| A review of evidence leading to the prediction that 1,4-butanediol is not a carcinogen. | |
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MedLine Citation:
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PMID: 16193534 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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1,4-Butanediol is an industrial chemical used primarily as an intermediate in the manufacture of other organic chemicals. It has recently been associated with deaths, addiction and withdrawal related to its promotion and use as a dietary supplement. The rapid absorption and conversion of 1,4-butanediol to gamma-hydroxybutyric acid (GHB, or date rape drug) in animals and humans is well documented and is the basis for its abuse potential. A disposition and metabolism study conducted in F344 rats by the National Toxicology Program (NTP) confirmed the rapid conversion of 1-(14)C-1,4-butanediol to (14)CO2. Because of this, the toxicological profile of 1,4-butanediol resembles that of gamma-hydroxybutyric acid. Gamma-hydroxybutyric acid occurs naturally in the brain and peripheral tissues and is converted to succinate and metabolized through the TCA cycle. Although the function of gamma-hydroxybutyric acid in peripheral tissues is not known, the presence of specific high affinity receptors for gamma-hydroxybutyric acid suggests that it functions as a neuromodulator in the brain and neuronal tissue. Gamma-hydroxybutyric acid readily crosses the blood-brain barrier and elicits characteristic neuropharmacologic responses after oral, i.p., or i.v. administration. The same responses are observed after administration of 1,4-butanediol. The cyclic lactone of gamma-hydroxybutyric acid, gamma-butyrolactone, is also rapidly converted to gamma-hydroxybutyric acid by enzymes in the blood and liver in animals and humans, and produces pharmacological effects identical to those produced by 1,4-butanediol and gamma-hydroxybutyric acid. Gamma-butyrolactone was previously evaluated by the NTP in 14-day and 13-week prechronic toxicology studies and in 2-year chronic toxicology and carcinogenesis studies in F344 rats and B6C3F1 mice. No organ specific toxicity occurred. In the carcinogenesis studies there was an equivocal response in male mice based on a marginal increase in the incidence of pheochromocytomas of the adrenal medulla. Because the absence of chronic toxicity and significant carcinogenicity of gamma-hydroxybutyric acid were established in NTP prechronic and chronic studies with gamma-butyrolactone, it is concluded that similar results would be obtained in a 2-year study with 1,4-butanediol, and that 1,4-butanediol is not a carcinogen. |
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Authors:
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Richard D Irwin |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Journal of applied toxicology : JAT Volume: 26 ISSN: 0260-437X ISO Abbreviation: J Appl Toxicol Publication Date: 2006 Jan-Feb |
Date Detail:
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Created Date: 2006-01-04 Completed Date: 2006-03-28 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8109495 Medline TA: J Appl Toxicol Country: England |
Other Details:
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Languages: eng Pagination: 72-80 Citation Subset: IM |
Copyright Information:
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2005 John Wiley & Sons, Ltd. |
Affiliation:
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National Toxicology Program, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA. irwin@niehs.nih.gov |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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4-Butyrolactone
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toxicity Animals Biotransformation Butylene Glycols / pharmacokinetics, toxicity* Carcinogenicity Tests Humans Hydroxybutyrates / metabolism, toxicity Solvents / toxicity |
| Chemical | |
Reg. No./Substance:
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0/Butylene Glycols; 0/Hydroxybutyrates; 0/Solvents; 110-63-4/1,4-butanediol; 591-81-1/4-hydroxybutyric acid; 96-48-0/4-Butyrolactone |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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