title: Oral, short-term exposure to titanium dioxide nanoparticles in Sprague-Dawley rat: focus on reproductive and endocrine systems and spleen.
abstract: The study explored possible reproductive and endocrine effects of short-term (5 days) oral exposure to anatase TiO2 nanoparticles (0, 1, 2 mg/kg body weight per day) in rat. Nanoparticles were characterised by scanning electron microscopy (SEM) and transmission electron microscopy, and their presence in spleen, a target organ for bioaccumulation, was investigated by single-particle inductively coupled plasma mass spectrometry and SEM/energy-dispersive X-ray. Analyses included serum hormone levels (testosterone, 17-β-estradiol and triiodothyronine) and histopathology of thyroid, adrenals, ovary, uterus, testis and spleen. Increased total Ti tissue levels were found in spleen and ovaries. Sex-related histological alterations were observed at both dose levels in thyroid, adrenal medulla, adrenal cortex (females) and ovarian granulosa, without general toxicity. Altered thyroid function was indicated by reduced T3 (males). Testosterone levels increased in high-dose males and decreased in females. In the spleen of treated animals TiO2 aggregates and increased white pulp (high-dose females) were detected, even though Ti tissue levels remained low reflecting the low doses and the short exposure time. Our findings prompt to comprehensively assess endocrine and reproductive effects in the safety evaluation of nanomaterials.
authors.affiliation: Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Tassinari
authors.forename: Francesco
authors.initials: F
authors.lastname: Cubadda
authors.forename: Gabriele
authors.initials: G
authors.lastname: Moracci
authors.forename: Federica
authors.initials: F
authors.lastname: Aureli
authors.forename: Marilena
authors.initials: M
authors.lastname: D'Amato
authors.forename: Mauro
authors.initials: M
authors.lastname: Valeri
authors.forename: Barbara
authors.initials: B
authors.lastname: De Berardis
authors.forename: Andrea
authors.initials: A
authors.lastname: Raggi
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.forename: Daniele
authors.initials: D
authors.lastname: Passeri
authors.forename: Marco
authors.initials: M
authors.lastname: Rossi
authors.forename: Francesca
authors.initials: F
authors.lastname: Maranghi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood*; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000633:toxicity*; D010053:Ovary / Q000737:chemistry / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000737:chemistry / Q000187:drug effects*; D013961:Thyroid Gland / Q000737:chemistry / Q000187:drug effects; D013963:Thyroid Hormones / Q000097:blood*; D014018:Tissue Distribution; D014025:Titanium / Q000008:administration & dosage / Q000633:toxicity*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D012739:Gonadal Steroid Hormones; D013963:Thyroid Hormones; C009495:titanium dioxide; D014025:Titanium