COLCHICINE

COLCHICINE
ACETAMIDE, N-(5,6,7,9-TETRAHYDRO-1,2,3,10- TETRAMETHOXY-9-OXOBENZO(alpha)HEPTALEN-7-YL)-
ACETAMIDE, N-(5,6,7,9-TETRAHYDRO-1,2,3,10- TETRAMETHOXY-9-OXOBENZO(alpha)HEPTALEN-7-YL)-,(S)-
7-ACETAMIDO-6,7-DIHYDRO-1,2,3,10-TETRAMETHOXY-
BENZO(a)HEPTALEN-9(5H)-ONE
N-ACETYL TRIMETHYLCOLCHICINIC ACID METHYLETHER
BENZO(a)HEPTALEN-9(5H)-ONE
BENZO(a)HEPTALEN-9(5H)-ONE, 7-ACETAMIDO-6,7-
DIHYDRO-1,2,3,10-TETRAMETHOXY-
COLCHICENOS
COLCHICIN (German)
COLCHICINA (Italian)
COLCHICINUM
7-alpha-H-COLCHICINE
7-alphaH-COLCHICINE
COLCHINEOS
COLCHISOL
COLCIN
COLSALOID
CONDYLON
N-(5,6,7,9-TETRAHYDRO-1,2,3,10-TETRAMETHOXY -9-OXOBENZO(alpha)HEPTALEN-7-YL)-ACETAMIDE
(S)-N-(5,6,7,9-TETRAHYDRO-1,2,3,10-TETRAMETHOXY -9-OXOBENZO[a]HEPTALEN-7-YL)-ACETAMIDE

IDENTIFIERS

CAS REGISTRY NUMBER

64-86-8(Colchicine)

NIOSH/RTECS NUMBER

GH 0700000

UN/NA NUMBER

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.

DESIGNATIONS

NSC NUMBER:757

MOLECULAR FORMULA

C22-H25-N-O6 (Prod Info COLCRYS(TM) oral tablets, 2009)

ERG GUIDE NUMBER

151-SUBSTANCES - TOXIC (NON-COMBUSTIBLE)

SYNONYM REFERENCE

(RTECS , 1991; Budavari, 1989; EPA, 1985; HSDB , 1991; Sax & Lewis, 1989)

USES/FORMS/SOURCES

USES

Colchicine is a naturally occurring alkaloid found in Colchicum autumnale at a concentration of approximately 0.1%.
Colchicine is indicated for the treatment of acute gout flares when taken at the first sign of a flare (Prod Info COLCRYS(TM) oral tablets, 2014).
Colchicine is indicated for the treatment of familial Mediterranean fever (FMF) in adults and children aged 4 years and older (Prod Info COLCRYS(TM) oral tablets, 2014).
Colchicine is indicated for the prophylaxis of gout flares (Prod Info MITIGARE(TM) oral capsules, 2014), including flares that may occur with initiation of uric acid-lowering therapy; at least 6 months of prophylaxis may be necessary (Prod Info COLCRYS(TM) oral tablets, 2014).

FORMS

Colchicine is available as 0.6 mg tablets and capsules (Prod Info COLCRYS(TM) oral tablets, 2014; Prod Info MITIGARE(TM) oral capsules, 2014). It is also available in combination with probenecid (colchicine 0.5 mg and probenecid 500 mg) (Prod Info probenecid colchicine oral tablets, 2009).
Intravenous colchicine products, including compounded injectable colchicine products, that do not have FDA approval, have been associated with serious adverse events, including low blood cell counts, cardiac events, organ failure, and death. Due to errors in the preparation of the compounded product, it was 8 times more potent than the amount stated on the label (United States Food and Drug Administration, 2008).

-CLINICAL EFFECTS

GENERAL CLINICAL EFFECTS

USES: Colchicine is a natural alkaloid found in plants such as the autumn crocus (Colchicum Autumnale) and glory lily (Gloriosa superba). As a medication, it functions as an antimitotic and anti-inflammatory agent used to treat gout, familial Mediterranean fever, secondary amyloidosis, and scleroderma. Exposure occurs by oral and IV routes.

PHARMACOLOGY: Colchicine binds to tubulin, a main component of microtubules, and causes cytoskeletal changes. Its anti-inflammatory properties are due to inhibiting the migration of leukocytes and proinflammatory cytokines into affected tissues. Finally, it inhibits uric acid crystal deposition in gout.

TOXICOLOGY: Colchicine inhibits mitosis of dividing cells and functions as a microtubule or spindle poison. In overdose, it preferentially affects rapidly dividing cells. In high concentrations it is a general cellular poison.

EPIDEMIOLOGY: Poisoning is very uncommon but causes significant morbidity and mortality.

