The metabolism and disposition of (14)C-labelled 2,2',4,4'-tetrabromodiphenyl ether (BDE47) were investigated in F344 rats and B6C3F1 mice. Approximately 75-85% of 1 micromol BDE47 kg(-1) was absorbed following oral administration to either rats or mice. Sex and species differences were observed in tissue distribution and excretion of BDE47-derived radioactivity. Absorption and distribution of (14)C to major tissues were dose-proportional in male rats from 0.1 to 1,000 micromol kg(-1). BDE47-derived radioactivity increased in all rat and mouse tissues examined following repeated daily doses of 1 micromol kg(-1). Accumulation of (14)C in tissues of mice was less than in corresponding rat tissues. Glutathione conjugates of BDE47 were excreted in rat bile. A glucuronide and a sulfate conjugate of 2,4-dibromophenol were detected in the urine of BDE47-treated rats. BDE47 appears to induce its own metabolism. Increased formation of reactive metabolites over time may correlate with toxicological effects in BDE47-treated rodents.
1.The disposition of the 14 C-labeled polybrominated diphenyl ether (PBDE), 2,2′,4,4′,5,5′-hexaBDE (BDE153) was investigated in rodents following single and multiple doses and in a mixture with radiolabeled 2,2′,4,4′-tetraBDE (BDE47) and 2,2′,4,4′,5-pentaBDE (BDE99). 2.In single exposure studies, there was little or no effect of dose on BDE153 disposition in male rats in the range of 1-100 µmol/kg. No major sex or species differences in the in vivo fate of BDE153 were detected. BDE153 was: 1) approximately 70% absorbed in rats or mice following gavage. 2) retained in tissues. 3) poorly metabolized and slowly excreted. 3.Mixture studies indicated that, relative to each other, more BDE47 was distributed to adipose tissue, more BDE153 accumulated in liver, and BDE99 was metabolized to the greatest extent. BDE153 was probably retained in liver due to minimal metabolism and elimination after "first pass" distribution to the tissue following gavage.
1. The metabolism and disposition of Luminol (LMN, 3-aminophthalhydrazide), a widely used forensic and laboratory reagent that chemiluminesses upon oxidation, was determined as part of its overall toxicological characterization. 2. Radiolabelled LMN was well absorbed, metabolized and excreted following p.o. administration of a range of doses. About 90% of the total dose was recovered within 24 h of administration in urine in the form of two metabolites identified as LMN N8-glucuronide and LMN N8-sulphamic acid. 3-Aminophthalic acid, the oxidative product of LMN in the light-emitting reaction, was apparently not formed in vivo. 3. Metabolism and disposition of an i.v. administered dose was similar to that following gavage. Little or no LMN-derived radioactivity was present in tissue within 12 h post-dosing. Excretion of radioactivity in bile following i.v. injection was minimal (approximately 8% of the total dose in 6 h) and consisted of the same urinary-excreted glucuronide and sulphate conjugates. 4. LMN was not absorbed dermally in rat, potentially a major route of exposure to human. If the fate of LMN is similar between species, this compound should have little potential for either dermal absorption, bioaccumulation in tissues following other routes of exposure or chronic toxicity in humans.
The metabolism and disposition of 14C-labelled juglone in male F344 rats following oral, intravenous and dermal administration were studied. Approximately 40-50% of an oral dose (0.1 to 10 mg kg-1) and less than 20% of the dermal dose (4 mg kg-1) were absorbed within 24 h. Most of the oral dose was excreted in faeces and urine within 24 h and only 1-3% remained in the tissues. High concentrations of juglone-derived radioactivity were found in kidney for all three dosing routes. The accumulation in kidney can be attributed to covalent binding of juglone and/or metabolites to cytosolic protein. Five metabolites were identified in the urine of rats treated with an oral dose: 1,4,5-trihydroxynaphthalene di-glucuronide, 1,4,5-trihydroxynaphthalene mono-glucuronide mono-sulfate, 2-sulfo-2,3-dihydrojuglone, 4,8-dihydroxy-1-tetralone mono-glucuronide and 1,4,5-trihydroxynaphthalene mono-glucuronide. Liver microsomal incubations of juglone in the presence of NAD(P)H and UDP-glucuronic acid gave rise to two 1,4,5-trihydroxynaphthalene mono-glucuronides.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.