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Through our daily diet, we are exposed to a variety of food contaminants. Yet, assessing the cumulative health risk of chemical mixtures remains a challenge. Using a recently developed method, the modified Reference Point Index (mRPI), the cumulative risks posed by contaminant mixtures were assessed for their effects on reproduction and development. Since these effects can be quite diverse, a tiered approach was adopted to elucidate the risks at a more detailed level based on specific toxicological endpoints. An additional analysis was performed using the modified Maximum Cumulative Ratio (mMCR), which provides the determination of risk-dominating substances in the mixture. Our method represents a novel useful tool to screen and prioritise contaminant mixtures regarding their potential health risks. We found, that in the majority of the calculated scenarios a single substance dominates the cumulative risks. Lead was found to be the primary factor for adverse effects on reproduction and neuronal development of children. Perchlorate was identified as the most prominent risk factor for child development in generalCumulative risks of trichothecenes were dominated by deoxynivalenol. Concerning the impact on pre- and neonatal development, the co-exposure of several substances resulted in increased risks, with none of the considered contaminants dominating substantially.

Nitrites are present in the food chain as naturally occurring species or contaminants. Additionally, sodium and potassium nitrites are authorised food additives. Nitrites exert acute toxicity through methemoglobinemia or cardiovascular effects, chronic toxicity associated with endocrine, reproductive and developmental effects and have been classified as probable gastric carcinogens. Ingestion of food and water are the main sources of human exposure. This study comprises a tiered risk assessment of nitrites for the Austrian adult population, along with the identification of the food categories most contributing to their intake. The dietary exposure, based on Austrian occurrence and consumption data, was modelled with the Monte Carlo simulation method. In an additional scenario, data gaps were addressed with the usage of occurrence data published by the European Food Safety Authority and from the available literature to account for the exposure from all sources. Risk estimates regarding only the exposure to nitrite additives and to contaminated water indicate low level of concern. However, when exposure from all sources is considered, the estimated exposure is elevated and exceeds the Acceptable Daily Intake for high consumers. Mean exposure attributed to the use of nitrites as additives accounts for only a very small proportion of the total intake.

Risk assessment of chemical mixtures remains a challenging task in all areas of food and consumer safety. So far, no general method has been developed that is best suited to several subject areas (e.g. food contaminants, additives and supplements, plant protection products). Especially for mixtures of food contaminants sophisticated methods are typically not applicable due to a general lack of complete toxicological data sets. We developed a new approach, the modified Reference Point Index (mRPI), that combines the advantages of the Hazard Index and the Reference Point Index. Furthermore, we developed a decision tree for the determination of specific uncertainty factors that makes the mRPI an easy to use method for cumulative risk assessment even in a data poor field such as food contaminants. To further characterise the estimated cumulative risks, the Maximum Cumulative Ratio (MCR) was adapted to be applied on the mRPI, and the modified Maximum Cumulative Ratio (mMCR) was established to identify whether the risks are dominated by a single substance. We present two case studies assessing the nephrotoxic and neurotoxic risks for the Austrian population originating from food contaminant mixtures. Calculations could not rule out potential cumulative risks, yet, they seemed to be dominated by single substances.

After heart transplantation (HTx), endomyocardial biopsy (EMB) is currently the standard method to diagnose acute graft rejection. A non-invasive marker of rejection would be desirable as an alternative or to permit more selective use of the costly and invasive EMB.In this retrospective study, outcomes of routinely taken EMBs were used to select 28 patients after HTx EMB Grade 0R (8 patients), 1R (9 patients) or 2R (11 patients). For these patients, myeloperoxidase (MPO) and carbonyl proteins (CP) in serum were measured using enzyme-linked immunoassay (ELISA).MPO and CP levels in post-HTx patients with Grade 2R rejection were significantly (MPO: p0.01; CP: p0.001) elevated at the time of rejection compared with levels 1 month earlier. MPO and CP levels predicted Grade 2R rejection and the best cut-off point was 237.5 μg/l for MPO and 222.5 pmol/mg for CP, respectively. Clinically most important was the marked increase (doubling of basic values within 1 month) of MPO and CP levels in cases of Grade 2R rejection in post-HTx patients.MPO and CP seem to be appropriate parameters to monitor rejection events non-invasively and to minimize the application of EMBs after HTx.