Journal of Applied Toxicology

Cover image for Journal of Applied Toxicology

March 2010

Volume 30, Issue 2

Pages 91–182

  1. Reviews

    1. Top of page
    2. Reviews
    3. Research Articles
    1. Percutaneous absorption and exposure assessment of pesticides (pages 91–114)

      Mai A. Ngo, Michael O'Malley and Howard I. Maibach

      Version of Record online: 23 DEC 2009 | DOI: 10.1002/jat.1505

      Dermal exposure to a diverse range of chemicals may result from various uses. In order to assess exposure and estimate potential risks, accurate quantitative data on absorption are required. Various factors will influence the final results and interpretations of studies designed to assess the ability of compounds to penetrate the skin. This overview will discuss skin penetration by pesticides, emphasizing key parameters to be considered from the perspective of exposure assessment.

  2. Research Articles

    1. Top of page
    2. Reviews
    3. Research Articles
    1. Implication of agathic acid from Utah juniper bark as an abortifacient compound in cattle (pages 115–119)

      Dale R. Gardner, Kip E. Panter and Bryan L. Stegelmeier

      Version of Record online: 15 SEP 2009 | DOI: 10.1002/jat.1476

      Utah juniper (Juniperus osteosperma) bark was dosed to three pregnant cows. All three cows aborted the calves after 4, 5 and 6 days of treatment. The major diterpene acid in the bark was identified as agathic acid at a concentration of 1.5% (percentage dry weight). Metabolites in sera from treated cows showed detectable quantities of agathic acid, dihydroagathic acid and tetrahydroagathic acid. It is concluded that agathic acid is an abortifacient compound in late-term pregnant cattle.

    2. The influence of combinations of oximes on the reactivating and therapeutic efficacy of antidotal treatment of tabun poisoning in rats and mice (pages 120–124)

      Jiri Kassa, Jana Zdarova Karasova, Ruzena Pavlikova, Jan Misik, Filip Caisberger and Jiri Bajgar

      Version of Record online: 10 SEP 2009 | DOI: 10.1002/jat.1477

      The ability of two combinations of oximes (HI-6 + obidoxime and HI-6 + K203) to reactivate tabun-inhibited acetylcholinesterase and reduce acute toxicity of tabun was compared with the reactivating and therapeutic efficacy of antidotal treatment involving single oxime (HI-6, obidoxime, K203). Based on the obtained data, the antidotal treatment involving chosen combinations of oximes brings beneficial effects for the potency of antidotal treatment to reactivate tabun-inhibited acetylcholinesterase in rats and to reduce acute toxicity of tabun in mice.

    3. Tertiary butyl alcohol in drinking water induces phase I and II liver enzymes with consequent effects on thyroid hormone homeostasis in the B6C3F1 female mouse (pages 125–132)

      O. Blanck, J. Fowles, F. Schorsch, C. Pallen, H. Espinasse-Lormeau, E. Schulte-Koerne, M. Totis and M. Banton

      Version of Record online: 17 SEP 2009 | DOI: 10.1002/jat.1478

      Tertiary butyl alcohol was administered to groups of 15 female B6C3F1 mice at concentrations of 0, 2.0 or 20 mg TBA ml−1, for 14 days. Assessment of histological changes in the liver and thyroid, of the thyroid hormones, of the hepatic enzyme content and activities as well as of the quantitative PCR analysis of phase I and phase II gene transcripts was performed. Phenobarbital was administered to a positive control group by oral gavage at 80 mg kg−1 day−1.

    4. Sequencing analysis of mutations induced by N-ethyl-N-nitrosourea at different sampling times in mouse bone marrow (pages 133–141)

      Jianyong Wang and Tao Chen

      Version of Record online: 17 SEP 2009 | DOI: 10.1002/jat.1479

      Sequencing analysis of the ENU-induced mutations revealed that the mutation frequencies in the cII gene were 33, 217, 305 and 144 × 10−6 for control and days 1, 3 and 120 after ENU treatment, respectively. The mutation spectra at days 1 and 3 were significantly different from that at day 120. The results suggest that the high mutation induction by ENU at days 1 and 3 is due to the sensitivity of transit cells to the mutagenicity of ENU.

