Modeling chlordecone toxicokinetics data in growing pigs using a nonlinear mixed-effects approach.

Area of Science:

• Environmental Science
• Toxicology
• Veterinary Medicine

Background:

• Chlordecone (CLD), a persistent organic pollutant (POP), pollutes French West Indies banana fields, entering the food chain.
• CLD is readily absorbed by animals ingesting contaminated soil, posing risks to livestock.
• Understanding CLD toxicokinetics is crucial for managing agricultural contamination.

Purpose of the Study:

• To model the toxicokinetics (TKs) of chlordecone (CLD) in growing pigs.
• To utilize non-compartmental and nonlinear mixed-effects modeling (NLME) approaches.
• To identify factors influencing CLD's absorption, distribution, metabolism, and excretion in pigs.

Main Methods:

• Intravenous administration of CLD (1 mg/kg) to Creole and Large White growing pigs.
• Serum CLD concentration measurement via GCMS/MS over 84 days.
• Modeling CLD kinetics using Monolix software with NLME, evaluating covariates like breed, weight, and daily gain.

Main Results:

• A bicompartmental model accurately described CLD serum kinetics.
• Average daily gain was identified as the primary covariate affecting inter-individual TKs variability.
• Key parameters: body clearance of 76.7 mL/kg/d and steady-state volume of distribution of 6 L/kg.

Conclusions:

• This study presents the first NLME application for CLD TKs in farm animals.
• Average daily gain is a significant factor in CLD toxicokinetics variability in pigs.
• Findings support improved rearing management strategies in CLD-contaminated agricultural zones.