Linking a dermal permeation and an inhalation model to a simple pharmacokinetic model to study airborne exposure to di(n-butyl) phthalate

Six males clad only in shorts were exposed to high levels of airborne di(n-butyl) phthalate (DnBP) and diethyl phthalate (DEP) in chamber experiments conducted in 2014. In two 6 h sessions, the subjects were exposed only dermally while breathing clean air from a hood, and both dermally and via inhalation when exposed without a hood. Full urine samples were taken before, during, and for 48 h after leaving the chamber and measured for key DnBP and DEP metabolites. The data clearly demonstrated high levels of DnBP and DEP metabolite excretions while in the chamber and during the first 24 h once leaving the chamber under both conditions. The data for DnBP were used in a modeling exercise linking dose models for inhalation and transdermal permeation with a simple pharmacokinetic model that predicted timing and mass of metabolite excretions. These models were developed and calibrated independent of these experiments. Tests included modeling of the “hood-on” (transdermal penetration only), “hood-off” (both inhalation and transdermal) scenarios, and a derived “inhalation-only” scenario. Results showed that the linked model tended to duplicate the pattern of excretion with regard to timing of peaks, decline of concentrations over time, and the ratio of DnBP metabolites. However, the transdermal model tended to overpredict penetration of DnBP such that predictions of metabolite excretions were between 1.1 and 4.5 times higher than the cumulative excretion of DnBP metabolites over the 54 h of the simulation. A similar overprediction was not seen for the “inhalation-only” simulations. Possible explanations and model refinements for these overpredictions are discussed. In a demonstration of the linked model designed to characterize general population exposures to typical airborne indoor concentrations of DnBP in the United States, it was estimated that up to one-quarter of total exposures could be due to inhalation and dermal uptake

The Indoor Chemical Human Emissions and Reactivity Project (ICHEAR): Methods

Here we present the new project “Indoor Chemical Human Emissions and Reactivity” (ICHEAR), which is focused on examining the role of human emissions on indoor air chemistry. The specific goal of this project is to investigate the impact of exhaled and dermally emitted human bioeffluents on the chemical compounds present in indoor air, their chemical transformations and total OH reactivity (overall loss rate of OH radical) under different conditions comprising a variety of factors (temperature, relative humidity, ozone, clothing level, age of human participants). The measurements were conducted in stainless steel climate chambers at the Technical University of Denmark (DTU) using state-of-the-art instruments from the Max Planck Institute for Chemistry (MPIC), the Swedish Environmental Research Institute (IVL), and École Polytechnique Fédérale de Lausanne (EPFL). During April-May 2019, groups of four persons (two males and two females) occupied the chamber daily and their emissions were quantified. This poster describes the chambers, instrumentation and the overall experimental approach used in ICHEAR