Pharmacokinetics, metabolism and excretion of 14C-monoethyl phthalate (MEP) and 14C-diethyl phthalate (DEP) after single oral and IV administration in the juvenile dog

Abstract

The pharmacokinetics, metabolism and excretion of monoethyl phthalate (MEP) and diethyl phthalate (DEP) were compared after intravenous or oral administration of [14C]MEP or [14C]DEP in juvenile beagle dogs. Four male juvenile beagle dogs were treated with a single oral or bolus intravenous dose of either [14C]MEP or [14C]DEP (164 μg/kg).The absorption, metabolism, excretion and pharmacokinetics of [14C]MEP and [14C]DEP were nearly identical. [14C]DEP was rapidly and nearly completely metabolized to [14C]MEP following either intravenous or oral administration. [14C]MEP and[14C]DEP were rapidly absorbed, the elimination half-life was estimated to be 1 hour. Approximately 90%–96% of the dose was excreted in urine with 2%–3% of the dose in faeces. MEP accounted for the majority of the dose in plasma and urine; in addition, three minor metabolites (M1, M2 and M3) were detected. The minor metabolites were neither phthalic acid nor glucuronide/sulfate conjugates.The nearly identical metabolism and pharmacokinetics of MEP and DEP in juvenile dogs justifies the use of DEP toxicity data in the risk assessment of MEP exposure.