Metabolism of ALS Inhibitory Herbicide Bispyribac-sodium [KIH-2023] in Rats

Abstract

Absorption, distribution and metabolism of Bispyribac-sodium [sodium 2, 6-bis(4, 6dimethoxypyrimidin-2-yloxy)benzoate] or [KIH-2023] in rats orally dosed with 14C-KIH-2023 were investigated. More than 90% of the dosed radioactivity was detected in the excreta within 96 hr after dosing. Level of the radioactivity in the blood of male and female rats reached maxima at 2 and 1 hr after dosing, respectively, and then decreased rapidly to about a half level of maxima (C112). The radioactivity of tissues was lower at 96 hr after dosing than that at C112-time. Most of the radioactivity in the urine, feces, liver and plasma was detected as unchanged KIH-2023. The major radioactive compounds excreted into the bile were KIH-2023 and its glucuronide. Repeated oral administration of KIH-2023 for 15 days gave similar results from the single oral one in the excretion, tissue distribution and metabolism of 14C-KIH-2023.

In vivo pharmacokinetics of pyribenzoxim in rats

“…These results were supported by earlier work9 with [ 14 C]pyribenzoxim which had reported that cumulative recovery up to 72 h was approximately 80% in feces, and again with another pyrimidinylthiobenzoate herbicide (KIH‐2023), for which more than 90% of the dosed radioactivity appeared in the excreta within 96 h 5…”

“…2 It has been used as a foliar‐applied herbicide in Korea for the control of weeds such as barnyard grass in dry‐seeded rice. This chemical belongs to the pyrimidinylthiobenzoate group which includes pyrithiobac,3 KIH‐20234, 5 and KIH‐6127,6 which were developed for cotton or rice. As do the sulfonylurea and imidazolinone herbicides, these chemicals are known to inhibit acetolactate synthase7 in the biosynthetic pathway of the branched‐chain amino acids, such as valine, leucine and isoleucine 8.…”

Acute human self-poisoning with bispyribac-containing herbicide Nominee®: a prospective observational study

“…Toxicokinetic studies of bispyribac in the rat demonstrated a peak plasma concentration 1-2 hours following enteral administration followed by an apparent elimination half-life of 5-7 hours11. More than 60% of the dose administered to rats is eliminated unchanged, mostly in the faeces following biliary excretion.…”

Biochemical, Hematological and Pathological Effects of Bispyribac Sodium in Female Albino Rats

“…Animals accommodated for 2 weeks before the experiment and maintained on a balanced ration also feed and water given ad libitium throughout the experiment. Rats divided into four groups each one contains eight rats weighted 115 ± 5 GM; intubated orally with 0, 16.47, 32.94, 65.88 mg/kg of bispyribac-sodium (equivalent to 1/160, 1/80 and 1/40 of the LD50 of bispyribac-sodium) for three months twice per week [7]. Animals weighted twice per week before dosing to maintain constant dose throughout the experimental period.…”

“…While its tissue distribution in male larger than female due to superiority in the excretion in female besides repeated administration not affect absorption nor metabolism and excretion [7]. Bispyribac mostly absorbed from gastrointestinal tract completely, had no accumulation effect and excreted mostly as the parent compound and its elimination in male more than female (Australian Pesticides & Veterinary Medicines Authority 2011) [8].…”