Assessing human exposure risk and lung disease burden posed by airborne silver nanoparticles emitted by consumer spray products

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.

Keywords: lung burdens; nanotoxicity; risk assessment; silver nanoparticles; spray product.

Figure 1

Schematic showing the overall study framework. Notes: (A) Problem formulation of human health risk or lung burdens posed by exposures of airborne AgNPs emitted from spray products, (B) exposure analysis of mass concentrations and particle size distributions of aerosolized AgNPs, (C) effect analysis of relationship between BALF neutrophil number and AgNPs dose in human lung, (D) threshold estimation of AgNPs lung burdens, and (E) risk characterization of airborne AgNPs toxicities in human lung. Abbreviation: BALF, bronchoaveolar lavage fluid.

Figure 2

Schematic showing the compartmentalized PBAD model. Abbreviations: PBAD, physiologically based alveolar deposition; A, alveolar region; M, alveolar macrophage region; I, interstitial region; L, lymph node region; X₁, AgNPs in alveolar region; X₂, AgNPs in alveolar macrophage; X₃, AgNPs in interstitial region; X₄, AgNPs in lymph node region; k_i, transfer rate of AgNPs from alveolar region to interstitial region; k_l, transferred rate of AgNPs from interstitial region to lymph node; k_p, phagocytosis rate of macrophage; k_a, apoptosis rate of macrophage; k_c, physical clearance rate of AgNPs; AgNP, silver nanoparticle.

Figure 3

Estimated mass concentrations of aerosols based on size distributions of droplets in spray (A, B) DI, (C, D) DO_S, and (E, F) DO_L in non-intensive or intensive application. Abbreviations: DI, disinfectant; DO_S, deodorant of AgNPs in smaller scales; DO_L, deodorant of AgNPs in larger scales; LN, lognormal; AUC, area under the curve; AgNP, silver nanoparticle.

Figure 4

(A, B) Total AgNP lung burden and (C, D) accumulation rates after long-term exposure of aerosolized AgNPs released by AgNP-containing spray products in non-intensive and intensive using condition. Abbreviations: AgNP, silver nanoparticle; DO_S, deodorant of AgNPs in smaller scales; DO_L, deodorant of AgNPs in larger scales; DI, disinfectant.

Figure 5

Dose–response describing relationship between lung burdens of (A) 34 nm and (B) 60 nm AgNPs and increase of neutrophils in BALF-based on the Hill model. Abbreviations: AgNP, silver nanoparticle; BALF, bronchoalveolar lavage fluid.

Figure 6

(A) Box and whisker plots of HQs in the criteria of γ₁-based threshold for the elevation of neutrophils in BALF. (B) Probability distribution of HQ exposed to spray DO_S in intensive application, and ERs for HQ of using (C, D) DO_S and (E, F) DO_L in non-intensive or intensive applications. Abbreviations: HQ, hazard quotients; γ₁, threshold dose preventing from causing 1% maximum effects on neutrophil elevations; DO_S, deodorant of AgNPs in smaller scales; DO_L, deodorant of AgNPs in larger scales; BALF, bronchoalveolar lavage fluid; ER, exceedance risk; AgNP, silver nanoparticle.

Figure 7

Sensitivity analysis for physiological parameters used in the PBAD model against total AgNP accumulation in human lung (μg) posed by aerosolized AgNP spray products. Abbreviations: AgNP, silver nanoparticle; PBAD, physiologically based alveolar deposition; k_i, transfer rate of AgNPs from alveolar region to interstitial region; k_l, transfer rate of AgNPs from interstitial region to lymph node; k_p, phagocytosis rate of macrophage; k_a, apoptosis rate of macrophage; k_c, physical clearance rate of nanoparticle.

Figure 8

A conceptual model showing mechanisms of inflammation response exposed to aerosolized AgNPs via inhalation. Abbreviations: AgNP, silver nanoparticle; PBAD, physiologically based alveolar deposition.