Biological monitoring for exposure to pirimicarb: method development and a human oral dosing study

This study has developed and validated an assay to quantify metabolites of the carbamate insecticide pirimicarb, whose residues are commonly found on a variety of food products, at levels that might be expected to arise from dietary exposure at or below the acceptable daily intake (ADI, 0.02mg/kg). A novel method for the determination of pirimicarb metabolites in human urine by liquid chromatography with mass spectrometry detection has been developed and validated. It has been used to quantify the elimination kinetics of 2-(dimethylamino)-5,6-dimethylpyrimidin-4-ol (DDHP) and 5,6-dimethyl-2-(methylamino)pyrimidin-4-ol (MDHP) in five volunteers given a single oral dose of pirimicarb at the ADI (0.02mg/kg). MDHP was found to be the major urinary metabolite. However, significant levels of conjugated MDHP and DDHP were released upon hydrolysis. Total MDHP and DDHP recovered over 48h accounted for 74% (range 32-123%) of the administered dose. Both free and conjugated metabolites exhibited similar excretion profiles, characterised by fairly short elimination half-lives (2.8-4.6h). Urinary excretion of MDHP and DDHP was almost complete within 24h. MDHP (either free or total) exhibited the least variability between volunteers. No clinically significant depressions in blood cholinesterases were detected during the dosing study. MDHP is recommended as a sensitive and specific biomarker for pirimicarb exposure, suitable for use in dietary or occupational surveys. We calculate that a 70kg person receiving a dose of pirimicarb at the ADI would be expected to have a 24h sample level of 111-157micromol/mol creatinine total MDHP or 56-95micromol/mol creatinine free MDHP (95% confidence interval).