Fluometuron

Endpoint summary

Description of key information

Toxicokinetics, metabolism and distribution:
1. Rat oral dose toxicokinetic study (single and multiple dose levels, radiolabelled), Half-life elimination (hours) ranges from 21.2 to 26.9 for Charles River CD rats m/f, EPA FIFRA, Subdivision F, §85-1 (1984)
2. Rat oral dose toxicokinetic study (single and multiple dose levels): oxidative metabolism and hydroxylated metabolites, Charles River CD rats m/f, EPA FIFRA, Subdivision F, §85-1 (1984).
3. Rat oral dose toxicokinetic study (single level): 82 %  Absorption rate (0-168 hours) for Charles River CD rats m/f, Guideline follows the Inclusion of Active Substances in Annex I to EEC Council Directive 91/414/EEC as amended by Commission directive 74/79/EC

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

82

Additional information

The metabolism of fluometuron was studied in rats after oral administration of 14C-phenyl fluometuron at nominal doses of 0.5 mg/kg (single and repeat doses) and 100 mg/kg (single) and a single oral dose of 14C-fluometuron at 0.5 mg/kg. Both studies were undertaken for 168 hours. In the initial study the majority of radioactivity was eliminated via the urine (71-84%) and faeces (9-12%). No sex difference or dose related response was detected. Low levels of radioactivity residues remained in the tissues of all three test groups, ranging from 0.06, 0.07 and 0.045% of dose respectively, showing a trend to increasing tissue residues with increased dose. The majority of residue was detected in the red blood cells and the highly perfused metabolically active tissues liver, kidney, spleen, lung and heart. There were no treatment-related differences in tissue concentrations between groups and gender. The half-life for the elimination of radioactivity ranged from 21.2 to 26.5 hours. The findings of the initial study were supported in the second study. After 168 hours the majority of radioactivity was excreted via the urine (82%) and faeces (14.2%), with 95% of the dose excreted in the urine within 24 hours. The majority of the radioactivity in the tissues was detected in the whole blood, kidney and liver, 0.05, 0.20, 0.11 µg equiv/g and 0.07, 0.30, 0.12 µg equiv/g for male and female rats respectively. Concentrations in the tissues were typically ten times higher at 4-hours post treatment than 24-hours post treatment. The elucidation of the metabolic pathway in both studies was determined in the urine and faeces after extensive enzyme hydrolysis. Confirmation of the presence of fluometuron and/or metabolites was by either, two-dimensional thin layer chromatography, mass spectrometry, or nuclear magnetic resonance spectrometry. The metabolism of fluometuron in rats proceeds via two main oxidative pathways. Stepwise demethylation of fluometuron to desmethyl fluometuron, di-desmethyl fluometuron and corresponding hydroxyl metabolites Ring hydroxylation of metabolites, which can be excreted directly or further metabolised and/or conjugated to -glucuronides or aryl sulphates, prior to excretion.