Biodistribution and toxic potential of silver nanoparticles when introduced to the female rat reproductive tract

The prevalence of ionic silver and silver nanomaterials in hygiene products has been increasing due to their antimicrobial activity. While numerous studies have examined the effects of nanosilver in laboratory settings, there is a limited understanding of its impact on reproductive tissues, as well as its biodistribution and toxicity upon intra-vaginal exposure. If ionic or nanosilver enters adjacent and internal tissues via intra-vaginal exposure, the overuse of hygiene products containing silver may potentially threaten woman's health. This study investigated the effects of intra-vaginal silver exposure in Female Fischer 344 rats to single and multiple doses of a commercial product containing silver, along with standard nanosilver materials. Custom tampons were developed to simulate practical usage scenarios. The analysis of tissue biodistribution revealed that epithelial penetration and redistribution of silver was observed with most administered silver eliminated in feces (8-44 %), and secondary tissues containing 1-18 % of the dose, predominantly localized in the reproductive tract. In a subsequent toxicity study, vaginal histopathology indicated a cellular inflammatory reaction (neutrophil infiltration) associated with the presence of foreign silver material upon a single administration. Interestingly, no noticeable difference in histopathology incidence was observed upon multiple exposures to silver compared to the control group. Clinical chemistry and hematology analyses following acute exposure to silver nanomaterials showed no significant abnormalities. Overall, acute vaginal exposure to silver nanomaterials and ionic silver resulted in limited silver persistence, local tissue reactivity, epithelial penetration of silver resulting in accumulation in distant organs, and elimination primarily through feces. In vitro data suggested potential alterations in normal vaginal flora. Long-term studies are still lacking in this area.