Prenatal exposure estimation of BPA and DEHP using integrated external and internal dosimetry: A case study

Abstract

Prenatal exposure to Endocrine disruptors (EDs), such as Bisphenol A (BPA) and di (2-ethylhexyl) phthalate (DEHP), has been associated with obesity and diabetes diseases in childhood, as well as reproductive, behavioral and neurodevelopment problems. The aim of this study was to estimate the prenatal exposure to BPA and DEHP through food consumption for pregnant women living in Tarragona County (Spain). Probabilistic calculations of prenatal exposure were estimated by integrated external and internal dosimetry modelling, physiologically based pharmacokinetic (PBPK) model, using a Monte-Carlo simulation. Physical characteristic data from the cohort, along with food intake information from the questionnaires (concentrations of BPA and DEHP in different food categories and the range of the different food ratios), were used to estimate the value of the total dietary intake for the Tarragona pregnancy cohort. The major contributors to the total dietary intake of BPA were canned fruits and vegetables, followed by canned meat and meat products. In turn, milk and dairy products, followed by ready to eat food (including canned dinners), were the most important contributors to the total dietary intake of DEHP. Despite the dietary variations among the participants, the intakes of both chemicals were considerably lower than their respective current tolerable daily intake (TDI) values established by the European Food Safety Authority (EFSA). Internal dosimetry estimates suggest that the plasma concentrations of free BPA and the most important DEHP metabolite, mono (2-ethylhexyl) phthalate (MEHP), in pregnant women were characterized by transient peaks (associated with meals) and short half-lives (< 2h). In contrast, fetal exposure was characterized by a low and sustained basal BPA and MEHP concentration due to a lack of metabolic activity in the fetus. Therefore, EDs may have a greater effect on developing organs in young children or in the unborn child.

Main components of PM10 in an area influenced by a cement plant in Catalonia, Spain: Seasonal and daily variations

“…Regarding DEHP, Figure 2 shows that non-dietary sources contribute with 37 % of the 383 total exposure. The mean dietary daily intake of DEHP exposure from Reus cohort was 384 1.00 µg/kg bw /day (Martínez et al, 2017), and the mean exposure estimated for non-385 dietary ingestion, inhalation, and dermal contact were 0.485, 0.025, 0.087 µg/kg bw /day 386 respectively. According to total non-dietary exposure, the maximum dose was 3.86 387 µg/kg bw /day and the 95 th percentile was 1.51 µg/kg bw /day, and mean value was 0.60 388 µg/kg bw /day.…”

“…to the DEHP mean non-dietary exposure. Indoor exposure and sleeping inhalation 348 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 the dietary exposure was previously estimated using the same cohort population 364 (Martínez et al, 2017). 365…”

“…Regarding BPA, mean dietary daily intake from Reus (Tarragona, Spain) cohort was 366 0.715 µg/kg bw /day (Martínez et al, 2017), and the mean exposure estimated for non-367 dietary ingestion, inhalation, and dermal contact were 9.62·10 -4 , 5.90·10 -4 , 6.39·10 -5 368 µg/kg bw /day, respectively. In general, in the present study according to non-dietary 369 exposure, the maximum exposure estimated for BPA was 0.0072 µg/kg bw /day and the 370 95% of the population were under 0.0040 µg/kg bw /day.…”

Development of a human physiologically based pharmacokinetic (PBPK) model for phthalate (DEHP) and its metabolites: A bottom up modeling approach

“…The current PBPK model can be further extended for 2-cx MEPP, 580 once the metabolic data are available. Detailed rat's pharmacokinetic studies that 581 include all metabolites could be very useful for further understanding metabolites tissue 582 exposome studies for the human health risk assessment (Martínez et al, 2017(Martínez et al, , 2018 Fromme, H., Gruber, L., Schlummer, M., Wolz, G., Böhmer, S., Angerer, J., Mayer, R.,…”

Comparing dietary and non-dietary source contribution of BPA and DEHP to prenatal exposure: A Catalonia (Spain) case study

“…The mean dietary daily intake of DEHP exposure from Reus cohort was 384 1.00 µg/kg bw /day (Martínez et al, 2017), and the mean exposure estimated for non-385 dietary ingestion, inhalation, and dermal contact were 0.485, 0.025, 0.087 µg/kg bw /day 386 respectively. According to total non-dietary exposure, the maximum dose was 3.86 387 µg/kg bw /day and the 95 th percentile was 1.51 µg/kg bw /day, and mean value was 0.60 388 µg/kg bw /day.…”