Subchronic Inhalation Toxicity of Silver Nanoparticles

Abstract

The subchronic inhalation toxicity of silver nanoparticles was studied in Sprague-Dawley rats. Eight-week-old rats, weighing approximately 253.2 g (males) and 162.6 g (females), were divided into four groups (10 rats in each group): fresh-air control, low dose (0.6 x 10(6) particle/cm(3), 49 microg/m(3)), middle dose (1.4 x 10(6) particle/cm(3), 133 microg/m(3)), and high dose (3.0 x 10(6) particle/cm(3), 515 microg/m(3)). The animals were exposed to silver nanoparticles (average diameter 18-19 nm) for 6 h/day, 5 days/week, for 13 weeks in a whole-body inhalation chamber. In addition to mortality and clinical observations, body weight, food consumption, and pulmonary function tests were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for hematology and clinical chemistry tests, and the organ weights were measured. Bile-duct hyperplasia in the liver increased dose dependently in both the male and female rats. Histopathological examinations indicated dose-dependent increases in lesions related to silver nanoparticle exposure, including mixed inflammatory cell infiltrate, chronic alveolar inflammation, and small granulomatous lesions. Target organs for silver nanoparticles were considered to be the lungs and liver in the male and female rats. No observable adverse effect level of 100 microg/m(3) is suggested from the experiments.

A systematic review of evidence for silver nanoparticle-induced mitochondrial toxicity

“…This is directly related to the likelihood that AgNPs are distributed to, and exert mitochondrial toxicity within, tissues with relatively high metabolic demand. Silver nanoparticles are distributed throughout the body upon oral administration [105][106][107] and inhalational exposure, 108 with liver being the predominant target tissue in oral exposure 105 and both liver and lung in inhalational exposure. 108 However, long-term clearance kinetics of silver after oral AgNP exposure indicates that elimination of silver from AgNPs is slowest in tissues with biological barriers (brain and testis).…”

Potential risks and benefits of nanotechnology: perceptions of risk in sunscreens

“…Unfortunately, silver levels in these organs were not reported. As the NOAELs of 100 µg/m 3 and 117 µg/m 3 (based on liver and lung toxicity) in subchronic inhalation toxicity studies are significantly higher (Sung et al 2009;Song et al 2013), an absence of effects in the male reproductive organs at 60 µg/m 3 in the study by Ji et al (2007) would, however, not be sufficient to exclude those as possible targets of silver toxicity.…”

“…Besides uptake via the blood, presence in brain might be explained by uptake via the nasal epithelium and the olfactory nerve (Oberdörster et al 2004). Some differences were observed between male and female rats, with female rats having a higher Ag content in the kidneys compared to the male rats (Sung et al 2009). …”

“…Two repeated dose inhalation toxicity studies over 28 and 90 days respectively were published that included investigations into systemic uptake from the lung (Ji et al 2007, Sung et al 2009). Silver nanoparticles were generated by evaporation/condensation of Ag source material using a small ceramic heater, which produced particles in the size range of 2 -65 nm.…”

“…Tier 1 of testing included, amongst other studies, subchronic oral and inhalation toxicity testing as well as a screening assay for reproductive / developmental toxicity with the specific material. To complete a provisional risk assessment, US EPA used reference values obtained in studies with other nanosilver materials: an inhalation NOAEC of 133 µg/m 3 based on a 90-day study in rats (Sung et al 2009), an oral NOAEL of 0.5 mg/kg bw/d based on a 28-day study in mice , and route-to-route extrapolation from the oral to the dermal route. An additional uncertainty factor of 10 for quality of database was included, resulting in a reference margin-of-exposure (MoE) of 1000 and 3000 for incidental and chronic exposures.…”