Journal of Applied Toxicology

Cover image for Vol. 32 Issue 8

August 2012

Volume 32, Issue 8

Pages 537–641

  1. Review Articles

    1. Top of page
    2. Review Articles
    3. Research Articles
    1. Percutaneous absorption in diseased skin: an overview (pages 537–563)

      Audris Chiang, Emilie Tudela and Howard I. Maibach

      Article first published online: 10 JAN 2012 | DOI: 10.1002/jat.1773

      The stratum corneum's functions include protection from hazardous environments, water loss prevention and body temperature regulation. While intact skin absorption studies are abundant, studies on compromised skin permeability are less common. We reviewed literature on absorption through abnormal skin models: tape-stripped, abraded, frozen, heated, delipidized, irritated, UV-exposed and diseased skin. Data summarized begins to characterize flux alteration associated with damaged skin. Understanding alteration requires consideration of involved conditions and enlarging our database to a more complete physicochemical spectrum.

  2. Research Articles

    1. Top of page
    2. Review Articles
    3. Research Articles
    1. Derivation of cardiac output and alveolar ventilation rate based on energy expenditure measurements in healthy males and females (pages 564–580)

      Pierre Brochu, Jules Brodeur and Kannan Krishnan

      Article first published online: 1 MAR 2011 | DOI: 10.1002/jat.1651

      Published doubly labeled water measurements were used to determine a complete and original set of key respiratory and cardiovascular parameters with their distributions, for healthy normal-weight males and females aged 5–96 years old during their aggregate daytime activities: minute energy expenditures, oxygen consumption rates, minute ventilation rates, ratios of the physiological dead space to the tidal volume, alveolar ventilation rates, arterioveinous oxygen content differences, cardiac outputs and ventilation–perfusion ratios.

    2. Structure–function alteration of hemoglobin in arsenicosis patients: a probable pathway to exert toxicity (pages 581–589)

      Bibaswan Mondal, Debdutta Chatterjee and Maitree Bhattacharyya

      Article first published online: 11 MAR 2011 | DOI: 10.1002/jat.1656

      Millions of people around the world are suffering from chronic arsenicosis predominantly via ingestion of arsenic contaminated ground water. Though this problem has been studied extensively, the mechanism of toxicity remains unknown. Our work explores structure-function property of hemoglobin in chronic arsenicosis subjects and reveals that the molecule is modified in such a way that comparatively weak binding with oxygen and strong binding with arsenic occur simultaneously. This association plays a crucial role in exerting the pathway for arsenic toxicity.

    3. Experience with local lymph node assay performance standards using standard radioactivity and nonradioactive cell count measurements (pages 590–596)

      David Basketter, Susanne N. Kolle, Arnhild Schrage, Naveed Honarvar, Armin O. Gamer, Bennard van Ravenzwaay and Robert Landsiedel

      Article first published online: 25 MAY 2011 | DOI: 10.1002/jat.1684

      In this paper, the standard LLNA is compared with a non-radioactive variant using lymph node cell counts (LNCC). The assays were run in parallel, using the 22 chemicals recommended in globally harmonised performance standards. The results from the two assays showed very high concordance (95%), whereas agreement with the performance standard results was lower (approximately 75%). It is suggested that when assays are judged against performance standards, then this requires a balanced analysis rather than a simple checklist approach.

    4. Further experience with the local lymph node assay using standard radioactive and nonradioactive cell count measurements (pages 597–607)

      Susanne N. Kolle, David Basketter, Arnhild Schrage, Armin O. Gamer, Bennard van Ravenzwaay and Robert Landsiedel

      Article first published online: 25 MAY 2012 | DOI: 10.1002/jat.2754

      The standard LLNA is compared with a non-radioactive variant using lymph node cell counts (LNCC). The assays were run in parallel, using the 180 chemicals, mixtures and formulations. Results from the two assays showed high level of concordance (86%). Potency predictions for positive results (n=101) showed over 93% agreement. It is concluded that the LNCC provides a viable non-radioactive alternative to the LLNA for the assessment of substances, including potency predictions, as well as for the evaluation of preparations.

    5. A battery of genotoxicity studies with an allergy vaccine adjuvanted with monophosphoryl lipid A (MPL®) for the treatment of grass pollen allergy (pages 608–616)

      Lesley Reeve, Paul Baldrick, Simon Hewings and Murray Skinner

      Article first published online: 14 SEP 2011 | DOI: 10.1002/jat.1726

      A new allergy therapeutic product, Pollinex® Quattro Grass, has undergone a battery of genotoxicity studies. This is the first such publication on this type of product. Two in vitro studies (Ames and MLA assays) and two in vivo studies (bone marrow micronucleus and Comet assays) have been performed. Positive results in the MLA may have been an artifact of the exogenous metabolizing system, all other tests were negative. Overall the studies support safe clinical use of Pollinex® Quattro Grass.

    6. Embryotoxicity assessment of developmental neurotoxicants using a neuronal endpoint in the embryonic stem cell test (pages 617–626)

      Dae Hyun Baek, Tae Gyun Kim, Hwa Kyung Lim, Jin Wook Kang, Su Kyoung Seong, Seung Eun Choi, So Yun Lim, Sung Hee Park, Bong-hyun Nam, Eun Hee Kim, Mun Sin Kim and Kui Lea Park

      Article first published online: 1 DEC 2011 | DOI: 10.1002/jat.1747

      The embryonic stem cell test (EST) is a validated in vitro embryotoxicity test; however, as the inhibition of cardiac differentiation alone is used as a differentiation endpoint in the EST, it may not be a useful test to screen embryotoxic chemicals that affect the differentiation of noncardiac tissues. Previously, methylmercury (MeHg), cadmium and arsenic compounds, which are heavy metals that induce developmental neurotoxicity in vivo, were misclassified as nonembryotoxic with the EST.

    7. Pentachlorophenol decreases tumor-cell-binding capacity and cell-surface protein expression of human natural killer cells (pages 627–634)

      Tasia Hurd, Jasmine Walker and Margaret M. Whalen

      Article first published online: 22 DEC 2011 | DOI: 10.1002/jat.1781

      Pentachlorophenol (PCP) is an organochlorine pesticide that decreases the tumor-cell killing (lytic) function of human natural killer (NK) cells. Levels of PCP that decreased lysis were tested for effects on binding function and those that decreased binding were examined for effects on cell-surface proteins. 10 µm PCP for 24 h decreased NK binding function (34.6%), and CD11a (21.7%) and CD56 (26.2%) cell-surface proteins. Both binding function and cell-surface proteins were decreased after longer exposures to lower concentrations of PCP.

    8. Developing in vitro reporter gene assays to assess the hormone receptor activities of chemicals frequently detected in drinking water (pages 635–641)

      Hong Sun, Chaozong Si, Qian Bian, Xiaodong Chen, Liansheng Chen and Xinru Wang

      Article first published online: 10 JAN 2012 | DOI: 10.1002/jat.1790

      Estrogen receptor (ER), androgen receptor (AR), thyroid hormone receptor (TR) mediated reporter gene assays were developed in Vero cells. Bisphenol A, di-2-ethylhexyl-phthalate (DEHP), chlorpyrifos (CPF) and 2,4-dichlorophenoxyacetic acid (2,4-D) showed different activities via ER, AR and TR; CPF and 2,4-D could not activate or suppress TR at the concentration of 100-fold their maximum contaminant level in drinking water. The combined effect of DEHP and CPF was weaker than the additional models.

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