Search

Currently, protocols for the dispersal of titanium dioxide (TiO 2 ) nanoparticles are not standardized and often yield non-uniform particles and/or insufficient dispersal in liquid medium. Our study aimed to improve dispersal so that TiO 2 nanoparticles are of uniform size, making nanotoxicity testing more reliable. Various combinations of vehicles, sonication durations, and sonication volumes were assessed for optimizing preparations of TiO 2 nanoparticles. We tested each of five vehicles: ultrapure water (UPW), 0.2% disodium hydrogen phosphate (DSP), Dulbecco's phosphate-buffered saline (PBS), 0.9% saline (S), or S containing 0.05% Tween 80 (ST). We also assessed two sonication durations and three sonication volumes. Each suspension underwent ultrasonication and centrifugation; the supernatants were then analyzed. Particle size was measured by dynamic light scattering. P25 nanoparticles (~100 nm; the type of TiO 2 nanoparticles used in our study) in UPW and 0.2% DSP were effectively dispersed; however, those in PBS, S, or ST were not. Relevant duration time and volume for sonication were examined with 0.2% DSP. A sonication time of 30 min and volume of 10 mL for each vial were determined to be optimal sonication conditions as determined with our dispersal assay. Under these optimal conditions, P25 nanoparticles sonicated/centrifuged in UPW or 0.2% DSP remained dispersed and exhibited long-term stability (90 days). We thus have developed a reliable procedure for preparing TiO 2 nanoparticles in liquid-phase dispersions for toxicity testing.

The role of thyroid hormones in gonad development remains incompletely understood. We examined the dose-related effects of perinatal hypothyroidism induced by a reversible goitrogen, 6-propyl-2-thiouracil (PTU), on reproductive development in male rat offspring. Timed-pregnant Sprague-Dawley rats were orally administered PTU (0, 0.5, 1.0, or 2.0 mg/kg/day) by gavage from gestational day 15 through postnatal day 20. We observed a significant dose-dependent decrease in body weight in offspring with PTU exposure up to 13 weeks of age, but body weight became comparable among groups by 26 weeks of age. Testicular weight tended to be lower up to 7 weeks but was higher after 13 weeks of age. Epididymis weight was not different among the groups at any age. Plasma concentrations of thyroxine and triiodothyronine in the PTU groups were significantly lower at 3 weeks of age but recovered to normal levels by 26 weeks of age. No dose-related trend in plasma testosterone concentrations was found. Seminiferous tubules were larger at 13 and 26 weeks of age with PTU exposure. The number of Sertoli cells was significantly higher from 3 through 26 weeks of age. The number of Leydig cells was significantly lower up to 7 weeks of age but was comparable among groups from 13 weeks of age onwards. Thus, transient gestational and lactational thyroid hormone suppression induced small testes in early life but led to paradoxical dose-dependent testicular enlargement in adults as indicated partly by larger seminiferous tubules with numerous Sertoli cells in male rat offspring.

The potential for health effects on humans with exposure to bisphenol A (BPA) has raised concerns, and the adverse effects of low-dose exposure to BPA on reproduction have been controversial. The purpose of the present study was to investigate the effects of low-dose exposure to BPA on reproductive development in F(1) rat offspring. Pregnant female Sprague-Dawley rats (F(0)) were fed a diet containing low doses of BPA (0, 0.33, 3.3, or 33 ppm) from gestational day (GD) 6 through postnatal day (PND) 21. The weanlings (F(1)) from all dose groups were fed a normal diet ad libitum after weaning and then were subjected to necropsy at 5 weeks or 3 months of age. No BPA-related changes were observed in body weight or weight of any of the major reproductive organs in F(1) males and females. Epididymis weight was significantly lower only in 3-month-old F(1) males exposed to 33 ppm BPA. Anogenital distance (AGD), the ratio of AGD to the cube root of body weight, and relative ovary weight were significantly lower in 5-week-old F(1) females exposed to 3.3 and 33 ppm BPA, but significant differences were not observed in 3-month-old females. There were no BPA-related effects on cauda epididymal sperm motility in 3-month-old F(1) males. Plasma reproductive steroid hormone concentrations were not altered among groups in either sex. These outcomes indicate that low-dose exposure to BPA in the diet does not adversely affect reproductive development in F(1) rat offspring.