Weight-of-evidence process for assessing human health risk of mixture of metal oxide nanoparticles and corresponding ions in aquatic matrices

This study proposed a framework to estimate health risks due to exposure of mixture of nanoparticles (NPs) from surface water, for the first time, as per authors’ best knowledge. The framework consisted of hazard identification, exposure assessment, dose-response assessment, risk characterization and risk management steps. Concentrations of mixture of NPs and associated ions were compiled and range of values were used for exposure estimation. The resulting concentrations of nanoparticle and metal ions in simulated digestive fluid were calculated and used to estimate exposure dose to digestive system organs during a hypothetical exposure of water during recreational activity. Exposure doses of different possible combinations of ZnO NP, CuO NP, Zn2+ and Cu2+ ions were considered. The ECHA weight-of- evidence framework was used for formulating hypotheses and collecting evidence for determining reference dose (RfD) and interaction parameter for estimating hazard interaction value (an index for risk) as per the USEPA modified weight-of-evidence method for estimating risks of binary NPs and ions. RfD values of CuO (0.0262 mg/kg/d) and ZnO NP (0.0315 mg/kg/d) were derived using information from rat-based oral toxicity studies and assumed values of uncertainty factors. The results showed that mixture of NPs under environmentally-relevant conditions do not pose any health risk. The uncertainty analysis indicated that ZnO + CuO + Zn + Cu ion suspension posed the highest risk. The switchover analysis indicated that NP concentration >0.207 mg/L resulted in risk estimate greater than 1 and pose risk. Although risk estimate was found to be smaller than 1 under the studied natural water condition, efforts should be made to continue monitoring mixture of NPs as a precautionary approach. More efforts are required to obtain data on (i)toxicity of mixture of NPs, (ii)their interaction effects, (iii)fractions of NPs reaching target organ in order to accurately predict risk. Potential benefit of this framework is in its usage for development of structure for estimating exposure risks due to mixture of NPs and ions from surface water. This can also be used to adopt methodology for gathering information on evidence required in different steps of risk assessment process, like obtaining RfD/uncertainty factor -related parameters in dose-response assessment step, deriving interaction and mixture toxicity-related parameters in risk estimation step.