Cantharidin

196.2

196.20

200-263-3

IGL471WQ8P

61805

2811

DTXSID7041752

Orthorhombic plates, scales

29329990

52.6

0.10

white

1.38 g/cm³

218 °C

Sublimes @ 84 deg C

146.1±26.0 °C

1.547

soluble in DMSO (25 mg/ml warm), acetone (8 mg/ml), ethanol (8 mg/ml warm), chloroform (1:65), ether (1:560), and ethyl acetate (1:150).

Store at RT

Peritoneal-mouse LD50: 1 mg/kg

Open flame is flammable; thermal decomposition is spicy and stimulates smoke

Sublimes at about 110 °C (12 mm Hg, 3-5 mm distance)|Hydrolyzed to cantharinic acid.

No rapid reaction with air. No rapid reaction with water.

Anhydrides

Organic anhydrides, such as CANTHARIDIN, are incompatible with acids, strong oxidizing agents, alcohols, amines, and bases.

I

6.1(a)

UN 2811 6.1/PG 1

3

28-36/37/38-38-37-36-23/24/25

53-45-36/37/39

RN8575000

T+,T

The warehouse is ventilated, low temperature and dry; stored and transported separately from food materials

Stable at normal temperatures and pressures.

Missing Phrase - N15.00950417-P305 + P351 + P338

H300-H315-H319-H335

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

When heated to decomposition it emits acrid smoke and irritating fumes. (EPA, 1998)

|Danger|H300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P310, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 46 companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]: SMALL FIRE: Dry chemical, CO2 or water spray. LARGE FIRE: 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. FIRE INVOLVING TANKS OR CAR/TRAILER LOADS: 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. (ERG, 2016)

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]: 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. SPILL: Increase, in the downwind direction, as necessary, the isolation distance shown above. FIRE: 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. (ERG, 2016)

Avoid inhalation and skin contact. (EPA, 1998)

For emergency situations, wear a positive pressure, pressure-demand, full facepiece self-contained breathing apparatus (SCBA) or pressure- demand supplied air respirator with escape SCBA and a fully-encapsulating, chemical resistant suit. (EPA, 1998)

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Cantharidin is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 100/10,000 lbs.

highly toxic

Side effects observed from the topical application of cantharidin include blistering, erythema, pain, bleeding, ring warts, post-inflammatory hyperpigmentation, lymphangitis, secondary bacterial cellulitis, scarring, and varicelliform vesicular dermatitis.

CANTHARIDIN, IN THE INCUBATION MEDIUM CONTAINING SUCCINATE OR SODIUM D,L-BETA-HYDROXYBUTYRATE, CAUSES UNCOUPLING OF OXIDATIVE PHOSPHORYLATION IN MITOCHONDRIA FROM LIVER OF THE RAT.

TOXIC DOSES OF CANTHARIDES ARE ... 15 G IN HORSE AND OX ... 4 G IN SHEEP, & 2 G IN DOG.|LD50 Mouse ip 1 mg/kg

Little pharmacodynamic and pharmacokinetic data regarding cantharidin in the human body currently exists; recruitment for First-Time-In-Human clinical trials regarding such information have been ongoing in 2018. There are however some studies regarding such data in animal models like beagle dogs.

Cantharidin, the active ingredient in the crude drug cantharides, is obtained from the dried insects Cantharis vesicatoria.

The only therapeutic use for which cantharidin is currently primarily indicated for is as an active ingredient in topical agents for treating common warts (verruca vulgaris), periungual warts, plantar warts, and molluscum contagiosum. At the same time, such topical cantharidin applications have also been used for a number of off-label indications like callus removal, cutaneous leishmaniasis, herpes zoster, and acquired perforating dermatosis. Furthermore, since most topical cantharidin applications are most commonly available in a 0.7% formulation or a more potent 1% mixture, the 0.7% formulation is most commonly indicated for the treatment of common warts, periungual warts, and molluscum contagiosum while the more potent 1% mixture is typically limited only for use by healthcare professionals in a clinical setting for treating plantar warts and other more specialized off-label conditions. Moreover, there have also been studies into whether or not cantharidin could be effective at being used as an inflammatory model or in cancer treatment - either of which has yet to formally elucidate any results.

