National Toxicology Program

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

Names (NTP)

• Actinomycin D
• ACTINOMYCIN C1

Human Toxicity Excerpts

• PATIENT MAY...EXPERIENCE MALAISE, FATIGUE, LETHARGY, MYALGIA, & FEVER. ... ANAPHYLAXIS HAS BEEN REPORTED. ... DRUG IS LOCALLY TOXIC, & PHLEBITIS & CELLULITIS MAY OCCUR @ SITE OF INJECTION; EXTRAVASATION MAY CAUSE SERIOUS LOCAL TISSUE DAMAGE. VENOUS THROMBOSIS MAY ALSO RESULT FROM LOCAL EFFECTS. [Osol, A. (ed.). Remington's Pharmaceutical Sciences. 16th ed. Easton, Pennsylvania: Mack Publishing Co., 1980., p. 1089]**PEER REVIEWED**
  
• PROCTITIS, DIARRHEA, GLOSSITIS, CHEILITIS, & ULCERATIONS OF THE ORAL MUCOSA ARE COMMON; DERMATOLOGICAL MANIFESTATIONS INCL ALOPECIA, AS WELL AS ERYTHEMA, DESQUAMATION, & INCR INFLAMMATION AND PIGMENTATION IN AREAS PREVIOUSLY OR CONCOMITANTLY SUBJECTED TO X-RADIATION. SEVERE INJURY MAY OCCUR AS A RESULT OF LOCAL TOXIC EXTRAVASATION. [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. 1241]**PEER REVIEWED**
  
• TOXIC MANIFESTATIONS INCL ANOREXIA, NAUSEA, & VOMITING, USUALLY BEGINNING A FEW HR AFTER ADMIN. HEMATOPOIETIC SUPPRESSION WITH PANCYTOPENIA MAY OCCUR IN THE FIRST WEEK AFTER COMPLETION OF THERAPY. [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. 1241]**PEER REVIEWED**
  
• ACTINOMYCIN D OF UNSPECIFIED ORIGIN & PURITY INDUCED CHROMATID BREAKS & TRANSLOCATIONS IN SHORT-TIME HUMAN PERIPHERAL LEUCOCYTE CULTURES, HUMAN EPIDERMAL FIBROBLASTS & HELA CELLS. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V10 36]**PEER REVIEWED**
  
• Hematologic toxicity is one of the major and dose-limiting adverse effects of dactinomycin and is manifested primarily by leukopenia and thrombocytopenia. Anemia, pancytopenia, reticulopenia, agranulocytosis, and aplastic anemia may also occur. Myelosuppression, which is often first manifested by a decrease in the platelet count, usually occurs 1-7 days after completion of a course of therapy with dactinomycin. Leukocyte and platelet nadirs generally occur 14-21 days following completion of a course of therapy, and leukocyte and platelet counts usually return to normal levels within 21-25 days. The patient's hematologic status must be carefully monitored. [McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 95. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1995 (Plus Supplements 1995)., p. 633]**PEER REVIEWED**
  
• The other major and dose-limiting adverse effects of dactinomycin are GI and oral mucosal toxicities. Nausea and vomiting usually occur within a few hours after administration of the drug and can last up to 24 hours. Antiemetics may be effective in preventing or treating nausea and vomiting. Anorexia, abdominal pain, diarrhea, proctitis, and GI ulceration may also occur. Stomatitis, cheilitis, glossitis, dysphagia, and oral ulceration occur often in patients receiving dactinomycin; esophagitis and pharyngitis may also occur. If stomatitis or diarrhea develops in patients who receive dactinomycin with other antineoplastic agents, the manufacturer recommends that therapy be discontinued until these symptoms have subsided. [McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 95. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1995 (Plus Supplements 1995)., p. 633]**PEER REVIEWED**
  
• Dactinomycin inhibits rapidly proliferating cells of normal and neoplastic origin and, on a molar basis, is among the most potent antitumor agents known. [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. 1241]**PEER REVIEWED**
  

