

References: RTECS, 1990
- LD50- (INTRAPERITONEAL)CAT:
- LD50- (ORAL)CAT:
- LD50- (INTRAPERITONEAL)GUINEA_PIG:
- LD50- (ORAL)GUINEA_PIG:
- LD50- (INTRACEREBRAL)MOUSE:
- LD50- (INTRAPERITONEAL)MOUSE:
- LD50- (INTRAVENOUS)MOUSE:
- LD50- (ORAL)MOUSE:
- LD50- (SUBCUTANEOUS)MOUSE:
- LD50- (INTRAVENOUS)RAT:
- LD50- (ORAL)RAT:

-STANDARDS AND LABELS

WORKPLACE STANDARDS

ACGIH TLV Values for CAS71-63-6 (American Conference of Governmental Industrial Hygienists, 2010):

Not Listed

AIHA WEEL Values for CAS71-63-6 (AIHA, 2006):

Not Listed

NIOSH REL and IDLH Values for CAS71-63-6 (National Institute for Occupational Safety and Health, 2007):

Not Listed

OSHA PEL Values for CAS71-63-6 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

Not Listed

OSHA List of Highly Hazardous Chemicals, Toxics, and Reactives for CAS71-63-6 (U.S. Occupational Safety and Health Administration, 2010):

Not Listed

ENVIRONMENTAL STANDARDS

EPA CERCLA, Hazardous Substances and Reportable Quantities for CAS71-63-6 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA CERCLA, Hazardous Substances and Reportable Quantities, Radionuclides for CAS71-63-6 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA RCRA Hazardous Waste Number for CAS71-63-6 (U.S. Environmental Protection Agency, 2010b):

Not Listed
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 CAS71-63-6 (U.S. Environmental Protection Agency, 2010):

Listed as: Digitoxin
Reportable Quantity, in pounds: 100

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): b

b: The calculated TPQ changed after technical review as described in a technical support document for the final rule, April 22, 1987.

EPA SARA Title III, Community Right-to-Know for CAS71-63-6 (40 CFR 372.65, 2006; 40 CFR 372.28, 2006):

Not Listed

DOT List of Marine Pollutants for CAS71-63-6 (49 CFR 172.101 - App. B, 2005):

Not Listed

EPA TSCA Inventory for CAS71-63-6 (EPA, 2005):

Listed as: Card-20(22)-enolide, 3-[(O-2,6-dideoxy-.beta.-D-ribo-hexopyranosyl-(1.fwdarw.4)-O-2,6-dideoxy-.beta.-D-ribo-hexopyranosyl-(1.fwdarw.4)-2,6-dideoxy-.beta.-D-ribo-hexopyranosyl)oxy]-14-hydroxy-, (3.beta.,5.beta.)-

SHIPPING REGULATIONS

SURFACE

DOT -- Table of Hazardous Materials and Special Provisions (49 CFR 172.101, 2005):

Not Listed

ICAO International Shipping Name (ICAO, 2002):

Not Listed

LABELS

NFPA

NFPA Hazard Ratings for CAS71-63-6 (NFPA, 2002):

Not Listed

-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.

RESPIRATORY PROTECTION

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

Self-contained (positive pressure) breathing apparatus is recommended for fire fighting and handling spills (EPA, 1985).

PROTECTIVE CLOTHING

CHEMICAL PROTECTIVE CLOTHING. Search results for CAS 71-63-6.

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

Editor's Note: This material is not listed in the Emergency Response Guidebook. Based on the material's physical and chemical properties, toxicity, or chemical group, a guide has been assigned. For additional technical information, contact one of the emergency response telephone numbers listed under Public Safety Measures.
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.

FLAMMABILITY CLASSIFICATION

NFPA Flammability Rating for CAS71-63-6 (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 CAS71-63-6 (NFPA, 2002):

Not Listed

COMBUSTION TOXICITY

When heated to decomposition, digitoxin emits acrid smoke and irritating fumes (Sax & Lewis, 1989).

DUST/VAPOR HAZARD

When heated to decomposition, digitoxin emits acrid smoke and irritating fumes (Sax & Lewis, 1989).

REACTIVITY HAZARD

There was no information on reactivity hazards for digitoxin in available references at the time of this review.

Environmental Hazard: There was no information on environmental hazards for digitoxin in available references at the time of this review.

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.

