CANTHARIDIN

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

C10-H12-O4

ERG GUIDE NUMBER

154-SUBSTANCES - TOXIC and/or CORROSIVE (NON-COMBUSTIBLE)

SYNONYM REFERENCE

(RTECS , 1991; EPA, 1985)

USES/FORMS/SOURCES

USES

HOMICIDAL AGENT: It has been used as a homicidal agent in South Africa (Till & Majmudar, 1981).
HERBAL USES: Other herbalist uses included treatment for dropsy, pleurisy, pericarditis, kidney infections, kidney stones, stranguria, certain venereal diseases, and amenorrhea. It has a well-known, but undeserved reputation as an aphrodisiac known as "Spanish Fly" (Friesen et al, 1979). Cantharidin has been used in traditional Chinese medicine to treat fungal infections, warts, various dermatologic conditions and to induce abortion; it is believed also to have antitumor effects (Chen & Leung, 1995).
POWDER: A brown powder found in the possession of a deceased 36-year-old black male contained 0.87% cantharidin (Hundt et al, 1990). The source of the powder may have been an herbal doctor.
MODERN USES: Cantharidin has been used as a counter-irritant and vesicant, and for removal of benign epithelial growths such as warts and molluscum contagiosum. It is an experimental antitumor agent (HSDB , 1990).

FORMS

Types of cantharidin preparations:

Cantharidin in flexible collodion
Cantharidis pulvis
Emplastrum cantharidini in massa
Liquor cantharidini
Liquor Epispasticus

Cantharidin is available as cantharidin collodion (cantharone), which contains 0.7% cantharidin in a film-forming vehicle containing acetone, ethocel, flexible collodion, ether (35%), and alcohol (11%) (HSDB , 1990).

SOURCES

NATURAL SOURCES - Representative beetle species include (Nickolls & Teare, 1954; (Ross, 1948; Nicholls et al, 1990):

Alloxacis species
Cantharis vesicatoria
Eobia decolor
Eobia kanack
Meloidae Family

Epicanta species
Meloe species
Henous species

Mylabris cicorii
Mylabris phalerata
Oxacis species
Oxycopsis species
Thelyphassa lineata

BLISTER BEETLES: Especially Cantharis vesicatoria, are a natural source of cantharidin. The ovaries, soft tissues, and blood of these beetles contain the greatest concentrations.

The average concentration is 2.6 to 4.3%, but the South African beetle, Mylabridae, may contain as much as 11% (Till & Majmudar, 1981; Schmitz & Reagor, 1987).

EPICAUTA BLISTER BEETLES: Include (Edwards et al, 1989; Ray et al, 1989; Beasley et al, 1983): Name% cantharidinEpicauta albidaEpicauta attrivittataEpicauta callosaEpicauta confertaMale: 2.48 Female: 0.77Epicauta fictaEpicauta funebrisEpicauta immaculataEpicauta lemniscata0.47Epicauta maculataEpicauta murinaEpicauta occidentalisMale: 3.31 Female: 0.47Epicauta pardalisEpicauta pennsylvanica1.23Epicauta pestiferaEpicauta sericansEpicauta texemaEpicauta torsa

Cantharidin is found in the hemolymph, genitalia, and possibly other Epicauta beetle tissues (Schmitz & Reagor, 1987).

-CLINICAL EFFECTS

GENERAL CLINICAL EFFECTS

USES: Cantharidin is a lipid soluble extract derived from the blister beetle. There are more than 200 species of blister beetle worldwide. The most commonly implicated beetle is "Spanish Fly" (Cantharis vesicatoria); however, the highest concentration of cantharidin is found in the Chinese blister beetle (Mylabris cichorii L.). It has historically been utilized for its aphrodisiac properties and is known as "Spanish Fly." Cantharidin has also been utilized in Chinese medicine to treat fungal infections, warts, and various dermatologic conditions and to induce abortions. Currently, cantharidin is occasionally used by dermatologists to remove warts and molluscum contagiosum. It has also been studied as an experimental antitumor agent.

PHARMACOLOGY: Cantharidin is a powerful vesicant and potent irritant. It is a volatile double-ringed structure that is crystalline, colorless, odorless, and water insoluble. It is secreted by adult male beetles near the leg joints in hemolymph. Females do not produce cantharidin but can extrude it as a result of copulation deposition.

