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Chlorinated bis-phenolic disinfectants inhibit human and rat aromatase.

Wumin Jin1, Chaochao Gong2, Yilin Xu3

  • 1Department of Gynecology and Obstetrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China; Reproductive Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.

Chemico-Biological Interactions
|July 4, 2026
PubMed
Summary

Chlorinated bis-phenolic disinfectants inhibit aromatase (CYP19A1), an enzyme crucial for estrogen production. This endocrine disruption potential varies by chemical structure and may impact reproductive health.

Keywords:
AromataseChlorinated bis-phenolic disinfectantsDocking analysisLipophilicityLogPNetwork toxicology analysis

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Area of Science:

  • Endocrinology
  • Toxicology
  • Biochemistry

Background:

  • Chlorinated bis-phenolic disinfectants (CBPDs) are prevalent in consumer products.
  • Potential endocrine-disrupting effects of CBPDs, particularly via aromatase (CYP19A1) inhibition, require investigation.

Purpose of the Study:

  • To evaluate the inhibitory effects of various CBPDs on human and rat aromatase (CYP19A1) activity.
  • To elucidate the structure-activity relationships and molecular mechanisms underlying CBPD-mediated aromatase inhibition.

Main Methods:

  • In vitro enzyme inhibition assays using placental microsomes from humans and rats.
  • Enzyme kinetics, Lineweaver-Burk plot analysis, and molecular docking simulations.
  • Cell-based assays (BeWo cells) to assess estradiol secretion and network toxicology analysis.

Main Results:

  • CBPDs demonstrated structure-dependent inhibition of CYP19A1, with human aromatase being more sensitive than rat.
  • Hexachlorophene, bithionol, and bromochlorophene exhibited the highest inhibitory potency (lowest IC50 values).
  • CBPDs displayed mixed/competitive inhibition, reduced estradiol secretion in BeWo cells, and molecular docking revealed binding at the steroid-heme interface.

Conclusions:

  • CBPDs possess endocrine-disrupting potential by inhibiting aromatase, with potency influenced by hydrophobicity and halogen number.
  • Findings highlight the structure-activity dependency of CBPDs on CYP19A1 and inform endocrine risk assessment.
  • CBPDs are linked to estrogen signaling disruption, relevant in conditions like hypertensive disorders of pregnancy.