Toxicokinetics of silver element following inhalation of silver nitrate in rats.

Silver (Ag) and its compounds are priority contaminants, for which toxicological effects are well documented, but their toxicokinetics are not fully documented for a proper risk assessment. While the toxicokinetics of insoluble Ag nanoparticles (Ag NPs) was recently documented, there is a lack of data on the kinetic behavior of the soluble form, such as one of the mostly used silver nitrate (AgNO3) form. This study aimed to better document the toxicokinetics of Ag element following inhalation of soluble AgNO3 for comparison with a previous study on the kinetics of inhaled Ag NPs using a similar experimental design. We exposed male Sprague-Dawley rats to AgNO3 during 6 continuous hours (typical of a daily worker exposure) to determine the kinetic time courses of Ag element in blood, tissues, and excreta over a 14-day period post-exposure. Only a small fraction of Ag was found in lungs following the onset of the 6-h inhalation of AgNO3 (on average (± SD) 0.3 ± 0.1% at the end of the 6-h inhalation). Blood profiles of Ag element showed peak levels right after the end of the 6-h inhalation period and levels decreased rapidly thereafter. Toxicokinetic parameter values calculated from the average blood-concentration profiles showed a mean residence time (MRT) of 135 h and mean half-life (t1/2) of 94 h, with AUC of 2.5 mg/L × h and AUMC of 338 mg/L × h2. In terms of percent of inhaled dose, highest levels of Ag in extrapulmonary organs were found in liver, which represented on average (± SD) 1.6 ± 0.6% of calculated inhaled dose followed by the kidney with 0.1 ± 0.08%. Peak levels in the GI tract (including contents) were found at the end of the 6-h inhalation and represented 20 ± 15.6% of the inhaled dose. The dominant excretion route of Ag was through feces. The time course of Ag element in the GI tract and feces following AgNO3 inhalation is also compatible with an intestinal reabsorption of Ag. When compared to results of Ag NPs of a prior study with the same design, this study showed differences in the kinetics of soluble AgNO3 compared to insoluble Ag NPs, with higher levels in blood, GI tract, and extrapulmonary tissues but lower levels in lungs following AgNO3 exposure.

Kinetic time courses of inhaled silver nanoparticles in rats.

Silver nanoparticles (Ag NPs) are priority substances closely monitored by health and safety agencies. Despite their extensive use, some aspects of their toxicokinetics remain to be documented, in particular following inhalation, the predominant route of exposure in the workplace. A same experimental protocol and exposure conditions were reproduced two times (experiments E1 and E2) to document the kinetic time courses of inhaled Ag NPs. Rats were exposed nose-only to 20 nm Ag NPs during 6 h at a target concentration of 15 mg/m3 (E1: 218,341 ± 85,512 particles/cm3; E2, 154,099 ± 5728 particles/cm3). The generated aerosol showed a uniform size distribution of nanoparticle agglomerates with a geometric mean diameter ± SD of 79.1 ± 1.88 nm in E1 and 92.47 ± 2.19 nm in E2. The time courses of elemental silver in the lungs, blood, tissues and excreta were determined over 14 days following the onset of inhalation. Excretion profiles revealed that feces were the dominant excretion route and represented on average (± SD) 5.1 ± 3.4% (E1) and 3.3 ± 2.5% (E2) of the total inhaled exposure dose. The pulmonary kinetic profile was similar in E1 and E2; the highest percentages of the inhaled dose were observed between the end of the 6-h inhalation up to 6-h following the end of exposure, and reached 1.9 ± 1.2% in E1 and 2.5 ± 1.6% in E2. Ag elements found in the GIT followed the trend observed in lungs, with a peak observed at the end of the 6-h inhalation exposure and representing 6.4 ± 4.9% of inhaled dose, confirming a certain ingestion of Ag NPs from the upper respiratory tract. Analysis of the temporal profile of Ag elements in the liver showed two distinct patterns: (i) progressive increase in values with peak at the end of the 6-h inhalation period followed by a progressive decrease; (ii) second increase in values starting at 72 h post-exposure with maximum levels at 168-h followed by a progressive decrease. The temporal profiles of Ag elements in lymphatic nodes, olfactory bulbs, kidneys and spleen also followed a pattern similar to that of the liver. However, concentrations in blood and extrapulmonary organs were much lower than lung concentrations. Overall, results show that only a small percentage of the inhaled dose reached the lungs-most of the dose likely remained in the upper respiratory tract. The kinetic time courses in the gastrointestinal tract and liver showed that part of the inhaled Ag NPs was ingested; lung, blood and extrapulmonary organ profiles also suggest that a small fraction of inhaled Ag NPs progressively reached the systemic circulation by a direct translocation from the respiratory tract.