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<p><i>ortho</i>-Phthalaldehyde (OPA) is a high-level chemical disinfectant used for sterilizing heat-sensitive medical equipment. OPA has been reported to be an airway irritant in animal studies, in human case reports, and in a human in vitro organotypic air–liquid-interface (ALI) airway culture model; there are also data indicating that it may be a direct-acting bacterial mutagen. In this study, we investigated the genotoxic potential of OPA using human ALI airway cultures, human lymphoblastoid TK6 cells, and the Ames test. Human airway cultures were exposed to OPA aerosol deposition doses ranging from 0.74 to 5.85&#xa0;µg/cm<sup>2</sup> for 4&#xa0;h/day over 5&#xa0;days, followed by a 28-day recovery period. Cytotoxicity, cilia beat frequency, and DNA damage were evaluated after 3&#xa0;days of OPA aerosol exposure, while mutagenicity was assessed by Duplex Sequencing (DS) after the 28-day recovery following the 5-day exposure. While OPA was cytotoxic, no DNA damage was detected in ALI cultures using the Comet-Chip and Multi-flow assays, and no mutagenicity was observed in the DS analysis. In contrast, treating TK6 cells with up to 2.5&#xa0;µg/mL OPA did not induce DNA damage but produced small increases in frequency of micronuclei, and mutations in the <i>HPRT</i> and <i>TK</i> genes. Additionally, OPA was negative in the Ames test both with and without S9 activation. Taken together, OPA was weakly positive in mammalian cell assays measuring genotoxic hazard, but not in more complex organotypic human ALI airway cultures, even at a highly cytotoxic concentration, suggesting that the airway model may possess detoxification systems that mitigate OPA’s genotoxic potential.</p>

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Comparative genotoxicity assessment of ortho-phthalaldehyde using human in vitro organotypic airway epithelial cultures and standard in vitro genotoxicity assays

  • 期刊论文

  • 发表日期：

    2026年3月5日

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  • Yuan Le,
  • Yueyi Sun,
  • Xilin Li,
  • Rebecca Wynne,
  • Nathan Twaddle,
  • Michelle E. Bishop,
  • Frederick A. Beland,
  • William M. Gwinn,
  • Robert H. Heflich,
  • Xuefei Cao,
  • Yiying Wang

摘要

ortho-Phthalaldehyde (OPA) is a high-level chemical disinfectant used for sterilizing heat-sensitive medical equipment. OPA has been reported to be an airway irritant in animal studies, in human case reports, and in a human in vitro organotypic air–liquid-interface (ALI) airway culture model; there are also data indicating that it may be a direct-acting bacterial mutagen. In this study, we investigated the genotoxic potential of OPA using human ALI airway cultures, human lymphoblastoid TK6 cells, and the Ames test. Human airway cultures were exposed to OPA aerosol deposition doses ranging from 0.74 to 5.85 µg/cm2 for 4 h/day over 5 days, followed by a 28-day recovery period. Cytotoxicity, cilia beat frequency, and DNA damage were evaluated after 3 days of OPA aerosol exposure, while mutagenicity was assessed by Duplex Sequencing (DS) after the 28-day recovery following the 5-day exposure. While OPA was cytotoxic, no DNA damage was detected in ALI cultures using the Comet-Chip and Multi-flow assays, and no mutagenicity was observed in the DS analysis. In contrast, treating TK6 cells with up to 2.5 µg/mL OPA did not induce DNA damage but produced small increases in frequency of micronuclei, and mutations in the HPRT and TK genes. Additionally, OPA was negative in the Ames test both with and without S9 activation. Taken together, OPA was weakly positive in mammalian cell assays measuring genotoxic hazard, but not in more complex organotypic human ALI airway cultures, even at a highly cytotoxic concentration, suggesting that the airway model may possess detoxification systems that mitigate OPA’s genotoxic potential.