WITH POISONING/EXPOSURE

MILD TO MODERATE POISONING: Mild overdose causes mainly nausea, vomiting, diarrhea, and abdominal pain.
SEVERE POISONING: Severe overdose causes clinical findings in 3 phases but may be delayed initially a few hours:

PHASE I (0 TO 24 HOURS) – GASTROINTESTINAL: Nausea, vomiting, diarrhea (bloody), abdominal pain, dehydration, leukocytosis, volume depletion, and hypotension.
PHASE II (1 TO 7 DAYS) – MULTIORGAN SYSTEM FAILURE: Possible risk of sudden cardiac death, dysrhythmias; confusion, coma, seizures; pancytopenia, renal failure, hepatic failure, sepsis, acute lung injury, electrolyte imbalances, rhabdomyolysis. Patients with severe overdose may die during this phase.
PHASE III (OVER 7 DAYS) – RECOVERY OR DEATH: Alopecia; myopathy, neuropathy, myoneuropathy, or rebound leukocytosis; death usually is caused by respiratory failure, intractable shock, dysrhythmias, and cardiovascular collapse.

FACTORS ASSOCIATED WITH POOR PROGNOSIS POST-INGESTION: A large dose; increased INR; WBC greater than 18K within 24 hours of ingestion; cardiogenic shock within 72 hours.

WITH THERAPEUTIC USE

ADVERSE EFFECTS: COMMON: At therapeutic doses, gastrointestinal symptoms (nausea, vomiting, diarrhea, and abdominal pain) are commonly seen. LESS COMMON: Alopecia and anorexia may occur less frequently. RARE: Agranulocytosis, aplastic anemia, dysrhythmias, bone marrow suppression, hepatotoxicity, myopathy, peripheral neuritis, and rash may rarely be observed.
DRUG INTERACTIONS: Substances that inhibit CYP 3A4 (eg; atazanavir, erythromycin, clarithromycin, ketoconazole, nefazodone, and grapefruit juice) and substances that inhibit P-glycoprotein (eg; cyclosporine, ranolazine) increase colchicine plasma concentrations, and cause toxicity at lower doses.

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

SUMMARY

PHARMACOLOGY: Colchicine binds to tubulin, a main component of microtubules, and causes cytoskeletal changes. Its anti-inflammatory properties are due to inhibiting the migration of leukocytes and proinflammatory cytokines into affected tissues. Finally, it inhibits uric acid crystal deposition in gout.
TOXICOLOGY: Colchicine inhibits mitosis of dividing cells and functions as a microtubule or spindle poison. In overdose, it preferentially affects rapidly dividing cells. In high concentrations it is a general cellular poison.
EPIDEMIOLOGY: Poisoning is very uncommon but causes significant morbidity and mortality.
ADVERSE EFFECTS: COMMON: At therapeutic doses, gastrointestinal symptoms (nausea, vomiting, diarrhea, and abdominal pain) are commonly seen. LESS COMMON: Alopecia and anorexia may occur less frequently. RARE: Agranulocytosis, aplastic anemia, dysrhythmias, bone marrow suppression, hepatotoxicity, myopathy, peripheral neuritis, and rash may rarely be observed.
DRUG INTERACTIONS: Substances that inhibit CYP 3A4 (eg; atazanavir, erythromycin, clarithromycin, ketoconazole, nefazodone, and grapefruit juice) and substances that inhibit P-glycoprotein (eg; cyclosporine, ranolazine) increase colchicine plasma concentrations, and cause toxicity at lower doses.
MILD TO MODERATE POISONING: Mild overdose causes mainly nausea, vomiting, diarrhea, and abdominal pain.
SEVERE POISONING: Severe overdose causes clinical findings in 3 phases but may be delayed initially a few hours:

PHASE I (0 TO 24 HOURS) – GASTROINTESTINAL: Nausea, vomiting, diarrhea (bloody), abdominal pain, dehydration, leukocytosis, volume depletion, and hypotension.
PHASE II (1 TO 7 DAYS) – MULTIORGAN SYSTEM FAILURE: Possible risk of sudden cardiac death, dysrhythmias; confusion, coma, seizures; pancytopenia, renal failure, hepatic failure, sepsis, acute lung injury, electrolyte imbalances, rhabdomyolysis. Patients with severe overdose may die during this phase.
PHASE III (OVER 7 DAYS) – RECOVERY OR DEATH: Alopecia; myopathy, neuropathy, myoneuropathy, or rebound leukocytosis; death usually is caused by respiratory failure, intractable shock, dysrhythmias, and cardiovascular collapse.

FACTORS ASSOCIATED WITH POOR PROGNOSIS POST-INGESTION: A large dose; increased INR; WBC greater than 18K within 24 hours of ingestion; cardiogenic shock within 72 hours.

ACID-BASE

ACIDOSIS: Significant metabolic acidosis may develop with severe poisoning (Blackham et al, 2007; Maxwell et al, 2002; Hung et al, 2001).

