An assessment of the dietary uptake of di-2-(ethylhexyl) adipate (DEHA) in a limited population study.

The plasticizer di-2-(ethylhexyl) adipate (DEHA), which may be present in food-contact films, can migrate into certain foodstuffs. Results from plasticizer migration studies into food have enabled an indirect estimate of the maximum daily dietary intake of DEHA. A previous study of the metabolism and pharmacokinetics of DEHA in humans identified the urinary metabolite 2-ethylhexanoic acid (EHA) as a useful marker metabolite for assessing DEHA intake. The present study was designed to investigate urinary EHA concentrations following a controlled dose of DEHA presented with food, and to assess the average daily intake of DEHA in a limited population survey. The urinary elimination profile of EHA, following a dose of DEHA in food, showed that in order to extrapolate DEHA intake from EHA measurements, a 24-hr urine sample was required. In the survey the elimination of EHA was determined in 24-hr urine samples in 112 individuals from five different geographical locations in the UK. No restrictions were placed on age or gender. Estimates of daily intake of DEHA show a skewed distribution with a median value of 2.7 mg. This is similar to an estimated maximum daily intake of 8.2 mg/day, derived using an indirect method by the UK Ministry of Agriculture, Fisheries and Food.

Metabolism and pharmacokinetics of deuterium-labelled di-2-(ethylhexyl) adipate (DEHA) in humans.

The metabolism and pharmacokinetics of [2H10]di-2-(ethylhexyl) adipate (DEHA) labelled on the ethyl side-chains was determined in six male volunteers. The dose administered was 46 mg [2H10]DEHA given orally. No parent molecule was found in plasma; however, the metabolite [2H5]2-ethylhexanoic acid (EHA) was detected (mean rate of formation: 1.63 +/- 1.19/hr; mean rate of elimination: 0.42 +/- 0.1/hr). Further oxidative metabolism products were detected in urine; the dominant metabolite identified was EHA present as a conjugate and accounted for an average of 8.6% of the administered dose. [2H5]2-Ethyl-5-hydroxyhexanoic acid, [2H5]2-ethylhexanedioic acid, [2H5]2-ethyl-5-keto-hexanoic acid and [2H5]2-ethylhexanol together accounted for a further 3.5% of the dose. The fate of the remainder was not determined.

Determination of plasma nefopam by liquid chromatography and electrochemical detection.

A liquid chromatographic method for the determination of plasma nefopam is presented. A combination of liquid- and solid-phase extraction and electrochemical detection gave clean extracts and, hence, a low limit of detection. Calibration curves were linear over at least two orders of magnitude (1-100 ng/ml) making the method suitable for pharmacokinetic studies.