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Non-Human Toxicity Excerpts

• IN RATS...50-100 UG/KG...INDUCED MALFORMATIONS OF CNS, VISCERA & SKELETON; IN RABBITS, EVEN SMALL DOSES...MORE EMBRYOTOXIC & LESS TERATOGENIC. IN HAMSTERS GIVEN 100 UG/KG...ON DAYS 7 & 8 OF PREGNANCY, EMBRYOTOXICITY & TERATOGENICITY ON OSSIFICATION...OBSERVED. WITH LOWER DOSE LEVELS NO EMBRYOTOXIC OR TERATOGENIC EFFECTS... [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V10 36 (1976)]**PEER REVIEWED**
  
• AQ SOLN OF ACTINOMYCIN D OF UNSPECIFIED PURITY WAS INJECTED IP INTO ICR/HA SWISS MICE...0.34-1.67 MG/KG BODY WT. ...REDN IN NUMBER OF IMPLANTATION SITES & INCR IN EARLY EMBRYONIC DEATHS...OBSERVED. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V10 36 (1976)]**PEER REVIEWED**
  
• ...5-10 MG/L INDUCED MITOTIC CROSSING OVER IN SOYABEAN GLYCINE MAX L...50 MG/L...INDUCED MEIOTIC CROSSING OVER IN BARLEY. ...INDUCTION OF FORWARD MUTATIONS IN AD-3A & AD-3B REGIONS OF NEUROSPORA CRASSA. .../IN/ OREGON R DROSOPHILA MELANOGASTER FEMALES INCR FREQUENCIES OF CROSSING OVER IN MEIOTIC & PREMEIOTIC CELLS. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V10 36 (1976)]**PEER REVIEWED**
  
• INHIBITION OF RNA SYNTH, NECROSIS, HYPERPLASIA & ALTERED MITOTIC INDEX WERE OBSERVED IN MOUSE SKIN WITHIN 4 DAYS AFTER 6 APPLICATIONS OF 15 UG ACTINOMYCIN D. AFTER SINGLE APPLICATION OF 1 UG, ONLY RNA SYNTH WAS INHIBITED. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V10 35 (1976)]**PEER REVIEWED**
  
• IN DOG, IV...OF 15 UG/KG...FOR 5 DAYS PRODUCED ANOREXIA, DEHYDRATION FROM VOMITING & HEMORRHAGES &/OR ULCERS IN INTESTINE & COLON. ...ACTINOMYCIN D... TOXIC TO BLOOD-FORMING TISSUES, LYMPHOID TISSUES & INTESTINAL EPITHELIUM IN DOGS. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V10 35 (1976)]**PEER REVIEWED**
  
• 2 GROUPS...OF 11 & 15 MALE FISCHER 344 RATS...REPEATED IP...0.025-0.05 OR 0.05 MG/KG...2-5 TIMES/WK...18 WK (TOTAL...0.65 & 0.8 MG)...OBSERVATION FOR UP TO 50 WK. 6 & 12 MESENCHYMAL TUMORS...RESPECTIVELY...APPEARANCE OF 1ST TUMOR WAS 23 WK. ...NO TUMORS OCCURRED IN 10 CONTROLS GIVEN IP...0.9% SALINE THRICE WEEKLY FOR 50 WK. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V10 34 (1976)]**PEER REVIEWED**
  
• .../MESENCHYMOMAL TUMOR/ WAS SEEN AFTER 42 WK IN 1/9 RATS GIVEN SINGLE /IP/ INJECTIONS OF 2 MG/KG BODY WT BUT IN NONE OF 15 RATS GIVEN SINGLE INJECTIONS OF 0.5 OR 1 MG/KG BODY WT. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V10 34 (1976)]**PEER REVIEWED**
  
• TWO GROUPS OF 25 MALE & 25 FEMALE CHARLES RIVER CD RATS WERE GIVEN IP INJECTIONS OF 0.022 OR 0.045 MG/KG BODY WT ACTINOMYCIN D THRICE WEEKLY FOR 6 MO, FOLLOWED BY OBSERVATION FOR FURTHER 12 MO...PERITONEAL SARCOMAS DEVELOPED IN 32/38 MALES & 25/36 FEMALES. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V10 34 (1976)]**PEER REVIEWED**
  