    5. Evaluation of aging influence on renal toxicity caused by segment-specific nephrotoxicants of the proximal tubule in rat (pages 142–150)

      Edoardo Zanetti, Arianna Chiusolo, Rossella Defazio, Alessandro Casartelli, Eleonora Cappelletti, Nicola Bocchini, Federica Chiara, Patrizia Cristofori and Andrea Trevisan

      Version of Record online: 9 SEP 2009 | DOI: 10.1002/jat.1480

      Rats were treated at different ages with a single dose of hexachloro-1:3-butadiene (HCBD) or potassium dichromate (chromate). HCBD treatment induced proximal tubular necrosis associated with changes of toxicological markers unrelated to the age, whereas chromate treatment induced an increased kidney damage related to the rat age. The results show that during aging there is an increased sensitivity of kidney to chromate but not to HCBD-induced damage and evidence differential age-related selectivity of rats for nephrotoxic compounds.

    6. PPARα and PPARγ are co-expressed, functional and show positive interactions in the rat urinary bladder urothelium (pages 151–162)

      Frederikke Lihme Egerod, Nils Brünner, Jette E. Svendsen and Martin B. Oleksiewicz

      Version of Record online: 15 SEP 2009 | DOI: 10.1002/jat.1481

      PPARα and PPARγ exhibited positive interactions in the rat bladder urothelium, based on Western analysis of the the Egr-1 and PMP70 candidate biomarkers in the bladder urothelium of rosiglitazone and fenofibrate-treated rats. Males exhibited a higher PPARα/PPARγ expression balance in the bladder urothelium than females. Fenofibrate induced the peroxisome membrane protein PMP70 in the bladder urothelium. Our findings support that dual-acting PPAR agonists could cause bladder cancer in rodents by receptor-mediated mechanisms potentially also involving peroxisome proliferation and oxidative stress.

    7. Cytotoxic effects of polychlorinated biphenyl hydroquinone metabolites in rat hepatocytes (pages 163–171)

      Katie Chan, Hans-Joachim Lehmler, Milani Sivagnanam, Cynthia Yan Feng, Larry Robertson and Peter J. O'Brien

      Version of Record online: 14 OCT 2009 | DOI: 10.1002/jat.1483

      The cytotoxic effects of polychlorinated biphenyl hydroquinone metabolites were investigated in freshly isolated rat hepatocytes. It was found that these metabolites severely depleted glutathione by conjugation and produced high levels of oxidative stress. The prior depletion of glutathione in hepatocytes resulted in resistance to oxidative stress and inhibited cytotoxicity normally induced by these hydroquinones. This finding suggests a toxic rather than protective role of glutathione as well as a novel type of quinone toxicity mechanism involving GSH-conjugates.

    8. Age-related differences in susceptibility to cisplatin-induced renal toxicity (pages 172–182)

      P. Espandiari, B. Rosenzweig, J. Zhang, Y. Zhou, L. Schnackenberg, V. S. Vaidya, P. L. Goering, R. P. Brown, J. V. Bonventre, K. Mahjoob, R. D. Holland, R. D. Beger, K. Thompson, J. Hanig and N. Sadrieh

      Version of Record online: 16 OCT 2009 | DOI: 10.1002/jat.1484

      Limited experimental models exist to assess drug toxicity in pediatric populations. We recently reported how a multi-age rat model could be used for pre-clinical studies of comparative drug toxicity in pediatric populations. The objective of this study was to expand the utility of this animal model, which previously demonstrated an age-dependent sensitivity to the classic nephrotoxic compound, gentamicin, to another nephrotoxicant, namely cisplatin (Cis).

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