Enzyme Inhibitors; Irritants|EXPTL USE: CANTHARIDIN AS ANTICANCER AGENTS.|EXPTL USE: APPLICATION OF MYLABRIS CANTHARIDIN IS AN ACTIVE COMPONENT OF MYLABRIS IN CANCER TREATMENT.|EXPTL USE: IN MICE INOCULATED WITH 2 MILLION CELLS OF ASCITES HEPATOMA, ADMIN OF CANTHARIDIN (1.25 MG/KG/DAY FOR 7 DAYS, IP) PROLONGED SURVIVAL PERIOD BY 20.8-61.5%. CANTHARIDIN HAD NO THERAPEUTIC ACTION ON SARCOMA 180 IN MICE OR WALKER TUMOR IN RATS.|For more Therapeutic Uses (Complete) data for CANTHARIDINE (9 total), please visit the HSDB record page.

Cantharidin is a natural toxin produced by the blistering beetle that possesses both vesicant (blistering) and keratolytic effects. The substance elicits these effects by inducing acantholysis (loss of intercellular connections) through the targeting of the desmosomal dense plaque, resulting in the detachment of the desmosomes from the tonofilaments. Cantharidin's effectiveness against warts is proposed to be a result of the exfoliation of the wart body as a consequence of the compound's acantholytic action. This acantholytic action generally does not go beyond the epidermal cells so that the basal layer remains intact and minimal effect occurs on the corium. There is consequently no scarring from the topical application of cantharidin.

Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. (See all compounds classified as Enzyme Inhibitors.)|Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. (See all compounds classified as Irritants.)

Cantharidin is absorbed from the gastrointestinal tract, and, to a limited extent from the skin as well. Little pharmacodynamic and pharmacokinetic data regarding cantharidin in the human body currently exists; recruitment for First-Time-In-Human clinical trials regarding such information have been ongoing in 2018. There are however some studies regarding such data in animal models like beagle dogs.|It has been observed that absorbed cantharidin is excreted by the kidney. Little pharmacodynamic and pharmacokinetic data regarding cantharidin in the human body currently exists; recruitment for First-Time-In-Human clinical trials regarding such information have been ongoing in 2018. There are however some studies regarding such data in animal models like beagle dogs.|After oral or IP injection of (3)H-labeled cantharidin, high levels of radioactivity distributed to and were exhibited in the bile, kidney, liver, stomach, and tumor cells of ascites hepatoma-bearing mice. Such distribution suggests the agent has an affinity for liver and tumor tissues. Little pharmacodynamic and pharmacokinetic data regarding cantharidin in the human body currently exists; recruitment for First-Time-In-Human clinical trials regarding such information have been ongoing in 2018. There are however some studies regarding such data in animal models like beagle dogs.|Little pharmacodynamic and pharmacokinetic data regarding cantharidin in the human body currently exists; recruitment for First-Time-In-Human clinical trials regarding such information have been ongoing in 2018. There are however some studies regarding such data in animal models like beagle dogs.|THE DRUG IS ABSORBED FROM GI TRACT AND, TO LIMITED EXTENT, FROM SKIN. IT IS EXCRETED BY KIDNEY.|BILE, KIDNEY, LIVER, STOMACH & TUMOR CELLS OF ASCITES HEPATOMA-BEARING MICE EXHIBITED A HIGH LEVEL OF RADIOACTIVITY AFTER ORAL OR IP INJECTION OF (3)H-LABELED CANTHARIDIN. DISTRIBUTION SUGGESTS IT HAS AFFINITY TO LIVER & TUMOR TISSUES.

Little pharmacodynamic and pharmacokinetic data regarding cantharidin in the human body currently exists; recruitment for First-Time-In-Human clinical trials regarding such information have been ongoing in 2018. There are however some studies regarding such data in animal models like beagle dogs.

Little pharmacodynamic and pharmacokinetic data regarding cantharidin in the human body currently exists; recruitment for First-Time-In-Human clinical trials regarding such information have been ongoing in 2018. There are however some studies regarding such data in animal models like beagle dogs.

