Dose reconstruction from urinary biomarkers in a human panel exposed to bis (2-ethylhexyl) phthalate via inhalation

Abstract

While oral consumption has been considered as the main exposure route of bis (2-ethylhexyl) phthalate (DEHP) for general public, dermal and inhalation cannot be ignored as alternative ones especially for consumer products. However, there were very limited information on quantitative contribution of exposure and metabolic profiles via inhalation after using consumer products. The purposes of the present study are: 1) quantitation of inhaled amounts of DEHP after use of a spray-type of consumer product, and 2) suggestion of fractional urinary excretion amounts of key metabolites of DEHP after inhalation exposure in humans. In order to do so, seven young male Korean volunteers were recruited for an inhalation experiment, where they were located at a closed office room before single exposure to deuterium-labelled DEHP (DEHP-d4) with a compressible spraying anti-fog solution of DEHP-d4 at 500 mg/kg. Personal air monitoring of DEHP-d4 at breathing-zone was made and total excreted urine samples for forty eight hours after exposure were collected to measure key metabolites of DEHP-d4. Most aerosols of DEHP-d4 was clear out in about five minutes, and its air concentration was 1.73 ± 0.42 mg/m3 for the first five minutes. The total cumulative excreted amount of the metabolites was 0.8 ± 0.5, 1.6 ± 0.4 and 3.3 ± 0.9 μg for mono-(2-ethyl-5-hydroxyhexyl) phthalate-d4 (MEHHP-d4), mono(2-ethyl-5-oxohexyl) phthalate-d4 (MEOHP-d4) and mono-(2-ethyl-5-carboxypentyl) phthalate-d4 (5cxMEPP-d4), respectively. The estimated inhaled amounts were 70.8 ± 17.3 μg (AM ± SD) based on an exposure model using the air measurements. MEHHP-d4, MEOHP-d4 and 5cxMEPP-d4 were determined as key metabolites of DEHP in urine as in other studies for exposure through ingestion

however, the relative production of metabolites among the analytes and fractional urinary excretion (Fue) relative to absorbed dose were different: 1.54 ± 0.74 %, 3.26 ± 1.49 % and 6.42 ± 3.42 % for MEHHP-d4, MEOHP-d4 and 5cxMEPP-d4, respectively, which was about 2~20 folds lower than those though ingestion of DEHP. While personal exposure amounts after single spraying action appeared about 3% of total released amounts of DEHP, inhalational exposure contributed to internal dose of DEHP, it would increase in multiple actions of spraying or continuous exposure. The fractional urinary excretion of DEHP metabolites indicate relatively low metabolism through exposure via inhalation, and dose estimation from urinary metabolites of DEHP with oral Fue could underestimate actual exposure as in occupational places where the main exposure route is inhalation.