Environmental Chemistry

Detection of retinoic acid receptor agonistic activity and identification of causative compounds in municipal wastewater treatment plants in Japan

  1. Kazuko Sawada1,
  2. Daisuke Inoue1,
  3. Yuichiro Wada1,
  4. Kazunari Sei1,
  5. Tsuyoshi Nakanishi2,
  6. Michihiko Ike1,*

Article first published online: 21 DEC 2011

DOI: 10.1002/etc.741

Issue

Environmental Toxicology and Chemistry

Environmental Toxicology and Chemistry

Volume 31, Issue 2, pages 307–315, February 2012

Additional Information

How to Cite

Sawada, K., Inoue, D., Wada, Y., Sei, K., Nakanishi, T. and Ike, M. (2012), Detection of retinoic acid receptor agonistic activity and identification of causative compounds in municipal wastewater treatment plants in Japan. Environmental Toxicology and Chemistry, 31: 307–315. doi: 10.1002/etc.741

Author Information

  1. 1

    Division of Sustainable Energy and Environmental Engineering, Osaka University, Suita, Osaka, Japan

  2. 2

    Laboratory of Hygienic Chemistry and Molecular Toxicology, Gifu Pharmaceutical University, Gifu, Japan

*Division of Sustainable Energy and Environmental Engineering, Osaka University, Suita, Osaka, Japan.

Publication History

  1. Issue published online: 12 JAN 2012
  2. Article first published online: 21 DEC 2011
  3. Accepted manuscript online: 17 NOV 2011 07:09PM EST
  4. Manuscript Accepted: 9 OCT 2011
  5. Manuscript Revised: 10 JUL 2011
  6. Manuscript Received: 26 MAY 2011
Corrected by:

Erratum: Erratum: Detection of retinoic acid receptor agonistic activity and identification of causative compounds in municipal wastewater treatment plants in Japan

Vol. 31, Issue 9, 2189–2190, Article first published online: 17 AUG 2012

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Keywords:

  • Retinoic acid receptor;
  • Retinoic acid receptor agonist;
  • Wastewater treatment plant;
  • Retinoic acid;
  • 4-oxo-retinoic acid

Abstract

Retinoic acid (RA) receptor (RAR) agonists are potential toxicants that can cause teratogenesis in vertebrates. To determine the occurrence of RAR agonists in municipal wastewater treatment plants (WWTPs), we examined the RARα agonistic activities of influent and effluent samples from several municipal WWTPs in Osaka, Japan, using a yeast two-hybrid assay. Significant RARα agonistic activity was detected in all the influent samples investigated, suggesting that municipal wastewater consistently contains RAR agonists. Fractionations using high-performance liquid chromatography, directed by the bioassay, found several bioactive peaks from influent samples. The RAR agonists, all-trans RA (atRA), 13-cis RA (13cRA), 4-oxo-atRA, and 4-oxo-13cRA, possibly arising from human urine, were identified by liquid chromatography ion trap time-of-flight mass spectrometry. Quantification of the identified compounds in municipal WWTPs confirmed that they were responsible for the majority of RARα agonistic activity in WWTP influents, and also revealed they were readily removed from wastewater by activated sludge treatment. Simultaneous measurement of the RARα agonistic activity revealed that although total activity typically declined concomitant with the reduction of the four identified compounds, it remained high after the decline of RAs and 4-oxo-RAs in one WWTP, suggesting the occurrence of unidentified RAR agonists during the activated sludge treatment. Environ. Toxicol. Chem. 2012;31:307–315. © 2011 SETAC

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