CARDIOVASCULAR

CARDIAC ARREST: Cardiac arrest with subsequent fatalities were reported following colchicine ingestions (Stapczynski et al, 1981) of 18 (Hobson & Rankin, 1986) to 26.5 mg (Maxwell et al, 2002).
ATRIOVENTRICULAR BLOCK: Complete atrioventricular block and death were reported in a patient who received IV colchicine therapy for 2 days (Wallace & Singer, 1988).
HYPOTENSIVE EPISODE: Hypotension may occur during the early phase of toxicity (Baud et al, 1995; Blackham et al, 2007; Harris et al, 2000) or may develop in later stages (Mullins et al, 2000a; Hung et al, 2001; Maxwell et al, 2002). Early monitoring for serum troponin I and ECG may alert the clinician to impending cardiovascular collapse (Mullins et al, 2000a). Acute circulatory insufficiency within 72 hours is associated with high mortality (Sauder et al, 1983; Mullins et al, 2000a).
CARDIOMYOPATHY: Decreased cardiac index and increased systemic vascular resistance have been reported (Baud et al, 1995; Sauder et al, 1983). Elevated Serum troponin I (TnI) with myocardial depression was reported in 1 case secondary to severe colchicine poisoning (Mullins et al, 2000). Myocardial injury with elevated ST segment, decreased contractility, and decreased pulmonary artery wedge pressured occurred in 1 case following ingestion of 24 mg (Murray et al, 1983).

DERMATOLOGIC

ALOPECIA: Reversible hair loss has been reported, usually developing up to 3 weeks after toxic exposure (Blackham et al, 2007; Bicer et al, 2007; Harris et al, 2000). Complete scalp baldness and loss of secondary sexual hair occurs over days to weeks, with variable recovery over weeks to months (Harris & Gillett, 1998).

ENDOCRINE

HYPERGLYCEMIA: Colchicine inhibits release of insulin from beta cells (Boehnert & McGuigan, 1983).

FLUID ELECTROLYTE

ELECTROLYTE DEPLETION: Marked hypovolemia, resulting from vomiting and persistent diarrhea, is common following an overdose. Hypocalcemia, hypokalemia, and hypophosphatemia may develop following overdose (Kubler, 2000; Huang et al, 2007; Blackham et al, 2007) and can persist for 10 days. Magnesium may also be low (Murray et al, 1983).

GASTROINTESTINAL

GASTROENTERITIS: Nausea, vomiting, severe diarrhea, and hemorrhagic gastroenteritis commonly occur 2 to 12 hours post ingestion and result in loss of fluids and electrolytes (Blackham et al, 2007; Huang et al, 2007; Gilbert & Byard, 2002).

GENITOURINARY

RENAL FAILURE: Acute oliguric renal failure develops in patients with severe toxicity (Borras-Blasco et al, 2005; Berlin et al, 1997; Hung et al, 2001). Acute renal failure occurred in 6 patients who died after receiving cumulative IV doses of colchicine (ranging from 5.5 to 19 mg), which exceeded the recommended cumulative maximum dose of 2 to 4 mg during a course of therapy (Bonnel et al, 2002). Azotemia, proteinuria, myoglobinuria, and hematuria have also been reported with exposure (Wallace, 1974; Baud et al, 1992; Van Der Naalt et al, 1992).

HEMATOLOGIC

PANCYTOPENIA: Rarely, colchicine toxicity with pancytopenia may occur following therapeutic use. This may be seen in patients with risk factors, such as renal insufficiency, hepatic dysfunction, drug interactions, and IV colchicine use (Yoon, 2001).

CASE SERIES: Sixteen of 20 patients (80%) who died following IV administration of colchicine developed significant myelosuppression prior to death. Colchicine doses that were administered ranged from 5.5 to 19 mg, exceeding the cumulative maximum dose of 2 to 4 mg recommended during a course of therapy (Bonnel et al, 2002).

ABNORMAL COAGULATION TESTS: A consumptive coagulopathy with prolongation of coagulation times, a decrease in fibrinogen, elevated fibrin degradation products and thrombocytopenia has been reported (Bismuth et al, 1977; Ferrannini & Pentimone, 1984).
LEUKOCYTOSIS: Marked elevations in the white blood cell count are common early in the course of intoxication due to significant volume depletion (Kocak et al, 2008; Kubler, 2000; Baud et al, 1995). A rebound leukocytosis typically follows initial leukopenia (Folpini & Furfori, 1995; Nadius et al, 1977; Murray et al, 1983).
DISSEMINATED INTRAVASCULAR COAGULATION (DIC): Severe overdoses may result in DIC at the second stage of poisoning (24 hours or more after ingestion) (Bicer et al, 2007; Weakley-Jones et al, 2001).

CASE SERIES: Disseminated intravascular coagulation, with subsequent death, occurred in 4 patients who received IV colchicine in cumulative doses ranging from 5.5 to 19 mg, which exceeds the recommended cumulative maximum dose of 2 to 4 mg (Bonnel et al, 2002).

HEPATIC

LIVER DAMAGE: Acute renal and hepatic failure have been reported following severe overdose (Bruns, 1968; Hung et al, 2001). In colchicine fatalities, autopsies have revealed focal hepatocyte necrosis (Gilbert & Byard, 2002; Weakley-Jones et al, 2001).

