3-NOP: ADME studies in rats and ruminating animals. (March 2019)

• Record Type: Journal Article
• Authors: Thiel, A.; Rümbeli, R.; Mair, P.; Yeman, H.; Beilstein, P.
• Is Part Of: Food and chemical toxicology. Volume 125(2019)
• Page Start: 528
• Page End: 539
• Publication Date: 2019-03
• Subjects: 3-NOP -- Metabolism -- Organic nitrate ester -- Methanogenesis inhibition -- Ruminants -- ADME; AD(M)E Absorption, distribution, (metabolism), and excretion -- bw body weight -- dsm disintegration per minute -- GIT gastrointestinal tract -- (HP)LC (High Performance) Liquid Chromatography -- HPA 3-hydroxypropionic acid -- HILIC hydrophilic interaction chromatography -- KEGG Kyoto Encyclopedia of Genes and Genomes -- LSC liquid scintillation counting -- (L)LOQ (lower) limit of quantification -- MS mass spectrometry -- NMR nuclear magnetic resonance spectroscopy -- 3-NOP 3-nitrooxypropanol -- NOPA 3-nitrooxypropionic acid -- RI refractive index -- TCA trichloroacetic acid -- TRR total radioactive residues -- UV ultraviolett -- Study 1 ADME tissue distribution and plasma kinetics in male rats -- Study 2 ADE study in rats with trapping of volatiles -- Study 3 Metabolite profiling in rats -- Study 4 ADME study in lactating goats -- Study 5 NOPA in beef cattle plasma -- Study 6 inorganic nitrate kinetic profile in rats; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2019.02.002
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: 3-NOP (3-nitrooxypropanol) reduces enteric methane formation in ruminants. A series of ADME studies in rats, lactating goats and beef cattle was performed. 3-NOP was entirely absorbed from the GIT of rats: approximately 75% of the administered 3-NOP was eliminated as carbon dioxide via exhalation and approximately 20% were excreted via urine. 3-NOP is oxidized to 3-nitrooxypropionic acid (NOPA) which is then hydrolyzed to 3-hydroxypropionic acid (HPA) and inorganic nitrate, the major rat plasma metabolites. NOPA is also a plasma metabolite in beef. The metabolism of 3-NOP is fast as indicated by the negligible amounts of 3-NOP found in rat plasma 2 h after dosing. HPA is a naturally occurring metabolite. It is either metabolized into carbon dioxide and acetyl-CoA or into propanoyl-CoA, the latter serves as substrate for gluconeogenesis. Gluconeogenesis is very prominent in lactating ruminants which use propanoyl-CoA as their main carbon source. Thus, the formation of lactose from 3-NOP by lactating goats is not unexpected. Lactose was the major metabolite of 3-NOP in the aqueous phase of milk. The incorporation of 3-NOP into endogenous metabolism makes it difficult to derive a marker residue, however, conservative risk assessment could be based on the measured radioactivity in tissues. Highlights: The majority of 3-NOP is metabolized into carbon dioxide. 3-NOP is metabolized into endogenous compounds. Xenobiotic residues are unlikely in aqueous phase of milk.