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AMYGDALIN

CASRN: 29883-15-6
Chemical structure for AMYGDALIN
For more information, search the NLM HSDB database.

Human Health Effects:


Human Toxicity Excerpts:
TWO CASES OF LAETRILE (AMYGDALIN) TOXICITY WERE REPORTED IN A 48-YR-OLD WOMAN WITH LYMPHOMA & A 46-YR-OLD MAN WITH A LARGE CELL ANAPLASTIC CARCINOMA OF THE LUNG. THE WOMAN EXHIBITED FEVER, MALAISE, HEADACHE, SEVERE ABDOMINAL CRAMPS, A DIFFUSE MACULAR ERYTHEMATOUS RASH, LYMPHADENOPATHY & HEPATOSPLENOMEGALY FOLLOWING A WEEKLY 6 MG IV INJECTION & 5OO MG 3 TIMES DAILY ORALLY. THE MAN PRESENTED WITH PROGRESSIVE NEUROMUSCULAR WEAKNESS OF BOTH LOWER & UPPER EXTREMITIES FOLLOWING ORAL ADMIN OF 500 MG OF AMYGDALIN DAILY. BOTH CASES OF TOXICITY RESULTING FROM ORAL ADMIN WAS RESOLVED FOLLOWING DISCONTINUATION OF THE DRUG.
[SMITH FP ET AL; LAETRILE TOXICITY: REPORT OF TWO CASES; J AM MED ASSOC 238(SEPT 26) 1361 (1977)] **PEER REVIEWED**

A FATAL LAETRILE (AMYGDALIN) INGESTION BY A 57-YR-OLD FEMALE WITH BREAST CARCINOMA WAS PRESENTED. CYANIDE LEVEL ON ADMISSION TO HOSPITAL WAS 29.0 MCG/DL. THE PT IMPROVED WITH SYMPTOMATIC THERAPY & WAS TRANSFERRED TO ANOTHER HOSPITAL FROM WHICH SHE WAS DISCHARGED 3 DAYS LATER. TWELVE DAYS LATER, THE PT WAS RETURNED TO THE EMERGENCY DEPARTMENT WITH NO SIGN OF LIFE. AN AUTOPSY REVEALED A CYANIDE LEVEL OF 218 MCG/DL & DOCUMENTED THE CAUSE OF DEATH AS CYANIDE POISONING.
[VOGEL SN ET AL; CYANIDE POISONING; CLIN TOXICOL 18(MAR) 367 (1981)] **PEER REVIEWED**

A NEAR FATAL CASE OF CYANIDE POISONING IS REPORTED IN A 48-YR-OLD WOMAN AFTER A 9 DAY COURSE OF LAETRILE (AMYGDALIN). LAETRILE WAS ADMIN IV, IM, ORALLY, & RECTALLY ALONG WITH A "DETOXIFICATION DIET". BLOOD LEVELS OF CYANIDE ON ADMISSION WERE 116 MUG/DL.
[MORSE DL ET AL; MORE ON CYANIDE POISONING FROM LAETRILE; N ENGL J MED 301(OCT) 892 (1979)] **PEER REVIEWED**

TWO EPISODES OF CYANIDE POISONING OCCURRED IN CHILDREN AFTER INGESTION OF APRICOT KERNELS. THE 1ST EPISODE INVOLVED 8 CHILDREN WHO EXHIBITED TYPICAL SIGNS & SYMPTOMS OF CYANIDE POISONING 2 HR AFTER INGESTION OF LARGE AMOUNTS; 7 CHILDREN RECOVERED & 1 DIED. THE 2ND EPISODE INVOLVED 16 CHILDREN WHO HAD EATEN SWEETS PREPARED FROM KERNELS. SYMPTOMS & SIGNS WERE THE SAME AS THOSE IN THE 1ST GROUP BUT APPEARED 1/2 HR AFTER INGESTION & WERE VERY SEVERE. THREE OF THE CHILDREN DIED.
[LASCH EE, SHAWA R; MULTIPLE CASES OF CYANIDE POISONING BY APRICOT KERNELS IN CHILDREN FROM GAZA, ISRAEL; PEDIATRICS 68(1) 5 (1981)] **PEER REVIEWED**

AMYGDALIN IS A CHEMICAL COMBINATION OF GLUCOSE, BENZALDEHYDE, & CYANIDE FROM WHICH THE LATTER CAN BE RELEASED... AMYGDALIN IS THE MAJOR INGREDIENT OF LAETRILE, & THIS ALLEGED ANTICANCER DRUG HAS ALSO BEEN RESPONSIBLE FOR HUMAN CYANIDE POISONING.
[Doull, J., C.D. Klaassen, and M. D. Amdur (eds.). Casarett and Doull's Toxicology. 2nd ed. New York: Macmillan Publishing Co., 1980., p. 328] **PEER REVIEWED**


Emergency Medical Treatment:


Emergency Medical Treatment:
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The following Overview, *** PLANTS-CYANOGENIC GLYCOSIDES ***, is relevant for this HSDB record chemical.

