The Toxicologist - Society of Toxicology

een explored. This study investigated the effects of acetaminophen (APAP) metabolism
and hepatotoxicity in Balb/C mice pretreated with a single dose of citrate-stabilized
10 nm gold nanoparticles (AuNP) (0.5 – 10 mg/kg i.v.). After 72 hours of
exposure to AuNP, mice were given a single dose of APAP (30-700 mg/kg i.p.).
Blood was collected at multiple time points, and the mice were sacrificed at either 6
or 24 hours following APAP dosing. Multiple assays were used to evaluate liver or
serum glutathione concentrations, liver enzyme levels, and APAP metabolites.
Preliminary results show an increased mortality associated with a single dose of
APAP following a single dose of AuNP. In addition, mice dosed with both AuNP
and APAP exhibited increased microscopic liver damage 24 hours after dosing compared
to mice that received either agent alone. The observed toxicity is thought to
be due at least in part to AuNP depleting glutathione levels, causing a subsequent
increase in the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). These
results suggest that nanoparticles may contribute to toxicity indirectly by interfering
with the response to a secondary insult and reveal the potential importance of
additional studies in assessing the safety of nanoparticle-based drugs.
2075 SILVER NANOPARTICLES-INDUCED GENOTOXICITY
IN BONE MARROW CELLS OF SPRAGUE-DAWLEY RATS.
A. Patlolla 1 and D. Hackett 1, 2 . 1 Molecular Toxicology Research Laboratory, Jackson
State University, Jackson, MS and 2 Biology, Jackson State University, Jackson, MS.
The antibacterial effect of silver nanoparticles (Ag-NPs) has resulted in their extensive
application in health, electronic, and household products. However, while the
population exposed to AgNPs continues to increase with ever new applications, silver
nanoparticles research remains a controversial with regard to their toxicity to biological
systems. In particular, the oral toxicity of AgNPs is of special concern to ensure
public and consumer health. Due to the intensive commercial application of
AgNPs, their health risk assessment is of great importance. The previous in vitro
studies demonstrated that AgNPs caused toxicity in various cell-lines. However, the
data on the toxicity of AgNPs in vivo is largely lacking. The aim of this investigation
was to determine the clastogenic/genotoxic potential of AgNPs in bone marrow
cells of Sprague-Dawley rats; using mitotic index (MI), structural chromosome
aberrations (SCA) and micronuclei (MN) formation as genetic endpoints. Four
groups of five male rats, each weighing approximately 80 + 2 g, were administered
orally, once a day for five days with doses of 5, 25, 50, 100, mg/kg body weight
(BW) of AgNPs. A control group was also made of five rats. Chromosome and micronuclei
from bone marrow cells were processed and examined following standard
protocols. The results demonstrated that AgNPs exposure significantly increases
(p