Absorption, distribution, metabolism and excretion of 4-chloro-2-methylphenoxyacetic acid (MCPA) in rats

Abstract

The metabolism of 14C-MCPA (4-chloro-2-methylphenoxyacetic acid) in male and female rats was compared to that of 14C- MCPA dimethylamine salt (MCPA.DMA) or 14C-MCPA ethylhexyl ester (MCPA-EHE) in adsorption, distribution, metabolism and excretion studies. Compounds were administered by the oral route. The studies demonstrated the bioequivalence of the various forms of MCPA, established the extent of metabolism and metabolite identity. Following single or multiple oral administration of 5 mg/kg 14C-MCPA quantitative recovery of radioactivity, predominantly in urine, was obtained within 168 h. Rats dosed at 100 mg/kg showed similar absorption kinetics but apparent saturation of urinary excretion led to a prolonged elimination phase. MCPA was not extensively metabolised but the oxidation product HMCPA (4-chloro-2-hydroxymethylphenoxyacetic acid) was found at low levels, together with the glycine conjugate. These metabolites were more prominent shortly after dosing, suggesting that MCPA is not retained in the liver and that these metabolites may be excreted faster than MCPA itself. MCPA.DMA and MCPA-EHE were very rapidly converted into MCPA and toxicokinetics and metabolism were indistinguishable from parent compound.