Testing Information

Testing Status of Agents at NTP

CAS Registry Number: 11056-06-7 (Bleomycin) Toxicity Effects

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Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 1

Human Toxicity Excerpts

  • MOST SERIOUS ADVERSE REACTION TO THIS DRUG IS PULMONARY TOXICITY, WHICH BEGINS WITH FINE RALES, COUGH, & DIFFUSE BASILAR INFILTRATES, PROGRESSES TO SEVERE, & SOMETIMES FATAL, PULMONARY FIBROSIS. [Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 1246]**PEER REVIEWED**
  • ... BLEOMYCIN CAUSES MINIMAL BONE-MARROW TOXICITY. MOST COMMONLY ENCOUNTERED ADVERSE EFFECTS ARE MUCOCUTANEOUS REACTIONS, INCL STOMATITIS & ALOPECIA AS WELL AS HYPERPIGMENTATION, HYPERKERATOSIS, PRURITIC ERYTHEMA, ULCERATION, & VESICULATION OF SKIN. [Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 1246]**PEER REVIEWED**
  • BLEOMYCIN COMMONLY CAUSES ... CHILLS ... OTHER OCCASIONAL ADVERSE EFFECTS ARE CUTANEOUS DESQUAMATION, HYPERESTHESIA, PRURITUS, TENDERNESS ... . /SULFATE SALT/ [Osol, A. (ed.). Remington's Pharmaceutical Sciences. 16th ed. Easton, Pennsylvania: Mack Publishing Co., 1980., p. 1086]**PEER REVIEWED**
  • OTHER TOXIC REACTIONS TO BLEOMYCIN INCL HYPERPYREXIA, HEADACHE, NAUSEA, & VOMITING ... . [Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 1246]**PEER REVIEWED**
  • BLEOMYCIN CAUSES CHROMOSOMAL ABNORMALITIES, PROBABLY AS A RESULT OF ITS ABILITY TO CAUSE STRAND SCISSION OF DNA. /SULFATE SALT/ [Booth, N.H., L.E. McDonald (eds.). Veterinary Pharmacology and Therapeutics. 5th ed. Ames, Iowa: Iowa State University Press, 1982., p. 793]**PEER REVIEWED**
  • Rarely, disorientation, aggressive behavior, hematuria, and cystitis have been reported. Anorexia and wt loss are common and may persist after discontinuance of bleomycin; whether these effects are results of malignancy or drug therapy is difficult to determine. /Bleomycin sulfate/ [McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 489]**PEER REVIEWED**
  • For use in iv infusion fluid a concn of 10 ug/ml for single injection, has been reported non-toxic to the retina. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 150]**PEER REVIEWED**
  • Bleomycin may be ototoxic when it is given in high dosage. [Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 192]**PEER REVIEWED**
  • The main reported side effect with intralesional use is local burning or pain within 24 to 48 hours after injection. Blackening and eschar at the site of the lesion within 1 or 2 weeks and healing usually occurs within 2 to 3 weeks without scarring. Cases of urticaria, nail loss, and Raynaud's phenomenon have also been reported. [US Pharmacopeial Convention; US Pharmacopeia Dispensing Information (USP DI); Drug Information for the Health Care Professional 12th ed, V.I p.669 (1992)]**PEER REVIEWED**
  • Pulmonary toxicity occurs in 10 to 40% of treated patients, usually 4 to 10 weeks after initiation of treatment; approximately 1% of treated patients have died of pulmonary fibrosis. Pulmonary toxicity is age- and dose-related, occurring most frequently in patients over 70 years of age and/or receiving a total dose greater than 400 Units (although) it has been reported with doses as low as 20 to 60 Units. It may be irreversible and fatal; however, there is some evidence that in patients who survive, symptoms and pulmonary function parameters return to normal in approximately 2 years. It occurs at lower doses in patients who have received other antineoplastics or thoracic radiation; mortality may be as high as 10% in patients who have received pulmonary irradiation. A low-dose allergic pneumonitis has also been reported. [US Pharmacopeial Convention; US Pharmacopeia Dispensing Information (USP DI); Drug Information for the Health Care Professional 12th ed, V.I p.669 (1992)]**PEER REVIEWED**
  • Mucocutaneous toxicity is the most frequent adverse effect of bleomycin, occurring in at least 50% of patients receiving the drug. Adverse mucocutaneous effects usually are evident with 1 to 3 weeks following the initiation of therapy. Mucocutaneous effects appear to be reversible and related to total dosage, occurring usually after 150 to 200 units of bleomycin have been administered. Occasionally, mucocutaneous toxicity may necessitate discontinuation of drug or reduction of dosage. /Bleomycin sulfate/ [McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 489]**PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • IN DOGS, BLEOMYCIN PRODUCES INTERSTITIAL PNEUMONIA AND AFTER INTENSIVE TREATMENT CAUSES PLEURAL SCARRING AND PULMONARY FIBROSIS. ... TOXIC EFFECTS ON THE SKIN INCLUDE DESQUAMATION, HYPERPIGMENTATION, & PRURITIC ERYTHEMA. /SULFATE SALT/ [Booth, N.H., L.E. McDonald (eds.). Veterinary Pharmacology and Therapeutics. 5th ed. Ames, Iowa: Iowa State University Press, 1982., p. 793]**PEER REVIEWED**
  • STRAINS OF ESCHERICHIA COLI DEFICIENT IN POSTREPLICATION RECOMBINATION REPAIR WERE MORE SENSITIVE TO BLEOMYCIN THAN WILD-TYPE, REPAIR-PROFICIENT STRAINS. MUTANTS LACKING EXCISION REPAIR FUNCTIONS WERE NO MORE SENSITIVE TO BLEOMYCIN THAN THE WILD-TYPE STRAINS, INDICATING THAT THIS PATHWAY IS NOT INVOLVED IN THE REPAIR OF BLEOMYCIN-DAMAGED DNA. [ATTFIELD PV, PINNEY RJ; J GEN MICROBIOL 128 (3): 539 (1982)]**PEER REVIEWED**
  • Bleomycin sulfate produces cataracts in newborn white rats after ip injection. Cataracts appear 14 to 16 days and progress to become nearly complete. If the drug is not administered until 10 or more days after birth, no cataracts are produced. /Bleomycin sulfate/ [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 150]**PEER REVIEWED**
  • Bleomycin has been found to be teratogenic in mice given intraperitoneal doses of 0.6 to 5 units/kg body wt on days 7 to 12 of gestation; increased fetal resorption occurred at doses of 3 and 5 Units per kg of body weight. [US Pharmacopeial Convention; US Pharmacopeia Dispensing Information (USP DI); Drug Information for the Health Care Professional 12th ed, V.I p.668 (1992)]**PEER REVIEWED**
  • Bleomycin has not been found to be mutagenic according to the Ames assay. However, chromosomal aberrations were reported in bone marrow cells and spermatogonia of mice given very high doses. [US Pharmacopeial Convention; US Pharmacopeia Dispensing Information (USP DI); Drug Information for the Health Care Professional 12th ed, V.I p.668 (1992)]**PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • None found

