TABLE 1.

in vivo Aerosol Studies of Silver Nanoparticles that Quantified Silver Concentration in the Lung

Reference	Physical Properties	Exposure Regimen	Dose	Species	PE Timepoint	Endpoints	Findings	Measured Ag in Lung (Method)
Ji et al. (2007)	18 nm uncoated generated in ceramic heater	6 h/day 5 day/week For 4 week whole body	0.5, 3.5, and 61 µg/m3	Rat (S/D) Male and female	0 h	Hematology Organ Wt Histopathology Silver Quantification	No significant effects	Low Mid Hi (AA)	Male 0.32 1.25 1.18	Female 0.27 ng/g 1.19 ng/g 1.50 µg/g (ww)
Sung et al. (2009)	18 nm uncoated generated in ceramic heater	6 h/day 5 day/week For 13 week whole body	49, 133, and 515 µg/m3	Rat (S/D) Male and female	0 h	Hematology Organ Wt Histopathology Silver Quantification	No change in organ weights. Alveolar inflammation and macrophage accumulation in high dose animals	Low Mid Hi (AA)	Male 0.30 4.24 20.6	Female 0.61 µg/g 5.45 µg/g 14.7 µg/g (ww)
Stebounova et al. (2011)	5 nm uncoated, suspended in water	6 h/day 5 day/week For 2 week whole body	3.3 mg/m3	Mouse (C57BL/6) male	0 h and 3 weeks	BAL Silver Quantification	Increase in BAL macrophages and neutrophils at both timepoints. No increase in LDH Increase in IL-12 and KC at 0 h.	31 µg/g (0 h) 10 µg/g (3 weeks) (ICP-AES) (dw)
Takenaka et al. (2001)	15 nm uncoated Spark generated	Single 6 h whole body	133 µg/m3	Rat (Fischer 344)	0 h, 1, 4, and 7 days	Silver Quantification	Decrease in concentration of Ag in lung over time post-exposure.	2.38 µg/g (0 h) 0.90 µg/g (1 day) 0.20 µg/g (4 days) 0.10 µg/g (7 days) (ICP-MS) (ww)
Kwon et al. (2012)	20 nm uncoated generated in ceramic heater	Single 6 h Nose-only	2.9 mg/m3	Mouse (C57BL/6) Male	0 and 24 h	BAL Western blot Silver Quantification	No change in BAL protein or LDH levels and no change in BAL cells Increase in ERK1/2 and p38 at 0 h and JNK at 0 and 24 h	0.51 µg/g (0 h) 0.12 µg/g (24 h) (AA) (dw)
Braakhuis et al. (2014)	15 nm (spark generated) and 410 nm (PVP-coated 200 nm primary particles)	6 h/day for 4 days Nose-only	179 µg/m3 (15 nm) 167 µg/m3 (410 nm)	Rat (Fischer 344)	1 and 7 days	BAL ELISA TEM Histopathology Silver Quantification	Neutrophil influx (15 nm) Increase in proinflammatory cytokines	15 nm: 3.4 µg/g (24 h) 1.3 µg/g (7 days) 410 nm: 6.0 µg/g (24 h) 3.9 µg/g (7 days) (HP-ICP-MS)

Abbreviations: S/D, Sprague Dawley; BAL, bronchoalveolar lavage fluid; PE, post-exposure; AA, atomic absorption spectroscopy; ICP-AES, inductively coupled plasma atomic emission spectroscopy; HP-ICP-MS, high-performance inductively coupled plasma mass spectroscopy; ww, wet organ weight; dw, dry organ weight.