The objective of study is to understand challenges in assessing risk due to exposures of mixture of polymers released into water during reuse and recycling activities of plastic materials on human health. A four-step human health risk assessment framework consist of hazard identification, dose response assessment, risk estimation, uncertainty characterization was developed for assessing risk. Mixture of Bisphenol A (BPA) and Di (2-ethylhexyl) phthalate (DEHP): endocrine disrupting substances was taken as an example. Both of these chemicals are used in packaging bottles, beverage and food containers and are probable to occur in water cycle simultaneously, and thus, assessment of their combined risk is required. Information on cooccurrence of these chemicals in water medium, their associated toxic effects to human were obtained from published reports and current knowledge gaps were identified. Findings of this study indicated that there exists data gaps in (1) lack of information on simultaneous exposure of two chemicals,(2) their combined mode of action,(3) mixture toxicity dose and concentration dose-response relationships,(4) lack of knowledge about interaction of chemicals (5) variation of exposure with time and location,(6) complex effects at different level and segments of community, including indirect effects on ecosystem. These identified data gaps need to be filled by conducting more research in this direction so that exposure of population to polymeric compounds and chemicals in water from plastic waste can be estimated with more confidence and efforts for protecting them can be made. This information is required in properly understanding toxic effects of mixture of plastic compounds on human health.