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Toxic Response (toxic + response)
Selected AbstractsToxic responses of medaka, D-rR strain, to polychlorinatednaphthalene mixtures after embryonic exposure by in ovo nanoinjection: A partial life-cycle assessmentENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2000Sergio A. Villalobos Abstract Polychlorinated naphthalenes (PCNs) are organic compounds with some chemical properties and uses similar to polychlo-rinated biphenyls. Polychlorinated naphthalenes have been detected in biota from certain aquatic environments. The toxicities of several PCN technical mixtures (Halowax) to medaka (Oryzias latipes) were determined by use of an embryo nanoinjection method. Medaka eggs (early gastrula) were injected with 0.5 nl of triolein (vehicle control) or 0.5 nl of four to five graded doses (0.3,30 ng/egg) of Halowax 1014, Halowax 1013, or Halowax 1051 in triolein. Following exposure, embryos developed, and fry were reared to sexual maturity (4 months), at which time they were euthanized. Responses were evaluated as early life stage (ELS) and early adult life stage (EALS) assessments. For ELS, lethality and sublethal alterations in embryos and larvae (<16 d old), such as craniofacial, cardiovascular, and myoskeletal deformities and abnormal or delayed hatch, were monitored for the first 9 d, and a dose severity index was computed. The EALS assessment examined the survival of 16-d-old larvae until early adulthood (123 ± 3 d old), including gonadosomatic index (GSI) and morphometry. Halowax 1014 was found to be the most toxic mixture (LD50 4.2 ng/egg), whereas Halowax 1013 and 1051 were significantly less toxic (LD50s could not be determined). The gonadosomatic index of females was significantly less in fish dosed with Halowax 1014 or 1051. The LD50 for medaka embryos nanoinjected with 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) is about 0.75 pg/egg. Thus, Halowax 1014 was 5,585-fold less potent than TCDD. For Halowax 1014, ELS assessments accurately predicted the results of EALS assessments. [source] Synergistic genotoxicity caused by low concentration of titanium dioxide nanoparticles and p,p,-DDT in human hepatocytesENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 3 2010Yun Shi Abstract The use of titanium dioxide nanoparticles (nano-TiO2) for the degradation of dichlorodiphenyltrichloroethane (p,p,-DDT) increases the risk of exposure to trace nano-TiO2 and p,p,-DDT mixtures. The interaction of p,p,-DDT and nano-TiO2 at low concentrations may alter toxic response relative to nano-TiO2 or p,p,-DDT alone. In this work, the combined genotoxicity of trace nano-TiO2 and p,p,-DDT on human embryo L-02 hepatocytes without photoactivation was studied. Nano-TiO2 (0.1 g/L) was mixed with 0.01,1 mmol/L p,p,-DDT to determine adsorption isotherms. L-02 cells were exposed to different levels of p,p,-DDT (0, 0.001, 0.01, and 0.1 ,mol/L) and nano-TiO2 (0, 0.01, 0.1, and 1 ,g/mL) respectively. The adsorption of p,p,-DDT by nano-TiO2 was approximately 0.3 mmol/g. Cell viability, apoptosis, and DNA double strand breaks were similar among all test groups. Nano-TiO2 alone (0.01,1 ,g/mL) increased the levels of oxidative stress and oxidative DNA adducts (8-OHdG), but it did not induce DNA breaks or chromosome damage. Addition of trace nano-TiO2 with trace p,p,-DDT synergistically enhanced genotoxicity via increasing oxidative stress, oxidative DNA adducts, DNA breaks, and chromosome damage in L-02 cells. Low concentrations of nano-TiO2 and p,p,-DDT increased oxidativestress by reactive oxygen species (ROS) formation and lipid oxidation. Oxidative stress is a major pathway for DNA and chromosome damage. Dose-dependent synergistic genotoxicity induced by combined exposure of trace p,p,-DDT and nano-TiO2 suggests a potential environmental risk of nano-TiO2 assisted photocatalysis. Environ. Mol. Mutagen., 2010. © 2009 Wiley-Liss, Inc. [source] Effects of metal and organophosphate mixtures on Ceriodaphnia dubia survival and reproductionENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2005Amy M. Mahar Abstract The toxicity of mixtures of copper, zinc, and diazinon were determined for Ceriodaphnia dubia using 7-d survival and reproduction tests. Fifteen treatments, including combinations of the chemicals at 0, 25, 50, 75, and 100% of their individual median lethal concentrations, adding up to one toxic unit (TU) were tested. The TU was then used to classify each mixture response as additive, greater than additive, or less than additive. For survival, additive responses occurred in the 75% zinc plus 25% diazinon and the 50% copper plus 25% zinc plus 25% diazinon treatments. For reproduction, additive responses occurred in the 75% copper plus 25% zinc, 75% copper plus 25% diazinon, and 75% zinc plus 25% diazinon treatments. Copper and zinc played a greater role in toxicity than diazinon did. Less-than-additive interactions were found in all remaining mixtures, perhaps because of differences in mode of action between diazinon and metals. Consideration of dose-response curves can help to explain inconsistencies regarding toxic response in treatments with different ratios of the same chemicals. As TU percentages changed, mixture components were taken from different locations on differently shaped dose-response curves. Because most responses were less than additive, however, water-quality criteria based on individual concentrations probably are protective for most metal-organophosphate mixtures. [source] Fabrication of CdSe-Nanofibers with Potential for Biomedical ApplicationsADVANCED FUNCTIONAL MATERIALS, Issue 