الفهرس 
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Abstract
Nano-based technology invaded many fields with extreme improvements such as in medicine, cosmetics, agriculture and food industry. Consequently, the human beings have been exposed more often to nanoparticles after their intrusion in our environment.
One of the main food additives and world widely used is TiO2 nanoparticles that are found in candies, sweets and chewing gums. Their oral exposure is more likely occurring to the coming generations due to great use in many dietary products.
Nano-TiO2 particles that enter the body via the gastrointestinal tract are absorbed and reach different body organs. These nanoparticles are progressively manufactured, therefore increased exposure can be expected, which has put TiO2 NPs under toxicological inspection. To investigate the toxic effect of titanium dioxide food additive nanoparticles and the possible recovery after withdrawal on the submandibular salivary gland of albino rats.
The aim of this investigation was to study the toxic effect of oral administration of TiO2 nanoparticles on the submandibular salivary glands of albino rats and the possible effect of 2,4, and 6 weeks recovery periods.
Materials and methods:
Forty-eight male albino rats of two months’ age (weighing 100 gms +/- 50 gms each) were used in this study, divided into five main groups as follows:
I. group I consisted of 20 rats served as controls. They were subdivided into four subgroups (n=5) correspondent to the experimental periods:
Subgroup IA received intragastric administration of distilled water once daily for 30 days.
Subgroup IB were treated the same way as subgroup IA and then left untreated for 2 weeks.
Subgroup IC were treated the same way as subgroup IA and then left untreated for 4 weeks.
Subgroup ID were treated the same way as subgroup IA and then left untreated for 6 weeks.
Experimental groups (n=7):
II. group II: rats received 50 mg/kg b.w of TiO2 NPs I.G daily for 30 days.
III. group III: rats received 50 mg/kg b.w of TiO2 NPs I.G daily for 30 days and tracing the possible recovery after 2 weeks.
IV. group IV: 7 rats received 50 mg/kg b.w of TiO2 NPs I.G daily for 30 days and tracing the possible recovery after 4 weeks.
V. group V: 7 rats received 50 mg/kg b.w of TiO2 NPs I.G daily for 30 days and tracing the possible recovery after 6 weeks.
The submandibular salivary glands were surgically excised. Deparaffinized sections were stained for histological and immunohistochemical studies by the following methods:
• Hematoxylin and eosin stained sections that were examined with LM, for detection of histological changes in the submandibular salivary glands.
• Active caspase 3 staining, for detection of apoptosis.
• Statistical analysis using one way ANOVA test was used to compare between the studied groups regarding the surface area of positive reaction to anti active caspase 3.
Results:
1. Histological results:
The control group (subgroups A, B, C and D):
• All control subgroups showed same results where submandibular salivary glands presented the typical normal histological picture with well-defined capsule, C.T. septa, parenchymal elements and duct system.
The experimental groups:
• group II that received TiO2 NPs daily for 30 days showed apparent reduction in the size of lobules and acini inspected as separation and spacing surrounding the acini. Nuclei of the secretory terminal portions appeared either hyperchromatic, pyknotic or crescent in shape. Also, they showed different sized cytoplasmic vacuolations. The ducts showed reduction in size, cytoplasmic vacuolations, loss of regular configuration and cellular degeneration. Dilatation of the blood vessels and their engorgement with RBCs were observed.