Internal exposure with bisphenol A by medical devices – Comparison with t-TDI

Bisphenol A (BPA) is a high production volume chemical. It is used to produce polycarbonate (PC) plastics and other polymeric materials, and also for the production of special papers (e.g. thermal paper). PC is used for tableware (plates and mugs), BPA-based epoxy-phenolic resins are used as coatings for canned food and beverages. Human exposure is by food via the oral route and by thermal papers via the dermal route. The presystemic elimination of BPA requires calculating internal exposure for the assessment of exposure via several routes. Animal toxicity studies have been performed by the oral route and in some instances by subcutaneous route. Internal doses rather than the administered doses have to be calculated using the human equivalent dose (HED) approach. Here we assess BPA exposures occurring during prolonged medical procedures via the intravenous route by medical devices. From a paper reporting on urinary BPA concentrations in premature and newborn babies in neonatal intensive care units we calculated the urinary BPA excretion as a measure of the daily dose. The geometric mean of the urinary BPA excretion was 3.05 μg/day with a maximum of 94.6 μg/day for prematurely born infants in neonatal intensive care units. Assuming an exposure from medical devices exclusively via the intravenous route, we employed physiologically based toxicokinetic (PBTK) modelling to calculate from the urinary BPA excretions the serum concentrations of unconjugated BPA in newborns and compared these concentrations with those for older children and adults. Based on the urinary excretions of 3.05 μg/day (geometric mean) and 94.6 μg/day (maximum), the predicted steady-state concentrations in blood were 19 ng/ml and 600 ng/ml for newborns, 14 ng/ml and 440 ng/ml for 3 months, 4 ng/ml and 120 ng/ml for e 6 months and 1.5 years old, and 1.35 ng/ml and 42 ng/ml for adults. Converting the steady state concentrations into AUCs, the AUCs exceed the AUC related to the currently used temporary TDI of 5 μg/kg/day. Two aspects should be noted: (i) the TDI is meant for life-long exposure whereas exposure in a neonatal intensive care unit is a special situation for a limited time period, and (ii) the health benefits of the medical interventions needs to be taken into consideration.