Kazuko Sawada

Osaka University, Suika, Ōsaka, Japan

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Publications (6)15.09 Total impact

  • D Inoue · K Sawada · Y Wada · K Sei · M Ike
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    ABSTRACT: Retinoic acid (RA) receptor (RAR) agonists are potential teratogens to various vertebrates. Their contamination has been detected in municipal wastewater in different countries. This study involved field investigations and laboratory batch treatment experiments to elucidate the removal characteristics by activated sludge treatment of RAs (all-trans RA and 13-cis RA) and 4-oxo-RAs (4-oxo-all-trans RA and 4-oxo-13-cis RA), which were identified as major RAR agonists in municipal wastewater. Results obtained in this study show that currently employed activated sludge treatments can remove RAs, 4-oxo-RAs and overall RAR agonist contamination effectively from municipal wastewater in general, although high RAR agonistic activity might sometimes remain in the effluent. Laboratory experiments revealed that RAs were removed rapidly from the aqueous phase by adsorption to the sludge, after which they were removed further by biological and/or chemical degradation. Aside from adsorption to the sludge, 4-oxo-RAs were also apparently removed by biological and chemical degradation. Biodegradation contributed greatly to the removal. Results of additional experiments indicated that novel non-identifiable RAR agonists can occur through the biodegradation of 4-oxo-RAs by activated sludge and that they can persist for a long period.
    No preview · Article · Jun 2013 · Water Science & Technology
  • Kazuko Sawada · Daisuke Inoue · Kazunari Sei · Michihiko Ike
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    ABSTRACT: Retinoic acid (RA) receptors (RARs) are nuclear receptors whose specific natural ligands are all-trans RA (atRA) and 9-cis RA. RARs control aspects of vision, cell differentiation, immune response, and embryonic development in vertebrates. However excess RAR signaling can cause various teratogenic effects on developing vertebrates. In our previous studies, we have revealed that municipal wastewater generally contains RAR agonists, and identified that the major causative compounds are RAs [atRA and 13-cis RA (13cRA)] and 4-oxo-RAs (4-oxo-atRA and 4-oxo-13cRA), which are oxidative metabolites of RAs. In this study, to elucidate the fates of RAs and 4-oxo-RAs during wastewater treatment, we investigated the variations in their concentrations and the overall RAR agonistic activity in municipal wastewater treatment plants in Osaka, Japan. Results of this study suggested that RAs and 4-oxo-RAs in wastewater can be readily removed by activated sludge treatment, regardless of season and treatment type, and that unidentified RAR agonists are produced during the treatment and persist in the final effluent under certain conditions. However, the current RAR agonist level in the final effluent is unlikely to cause deleterious biological effects.
    No preview · Article · Mar 2013 · Journal of Japan Society on Water Environment
  • K Sawada · D Inoue · Y Wada · K Sei · T Nakanishi · M Ike

    No preview · Article · Sep 2012 · Environmental Toxicology and Chemistry
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    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.
    Full-text · Article · Feb 2012 · Environmental Toxicology and Chemistry
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    ABSTRACT: To assess the potential endocrine disruptive effects through multiple nuclear receptors (NRs), especially non-steroidal NRs, in municipal wastewater, we examined the agonistic activities on four NRs (estrogen receptor alpha, thyroid hormone receptor alpha, retinoic acid receptor alpha and retinoid X receptor alpha) of untreated and treated wastewater from municipal wastewater treatment plants (WWTPs) in Japan using a yeast two-hybrid assay. Investigation of the influent and effluent of seven WWTPs revealed that agonistic activities against steroidal and non-steroidal NRs were always detected in the influents and partially remained in the effluents. Further investigation of four WWTPs employing conventional activated sludge, pseudo-anoxic-oxic, anoxic-oxic and anaerobic-anoxic-oxic processes revealed that the ability to reduce the agonistic activity against each of the four NRs varies depending on the treatment process. These results indicated that municipal wastewater in Japan commonly contains endocrine disrupting chemicals that exert agonistic activities on steroidal and non-steroidal NRs, and that some of these chemicals are released into the natural aquatic environment. Although the results obtained in yeast assays suggested that measured levels of non-steroidal NR agonists in the effluent of WWTPs were not likely to cause any biological effect, further study is required to assess their possible risks in detail.
    Full-text · Article · Jan 2011 · Journal of Environmental Sciences
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    ABSTRACT: This study was conducted to investigate the agonistic activity against human retinoic acid receptor (RAR) α in the Lake Biwa-Yodo River and the Ina River in the Kinki region of Japan. To accomplish this, a yeast two-hybrid assay was used to elucidate the spatial and temporal variations and potential sources of RARα agonist contamination in the river basins. RARα agonistic activity was commonly detected in the surface water samples collected along two rivers at different periods, with maximum all-trans retinoic acid (atRA) equivalents of 47.6. ng-atRA/L and 23.5. ng-atRA/L being observed in Lake Biwa-Yodo River and Ina River, respectively. The results indicated that RARα agonists are always present and widespread in the rivers. Comparative investigation of RARα and estrogen receptor α agonistic activities at 20 stations along each river revealed that the spatial variation pattern of RARα agonist contamination was entirely different from that of the estrogenic compound contamination. This suggests that the effluent from municipal wastewater treatment plants, a primary source of estrogenic compounds, seemed not to be the cause of RARα agonist contamination in the rivers. Fractionation using high performance liquid chromatography (HPLC) directed by the bioassay found two bioactive fractions from river water samples, suggesting the presence of at least two RARα agonists in the rivers. Although a trial conducted to identify RARα agonists in the major bioactive fraction was not completed as part of this study, comparison of retention times in HPLC analysis and quantification with liquid chromatography-mass spectrometry analysis revealed that the major causative contaminants responsible for the RARα agonistic activity were not RAs (natural RAR ligands) and 4-oxo-RAs, while 4-oxo-RAs were identified as the major RAR agonists in sewage in Beijing, China. These findings suggest that there are unknown RARα agonists with high activity in the rivers.
    Full-text · Article · Apr 2010 · Water Research