Cantharidin is specifically absorbed by lipids in the membrane of epidermal keratinocytes, where it activates the release of neutral serine proteases. These enzymes subsequently break the peptide bonds in surrounding proteins, leading to the progressive degeneration of desmosomal dense plaques, which are important cellular structures that participate in cell-to-cell adhesion. Such degeneration results in the detachment of the tonofilaments that hold cells together. This process as a whole leads to the selective acantholysis (loss of cellular connections) and blistering of the skin when the cantharidin topical application is applied upon specific topical developments like warts. A blister(s) at the application site develop within 24 to 48 hours of application and typically resolve within 4 to 7 days. Factors that can modify this proposed time frame include the volume or concentration of cantharidin used, physical contact time of the applied compound (usually between 4 to 24 hours), the presence of any occlusive dressings, or even patient sensitivity to cantharidin. The blistered lesions ultimately heal without scarring. Finally, there are some studies that suggest cantharidin's chemical profile as a potent and selective inhibitor of protein phosphatase 2A confers upon it an oxidative stress-independent growth inhibition of pancreatic cancer cells through cancer cell-cycle arrest and apoptosis. Nevertheless, the fact that little data regarding the pharmacodynamics and pharmacokinetics of cantharidin in the human body exists and certain toxic effects of cantharidin that have been observed following oral ingestion in humans like ulceration of the gastrointestinal and genitourinary tracts, along with electrolyte and renal function disturbance are strong reasons as to why the compound currently lacks FDA approval is used fairly limitedly for formal therapeutic indications.|Cantharidine totally inhibits the phosphorylase a phosphatase activity in mouse liver, muscle, and skin cytosol at 5000 nM, with IC50s of 110-250 nM. About 50% of the phosphorylase a phosphatase activity of brain cytosol is sensitive to cantharidine with an IC50 of approximately 80 nM and the remaining half is not inhibited even at 5000 nM.

It is classified as super toxic. Probable oral lethal dose in humans is less than 5 mg/kg or a taste of less than 7 drops for a 70 kg (150 lb.) person. It is very toxic by absorption through skin. (EPA, 1998)

Signs and Symptoms of Acute Cantharidin Exposure: Acute exposure to cantharidin may produce the following signs and symptoms: salivation, difficulty in swallowing, thirst, severe vesication (blistering) of the upper gastrointestinal tract following ingestion, abdominal pain, vomiting and bloody diarrhea. Excessive, painful and bloody urination may be noted. Tachycardia (rapid heart beat) with normal blood pressure, hypotension (low blood pressure), and abnormal heart conduction are not uncommon. Eye contact may cause irritation with swelling of the lids; dermal contact may cause swelling followed by formation of blisters within 24 hours. Mental confusion, tetanic convulsions and fainting may be noted. Ataxia may progress to coma. Emergency Life-Support Procedures: Acute exposure to cantharidin may require decontamination and life support for the victims. Emergency personnel should wear protective clothing appropriate to the type and degree of contamination. Air-purifying or supplied-air respiratory equipment should also be worn, as necessary. Rescue vehicles should carry supplies such as plastic sheeting and disposable plastic bags to assist in preventing spread of contamination. Inhalation Exposure: 1. Move victims to fresh air. Emergency personnel should avoid self-exposure to cantharidin. 2. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer oxygen or other respiratory support. 3. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures. 4. RUSH to a health care facility! Dermal/Eye Exposure: 1. Remove victims from exposure. Emergency personnel should avoid self-exposure to cantharidin. 2. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer oxygen or other respiratory support. 3.Remove and isolate contaminated clothing as soon as possible. 4. If eye exposure has occurred, eyes must be flushed with lukewarm water for at least 15 minutes. 5. Wash exposed skin areas thoroughly with soap and water. 6. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures. 7. RUSH to a health care facility! Ingestion Exposure: 1. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer oxygen or other respiratory support. 2. DO NOT induce vomiting or attempt to neutralize! 3. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures. 4. Activated charcoal may be administered if victims are conscious and alert. Use 15 to 30 g (1/2 to 1 oz) for children, 50 to 100 g (1-3/4 to 3-1/2 oz) for adults, with 125 to 250 mL (1/2 to 1 cup) of water. 5. Promote excretion by administering a saline cathartic or sorbitol to conscious and alert victims. Children require 15 to 30 g (1/2 to 1 oz) of cathartic; 50 to 100 g (1-3/4 to 3-1/2 oz) is recommended for adults. 6. RUSH to a health care facility! (EPA, 1998)

