Incorporating Size-Dependent Reference Dose (RfD) and Gastric System Effect in Estimation of Nanoparticles Risks to Human

The increasing use and release of a mixture of nanoparticles from various sources have raised concerns about the harm these contaminants can cause. These nanoparticles can enter the human body and undergo multiple transformations. The effect of change of nanoparticle properties while assessing health risk is essential and should be incorporated. This study attempted to determine an oral ingestion risk due to exposure to a mixture of nanoparticles by incorporating the effect of gastric fluid on the physicochemical properties of nanoparticles. The methodology adopted in this work included the development of structure by experimentally determining the impact of human biological fluids (saliva, gastric, and intestinal) on nanoparticle size change, which is a crucial exposure step for risk assessment. The conversion factor, the ratio of nanoparticle size from de-ionized water to natural water to gastric system, was theoretically incorporated in the framework for calculating the Reference Dose. Different exposure scenarios were considered to determine the risk in the absence and presence of antibiotics. The reference dose was determined for (a) no interaction between nanoparticles, i.e., no heteroaggregate formation; (b) nanoparticle heteroaggregate formation in the system. The results indicated that the RfD value for mixture aggregate (nZnO + nCuO) was found to be 0.543 mg/kg/d in the presence of Triclosan (0.243 mg/kg/d) and Sulfadimethoxine (0.282 mg/kg/d), indicating an increase in toxicity. The risk was higher for the scenarios when ZnO, CuO, Zn, and Cu ions were separately present in the mixture system. Our results help us understand nanoparticle fate in the natural and gastric systems and the behavior of a mixture of nanoparticles in the human digestive system.