Update and Evaluation of a High-Throughput In Vitro Mass Balance Distribution Model: IV-MBM EQP v2.0

This study demonstrates the utility of an updated mass balance model for predicting the distribution of organic chemicals in in vitro test systems (IV-MBM EQP v2.0) and evaluates its performance with empirical data. The IV-MBM EQP v2.0 tool was parameterized and applied to four independent data sets with measured ratios of bulk medium or freely-dissolved to initial nominal concentrations (e.g., C24/C0 where C24 is the measured concentration after 24 h of exposure and C0 is the initial nominal concentration). Model performance varied depending on the data set, chemical properties (e.g., “volatiles” vs. “non-volatiles”, neutral vs. ionizable organics), and model assumptions but overall is deemed acceptable. For example, the r2 was greater than 0.8 and the mean absolute error (MAE) in the predictions was less than a factor of two for most neutral organics included. Model performance was not as good for the ionizable organic chemicals included but the r2 was still greater than 0.7 and the MAE less than a factor of three. The IV-MBM EQP v2.0 model was subsequently applied to several hundred chemicals on Canada’s Domestic Substances List (DSL) with nominal effects data (AC50s) reported for two in vitro assays. We report the frequency of chemicals with AC50s corresponding to predicted cell membrane concentrations in the baseline toxicity range (i.e., >20–60 mM) and tabulate the number of chemicals with “volatility issues” (majority of chemical in headspace) and “solubility issues” (freely-dissolved concentration greater than water solubility after distribution). In addition, the predicted “equivalent EQP blood concentrations” (i.e., blood concentration at equilibrium with predicted cellular concentration) were compared to the AC50s as a function of hydrophobicity (log octanol-water partition or distribution ratio). The predicted equivalent EQP blood concentrations exceed the AC50 by up to a factor of 100 depending on hydrophobicity and assay conditions. The implications of using AC50s as direct surrogates for human blood concentrations when estimating the oral equivalent doses using a toxicokinetic model (i.e., reverse dosimetry) are then briefly discussed.

Occurrence of aliphatic and aromatic compounds associated with atmospheric particulate matter in three cities of Gujarat, India

The organic pollutants associated with atmospheric particulate matter (PM) in the environment, especially PM2.5 (particles <2.5 μm) have become a major issue worldwide in the past decade. The ambient air samples of four different sizes of particles were collected using an active air sampler (cascade impactor) from three cities of Gujarat: Anand, Ahmedabad and Surat. To study morphology and elemental composition, Scanning electron microscope (SEM) and Energy dispersive X-ray system (EDX) were used for fine particle size <1.0 μm. Besides, organic pollutants associated with particulate matter were analyzed using Gas Chromatography-Mass Spectrometry (GC–MS). Total 54 organic chemicals including 29 aliphatic (alkanes and alkanoic acids) and 25 aromatic chemical compounds were identified qualitatively. Phthalate, the well-known plasticizer was found in the atmosphere of all three study sites. In addition, polycyclic aromatic hydrocarbons (PAHs) such as naphthalene and fluorene were quantified at high concentrations in Ahmedabad (315 ng/m3 and 509 ng/m3 respectively) followed by Surat (310 ng/m3 and 382 ng/m3) and Anand (76.1 ng/m3 and 123 ng/m3). The distribution of organic chemicals was found diverse at three locations which might be influenced by the different sources and landmass usage in each city. The presence of the carbonaceous elements in the particles indicates biomass burning emissions during the winter season which might be a source of pollutants in the studied areas.