TOXICOLOGY: The irritant contact dermatitis results in intraepidermal and subepidermal blistering, epidermal necrosis, and acantholysis. It is caused by activation of neutral proteases that destroy dense desmosomal plaques. Cantharidin is also a potent inhibitor of protein phosphatases 1 and 2A. This results in the detachment of tonofilaments from desmosomes and the appearance of intraepidermal blisters. Biopsies reveal intraepidermal vesicles with fibrin, polymorphonuclear cells, and acanthocytes. Large ingestions may produce acute renal tubular necrosis with loss of brush borders, cloudy swelling, and hydropic degeneration resulting in renal injury and hematuria. Because cantharidin is a powerful vesicant and irritant, oral and ophthalmic exposures can result in vesiculobullous lesions, mucosal edema, and keratoconjunctivitis.

EPIDEMIOLOGY: Cantharidin exposure/ingestions are rare poisonings that very rarely result in serious morbidity or death.

WITH POISONING/EXPOSURE

MILD TO MODERATE TOXICITY: Mild inflammation of the dermis, oral or genital mucosa, and conjunctiva, fever, nausea, vomiting, wheeze, and lymphadenopathy.
SEVERE TOXICITY: Severe mucosal, dermal, or conjunctival injury, renal failure, liver injury, gastrointestinal hemorrhage, coagulopathy, airway obstruction, seizure, dysrhythmias, and shock.

WITH THERAPEUTIC USE

COMMON: The most commonly reported adverse effects include irritant dermatitis, dermal vesicles and bullae, conjunctivitis, priapism, and hematuria.
RARE: Other more rare adverse effects include renal failure, liver injury, gastrointestinal hemorrhage, coagulopathy, airway obstruction, seizure, dysrhythmias, and shock.

POTENTIAL HEALTH HAZARDS - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 154 (ERG, 2004)

TOXIC; inhalation, ingestion or skin contact with material may cause severe injury or death.
Contact with molten substance may cause severe burns to skin and eyes.
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

SUMMARY

PHARMACOLOGY: Cantharidin is a powerful vesicant and potent irritant. It is a volatile double-ringed structure that is crystalline, colorless, odorless, and water insoluble. It is secreted by adult male beetles near the leg joints in hemolymph. Females do not produce cantharidin but can extrude it as a result of copulation deposition.
TOXICOLOGY: The irritant contact dermatitis results in intraepidermal and subepidermal blistering, epidermal necrosis, and acantholysis. It is caused by activation of neutral proteases that destroy dense desmosomal plaques. Cantharidin is also a potent inhibitor of protein phosphatases 1 and 2A. This results in the detachment of tonofilaments from desmosomes and the appearance of intraepidermal blisters. Biopsies reveal intraepidermal vesicles with fibrin, polymorphonuclear cells, and acanthocytes. Large ingestions may produce acute renal tubular necrosis with loss of brush borders, cloudy swelling, and hydropic degeneration resulting in renal injury and hematuria. Because cantharidin is a powerful vesicant and irritant, oral and ophthalmic exposures can result in vesiculobullous lesions, mucosal edema, and keratoconjunctivitis.
EPIDEMIOLOGY: Cantharidin exposure/ingestions are rare poisonings that very rarely result in serious morbidity or death.
THERAPEUTIC: COMMON: The most commonly reported adverse effects include irritant dermatitis, dermal vesicles and bullae, conjunctivitis, priapism, and hematuria.
THERAPEUTIC: RARE: Other more rare adverse effects include renal failure, liver injury, gastrointestinal hemorrhage, coagulopathy, airway obstruction, seizure, dysrhythmias, and shock.
MILD TO MODERATE TOXICITY: Mild inflammation of the dermis, oral or genital mucosa, and conjunctiva, fever, nausea, vomiting, wheeze, and lymphadenopathy.
SEVERE TOXICITY: Severe mucosal, dermal, or conjunctival injury, renal failure, liver injury, gastrointestinal hemorrhage, coagulopathy, airway obstruction, seizure, dysrhythmias, and shock.

CARDIOVASCULAR

CONDUCTION DISORDER OF THE HEART: The most common cardiac abnormalities are ventricular ectopic beats, ventricular tachycardia, and ventricular fibrillation (Till & Majmudar, 1981; Rabkin et al, 1979). ST elevations, transient T wave inversions, and T wave amplitude changes have been noted in humans (Oaks et al, 1960; Friesen et al, 1979).
TACHYARRHYTHMIA: Sinus tachycardia with normal blood pressure has been observed (Ewart et al, 1978). Heart rate may be briefly stimulated and then become greatly depressed (HSDB , 1992).

