title: Effects of developmental exposure to silver in ionic and nanoparticle form: A study in rats.
abstract: BACKGROUND
  Evaluations of silver in both nanoparticle (Ag-NPs) and ionic forms indicate some adverse effects on living organisms, but little is known about their potential for developmental toxicity. In this study, developmental toxicity of Ag-NPs (from 0.2 to 20 mg/kg/day) and ionic Ag (AgNO3, 20 mg Ag/kg/day) were investigated in rats.
  
  
  METHODS
  Animals were dosed by gavage from gestation day 7 - 20. The day after parturition, dams and pups were sacrificed and Ag level assessed in several maternal and pup organs. In addition, hepatotoxicity and oxidative stress parameters and histopathology were evaluated.
  
  
  RESULTS
  No treatment related effects were found for gestational parameters including pregnancy length, maternal weight gain, implantations, birth weight and litter size at any dose level of Ag-NPs. Maternal weight gain was lower in dams receiving AgNO3compared to the other groups, suggesting that the ionic form may exert a higher degree of toxicity compared to the NP form. Tissue contents of Ag were higher in all treated groups compared to control dams and pups, indicating transfer of Ag across the placenta. The findings furthermore suggest that Ag may induce oxidative stress in dams and their offspring, although significant induction was only observed after dosing with AgNO3. Histopathological examination of brain tissue revealed a high incidence of hippocampal sclerosis in dams treated with nanoparticle as well as ionic Ag.
  
  
  CONCLUSIONS
  The difference in offspring deposition patterns between ionic and NP Ag and the observations in dam brain tissue, requires scrutiny, and, if corroborated, indicate that ionic and NP forms maybe need separate risk assessments and that the hazard ratings of silver in both ionic and nanoparticle forms should be increased, respectively.
  
  
  BACKGROUND
  Not applicable. Developmental Toxicity of Ag-NPs.
authors.affiliation: Department of Toxicology, Yeditepe University, Faculty of Pharmacy, Atasehir, Istanbul, Turkey. mohammad.saz@yeditepe.edu.tr.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Charehsaz
authors.affiliation: National Research Center for the Working Environment, Danish Nanosafety Centre, Copenhagen, Denmark.
authors.forename: Karin Sørig
authors.initials: KS
authors.lastname: Hougaard
authors.affiliation: Department of Toxicology, Yeditepe University, Faculty of Pharmacy, Atasehir, Istanbul, Turkey.
authors.forename: Hande
authors.initials: H
authors.lastname: Sipahi
authors.affiliation: Department of Pathology, Yeditepe University, Faculty of Medicine, Istanbul, Turkey.
authors.forename: Asiye Işın Doğan
authors.initials: AI
authors.lastname: Ekici
authors.affiliation: Department of Biostatistics, Yeditepe University, Faculty of Medicine, Istanbul, Turkey.
authors.forename: Çiğdem
authors.initials: Ç
authors.lastname: Kaspar
authors.affiliation: Department of Genetics and Bioengineering, Yeditepe University, Istanbul, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Culha
authors.affiliation: Department of Toxicology, Hacettepe University, Faculty of Pharmacy, Ankara, Turkey.
authors.forename: Ülkü Ündeğer
authors.initials: ÜÜ
authors.lastname: Bucurgat
authors.affiliation: Department of Toxicology, Yeditepe University, Faculty of Pharmacy, Atasehir, Istanbul, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Aydin
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D005260:Female; D008297:Male; D008431:Maternal-Fetal Exchange; D053768:Metal Nanoparticles / Q000633:toxicity*; D008892:Milk / Q000737:chemistry; D018384:Oxidative Stress / Q000187:drug effects; D011247:Pregnancy; D017207:Rats, Sprague-Dawley; D012834:Silver / Q000493:pharmacokinetics / Q000633:toxicity*; D012835:Silver Nitrate / Q000493:pharmacokinetics / Q000633:toxicity*; D014018:Tissue Distribution; D015430:Weight Gain / Q000187:drug effects
chemical_list: D012834:Silver; D012835:Silver Nitrate
keywords: Hippocampal sclerosis; Oxidative stress; Pregnancy; Rat; Silver