Benchmark Dose for Dioxin Based on Gestational Diabetes Mellitus Using Coexposure Statistical Methods and an...

Area of Science:

• Environmental Health Sciences
• Toxicology
• Endocrinology

Background:

• Dioxins are ubiquitous endocrine-disrupting substances.
• Assessing coexposure effects and benchmark doses is challenging.
• Gestational diabetes mellitus (GDM) is a significant pregnancy complication.

Purpose of the Study:

• To assess the relationship between dioxin exposure and GDM.
• To calculate benchmark doses (BMD) for dioxins in coexposure scenarios.
• To derive a daily exposure threshold using a physiologically based toxicokinetic (PBTK) model.

Main Methods:

• Nested case-control study (77 GDM cases, 154 controls).
• Serum levels of dioxin-like compounds (DLCs), PFAAs, PBDEs, and ndl-PCBs measured.
• Bayesian machine kernel regression (BKMR), probit, logistic models, and PBTK model used for analysis.

Main Results:

• Individuals in the highest quantile of total dioxin toxic equivalent (TEQ) had significantly higher odds of GDM (OR, 8.87).
• Dioxin TEQ and BDE-153 were identified as key influential compounds.
• BMD10 and BMDL10 were 3.71 and 3.46 pg TEQ/g fat, respectively, considering BDE-153 coexposure.
• Estimated daily exposure threshold below 4.34 pg TEQ kg-1 bw week-1 to avoid harmful serum concentrations for GDM.

Conclusions:

• Dioxin exposure is associated with an increased risk of GDM.
• Coexposure to other chemicals, like BDE-153, influences dioxin's effects.
• PBTK models and coexposure statistical methods are crucial for accurate risk assessment and setting exposure limits.