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 (t_1/2) 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.