Volatile methyl siloxanes (VMS) are ubiquitous in indoor environments due to their use in personal care products. This paper builds on previous work identifying sources of VMS by synthesizing time-resolved proton-transfer reaction time-of-flight mass spectrometer VMS concentration measurements from four multiweek indoor air campaigns to elucidate emission sources and removal processes. Temporal patterns of VMS emissions display both continuous and episodic behavior, with the relative importance varying among species. We find that the cyclic siloxane D5 is consistently the most abundant VMS species, mainly attributable to personal care product use. Two other cyclic siloxanes, D3 and D4, are emitted from oven and personal care product use, with continuous sources also apparent. Two linear siloxanes, L4 and L5, are also emitted from personal care product use, with apparent additional continuous sources. We report measurements for three other organosilicon compounds found in personal care products. The primary air removal pathway of the species examined in this paper is ventilation to the outdoors, which has implications for atmospheric chemistry. The net removal rate is slower for linear siloxanes, which persist for days indoors after episodic release events. This work highlights the diversity in sources of organosilicon species and their persistence indoors.

The multi-compound, and multi-dose (MC-MD) route physiologically based pharmacokinetic (PBPK) model for cyclic siloxanes reported by McMullin et al. (2016) brought together the series of models for octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) in rat and human into a unified code structure that would allow simulation of both compounds following the inhalation and dermal routes of exposure. The refined MC-MD PBPK model presented here expands upon this effort to include representation of rat kinetic data in plasma, tissues and exhaled breath for the parent compounds after oral bolus administration. Additional refinements were made with regards to hepatic induction of metabolism in the liver and allometric scaling of rate constants for the deep tissue compartments which will allow the MC-MD model to be used in uncertainty analysis. Overall, the refined MC-MD model was able to reproduce both parent D4 and D5 kinetic data in rat and human after inhalation exposure (rat and human) or dermal exposure (human). The inclusion of sequestered (i.e., lipid associated) oral absorption into plasma after oral bolus dosing successfully described the lack of exhalation as well as the initial distribution of siloxane to the liver which was higher than simple partitioning from plasma would allow. The refined MC-MD PBPK model presented here can be incorporated into uncertainty and variability analysis and cross-species dosimetry for both D4 and D5.

There are currently seven published physiologically based pharmacokinetic (PBPK) models describing aspects of the pharmacokinetics of octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) for various exposure routes in rat and human. Each model addressed the biological and physico-chemical properties of D4 and D5 (highly lipophilic coupled with low blood: air partition coefficient and high liver clearance) that result in unique kinetic behaviors as well differences between D4 and D5. However, the proliferation of these models resulted in challenges for various risk assessment applications when needing to determine the optimum model for estimating dose metrics. To enhance the utility of these PBPK models for risk assessment, we integrated the suite of structures into one coherent model capable of simulating the entire set of existing data equally well as older more limited scope models. In this paper, we describe the steps required to develop this integrated model, the choice of physiological, partitioning and biochemical parameters for the model, and the concordance of the model behavior across key data sets. This integrated model is sufficiently robust to derive relevant dose metrics following individual or combined dermal and inhalation exposures of workers, consumer or the general population to D4 and D5 for route-to-route, interspecies and high to low dose extrapolations for risk assessment.