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Tissue distribution and toxicity of titanium dioxide nanoparticles in rats after repeated dermal exposure
S278
Abstracts / Toxicology Letters 196S (2010) S37–S351
vs. 157.7 ± 50.6 ng/g; background values: 30–50 ng/g) 7 days after exposure. Hepatic Cd levels diminished by 30% in CdCl2 and 60% in NP-Cd, 30 days after exposure. Higher Cd intake was also observed in kidney of rats treated with NP-Cd (325.9 ± 159.2 ng/g in NP-Cd vs. 162.0 ± 60.2 ng/g in CdCl2 ; background values: 30–80 ng/g) after 7 days. Renal Cd levels increased (by 35%) in CdCl2 group and diminished (by 20%) in NP-Cd group, after 1 month. In conclusion, similar effects on oxidative stress were observed in both NP-Cd and CdCl2 treated rats, whereas different biokinetics behaviour was observed in liver and kidney (Italian Ministries of Health, Research and Education-PRIN 2007). doi:10.1016/j.toxlet.2010.03.1139
P303-019 Tissue distribution and toxicity of titanium dioxide nanoparticles in rats after repeated dermal exposure Y. Ikarashi, Y. Aiba, Y. Takita, T. Uchino, T. Nishimura National Institute of Health Sciences, Japan The aim of this study was to assess skin penetration, tissue distribution, and toxicity of titanium dioxide (TiO2 ) nanoparticles after repeated dermal exposure for 28 days. Surface-treated rutile TiO2 nanoparticles were dispersed at a concentration of 10% in silicone oil or distilled water. Crl:CD (SD) rats were topically treated with a closed patch of TiO2 suspension for 24 h. After repeated dermal exposure for 28 days, the titanium concentration in tissues was determined by inductively coupled plasma mass spectrometry. Histopathological examinations of the liver, kidney, lung, and skin were also performed. Blood samples were collected for hematological and serum biochemical tests. No significant difference in body and organ weight was observed between the control and TiO2 groups. Hematological examination revealed increased lymphocyte and monocyte counts in the TiO2 group. The total cholesterol, triglyceride, and phospholipid concentrations were also found to be increased. However, the increased levels were within the normal range. The organs showed no abnormal histological changes. The TiO2 particles applied were removed from the skin surface by washing, and the titanium content in the skin was determined. A detectable level of titanium was observed in the skin of rats in the TiO2 groups. Electron microscopy revealed the presence of TiO2 particles as aggregates, and not individual particles, in the layer interval of the stratum corneum. The titanium levels in other tissues and organs were within the analytical determination limits. There were no significant differences in the titanium levels in all organs between the control and TiO2 groups. These results indicated that repeated dermal exposure to TiO2 nanoparticles did not cause obvious systemic toxicity and that TiO2 did not penetrate the skin or spread to tissues. doi:10.1016/j.toxlet.2010.03.1140
P303-020 A size dependent toxicity study of a nanoemulsion containing dead sea minerals as the active agent and designed to treat skin conditions ˜ 1 , A. Aspiazu 1 , L. Larush 2 , F. B. Suarez-Merino 1 , C. Aristimuno 1 ˜ De Cerio Goni 1
Gaiker Technological Centre, Spain, 2 The Center of Nanoscience and Nanotechnology, Israel Economical and medical concerns in skin health are fast growing in Europe, matching with the remarkable extension of life expectancy in western countries, and the increased awareness of UV risks. Over recent years a personalized health care approach regarding skin conditions has been discussed due to the high skin type deviation among the population. The SkinTreat Project (EU FP7) aims to develop novel usercentered customized topical nanotherapeutic strategies, and novel drug delivery systems, for skin diseases, based on personalized skin protocols. A combination of conventional drugs as well as dead sea minerals are being used as the therapeutic agent of the nanosystems. Dead Sea minerals have well-established efficacy against psoriasis, atopic dermatitis