305-03-3

White to pale beige crystalline or granular powder with a slight odor. Melting point 65-69°C.

CHLORAMBUCIL(305-03-3) is an alkylating agent. Reacts with proteins and a variety of nucleophilic compounds .

Insoluble in water.

Chlorambucil, an anticancer drug, is a derivative of nitrogen mustard. This drug is primarily used as an antineoplastic agent for treating lymphocytic leukemia; malignant lymphomas; follicular lymphoma; and Hodgkin’s disease. The treatments are not curative but do produce some marked remissions. Chlorambucil has also been tested for treatment of chronic hepatitis, rheumatoid arthritis; and as an insect chemosterilant. All of the chemical used in this country is imported from the United Kingdom. Work exposure in the United States would be limited to workers formulating the tablets, or to those patients receiving the drug.

Literature sources indicate that this chemical is nonflammable.

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. Medical observation is recommended for 24 to 48 hours after breathing overexposure, as pulmonary edema may be delayed. As first aid for pulmonary edema, a doctor or authorized paramedic may consider administering a drug or other inhalation therapy.

UN2811 Toxic solids, organic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials, Technical Name Required.

Moisture. Chlorambucil is an alkylating agent. Reacts with proteins and a variety of nucleophilic compounds. Compounds of the carboxyl group react with all bases, both inorganic and organic (i.e., amines) releasing substantial heat, water, and a salt that may beharmful. Incompatible with arsenic compounds (releases hydrogen cyanide gas), diazo compounds, dithiocarbamates, isocyanates, mercaptans, nitrides, sulfides (releasing heat, toxic, and possibly flammable gases), thiosulfates, and dithionites (releasing hydrogen sulfate and oxides of sulfur).

Chlorambucil, approved by the Food and Drug Administration (FDA) in 1957, is an antineoplastic/alkylating agent with a broad spectrum of antitumor activity used to treat chronic lymphocytic leukemia (CLL), Hodgkin’s and non-Hodgkin’s lymphomas.

beige powder

Chlorambucil is a crystalline solid

It is inappropriate and possibly dangerous to the environment to dispose of expired or waste drugs and pharmaceuticals by flushing them down the toilet or discarding them to the trash. Household quantities of expired or waste pharmaceuticals may be mixed with wet cat litter or coffee grounds, double-bagged in plastic, discard in trash. Larger quantities shall carefully take into consideration applicable DEA, EPA, and FDA regulations. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properlylabel and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged, and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator. Permanganate oxidation, high temperature incineration with scrubbing equipment, or microwave plasma treatment.

Leukeran,BurroughsWellcome,US,1957

antineoplastic, alkylating agent

Chlorambucil is a alkylating agent that is used as an chemotherapy drug in the treatment of chronic lymphocytic leukemia. Chlorambucil is also used to treat non-Hodgkin's lymphoma (NHL) and Hodgkin's disease.

Chlorambucil-d8 is the isotope labelled analogue of Chlorambucil (C324050), an alkylating agent that is used in the treatment of chronic lymphocytic leukemia. Chlorambucil is also used to treat non-Ho dgkin's lymphoma (NHL) and Hodgkin's disease.

tranquilization aid

ChEBI: A monocarboxylic acid that is butanoic acid substituted at position 4 by a 4-[bis(2-chloroethyl)amino]phenyl group. A chemotherapy drug that can be used in combination with the antibody obinutuzumab for the treatment of chronic lymphocytic leukemia.

Chlorambucil (Leukeran) is an aromatic nitrogen mustard that is intermediate in chemical reactivity between mechlorethamine and melphalan. Its mechanisms of action and range of antitumor activity are similar to theirs. It is well absorbed orally, but detailed information concerning its metabolic fate in humans is lacking.
Chlorambucil is used primarily as daily palliative therapy for chronic lymphocytic leukemia, Waldenstr?om’s macroglobulinemia, myeloma, and other lymphomas.
Bone marrow toxicity is the major side effect of chlorambucil. Nausea is uncommon or mild, and hair loss does not occur. Chlorambucil shares the immunosuppressive, teratogenic, and carcinogenic properties of the nitrogen mustards.

