Dose–dependent biodistribution of prenatal exposure to rutile-type titanium dioxide nanoparticles on mouse testis
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Titanium dioxide nanoparticles (nano-TiO2), believed to be inert and safe, are used in many products especially rutile-type in cosmetics. Detection, localization, and count of nanoparticles in tissue sections are of considerable current interest. Here, we evaluate the dose–dependent biodistribution of rutile-type nano-TiO2 exposure during pregnancy on offspring testes. Pregnant mice were subcutaneously injected five times with 0.1 ml of sequentially diluted of nano-TiO2 powder, 35 nm with primary diameter, suspensions (1, 10, 100, or 1,000 μg/ml), and received total doses of 0.5, 5, 50, and 500 μg, respectively. Prior to injection, the size distribution of nano-TiO2 was analyzed by dynamic light scattering measurement. The average diameter was increased in a dose–dependent manner. The most diluted concentration, 1 μg/ml suspension, contained small agglomerates averaging 193.3 ± 5.4 nm in diameter. The offspring testes were examined at 12 weeks postpartum. Individual particle analysis in testicular sections under scanning and transmission electron microscopy enabled us to understand the biodistribution. The correlation between nano-TiO2 doses injected to pregnant mice, and the number of agglomerates in the offspring testes was demonstrated to be dose–dependent by semiquantitative evaluation. However, the agglomerate size was below 200 nm in the testicular sections of all recipient groups, independent from the injected dose during pregnancy.
KeywordsRutile-type nano-TiO2 Agglomerates Dose–dependence Prenatal exposure Offspring testis In-vivo testing Nanomedicine
This work was supported in part by a Grant-in-Aid for Science Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, a Grant-in Aid for the Private University Science Research Upgrade Promotion Business Academic Frontier Project, a grant of Strategic Research Foundation Grant-aided Project for Private Universities from Ministry of Education, Culture, Sport, Science, and Technology, and a Grant-in Aid for Health and Labour Sciences Research Grants, Research on Risk of Chemical Substances, from the Ministry of Health, Labour and Welfare”.
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