Jonghye Choi

Combined repeated-dose toxicity study of silver nanoparticles with the reproduction/developmental toxicity screening test

Abstract Combined repeated-dose toxicity study of citrate-capped silver nanoparticles (7.9 ± 0.95 nm) with reproduction/developmental toxicity was investigated in rats orally treated with 62.5, 125 and 250 mg/kg, once a day for 42 days for males and up to 52 days for females. The test was performed based on the Organization for Economic Cooperation and Development test guideline 422 and Good Laboratory Practice principles. No death was observed in any of the groups. Alopecia, salivation and yellow discolouration of the lung were observed in a few rats but the symptoms were not dose-dependent. Haematology, serum biochemical investigation and histopathological analysis revealed no statistically significant differences between control group and the treated groups. Toxicity endpoints of reproduction/developmental screening test including mating, fertility, implantation, delivery and foetus were measured. There was no evidence of toxicity.

Toxicity of Zinc Oxide Nanoparticles in Rats Treated by Two Different Routes: Single Intravenous Injection and Single Oral Administration

Toxicokinetics of zinc oxide nanoparticles (ZnONP) was studied in rats via a single intravenous (iv) injection and a single oral administration (3 mg/kg or 30 mg/kg), respectively. Blood concentrations of zinc (Zn) were monitored for 7 d and tissue distribution were determined in liver, kidneys, lung, spleen, thymus, brain, and testes. To ascertain the excretion of ZnONP, Zn levels in urine and feces were measured for 7 d. ZnONP were not readily absorbed from the gastrointestinal tract (GIT) after oral administration and were excreted mostly in feces. When the nanoparticles were injected iv to rats at a dose of 30 mg/kg, peak concentration appeared at 5 min but returned to normal range by d 2 (48 h after injection). ZnONP were distributed mainly to liver, kidneys, lung, and spleen, but not to thymus, brain, and testes. The distribution level was significantly decreased to normal by d 7. Feces excretion levels after iv injection supported biliary excretion of ZnONP. In rats injected iv with 30 mg/kg, mitotic figures in hepatocytes were significantly increased and multifocal acute injuries with dark brown pigment were noted in lungs, while no significant damage was observed in rats treated orally with the same dosage. Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/uteh

A Transfer of Silver Nanoparticles from Pregnant Rat to Offspring

Silver nanoparticles (size: 7.9 ± 0.95 nm, dosage: 250 mg/kg) were orally administered to pregnant rats. At 4 days after parturition, four pups were randomly selected (one pup from one dam) and silver level in liver, kidney, lung and brain was determined by ICP-MS and electron microscope. As results, silver nanoparticles highly accumulated in the tissues of the pups. Silver level in the treated group was 132.4 ± 43.9 ng/g in the kidney (12.3 fold compared to control group), 37.3 ± 11.3 ng/g in the liver (7.9 fold), 42.0 ± 8.6 ng/g in the lung (5.9 fold), and 31.1 ± 4.3 ng/g in the brain (5.4 fold). This result suggested that the possible transfer of silver nanoparticles from pregnant dams to the fetus through mainly placenta.

Skin Corrosion and Irritation Test of Nanoparticles Using Reconstructed Three-Dimensional Human Skin Model, EpiDerm(TM).

Effects of nanoparticles (NPs) on skin corrosion and irritation using three-dimensional human skin models were investigated based on the test guidelines of Organization for Economic Co-operation and Development (OECD TG431 and TG439). EpiDermTM skin was incubated with NPs including those harboring iron (FeNPs), aluminum oxide (AlNPs), titanium oxide (TNPs), and silver (AgNPs) for a defined time according to the test guidelines. Cell viabilities of EpiDermTM skins were measured by the 3-(4, 5-dimethylthi-azol-2-yl)-2.5-diphenyltetrazolium bromide based method. FeNPs, AlNPs, TNPs, and AgNPs were non-corrosive because the viability was more than 50% after 3 min exposure and more than 15% after 60 min exposure, which are the non-corrosive criteria. All NPs were also non-irritants, based on viability exceeding 50% after 60 min exposure and 42 hr post-incubation. Release of interleukin 1-alpha and histopathological analysis supported the cell viability results. These findings suggest that FeNPs, AlNPs, TNPs, and AgNPs are ‘non-corrosive’ and ‘non-irritant’ to human skin by a globally harmonized classification system.

Skin corrosion and irritation test of sunscreen nanoparticles using reconstructed 3D human skin model

Objectives Effects of nanoparticles including zinc oxide nanoparticles, titanium oxide nanoparticles, and their mixtures on skin corrosion and irritation were investigated by using in vitro 3D human skin models (KeraSkinTM) and the results were compared to those of an in vivo animal test. Methods Skin models were incubated with nanoparticles for a definite time period and cell viability was measured by the 3-(4, 5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide method. Skin corrosion and irritation were identified by the decreased viability based on the pre-determined threshold. Results Cell viability after exposure to nanomaterial was not decreased to the pre-determined threshold level, which was 15% after 60 minutes exposure in corrosion test and 50% after 45 minutes exposure in the irritation test. IL-1α release and histopathological findings support the results of cell viability test. In vivo test using rabbits also showed non-corrosive and non-irritant results. Conclusions The findings provide the evidence that zinc oxide nanoparticles, titanium oxide nanoparticles and their mixture are ‘non corrosive’ and ‘non-irritant’ to the human skin by a globally harmonized classification system. In vivo test using animals can be replaced by an alternative in vitro test.