Life Support:
o   This overview assumes that basic life support measures
       have been instituted.
Clinical Effects:
0.2.1 SUMMARY OF EXPOSURE
    A)  SOURCES: Genera that contain cyanogenic compounds
        include: Eriobotrya (toxic part: pit kernel), Hydrangea
        (toxic part: flower bud), Malus (toxic part: seeds),
        Prunus (toxic part: pit kernel) and Sambucus (toxic
        part: whole plant in particular the root; the fruit is
        harmless with cooking). Common cyanogenic plant species
        include: bitter almond, apricot, peach, apple, black or
        wild cherry, choke berry, elderberry, hydrangea, jetbead
        or jetberry bush, and Puerto Rican lima bean. The
        cyanide content of cyanogenic plant species may vary
        significantly.
    B)  PHARMACOLOGY: Rapid cellular energy fails because
        cyanide can inhibit the final step of the mitochondrial
        electron transport chain. Cyanogenic compounds must be
        metabolized to release cyanide.
    C)  TOXICOLOGY: Amygdalin is the cyanogenic diglucoside
        D-mandelonitrile- beta-D-gentiobioside and is not toxic
        until it is metabolized by the enzyme emulsin which is
        present in the seeds of these plants. Inadvertent
        ingestion of whole seeds or pits is unlikely to result
        in acute cyanide toxicity. Toxicity occurs after
        enzymatic hydrolysis in the GI tract. Onset of symptoms
        is often delayed up to 2 hours or more after ingesting
        masticated pits that contain amygdalin. The most common
        plants to produce human cyanide toxicity in the US are
        the seeds of the Rosacea family, including apricots
        (Prunus armeniaca) bitter almond (Prunus amygdalus),
        peach (Prunus persica), pear (Pyrus communis), apple
        (Malus sylvestris) and plum (Prunus domestica).
    D)  EPIDEMIOLOGY: Acute cyanide ingestion due to inadvertent
        ingestion of these plants is very rare. Acute cyanide
        toxicity occasionally results from ingestion of
        significant amounts of masticated pits of fruits and
        chronic consumption of "nontraditional" preparation of
        cyanogenic plants which may result in spastic paresis
        and tropical ataxic neuropathy. Most cases are due to
        use of these plants as food in less developed countries.
    E)  WITH POISONING/EXPOSURE
     1)  MILD TO MODERATE TOXICITY: Signs and symptoms
         association with ingestion of significant amount of
         masticated pits containing amygdalin include dyspnea,
         cyanosis, weakness, and lightheadedness.
     2)  SEVERE TOXICITY: Coma, seizures, stupor, dysrhythmias,
         cardiovascular collapse, and metabolic acidosis.
     3)  CHRONIC TOXICITY: Chronic consumption of cyanogenic
         glycoside containing plants as a food staple may result
         in chronic polyneuropathies which includes spastic
         paresis and tropical ataxic neuropathy. Spastic paresis
         is characterized by bilateral and symmetrical
         involvement of the pyramidal tracts affecting the lower
         extremities resulting in spastic gait, paraplegia,
         extensor plantar responses, spastic bladder,
         constipation and impotence, with visual involvement
         rarely reported. Chronic poisoning should be considered
         when nonspecific or neurologic symptomatology is
         associated with a large or chronic ingestion of
         cyanogenic plants.
  0.2.3 VITAL SIGNS
    A)  WITH POISONING/EXPOSURE
     1)  TACHYPNEA - Initial tachypnea is replaced by
         respiratory depression and cyanosis in severe
         poisonings.
     2)  KUSSMAUL'S RESPIRATION - Rapid deep respirations may be
         evidence of acidosis.
     3)  RESPIRATORY ARREST may occur initially or be delayed.
     4)  HYPOTHERMIA - A 41-year-old woman presented with mild
         hypothermia (rectal temperature 33.6 C) after ingesting
         30 apricot kernels.
     5)  HYPOTENSION and shock may be present.
  0.2.5 CARDIOVASCULAR
    A)  Initial hypertension followed by hypotension and
        cardiovascular collapse may occur.
  0.2.6 RESPIRATORY
    A)  Initial tachypnea and dyspnea followed by depressed,
        labored respirations may occur which may progress to
        respiratory arrest. Kussmaul's respiration may be
        evident.
  0.2.7 NEUROLOGIC
    A)  Headaches, dizziness, lightheadedness, disorientation,
        irritability, unresponsiveness, lethargy, stupor,
        weakness, paralysis, areflexia, syncope coma, and
        seizures may follow gastrointestinal symptoms.
    B)  Chronic consumption of plants containing high
        concentrations of cyanogenic glycosides has been
        associated with polyneuropathy which include optic
        atrophy, nerve deafness, spastic paraparesis, ataxia,
        clonus and peripheral neuropathy.
  0.2.8 GASTROINTESTINAL
    A)  Nausea, vomiting, diarrhea, and epigastric pain may be
        the first symptoms. Pancreatitis and endemic goiter have
        been reported in patients from cassava-consuming areas.
  0.2.11 ACID-BASE
    A)  Metabolic acidosis and lactic acidosis may be present.
  0.2.14 DERMATOLOGIC
    A)  WITH POISONING/EXPOSURE
     1)  Face petechiae has been reported following Cycas seed
         poisoning.
  0.2.20 REPRODUCTIVE
    A)  The use of cassava or Laetrile(R) in animal studies
        produced limb defects, open eye defects, microcephaly,
        fetal growth retardation in fetuses. Sodium thiosulfate
        administration protected the fetus from teratogenic
        effects.
Laboratory:
A)  Monitor serum chemistry and lactate concentrations.
   B)  Monitor arterial and venous blood gases.
   C)  Cyanide levels can be measured to confirm the diagnosis,
       but are usually not available in a timely manner to be
       clinically useful.
   D)  Institute continuous cardiac monitoring and obtain an
       ECG.
   E)  Methemoglobin should also be monitored frequently in
       patients receiving intravenous sodium nitrite.
   F)  Consider a head CT for comatose patients.
Treatment Overview:
0.4.2 ORAL/PARENTERAL EXPOSURE
    A)  MANAGEMENT OF MILD TO MODERATE TOXICITY
     1)  In symptomatic patients, advance life support including
         the use of a cyanide antidote should be initiated as
         gastrointestinal decontamination is being prepared.
         Supplemental oxygen should be administered immediately
         with continuous monitoring of vital signs. Establish IV
         access immediately. An antidote kit should available at
         the bedside. Worsening or severe acidosis, hypotension,
         seizures, dysrhythmias and coma indicate a more severe
         poisoning.
    B)  MANAGEMENT OF SEVERE TOXICITY
     1)  Elevated lactate, increased anion gap metabolic
         acidosis, and an elevated venous oxygen saturation all
         suggest a significant cyanide exposure. Manage airway
         early. Patients who are comatose or severely ill due to
         suspected cyanide toxicity should be administered a
         cyanide antidote kit. In addition, standard ACLS or
         PALS therapy should be provided to manage symptoms.
         Administer sodium bicarbonate for severe acidemia.
    C)  DECONTAMINATION
     1)  PREHOSPITAL: Prehospital activated charcoal can be
         considered for large ingestions in which there will be
         a delay in definitive healthcare; however, a poison
         center should initially be consulted. Avoid inducing
         vomiting.
     2)  HOSPITAL: Activated charcoal binds poorly to cyanide
         salts; however, the lethal dose is so small that the
         use of activated charcoal should be considered in a
         symptomatic patient. Symptoms are often delayed up to 2
         hours or more after ingestion of the masticated pits
         containing amygdalin.
    D)  AIRWAY MANAGEMENT
     1)  Patients who are comatose or with altered mental status
         need early endotracheal intubation and mechanical
         ventilation.