6 2010Amir Fahmi Abstract The design and synthesis of nanostructured functional hybrid biomaterials are essential for the next generation of advanced diagnostics and the treatment of disease. A simple route to fabricate semiconductor nanofibers by self-assembled, elastin-like polymer (ELP)-templated semiconductor nanoparticles is reported. Core,shell nanostructures of CdSe nanoparticles with a shell of ELPs are used as building blocks to fabricate functional one-dimensional (1D) nanostructures. The CdSe particles are generated in situ within the ELP matrix at room temperature. The ELP controls the size and the size-distribution of the CdSe nanoparticles in an aqueous medium and simultaneously directs the self-assembly of core,shell building blocks into fibril architectures. It was found that the self-assembly of core,shell building blocks into nanofibers is strongly dependent on the pH value of the medium. Results of cytotoxicity and antiproliferation of the CdSe-ELP nanofibers demonstrate that the CdSe-ELP does not exhibit any toxicity towards B14 cells. Moreover, these are found to be markedly capable of crossing the cell membrane of B14. In contrast, unmodified CdSe nanoparticles with ELPs cause a strong toxic response and reduction in the cell proliferation. This concept is valid for the fabrication of a variety of metallic and semiconductor 1D-architectures. Therefore, it is believed that these could be used not only for biomedical purposes but for application in a wide range of advanced miniaturized devices. [source] Acute oral toxicity of colchicine in rats: effects of gender, vehicle matrix and pre-exposure to lipopolysaccharideJOURNAL OF APPLIED TOXICOLOGY, Issue 5 2007Paddy L. Wiesenfeld Abstract The oral toxicity of a single administration by gavage (10, 20 or 30 mg kg,1 body weight) of colchicine (COL) was determined in young, mature male and female Sprague-Dawley rats. The effect of COL was evaluated in the presence or absence of additional treatment variables that included vehicle and lipopolysaccharide (LPS) pre-exposure. The vehicle for COL was either Half and Half cream (H & H) or saline, and each group included pretreatment with either saline or a low, minimally toxic dose (83 µg kg,1 body weight) of LPS. Colchicine toxicity in both male and female age-matched rats was characterized by progressively more severe dose-related clinical signs of toxicity. These included mortality, decreased body weight and feed intake during the first several days after dosing, with recovery thereafter in surviving animals. There were differences in the severity of the toxic response to COL between male and female rats. The most notable sex-related difference was in COL lethality. Female rats were two times more susceptible to the lethal effects of COL than male rats. Saline or H & H delivery vehicles did not result in any apparent qualitative or quantitative differences in COL toxicity. LPS pretreatment significantly potentiated COL lethality in both males and females, although the potentiation in males was greater than in females. LPS pretreatment modestly increased the COL induced anorexic effect in surviving males, but not in surviving female animals. LPS did not appear to modulate either the body weights or clinical signs of COL induced toxicity in surviving males or females. Copyright © 2007 John Wiley & Sons, Ltd. [source] Biomarkers as biological indicators of xenobiotic exposureJOURNAL OF APPLIED TOXICOLOGY, Issue 4 2001Fernando Gil Abstract The presence of a xenobiotic in the environment always represents a risk for living organisms. However, to talk about impregnation there is a need to detect toxicity in the organism, and the concept of intoxication is related to specific organ alterations and clinical symptoms. Moreover, the relationship between the toxic levels within the organism and the toxic response is rather complex and has a difficult forecast because it depends on several factors, namely toxicokinetic and genetic factors. One of the methods to quantify the interaction with xenobiotics and its potential impact on living organisms, including the human being, is monitoring by the use of the so-called biomarkers. They can provide measures of the exposure, toxic effect and individual susceptibility to environmental chemical compounds and may be very useful to assess and control the risk of long-term outcomes associated with exposure to xenobiotic (i.e. heavy metals, halogenated hydrocarbons, pesticides). Copyright © 2001 John Wiley & Sons, Ltd. [source] The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: Results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo,,ARTHRITIS & RHEUMATISM, Issue 7 2009Joel M. Kremer Objective To determine the efficacy, safety, and tolerability of 3 different dosages of CP-690,550, a potent, orally active JAK inhibitor, in patients with active rheumatoid arthritis (RA) in whom methotrexate, etanercept, infliximab, or adalimumab caused an inadequate or toxic response. Methods Patients (n = 264) were randomized equally to receive placebo, 5 mg of CP-690,550, 15 mg of CP-690,550, or 30 mg of CP-690,550 twice daily for 6 weeks, and were followed up for an additional 6 weeks after treatment. The primary efficacy end point was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at 6 weeks. Results By week 6, the ACR20 response rates were 70.5%, 81.2%, and 76.8% in the 5 mg, 15 mg, and 30 mg twice daily groups, respectively, compared with 29.2% in the placebo group (P < 0.001). Improvements in disease activity in CP-690,550,treated patients compared with placebo were seen in all treatment