National Toxicology Program

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

Names (NTP)

• 4,4'-(2-PYRIDINYLMETHYLENE)BISPHENOL DIACETATE (9CI)
• DULCOLAX
• Bisacodyl

Human Toxicity Excerpts

• SIGNS AND SYMPTOMS: With long term use or overdosage of stimulant laxatives, electrolyte disturbances including hypokalemia, hypocalcemia, metabolic acidosis or alkalosis, abdominal pain, diarrhea, malabsorption, weight loss , and protein-losing enteropathy may occur Electrolyte disturbances may produce vomiting and muscle weakness; rarely osteomalacia, secondary aldosteronism, and tetany may occur. Pathologic changes in including structural damage to the myenteric plexus, severe and permanent interference with colonic motility, and hypertrophy of the muscularis mucosae may occur with chronic use. /Stimulant laxatives/ [McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 2784]**PEER REVIEWED**
  

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Non-Human Toxicity Excerpts

• LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Dietary supplementation with bisacodyl at concentrations ranging from 1 to 0.3% was found to induce both calculi and epithelial proliferation lesions, including a transitional-cell carcinoma, in the urinary bladder of F344uCrj rats. In order to clarify the relationship between the bisacodyl-associated urinary bladder calculi and the development of proliferative lesions in the urinary bladder, male and female rats were administered bisacodyl-diets at concentrations of 0.3, 0.1, and 0.03% for 32 wk. Both sexes of animals treated with bisacodyl suffered from diarrhea throughout the experimental period. Epithelial proliferative lesions and calculus formation were observed only in the urinary bladder of male rats given the 0.3% bisacodyl diet. Proliferative lesions and increases of bromouracil deoxyriboside (BUdR) labeling indices were found only in the urinary bladder epithelium of rats with calculi, the severity of the former correlating with the calculus weight ... [Toyoda K et al; J Toxicol Environ Health 39 (1): 59-78 (1993) ]**PEER REVIEWED**
  

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Human Toxicity Values

• None found

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Non-Human Toxicity Values

• LD50 Dog oral >15 g/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2840]**PEER REVIEWED**
  
• LD50 Mouse oral 17.5 g/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2840]**PEER REVIEWED**
  
• LD50 Rat oral 4.3 g/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2840]**PEER REVIEWED**
  
• LD50 Rat oral >3 g/kg [O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 212]**PEER REVIEWED**
  

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Absorption, Distribution and Excretion

• Absorption of bisacodyl ... is minimal following oral or rectal administration. Any bisacodyl that is absorbed is metabolized in the liver and excreted in the urine and/or distributed in milk. [McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 2787]**PEER REVIEWED**
  
• Following oral administration of therapeutic dosages of diphenylmethane derivatives, /bowel/ evacuation is produced in 6 to 8 hours. Rectally administered bisacodyl ... produces evacuation of the colon in within 15 minutes to 1 hour. [McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 2787]**PEER REVIEWED**
  
• As much as 5% of orally administered dose is absorbed & excreted in urine as glucuronide. [Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1046]**PEER REVIEWED**
  
• Excreted primarily in the feces ... [Cowl, C.T. Physician's Handbook 10th edition. Lippincott Williams & Wilkins, Philadelphia, PA. 2003, p. 209]**PEER REVIEWED**
  
• The absorption and plasma level profile and laxative effects of 10 mg bisacodyl as an experimental solution ... in 12 healthy volunteers are described. Results indicate only small amounts of drug were systemically available after administration of /solution/, dragee /(sugar coated capsule)/ and suppository. Urinary excretion was 43.4% for solution, 9.2% for dragee and 3.1% for suppository. [Roth W; Arzneim Forsch 39 (4): 570-74 (1988) ]**PEER REVIEWED**
  

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Metabolism/Metabolites

• Following oral or rectal administration bisacodyl is converted to the active desacetyl metabolite bis(p-hydroxyphenyl)pyridyl-2-methane by intestinal and bacterial enzymes. [Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 1363]**PEER REVIEWED**
  
• HPLC method which permits simultaneous detection of bisacodyl (BIS) & its monodesacetylated (mono) as well as totally desacetylated (DES) form, was used to study the intestinal handling of BIS (20 nmol/mL), when incubated for 60 min at the mucosal side of the preparations specified. In jejunal mucosa fluid, BIS disappeared completely in short time, & there was nearly equivalent rise in DES; mono was transitorily present. Hydrolysis was also rapid in mucosal fluid which had been in contact with jejunal sacs for 30 sec, but BIS was stable in blank incubations. Hydrolysis of BIS was slower by colonic than by jejunal sacs, & all 3 forms were present during incubation. It seemed still lower in mucosal fluid which had been in contact with colonic sac for 5 min. BIS & DES accumulate in jejunal & colonic serosal fluid mainly as conjugates (above 95%), & DES was in all cases the only conjugated metabolite present. Accumulation in jejunal serosal fluid was same whether BIS or DES was added. [Hillestad B et al; Intestinal Handling of Bisacodyl and Picosulphate by Everted Sacs of the Rat Jejunum and Stripped Colon; Acta Pharmacol Toxicol 51(4) 388 (1982) ]**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.