    E)  CYANIDE ANTIDOTE
     1)  A cyanide antidote, either hydroxocobalamin OR the
         sodium nitrite/sodium thiosulfate kit, should be
         administered to symptomatic patients (metabolic
         acidosis, depressed mental status, hypotension,
         dysrhythmias, seizures).
     2)  HYDROXOCOBALAMIN
      a)  ADULT: Administer 5 g IV over 15 minutes. A second
          dose may be given (infused over 15 to 120 minutes) in
          patients with severe toxicity. PEDIATRIC: A dose of 70
          mg/kg has been used. Hydroxocobalamin forms
          cyanocobalamin which is a nontoxic, water soluble
          metabolite that is eliminated in the urine. It is
          generally safer and easier to use than other antidotes
          (i.e., cyanide antidote (sodium nitrite and sodium
          thiosulfate). Sodium thiosulfate may also be
          administered with hydroxocobalamin, but it is not part
          of the kit. ADVERSE EFFECTS: Flushing is common.
          Hydroxocobalamin is bright red and causes
          discoloration of the skin, urine, and serum. It can
          also interfere with many colorimetric based tests.
     3)  CYANIDE ANTIDOTE KIT
      a)  An alternative, a sodium nitrite/sodium thiosulfate
          kit, is administered as follows: SODIUM NITRITE:
          ADULT: Administer 300 mg (10 mL of 3% solution) IV at
          a rate of 2.5 to 5 mL/min; PEDIATRIC (with normal
          hemoglobin concentration): 0.2 mL/kg of a 3% solution
          (6 mg/kg) IV at a rate of 2.5 to 5 mL/min, not to
          exceed 10 mL (300 mg). The dose may be lowered if the
          patient is severely anemic, but administration should
          not be delayed for laboratory results. Nitrites may
          also cause vasodilatory effects which may contribute
          to hypotension. A second dose, one-half of the first
          dose, may be administered 30 minutes later if there is
          inadequate clinical response. Use with caution if
          carbon monoxide poisoning is also suspected. SODIUM
          THIOSULFATE: Follow sodium nitrite with IV sodium
          thiosulfate. ADULT: Administer 50 mL (12.5 g) of a 25%
          solution IV; PEDIATRIC: 1 mL/kg of a 25% solution (250
          mg/kg), not to exceed 50 mL (12.5 g) total dose. A
          second dose, one-half of the first dose, may be
          administered if signs of cyanide toxicity reappear.
          This agent enhances conversion of cyanide to
          thiocyanate which is eliminated in the urine. Patients
          with renal failure may need dialysis to eliminate
          thiocyanate. ALTERNATE ANTIDOTES: Kelocyanor(R)
          (dicobalt-EDTA) and 4-DMAP (4-dimethylaminophenol) are
          among the cyanide antidotes in clinical use outside
          the US.
    F)  METHEMOGLOBINEMIA
     1)  Blood methemoglobin levels should be monitored for 30
         to 60 minutes following the infusion of sodium nitrite
         to prevent severe toxicity. Treat with methylene blue
         if patient is symptomatic (usually at methemoglobin
         concentrations greater than 20% to 30% or at lower
         concentrations in patients with anemia, underlying
         pulmonary or cardiovascular disease). METHYLENE BLUE:
         INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30
         minutes; a repeat dose of up to 1 mg/kg may be given 1
         hour after the first dose if methemoglobin levels
         remain greater than 30% or if signs and symptoms
         persist. NOTE: Methylene blue is available as follows:
         50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose
         ampules and 10 mg/1 mL (1% solution) vials. Additional
         doses may sometimes be required. Improvement is usually
         noted shortly after administration if diagnosis is
         correct. Consider other diagnoses or treatment options
         if no improvement has been observed after several
         doses. If intravenous access cannot be established,
         methylene blue may also be given by intraosseous
         infusion. Methylene blue should not be given by
         subcutaneous or intrathecal injection. NEONATES: DOSE:
         0.3 to 1 mg/kg.
    G)  ENHANCED ELIMINATION
     1)  Antidotes increase elimination, however, the role of
         hemodialysis is uncertain.
    H)  PATIENT DISPOSITION
     1)  HOME CRITERIA: Home management is not indicated in
         patients with acute cyanide toxicity following exposure
         to a cyanogenic glycoside. Toxicity can vary widely
         depending on the plant and stage of development.
         Asymptomatic children with exploratory or "taste"
         ingestions of cyanogenic plants can generally be
         managed at home with telephone follow up.
     2)  OBSERVATION CRITERIA: Symptomatic patients should be
         referred to a healthcare facility. If laboratory
         evaluations are normal and the patient remains
         asymptomatic for at least 8 hours, they may be
         discharged from the hospital with appropriate follow-up
         instructions.
     3)  ADMISSION CRITERIA: Any patient with symptomatic
         poisoning should be admitted to an intensive care unit.
     4)  CONSULT CRITERIA: Consult a poison center or medical
         toxicologist for assistance in managing symptomatic
         patients.
    I)  PITFALLS
     1)  Treatment should not be delayed for laboratory results
         if a cyanide exposure is strongly suspected.
    J)  PHARMACOKINETICS
     1)  Cyanogenic glycosides release hydrogen cyanide after
         complete hydrolysis. Amygdalin is a cyanogenic
         diglucoside D-mandelonitrile-beta-D- gentiobioside,
         which is not toxic until it is metabolized by the
         enzyme emulsin which is present in the seeds of the
         plants. The presence of amygdalin in the seed kernels
         of a plant is usually not considered dangerous.
         However, the crushed (masticated) moistened seed
         release emulsin, an enzyme that catalyzes the
         hydrolysis of amygdalin to glucose, benzaldehyde, and
         cyanide.
    K)  TOXICOKINETICS
     1)  Toxicity is highly variable and dependent on multiple
         factors including the amount of glycosides present in a
         plant, which can vary with species, the stage of plant
         development and plant part. Cassava species (including
         linamarin and Prunus species) contain amygdalin which
         are of most concern to humans. Cyanogenic glycosides
         need to be hydrolyzed in the gastrointestinal tract
         before the release of cyanide; therefore, the onset of
         symptoms are often delayed up to 2 hours after
         ingestion of masticated pits containing amygdalin.
         Chronic consumption of cyanogenic glycoside containing
         plants as food staple may result in chronic
         polyneuropathies which includes spastic paresis and
         tropical ataxic neuropathy.
    L)  DIFFERENTIAL DIAGNOSIS
     1)  Ingestion of plants that may produce similar symptoms.
         Other agents that may produce metabolic acidosis.
Range of Toxicity:
A)  Inadvertent ingestion of whole seeds or pits is unlikely
       to result in acute cyanide toxicity.
   B)  TOXICITY: For 100 grams of moistened seed; the peach pit
       contains approximately 88 mg of hydrocyanic acid,
       cultivated apricot pit 8.9 mg, wild apricot pit 217 mg.
       The ingestion of 500 mg of amygdalin may release as much
       as 30 mg of cyanide. The amount of hydrogen cyanide (HCN)
       potentially released from bitter almond seeds, apricot
       seeds, peach seeds, and apple seeds are 0.9 to 4.9 mg
       HCN/g, 0.1 to 4.1 mg HCN/g, 0.4 to 2.6 mg HCN/g, and 0.6
       mg HCN/g, respectively. CYANIDE: Lethal dose has been
       estimated to be 50 to 300 mg for an adult, depending on
       the specific agent, but not well defined. The fatal dose
       of cyanide salts is estimated at 200 to 300 mg for an
       adult, and 50 to 100 mg of hydrocyanic acid.

