The French High Council for Public Health (HCSP) was asked to assess the health impact of potentially present quantities of chlordecone (CLD) in all types of labile blood products (LBP) for patients receiving repeated transfusions in Guadeloupe and Martinique. This toxic substance was used between 1972 and 1993 to combat the black banana weevil and caused very long-term contamination of the terrestrial and aquatic environment of the two islands, as well as affecting a significant proportion of the Caribbean population. Following this ecological disaster, actions and plans were implemented by public authorities, notably to assess the CLD exposure of the Caribbean population and its medium- and long-term impact on human health. After summarizing this context, the HCSP presents a structured risk assessment approach integrating available biomonitoring data, toxicological and toxicokinetic knowledge related to CLD, as well as internal exposure simulations using PBPK-type pharmacokinetic modeling based on human physiology (Emond & Multigner, Arch. Toxicol. 2022). The proposed modeling allows for the evaluation of CLD plasma concentrations likely to be reached in adult or child recipients considered free of exposure, in the context of repeated transfusions under several scenarios constructed from deliberately maximalist assumptions, such as high transfusion frequency, high levels of donor exposure, and high assumptions regarding CLD distribution in the blood components that were investigated (exclusively platelets and red blood cell concentrates, since all the plasma used in the French West Indies is imported from mainland France). The modeled steady-state concentrations were compared to the internal toxicological reference value (ITRV) defined by the French “Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail” (Anses) as the blood concentration of CLD below which, over a long period, the risk of adverse effects in the exposed population is considered negligible. The results show that, even in the most unfavorable scenarios, the steady-state CLD blood concentration reached over a 1,000-day period from the first transfusion remains below the ITRV. For the most realistic scenarios, the model indicates that repeated transfusions do not lead to any plasma accumulation of CLD at the detection threshold of 0.01 µg/l. Finally, taking into account the safety margins shown by the modeling, the uncertainties considerd in a conservative manner and the major therapeutic benefits that iterative transfusions of blood products collected in the West Indies represent for patients suffering in particular from constitutional hemoglobin pathologies, the HCSP concludes, in view of the presumed very low excess risk induced by the iterative transfusion contribution of blood products, that no specific adaptation of transfusion practices is justified in the West Indies context.