groups as early as week 1. ACR50 and ACR70 response rates significantly improved in all treatment groups by week 4. The most common adverse events reported were headache and nausea. The infection rate in both the 15 mg twice daily group and the 30 mg twice daily group was 30.4% (versus 26.2% in the placebo group). No opportunistic infections or deaths occurred. Increases in mean low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels, and increases in mean serum creatinine level (0.04,0.06 mg/dl) were seen in all CP-690,550 treatment arms. Conclusion Our findings indicate that CP-690,550 is efficacious in the treatment of RA, resulting in rapid, statistically significant, and clinically meaningful reductions in the signs and symptoms of RA. Further studies of CP-690,550 in RA are warranted. [source] Differential tolerance among cryptic species: A potential cause of pollutant-related reductions in genetic diversityENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 9 2004Axayácatl Rocha-Olivares Abstract Differential mortality of cryptic species (i.e., morphologically similar but genetically distinct sibling species) may contribute to observed reductions in genetic diversity at contaminated sites if the members of a complex of cryptic species exhibit differential responses to the contaminants that are present. We conducted toxicity bioassays with both polynuclear aromatic hydrocarbon and metal contamination on Cletocamptus fourchensis and C. stimpsoni from two intensively sampled locations. Previous molecular and detailed morphological analyses segregated these as cryptic species from the cosmopolitan C. deitersi. We found that these species occur together at two field sites and that they exhibit unique toxic responses to heavy metals, suggesting differential tolerances at contaminated sites. These findings suggest that reported losses of genetic diversity at contaminated sites may represent a reduction in species diversity rather than a loss of the presumed less-tolerant genotypes within a species. They also suggest that members of a cryptic species complex should not be used in laboratory toxicity tests unless populations are genetically characterized. Future studies using genetic diversity as a marker of contaminant effects should consider the possibility of undetected cryptic species. [source] The influence of pH and salinity on the toxicity of heavy metals in sediment to the estuarine clam Ruditapes philippinarum,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 5 2004Inmaculada Riba Abstract An approach is presented for determining the influence of two key variables, pH and salinity(S), on the toxicity of four common heavy metals bound to sediments in estuaries. Two samples of environmental sediment taken from two estuaries in southern Spain (the Huelva estuary and the Guadalquivir River estuary), together with a dilution of toxic mud from the Aznalcóllar (Spain) mining spill (April 1998) were used to determine their toxicity at different values of pH (6.5, 7.5, and 8.5) and salinity (10, 20, and 30) on the estuarine clam Ruditapes philippinarum. Two different endpoints, sublethal, indicated by clam reburial (median effective burial time [ET50]), and relative mortality (median lethal concentration [LC50]), were used to quantify the toxicity associated with the heavy metals. Neither salinity nor pH was found to influence the toxic responses measured by the behavioral endpoint (ET50). However, a strong effect on the LC50 related to pH and salinity was detected, with the toxicity of the heavy metals being increased at low values of both variables (pH = 6.5 and S = 10). The mechanism of heavy metals uptake through water may explain this influence of pH and salinity on the lethal toxicity detected. The results show differences in the toxicity of these heavy metals bound to sediments depending on whether the origin of metal contamination is chronic or acute. [source] Hepatic covalent adduct formation with zomepirac in the CD26-deficient mouseJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 1 2002MIN WANG Abstract Background and Aims: Zomepirac (ZP), a non-steroidal anti-inflammatory drug (NSAID), has been reported to cause immune-mediated liver injury. In vivo, ZP is metabolized to a chemically reactive acyl glucuronide conjugate (ZAG) which can undergo covalent adduct formation with proteins. Such acyl glucuronide-derived drug-protein adducts may be important in the development of immune and toxic responses caused by NSAID. We have shown using immunoabsorptions that the 110 kDa CD26 (dipeptidyl peptidase IV) is one of the hepatic target proteins for covalent modification by ZAG. In the present study, a CD26-deficient mouse strain was used to examine protein targets for covalent modification by ZP/metabolites in the liver. Methods and Results: The CD26-deficient phenotype was confirmed by immunohistochemistry, flow cytometry analysis, RT-PCR, enzyme assay and immunoblotting. Moreover, by using monoclonal antibody immunoblots, CD26 was not detected in the livers of ZP-treated CD26-deficient mice. Immunoblots using a polyclonal antiserum to ZP on liver from ZP-treated mice showed three major sizes of protein bands, in the 70, 110 and 140 kDa regions. Most, but not all, of the anti-ZP immunoreactivity in the 110 kDa region was absent from ZP-treated CD26-deficient mice. Conclusion: These data definitively showed that CD26 was a component of ZP-modified proteins in vivo. In addition, the data suggested that at least one other protein of approximately 110 kDa was modified by covalent adduct formation with ZAG. [source] | |||||||||||||