• ...10 MALE BTK MICE...GIVEN 35 TWICE WEEKLY SC...0.2 UG/ANIMAL ACTINOMYCIN D. LOCAL SARCOMAS...IN 2/10 MICE BETWEEN 36 & 41 WK AFTER START OF TREATMENT. ... NO TUMORS...OBSERVED IN 20 CONTROLS INJECTED WITH OLIVE OIL OR SALINE & OBSERVED FOR 66 WK. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V10 33 (1976)]**PEER REVIEWED**
  
• Atrophy of thymus, spleen, and other lymphatic tissues occurs in experimental animals. It may produce alopecia, and, when extravasated subcutaneously, the drug causes marked local inflammation. Erythema sometimes progressing to necrosis has been noted in areas of the skin exposed to x-radiation either before, during, or after administration of dactinomycin. [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. 1241]**PEER REVIEWED**
  
• DOSAGE OF ACTINOMYCIN D TO RATS OF 0.1-0.3 MG/KG CAUSED DEATH, RESORPTION OF EMBRYOS RANGING FROM 7.7-99.2% & MALFORMATION OF SURVIVORS RANGING FROM 0.9-100.0%. /FROM TABLE/ [Hayes, W.J., Jr., E.R. Laws Jr., (eds.). Handbook of Pesticide Toxicology Volume 1. General Principles. New York, NY: Academic Press, Inc., 1991., p. 190]**PEER REVIEWED**
  
• In rabbits, injection of actinomycin either into the lens or into the vitreous body has caused a severe intraocular reaction of both anterior and posterior segments, with opacification of the lens and the cornea. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 51]**PEER REVIEWED**
  
• In bullfrogs, intraperitoneal injection of actinomycin D interferes with healing of experimental wounds in the epithelium of the lens. It is believed that actinomycin D blocks the normal process of healing by suppressing RNA and DNA manufacture in the epithelial cells, inhibiting their mitosis and migration. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 51]**PEER REVIEWED**
  
• DACTINOMYCIN FOUND TO PRODUCE PULMONARY EDEMA FOLLOWING INTRATRACHEAL ADMIN IN RATS. SEVERITY OF LUNG DAMAGE DOSE-RELATED. CONFLUENT EDEMA OF ENTIRE LUNG REVEALED. EFFECTS APPEAR TO BE LOCALIZED IN PULMONARY TISSUE. [GIRI SN ET AL; TOXICOLOGY 4(1): 53 (1975)]**PEER REVIEWED**
  
• NUCLEI ISOLATED FROM RAT LIVER, HEART, & KIDNEY CATALYZE OXYGEN CONSUMPTION IN THE PRESENCE OF NADPH & ACTINOMYCIN D. [BACHUR NR ET AL; CANCER RES 42(3): 1078 (1982)]**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

• IN RABBITS GIVEN 1 MG/KG BODY WT ACTINOMYCIN D BY IV INJECTION, LESS THAN 1/10 OF INITIAL CONCN IN BLOOD COULD BE DETECTED AFTER 2 HR; AFTER 10 HR SLIGHT INCR IN BLOOD LEVEL WAS OBSERVED. 30 MIN AFTER ITS INJECTION HIGHEST LEVELS WERE FOUND IN KIDNEY, HEART, SPLEEN & LIVER; IT WAS ALSO PRESENT IN BILE & URINE. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V10 35 (1976)]**PEER REVIEWED**
  
• FOLLOWING INTRACARDIAC ADMIN OF [(3)H]ACTINOMYCIN D TO RAT (3)H WAS RAPIDLY TAKEN UP BY TISSUES. DRUG WAS POORLY PROTEIN-BOUND, & 27% WAS EXCRETED IN BILE IN 1 HR, 31% IN 4 HR.[The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 2: A Review of the Literature Published Between 1970 and 1971. London: The Chemical Society, 1972., p. 117]**PEER REVIEWED**
  
• Actinomycin is much less potent when given orally than when administered by parenteral injection. The drug is excreted both in bile and in the urine, and disappears from plasma with a terminal half-life of 36 hours. [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. 1241]**PEER REVIEWED**
  

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Metabolism/Metabolites

• None found

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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.