Combined exposure to multiple mycotoxins in food: are we ready for risk assessment and risk management?

It is nowadays recognized that the risk of human co-exposure to multiple mycotoxins is real. In the last years, a number of studies have approached the issue of co-exposure and the best way to develop a more precise and realistic assessment. Likewise, the growing concern about the combined effects of mycotoxins and their potential impact on human health has been reflected by the increasing number of toxicological studies on the combined toxicity of these compounds. Nevertheless, risk assessment of these toxins, still follows the conventional paradigm of single exposure and single effects, incorporating only the possibility of additivity but not taking into account the complex dynamics associated to interactions between different mycotoxins or between mycotoxins and other food contaminants. Considering that risk assessment is intimately related to the establishment of regulatory guidelines, once the risk assessment is completed, an effort to reduce or manage the risk should be followed to protect public health. Risk assessment of combined human exposure to multiple mycotoxins thus poses several challenges to scientists, risk assessors and risk managers and opens new avenues for research. This presentation aims to give an overview of the different challenges posed by the likelihood of human co-exposure to mycotoxins and the possibility of interactive effects occurring after absorption, towards knowledge generation to support a more accurate human risk assessment and risk management. For this purpose, a physiologically-based framework that includes knowledge on the bioaccessibility, toxicokinetics and toxicodynamics of multiple toxins is proposed. Regarding exposure assessment, the need of harmonized food consumption data, availability of multianalyte methods for mycotoxin quantification, management of left-censored data and use of probabilistic models will be highlight, in order to develop a more precise and realistic exposure assessment. On the other hand, the application of predictive mathematical models to estimate mycotoxins’ combined effects from in vitro toxicity studies will be also discussed. Results from a recent Portuguese project aimed at exploring the toxic effects of mixtures of mycotoxins in infant foods and their potential health impact will be presented as a case study, illustrating the different aspects of risk assessment highlighted in this presentation. Further studies on hazard and exposure assessment of multiple mycotoxins, using harmonized approaches and methodologies, will be crucial towards an improvement in data quality and contributing to holistic risk assessment and risk management strategies for multiple mycotoxins in foodstuffs.

Manufactured Nanomaterials: is there a correlation between toxicological effects and the physicochemical properties?

Toxicological information on nanomaterials (NMs) is of major importance for safety assessment, since they are already used in many consumer products and promise cutting-edge applications in the future. While the number of different NMs increases exponentially, new strategies for risk assessment are needed to cope with the safety issues, keeping pace with innovation. However, recent studies have suggested that even subtle differences in the physicochemical properties of NMs that are closely related may define different nano-bio interactions, thereby determining their toxic potential. Further research in this field is necessary to allow straightforward grouping strategies leading time-effective risk assessment to enable the safe use of the emerging NMs. In this presentation the case study of the in vitro toxicity testing of a set of multi-walled carbon nanotubes (MWCNTs) in two human cell lines from the respiratory tract will be described. Those MWCNT have been previously characterized in detail, and differ in thickness, length, aspect ratio and morphology. This comprehensive toxicological investigation undertaken in parallel with physicochemical characterization in the cellular moiety showed that the same NM did not display a consistent effect in different cell types, and that, within the same class of NM, different toxic effects could be observed. The correlation of the cytotoxic and genotoxic effects characterized in the two cell lines with their physicochemical properties will be presented and the relevance of considering the NMs properties in the biological context will be discussed. Overall, this case study suggests that nanotoxicity of closely related MWCNTs depends not only on their primary physicochemical properties, or combinations of these properties, but also on the cellular system, and its context. Challenges posed to toxicologists, risk assessors and regulators when addressing the safety assessment of NMs will be highlighted.

Portuguese children exposure to multiple mycotoxins through food consumption: toward a holistic approach for multiple mycotoxins risk assessment

Humans can be exposed to multiple chemicals at once from a variety of sources, and human risk assessment of multiple chemicals poses several challenges to scientists, risk assessors and risk managers. Ingestion of food is considered a major route of exposure to many contaminants, namely mycotoxins, especially for vulnerable population groups, as children. A lack of sufficient data regarding mycotoxins children risk assessment, could contribute to an inaccuracy of the estimated risk. Efforts must be undertaken to develop initiatives that promote a broad overview of multiple mycotoxins risk assessment. The present work, developed within the MYCOMIX project, aims to assess the risk associated to the exposure of Portuguese children (< 3 years old) to multiple mycotoxins through consumption of foods primarily marketed for this age group. A holistic approach was developed applying deterministic and probabilistic tools to the calculation of mycotoxin daily intake values, integrating children food consumption (3-days food diary), mycotoxins occurrence (HPLC-UV, HPLC-FD, LC-MS/MS and GC-MS), bioaccessibility (standardized in vitro digestion model) and toxicological data (in vitro evaluation of cytotoxicity, genotoxicity and intestinal impact). A case study concerning Portuguese children exposure to patulin (PAT) and ochratoxin A (OTA), two mycotoxins co-occurring in processed cereal-based foods (PCBF) marketed in Portugal, was developed. Main results showed that there is low concern from a public health point of view relatively to PAT and OTA Portuguese children exposure through consumption of PCBF, considering the estimated daily intakes of these two mycotoxins (worst case scenarios, 22.930 ng/kg bw/day and 0.402 ng/kg bw/day, for PAT and OTA, respectively), their bioaccessibility and toxicology results. However, the present case study only concerns the risk associated with the consumption of PCBF and child diet include several other foods. The present work underlines the need to adopt a holistic approach for multiple mycotoxins risk assessment integrating data from exposure, bioacessibility and toxicity domains in order to contribute to a more accurate risk assessment.