Aryl Organophosphate Esters and Hemostatic Disruption: Identifying Risk through Machine Learning and Experimental...

Area of Science:

• Environmental Health
• Toxicology
• Hematology

Background:

• Organophosphate esters (OPEs) are widespread environmental contaminants with potential human health risks.
• OPEs in blood suggest hematological interactions, potentially compromising hemostatic balance.
• The impact of OPEs on hemostasis is not well understood.

Purpose of the Study:

• To investigate the effects and mechanisms of OPEs on hemostasis.
• To identify specific OPEs that disrupt hemostatic balance.
• To elucidate the molecular pathways involved in OPE-induced hemostatic dysfunction.

Main Methods:

• Computational analysis of 85 prevalent OPEs for structural properties and protein affinity.
• High-throughput in vitro hemostatic balance assays.
• Network toxicology, AI (α-Fold), and agonist cotreatment assays to identify mediator proteins.

Main Results:

• Aryl-OPEs, characterized by a benzene ring, were identified as potent hemostatic disruptors.
• Proliferator-activated receptor γ (PPARγ) was identified as a key mediator of aryl-OPE induced hemostatic disruption.
• Specific OPEs, including bisphenol a bis (diphenyl phosphate) (BDP) and cresyl diphenyl phosphate (CDP), were found to pose a moderate risk.

Conclusions:

• Aryl-OPEs present a moderate risk to the hemostatic balance of the general population.
• PPARγ is a critical mediator in OPE-induced hemostatic disruption.
• The study provides a methodology for assessing the hematological toxicity of emerging pollutants.