Sahrish Naqvi and Amina Jafri
Abstract
This review evaluates cumulative human exposure and health risks associated with pesticideâheavy metal co-contamination in agro-industrial regions. Evidence was synthesized from recent studies on environmental fate, multi-pathway exposure, interaction mechanisms, and risk assessment approaches. Deterministic and probabilistic assessments indicate that cumulative hazard indices in high-exposure populations frequently exceed acceptable safety thresholds under chronic conditions. Combined exposure is associated with oxidative stress, inflammation, endocrine disruption, neurotoxicity, and genotoxicity, reflecting additive and synergistic toxic effects. Advanced tools, including artificial intelligenceâbased exposure modelling, high-throughput toxicity screening, and exposome approaches, improve mixture toxicity assessment. However, limitations persist due to insufficient environmentally realistic mixture datasets and lack of long term biomonitoring data. Strengthening cumulative exposure assessment frameworks is essential for developing mixture-informed regulatory policies and enhancing environmental health protection in agro-industrial systems.