[Rumack BH POISINDEX(R) Information System Micromedex, Inc., Englewood, CO, 2017; CCIS Volume 172, edition expires May, 2017. Hall AH & Rumack BH (Eds): TOMES(R) Information System Micromedex, Inc., Englewood, CO, 2017; CCIS Volume 172, edition expires May, 2017.] **PEER REVIEWED**


Animal Toxicity Studies:


Non-Human Toxicity Excerpts:
DIETS CONTAINING 10% GROUND APRICOT KERNELS WERE FED TO BREEDING MALE & FEMALE SPRAGUE-DAWLEY RATS. OFFSPRING OF RATS FED HIGH-AMYGDALIN DIET (MORE THAN 200 MG CYANIDE/100 G) FOR 18 WK HAD LOWER 3-DAY SURVIVAL INDICES, LACTATION INDICES, & WEANING WEIGHTS THAN THOSE IN THE LOW-AMYGDALIN GROUP (LESS THAN 50 MG CYANIDE/100 G). THIS MAY INDICATE THAT THE CYANIDE PRESENT IN THE MILK MAY NOT BE EFFICIENTLY DETOXIFIED TO THIOCYANATE & EXCRETED BY NEONATES.
[MILLER KW ET AL; AMYGDALIN METABOLISM AND EFFECT ON REPRODUCTION OF RATS FED APRICOT KERNELS; J TOXICOL ENVIRON HEALTH 7(3-4) 457 (1981)] **PEER REVIEWED**

DOGS WERE FED LAETRILE & FRESH, SWEET ALMONDS UNDER VARIOUS CONDITIONS. THE DOSES OF LAETRILE WERE SIMILAR TO THOSE PRESCRIBED FOR PATIENTS WITH CANCER. SIX OF THE 10 DOGS DIED OF CYANIDE POISONING. ONE DOG RECOVERED & 3 AT TIME OF SACRIFICE, DEMONSTRATED VARIOUS LEVELS OF NEUROLOGIC IMPAIRMENT, RANGING FROM DIFFICULTY IN WALKING TO COMA.
[SCHMIDT ES ET AL; LAETRILE TOXICITY STUDIES IN DOGS; J AM MED ASSOC 239(10) 943 (1978)] **PEER REVIEWED**

LAETRILE ADMIN ORALLY TO PREGNANT HAMSTERS CAUSED SKELETAL MALFORMATIONS IN THE OFFSPRING. ORAL LAETRILE SIGNIFICANTLY INCREASED IN SITU CYANIDE CONCENTRATIONS, WHILE IV LAETRILE DID NOT. THIOSULFATE ADMIN PROTECTED EMBRYOS FROM THE TERATOGENIC EFFECTS OF ORAL LAETRILE. THE EMBRYOPATHIC EFFECTS OF ORAL LAETRILE APPEAR TO BE DUE TO CYANIDE RELEASED BY BACTERIAL BETA-GLUCOSIDASE ACTIVITY.
[WILLHITE CC; CONGENITAL MALFORMATIONS INDUCED BY LAETRILE; SCIENCE 215(4539) 1513 (1982)] **PEER REVIEWED**

THE ORAL LD50 VALUE OF AMYGDALIN IN RATS WAS APPROX 522 MG/KG. THE 1ST SIGNS OF NEUROLOGICAL DAMAGE APPEARED 80 MIN AFTER ADMIN & WAS EXEMPLIFIED BY HIND-QUARTER ATAXIA.
[NEWTON GW ET AL; AMYGDALIN TOXICITY STUDIES IN RATS PREDICT CHRONIC CYANIDE POISONING IN HUMANS; WEST J MED 134(2) 97 (1981)] **PEER REVIEWED**

