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Titanium dioxide particles inhibit the inflammatory responses in asthmatic mice
S200
Abstracts / Toxicology Letters 211S (2012) S43–S216
P33-08 Titanium dioxide particles inhibit the inflammatory responses in asthmatic mice Gustafsson Åsa, Sofia Jonasson, Anders Bucht Swedish Defence Research Agency, FOI, Sweden Purpose: Titanium dioxide (TiO2 ) nanoparticles are manufactured worldwide and although TiO2 is regarded as relative non-toxic in concentrations occurring in occupational environments, it is conceivable that adverse health effects may develop in sensitive populations such as asthmatic individuals. We investigated if a single or multiple exposures of TiO2 before or during challenge of aerosolized allergen could aggravate inflammatory responses and respiratory dysfunction in BALB/c mice with ovalbumin (OVA)-induced airway inflammation. Methods: Inhalation of aerosolized TiO2 nanoparticles was performed during OVA sensitization, before lavage (BAL), and for analyses of inflammatory mediators in BAL and serum. Results and conclusion(s) of the study: Single TiO2 exposure before challenge but not during challenge OVA challenge or during the OVA challenge period. The experiment ended with assessment of lung mechanics. Samples were taken for differential counting of inflammatory cells in bronchoalveolar had a marked effect on peripheral airways. Single exposure increased the infiltration of neutrophils in both healthy and inflamed airways. Multiple exposures of TiO2 both during sensitization and challenge inhibited the OVA-induced airway response but concomitant administration of OVA and TiO2 resulted in decline in general health condition as indicated by the loss of body weight and an altered systemic inflammatory response. From these results we conclude that inhalation of TiO2 may aggravate allergic airway disease but we also demonstrated that symptoms displayed in the experimentally induced allergic disease are highly dependent on the accumulated nanoparticles’ dose and timing of exposure. Our data imply enhanced risk for adverse responses of inhaled nanoparticles in sensitive populations. doi:10.1016/j.toxlet.2012.03.718
P33-09 Toxicity of nanomaterials—Focus on the perspective of the technology assessment Jutta Schimmelpfeng Karlsruhe Institute of Technology, Institute of Technology Assessment and Systems Analysis, Germany Technology assessment develops knowledge of the consequences of human action in relation to the development and the application of new technologies. It supports policy and science concerning future decisions on the basis of currently available knowledge and rational assessments. In the case of nanotechnology, studies on the effects of nanoscale particles released into the environment accompany their further development. Meanwhile it is known that in addition to the technological and medical benefits unintended adverse effects on humans and the environment are possible. This area of toxicological research is very extensive, because many different types and designs of nanoscale particles need to be investigated experimentally. Thus, there are many knowledge gaps and the problem of governmental decision-making and action under uncertainty about potential health risks in the new technology. In the framework of technology assessment, relevant
toxicological knowledge is evaluated based on rational and with regard to risk assessment. Hazard identification, hazard characterization and exposure characterisation are pre-conditions for the rational based risk assessment. In addition aspects like the biodistribution of nanosized particles in the human body, the mechanisms of action leading to negative health effects, and the molecular interactions between specific nanoscale particles and organic molecules lead to further scientific impact. The integration of these toxicological evaluation results in larger contexts and the use in risk assessment improves the scientific knowledge and supports the prospective development of appropriate strategies and options for further action, such as the regulation of nanotechnological materials and the development of alternative strategies. doi:10.1016/j.toxlet.2012.03.719
P33-10 Effect of nanoparticles on the cytotoxicity of coexisting metal salts Kazuo Isama, Tsuyoshi Kawakami, Keiko Sakai, Atsuko Miyajima, Atsuko Matsuoka National Institute of Health Sciences, Japan Purpose: Although nanomaterials are already being used for various applications in the industry, the safety of nanomaterials has not yet been sufficiently elucidated. In vitro toxicities of nanomaterials alone are gradually becoming clear, but their interaction with other materials is still unknown. In this study, we examined the cytotoxic effects of nanomaterials coexisting with some metal salts. Methods: Silicon dioxide (SiO2 ) and titanium dioxide (TiO2 ) nanoparticles (CIK NanoTek Corporation) were used in this study. The particle diameter and zeta potential of the nanoparticles were measured by dynamic light scattering. The cytotoxicities of aluminum chloride (AlCl3 ), copper (II) chloride (CuCl2 ), and zinc chloride (ZnCl2 ), coexisting with and without the nanoparticles, were evaluated by the colony formation assay using Chinese hamster V79 lung fibroblasts. Results and conclusions: Weak cytotoxicity was observed at 25 g/ml and above of TiO2 nanoparticles. However, cytotoxicity was not observed at 100 g/ml and below of SiO2 nanoparticles. The cytotoxicity of the three metal salts did not change when they coexisted with 10 and 100 g/ml of TiO2 nanoparticles. In contrast, though the cytotoxicity of ZnCl2 did not change, the cytotoxicity of AlCl3 and CuCl2 increased when they coexisted with 100 g/ml of SiO2 nanoparticles. In conclusion, SiO2 nanoparticles increased the cytotoxicity of some of the coexisting metal salts. Acknowledgment: This study was supported by the Health Labour Sciences Research Grant (H23-kagaku-ippan-006) from the Japanese Ministry of Health, Labour and Welfare. doi:10.1016/j.toxlet.2012.03.720