Basic Treatment: Establish a patent airway. Suction if necessary. Encourage patient to take deep breaths. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . /Irritating materials/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Early intubation at the first sign of upper airway obstruction may be necessary. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . Treat seizures with diazepam (Valium) ... Use proparacaine hydrochloride to assist eye irrigation ... . /Irritating materials/

WHEN TAKEN ORALLY IT CAUSES VOMITING, PURGING, ABDOMINAL PAIN, AND SHOCK. ... /IT/ IRRITATES ENTIRE URINARY TRACT. IRRITATION OF BLADDER CAUSES URGENCY OF URINATION, AND IRRITATION OF URETHRA MAY RESULT IN PRIAPISM.|DEATH MAY OCCUR RAPIDLY IN HYPOVOLEMIC SHOCK.|... IN CONTACT WITH HUMAN ... EYES CAUSES CONJUNCTIVITIS, KERATITIS, AND IRITIS, WITH MUCH EDEMA OF THE LIDS.|VESICANT CONTACTS SKIN WHEN BEETLE IS KILLED BY CRUSHING BLOW ... INITIAL TISSUE REACTION IS ERYTHEMA FOLLOWED BY VESICLE FORMATION WITHIN 24 HR.|For more Human Toxicity Excerpts (Complete) data for CANTHARIDINE (12 total), please visit the HSDB record page.

Cantharides

IT IS AVAILABLE AS CANTHARIDIN COLLODION (CANTHARONE), CANTHARIDIN (0.7%) IN A FILM-FORMING VEHICLE CONTAINING ACETONE, ETHOCEL, FLEXIBLE COLLODION, ETHER (35%) AND ALCOHOL (11%).|Cantharone (Seres). Liquid containing cantharidin 0.7% in a vehicle containing ether 35%, acetone, ethocel, and flexible collodion in 7.5 ml containers.

4,7-Epoxyisobenzofuran-1,3-dione, hexahydro-3a,7a-dimethyl-, (3aR,4S,7R,7aS)-rel-: ACTIVE|CANTHARIDIN IS ANHYDRIDE OF ... CANTHARIDIC ACID, WHICH FORMS BIOLOGICALLY ACTIVE SOL SALTS WITH ALKALI.|Cantharis vesicatoria. Habitat: southern and central Europe, mainly upon Oleaceae and Caprifoliaceae. Constituents: 0.6-1% cantharidin, 10-15% fat, resinous substances, acetic and uric acids. /Cantharides/|Active principle of cantharides and other insects in notorious "Spanish Fly" aphrodisiac.

Cantharidin has been determined in plasters containing preparations of cantharides by GC.

CANTHARIDIN WAS DETECTED QUALITATIVELY BY TLC ON SILICA GEL PLATES & QUANTITATED BY GC USING CAFFEINE AS AN INTERNAL STD. ANALYTES WERE BLOOD AND TISSUES OF ANIMALS.|EXPTL ANIMALS GIVEN CANTHARIDIN OF DRIED PREPN OF BLISTER BEETLES TO SIMULATE NATURALLY OCCURRING TOXICOSIS. SENSITIVE HPLC METHOD DEVELOPED TO DETECT TOXIN IN EXTRACTS OF INGESTA, FLUIDS & TISSUES FROM SEVERELY POISONED ANIMALS.|ANALYSIS OF URINE AND STOMACH CONTENTS OF CATTLE BY GC/MS.|METHOD FOR CANTHARIDIN USING HPLC WAS APPLIED TO FIELD SPECIMENS FROM HORSES & SHEEP WITH BLISTER BEETLE POISONING. STOMACH CONTENT & URINE WERE ANALYZED.|For more Clinical Laboratory Methods (Complete) data for CANTHARIDINE (6 total), please visit the HSDB record page.