AMYGDALIN GIVEN TO FISCHER 344 RATS IN DOSES OF 250, 500, & 750 MG/KG IP DAILY FOR 5 DAYS CAUSED MORTALITIES OF 30.8%, 44.1%, & 56.8% RESPECTIVELY. THE MODE OF DEATH & ELEVATED CYANIDE POISONING LEVELS IN THE DYING ANIMALS STRONGLY SUGGESTED CYANIDE POISONING AS THE CAUSE OF DEATH. THESE FINDINGS SERIOUSLY QUESTION THE USE OF LAETRILE IN CLINICAL MEDICINE UNDER ANY CIRCUMSTANCES
[KHANDEKAR JD, EDELMAN H; STUDIES OF AMYGDALIN (LAETRILE) TOXICITY IN RODENTS; J AM MED ASSOC 242(2) 169 (1979)] **PEER REVIEWED**


Metabolism/Pharmacokinetics:


Metabolism/Metabolites:
AMYGDALIN IS A CHEMICAL COMBINATION OF GLUCOSE, BENZALDEHYDE, & CYANIDE FROM WHICH THE LATTER CAN BE RELEASED BY THE ACTION OF BETA-GLUCOSIDASE OR EMULSIN. ALTHOUGH THESE ENZYMES ARE NOT FOUND IN MAMMALIAN TISSUES, THE HUMAN INTESTINAL MICROFLORA APPEARS TO POSSESS THESE OR SIMILAR ENZYMES CAPABLE OF EFFECTING CYANIDE RELEASE RESULTING IN HUMAN POISONING. FOR THIS REASON AMYGDALIN MAY BE AS MUCH AS 40 TIMES MORE TOXIC BY THE ORAL ROUTE AS COMPARED WITH IV INJECTION.
[Doull, J., C.D. Klaassen, and M. D. Amdur (eds.). Casarett and Doull's Toxicology. 2nd ed. New York: Macmillan Publishing Co., 1980., p. 328] **PEER REVIEWED**

...PLANT GLYCOSIDES ARE CHARACTERIZED BY PRODN OF CYANIDE, TOGETHER WITH A SUGAR & AROMATIC ALDEHYDE, ON ENZYMIC OR ACID HYDROLYSIS. COMMON EXAMPLES ARE AMYGDALIN (GENTIOBIOSE + BENZALDEHYDE + HCN) WHICH IS PRESENT IN BITTER ALMONDS... AN ENZYME COMPLEX, EMULSIN, IS PRESENT TOGETHER WITH GLYCOSIDES IN PLANT TISSUES & CATALYZES THE HYDROLYSIS OF GLYCOSIDES, FIRST TO MANDELONITRILE OR P-HYDROXYMANDELONITRILE, & THEN TO BENZALDEHYDE OR P-HYDROXYBENZALDEHYDE, & HCN. ... THE ALDEHYDES ARE OXIDIZED TO CORRESPONDING AROMATIC ACIDS & EXCRETED AS PEPTIDE CONJUGATES.
[Parke, D. V. The Biochemistry of Foreign Compounds. Oxford: Pergamon Press, 1968., p. 155] **PEER REVIEWED**

...VARIOUS PRUNUS SPECIES CONTAIN...AMYGDALIN, WHICH IS HYDROLYZED BY ENZYME EMULSIN... IN INTACT PLANT NO SUCH ACTION TAKES PLACE; IT IS NOT UNTIL PLANT TISSUE IS DAMAGED OR STARTS TO DECAY THAT LIBERATION OF HCN BEGINS.
[Clarke, M. L., D. G. Harvey and D. J. Humphreys. Veterinary Toxicology. 2nd ed. London: Bailliere Tindall, 1981., p. 175] **PEER REVIEWED**

BREAKDOWN /OF GLYCOSIDES/ OFTEN OCCURS MORE READILY OR MORE RAPIDLY IN RUMEN THAN IN DIGESTIVE TRACT OF MONOGASTRIC ANIMALS. ALSO, SMALL MOLECULES CAN BE ABSORBED AT THE RUMEN & THUS ENTER CIRCULATION RAPIDLY. BREAKDOWN OF CYANOGENIC GLYCOSIDES, SUCH AS AMYGDALIN, FROM MEMBERS OF ROSE FAMILY...IS AN EXAMPLE.
[Doull, J., C.D. Klaassen, and M. D. Amdur (eds.). Casarett and Doull's Toxicology. 2nd ed. New York: Macmillan Publishing Co., 1980., p. 585] **PEER REVIEWED**

YIELDS PRUNASIN IN BIDENS, DATURA, ROSE, YEAST, & BEEF: SUZUKI H; ARCHS BIOCHEM BIOPHYS 99: 476 (1962). /FROM TABLE/
[Goodwin, B.L. Handbook of Intermediary Metabolism of Aromatic Compounds. New York: Wiley, 1976., p. A-54] **PEER REVIEWED**

PHARMACOKINETIC OF AMYGDALIN WAS INVESTIGATED IN BEAGLE DOG AFTER BOTH IV & ORAL ADMIN. EXCRETION OF AMGYDALIN HAS ALSO BEEN STUDIED IN THE RAT. PHARMACOKINETICS OF AMYGDALIN AFTER IV ADMIN WERE COMPARED WITH THOSE OF DIATRIZOATE, A MODEL SUBSTANCE FOR EXTRACELLULAR VOL & GLOMERULAR FILTRATION. AMYGDALIN CLEARANCE IS SIGNIFICANTLY LARGER THAN THAT OF DIATRIZOATE. THE VOLUMES OF DISTRIBUTION OF BOTH SUBSTANCES ARE THE SAME. AFTER ORAL ADMIN ONLY A FEW PERCENT OF THE AMYGDALIN DOSE ARE SYSTEMICALLY AVAILABLE. A PART OF THE ORAL DOSE IS RECOVERED FROM THE URINE AS PRUNASIN.
[RAUWS AG ET AL; THE PHARMACOKINETICS OF AMYGDALIN; ARCH TOXICOL 49(3-4) 311 (1982)] **PEER REVIEWED**

