Toxicokinetics of silver element following inhalation of silver nitrate in rats

Sandra Nirina Andriamasinoro; Denis Dieme; Sami Haddad; Michèle Bouchard

doi:10.1007/s00204-022-03424-w

Toxicokinetics of silver element following inhalation of silver nitrate in rats

Arch Toxicol. 2023 Mar;97(3):663-670. doi: 10.1007/s00204-022-03424-w. Epub 2022 Nov 27.

Authors

Sandra Nirina Andriamasinoro¹, Denis Dieme¹, Sami Haddad¹, Michèle Bouchard²

Affiliations

¹ Department of Environmental and Occupational Health, Chair in Toxicological Risk Assessment and Management, and Public Health Research Center (CReSP), University of Montreal, Roger-Gaudry Building, U436, Main Station, P.O. Box 6128, Montreal, QC, H3C 3J7, Canada.
² Department of Environmental and Occupational Health, Chair in Toxicological Risk Assessment and Management, and Public Health Research Center (CReSP), University of Montreal, Roger-Gaudry Building, U436, Main Station, P.O. Box 6128, Montreal, QC, H3C 3J7, Canada. michele.bouchard@umontreal.ca.

PMID: 36436015
DOI: 10.1007/s00204-022-03424-w

Abstract

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.

Keywords: In vivo; Inhalation exposure; Silver nitrate; Toxicokinetics.

MeSH terms

Animals
Male
Metal Nanoparticles*
Rats
Rats, Sprague-Dawley
Silver
Silver Nitrate* / pharmacokinetics
Toxicokinetics

Substances

Silver Nitrate
Silver