Metabolic alterations resulting in the onset of diverse disease conditions are often implicated by exposure of susceptible biota to a load of contaminants. This empirical investigation embraced the potential metabolic health risk associated with the intake of potable water contaminated by different doses of cadmium (Cd) and nickel (Ni) at optimized conditions in male Wistar albino rats. The contamination of the water by Cd (0-150 mg/L) and Ni (0-150 mg/L), and the 20-60 days exposure of rat models as input factors led to seventeen treatment combinations (N=17) with three replications (n=3) in each case using the Box-Behnken design (BBD). Predictive markers, which included blood glucose level (BGL), atherogenic index of plasma (AIP), cardiac risk ratio (CRR) and atherogenic coefficient (AC) were analyzed using blood samples to ascertain metabolic changes. Moreover, four quadratically fit models for the markers with regression coefficient (r2 values) above 98 %, and no significant lack of fit (P >0.05) respectively were developed. These models further revealed a synergistic interaction between Cd and Ni through the three-dimension (3D) surface plots, resulting in a predictively si
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