DIETS CONTAINING 10% GROUND APRICOT KERNELS WERE FED TO RATS. IN FEMALE RATS, BUT NOT IN MALES, LIVER RHODANESE ACTIVITY & THIOCYANATE (SCN) BLOOD LEVELS WERE INCREASED WITH HIGH-AMYGDALIN DIET, BUT BOTH MALE & FEMALE RATS EFFICIENTLY EXCRETED THIOCYANATE, INDICATING EFFICIENT DETOXICATION & CLEARANCE OF CYANIDE HYDROLYZED FROM DIETARY AMYGDALIN. OFFSPRING OF BREEDING RATS FED HIGH-AMYGDALIN HAD LOWER 3-DAY SURVIVAL INDICES, LACTATION INDICES, & WEANING WEIGHTS THAN THOSE IN THE LOW-DOSE GROUP. THIS MAY INDICATE THAT THE CYANIDE PRESENT IN THE MILK MAY NOT BE EFFICIENTLY DETOXIFIED TO THIOCYANATE & EXCRETED BY NEONATES.
[MILLER KW ET AL; AMYGDALIN METABOLISM AND EFFECT ON REPRODUCTION OF RATS FED APRICOT KERNELS; J TOXICOL ENVIRON HEALTH 7(3-4) 457 (1981)] **PEER REVIEWED**

BETA-GLUCOSIDASE WAS DEMONSTRATED IN CAT, RAT, & RABBIT KIDNEY TISSUE THAT CATALYZED THE HYDROLYTIC CLEAVAGE OF TERMINAL GLUCOSE RESIDUE OF AMYGDALIN.
[FREESE A ET AL; A BETA-GLUCOSIDASE IN FELINE KIDNEY THAT HYDROLYZES AMYGDALIN (LAETRILE); ARCH BIOCHEM BIOPHYS 201(2) 363 (1980)] **PEER REVIEWED**

WHEN CONVENTIONAL RATS WERE GIVEN SINGLE ORAL DOSES OF AMYGDALIN (600 MG/KG), THEY SOMETIMES EXPERIENCED LETHARGY & CONVULSIONS, & USUALLY DIED WITHIN 2-5 HR. RATS AFFECTED IN THIS WAY HAD HIGH CONCENTRATIONS OF CYANIDE (CN) IN THEIR BLOOD (2.6-4.5 MUG/ML). GERMFREE RATS RECEIVING THE SAME DOSE OF AMYGDALIN DID NOT EXHIBIT THESE SYMPTOMS & HAD BLOOD CN CONCENTRATIONS (LESS THAN 0.4 MUG/ML) INDISTINGUISHABLE FROM CONVENTIONAL RATS WHICH DID NOT RECEIVE AMYGDALIN. THE GI FLORA ARE EVIDENTLY OBLIGATORY FOR THE REACTION WHICH LEAD TO THE RELEASE OF TOXIC AMOUNTS OF CN FROM AMYGDALIN (LAETRILE).
[CARTER JH ET AL; ROLE OF THE GASTROINTESTINAL MICROFLORA IN AMYGDALIN (LAETRILE)-INDUCED CYANIDE TOXICITY; BIOCHEM PHARMACOL 29(3) 310 (1980)] **PEER REVIEWED**


Absorption, Distribution & Excretion:
THE MAX CYANIDE LEVEL AFTER ORAL ADMIN OF AMYGDALIN TO MICE WAS REACHED AT ABOUT 1 1/2-2 HR & WAS WITHIN THE RANGE OF VALUES SEEN AFTER KCN ADMIN. THE ABILITY OF THE CONTENTS OF VARIOUS REGIONS OF THE GI TRACT & OF TUMOR TISSUE TO RELEASE CYANIDE FROM AMYGDALIN WAS ASSESSED. THE STOMACH & UPPER INTESTINE HAD LITTLE ACTIVITY WHILE THE LOWER INTESTINE & FECES RELEASED LARGE AMOUNTS. THERE WAS A LARGE VARIATION BETWEEN MICE.
[HILL HZ ET AL; BLOOD CYANIDE LEVELS IN MICE AFTER ADMINISTRATION OF AMYGDALIN; BIOPHARM DRUG DISPOS 1(4) 211 (1980)] **PEER REVIEWED**


Biological Half-Life:
PLASMA & URINE CONCN OF AMYGDALIN, WHOLE-BLOOD CONCN OF CN- & SCN- CONCN IN SERUM & URINE WERE DETERMINED IN CANCER PT FOLLOWING IV (4.5 G/SQUARE M) & ORAL (500-MG TABLET) ADMIN OF AMYGDALIN. FOLLOWING IV ADMIN, CONCN OF PARENT DRUG AS HIGH AS 1401 MUG/ML WERE OBSERVED WITH NO INCR IN PLASMA CONCN OF CN- OR SERUM CONCN OF SCN-. PLASMA ELIM OF AMYGDALIN WAS BEST DESCRIBED BY 2-COMPARTMENT OPEN MODEL WITH MEAN DISTRIBUTIVE PHASE T/2 OF 6.2 MIN, MEAN ELIM PHASE T/2 OF 120.3 MIN, & MEAN CLEARANCE OF 99.3 ML/MIN. FOLLOWING ORAL ADMIN OF AMYGDALIN, PLASMA CONCN WERE MUCH LOWER, WITH PEAK VALUES OF LESS THAN 525 NG/ML. CN- CONCN INCR TO VALUES AS HIGH AS 2.1 MUG/ML WHOLE BLOOD. SCN- CONCN DID NOT INCR FOR SEVERAL DAYS, PLATEAUING AT VALUES AS HIGH AS 38 MUG/ML SERUM.
[AMES MM ET AL; PHARMACOLOGY OF AMYGDALIN (LAETRILE) IN CANCER PATIENTS; CANCER CHEMOTHER PHARMACOL 6(1) 51 (1981)] **PEER REVIEWED**


