Pulmonary toxicity study in rats with three forms of ultrafine-TiO2 particles: Evidence for differential responses
ABSTRACT Surface properties are critical to assess effects of ultrafine-TiO(2) particles. The aim of this study was to assess lung toxicity in rats of newly developed, well characterized, ultrafine-TiO(2) particles and compare them to TiO(2) samples in two different size ranges and surface modifications. Groups of rats were intratracheally instilled with doses of 1 or 5mg/kg of either two ultrafine rutile TiO(2) particles (uf-1 or uf-2); rutile R-100 fine-TiO(2) (F-1); 80/20 anatase/rutile P25 ultrafine-TiO(2) (uf-3); or alpha-quartz particles. Phosphate-buffered saline (PBS) solution instilled rats served as vehicle controls. Following exposures, the lungs of PBS and particle-exposed rats were evaluated for bronchoalveolar lavage (BAL) fluid inflammatory markers, cell proliferation, and by histopathology at post-instillation time points of 24h, 1 week, 1 and 3 months. The ranking of lung inflammation/cytotoxicity/cell proliferation and histopathological responses was quartz>uf-3>F-1=uf-1=uf-2. Exposures to quartz and to a lesser degree, uf-3 anatase/rutile TiO(2) particles produced pulmonary inflammation, cytotoxicity and adverse lung tissue effects. In contrast, exposures to F-1 fine-TiO(2) particles or to uf-1/uf-2 ultrafine-TiO(2) particle-types produced transient inflammation. We conclude that differences in responses to anatase/rutile uf-3 TiO(2) particles versus the rutile uf-1 and uf-2 TiO(2) particles could be related to crystal structure, inherent pH of the particles, or surface chemical reactivity. Thus, based on these results, inhaled rutile ultrafine-TiO(2) particles are expected to have a low risk potential for producing adverse pulmonary health effects. Finally, the results demonstrate that exposures to ultrafine-TiO(2) particle-types can produce differential pulmonary effects, based upon their composition, and crystal structure. Thus, the lung toxicity of anatase/rutile uf-3 should not be viewed as representative for all ultrafine-TiO(2) particle-types.
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- "and are distributed to important organ systems, including the lymph, brain, lung, liver, and kidney (Bermudez et al. 2004; Wang et al. 2007). Other studies have shown that it produced pulmonary inflammation, cytotoxicity, and histopathological changes by intratracheally instillation (Warheit et al. 2007), intraperitoneal injection, or oral administration. Many studies have unequivocally showed that exposure to TiO 2 NPs could be translocated into the central nervous system (CNS) via the olfactory pathway and damaged brain neurocyte and tissue in vitro and in vivo (Hu et al. 2010). "
ABSTRACT: Titanium dioxide nanoparticles (TiO2 NPs) have a wide range of applications in many fields (paint, industry, medicine, additives in food colorants, and nutritional products). Over the past decade research, TiO2 NPs have been focused on the potential toxic effects of these useful materials. In the present study, we investigated the effects of subacute exposure to TiO2 NPs on emotional behavior in adult Wistar rats, the biochemical parameters, and the histology of organs. Animals were injected intraperitoneally (ip) with TiO2 NPs (20 mg/kg body weight) every 2 days for 20 days. The elevated plus-maze test showed that subacute TiO2 NPs treatment increased significantly the anxious index (AI) compared to control group. The toxicological parameters were assessed 24 h and 14 days after the last injection of TiO2 NPs. Subacute exposure to nanoparticles increased the AST/ALT enzyme ratio and LDH activity. However, the blood cell count remained unchanged, except the platelet count increase. Histological examination showed a little inflammation overall. Moreover, our results provide strong evidence that the TiO2 NPs can induce the liver pathological changes of rats. The intraperitoneal injection of TiO2 NPs increased the accumulation of titanium in the liver, lung, and the brain. The results suggest that TiO2 NPs could alter the neurobehavioral performance of adult Wistar rats and promotes alterations in hepatic tissues.Environmental Science and Pollution Research 01/2015; 22(11). DOI:10.1007/s11356-014-4002-5 · 2.76 Impact Factor