IMMUNOLOGIC

SYSTEMIC INFECTION: Following severe poisoning, widespread invasive fungal or bacterial invasion of the aerodigestive tract may occur. Infections complicating severe bone marrow suppression are common. Overwhelming sepsis, a complication of colchicine toxicity, may be a cause of death (Kocak et al, 2008; Iacobuzio-Donahue et al, 2001; Hung et al, 2001).

MUSCULOSKELETAL

RHABDOMYOLYSIS: A limited number of cases of therapeutic colchicine-induced rhabdomyolysis have been reported, most in conjunction with risk factors, such as renal insufficiency and liver dysfunction. Following discontinuation of colchicine, rhabdomyolysis has been reversible (Boomershine, 2002).
MYOPATHY: Colchicine myopathy occurs in patients with gout who take customary doses. It presents with proximal weakness, increased serum creatinine kinase, and axonal neuropathy (Altiparmak et al, 2002; Van Der Naalt et al, 1992; Kuncl et al, 1987).

NEUROLOGIC

COMA: CNS depression progressing to coma may develop following overdose (Clevenger et al, 1991).
PARALYSIS: Toxic doses produce mental confusion, loss of deep tendon reflexes and ascending paralysis (Nadius et al, 1977; Carr, 1965). Peripheral neuropathy and ascending paralysis may occur during the second phase of poisoning, up to 7 days after ingestion (Maxwell et al, 2002).
SEIZURE: Seizures may occur following overdose (Simons & Kingma, 1989; Heaney et al, 1976; Carr, 1965) and are usually seen in the second phase of poisoning, up to 7 days after ingestion (Maxwell et al, 2002).
TOXIC ENCEPHALOPATHY: One case of encephalopathy with respiratory failure and pancytopenia 3 days following exposure was reported (Berlin et al, 1997).

RESPIRATORY

APNEA: Respiratory arrest may result from an ascending paralysis occurring more than 4 hours post exposure (Murray et al, 1983).
RESPIRATORY DISTRESS: Severe cases of colchicine toxicity may result in adult respiratory distress syndrome (ARDS), which generally occurs in the second stage of poisoning (24 hours or more after ingestion) (Milne & Meek, 1998; Kubler, 2000; Weakley-Jones et al, 2001).

VITAL SIGNS

FEVER: Fever may develop following overdose (McIntyre et al, 1994; Baud et al, 1995; Berlin et al, 1997; Guven et al, 2002; Kocak et al, 2008) and can persist for several weeks (Murray et al, 1983).

CHRONIC CLINICAL EFFECTS

In cases where diarrhea develops rapidly and where visceral compromise is not present, chronic toxicity from colchicine is rare because treatment is usually stopped upon development of diarrhea (Montseny et al, 1996).

Effects of chronic exposure to colchicine are mainly known from its use as a drug in human medicine. A particular form of neuromyopathy and myocardial failure are characteristic features of chronic colchicine toxicity (Montseny et al, 1996).

Reversible myopathy and neuropathy with generalized myalgia, proximal muscle weakness, paresthesias, and elevated serum levels of muscle enzymes have developed in patients receiving chronic colchicine therapy (Llama et al, 1994) Dedeyn et al, 1995). Profound muscle weakness and respiratory insufficiency can ensue from a neuropathy of the pure motor type (Neuss et al, 1986; Riggs et al, 1986; Kuncl et al, 1987). Evidence of muscle damage (rhabdomyolysis, myoglobinuria, and myopathy) has been seen with chronic use of colchicine for gout (Kontos, 1962).

A creatinine clearance of 50 mL/min or less was found to be the best practical predictor of risk of colchicine myotoxicity in patients receiving the drug chronically for prevention of recurrent gout (Wallace et al, 1991).

Chronic use has also caused nausea, diarrhea, vomiting, and abdominal pain, with resulting electrolyte derangement (Neuss et al, 1986). Elevations in serum levels of liver enzymes have been seen after chronic colchicine treatment (Ferrannini & Pentimone, 1984).

Various signs of bone marrow depression have also been seen, including thrombocytopenia, leukopenia, anemia, and granulocytopenia (Ferrannini & Pentimone, 1984; Finklestein et al, 1987). Multiple organ failure and bone marrow suppression developed in a 24-year-old woman after suicidal ingestion of 50 mg of colchicine (Folpini & Furfori, 1995).

-FIRST AID

FIRST AID AND PREHOSPITAL TREATMENT

Consider activated charcoal if vomiting is controlled.

ACTIVATED CHARCOAL

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).

CHARCOAL DOSE

Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).

Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

ADVERSE EFFECTS/CONTRAINDICATIONS

Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).

