Food and Chemical Toxicology | VOL. 125
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3-NOP: ADME studies in rats and ruminating animals

Publication Date Mar 1, 2019

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.

Concepts

Methane Formation In Ruminants Aqueous Phase Of Milk Substrate For Gluconeogenesis Main Carbon Source Radioactivity In Tissues Inorganic Nitrate Carbon Dioxide Plasma Metabolite Rat Plasma Major Plasma Metabolites

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No potential conflict of interest was reported by the authors. The conception and design of the study, acquisition of data, analysis and interpretatio...

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