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- "PM 2.5 has been listed as one of the six 'criteria air pollutants' by USEPA National Ambient Air Quality Standards. Although UFP is not a regulated air pollutant yet, animal studies have shown that UFP is also associated with cardiovascular and pulmonary risk (Delfino et al., 2005; Elder et al., 2006; Warheit et al., 2007). In an urban environment, PM 2.5 concentrations are usually more influenced by its regional background while UFP concentrations have much more spatial variations caused by local sources such as motor vehicles and restaurants (Kinney et al., 2000). "
ABSTRACT: The California Complete Streets Act of 2008 requires local governments to update general plans so that new construction or modification of roadways considers all transportation modes, which include but are not limited to walking, cycling, and driving. This work evaluates the effect of a complete street retrofit on Ocean Park Boulevard (hereafter referred to as "the retrofit") in Santa Monica, California, in terms of the street use by different transportation modes and corresponding ultrafine particle (UFP) and fine particle (PM2.5) concentrations. After subtracting background concentrations, UFP decreased after the retrofit by 4200 particles cm(-3) while PM2.5 had no statistically significant change. The emission-weighted traffic volume, an index used to account for flows of vehicles with different pollutant-emitting capacities, decreased 26%, which may explain why UFP reductions were observed while total traffic flow remained the same. The number of pedestrians increased by 37% compared to pre-retrofit conditions and the number of cyclists remained approximately the same. Although no causality could be reached, this study observed improved air quality on street after retrofit. Nonetheless, a full evaluation of the health impacts of the retrofit requires further information about how travel behavior, not just traffic, has changed.Transportation Research Part D Transport and Environment 10/2014; 32:387–396. DOI:10.1016/j.trd.2014.08.024 · 1.29 Impact Factor
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- "The pulmonary clearance rate constants estimated using a classical 2-compartment model were compared over a range of doses. AEROSIL 1 P25 TiO 2 nanoparticles, which have often been employed for toxicity testing of TiO 2 nanoparticles and have been shown to induce lung inflammation (Rehn et al., 2003; Sager et al., 2008; Warheit et al., 2007) were used in the present study. "
ABSTRACT: AEROSIL(®) P25 titanium dioxide (TiO2) nanoparticles dispersed in 0.2% disodium phosphate solution were intratracheally administered to male F344 rats at doses of 0 (control), 0.375, 0.75, 1.5, 3.0, and 6.0mg/kg. The rats were sacrificed under anesthesia at 1 day, 3 days, 7 days, 4 weeks, 13 weeks, and 26 weeks after administration. Ti levels in various pulmonary and extrapulmonary organs were determined using sensitive inductively coupled plasma sector field mass spectrometry. One day after administration, the lungs contained 62-83% of TiO2 administered dose. Twenty-six weeks after administration, the lungs retained 6.6-8.9% of the TiO2 administered at the 0.375, 0.75, and 1.5mg/kg doses, and 13% and 31% of the TiO2 administered at the 3.0 and 6.0mg/kg doses, respectively. The pulmonary clearance rate constants from compartment 1, k1, were estimated using a 2-compartment model and were found to be higher for the 0.375 and 0.75mg/kg doses of TiO2 (0.030/day for both) than for TiO2 doses of 1.5-6.0mg/kg (0.014-0.022/day). The translocation rate constants from compartment 1 to 2, k12, were estimated to be 0.015 and 0.018/day for the 0.375 and 0.75mg/kg doses, and 0.0025-0.0093/day for doses of 1.5-6.0mg/kg. The pulmonary clearance rate constants from compartment 2, k2, were estimated to be 0.0086 and 0.0093/day for doses of 0.375 and 0.75mg/kg, and 0-0.00082/day for 1.5-6.0mg/kg doses. Translocation of TiO2 from the lungs to the thoracic lymph nodes increased in a time- and dose-dependent manner, accounting for 0.10-3.4% of the administered dose at 26 weeks. The measured thoracic lymph node burdens were a much better fit to the thoracic lymph node burdens estimated assuming translocation from compartment 1 to the thoracic lymph nodes, rather than those estimated assuming translocation from compartment 2 to the thoracic lymph nodes. The translocation rate constants from the lungs to the thoracic lymph nodes were 0.37-0.00081/day, and these also increased with increasing doses of TiO2. Although a small amount of TiO2 had translocated to the liver by 3 days after the administration (0.0023-0.012% of the highest dose administered, 6.0mg/kg), translocation to the other extrapulmonary organs was not detected.Toxicology 08/2014; 325. DOI:10.1016/j.tox.2014.08.003 · 3.75 Impact Factor