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The current study assessed the spatiotemporal variations and human health surveillance associated with organochlorine pesticide (OCP) contamination in water, sediments, and fish from Chenab River, Pakistan. The OCP determinations were performed using high-performance liquid chromatography with a reverse-phase C18 column. The total OCP levels ranged from 13.33 to 274.59 ng/L in water, 4.63 to 239.11 ng/g in sediments, and 23.79 to 387.12 ng/g in fish species. The overall pattern of mean OCP concentrations followed the order as ΣDDTs > Σendosulfan > aldrin and OCP pollution pattern among the headworks were Khanki Barrage > Qadirabad Barrage > Trimmu Barrage > Marala Barrage in all three environmental matrixes during both seasons. The estimated daily intake (EDI) for ∑OCPs was found to be 22.44 ng/kg/day. The hazard ratios calculated to assess the carcinogenic risk indicated that the values for ∑DDT and aldrin at the 95th percentile concentrations were greater than one, indicating the probability of carcinogenic risk occurrence of one in million populations due to fish consumption. Therefore, these high levels of OCPs and carcinogenic risk through fish consumption highlight the needs of immediate elimination of OCPs from riverine environment of Chenab River and we recommend long-term monitoring-based freshwater ecological studies to be conducted in the study area. [ABSTRACT FROM AUTHOR]