Journal of Applied Toxicology

Cover image for Journal of Applied Toxicology

May 2009

Volume 29, Issue 4

Pages 275–366

  1. Reviews

    1. Top of page
    2. Reviews
    3. Research Articles
    4. Short Communications
    1. Using Biomonitoring Equivalents to interpret human biomonitoring data in a public health risk context (pages 275–288)

      Sean M. Hays and Lesa L. Aylward

      Article first published online: 29 DEC 2008 | DOI: 10.1002/jat.1410

      Increasingly sensitive analytical tools allow measurement of trace concentrations of chemicals in human biologic media; however, few screening tools are available for interpretation of such data in a health risk assessment context. This review describes the concept and implementation of Biomonitoring Equivalents (BEs), estimates of the concentration of a chemical or metabolite in a biological medium that is consistent with an existing exposure guidance value, and presents case studies for toluene, cadmium, 2,4-dichlorophenoxyacetic acid, and acrylamide.

  2. Research Articles

    1. Top of page
    2. Reviews
    3. Research Articles
    4. Short Communications
    1. Benomyl induction of brain aromatase and toxic effects in the zebrafish embryo (pages 289–294)

      Dong-Jae Kim, Seung-Hyeok Seok, Min-Won Baek, Hui-Young Lee, Yi-Rang Na, Sung-Hoon Park, Hyun-Kyoung Lee, Noton Kumar Dutta, Koichi Kawakami and Jae-Hak Park

      Article first published online: 4 DEC 2008 | DOI: 10.1002/jat.1405

      In this study, we determined that benomyl has estrogenic potential based on zebrafish brain aromatase gene induction, and that concentration of 20×10-6 m and higher benomyl induced decreased survival, hatching, heart rates, and increased incidence of malformations, such as pericardial edema, spinal lordosis, elongated heart, head edema, eye lens protrusion, and caudal fin disappearancer in zebrafish embryos. These results demonstrate the usefulness of zebrafish embryos as an in vivo system to examine the estrogenic and developmental toxic potential of unknown compounds.

    2. Antioxidant responses and metal accumulation in tissues of Nile tilapia Oreochromis niloticus under Zn, Cd and Zn + Cd exposures (pages 295–301)

      Özgür Fırat, Hikmet Y. Çogun, Sabahattin Aslanyavrusu and Ferit Kargın

      Article first published online: 4 DEC 2008 | DOI: 10.1002/jat.1406

      We investigated the effects of Zn, Cd and a Zn + Cd mixture on antioxidant parameters and metal accumulation in Oreochromis niloticus. Fish were exposed to 0.5 and 5.0 mg l−1 Zn, 0.1 and 1.0 mg l−1 Cd, and 0.5 mg l−1 Zn + 0.1 mg l−1 Cd and 5.0 mg l−1 Zn + 1.0 mg l−1 Cd mixtures for 7 and 28 days to determine Zn and Cd accumulation, reduced glutathione (GSH) level and glucose-6-phosphate dehydrogenase (G6PD) activity in gill and liver.

    3. Comparative protective effect of N-acetyl cysteine and tetramethylpyrazine in rats with gentamicin nephrotoxicity (pages 302–307)

      B. H. Ali, S. Al–Salam, I. Al-Husseini and A. Nemmar

      Article first published online: 30 DEC 2008 | DOI: 10.1002/jat.1409

      The effects of tertamethylpyrazine (TMP) and N-acetyl cysteine (NAC) on gentamicin (GM) -induced nephrotoxicity were compared. The GM-induced functional and structural alterations were significantly ameliorated by NAC treatment, while TMP had only a slight mitigating effect that was less marked than that produced by NAC. The concentration of GM in the renal cortex of the rats given GM + NAC (but not TMP) was lower than that found in rats treated with GM alone by about 25 %.