-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

Since colchicine overdose invariably causes gastrointestinal toxicity, specifically prolonged vomiting and diarrhea, the use of emetics or cathartics may only be appropriate prior to symptom onset. The occurrence of gastrointestinal symptoms denotes severe toxicity and indicates the need for aggressive management.
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

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.
Patient should be observed for at least 12 hours following history of acute exposure (a latent period of 2 to 12 hours occurs between exposure and onset of symptoms).
Monitor fluid and electrolytes carefully and replace as needed. Monitor potassium levels carefully.
Respiratory support should be provided with mechanical ventilation as needed.
HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (ADULT: begin infusion at 0.5 to 1 mcg/min; CHILD: begin infusion at 0.1 mcg/kg/min); titrate to desired response.
ABDOMINAL PAIN - Severe abdominal pain should be controlled with common analgesics or opiates with or without atropine. Be alert for possible toxic ileus.

-RANGE OF TOXICITY

MINIMUM LETHAL EXPOSURE

GENERAL/SUMMARY

Reported fatal doses of colchicine vary from 7 to 60 milligrams (Ellwood & Robb, 1971) and doses of 0.5 to 0.8 milligram/kilogram may be fatal (Bismuth et al, 1977; Rochdi et al, 1992). 11 to 14 milligrams intravenously or orally has led to death (Stennerman & Hayashi, 1971; Gaultier et al, 1969; Simons & Kingma, 1989).
PROGNOSIS: Factors associated with a poor prognosis following an overdose include amount ingested, an increase in prothrombin time, and an increase in white blood cell count = 18 x 10(9)/L within 24 hours of the ingestion, and the onset of cardiogenic shock within 72 hours of hospital admission. Prognosis does not appear to be related to colchicine plasma concentrations measured on admission, but rather to plasma toxicokinetics. The authors suggested a larger multi-center study to confirm these results (Megarbane et al, 2001).

ADULT/CASE REPORTS

A 30-year-old man died due to cardiovascular collapse about 35 hours following a colchicine overdose of 39.6 milligrams (0.40 milligrams/kilogram). Serum colchicine concentration reported 13 hours before death (approximately 22 hours after ingestion) was 29 nanograms/milliliter (Mullins et al, 2000).
A fatality 45 hours after ingestion of 750 milligrams of colchicine (9.5 milligrams/kilogram) powder has been described (Davies et al, 1988).
Fatal doses of intravenous colchicine given to patients with gout ranged from 7.2 milligrams (plus 1.2 milligrams orally) in 5 days to 18 milligrams in 11 days (Wallace & Singer, 1988; Roberts et al, 1987; Stennerman & Hayashi, 1971).
A 60-year-old woman entered the emergency department 3 days after receiving a total dose of 8 milligrams of intravenous colchicine, for an acute gouty attack, complaining of muscle weakness, fever, and respiratory distress. The patient developed profound bone marrow depression, toxic ileus, stomatitis, and renal failure. Death occurred 21 days after hospitalization (Luciani, 1989).
A patient with familial Mediterranean fever and amyloidosis almost died after taking 1 milligram daily chronically (Caraco et al, 1992).
30 milligrams proved fatal in a 36-year-old (Clevenger et al, 1991).
A 73-year-old man developed renal and respiratory failure with subsequent death approximately 18 hours after receiving 1 mg of IV colchicine for treatment of an acute gout attack. The patient had also been taking 0.6 mg colchicine orally the previous eight days (Jones et al, 2002).
A 37-year-old woman became comatose and developed hypotension, bradycardia, cyanosis, and dyspnea, necessitating intubation and mechanical ventilation, approximately 30 hours after intentionally ingesting 38 1-mg colchicine tablets. Cardiac arrest occurred approximately 36 hours post-ingestion. Despite cardiopulmonary resuscitative efforts, the patient died (Aghabiklooei et al, 2014).

CASE SERIES

A review of the medical literature as well as from the FDA's Adverse Event Reports System (AERS) database identified 20 deaths, occurring between 1983 to 2000, associated with IV administration of colchicine. All 20 patients received cumulative IV doses ranging from 5.5 to 19 mg, which exceeds the recommended maximum cumulative dose of 2 to 4 mg during a course of therapy. Sixteen of the 20 patients (80%) developed significant myelosuppression prior to death. Death occurred within 1 to 40 days following IV administration of colchicine (Bonnel et al, 2002).
One study done in France reported 150 cases of exposure. With less than 0.5 milligram/kilogram there were no deaths, but some isolated diarrhea and vomiting. With doses of 0.5 to 0.8 milligram/kilogram there was 10 percent mortality and marrow aplasia, and with doses of greater than 0.8 milligram/kilogram there was 10 percent mortality and cardiogenic shock (Bismuth et al, 1977).

