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DOSIMETRY MODELING OF INHALED FORMALDEHYDE: BINNING NASAL FLUX PREDICTIONS FOR QUANTITATIVE RISK ASSESSMENT
Citation:
Kimbell, J. S., J H. Overton, R. P. Subramaniam, P. M. Schlosser, K. T. Morgan, R. Conolly, AND F. J. Miller. DOSIMETRY MODELING OF INHALED FORMALDEHYDE: BINNING NASAL FLUX PREDICTIONS FOR QUANTITATIVE RISK ASSESSMENT. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 64:111-121, (2001).
Description:
Dosimetry Modeling of Inhaled Formaldehyde: Binning Nasal Flux Predictions for Quantitative Risk Assessment. Kimbell, J.S., Overton, J.H., Subramaniam, R.P., Schlosser, P.M., Morgan, K.T., Conolly, R.B., and Miller, F.J. (2001). Toxicol. Sci. 000, 000:000.
Interspecies extrapolations of tissue dose and tumor response have been a significant source of uncertainty in formaldehyde cancer risk assessment. The ability to account for species-specific variation of dose within the nasal passages would reduce some of this uncertainty. Three-dimensional, anatomically realistic, computational fluid dynamics (CFD) models of airflow and formaldehyde gas transport in the nasal passages of the F344 rat, rhesus monkey, and human were used to predict local patterns of formaldehyde wall mass flux (pmol/(mm2-hr-ppm). The surface of the nasal passages of each species was partitioned by flux into smaller regions (flux bins), each characterized by a surface area and an average flux value. Rat and monkey flux bins were predicted for steady-state inspiratory airflow rates corresponding to the estimated minute volume for each species. Human flux bins were predicted for 7.4, 15, 18, 25.8, 31.8, and 37 L/min and were extrapolated to 46 and 50 L/min. Nearly 20% of human nasal surface area was estimated to be associated with flux values above the median at 15 L/min, whereas only 5% of rat and less than 1% of monkey nasal surfaces were associated with fluxes higher than the median at 0.576 L/min and 4.8 L/min, respectively. Human nasal flux patterns shifted distally and uptake percentage decreased as inspiratory flow rate increased. Flux binning captures anatomical effects on flux and is thereby a basis for describing the effects of anatomy and airflow on local distributions of tissue response. Formaldehyde risk models that incorporate flux binning derived from anatomically realistic CFD models will have significantly reduced uncertainty compared with risk estimates based on default methods.