Dosimetry of nasal uptake of water-soluble and reactive gases: A first study of interhuman variability

Abstract

Certain inhaled chemicals, such as reactive, water-soluble gases, are readily absorbed by the nasal mucosa upon inhalation and may cause damage to the nasal epithelium. Comparisons of the spatial distribution of nasal lesions in laboratory animals exposed to formaldehyde with gas uptake rates predicted by computational models reveal that lesions usually occur in regions of the susceptible epithelium where gas absorption is highest. Since the uptake patterns are influenced by air currents in the nose, interindividual variability in nasal anatomy and ventilation rates due to age, body size, and gender will affect the patterns of gas absorption in humans, potentially putting some age groups at higher risk when exposed to toxic gases. In this study, interhuman variability in the nasal dosimetry of reactive, water-soluble gases was investigated by means of computational fluid dynamics (CFD) models in 5 adults and 2 children, aged 7 and 8 years old. Airflow patterns were investigated for allometrically scaled inhalation rates corresponding to resting breathing. The spatial distribution of uptake at the airway walls was predicted to be nonuniform, with most of the gas being absorbed in the anterior portion of the nasal passages. Under the conditions of these simulations, interhuman variability in dose to the whole nose (mass per time per nasal surface area) due to differences in anatomy and ventilation was predicted to be 1.6-fold among the 7 individuals studied. Children and adults displayed very similar patterns of nasal gas uptake; no significant differences were noted between the two age groups.

Acknowledgement

We thank Darin Kalisak, Regina Richardson, and Dr. Grace Kepler for their contributions to this project. We are also grateful to Dr. Todd Yokley, Dr. Brent Senior, Dr. Rose Eapen, Dr. Dário Martins, and Dr. Neil Bailie for the provision and medical evaluation of CT scans and Dr. Kambiz Nazridoust for assistance with Fluent. This study was funded by the U.S. EPA, project numbers EP05C000009 and EP06C000405, and by the American Chemistry Council.

The views expressed in this article are those of the authors and do not necessarily reflect the views or policies of the U.S. Environmental Protection Agency.

Declaration of interest: The authors report no conflicts of interest.

Notes

¹ According to the NRC report on Science and Judgment in Risk Assessment (NRC, 1994, p. 28), “[Default procedures] are generic approaches, based on general scientific knowledge and policy judgment, that are applied to various elements of the risk assessment process when specific scientific information is not available.”