This study uniquely describes all steps of the risk assessment process for the use of one specific nanomaterial (nanosilica) in food products. The aim was to identify gaps in essential knowledge and the difficulties and uncertainties associated with each of these steps. Several food products with added silica (E551) were analyzed for the presence, particle size and concentration of nanosilica particles, using experimental analytical data, and the intake of nanosilica via food was estimated. As no information is available on the absorption of nanosilica from the gastrointestinal tract, two scenarios for risk assessment were considered. The first scenario assumes that the silica is absorbed as dissolved silica, while the second scenario assumes that nanosilica particles themselves are absorbed from the gastrointestinal tract. For the first scenario no adverse effects are expected to occur. For the second scenario there are too many uncertainties to allow proper risk assessment. Therefore, it is recommended to prioritize research on how nanosilica is absorbed from the gastrointestinal tract.

Introduction: Increased use of nanomaterials has raised concerns about the potential for undesirable human health and environmental effects. Releases into the air may occur and, therefore, the inhalation route is of specific interest. Here we tested copper oxide nanoparticles (CuO NPs) after repeated inhalation as hazard data for this material and exposure route is currently lacking for risk assessment. Methods: Rats were exposed nose-only to a single exposure concentration and by varying the exposure time, different dose levels were obtained (C × T protocol). The dose is expressed as 6 h-concentration equivalents of 0, 0.6, 2.4, 3.3, 6.3, and 13.2 mg/m3 CuO NPs, with a primary particle size of 10 9.2–14 nm and an MMAD of 1.5 μm. Results: Twenty-four hours after a 5-d exposure, dose-dependent lung inflammation and cytotoxicity were observed. Histopathological examinations indicated alveolitis, bronchiolitis, vacuolation of the respiratory epithelium, and emphysema in the lung starting at 2.4 mg/m3. After a recovery period of 22 d, limited inflammation was still observed, but only at the highest dose of 13.2 mg/m3. The olfactory epithelium in the nose degenerated 24 h after exposure to 6.3 and 13.2 mg/m3, but this was restored after 22 d. No histopathological changes were detected in the brain, olfactory bulb, spleen, kidney and liver. Conclusion: A 5-d, 6-h/day exposure equivalent to an aerosol of agglomerated CuO NPs resulted in a dose-dependent toxicity in rats, which almost completely resolved during a 3-week post-exposure period.

Per‐ and polyfluoroalkyl substances (PFAS) often occur together as contamination in exposure media such as drinking water or food. The relative potency factor (RPF) methodology facilitates the risk assessment of mixture exposure. A database of liver endpoints was established for 16 PFAS, using data with the same species (rat), sex (male), and exposure route (oral) and comparable exposure duration (42–90 d). Dose–response analysis was applied to derive the relative potencies of 3 perfluoroalkyl sulfonic acids (perfluorobutane sulfonic acid, perfluorohexane sulfonic acid, perfluorooctane sulfonic acid), 8 perfluoroalkyl carboxylic acids (perfluorobutanoic acid, perfluorohexanoic acid, perfluorononanoic acid, perfluoroundecanoic acid, perfluorododecanoic acid, perfluorotetradecanoic acid, perfluorohexadecanoic acid, perfluorooctadecanoic acid), 2 perfluoroalkyl ether carboxylic acids (tetrafluoro‐2‐[heptafluoropropoxy]propanoic acid, 3H‐perfluoro‐3‐[(3‐methoxy‐propoxy)propanoic acid]), and 2 fluorotelomer alcohols (6:2 FTOH, 8:2 FTOH) compared to perfluorooctanoic acid (PFOA), based on liver effects. In addition, the RPFs of 7 other perfluoroalkyl acids were estimated based on read‐across. This resulted in the relative potencies of 22 PFAS compared to the potency of index compound PFOA. The obtained RPFs can be applied to measured PFAS quantities, resulting in the sum of PFOA equivalents in a mixture. This sum can be compared with an established PFOA concentration limit (e.g., in drinking water or food) or an external health‐based guidance value (e.g., tolerable daily intake, acceptable daily intake, or reference dose) to estimate the risk resulting from direct oral exposure to mixtures. Assessing mixture exposure is particularly relevant for PFAS, with omnipresent exposure in our daily lives. Environ Toxicol Chem 2021;40:859–870. © 2020 SETAC

