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Quantitative structure-activity relationships of selected phenols with non-monotonic dose-response curves

  • Articles/Environmental Science & Technology
  • Published:
Chinese Science Bulletin

Abstract

Particular non-monotonic dose-response curves of many endocrine disrupting chemicals (EDCs) suggest the existence of diverse toxicity mechanisms at different dose levels. As a result, the biological activities of EDCs cannot be simply exhibited by unique EC 50/LD 50 values, and the quantitative structure-activity relationship (QSAR) analysis for non-monotonic dose-response relationship becomes an unknown field in the environmental science. In this paper, nine phenols with inverted U-shaped dose-response curves in lymphocyte proliferation test of Carassius auratus were selected. The binding interactions between the phenols and several typical EDCs-related receptors were then explored in a molecular simulation study. The estrogen receptor (ER), androgen receptor (AR), thyroid hormone receptor (TR), bacterial O2 sensing FixL protein (FixL), aryl hydrocarbon receptor (AhR), and the peroxisome proliferator-activated receptor (PPAR) were the target receptors in the study. Linear regression QSAR models for the low and high exposure levels of the compounds were developed separately. The results indicated that the lymphocyte proliferation in the low-dose range might involve ER-mediated process, while the proliferation inhibition in the high dose range was dominated by the acute toxicity of phenols due to receptor occupancy and cell damage.

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Authors and Affiliations

  1. State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210093, China

    ChangAn Gao, AiQian Zhang, Yuan Lin & LianSheng Wang

  2. State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai, 200092, China

    DaQiang Yin

Authors
  1. ChangAn Gao
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  2. AiQian Zhang
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  3. Yuan Lin
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  4. DaQiang Yin
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  5. LianSheng Wang
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Corresponding author

Correspondence to AiQian Zhang.

Additional information

Supported by the National Natural Science Foundation of China (Grant Nos. 20777035 and 20377022) and National High Technology Research and Development Program of China (Grant Nos. 2007AA06Z416 and 2006AA06Z424)

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Gao, C., Zhang, A., Lin, Y. et al. Quantitative structure-activity relationships of selected phenols with non-monotonic dose-response curves. Chin. Sci. Bull. 54, 1786–1796 (2009). https://doi.org/10.1007/s11434-009-0174-7

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  • DOI: https://doi.org/10.1007/s11434-009-0174-7

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