and other inflammation skin diseases. In this current investigation we performed a battery of toxicity assays on a novel nanoemulsion which contained Dead Sea minerals as a therapeutic agent and its corresponding emulsion counterpart. The nanoemulsion was composed of: oil phase: hydrocarbon oil (15%), retinyl palmitate (5%), aqueous phase: H2 O (73–78%) and emulsifier (2.5–7%). To assess for cytotoxicity we used a colorimetric approach based on the activity of the mitochondrial dehydrogenase enzyme (MTT test). Mouse fibroblast (3T3 and L929) as well as human keratinocytes (HACAT) cells were inoculated in 96-well plates and incubated with the aforementioned nanoemulsion (144 nm) and emulsion (2–7 m) for 24 h. Cellular stress by means of ROS production (DCFDA) was also assessed upon emulsion exposure by flow cytometry. doi:10.1016/j.toxlet.2010.03.1141
P303-021 Possible role of PAPR-1 in protecting human HaCaT against cytotoxicity of SiO2 nanoparticles C.M. Gong, Z. Zhuang Shenzhen Center for Disease Control and Prevention, School of Public Health, Sun Yat-sen University, China Objective: To explore the toxicological mechanism of SiO2 nanoparticles in human HaCaT cells and to investigate whether PARP-1 is involved in protecting cells from damage caused by SiO2 nanoparticles. Methods: PARP-1 knock-out cell line was established via RNA interference as an experimental group. Normal HaCaT cells and cells transfected with the empty vector of pLKO.1 were used as controls. The general biological characteristics of these cells were verified by cell morphology, growth curve, cell cycle distribution, MN formation induced by mitocycin C and chromosome aberration analysis. Cells were treated with different concentrations of SiO2 nanoparticles (ranged from 2.5 g/mL to 10 g/mL) for 24 h. Results: A slight variation in the growth pattern was observed among stable transfectants from the third day to the sixth day. The shPARP-1 cells showed slower growth rate compared with the controls, but there is no statistical difference compare to pLKO and HaCaT cells. Cell cycle analysis result was consistent with the proliferation assay.
Abstracts / Toxicology Letters 196S (2010) S37–S351
vs. 157.7 ± 50.6 ng/g; background values: 30–50 ng/g) 7 days after exposure. Hepatic Cd levels diminished by 30% in CdCl2 and 60% in NP-Cd, 30 days after exposure. Higher Cd intake was also observed in kidney of rats treated with NP-Cd (325.9 ± 159.2 ng/g in NP-Cd vs. 162.0 ± 60.2 ng/g in CdCl2 ; background values: 30–80 ng/g) after 7 days. Renal Cd levels increased (by 35%) in CdCl2 group and diminished (by 20%) in NP-Cd group, after 1 month. In conclusion, similar effects on oxidative stress were observed in both NP-Cd and CdCl2 treated rats, whereas different biokinetics behaviour was observed in liver and kidney (Italian Ministries of Health, Research and Education-PRIN 2007). doi:10.1016/j.toxlet.2010.03.1139
P303-019 Tissue distribution and toxicity of titanium dioxide nanoparticles in rats after repeated dermal exposure Y. Ikarashi, Y. Aiba, Y. Takita, T. Uchino, T. Nishimura National Institute of Health Sciences, Japan The aim of this study was to assess skin penetration, tissue distribution, and toxicity of titanium dioxide (TiO2 ) nanoparticles after repeated dermal exposure for 28 days. Surface-treated rutile TiO2 nanoparticles were dispersed at a concentration of 10% in silicone oil or distilled water. Crl:CD (SD) rats were topically treated with a closed patch of TiO2 suspension for 24 h. After repeated dermal exposure for 28 days, the titanium concentration in tissues was determined by inductively coupled plasma mass spectrometry. Histopathological examinations of the liver, kidney, lung, and skin were also performed. Blood samples were collected for hematological and serum biochemical tests. No significant difference in body and organ weight was observed between the control and TiO2 groups. Hematological examination revealed increased lymphocyte and monocyte counts in the TiO2 group. The total cholesterol, triglyceride, and phospholipid concentrations were also found to be increased. However, the