Computational and ultrastructural toxicology of a nanoparticle, Quantum Dot 705, in mice.
We conducted pharmacokinetic and toxicology studies on Quantum Dot 705 (QD705) in male ICR mice for up to 6 months after a single intravenous dose. Time-course sacrifices were carried out at 1, 4, and 24 h; 3, 7, 14, and 28 days; and 6 months on groups of six mice per time point. Mass balance studies were also carried out at 24 h, 28 days, and 6 months. Using inductively coupled plasma mass spectrometry, various tissues, urine, and feces were analyzed for cadmium (Cd111), which is a major (46%) component of QD705. On the basis of these experimental studies, a physiologically based pharmacokinetic computer simulation model was developed with excellent predictive capability for the time-dependent kinetic and distributional changes of QD705 in tissues. QD705 persisted and accumulated in the spleen, liver, and kidneys for at least 28 days with little or no disposition but was gradually and partially eliminated by 6 months. Although histological alterations of the spleen, liver, and kidney by light microscopy are unremarkable, investigation using electron microscopy on numerous renal samples revealed definitive mitochondrial alterations in renal tubular epithelial cells at 28 days and 6 months postdosing. Health implications and potential beneficial applications of QD705 are suggested.
Lin
Pinpin
P
Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Taiwan.
Chen
Jein-Wen
JW
Chang
Louis W
LW
Wu
Jui-Pin
JP
Redding
Laurel
L
Chang
Han
H
Yeh
Teng-Kuang
TK
Yang
Chung Shi
CS
Tsai
Ming-Hsien
MH
Wang
Hsiu-Jen
HJ
Kuo
Yu-Chun
YC
Yang
Raymond S H
RS