8291031 Chloroacetanilide pesticides exposure and lymphoid malignancies risk in the French agriculture and cancer cohort

<h3>Objectives</h3> Several studies have reported an elevated risk of cancer, including lymphoid malignancies (LM), among farmers, particularly in relation to pesticide use. Chloroacetanilides are among the best-selling herbicides in France. Recent data on carcinogenic mechanisms and animals studies have prompted the IARC to initiate a new monography in late 2025 focusing on 3 molecules, including alachlor. The aim of our study was to evaluate risk for specific LM subtypes in relation to exposure to chloroacetanilide herbicides within the French AGRIculture and CANcer (AGRICAN) cohort. <h3>Material and Methods</h3> We included 155,173 individuals enrolled between 2005 and 2007. The main LM subtypes considered were chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma and multiple myeloma (MM). Incident cases were identified through linkage with French cancer registries. Exposure to 7 active ingredients of chloroacetanilides was estimated using the PESTIMAT crop-exposure matrix. Cox models with a 10-year follow-up and age as the time scale were used to estimate hazard ratios and 95% confidence intervals for ever vs never exposed, exposure duration and score for each LM subtype. <h3>Results</h3> We identified 22,858 chloroacetanilide users and 1,654 LM cases in our population. Among men (236 LM cases among chloroacetanilide users), we found some increased risks of MM, particularly for alachlor (1.41 [0.88-2.26]), metolachlor (1.44 [0.90-2.31])) and napropamide, for low and intermediate exposure categories (ranging from +67% to +100%). Higher risks of CLL/SLL were also observed in the first quartile of exposure scores for Alachlor and Metolachlor (+72% and +82% increases, respectively). Increased risks were also noted for other subtypes such as follicular lymphoma in association with specific chloroacetanilide molecules. Among female users, only 8 LM cases were recorded. <h3>Conclusion</h3> This study contributes new evidence to a limited body of literature on the association between chloroacetanilide herbicide exposure and the risk of haematological cancers.