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Toxicity Effects

CAS Registry Number: 1239-45-8

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 2.

Names 1

  • Ethidium bromide
  • HOMIDIUM BROMIDE
  • Homodium Bromide
  • Phenanthridinium, 3,8-Diamino-5-Ethyl-6-Phenyl-, Bromide (8ci)(9ci)

Human Toxicity Excerpts

  • None found

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Non-Human Toxicity Excerpts

  • GENOTOXICITY: /Ethidium bromide/ appears to affect segregation in yeast during meiosis. Ethidium bromide forms a highly fluorescent complex with native DNA by intercalation between base-pairs.[WHO Food Additive Series 25: Isometamidium (20438-03-3)(1990). Available from, as of March 21, 2005: http://www.inchem.org/pages/jecfa.html] **PEER REVIEWED**
  • GENOTOXICITY: Ethidium bromide, a frame-shift mutagen in Salmonella typhimurium strains with metabolic activation and ... is also mutagenic to yeast (Saccharomyces cerevisiae) producing respiratory deficient colonies (petite) by its effects on mitochondrial DNA.[WHO Food Additive Series 25: Isometamidium (20438-03-3)(1990). Available from, as of March 21, 2005: http://www.inchem.org/pages/jecfa.html] **PEER REVIEWED**
  • GENOTOXICITY: The effects of ethidium bromide (EtBr) on human lymphocytes were studied by the method of anomalous viscosity time dependence (AVTD) and by the comet assay. EtBr at low concentrations increased the maximum viscosity and time of radial migration as measured with AVTD at neutral conditions of lysis. A pronounced relaxation of DNA loops was observed with the neutral comet assay. The maximal comet length corresponded to 2 Mb DNA loops. At high concentrations of EtBr, 2 mg/mL, significant reduction in AVTD below control level was seen that suggested hypercondensation of chromatin. The hypercondensation was directly observed with the neutral comet assay. EtBr did not induce DNA strand breaks as measured by the alkaline comet assay. The hypercondensed nuclei could be decondensed by irradiation with gamma-rays or exposure to light. The data provide evidence that EtBr at high concentrations resulted in hypercondensation of chromatin below control level. The comet assay confirmed that the increase in AVTD peaks deals with relaxation of loops and AVTD decrease is caused by chromatin condensation. The prediction of the AVTD theory for a correlation between time of radial migration and condensation of chromatin was verified. Further, the data show that the comet assay at neutral conditions of lysis is rather sensitive to DNA loop relaxation in the absence of DNA damage. Finally, donor specificity was found for the hypercondensation.[Belyaev IY et al; Biochim Biophys Acta 1428 (2-3): 348-56 (1999)] **PEER REVIEWED** PubMed Abstract
  • LABORATORY ANIMALS: Acute Exposure: Homidium was a moderate eye irritant but not a skin irritant in the rabbit. /Homidium/[WHO Food Additive Series 25: Isometamidium (20438-03-3)(1990). Available from, as of March 21, 2005: http://www.inchem.org/pages/jecfa.html] **PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Respiratory impairment was seen after intravenous administration while necrosis at the injection site occurred following subcutaneous injection. /Homidium/[WHO Food Additive Series 25: Isometamidium (20438-03-3)(1990). Available from, as of March 21, 2005: http://www.inchem.org/pages/jecfa.html] **PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: The major signs of toxicity noted after intravenous and subcutaneous dosing /in rats/ included tremors, prostration and sedation. /Homidium/[WHO Food Additive Series 25: Isometamidium (20438-03-3)(1990). Available from, as of March 21, 2005: http://www.inchem.org/pages/jecfa.html] **PEER REVIEWED**
  • LABORATORY ANIMALS: Neurotoxicity: ...Ethidium bromide (EBr) injection can give rise to matrix-enriched megamitochondria and is known to inhibit or suppress mitochondrial RNA, DNA, and protein synthesis in mammalian cells. ...The neurotoxic properties of EBr /were investigated and it was/ found that status spongiosus of the white matter occurs in association with rodlike inclusions in oligodendrocytes visible by light microscopy. Electron microscopy confirmed the intramyelinic location of the edema and showed hypertrophic as well as degenerative changes of oligodendroglial cytoplasm; this was associated with "scroll-like" membranous inclusions similar to the whorled structures previously found in oligodendroglia of rats treated with hypercholesterolemic drugs.[Spencer PS, Schaumburg HH eds; Experimental and Clinical Neurotoxicology 1st ed p.131 (1980)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: Peripheral nerve ultrastructure was assessed after single or multiple local injections of the intercalating dye ethidium bromide. Thirty-four adult Wistar rats of both sexes were divided into five groups and maintained in a controlled environment with rat chow and water ad libitum throughout the experiment. The experimental animals were injected with 1 microl of 0.1% ethidium bromide in 0.9% saline into the central third of the left sciatic nerve 1 (group 1), 2 (group 2), 4 (group 3), 6 (group 4) or 8 (group 5) times. In groups 2 to 5 the injections were made at 28-day intervals. Control animals received the same amount of 0.9% saline. The animals were killed at different times after injection: group 1 at 7 days (2 rats) and 15 days (2 rats); for groups 2, 3, 4 and 5, all rats were killed 10 days after the last injection and the lesions were investigated by light and transmission electron microscopy. In the acute lesions, intoxicated Schwann cells showed a vacuolated cytoplasm and separation of the sheaths from the axon. Myelin sheaths underwent progressive vesiculation and subsequent segmental demyelination. Myelin debris were withdrawn by macrophages and remyelination by Schwann cells was prominent. With the increase in the number of injections collagen fibers also increased in number and progressively enveloped smaller numbers of remyelinated axons composing new fascicles. Wallerian degeneration of fibers apparently not affected by ethidium bromide was more intense in the nerves from groups 4 and 5. The peripheral nerve repairs itself after demyelinating challenges with a profusion of collagen fibers and new fasciculations. This experimental model is valid to mimic recurrent demyelinating neuropathies.[Riet-Correa G et al; Braz J Med Biol Res 35 (1): 99-104 (2002)] **PEER REVIEWED** PubMed Abstract