Abstracts / Toxicology Letters 211S (2012) S43–S216
P33-08 Titanium dioxide particles inhibit the inflammatory responses in asthmatic mice Gustafsson Åsa, Sofia Jonasson, Anders Bucht Swedish Defence Research Agency, FOI, Sweden Purpose: Titanium dioxide (TiO2 ) nanoparticles are manufactured worldwide and although TiO2 is regarded as relative non-toxic in concentrations occurring in occupational environments, it is conceivable that adverse health effects may develop in sensitive populations such as asthmatic individuals. We investigated if a single or multiple exposures of TiO2 before or during challenge of aerosolized allergen could aggravate inflammatory responses and respiratory dysfunction in BALB/c mice with ovalbumin (OVA)-induced airway inflammation. Methods: Inhalation of aerosolized TiO2 nanoparticles was performed during OVA sensitization, before lavage (BAL), and for analyses of inflammatory mediators in BAL and serum. Results and conclusion(s) of the study: Single TiO2 exposure before challenge but not during challenge OVA challenge or during the OVA challenge period. The experiment ended with assessment of lung mechanics. Samples were taken for differential counting of inflammatory cells in bronchoalveolar had a marked effect on peripheral airways. Single exposure increased the infiltration of neutrophils in both healthy and inflamed airways. Multiple exposures of TiO2 both during sensitization and challenge inhibited the OVA-induced airway response but concomitant administration of OVA and TiO2 resulted in decline in general health condition as indicated by the loss of body weight and an altered systemic inflammatory response. From these results we conclude that inhalation of TiO2 may aggravate allergic airway disease but we also demonstrated that symptoms displayed in the experimentally induced allergic disease are highly dependent on the accumulated nanoparticles’ dose and timing of exposure. Our data imply enhanced risk for adverse responses of inhaled nanoparticles in sensitive populations. doi:10.1016/j.toxlet.2012.03.718
P33-09 Toxicity of nanomaterials—Focus on the perspective of the technology assessment Jutta Schimmelpfeng Karlsruhe Institute of Technology, Institute of Technology Assessment and Systems Analysis, Germany Technology assessment develops knowledge of the consequences of human action in relation to the development and the application of new technologies. It supports policy and science concerning future decisions on the basis of currently available knowledge and rational assessments. In the case of nanotechnology, studies on the effects of nanoscale particles released into the environment accompany their further development. Meanwhile it is known that in addition to the technological and medical benefits unintended adverse effects on humans and the environment are possible. This area of toxicological research is very extensive, because many different types and designs of nanoscale particles need to be investigated experimentally. Thus, there are many knowledge gaps and the problem of governmental decision-making and action under uncertainty about potential health risks in the new technology. In the framework of technology assessment, relevant
toxicological knowledge is evaluated based on rational and with regard to risk assessment. Hazard identification, hazard characterization and exposure characterisation are pre-conditions for the rational based risk assessment. In addition aspects like the biodistribution of nanosized particles in the human body, the mechanisms of action leading to negative health effects, and the molecular interactions between specific nanoscale particles and organic molecules lead to further scientific impact. The integration of these toxicological evaluation results in larger contexts and the use in risk assessment improves the scientific knowledge and supports the prospective development of appropriate strategies and options for further action, such as the regulation of nanotechnological materials and the development of alternative strategies. doi:10.1016/j.toxlet.2012.03.719
P33-10 Effect of nanoparticles on the cytotoxicity of coexisting metal salts Kazuo Isama, Tsuyoshi Kawakami, Keiko Sakai, Atsuko Miyajima, Atsuko Matsuoka National Institute of Health Sciences, Japan Purpose: Although nanomaterials are already being used for various applications in the industry, the safety of nanomaterials has not yet been sufficiently elucidated. In vitro toxicities of nanomaterials alone are gradually becoming clear, but their interaction with other materials is still unknown. In this study, we examined the cytotoxic effects of nanomaterials coexisting with some metal salts. Methods: Silicon dioxide (SiO2 ) and titanium dioxide (TiO2 ) nanoparticles (CIK NanoTek Corporation) were used in this study. The particle diameter and zeta potential of the nanoparticles were measured by dynamic light scattering. The cytotoxicities of aluminum chloride (AlCl3 ), copper (II) chloride (CuCl2 ), and zinc chloride (ZnCl2 ), coexisting with and without the nanoparticles, were evaluated by the colony formation assay using Chinese hamster V79 lung fibroblasts. Results and conclusions: Weak cytotoxicity was observed at 25 g/ml and above of TiO2 nanoparticles. However, cytotoxicity was not observed at 100 g/ml and below of SiO2 nanoparticles. The cytotoxicity of the three metal salts did not change when they coexisted with 10 and 100 g/ml of TiO2 nanoparticles. In contrast, though the cytotoxicity of ZnCl2 did not change, the cytotoxicity of AlCl3 and CuCl2 increased when they coexisted with 100 g/ml of SiO2 nanoparticles. In conclusion, SiO2 nanoparticles increased the cytotoxicity of some of the coexisting metal salts. Acknowledgment: This study was supported by the Health Labour Sciences Research Grant (H23-kagaku-ippan-006) from the Japanese Ministry of Health, Labour and Welfare. doi:10.1016/j.toxlet.2012.03.720