Chlordecone: development of a physiologically based pharmacokinetic tool to support human health risks assessments.
Arch Toxicol
; 96(4): 1009-1019, 2022 04.
Article
in En
| MEDLINE
| ID: mdl-35122515
ABSTRACT
Chlordecone (CD; Kepone™) is a carcinogenic organochlorine insecticide with neurological, reproductive, and developmental toxicity that was widely used in the French West Indies (FWI) from 1973 to 1993 to fight banana weevils. Although CD has not been used there for more than 25 years, it still persists in the environment and has polluted the waterways and soil of current and older banana fields. Today, human exposure to CD in the FWI mainly arises from consuming contaminated foodstuffs. The aims of this study were to develop a physiologically based pharmacokinetic (PBPK) model in the rat and extrapolate it to humans based on available pharmacokinetic data in the literature. A comparison of simulations using the rat model with published experimental datasets showed reasonable predictability for single and repetitive doses, and, thus, it was extrapolated to humans. The human PBPK model, which has seven compartments, is able to simulate the blood concentrations of CD in human populations and estimate the corresponding external dose using the reverse dosimetry approach. The human PBPK model will make it possible to improve quantitative health risk assessments for CD contamination and reassess the current chronic toxicological reference values to protect the FWI population.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Soil Pollutants
/
Musa
/
Insecticides
/
Chlordecone
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
/
Humans
Country/Region as subject:
Caribe
Language:
En
Journal:
Arch Toxicol
Year:
2022
Type:
Article
Affiliation country:
Canada