Pharmacology:


Environmental Fate & Exposure:


Natural Pollution Sources:
THE ROSE FAMILY INCL MANY OF THE MOST COMMONLY GROWN FRUIT TREES: PLUM, CHERRY, PEACH, APRICOT, APPLE & ALMOND. THE KERNELS & LEAVES OF THESE (& THE PIPS OF THE APPLE) CONTAIN CYANOGENIC GLYCOSIDES. AMYGDALIN IS THE MOST COMMON, BUT PRUNASIN & PRULAURASIN ALSO OCCUR.
[Clarke, M. L., D. G. Harvey and D. J. Humphreys. Veterinary Toxicology. 2nd ed. London: Bailliere Tindall, 1981., p. 250] **PEER REVIEWED**


Environmental Standards & Regulations:


Chemical/Physical Properties:


Molecular Formula:
C20-H27-N-O11
**PEER REVIEWED**


Molecular Weight:
457.48
[U.S. Department of Health and Human Services, Public Health Service, Center for Disease Control, National Institute for Occupational Safety Health. Registry of Toxic Effects of Chemical Substances (RTECS). National Library of Medicine's current MEDLARS file., p. 83/8207] **PEER REVIEWED**


Melting Point:
223-226 DEG C
[Weast, R.C. (ed.). Handbook of Chemistry and Physics. 60th ed. Boca Raton, Florida: CRC Press Inc., 1979., p. C-111] **PEER REVIEWED**


Solubilities:
VERY SOL IN HOT WATER; SLIGHTLY SOL IN ALCOHOL; INSOL IN ETHER, CHLOROFORM; SOL IN HOT ALCOHOL
[Weast, R.C. (ed.). Handbook of Chemistry and Physics. 60th ed. Boca Raton, Florida: CRC Press Inc., 1979., p. C-111] **PEER REVIEWED**


Spectral Properties:
SPECIFIC OPTICAL ROTATION (WATER, C= 1): -42 DEG @ 20 DEG C/D; SADTLER REF NUMBER: 16450 (IR, PRISM); 5152 (UV)
[Weast, R.C. (ed.). Handbook of Chemistry and Physics. 60th ed. Boca Raton, Florida: CRC Press Inc., 1979., p. C-111] **PEER REVIEWED**


Chemical Safety & Handling:


Occupational Exposure Standards:


Manufacturing/Use Information:


Methods of Manufacturing:
OCCURS IN SEEDS OF ROSACEAE; PRINCIPALLY IN BITTER ALMONDS; ALSO IN PEACHES & APRICOTS. OBTAINED BY EXTRACTING DEFATTED ALMOND MEAL REPEATEDLY WITH BOILING 95% ALCOHOL.
[The Merck Index. 9th ed. Rahway, New Jersey: Merck & Co., Inc., 1976., p. 81] **PEER REVIEWED**


General Manufacturing Information:
AMYGDALIN IS A CHEMICAL COMBINATION OF GLUCOSE, BENZALDEHYDE, & CYANIDE... AMYGDALIN IS THE MAJOR INGREDIENT OF LAETRILE...ALLEGED ANTICANCER DRUG...
[Doull, J., C.D. Klaassen, and M. D. Amdur (eds.). Casarett and Doull's Toxicology. 2nd ed. New York: Macmillan Publishing Co., 1980., p. 328] **PEER REVIEWED**

ALTHOUGH AMYGDALIN HAS BEEN REPORTED TO HAVE BEEN USED IN CANCER CHEMOTHERAPY SINCE 1845, THERE IS AN ABSENCE OF PUBLISHED DATA SUBSTANTIATING ITS ANTICANCER ACTIVITY. THE TERM AMYGDALIN IS CURRENTLY USED INTERCHANGEABLY WITH LAETRILE.
[The Merck Index. 9th ed. Rahway, New Jersey: Merck & Co., Inc., 1976., p. 81] **PEER REVIEWED**

THE RECENT US SUPREME COURT RULINGS DEALING WITH CASES OF LAETRILE (AMYGDALIN) USE ARE DISCUSSED. THE COURT DECIDED THAT LAETRILE WAS INEFFECTIVE AS AN ANTINEOPLASTIC AGENT FOR THE TERMINALLY ILL.
[CURRAN WJ; LAETRILE FOR THE TERMINALLY ILL: SUPREME COURT STOPS THE NONSENSE; N ENGL J MED 302(MAR 13) 619 (1980)] **PEER REVIEWED**


Laboratory Methods:


Clinical Laboratory Methods:
AMYGDALIN & ITS MAJOR METABOLITE, PRUNASIN, IN BLOOD & URINE WERE SEPARATED FROM PROTEINS BY ULTRAFILTRATION & THEN SUBJECTED TO HIGH-PRESSURE LIQ CHROMATOGRAPHY, USING 10% METHYL CYANIDE AS ELUENT & DETERMINATION BY ABSORPTION AT 215 NM. THE METHOD GAVE LINEAR RESULTS IN THE RANGE 2-500 MG/L & WAS RELIABLE DOWN TO 1 MG/L.
[RAUWS AG ET AL; DETERMINATION OF AMYGDALIN AND ITS MAJOR METABOLITE PRUNASIN IN PLASMA AND URINE BY HIGH-PRESSURE LIQUID CHROMATOGRAPHY; PHARM WEEKBL, SCI ED 4(6) 172 (1982)] **PEER REVIEWED**

