Journal of Applied Toxicology

Cover image for Journal of Applied Toxicology

January 2011

Volume 31, Issue 1

Pages 1–93

  1. Research Articles

    1. Top of page
    2. Research Articles
    3. Toxicological Update
    4. Short Communications
    1. Manganese modulation of MAPK pathways: effects on upstream mitogen activated protein kinase kinases and mitogen activated kinase phosphatase-1 in microglial cells (pages 1–10)

      Patrick L. Crittenden and Nikolay M. Filipov

      Article first published online: 29 JUN 2010 | DOI: 10.1002/jat.1552

      Multiple studies demonstrate that manganese (Mn) exposure potentiates inflammatory mediator output from activated glia; this increased output is associated with enhanced mitogen activated protein kinase (MAPK: p38, ERK, and JNK) activity. Here, we sought to determine whether Mn activates MAPK by activating the kinases upstream of MAPK, i.e., MKK-3/6, MKK-1/2, and MKK-4 (responsible for activation of p38, ERK, and JNK, respectively) and/or by inhibiting a major phosphatase responsible for MAPK inactivation, MKP-1.

    2. Further studies on the potential contribution of acetaldehyde accumulation and oxidative stress in rat mammary tissue in the alcohol drinking promotion of breast cancer (pages 11–19)

      Silvia L. Fanelli, María E. Maciel, María I. Díaz Gómez, Aurora M.A. Delgado de Layño, Florencia M. Bietto, José A. Castro and Gerardo D. Castro

      Article first published online: 9 JUL 2010 | DOI: 10.1002/jat.1555

      Repetitive alcohol drinking was found to produce significant decreases in the mammary tissue content of GSH, alpha-tocopherol and enzymes involved in tissue defense against oxidative damage. Mammary microsomal metabolism of ethanol to acetaldehyde was not induced after an acute dose of ethanol or acetone. Cytosolic pathway instead was significantly enhanced. Results suggest that while acetaldehyde accumulation in mammary tissue could be a critical event resulting from increasing production in situ, poor handling of the accumulated acetaldehyde could be also relevant.

    3. A toxicokinetic comparison of norditerpenoid alkaloids from Delphinium barbeyi and D. glaucescens in cattle (pages 20–26)

      Benedict T. Green, Kevin D. Welch, Dale R. Gardner, Bryan L. Stegelmeier, James A. Pfister, Daniel Cook and T. Zane Davis

      Article first published online: 15 JUL 2010 | DOI: 10.1002/jat.1563

      Two species of larkspur containing toxic norditerpenoid alkaloids, D. barbeyi and D. glaucescens were orally dosed to Angus steers. There were significant differences between the maximum serum alkaloid concentrations and area under the curve for doses of D. glaucescens but not D. barbeyi. Results from this experiment suggest that approximately seven days are required to clear 99% of the toxic alkaloids from the serum of cattle orally dosed with D. barbeyi or D. glaucescens.

    4. Cytotoxic effects induced by unmodified and organically modified nanoclays in the human hepatic HepG2 cell line (pages 27–35)

      Sinéad Lordan, James E. Kennedy and Clement L. Higginbotham

      Article first published online: 30 JUL 2010 | DOI: 10.1002/jat.1564

      With the increase in manufacturing of nanoclay-containing products, information on the toxicological effects of nanoclay exposure is warranted. Thus, the objective of the present study was to evaluate the cytotoxicity of two different nanoclays. Cloisite Na+ induced intracellular reactive oxygen species (ROS) formation which coincided with increased cell membrane damage, whilst ROS generation did not play a role in Cloisite 93A-induced cell death. In cell culture medium, the nanoclays aggregated differently and this appeared to affect their mechanisms of toxicity.

    5. Developmental toxic potential of di-n-propyl phthalate administered orally to rats (pages 36–44)

      Anne-Marie Saillenfait, Alain-Claude Roudot, Frédéric Gallissot, Jean-Philippe Sabaté and Marie-Christine Chagnon

      Article first published online: 22 JUL 2010 | DOI: 10.1002/jat.1565

      The embryo-fetal toxic potential of the plasticizer, di-n-propyl phthalate (DnPP) was assessed in Sprague-Dawley rats following administration by gavage, at doses of 0, 0.5, 1, or 1.5 g kg−1 per day, on days 6 to 20 of gestation. Decreased anogenital distance in male fetuses, developmental delay, and increased incidence of fetal skeletal variations were observed at the mid and high doses, but there was no evidence of embryo lethal or teratogenic effects up to 1.5 g kg−1 per day.

    6. Proteomic identification of the differentially expressed proteins in human lung epithelial cells by airborne particulate matter (pages 45–52)

      Yu Mi Jeon, Bu Soon Son and Mi Young Lee

      Article first published online: 23 JUL 2010 | DOI: 10.1002/jat.1566

      Airborne particulate matter (PM10)-induced differentially expressed proteins were analyzed in human lung epithelial cells by proteomics. Analysis of 2-DE gels revealed more than 1270 protein spots in the cells, of which 36 showed changes of more than 2-fold on exposure to PM10. The glycolytic enzyme pyruvate kinase showed a marked increase in expression, whereas the cytoskeleton-related vinculin and anti-inflammatory annexin 1 showed marked decreases in expression.