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • LD50 Mouse intraperitoneal 20 mg/kg[Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1031] **PEER REVIEWED**
  • LD50 Mouse subcutaneous 110 mg/kg[Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1031] **PEER REVIEWED**
  • LD50 Rat dermal > 2000 mg/kg[WHO Food Additive Series 25: Isometamidium (20438-03-3)(1990). Available from, as of March 21, 2005: http://www.inchem.org/pages/jecfa.html] **PEER REVIEWED**
  • LD50 Rat iv 27 mg/kg[WHO Food Additive Series 25: Isometamidium (20438-03-3)(1990). Available from, as of March 21, 2005: http://www.inchem.org/pages/jecfa.html] **PEER REVIEWED**
  • LD50 Rat oral >2000 mg/kg[WHO Food Additive Series 25: Isometamidium (20438-03-3)(1990). Available from, as of March 21, 2005: http://www.inchem.org/pages/jecfa.html] **PEER REVIEWED**
  • LD50 Rat sc 80 mg/kg[WHO Food Additive Series 25: Isometamidium (20438-03-3)(1990). Available from, as of March 21, 2005: http://www.inchem.org/pages/jecfa.html] **PEER REVIEWED**

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Absorption, Distribution And Excretion

  • None found

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Metabolism/Metabolites

  • The metabolism of ethidium bromide by isolated rat hepatocytes is significantly enhanced by pre-treatment of animals with phenobarbitone (PB) and 3-methylcholanthrene (3-MC). Pre-treatment with PB and 3-MC results in a 2.5- and 1.5-fold increase, respectively in the amount of the principal metabolite, ethidium 8-N-glucuronide, compared with that formed by hepatocytes from untreated rats. The formation of ethidium 3-N-glucuronide is not enhanced by pre-treatment with either PB or 3-MC. Two new metabolites, hydroxyethidium glucuronide and a transient unidentified species, have been detected by HPLC and are formed only by hepatocytes from animals pre-treated with 3-MC.[Tettey JN et al; Chem Biol Interact 123 (2): 105-15 (1999)] **PEER REVIEWED** PubMed Abstract

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Tsca Test Submissions

  • None found

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Footnotes

1 Source: the NTP's CEBS database.

2 Source: the National Library of Medicine's Hazardous Substance Database, 02/28/2017.

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