DERMATOLOGIC

BULLOUS ERUPTION: Cantharidin is a vesicant and may cause blisters within 4 to 5 hours of application. Symptoms after dermal exposure may range anywhere from the mild inflammation mentioned above through severe blistering, ulceration, and necrosis (Till & Majmudar, 1981; Cheng et al, 1990). Bullous lesions develop when cantharidin is released from the body of 3 major groups of beetles at the time the insect is crushed or rubbed on exposed skin (Mendez et al, 1989; Nicholls et al, 1990).
ACANTHOLYSIS: Acantholysis has been reported (Stoughton & Bagatell, 1959; Weakley & Einbinder, 1962).

GASTROINTESTINAL

ULCERATIVE STOMATITIS: Ingestion may lead to desquamation or to a total loss of normal mucosal surfaces from the tongue to the pylorus. The mouth may initially be erythematous and edematous and later show patches of ulceration. There may be hemorrhage (Chen & Leung, 1995; Till & Majmudar, 1981) or blisters (Craven & Polak, 1954).
VOMITING/HEMATEMESIS: Vomiting and/or hematemesis may develop (Mallari et al, 1996; Karras et al, 1996). Petechial hemorrhage and mucosal erosion may be seen in the stomach (Till & Majmudar, 1981; Cheng et al, 1990; Presto & Muecke, 1970; EPA, 1985). In severe poisoning life-threatening gastrointestinal bleeding may occur (Chen & Leung, 1995)
TENESMUS: A prominent sympton is Tenesmus (Till & Majmudar, 1981; HSDB , 1991).
DIARRHEA has been observed following exposure (Craven & Polak, 1954).

GENITOURINARY

POLYURIA: Polyuria and mild dysuria may occur shortly after cantharidin poisoning. Cases have been reported when a patient may change from being polyuric to oliguric within a few hours (Till & Majmudar, 1981; Craven & Polak, 1954; HSDB , 1991).
BLOOD IN URINE: Gross and microscopic hematuria are common after significant ingestion (Tagwireyi et al, 2000; Karras et al, 1996). On autopsy, blood has been seen in the renal pelvises, ureters, and bladder. Kidneys can be engorged with blood (Till & Majmudar, 1981).
ALBUMINURIA: Proteinuria often develops in patients with hematuria (Karras et al, 1996; Tagwireyi et al, 2000; Mallari et al, 1996).
PRIAPISM: When used as an aphrodisiac, it may cause priapism (Till & Majmudar, 1981).
HEMATOMETRA: Uterine bleeding and pelvic edema occasionally occur in females when this agent is used as an aphrodisiac (Karras et al, 1996; Till & Majmudar, 1981).

HEENT

THROAT IRRITATION: POISONING/EXPOSURE: A burning sensation of the mouth and throat, and swelling and blistering of the tongue can develop after ingestion (Craven & Polak, 1954; Cheng et al, 1990; HSDB , 1991).

HEMATOLOGIC

BLOOD COAGULATION DISORDER: Mild coagulopathies (slightly prolonged INR/PT, PTT, depressed fibrinogen and the presence of fibrin split products) were reported in 4 patients who ingested cantharidin as an aphrodisiac (Karras et al, 1996). One of these patients also developed mild thrombocytopenia.
LEUKOCYTOSIS: Leukocytosis is common (Karras et al, 1996; Mallari et al, 1996).

NEUROLOGIC

FLACCID PARALYSIS: A Guillain-Barre type of flaccid paralysis has been reported with cantharidin poisoning; spontaneous reversal occurred in both cases (Harrisberg et al, 1984).

RESPIRATORY

HEMORRHAGE: Although edema and subpleural hemorrhages may be seen, the lungs are usually not seriously damaged (Till & Majmudar, 1981).
HYPERVENTILATION: Respirations may be briefly stimulated and then greatly depressed (HSDB , 1992).

VITAL SIGNS

HYPOTENSION: Shock has been reported with cantharidin poisoning (Chen & Leung, 1995).
PULSE: Heart rate may be briefly stimulated and then depressed (HSDB , 1992).

CHRONIC CLINICAL EFFECTS

WITH POISONING/EXPOSURE

No studies were found on possible effects of chronic exposure to cantharidin at the time of this review.

-FIRST AID

FIRST AID AND PREHOSPITAL TREATMENT

Do not administer activated charcoal as it is unlikely to affect tissue injury, and activated charcoal may obscure endoscopy.