    7. Effects of (+)catechin and (−)epicatechin on heterocyclic amines-induced oxidative DNA damage (pages 53–62)

      Ana Isabel Haza and Paloma Morales

      Article first published online: 28 JUN 2010 | DOI: 10.1002/jat.1559

      In the present study heterocyclic amines induced a significant increase of DNA damage in a dose dependent manner. (+)-Catechin exerted protection against oxidized purines induced by 8-MeIQx, 4,8-diMeIQx and PhIP. Oxidized pyrimidines and DNA strand breaks induced by PhIP were also prevented by (+)-catechin. Otherwise, (−)-epicatechin protected against the oxidized pyrimidines induced by PhIP and the oxidized purines induced by 8-MeIQx and 4,8-diMeIQx. The ethoxyresorufin O-deethylation activity was moderately inhibited by (+)-catechin. However, (+)-catechin showed the greatest increase on UDP-glucuronyltransferase activity.

    8. Inter-laboratory validation of the modified murine local lymph node assay based on 5-bromo-2′-deoxyuridine incorporation (pages 63–74)

      Hajime Kojima, Masahiro Takeyoshi, Takashi Sozu, Takumi Awogi, Kazunori Arima, Kenji Idehara, Yoshiaki Ikarashi, Yukiko Kanazawa, Eiji Maki, Takashi Omori, Atsuko Yuasa and Isao Yoshimura

      Article first published online: 30 JUL 2010 | DOI: 10.1002/jat.1567

      Takeyoshi M. et al. (2001) has developed a modified murine local lymph node assay (LLNA) based on the 5-bromo-2'-deoxyuridine (BrdU) incorporation (LLNA:BrdU-ELISA). We conducted the validation study to evaluate the reliability and relevance of LLNA:BrdU-ELISA. The experiment involved 7 laboratories, wherein 10 chemicals were examined under blinded conditions. The validation results indicate that the LLNA:BrdU-ELISA is a promising new version LLNA.

    9. Biochemical and histopathological evaluation of functionalized single-walled carbon nanotubes in Swiss–Webster mice (pages 75–83)

      Anita Patlolla, Brittney McGinnis and Paul Tchounwou

      Article first published online: 24 AUG 2010 | DOI: 10.1002/jat.1579

      The aim of this study was to assess the effects, after intra peritoneal injection, of functionalized SWCNTs (carboxyl groups) on reactive oxygen species (ROS) induction and various hepatotoxicity markers (ALT, AST, ALP, LPO and morphology of liver) in the mouse model. The cellular findings reported here do suggest that purified carboxylated functionalized SWCNT has the potential to induce hepatotoxicity in Swiss-Webster mice through the mechanisms of oxidative stress, which is of sufficient significance to warrant in vivo animal exposure studies.

  2. Toxicological Update

    1. Top of page
    2. Research Articles
    3. Toxicological Update
    4. Short Communications
    1. The low-dose issue and stochastic responses to endocrine disruptors (pages 84–88)

      Yoko Hirabayashi and Tohru Inoue

      Article first published online: 3 AUG 2010 | DOI: 10.1002/jat.1571

      Three independent factors, each only recently identified, are associated with what is termed the ‘low dose issue’. Following three factors are discussed after ‘Introduction’

      • 1
        Central premise of toxicology: Adverse effects are examined on the basis of higher doses and extrapolated to lower doses
      • 2
        Novel Unexplored Area of Toxicology: Homeostatic Regulatory Disturbances
      • 3
        Toxicology for stochastic xenobiotic responses

      Then, recommendations to help ascertain the effects of endocrine-disrupting chemicals at low doses are suggested in the last section, ‘Development and establishment of new toxicological tools to analyze low-dose effects’.

  3. Short Communications

    1. Top of page
    2. Research Articles
    3. Toxicological Update
    4. Short Communications
    1. Application of hybrid approach for estimating the benchmark dose of urinary cadmium for adverse renal effects in the general population of Japan (pages 89–93)

      Yasushi Suwazono, Kazuhiro Nogawa, Mirei Uetani, Katsuyuki Miura, Kiyomi Sakata, Akira Okayama, Hirotsugu Ueshima, Jeremiah Stamler and Hideaki Nakagawa

      Article first published online: 11 SEP 2010 | DOI: 10.1002/jat.1582

      We used an updated hybrid approach to estimate the benchmark doses and their 95% lower confidence limits (BMDL) for cadmium-induced renal effects in humans. When the benchmark response was set at 5%, the lowest BMDL for urinary cadmium was 0.6 µg g−1 creatinine in both men and women, which was somewhat lower than average urinary cadmium in Japanese older population. These results suggest the importance of measures to decrease cadmium exposure in Japan.