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Flame Retardant TDCIPP Reduces Heart Rate Variability Through Potential Direct Inhibition of Choline
Jiuhong Zhang1,2, Chenyang Yue1, Luling Nie1
1Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China.
Journal of Applied Toxicology : JAT
|June 23, 2026
Summary
Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) impairs cardiac autonomic function by reducing heart rate variability in rats. This flame retardant disrupts cholinergic neurotransmission by inhibiting choline acetyltransferase activity.
Area of Science:
- Environmental toxicology
- Cardiovascular physiology
- Neurotoxicology
Background:
- Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a common flame retardant with known neurotoxic potential.
- Its effects on cardiac autonomic function and underlying mechanisms are not well understood.
Purpose of the Study:
- To investigate the impact of TDCIPP on heart rate variability (HRV) in rats.
- To elucidate the molecular mechanisms by which TDCIPP affects cardiac autonomic function.
Main Methods:
- Rats were exposed to varying doses of TDCIPP (0-360 mg/kg/day) for 114 days.
- Heart rate variability parameters were analyzed.
- Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities, mRNA, and protein levels were measured.
- Molecular docking was used to predict TDCIPP's interaction with ChAT.
Main Results:
- TDCIPP exposure significantly reduced multiple HRV parameters, indicating impaired cardiac autonomic function.
- A threshold-like pattern, rather than a dose-dependent response, was observed for HRV changes.
- TDCIPP dose-dependently decreased ChAT activity and mRNA expression without altering protein levels.
- Molecular docking suggested TDCIPP competitively inhibits ChAT by binding to its choline site.
Conclusions:
- TDCIPP impairs cardiac autonomic function in rats, likely by disrupting cholinergic neurotransmission.
- The novel mechanism involves the competitive inhibition of ChAT activity by TDCIPP.
- These findings highlight potential cardiovascular risks associated with TDCIPP exposure.
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