PEDIATRIC

Four young children (12 months to 3.5 years) inadvertently ingested colchicine and developed characteristic clinical symptoms. Three patients had evidence of gastrointestinal symptoms and CNS depression (lethargy or coma) at the time of admission. One patient had no symptoms, but was evaluated within 1.5 hours of exposure. The dose ingested ranged between 0.37 to 1.72 mg/kg. Of the two children that died, the dose ingested was 0.37 mg/kg and 1 mg/kg, and they were admitted 13 and 19 hours after ingestion, respectively. The authors concluded that both the amount ingested, and the duration between ingestion and medical care can influence outcome (Atas et al, 2004).
A 10-year-old boy presented with severe nausea and vomiting approximately 4 hours after intentionally ingesting 30 1-mg colchicine tablets. Despite aggressive decontamination, including multiple doses of activated charcoal, the patient developed tachycardia, hypotension, fever, epigastric tenderness, hematuria, and severe tachypnea, requiring intubation. An ECG indicated non-specific T-wave changes. Continuous renal replacement therapy was initiated 26 hours post-ingestion and continued for 20 hours; however, the patient subsequently developed upper gastrointestinal hemorrhage, thrombocytopenia, and rhabdomyolysis, unresponsive to supportive therapy, including vitamin K, fresh frozen plasma, and platelet administration. Three days post-ingestion, the patient continued to deteriorate clinically, developing icter, severe agitation, pre-orbital edema, eyelash ecchymosis, and bleeding from his IV sites, with subsequent death due to acute respiratory distress syndrome and disseminated intravascular coagulopathy (Aghabiklooei et al, 2014).
A 12-year-old girl, receiving colchicine therapy for treatment of familial Mediterranean fever, presented to the ED with diarrhea, vomiting, and abdominal pain. Physical examination was consistent with signs of dehydration. Interview of the patient's family indicated a suspected ingestion of approximately 35 colchicine tablets (17 mg [0.48 mg/kg]) approximately 11 hours before presentation. Despite administration of IV fluids, her condition worsened and she was intubated and mechanically ventilated due to respiratory failure. Within a few hours, she developed decompensated shock and treatment with IV dopamine, epinephrine, and norepinephrine was initiated, with an increase in doses as her circulation worsened. However, her condition continued to deteriorate with non-palpable pulses, pulmonary edema, anuria, metabolic acidosis, and impairment of cardiac contractions with an ejection fraction of 40%. Despite continued aggressive supportive therapies, she died approximately 29 hours post-ingestion (Vatansever et al, 2015).

MAXIMUM TOLERATED EXPOSURE

CASE REPORTS

ADULT

A case of survival (prolonged recovery) was reported after intraurethral administration of 50 milligrams of colchicine (Nadius et al, 1977).
Two cases of ingestions of about 30 milligrams or more of colchicine were reported in suicide attempts. Polyneuritis and peripheral neuropathy were observed in these patients.(Mouren et al, 1969).
Baldwin et al (1990) reported a case of a 29-year-old man that mistakenly "snorted" (nasal insufflation) approximately 200 milligrams of colchicine powder instead of methamphetamine. The patient experienced gastrointestinal distress, myalgia, hypocalcemia, and thrombocytopenia. With supportive care and electrolyte replacement he was discharged after 8 days (Baldwin et al, 1990).
A 48-year-old man developed acute renal failure after ingesting more than 20 tablets of colchicine (total dose greater than 10 grams). He recovered with supportive care (Huang et al, 2007).
A 22-year-old woman presented to the emergency department with nausea, vomiting, abdominal pain, and diarrhea after ingesting 24 0.5-mg colchicine tablets. Physical exam revealed hypotension and sinus tachycardia, and laboratory analysis indicated elevated hepatic enzyme and creatine kinase concentrations. With supportive care, the patient gradually recovered and was discharged approximately 3 weeks post-ingestion (Altiparmak et al, 2002).
A 26-year-old woman developed abdominal pain, diarrhea, alopecia, elevated hepatic enzyme levels, transient myelosuppression, pneumonia, and vaginal candidiasis after intentionally ingesting 27.5 mg colchicine, as well as 600 mg famotidine and 5 grams paracetamol. The patient completely recovered with supportive care (Kocak et al, 2008).
CASE REPORT: A 25-year-old woman presented with vomiting approximately 4 hours after intentionally ingesting 25 1-mg colchicine tablets. Following administration of multiple doses of activated charcoal and 24 hours of observation, the patient was discharged without developing signs or symptoms of severe toxicity. Approximately 5 days later, the patient presented with severe back pain and thrombocytopenia (59,000). Three days post-admission, following administration of platelets, laboratory data revealed a white blood cell count of 2300, which increased to 5200 following administration of granulocyte colony stimulating factors. With supportive therapy, the patient continued to improve and was discharged 5 days later (Aghabiklooei et al, 2014).

CASE SERIES

In a series of 10 patients with colchicine overdose, those who ingested less than 0.3 milligrams/kilogram (maximum 0.28 milligrams/kilogram) survived (Rochdi et al, 1992).
Two patients developed severe myelosuppression following overdose ingestions of colchicine in amounts ranging from 20 to 48 mg. Both patients recovered following administration of granulocyte colony stimulating factor (G-CSF) (Harris et al, 2000).

