Document Detail


Acute toxicity, distribution, and metabolism of 2,4,6-trinitrophenol (picric acid) in Fischer 344 rats.
MedLine Citation:
PMID:  1404487     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Picric acid (2,4,6-trinitrophenol) is widely used in industry, by the military, and as a research/clinical chemistry reagent. Characterization of the toxicity of this chemical has been limited. Thus the acute toxicity, distribution, and metabolism of picric acid were investigated using Fischer 344 rats. The LD50 for picric acid following oral dosing of male and female rats was established as 290 and 200 mg/kg, respectively. Blood gas analysis indicated severe acidosis during acute intoxication. Metabolism of picric acid was limited to reduction of nitro groups to amines. Metabolites isolated from urine included N-acetylisopicramic acid (14.8%), picramic acid (18.5%), N-acetylpicramic acid (4.7%), and unidentified components (2.4%). Approximately 60% of the parent picric acid was excreted unchanged. The plasma half-life for picric acid was 13.4 h with a gut absorption coefficient (ka) of 0.069 h-1. Twenty-four hours following oral administration of [14C]picric acid (100 mg/kg), the primary depots of radioactivity (per gram tissue basis) were blood, spleen, kidney, liver, lung, and testes. Respective tissue/blood ratios were 0.37, 0.31, 0.28, 0.26, and 0.22. All other tissue assayed had partition ratios < 0.20, with brain and adipose tissue having the least amount of radioactivity. Tissue/blood ratios were essentially maintained over a 48-h postadministration period. Binding (in vitro) of [14C]picric acid to plasma proteins (whole blood preparations) demonstrated both high- and low-affinity binding sites, with dissociation constants of 3.18 x 10(-6) and 2.85 x 10(-4) M, respectively. The findings of this investigation provide information on the acute toxicity, metabolism, and distribution of picric acid, which can be used in risk assessment analyses and in the design of subchronic and chronic toxicity tests.
Authors:
J F Wyman; M P Serve; D W Hobson; L H Lee; D E Uddin
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Journal of toxicology and environmental health     Volume:  37     ISSN:  0098-4108     ISO Abbreviation:  J Toxicol Environ Health     Publication Date:  1992 Oct 
Date Detail:
Created Date:  1992-11-10     Completed Date:  1992-11-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7513622     Medline TA:  J Toxicol Environ Health     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  313-27     Citation Subset:  IM    
Affiliation:
Naval Medical Research Institute Detachment (Toxicology), Wright Patterson AFB, Ohio 45433-6503.
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MeSH Terms
Descriptor/Qualifier:
Acidosis / chemically induced*
Administration, Oral
Animals
Biological Availability
Blood Gas Analysis
Dose-Response Relationship, Drug
Female
Half-Life
Indicators and Reagents / administration & dosage,  pharmacokinetics,  toxicity*
Injections, Intravenous
Intestinal Absorption
Lethal Dose 50
Male
Picrates / administration & dosage,  pharmacokinetics,  toxicity*
Rats
Rats, Inbred F344
Tissue Distribution
Chemical
Reg. No./Substance:
0/Indicators and Reagents; 0/Picrates; 88-89-1/picric acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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