Mechlorethamine

CAS RN: 51-75-2

Health Effects

0.2.1 SUMMARY OF EXPOSURE
  • 0.2.1.1 ACUTE EXPOSURE
    • A) USES: Intravenous mechlorethamine is indicated for the palliative treatment of mycosis fungoides, stages III and IV Hodgkin disease, bronchogenic carcinoma, chronic lymphocytic leukemia (CLL), chronic myelocytic leukemia (CML), lymphosarcoma, and polycythemia vera. Mechlorethamine is also used intrapleurally, intraperitoneally, or intrapericardially for the palliative treatment of metastatic carcinoma resulting in effusion. Mechlorethamine gel is used for the topical treatment of stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy.
    • B) PHARMACOLOGY: Mechlorethamine hydrochloride, also known as HN2 hydrochloride, is an antineoplastic agent that is nitrogen analog of sulfur mustard. As a biologic alkylating agent, it exerts its cytotoxic effects by inhibiting the rapid proliferation of cancer cells.
    • C) TOXICOLOGY: Overdose effects are seen primarily in rapidly dividing cells (eg, bone marrow, gastrointestinal tract).
    • D) EPIDEMIOLOGY: Overdose is rare.
    • E) WITH THERAPEUTIC USE
      • 1) INTRAVENOUS: Nausea and vomiting (onset: 1 to 3 hours; duration: 8 to 24 hours), anorexia, thrombosis, thrombophlebitis, maculopapular skin eruption, erythema multiforme, extravasation injury, jaundice, alopecia, vertigo, hearing loss, tinnitus, weakness, headache, drowsiness, vertigo, lightheadedness, seizures, progressive muscle paralysis, paresthesia, cerebral degeneration, coma, and hypersensitivity reactions, including anaphylaxis. HEMATOLOGIC EFFECTS: Severe myelosuppression has occasionally occurred and may be observed for up to 50 days or more after initiating mechlorethamine therapy. Lymphocytopenia (onset within 24 hours), granulocytopenia (onset within 6 to 8 days and lasts for 10 days to 3 weeks), thrombocytopenia (onset and duration, similar to granulocyte levels), persistent pancytopenia, and hemorrhagic complications have been reported. DERMAL: COMMON (5% or greater): Dermatitis, pruritus, bacterial skin infection, skin ulceration or blistering, and hyperpigmentation.
    • F) WITH POISONING/EXPOSURE
      • 1) Overdose data are limited. Overdose effects are anticipated to be an extension of adverse effects following therapeutic doses. Severe leukopenia, anemia, thrombocytopenia, and a hemorrhagic diathesis with subsequent delayed bleeding may develop following total doses higher than 0.4 mg/kg of body weight for a single course. Exposure of the eyes to mechlorethamine results in inflammation, pain, burning, photophobia, and blurred vision. Irreversible anterior eye injury and blindness may occur.
0.2.20 REPRODUCTIVE HAZARDS
  • A) Mechlorethamine is classified as FDA pregnancy category D. There are no adequate and well-controlled studies of mechlorethamine use in pregnancy women. However, at least 2 cases of congenital malformations have been reported among 6 women who received mechlorethamine during pregnancy. Mechlorethamine was teratogenic in animals after a single subQ dose. Women should avoid pregnancy during mechlorethamine therapy. Inform patients of these risks if mechlorethamine is used during pregnancy or if a patient becomes pregnant during treatment with this drug
0.2.21 CARCINOGENICITY
  • 0.2.21.1 IARC CATEGORY
    • A) IARC Carcinogenicity Ratings for CAS51-75-2 (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):
      • 1) IARC Classification
        • a) Listed as: Nitrogen mustard
        • b) Carcinogen Rating: 2A
      • 1) The agent (mixture) is probably carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans. This category is used when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals. In some cases, an agent (mixture) may be classified in this category when there is inadequate evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals and strong evidence that the carcinogenesis is mediated by a mechanism that also operates in humans. Exceptionally, an agent, mixture or exposure circumstance may be classified in this category solely on the basis of limited evidence of carcinogenicity in humans.
  • 0.2.21.2 HUMAN OVERVIEW
    • A) Mechlorethamine is a probable carcinogen in humans.
0.2.22 GENOTOXICITY
  • A) POSITIVE for DNA damage, DNA inhibition, unscheduled DNA synthesis, DNA repair, mutations, locus test, chromosome aberrations, chromosome loss and nondisjunction, sister chromatid exchanges, micronucleus test, inducing aneuploidy and in vitro oncogenic transformation, in a variety of prokaryotic and eukaryotic test systems.
  • B) Mechlorethamine was genotoxic in multiple genetic toxicology studies including bacterial reverse mutation assay and chromosome aberrations (Prod Info VALCHLOR(TM) topical gel, 2013).
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