increased levels were within the normal range. The organs showed no abnormal histological changes. The TiO2 particles applied were removed from the skin surface by washing, and the titanium content in the skin was determined. A detectable level of titanium was observed in the skin of rats in the TiO2 groups. Electron microscopy revealed the presence of TiO2 particles as aggregates, and not individual particles, in the layer interval of the stratum corneum. The titanium levels in other tissues and organs were within the analytical determination limits. There were no significant differences in the titanium levels in all organs between the control and TiO2 groups. These results indicated that repeated dermal exposure to TiO2 nanoparticles did not cause obvious systemic toxicity and that TiO2 did not penetrate the skin or spread to tissues. doi:10.1016/j.toxlet.2010.03.1140
P303-020 A size dependent toxicity study of a nanoemulsion containing dead sea minerals as the active agent and designed to treat skin conditions ˜ 1 , A. Aspiazu 1 , L. Larush 2 , F. B. Suarez-Merino 1 , C. Aristimuno 1 ˜ De Cerio Goni 1
Gaiker Technological Centre, Spain, 2 The Center of Nanoscience and Nanotechnology, Israel Economical and medical concerns in skin health are fast growing in Europe, matching with the remarkable extension of life expectancy in western countries, and the increased awareness of UV risks. Over recent years a personalized health care approach regarding skin conditions has been discussed due to the high skin type deviation among the population. The SkinTreat Project (EU FP7) aims to develop novel usercentered customized topical nanotherapeutic strategies, and novel drug delivery systems, for skin diseases, based on personalized skin protocols. A combination of conventional drugs as well as dead sea minerals are being used as the therapeutic agent of the nanosystems. Dead Sea minerals have well-established efficacy against psoriasis, atopic dermatitis and other inflammation skin diseases. In this current investigation we performed a battery of toxicity assays on a novel nanoemulsion which contained Dead Sea minerals as a therapeutic agent and its corresponding emulsion counterpart. The nanoemulsion was composed of: oil phase: hydrocarbon oil (15%), retinyl palmitate (5%), aqueous phase: H2 O (73–78%) and emulsifier (2.5–7%). To assess for cytotoxicity we used a colorimetric approach based on the activity of the mitochondrial dehydrogenase enzyme (MTT test). Mouse fibroblast (3T3 and L929) as well as human keratinocytes (HACAT) cells were inoculated in 96-well plates and incubated with the aforementioned nanoemulsion (144 nm) and emulsion (2–7 m) for 24 h. Cellular stress by means of ROS production (DCFDA) was also assessed upon emulsion exposure by flow cytometry. doi:10.1016/j.toxlet.2010.03.1141
P303-021 Possible role of PAPR-1 in protecting human HaCaT against cytotoxicity of SiO2 nanoparticles C.M. Gong, Z. Zhuang Shenzhen Center for Disease Control and Prevention, School of Public Health, Sun Yat-sen University, China Objective: To explore the toxicological mechanism of SiO2 nanoparticles in human HaCaT cells and to investigate whether PARP-1 is involved in protecting cells from damage caused by SiO2 nanoparticles. Methods: PARP-1 knock-out cell line was established via RNA interference as an experimental group. Normal HaCaT cells and cells transfected with the empty vector of pLKO.1 were used as controls. The general biological characteristics of these cells were verified by cell morphology, growth curve, cell cycle distribution, MN formation induced by mitocycin C and chromosome aberration analysis. Cells were treated with different concentrations of SiO2 nanoparticles (ranged from 2.5 g/mL to 10 g/mL) for 24 h. Results: A slight variation in the growth pattern was observed among stable transfectants from the third day to the sixth day. The shPARP-1 cells showed slower growth rate compared with the controls, but there is no statistical difference compare to pLKO and HaCaT cells. Cell cycle analysis result was consistent with the proliferation assay.