PEDIATRIC

Viets (1977) reported a case of acute overdose in a 14-year-old girl who took 60 milligrams and survived. The patient developed severe toxicity including gastroenteritis with abdominal pain, persistent hypokalemia, toxic ileus, pancytopenia with epistaxis, liver damage, hallucinations, and complete alopecia .
A late diagnosis (3 to 4 days post-ingestion) of colchicine poisoning was made in a 4-year-old girl who ingested 1.3 to 1.5 milligrams/kilogram of colchicine. The girl developed gastrointestinal bleeding, bone marrow depression, confusion, muscle pain, severe skin lesions, and alopecia. Following symptomatic care, she recovered (Guven et al, 2002).
A 3-year-old girl ingested 20 colchicine tablets (0.7 mg/kg) and subsequently developed hypotension, hyponatremia, hypocalcemia, disseminated intravascular coagulation, pancytopenia, and a seizure. The patient recovered following aggressive supportive therapy (Bicer et al, 2007).
A 91.kg adolescent girl presented to the hospital with nausea, vomiting, and profuse diarrhea a day after intentionally ingesting up to a maximum of 43 0.5-mg colchicine tablets (0.24 mg/kg). With supportive care, the patient recovered and was discharged 6 days later without sequelae (Gresham et al, 2013).

A 6-year-old girl presented to the emergency department approximately 12 hours after ingesting colchicine at a possible maximum ingested dose of 0.9 mg/kg. She developed acute encephalopathy, moderate dehydration, acute respiratory distress syndrome, and multi-organ failure. Due to her continued clinical deterioration, plasma exchange was initiated. Following 2 plasma exchange sessions without plasma loss, her organ failures resolved, with improvement in her respiratory function. She was discharged 11 days post-admission (Demirkol et al, 2015).

Carcinogenicity Ratings for CAS64-86-8 :

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 CAS64-86-8 (U.S. Environmental Protection Agency, 2011):

Not Listed

TOXICITY VALUES

References: RTECS, 1991 Sax & Lewis, 1989 ITI, 1988
- LD50- (INTRAPERITONEAL)GERBIL:
- LD50- (INTRAPERITONEAL)GUINEA_PIG:
- LD50- (INTRAPERITONEAL)HAMSTER:
- LD50- (INTRAMUSCULAR)MOUSE:
- LD50- (INTRAPERITONEAL)MOUSE:
- LD50- (INTRAVENOUS)MOUSE:
- LD50- (ORAL)MOUSE:
- LD50- (SUBCUTANEOUS)MOUSE:
- LD50- (INTRAPERITONEAL)RAT:
- LD50- (INTRAVENOUS)RAT:
- LDLo- (ORAL)CAT:
- LDLo- (SUBCUTANEOUS)CAT:
- LDLo- (ORAL)DOG:
- LDLo- (SUBCUTANEOUS)DOG:
- LDLo- (ORAL)GUINEA_PIG:
- LDLo- (INTRAVENOUS)HUMAN:
- LDLo- (ORAL)HUMAN:
- LDLo- (INTRAPERITONEAL)MOUSE:
- LDLo- (SUBCUTANEOUS)MOUSE:
- LDLo- (INTRAVENOUS)RABBIT:
- LDLo- (ORAL)RABBIT:
- LDLo- (SUBCUTANEOUS)RABBIT:
- LDLo- (INTRACEREBRAL)RAT:
- LDLo- (INTRAVENOUS)RAT:
- LDLo- (SUBCUTANEOUS)RAT:

-STANDARDS AND LABELS

WORKPLACE STANDARDS

ACGIH TLV Values for CAS64-86-8 (American Conference of Governmental Industrial Hygienists, 2010):

Not Listed

AIHA WEEL Values for CAS64-86-8 (AIHA, 2006):

Not Listed

NIOSH REL and IDLH Values for CAS64-86-8 (National Institute for Occupational Safety and Health, 2007):

Not Listed

OSHA PEL Values for CAS64-86-8 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

Not Listed

OSHA List of Highly Hazardous Chemicals, Toxics, and Reactives for CAS64-86-8 (U.S. Occupational Safety and Health Administration, 2010):

Not Listed

ENVIRONMENTAL STANDARDS

EPA CERCLA, Hazardous Substances and Reportable Quantities for CAS64-86-8 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA CERCLA, Hazardous Substances and Reportable Quantities, Radionuclides for CAS64-86-8 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA RCRA Hazardous Waste Number for CAS64-86-8 (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 CAS64-86-8 (U.S. Environmental Protection Agency, 2010):

Listed as: Colchicine
Reportable Quantity, in pounds: 10

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

Threshold Planning Quantity, in pounds:

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

Note(s): d

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

EPA SARA Title III, Community Right-to-Know for CAS64-86-8 (40 CFR 372.65, 2006; 40 CFR 372.28, 2006):

Not Listed

DOT List of Marine Pollutants for CAS64-86-8 (49 CFR 172.101 - App. B, 2005):

Not Listed

EPA TSCA Inventory for CAS64-86-8 (EPA, 2005):

Listed as: Acetamide, N-[(7S)-5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo[a]heptalen-7-yl]-

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 CAS64-86-8 (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.

