Identification of a Potential Food Additive Mixture and Health Risk Assessment Using the Modified Reference Point Index (mRPI)

Food additives (FAs) are intended to be used to improve the quality of food. Within the European Union, more than 300 FAs are currently authorized. Due to their intensive use, humans consume several different FAs daily. The amount and consumption of FAs themselves are influenced by their individual consumption patterns and brand loyalty. Although humans ingest mixtures of several FAs, the substances are still assessed on an individual basis. This study investigated potential cumulative health risks from FA mixtures using currently available toxicological, occurrence and food-consumption data. Forty-two relevant FAs and food additive groups were selected, as their estimated intake exceeded 50% of their corresponding acceptable daily intake (ADI) and they are authorized in relevant food categories. Toxicological data were screened for FAs, and their endpoints for liver, kidney, gastrointestinal, developmental toxicity, reproductive toxicity and hematotoxicity were identified. Based on the availability of toxicological and analytical data, a mixture of 18 FAs was considered. A potential health concern was identified for kidney toxicity (mRPI: 1.8–10.8, refined mRPI: 0.3–1.6) and developmental toxicity (mRPI: 13.6–56.1, refined mRPI: 0.9–3.1). The main risk drivers were steviol glycosides (E 960 a–d), contributing to 40% of nephrotoxicity risks and 18% of developmental toxicity risks, and glutamic acid—glutamates (E 620–625), contributing to 40% of developmental toxicity risks. The study demonstrates the applicability of the mRPI as a screening and prioritization tool for FA mixtures and highlights the need for improved occurrence and co-exposure data.