Aerobic and anaerobic soil metabolism of a herbicide methiozolin and its pharmacokinetics and metabolism in rats

Abstract

Methiozolin is a new turf herbicide controlling annual bluegrass in various cool- and warm-season turfgrasses. This study was conducted to investigate the fate of methiozolin in soil under aerobic and anaerobic conditions using two radiolabeled tracers, [benzyl-14C] and [isoxazole-14C]methiozolin. The mass balance of applied radioactivity ranged from 92.0 to 104.5% in aerobic sterile, 97.5 to 101.2% in aerobic nonsterile, and 93.2 to 102.5% in anaerobic soils. In the aerobic nonsterile soil, [benzyl-14C] and [isoxazole-14C]methiozolin degraded with 17.9 and 15.9% remaining, respectively, at 120 days after treatment (DAT). [14C]Carbon dioxide and the nonextractable radioactivity increased up to 41.5 and 35.7% for [benzyl-14C]methiozolin at 120 DAT, respectively, while were 36.1 and 39.8% for [isoxazole-14C]methiozolin, respectively. The nonextractable residue was associated mainly with humin and fulvic acid fractions under aerobic condition. No significant volatile products or metabolites were detected in the soil under aerobic condition. The half-life of [14C]methiozolin was approximately estimated as 49 days in the nonsterile soil under aerobic condition

however, it could not be estimated in sterile soil under aerobic condition and in the soil under anaerobic conditions, because [14C]methiozolin degradation was limited. Particularly, one significant metabolite was produced in anaerobic soil (7.9% of the applied) and it was identified as 4-(2,6-difluorobenzyloxy)-3-hydroxy-3-methyl-1-(3-methylthiophen-2-yl)butan-1-one. Based on these results, methiozolin is considered to undergo fast degradation by aerobic microbes, but not by abiotic chemical reaction or anaerobic microbes in soil. The present study reports that elucidate absorption, tissue distribution, excretion, and metabolism of methiozolin in rats following oral administration. The pharmacokinetic parameters in the blood were observed as follows: Tmax = 6 h, Cmax = 168.7 μg equiv/mL, T1/2 = 49.4 h, AUC120 = 9921.5 μg equiv•h/mL, and clearance = 39.2 mL/h/kg. Those parameters and the depletion curve for 14C in the plasma were very similar to those in the blood. The total amounts excreted in urine and feces were 24.3 and 68.9%, respectively, during 120 h after administration

however, no excretion was found in exhaled. The 14C radioactivity excreted through bile was 40.1% of the administered. Excreted radioactivity peaked between 24 and 48 h, showing 51.0% of the total excretion within 48 h. The orally administrated 14C distributed across various tissues within 12 h after administration, showing 14.0% of the dosed, and was eliminated from all the tissues without accumulation. Numerous minor metabolites (<4% of the dosed) in urine and fecal extracts were detected within 72 h and two of those were identified. The identified metabolites in fecal extracts were AMet-1, 6-(5-(5-((2,6-difluorobenzyloxy)methyl)-4,5-dihydro-5-methylisoxazol-3-yl)-4-methylthiophen-2-yloxy)-tetrahydro-3,4,5-trihydroxy-2H-pyran-2-carboxylic acid, and AMet-2, (2-(5-((2,6-difluorobenzyloxy)methyl)-4,5-dihydro-5-methylisoxazol-3-yl)thiophen-3-yl)methanol. Conclusively, methiozolin was shown to readily absorb to the gastrointestinal tract, distributed throughout the tissues within 12 h, metabolized extensively, and eliminated through urine and feces mostly within 48 h, without tissue accumulation.