Abstract
BACKGROUND: No systematic investigations have been conducted to assess the lung burden imposed by the chronic inhalation of silver nanoparticles (AgNPs) emitted by spray products. OBJECTIVE: The objective of this study was to formulate a study framework that integrates a probabilistic risk assessment scheme with a mechanistic lung burden model for the estimation of health risks associated with the long-term inhalation of AgNP-containing spray products. MATERIALS AND METHODS: A compartmentalized physiologically based alveolar deposition (PBAD) model was used to estimate AgNP lung burden. Dose-response relationships were established using nanotoxicity data sets obtained from rats (as a model organism). Weibull model-based thresholds of AgNP lung burden based on neutrophil-elevated inflammation bio-markers were estimated from Hill-based exposure-response relationships. Finally, the risks of lung disease posed by various AgNP-containing spray products were assessed. RESULTS: Conservative thresholds for the prevention of pulmonary disease were estimated as follows (mean ± SE): 34 nm AgNPs (0.32±0.22 mg) and 60 nm AgNPs (1.08±0.64 mg). Our results indicate that the risk probability was ~0.5 that the hazard quotient (HQ) estimates of deodorant with a count median diameter (CMD) ≈30 nm exceeded 1. The primary risk posed by AgNPs is transferred from the interstitial region to lymph nodes. Under the condition of 50% risk probability, the 97.5 percentile of HQ for the spray products were as follows: CMD ≈30 nm (~3.4) and CMD ≈60 nm (~1.1). CONCLUSION: Our application of the proposed risk assessment scheme to the results obtained in an in vivo animal model proved highly effective in elucidating the relationship between the characteristics of metallic NP-containing spray products and their corresponding toxicity. The integration of the proposed PBAD model with a risk assessment framework enables the rapid assessment of risk posed by spray products containing metallic NPs over various time scales.