Wear full protective clothing and self-contained breathing apparatus (EPA, 1985).

Avoid bodily contact with material. Wash away any material which may have contacted the body with copious amounts of soap and water (EPA, 1985).

RESPIRATORY PROTECTION

Use of a self-contained breathing apparatus is recommended for fire fighting activities and safe handling and use of colchicine (EPA, 1985).

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 64-86-8.

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.
Colchicine poses only a slight fire potential (EPA, 1985).
As with any drug, solid, nos, avoid breathing dusts and fumes from burning material (EPA, 1985).
- When heated to decomposition, colchicine emits toxic fumes of nitrogen oxides (Sax & Lewis, 1989).
Extinguish fire using agent suitable for type of surrounding fire (EPA, 1985).
Use water in flooding quantities as fog (EPA, 1985).

FLAMMABILITY CLASSIFICATION

NFPA Flammability Rating for CAS64-86-8 (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 CAS64-86-8 (NFPA, 2002):

Not Listed

COMBUSTION TOXICITY

When heated to decomposition, colchicine emits toxic fumes of nitrogen oxides (Sax & Lewis, 1989).

DUST/VAPOR HAZARD

When heated to decomposition, colchicine emits toxic fumes of nitrogen oxides (Sax & Lewis, 1989).

REACTIVITY HAZARD

When heated to decomposition, colchicine emits toxic fumes of nitrogen oxides (Sax & Lewis, 1989).

Colchicine is unstable when exposed to light (Baselt & Cravey, 1989).

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 CAS64-86-8 (AIHA, 2006):

Not Listed

DOE TEEL Values for CAS64-86-8 (U.S. Department of Energy, Office of Emergency Management, 2010):

Listed as Colchicine
TEEL-0 (units = mg/m3): 0.04
TEEL-1 (units = mg/m3): 0.125
TEEL-2 (units = mg/m3): 0.9
TEEL-3 (units = mg/m3): 0.9
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 CAS64-86-8 (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 CAS64-86-8 (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.
Wear full protective clothing and self-contained breathing apparatus (EPA, 1985).
- Avoid bodily contact with material. Wash away any material which may have contacted the body with copious amounts of soap and water (EPA, 1985).

-ENVIRONMENTAL HAZARD MANAGEMENT

POLLUTION HAZARD

Clochicum is a naturally occuring substance, and is abundant in meadows throughout Europe. It is also naturalized in parts of America (HSDB, 2003).

ENVIRONMENTAL FATE AND KINETICS

OTHER

OTHER
- No information on the environmental kinetics of colchicine was found in the references consulted at the time of this review.

ENVIRONMENTAL TOXICITY

No information on the environmental toxicity of colchicine was found in the references consulted at the time of this review.

In a biotest used to observe male nematode, colchicine significantly inhibited the mobility of Heterodera schachtii males when pretreated for 2 or 4 h in a concentration of 100 mmol/L. It is hypothesized that the primary targets of colchicine were the microtubules of motor neurons, interneurons or of the cytoskeleton rather than sensory neuron microtubules, and that a limited adaptation to colchicine took place (Aumann, 1992).

-PHYSICAL/CHEMICAL PROPERTIES

MOLECULAR WEIGHT

399.4 (Prod Info COLCRYS(TM) oral tablets, 2009)

DESCRIPTION/PHYSICAL STATE

Colchicine is a pale yellow, nearly odorless, substance (scales or powder) which darkens on exposure to light. Colchicine has been crystallized from ethyl acetate, which produces pale yellow needles (Prod Info COLCRYS(TM) oral tablets, 2009; Budavari, 1996; Sax & Lewis, 1987). Colchicine is soluble in water (Prod Info COLCRYS(TM) oral tablets, 2009).

When colchicine is heated to decomposition, it emits toxic fumes of nitrogen oxides (Sax & Lewis, 1989).

5.9 (0.5% solution) (Budavari, 1996)

FREEZING/MELTING POINT

MELTING POINT

142-150 degrees C (Budavari, 1996; Sax & Lewis, 1989)
157 degrees C (Budavari, 1996; Sax & Lewis, 1989)

SOLUBILITY

IN WATER

1 g/22 mL

IN ORGANIC SOLVENTS

1 g/220 mL ether
1 g/100 mL benzene
Colchicine is freely soluble in alcohol or chloroform and practically insoluble in petroleum ether (Budavari, 1996; Sax & Lewis, 1989).
Colchicine is soluble in methanol and slightly soluble in carbon tetrachloride (HSDB , 1991).

-REFERENCES

GENERAL BIBLIOGRAPHY

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

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

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

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

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

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

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

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

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

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

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COLCHICINE

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Information to evaluate chemical incidents

Information to evaluate chemical incidents

Information to evaluate chemical incidents