Biomaterial Database

In vivo and in vitro metabolism of 2,4-dinitrotoluene in strain A mice. 1985

H A Schut, and R Dixit, and T R Loeb, and G D Stoner

The elimination and metabolism of a single dose (100 mg/kg) of 2,4-dinitrotoluene (2,4-DNT) in A/J mice were examined. After intraperitoneal administration, elimination was rapid, with 70% of the dose appearing in the urine within 4 hr. Four hours after oral administration, only 28.5% of the dose was excreted in the urine, which increased to 66% after 8 hr. Elimination via the feces was minimal (less than 2.1% of the dose) in both cases. From 0.5 to 4 hr after intraperitoneal administration, 3.6 to 8.8% of the urinary metabolites was unconjugated while 2.4 to 8.8% was present in the glucuronide fraction. After oral administration these amounts were 5.5 to 6.8% and 20.5 to 28.2% respectively. After both intraperitoneal and oral administration, no unchanged 2,4-DNT could be detected in the urine, and 2,4-dinitrobenzyl alcohol (2,4-DNBAlc) represented the most abundant identifiable neutral metabolite. Small amounts of 2,4-diaminotoluene, 2-amino-4-nitrobenzyl alcohol, 2-(N-acetyl)amino-4-nitrotoluene, 4-amino-2-nitrotoluene (4A2NT), and 2-amino-4-nitrotoluene (2A4NT) were also present. In almost all cases the largest proportion of metabolites represented unknowns, some of which exhibited the chromatographic properties of carboxylic acid metabolites. Metabolism of 2,4-DNT by liver and lung microsomes yielded mainly 2,4-DNBAlc with lower amounts of 4A2NT and 2A4NT, and their formation was dependent on the presence of oxygen and NADPH. Pretreatment of the animals with 2,3,7,8-tetrachlorodibenzo-p-dioxin resulted in increased yields of all three metabolites. Aerobic metabolism of 2,4-DNT by explants of the small intestine, large intestine, or by cecal contents yielded 2,4-DNBAlc, 2A4NT, 4A2NT and 4-(N-acetyl)amino-2-nitrotoluene (4Ac2NT). The proportion of reduced metabolites (2A4NT, 4A2NT, and 4Ac2NT) was much higher in these systems than with liver or lung microsomes and their formation by small intestine and cecal contents was enhanced several-fold under anaerobic conditions, while that of 2,4-DNBAlc was abolished. It is concluded that 2,4-DNT metabolism in the A/J mouse is rapid and complete and that the major neutral urinary metabolite is 2,4-DNBAlc. Minor amounts of reduced or partially reduced products appear to be formed mainly in the intestine, with a major role by its microflora.

UI	MeSH Term	Description	Entries
D007413	Intestinal Mucosa	Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI.	Intestinal Epithelium,Intestinal Glands,Epithelium, Intestinal,Gland, Intestinal,Glands, Intestinal,Intestinal Gland,Mucosa, Intestinal
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008168	Lung	Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.	Lungs
D008297	Male		Males
D009578	Nitrobenzenes	BENZENE derivatives carrying nitro group substituents.
D010084	Oxidation-Reduction	A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).	Redox,Oxidation Reduction
D002273	Carcinogens	Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.	Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D004136	Dinitrobenzenes	Benzene derivatives which are substituted with two nitro groups in the ortho, meta or para positions.	Dinitrobenzene,Dinitrophenyl Compound,Dinitrophenyl Compounds,Dinitrotoluene,Dinitrotoluenes,Compound, Dinitrophenyl
D005965	Glucuronates	Derivatives of GLUCURONIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the 6-carboxy glucose structure.	Glucosiduronates,Glucuronic Acids,Acids, Glucuronic
D000072317	Polychlorinated Dibenzodioxins	Dibenzodioxin derivatives that contain multiple chloride atoms bound to the benzene ring structures.	TCDD,Tetrachlorodibenzodioxin,2,3,7,8-Tetrachlorodibenzo-p-dioxin,Chlorinated Dibenzo-p-dioxins,Dibenzo(b,e)(1,4)dioxin, 2,3,7,8-tetrachloro-,PCDD,Polychlorinated Dibenzo-p-dioxins,Polychlorinated Dibenzodioxin,Polychlorodibenzo-4-dioxin,Polychlorodibenzo-p-dioxin,Tetrachlorodibenzo-p-dioxin,Chlorinated Dibenzo p dioxins,Dibenzo-p-dioxins, Chlorinated,Dibenzo-p-dioxins, Polychlorinated,Dibenzodioxin, Polychlorinated,Dibenzodioxins, Polychlorinated,Polychlorinated Dibenzo p dioxins,Polychlorodibenzo 4 dioxin,Polychlorodibenzo p dioxin,Tetrachlorodibenzo p dioxin