Oral exposures can be diluted with water or milk if there are no signs of airway obstruction.

DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).

-MEDICAL TREATMENT

LIFE SUPPORT

Support respiratory and cardiovascular function.

SUMMARY

FIRST AID - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 154 (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

There is no specific antidote and treatment is supportive. Special care should be taken to treat GI bleeding and kidney damage.
This toxin is very water insoluble but will dissolve in lipids, oils, or fats administered with or after ingestion. This may increase absorption and toxicity.
DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting.
Significant esophageal or gastrointestinal tract irritation or burns may occur following ingestion. The possible benefit of early removal of some ingested material by cautious gastric lavage must be weighed against potential complications of bleeding or perforation.
GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in the head down left lateral decubitus position or by endotracheal intubation. Control any seizures first.

CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion.

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.

-RANGE OF TOXICITY

MINIMUM LETHAL EXPOSURE

ACUTE

Although the minimum lethal exposure has not been well documented in the literature, as little as 10 milligrams has reportedly resulted in death (Melen, 1922), the usual "minimal lethal dose" quoted is between 32 to 65 milligrams (Cheng et al, 1990; Nickolls & Teare, 1954).
Ingestion of the crude extract from over 200 Mylabris phalerata beetles for abortion resulted in a fatality (Cheng et al, 1990).

MAXIMUM TOLERATED EXPOSURE

CASE REPORTS

Up to 50 milligrams has been tolerated (Melen, 1922).
Exposure to 175 milligrams caused second and third degree burns of the mouth, seizures, kidney damage, and hypotension, but the patient survived (Oaks et al, 1960).
Ewart et al (1978) reported a case where 105 to 140 milligrams was ingested. The oral mucosa became inflamed and ulcerated; the patient developed hematuria, and T wave abnormalities, but recovered.
As little as 0.5 milligram lodged in the mucosa will produce a blister and possible systemic effects, and as little as 32 to 65 milligrams may be fatal (Nickolls & Teare, 1954).
As few as 4 to 24 dried blister beetles may produce a serious or fatal ingestion (Cheng et al, 1990).

Carcinogenicity Ratings for CAS56-25-7 :

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): 3 ; Listed as: Cantharidin

3 : The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.

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 CAS56-25-7 (U.S. Environmental Protection Agency, 2011):

Not Listed

TOXICITY VALUES

LD50- (INTRAPERITONEAL)MOUSE:
- 1 mg/kg (RTECS, 2004)
LDLo- (ORAL)HUMAN:
- 428 mcg/kg (RTECS, 2004)

-STANDARDS AND LABELS

WORKPLACE STANDARDS

ACGIH TLV Values for CAS56-25-7 (American Conference of Governmental Industrial Hygienists, 2010):

Not Listed

AIHA WEEL Values for CAS56-25-7 (AIHA, 2006):

Not Listed

NIOSH REL and IDLH Values for CAS56-25-7 (National Institute for Occupational Safety and Health, 2007):

Not Listed

OSHA PEL Values for CAS56-25-7 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

Not Listed

OSHA List of Highly Hazardous Chemicals, Toxics, and Reactives for CAS56-25-7 (U.S. Occupational Safety and Health Administration, 2010):

Not Listed

ENVIRONMENTAL STANDARDS

EPA CERCLA, Hazardous Substances and Reportable Quantities for CAS56-25-7 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA CERCLA, Hazardous Substances and Reportable Quantities, Radionuclides for CAS56-25-7 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA RCRA Hazardous Waste Number for CAS56-25-7 (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 CAS56-25-7 (U.S. Environmental Protection Agency, 2010):

Listed as: Cantharidin
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): Not Listed

EPA SARA Title III, Community Right-to-Know for CAS56-25-7 (40 CFR 372.65, 2006; 40 CFR 372.28, 2006):

Not Listed

DOT List of Marine Pollutants for CAS56-25-7 (49 CFR 172.101 - App. B, 2005):

Not Listed

EPA TSCA Inventory for CAS56-25-7 (EPA, 2005):

Listed as: 4,7-Epoxyisobenzofuran-1,3-dione, hexahydro-3a,7a-dimethyl-, (3aR,4S,7R,7aS)-rel-

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 CAS56-25-7 (NFPA, 2002):

Not Listed

-PERSONAL PROTECTION

SUMMARY

RECOMMENDED PROTECTIVE CLOTHING - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 154 (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.