    4. 5-Fluorouracil and its active metabolite FdUMP cause DNA damage in human SW620 colon adenocarcinoma cell line (pages 308–316)

      Renata Matuo, Fabrício Garmus Sousa, Alexandre E. Escargueil, Ivana Grivicich, Daniel Garcia-Santos, José Artur Bogo Chies, Jenifer Saffi, Annette K. Larsen and João Antonio Pêgas Henriques

      Article first published online: 29 DEC 2008 | DOI: 10.1002/jat.1411

      Our study demonstrates that 5-FU induces SSB, DSB, and apoptosis earlier than FdUMP in SW620 cells. 5-FU induces an arrest in G1/S while FdUMP in G2/M. Independently of the temporal difference in strand breaks and apoptosis induction, as well as the differential cell cycle modulation, both drugs presented similar clastogenic effects. The different pattern of cell cycle arrest suggests that the two drugs induce different type of primary DNA lesions that recruit different DNA repair pathways.

    5. Permethrin induces lymphocyte DNA lesions at both Endo III and Fpg sites and changes in monocyte respiratory burst in rats (pages 317–322)

      Rosita Gabbianelli, Maria Letizia Falcioni, Franco Cantalamessa and Cinzia Nasuti

      Article first published online: 19 JAN 2009 | DOI: 10.1002/jat.1412

      Pyrethroids are widely used insecticides to control agricultural and domestic insect pests. In this work the effect of permethrin exposure on rat leukocytes was investigated. Permethrin treatment reduces the monocyte respiratory burst response to phorbol myristate acetate. Moreover a reduction in monocyte plasma membrane fluidity in the hydrophilic-hydrophobic interface of the lipid bilayer was measured. Data obtained from the comet assay show that permethrin induces lymphocyte DNA lesions at both Fpg and endonuclease III sites in rats.

    6. Selective blockade of mGlu5 metabotropic glutamate receptors is hepatoprotective against fulminant hepatic failure induced by lipopolysaccharide and d-galactosamine in mice (pages 323–329)

      Cristiano R. Jesse, Ethel A. Wilhelm, Cristiani F. Bortolatto, Lucielli Savegnago and Cristina W. Nogueira

      Article first published online: 19 JAN 2009 | DOI: 10.1002/jat.1413

      This study was designed to investigate the influence of 2-methyl-6-phenylethynyl pyridine hydrochloride (MPEP), an antagonist of metabotropic glutamate receptor subtype 5 (mGluR5), in lipopolysaccharide (LPS) and d-galactosamine (D-GalN)-induced fulminant hepatic failure in mice. The hepatoprotective effect of MPEP on fulminant hepatic failure induced by LPS and d-GalN in mice was demonstrated.

    7. You have free access to this content
      In vivo acute toxicity of titanium dioxide nanoparticles to mice after intraperitioneal injection (pages 330–337)

      Jinyuan Chen, Xia Dong, Jing Zhao and Guping Tang

      Article first published online: 20 JAN 2009 | DOI: 10.1002/jat.1414

      In present study, the acute toxicity of nano-sized TiO2 particles to adult mice was investigated by intraperitioneal injection. The data indicated that some TiO2 particles have entered spleen and caused severe lesion of spleen. Thrombosis was found in pulmonary vascular, which could be ascribed to the blocking blood vessel by TiO2 particles. In addition, titanium content examination showed that TiO2 nanoparticles could deposit in spleen, lung, kidney and liver, and transport between these tissues.

    8. Soman poisoning alters p38 MAPK pathway in rat cerebellar Purkinje cells (pages 338–345)

      Jaroslav Pejchal, Jan Osterreicher, Jiri Kassa, Ales Tichy, Stanislav Micuda, Zuzana Sinkorova and Lenka Zarybnicka

      Article first published online: 19 JAN 2009 | DOI: 10.1002/jat.1415

      Activated p38MAPK, elk-1, c-jun, and c-myc were evaluated in rat cerebellar Purkinje cells after soman poisoning. Male Wistar rats were intramuscularly administered with soman (80% LD50) and physiological saline. Samples were taken 1, 7, 14 days after poisoning. P38MAPK, p-c-jun, p-c-myc, and p-elk-1 expressions were measured. An increased expressions of p-p38MAPK and p-c-myc were found 14 days after soman poisoning, while p-elk-1 and p-c-jun expressions remained unchanged. Late p38MAPK activation might be the underlying mechanism of chronic neurophysiological adverse effects.