AIHA ERPG Values for CAS71-63-6 (AIHA, 2006):

Not Listed

DOE TEEL Values for CAS71-63-6 (U.S. Department of Energy, Office of Emergency Management, 2010):

Listed as Digitoxin
TEEL-0 (units = mg/m3): 0.0075
TEEL-1 (units = mg/m3): 0.025
TEEL-2 (units = mg/m3): 0.18
TEEL-3 (units = mg/m3): 0.25
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 CAS71-63-6 (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):

Not Listed

NIOSH IDLH Values for CAS71-63-6 (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.
No specific disposal guidelines have been recommended for this agent. The following information is general recommendations for non-specific medicines (EPA, 1985).
Shut off ignition sources; no flares, smoking or flames in hazard area.
Keep combustibles such as wood, paper, oil, etc away from spilled material.
Do not touch spilled material.

-ENVIRONMENTAL HAZARD MANAGEMENT

POLLUTION HAZARD

There was no specific information on pollution hazards for digitoxin in available references at the time of this review.

ENVIRONMENTAL FATE AND KINETICS

OTHER

OTHER
- There was no information on environmental kinetics for digitoxin in available references at the time of this review.

ENVIRONMENTAL TOXICITY

There was no information on environmental toxicity for digitoxin in available references at the time of this review.

-PHYSICAL/CHEMICAL PROPERTIES

MOLECULAR WEIGHT

764.92

DESCRIPTION/PHYSICAL STATE

white or pale buff microcrystalline powder (HSDB, 2005)

white, odorless, bitter leaflets or powder (Sax & Lewis, 1987)

very small elongated, rectangular plates from dilute alcohol (HSDB, 2005; Budavari, 1989)

FREEZING/MELTING POINT

MELTING POINT

ANHYDROUS: 256-257 degrees C (HSDB, 2005; Budavari, 1989)

SOLUBILITY

IN WATER

slightly soluble in water; 1 g/100 L (at 20 degrees C) (Budavari, 1989)

IN ORGANIC SOLVENTS

One gram dissolves in approximately 40 mL of chloroform, 60 mL of alcohol, and 400 mL of ethyl acetate (Budavari, 1989).
Also soluble in acetone, amyl alcohol, pyridine; sparingly soluble in ether and petroleum ether (Budavari, 1989).

-REFERENCES

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National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Automotive Gasoline Unleaded (Proposed). United States Environmental Protection Agency. Washington, DC. 2009a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cc17&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

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National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Boron Tribromide (Proposed). United States Environmental Protection Agency. Washington, DC. 2008a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ae1d3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bromine Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2007d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648039732a&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bromoacetone (Proposed). United States Environmental Protection Agency. Washington, DC. 2008e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809187bf&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Calcium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&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 Carbonyl Fluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2008b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ae328&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Carbonyl Sulfide (Proposed). United States Environmental Protection Agency. Washington, DC. 2007e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648037ff26&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Chlorobenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2008c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803a52bb&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Cyanogen (Proposed). United States Environmental Protection Agency. Washington, DC. 2008f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809187fe&disposition=attachment&contentType=pdf. As accessed 2010-08-15.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Dimethyl Phosphite (Proposed). United States Environmental Protection Agency. Washington, DC. 2009. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbf3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Diphenylchloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&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 Ethyl Isocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648091884e&disposition=attachment&contentType=pdf. As accessed 2010-08-15.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethyl Phosphorodichloridate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480920347&disposition=attachment&contentType=pdf. As accessed 2010-08-15.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2008g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809203e7&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 Germane (Proposed). United States Environmental Protection Agency. Washington, DC. 2008j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963906&disposition=attachment&contentType=pdf. As accessed 2010-08-15.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Hexafluoropropylene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064801ea1f5&disposition=attachment&contentType=pdf. As accessed 2010-08-15.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ketene (Proposed). United States Environmental Protection Agency. Washington, DC. 2007. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ee7c&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 Malathion (Proposed). United States Environmental Protection Agency. Washington, DC. 2009k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809639df&disposition=attachment&contentType=pdf. As accessed 2010-08-15.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Mercury Vapor (Proposed). United States Environmental Protection Agency. Washington, DC. 2009b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a8a087&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyl Isothiocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963a03&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 Methylchlorosilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2005. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5f4&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 Perchloryl Fluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2009c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e268&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Perfluoroisobutylene (Proposed). United States Environmental Protection Agency. Washington, DC. 2009d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e26a&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 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.

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DIGITOXIN

Classification | Information to evaluate chemical incidents

Information to evaluate chemical incidents

Information to evaluate chemical incidents

Information to evaluate chemical incidents