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Absorption, Distribution and Excretion

  • MICROBIOLOGICAL ASSAYS HAVE BEEN DEVISED FOR MEASURING DISTRIBUTION OF DRUG IN ANIMALS, & RELATIVELY HIGH CONCN HAVE BEEN DETECTED IN SKIN & LUNGS, MAJOR SITES OF TOXICITY. ... IN MAN BLEOMYCIN LOCALIZES IN VARIOUS TUMORS, SUGGESTING LOWER LEVEL OF INACTIVATING ENZYME @ THESE SITES. /BLEOMYCINS/ [Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1291]**PEER REVIEWED**
  • BLEOMYCIN IS POORLY ABSORBED ORALLY AND IS ALSO INACTIVATED IN THE GUT AND LIVER. CONSEQUENTLY, IT MUST BE ADMIN PARENTERALLY. [Osol, A. (ed.). Remington's Pharmaceutical Sciences. 16th ed. Easton, Pennsylvania: Mack Publishing Co., 1980., p. 1086]**PEER REVIEWED**
  • Bleomycin is absorbed systemically following intrapleural or ip admin. /Bleomycin sulfate/ [McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 489]**PEER REVIEWED**
  • Following parenteral admin of bleomycin in animals, the drug is distributed mainly into the skin, lungs, kidney, peritoneum, and lymphatics. Concn of the drugs in tumor cells of the skin and lungs are higher than those in hematopoietic tissue. The low concn of bleomycin found in bone marrow may be related to the high concn of bleomycin degradative enzymes present in that tissue. Results of an animal study suggest that the concn of bleomycin in chemically induced squamous cell carcinomas is higher than that in sarcomas, partially as a result of a lower concn of bleomycin degradative enzymes in squamous cell carcinomas than in sarcomas. /Bleomycin sulfate/ [McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 488]**PEER REVIEWED**
  • In patients with normal renal function, the serum or plasma terminal half-life of bleomycin is about 2 hr. In patients with creatinine clearances less than 35 ml/min, the terminal half-life of the drug is inversely related to creatinine clearance ... The metabolic fate of bleomycin has not been determined. In humans, 60-70% of a parenterally administered dose is excreted in the urine as active drug. /Bleomycin sulfate/ [McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 488]**PEER REVIEWED**
  • Following the im or iv injection of 15 mg bleomycin, peak plasma concn of about 1 and 3 ug per ml repectively have been reported. Up to 40% of a dose is excreted unchanged in the urine within 24 hr. [Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 192]**PEER REVIEWED**
  • Absorption: Approximately 45% of a dose is absorbed into the systemic circulation following intrapleural or ip administration. [US Pharmacopeial Convention; US Pharmacopeia Dispensing Information (USP DI); Drug Information for the Health Care Professional 12th ed, VI p.668 (1992)]**PEER REVIEWED**
  • Elimination: Renal, 60 to 70%, largely as unchanged drug; markedly reduced in renal failure. [US Pharmacopeial Convention; US Pharmacopeia Dispensing Information (USP DI); Drug Information for the Health Care Professional 12th ed, VI p.668 (1992)]**PEER REVIEWED**

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Metabolism/Metabolites

  • MOST TISSUES, EXCEPT LUNG & SKIN, HAVE RELATIVELY HIGH ACTIVITIES OF AN ENZYME, BLEOMYCIN HYDROLASE, THAT HYDROLYZES THE AMIDE GROUP OF THE BETA-AMINOALANINE AMIDE OF THE BLEOMYCIN CORE AND THEREBY INACTIVATES THE MOLECULE. /BLEOMYCINS/ [Gilman, A. G., L. S. Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 6th ed. New York: Macmillan Publishing Co., Inc. 1980., p. 1295]**PEER REVIEWED**

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TSCA Test Submissions

  • None found

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Footnotes

1 Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.

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Web page last updated on May 14, 2008