    9. Rapid responses of a melanophore cell line to chemical contaminants in water (pages 346–349)

      Aurel Iuga, Ethan Lerner, Tommy R. Shedd and William H. van der Schalie

      Article first published online: 11 FEB 2009 | DOI: 10.1002/jat.1416

      We have evaluated a Xenopus melanophore cell line as a potential sensor for detecting toxins in water. Melanophores responded rapidly by dispersing melanosomes following exposure to six (ammonia, arsenic, copper, mercury, pentachlorophenol and phenol) of 12 chemicals in the desired sensitivity range. For two additional chemicals (nicotine and paraquat) the melanophore response improved upon the response capabilities of several toxicity sensors. These results suggest that a melanophore-based sensor could be useful for the assessment of chemical toxicity in drinking water.

    10. OECD validation of phase 3 Hershberger assay in Korea using surgically castrated male rats with coded chemicals (pages 350–355)

      Hyun-Ju Moon, Tae Seok Kang, Tae Sung Kim, Il Hyun Kang, Ho Youn Ki, Seung Hee Kim and Soon Young Han

      Article first published online: 24 FEB 2009 | DOI: 10.1002/jat.1418

      As a participating laboratory for the OECD Hershberger validation program, we conducted a phase 3 trial to test the reliability of the Hershberger assay using coded substances. Male Sprague–Dawley rats were castrated at 6 weeks of age and allowed to recover for 8 days. All the coded agonists and antagonists were administered orally once daily for 10 consecutive days. In the antagonist version of the assay, 0.4mg kg−1 of testosterone propionate (TP), a reference androgen, was co-administered with the coded compounds C, D, H, I or K, by a subcutaneous injection. The five coded compounds, p,p′-DDE at two doses (codes C and I), linuron at two doses (codes D and K) and flutamide (code H), all significantly decreased the weights of the TP-stimulated sex organs. These results suggest the OECD Hershberger assay to be a reliable screening method for detecting androgen agonists and antagonists.

    11. In vitro assay for drug-induced hepatosteatosis using rat primary hepatocytes, a fluorescent lipid analog and gene expression analysis (pages 356–363)

      Hisako Fujimura, Naoko Murakami, Michie Kurabe and Wataru Toriumi

      Article first published online: 17 FEB 2009 | DOI: 10.1002/jat.1420

      To evaluate new drugs' potential for hepatosteatosis, we developed a cell-based assay using a fluorescent fatty acid analog: BODIPY558/568 en and rat primary hepatocytes. All positive reference compounds [cyclosporine A (CsA), clofibrate (CFR), tetracycline (TC), valproic acid (VPA), carbon tetrachloride (CC14), tamoxifen (TMX)] increased fluorescent particles in number and fluorescence intensity. Gene expression analysis of the hepatocytes showed two patterns: genes related to lipid metabolism/synthesis were down-regulated by CsA, TC and TMX, and up-regulated by CFR and VPA.

  3. Short Communications

    1. Top of page
    2. Reviews
    3. Research Articles
    4. Short Communications
    1. All-trans-retinoic acid alters Smads expression in embryonic neural tissue of mice (pages 364–366)

      Juntao Zhang, Rong Li, Quanren He, Wan-I. Li, Bo Niu, Niuliang Cheng, Ran Zhou, Ting Zhang, Xiaoying Zheng and Jun Xie

      Article first published online: 4 DEC 2008 | DOI: 10.1002/jat.1404

      The current study investigated all-trans-retinoic acid (ATRA)-induced alteration of Smad expression in the developing neural tubes of mice. Pregnant mice were treated with a single dose of 50 mg/kg ATRA orally on embryonic day(E) 7. Results showed that ATRA treatment significantly increased expression of both p-Smad1 and total Smad1, while Smad6 was decreased in neural tissues of ATRA-exposed embryos from E8 to E11. Data suggest that disruption of Smad signaling may be involved in neural tube defects.

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