In this project, the evidence for the non-monotonic dose-response (NMDR) hypothesis was evaluated by critically reviewing the scientific peer-reviewed literature in the last decade (from 2002 onwards) for substances in the area of food safety. The project was performed according to the systematic review methodology. After a detailed analysis of previous reports published on the issue of NMDRs, a literature search was performed to identify in vivo, in vitro and epidemiological/human studies containing evidence for potential NMDRs. Inclusion and reliability criteria were defined and used to select relevant and reliable studies. Of studies with at least 5 dose groups, dose-response datasets were extracted and analysed by PROAST software package. The resulting dose-response results were evaluated for possible evidence of NMDR by applying six checkpoints. These checkpoints addressed both random and non-random errors. The plausibility of NMDRs was assessed based on the number of fulfilled checkpoints. In total, 202 in vivo datasets (from 49 studies), 311 in vitro datasets (from 91 studies) and 9 epidemiological/human datasets (from 2 studies) were identified. Among them, 179 in vivo and 13 in vitro dose-response datasets were analysed and evaluated using the checkpoints. For 23 in vivo datasets there were data limitations, which made the data unsuitable for dose-response analysis. For the in vitro studies, only continuous dose-response datasets presented in tables were analysed. None of the datasets from epidemiological/human studies could be analysed (one of the epidemiological studies was not analysed due to quantal data and the other due to data limitations).In most of the in vivo datasets, the apparent NMDR might have been caused by a single outlying dose group. In total, only 10 out of the 179 in vivo datasets fulfilled all six checkpoints. The latter datasets included studies on the substances quercetin, resveratrol, alpha-benzene hexachloride, and methylmercury. Review of NMDR of substances for HRA ContributorsAGES: Boehm T., Coja T., Hrdina-Zoedl B., Pacher-Zavisin M., Steinparzer R.ANSES: Charles S., Gouze M.E., Guillou P., Lehegarat L., Manière I., Ormsby J.N., Papadopoulos A., Printemps N., Roudot A.C.RIVM: Smeet E. Acknowledgements:RIVM: Ossendorp B., Vermeire T.IMM: Gornitzki C., Moberg K., Karolinska Institutet University Library Reproduction is authorised provided the source is acknowledged.Permission to reproduce the images must be sought directly from the copyright holder SummaryThe overall objective of this project was to evaluate the evidence for the non-monotonic doseresponse (NMDR) hypothesis by critically reviewing the scientific peer-reviewed literature in the last decade (from 2002 onwards) for substances (other than essential nutrients) in the area of food safety. MethodologyThe project was based on a systematic review including the steps of Preparing the review (review protocol, review question and criteria for study eligibility), Searching for research studies, Selecting the stu...

Background Chemical exposures have been associated with a variety of health effects; however, little is known about the global disease burden from foodborne chemicals. Food can be a major pathway for the general population’s exposure to chemicals, and for some chemicals, it accounts for almost 100% of exposure.  Methods and Findings Groups of foodborne chemicals, both natural and anthropogenic, were evaluated for their ability to contribute to the burden of disease.  The results of the analyses on four chemicals are presented here - cyanide in cassava, peanut allergen, aflatoxin, and dioxin.  Systematic reviews of the literature were conducted to develop age- and sex-specific disease incidence and mortality estimates due to these chemicals.  From these estimates, the numbers of cases, deaths and disability adjusted life years (DALYs) were calculated.  For these four chemicals combined, the total number of illnesses, deaths, and DALYs in 2010 is estimated to be 339,000 (95% uncertainty interval [UI]: 186,000-1,239,000); 20,000 (95% UI: 8,000-52,000); and 1,012,000 (95% UI: 562,000-2,822,000), respectively.  Both cyanide in cassava and aflatoxin are associated with diseases with high case-fatality ratios.  Virtually all human exposure to these four chemicals is through the food supply.  Conclusion Chemicals in the food supply, as evidenced by the results for only four chemicals, can have a significant impact on the global burden of disease. The case-fatality rates for these four chemicals range from low (e.g., peanut allergen) to extremely high (aflatoxin and liver cancer).  The effects associated with these four chemicals are neurologic (cyanide in cassava), cancer (aflatoxin), allergic response (peanut allergen), endocrine (dioxin), and reproductive (dioxin).