PROTECTIVE CLOTHING

CHEMICAL PROTECTIVE CLOTHING. Search results for CAS 56-25-7.

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 154 (ERG, 2004)
- Non-combustible, substance itself does not burn but may decompose upon heating to produce corrosive and/or toxic fumes.
- Some are oxidizers and may ignite combustibles (wood, paper, oil, clothing, etc.).
- Contact with metals may evolve flammable hydrogen gas.
- Containers may explode when heated.

FLAMMABILITY CLASSIFICATION

NFPA Flammability Rating for CAS56-25-7 (NFPA, 2002):

Not Listed

FIRE CONTROL/EXTINGUISHING AGENTS

SMALL FIRE PRECAUTIONS - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 154 (ERG, 2004)

Dry chemical, CO2 or water spray.

LARGE FIRE PRECAUTIONS - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 154 (ERG, 2004)

Dry chemical, CO2, alcohol-resistant foam or water spray.
Move containers from fire area if you can do it without risk.
Dike fire control water for later disposal; do not scatter the material.

TANK OR CAR/TRAILER LOAD FIRE PRECAUTIONS - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 154 (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.

NFPA Extinguishing Methods for CAS56-25-7 (NFPA, 2002):

Not Listed

DUST/VAPOR HAZARD

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

REACTIVITY HAZARD

There was no information on reactivity hazard for cantharidin 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 154 (ERG, 2004)

Increase, in the downwind direction, as necessary, the isolation distance of at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids in all directions.

FIRE - PUBLIC SAFETY EVACUATION DISTANCES - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 154 (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 154 (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.
Ventilate enclosed areas.

AIHA ERPG Values for CAS56-25-7 (AIHA, 2006):

Not Listed

DOE TEEL Values for CAS56-25-7 (U.S. Department of Energy, Office of Emergency Management, 2010):

Listed as Cantharidin
TEEL-0 (units = mg/m3): 0.75
TEEL-1 (units = mg/m3): 2.5
TEEL-2 (units = mg/m3): 4.3
TEEL-3 (units = mg/m3): 4.3
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 CAS56-25-7 (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 CAS56-25-7 (National Institute for Occupational Safety and Health, 2007):

Not Listed

CONTAINMENT/WASTE TREATMENT OPTIONS

SUMMARY

SPILL OR LEAK PRECAUTIONS - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 154 (ERG, 2004)
- ELIMINATE all ignition sources (no smoking, flares, sparks or flames in immediate area).
- 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.
- 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 154 (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.

-ENVIRONMENTAL HAZARD MANAGEMENT

POLLUTION HAZARD

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

Cantharidin is a naturally occurring active principle of cantharides and other insects (HSDB , 1990).

ENVIRONMENTAL FATE AND KINETICS

OTHER

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

ENVIRONMENTAL TOXICITY

A laboratory study evaluated the effect of cantharidin in blister beetles on the health of livestock. Blister beetles accumulate the pesticide. The results showed that blister beetles crushed in the fields and subsequently ingested by livestock was a greater health risk than cantharidin contaminated hay free of blister beetles (Blodgett et al, 1992).

-PHYSICAL/CHEMICAL PROPERTIES

MOLECULAR WEIGHT

196.21

DESCRIPTION/PHYSICAL STATE

Cantharidin Crystals are colorless, and odorless.

Cantharidin is a solid, forming orthorhombic plates and scales (Budavari, 1996).

No information found at the time of this review.

FREEZING/MELTING POINT

MELTING POINT

Sublimes at approximately 110 degrees C (at 12 mmHg) (Budavari, 1996)
Sublimes at 84 degrees C (HSDB , 1990).

SOLUBILITY

IN WATER

Insoluble in cold water; somewhat soluble in hot water (Budavari, 1996).

IN ORGANIC SOLVENTS

1g/40 mL acetone (Budavari, 1996)
1g/65 mL chloroform (Budavari, 1996)
1g/560 mL ether (Budavari, 1996)
1g/150 mL ethyl acetate (Budavari, 1996)
ALCOHOLS: Slightly soluble (HSDB , 1995)

OTHER

Soluble in oils (Budavari, 1996)
Soluble in concentrated sulfuric acid and acetic acid; slightly soluble in benzene (HSDB , 1990)

-REFERENCES

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Classification | Information to evaluate chemical incidents

Information to evaluate chemical incidents

Information to evaluate chemical incidents

Information to evaluate chemical incidents