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.

Trinitrotoluene: assessment of occupational absorption during manufacture of explosives.

Trinitrotoluene (TNT) absorption was assessed in groups of workers at two explosives factories by measuring the urinary concentrations of dinitroaminotoluene (DNAT) metabolites. DNAT was detected in most of the urine samples analysed and for postshift samples the mean (SD) concentration was 9.7 (7.9) mg/l (range 0.1-44 mg/l (n = 219)). Individual workers showed substantial day to day variations in DNAT concentrations in postshift urine samples, but on a group basis the concentrations remained fairly constant throughout the working week. Preshift urine samples taken at the beginning of a working week showed low concentrations of DNAT which initially suggested that the elimination of TNT metabolites is fairly rapid. A survey carried out of preshift and postshift urine samples collected from a group of workers for a full working week showed wide variations in the rate of clearance of TNT metabolites from the body and in some cases higher concentrations of metabolites were seen in the samples taken the morning after exposure. When urine samples were collected from the same group of workers after 17 days away from the workplace DNAT was still detectable in samples from eight of the nine subjects, indicating that a proportion of TNT or its metabolites is slowly excreted. When five subjects were monitored more intensively during two workshifts TNT was shown to be absorbed rapidly during the exposure period. In most cases the highest concentrations were seen in the postshift urine samples but significant proportions were still present in samples taken the morning after exposure. Atmospheric levels of TNT were found to be too low to account for the observed excretion of DNAT and dermal uptake rather than inhalation appears to be the major route of absorption.

Dinitrotoluene: an assessment of occupational absorption during the manufacture of blasting explosives.

Two biological monitoring studies were carried out among workers in an explosives factory who were exposed to technical grade dinitrotoluene (DNT). In the first study urine samples from 28 workers were analysed for the metabolite 2,4-dinitrobenzoic acid (2,4-DNBA). Metabolite concentrations in urine were extremely low or non-detectable, prior to starting work at the beginning of the working week, but post-shift urine samples contained a mean 2,4-DNBA level of 17 mg/l. There were wide variations in the concentrations excreted in urine by different workers and by individual workers on consecutive days. Atmospheric levels of DNT (determined by personal monitoring) were found to be well below the recommended limit and therefore could not account for the observed excretion of 2,4-DNBA. It is suggested that skin may be the major route of absorption of DNT during this process. A second study was carried out to investigate the kinetics of absorption and excretion of DNT. Intensive urine sampling was carried out on five individuals over a 2-day period with additional samples over the subsequent 2 non-working days. Analysis for 2,4-DNBA showed that uptake of DNT is rapid and that the highest levels were normally seen in the end-of-shift specimens. Urine samples were analysed for other known metabolites of DNT which have been found in animal studies and it was shown that 2,4-DNBA is the major known metabolite which is excreted in human urine. Unchanged DNT was detected in blood samples taken during a single workshift at levels up to 250 ng/ml. It is concluded that there is a measurable uptake of DNT by the group of workers studied. The measurement of 2,4 DNBA in end-of-shift urine samples is an appropriate way of assessing the effectiveness of measures taken to reduce the absorption of DNT.

An evaluation of renal function in workers occupationally exposed to mercury vapour.

The renal function of a population of workers occupationally exposed to mercury in the chlor-alkali industry has been examined and compared to that of a population of workers with no occupational exposure to mercury. Measurement of specific urinary proteins and enzymes have been carried out on each individual on three separate occasions and have been complemented by blood plasma measurements at the final visit. Under the conditions of exposure to mercury sustained in this study, there is no evidence of an increased prevalence of renal dysfunction as indicated by enzyme and protein measurements. The urinary concentration of the low molecular weight protein, beta 2-microglobulin, is significantly lower in the mercury-exposed group than in the control group. In contrast to recently published literature, no relationship is seen between urinary mercury concentration and the appearance of high molecular weight protein in urine. A small increase in the prevalence of higher activities of the urinary enzyme N-acetyl-beta-glucosaminidase and gamma glutamyl transferase is observed when the urinary mercury concentration exceeds 100 micrograms/g creatinine. A small increase in the prevalence of raised urinary N-acetyl-beta-glucosaminidase activity is observed when the duration of exposure to mercury exceeds ten years. The pattern of proteinuria has been characterised in a total of sixteen individuals from both populations; a low molecular weight proteinuria is seen in three individuals from the control group whilst a high molecular weight proteinuria is seen in the remainder (seven in the control and six in the mercury group).