S118
Abstracts / Toxicology Letters 205S (2011) S60–S179
P1189 Toxicity of docetaxel-loaded solid lipid nanoparticles (DSNs) and Taxotere® —A comparative in vivo study R.
Yang 1,a ,
Y.
Gao 2,a ,
X.
Liu 1 ,
Y.
Li 2,∗ ,
Z.
Sun 1,∗
1
Department of Pharmacology and Toxicology, Shanghai Institute of Planned Parenthood Research & National Evaluation Centre for Toxicology of Fertility Regulating Drugs, Shanghai, China, 2 Department of Pharmacy, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
E-mail addresses:
[email protected] (Y. Li),
[email protected] (Z. Sun). Purpose: To compare of the systemic toxicity of docetaxelloaded solid lipid nanoparticles (DSNs) with Taxotere® in vivo. Methods: Acute, long-term, irritation and allergia toxicologic studies were carried out with healthy BALB/c mice, Beagle dogs, New Zealand rabbits and guinea pigs, respectively. Results of the study: (1) The maximum tolerated dose (MTD) of DSNs was as high as 400 mg/kg in mice while the medial lethal dose (LD50 ) of Taxotere® was 149.31 mg/kg. (2) The long-term toxicity of DSNs compared with Taxotere® in beagle dogs by intravenous infusion weekly for four weeks showed that the administration of Taxotere® at 1 mg/kg brought about severe signs of toxicity such as skin flushing, vocalization and salivation. However, no abnormal reactions appeared on animals treated with DSNs at dose of 4 mg/kg. At the same dose level, DSNs induced more minor decreases in body weight gains, slighter hemotoxicity (changes in some clinical hematology and biochemistry parameters), cardiac toxicity, hepatotoxicity and myelosuppression than Taxotere® . (3) The experimental results showed that noallergenicity and vascular irritation were induced by DSNs at the highest drug concentration of clinical infusion. Therefore, nanotechnology presents great potential for reducing the side-effects and toxicity of docetaxel. a Rongfu
Yang and Yu Gao contributed equally to this paper.
Environmental toxicology P1191 Mutagenicity analysis and heavy metal contents of water and sediments from Sakarya River (Turkey) A. Özata ∗ , V. Kılıc¸, G.A. Kılıc¸ Biology, Anadolu University, Eskis¸ehir, Turkey Purpose: Sakarya River is one of the most important freshwater sources in Turkey. However, it is polluted by urban, agricultural and industrial waste waters over the years. Previous studies have shown that Sakarya River water carries high levels of organic–inorganic contaminants and heavy metals. The aim of the present study was to carry out an initial mutagenicity screening for the water and sediments of Sakarya River. Methods: Samples were collected from five stations near urban, agricultural and industrial regions. Salmonella mutagenicity assay (Ames test) was applied by using TA 98 and TA 100 strains of Salmonella typhimurium. Plate incorporation assay was carried out in the absence of metabolic activation. Sediment samples were fractionated using solvents with different polarities. Water samples were used without concentration. Heavy metal contents of water and sediments were measured by ICP-OES. Results: Positive results were obtained for sediment samples in three of the sampling sites. The results were indicating the presence of mutagens causing frame-shift mutations in ¨ the sampling sites around the cities of AdapazarÄ and EskiÅYehir. Water samples were determined to be non mutagenic for both of the two strains. Heavy metal analysis of the samples showed that sediment samples from the sites that are observed to be mutagenic were also polluted by heavy metals. Sediment Cd and Pb levels were significantly higher than the other stations. Heavy metal levels in the water samples were under detectable limits for all of the analysed metals. doi:10.1016/j.toxlet.2011.05.425
doi:10.1016/j.toxlet.2011.05.423
P1190 Histological study of the effect of salbutamol on rat parotid salivary gland A. Yousofi Department of Pathological Sciences, School of Veterinary Medicine, Islamic Azad University, Kazerun Branch, Kazerun, Iran Salbutamol is asympathomimetic agent that has been used for treatment of respiratory diseases such as asthma in human and animals. Salbutamol stimulates adrenergic receptors in secretory units of parotid salivary glands and causes increasing of salivation and hstological changes. Fifteen adult male rats were used as control and treatment groups. Chronic treatment of salbutamol with dosage 4 mg/kg for 15 days revealed remarkable changes on weight of the parotid salivary glands. The weight of rats of treatment group had decreased, but this difference was not significant between control and treatment groups. Hypertrophy of secretory units in the parotid gland were detectable. doi:10.1016/j.toxlet.2011.05.424
P1192 Trace metals in edible tissues of nine fish species from Aegean and Mediterranean seas of Turkey N.E. Akbulut 1,∗ , A.M. Tuncer 2 , N. Özgül 2 , S. Burgaz 3 , E. Olcayto 1 , M. Gültekin 2 , V. Kürüm 4 1
Biology, Hacettepe University, Faculty of Science, Ankara, Turkey, Cancer Control Department, Ministry of Health of Turkey, Ankara, Turkey, 3 Faculty of Pharmacy, Gazi University, Ankara, Turkey, 4 General Directorate of Protection And Control Vision, Ministry of Agriculture and Rural Affairs of Turkey, Ankara, Turkey 2
Seafood may contain several chemical contaminants which are important sources of potential human exposure. Among the chemical contaminants in seafood, metals such as (methyl) mercury, cadmium, lead and arsenic deserve special attention. Therefore, potential human health risks from dietary exposure to these pollutants continue to be the subject of most research and regulation. In this study, nine fish species (n = 110) from Mediterranean and Aegean Seas were analyzed for content in heavy metals (As, Cd, Hg, Pb, Ni,Cu, Mn and Zn) in the muscle tissue. Human intake of these elements (e.g. inorganic As, Cd, Hg, Pb, Ni) from consumption of marine fish and potential human health risks were also estimated. The contents of studied metals in the samples were found to be in the range of total As 0.628–11.33; Cd < 0.025; Cu 0.242–3.879; Fe 3.55–41.14; Pb 0.025–0.165; Mn 0.283–4.86; Hg 0.01–0.361; Ni