AMYGDALIN WAS DETERMINED IN TISSUES OR SERUM INDIRECTLY OR DIRECTLY. IN THE INDIRECT METHOD, SERUM OR TISSUE HOMOGENATES WERE INCUBATED WITH BETA-GLUCOSIDASE & THE INCUBATE HYDROLYZED WITH AMMONIUM HYDROXIDE, ACIDIFIED, EXTRACTED WITH 95:5 METHYLENE CHLORIDE-HEPTANE, & THE FORMED BENZALDEHYDE DETERMINED SPECTROPHOTOMETRICALLY AT 243 NM OR BY MASS FRAGMENTOGRAPHY. IN THE DIRECT METHOD, AMYGDALIN WAS DETERMINED AFTER EXTRACTION WITH ACETONE BY TLC, HPLC & GC.
[BALKON J; METHODOLOGY FOR THE DETECTION AND MEASUREMENT OF AMYGDALIN IN TISSUES AND FLUIDS; J ANAL TOXICOL 6(5) 244 (1982)] **PEER REVIEWED**


Analytic Laboratory Methods:
A RAPID SCREENING TEST FOR DETECTING AMYGDALIN IN TABLETS, SOLUTIONS, POWDERS, & SEEDS, BASED ON THE LIBERATION OF BOTH HYDROGEN CYANIDE & BENZALDEHYDE AS A RESULT OF ENZYMATIC DECOMPOSITION, IS DESCRIBED.
[EGLI KL; SCREENING TEST FOR AMYGDALIN IN TABLETS, SOLUTIONS, POWDERS, & SEEDS; J ASSOC OFF ANAL CHEM 62(MAR) 308 (1979)] **QC REVIEWED**

THE INVESTIGATION OF 3 INJECTABLE DOSAGE FORMS OF AMYGDALIN AND DETERMINATION OF THEIR CYANIDE CONTENT BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY, GAS CHROMATOGRAPHY, MICRODIFFUSION ANALYSIS & NMR SPECTROSCOPY ARE PRESENT.
[DYBOWSKI R; EXAMINATION OF AMYGDALIN PREPARATIONS; ANAL PROC 18(JUL) 316 (1981)] **QC REVIEWED**

NMR ANALYTICAL PROCEDURES WERE DESCRIBED FOR THE QUALITATIVE & QUANTITATIVE DETERMINATION OF AMYGDALIN. THE SPECTRUM WAS VERY SPECIFIC FOR AMYGDALIN, PARTICULARLY THE SUGAR REGION.
[TURCZAN JW, MEDWICK T; QUALITATIVE AND QUANTITATIVE ANALYSIS OF AMYGDALIN USING NMR SPECTROSCOPY; ANAL LETT 10(7-8) 581 (1977)] **PEER REVIEWED**

AMYGDALIN WAS HYDROLYZED BY BETA-GLUCOSIDASE. THE LIBERATED BENZALDEHYDE WAS CONVERTED BY PENTAFLUOROBENZYLOXYLAMINE TO ITS O-PENTAFLUOROBENZYL OXIME. THE LATTER WAS DETERMINED BY GC USING A FLAME IONIZATION OR ELECTRON CAPTURE DETECTOR.
[KAWAI S ET AL; GAS CHROMATOGRAPHIC ENZYMIC DETERMINATION OF AMYGDALIN; J CHROMATOGR 210(2) 342 (1981)] **PEER REVIEWED**

AMYGDALIN WAS DETERMINED IN APRICOT KERNEL & APRICOT PRODUCTS BY HIGH-PRESSURE LIQUID CHROMATOGRAPHY.
[KAJIWARA N ET AL; DETERMINATION OF AMYGDALIN IN APRICOT KERNEL AND PROCESSED APRICOT PRODUCTS BY HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY; SHOKUHIN EISEIGAKU ZASSHI 24(1) 42 (1983)] **PEER REVIEWED**


Special References:


Synonyms and Identifiers:


Synonyms:
D-AMYGDALIN
**PEER REVIEWED**

R-AMYGDALIN
**PEER REVIEWED**

AMYGDALOSIDE
**PEER REVIEWED**

BENZENEACETONITRILE, ALPHA-((6-O-BETA-D-GLUCOPYRANOSYL-BETA-D-GLUCOPYRANOSYL)OXY)-, (R)-
**PEER REVIEWED**

(R)-ALPHA-((6-O-BETA-D-GLUCOPYRANOSYL-BETA-D-GLUCOPYRANOSYL)OXY)BENZENEACETONITR ILE
**PEER REVIEWED**

MANDELONITRILE-BETA-GENTIOBIOSIDE
**PEER REVIEWED**

D(-)-MANDELONITRILE-BETA-D-GENTIOBIOSIDE
**PEER REVIEWED**

D-MANDELONITRILE-BETA-D-GLUCOSIDO-6-BETA-D-GLUCOSIDE
**PEER REVIEWED**

NSC-15780
**PEER REVIEWED**


Administrative Information:


Hazardous Substances Databank Number: 3559

Last Revision Date: 20021108

Update History:
Complete Update on 11/08/2002, 1 field added/edited/deleted.
Complete Update on 01/14/2002, 1 field added/edited/deleted.
Complete Update on 08/09/2001, 1 field added/edited/deleted.
Complete Update on 05/15/2001, 1 field added/edited/deleted.
Complete Update on 02/02/2000, 1 field added/edited/deleted.
Complete Update on 09/21/1999, 1 field added/edited/deleted.
Complete Update on 08/27/1999, 1 field added/edited/deleted.
Complete Update on 06/02/1998, 1 field added/edited/deleted.
Complete Update on 10/31/1997, 1 field added/edited/deleted.
Complete Update on 05/09/1997, 1 field added/edited/deleted.
Complete Update on 10/18/1996, 1 field added/edited/deleted.
Complete Update on 01/26/1996, 1 field added/edited/deleted.
Complete Update on 12/30/1994, 1 field added/edited/deleted.
Complete Update on 11/01/1993, 1 field added/edited/deleted.
Complete Update on 05/25/1993, 1 field added/edited/deleted.
Field update on 12/31/1992, 1 field added/edited/deleted.
Field update on 12/29/1989, 1 field added/edited/deleted.
Complete Update on 06/04/1985