The number of cells, particularly macrophages, containing silver increased with dose exposure in both strains, with the number of silver-positive cells in the BN rat 2 to 3-fold higher than in the SD rat at each time-point for the high dose. The uptake of nanoparticles into macrophages is likely to result in oxidative stress, the release of pro-inflammatorymediators and subsequent pulmonary inflammation [
15,
29,
30]. Concomitantly, we found that the amount of silver in the lungs persisted to the seventh day, despite a small reduction by that time, but the levels found in the lungs of Brown-Norway rats were approximately 50 % higher than in the lungs of Sprague–Dawley rats after the high dose exposure. The levels of silver measured in our Sprague–Dawley rats were higher than those previously reported in Sprague–Dawley or Fischer rats exposed to spark-generated uncoated silver nanoparticles of a similar size, partly due to the higher levels of exposure we delivered in our study [
2,
6,
7,
31,
32]. The calculation of silver levels from the day 1 and day 7 measurements in the Sprague–Dawley rats indicate a clearance of 50 %, which is in a similar range to the clearance of 15 nm spark-produced AgNPs inhaled by Fischer rats at a lower concentration of 179 μg/m
3 (compared to ~700 μg/m
3 for our study) for a similar exposure pattern (6 h/day for 4 days) of 62 % between 1 and 7 days post exposure [
6]. Clearance of such uncoated AgNPs have been reported to be much faster, for example in the study of Takenaka et al. [
2], it was 62 % one day after exposure, increasing to 96 % on day 7 (clearance between 1 day and 7 days was 89 %) in Fischer rats. In a recent study of nebulised AgNPs of primary particle size 20 nm suspended in citrate buffer with a high mass concentration of 7.2 mg/m
3 delivered to Sprague–Dawley rats for 6 h, a clearance of 34 % between day 1 and day 7 was reported [
33]. The comparison between different studies is difficult because of differences in amount of exposure, dose of nanoparticles, method of generation of nanoparticle aerosols, particle size and even animal gender, but most of these studies would indicate that the silver persists for a period of at least 7 days after inhalation. In the study of Anderson et al. [
33], one third of the initial silver inhaled persisted even at 56 days, and this was associated with a greater persistence of silver-positive macrophages at 21 and 56 days. In our study, the clearance between 1 day and 7 days for the Brown-Norway rat compared to the Sprague–Dawley rat was lower at 33 %, and was associated with a 2 to 3-fold higher number of silver-containing lung macrophages compared to SD lungs. It is possible that the pre-inflamed lung of the Brown-Norway rat may retain more nanoparticles with a slower clearance rate leading to higher levels of silver found in the lungs when compared to the Sprague–Dawley rat.