Acetanilide and maleic acid are condensed to give beta-(p-acetaminobenzoyl) acrilic acid which is hydrogenated to give methyl-gamma-(p-aminophenyl) butyrate. That is reacted with ethylene oxide and then with phosphorus oxychloride to give the methyl ester which is finally hydrolyzed to give chlorambucil.

Leukeran (GlaxoSmithKline.

Antineoplastic

Chlorambucil is an anti-cancer drug that alkylates DNA and induces apoptosis. Death of chronic lymphocytic leukemia cells occurs via a p53-dependent mechanism.

It is used in the palliative treatment of chronic lymphocytic leukemia, malignant lymphoma, and Hodgkin's disease.

Chlorambucil, 4-[p-[bis-(2-chloroethyl)amino]phenyl]butyric acid (30.2.1.7), is made from acetanilide and succinic anhydride. In the first stage of synthesis, acetanilide is acylated by succinic anhydride, giving 4-(4-acetaminophenyl)-4-ketobutyric acid (30.2.1.3). The keto group in this compound is reduced by hydrogen in a methanol solution using palladium on carbon as a catalyst. This results in the formation of the methyl ester of 4-(4-acetaminophenyl)-butyric acid (30.2.1.4). This is treated with an alkali in order to hydrolyze both the amide and ester parts of the molecule, which forms 4-(4-aminophenyl)butyric acid (30.2.1.5), which upon reaction with ethylene oxide gives 4-[p-[bis(2-hydroxyethyl) amino]phenyl]butyric acid (30.2.1.7). Replacing all of the hydroxyl groups in this compound using phosphoryl chloride and subsequent treatment with water to hydrolyze the resulting intermediate acid chloride to an acid gives chlorambucil (30.2.1.7).

Chlorambucil may be useful in a variety of neoplastic diseases, including lymphocytic leukemia, multiple myeloma, polycythemia vera, macroglobulinemia, and ovarian adenocarcinoma. It may also be useful as adjunctive therapy for some immune-mediated conditions (e.g., glomerulonephritis, inflammatory bowel disease, nonerosive arthritis, or immune-mediated skin disease). It has found favor as a routine treatment for feline pemphigus foliaceous and severe feline eosinophilic granuloma complex due to the drug’s relative lack of toxicity in cats and efficacy.

Potentially hazardous interactions with other drugs
Ciclosporin: ciclosporin concentration possibly reduced.
Patients who receive phenylbutazone may require reduced doses of chlorambucil.

Chlorambucil is known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in humans.

The mechanism of action of chlorambucil is thought to be an alkylating agent and an aromatic nitrogen mustard derivative; it interferes with DNA replication and RNA transcription by alkylation and cross-linking the strands of DNA.

Chlorambucil is extensively metabolised in the liver via the hepatic microsomal enzyme oxidation system, principally to phenylacetic acid mustard, which is pharmacologically active, and which also undergoes some spontaneous degradation to further derivatives.
Chlorambucil is excreted in the urine, almost exclusively as metabolites with less than 1% unchanged.

Color Code—Blue: Health Hazard/Poison: Storein a secure poison location. Prior to working with chlorambucil you should be trained on its proper handling and storage. Store in cool, dry place. Store in sealed ampules or inamber screw-capped bottles or vials with Teflon? capliners. Solutions may be stored in bottles or vials with a silicone system having a Teflon? liner and sampled with needle and syringe. Prevent exposure to light. A regulated,marked area should be established where this chemical ishandled, used, or stored in compliance with OSHAStandard 1910.1045.

Chlorambucil is recrystallised from pet ether (flat needles) and has a solubility at 20o of 66% in EtOH, 40% in CHCl3, 50% in Me2CO but is insoluble in H2O [Everett et al. J Chem Soc 2386 1953]. [Beilstein 14 IV 1715.] CARCINOGEN.

The chemical is of a white to pale slight odorous powder, insoluble in water. It is very slightly dispersible in diethyl ether and acetone. It has a melting point of 69°C, boiling point of 424°C, and 5.75 pKa. The partition coefficient is 4.07 and has a molecular weight of 304.22 g mol^-1.