Probabilistic modelling techniques in dietary exposure assessment: application on the risk assessment of cadmium for Austrian adults.

Probabilistic exposure and risk assessment of chemical hazards in the diet have increasingly gained ground in recent years as a pragmatic approach for the approximation of reality. This work presents the outcomes of a project which aimed at applying probabilistic techniques for basic modelling of chronic dietary exposure to food contaminants following EFSA guidance. These techniques, based on Monte Carlo Risk Assessment (MCRA) software and on the programming language R, were employed for the risk assessment of cadmium for Austrian adults, enabling the validation and the critical comparison of the two approaches. Harmonisation and optimisation of procedures, refinement of exposure assessment skills and confidence in the results were the main benefits. Data amount and validity were identified as critical parameters, influencing the precision of the results. Cadmium was selected as a case study due to its toxicological properties, its ubiquitous presence in food and the availability of Austrian occurrence data. Similar exposure and risk estimates were generated through MCRA and R in alternative optimistic and pessimistic exposure scenarios, suggesting low levels of concern, except for vegetarians, whose upper tail exposures are close to the established Tolerable Weekly Intake. However, as occurrence data gaps have been identified as the major element of uncertainty, the estimated exposure and risk levels are characterised as underestimated. Grains and grain-based products, potatoes and leafy vegetables are the main contributors to the intake. The results will contribute to risk management and to a future refinement of the assessment.

Toxicological approaches for the quantitative inhalation risk assessment of toxic metals from tobacco smoke: application on the deterministic and probabilistic inhalation risk assessment of cadmium for Austrian smokers.

OBJECTIVE: The objective of this study was the assessment of risks from inhalation exposure of Austrian smokers to cadmium through established toxicological approaches with emphasis on the exposure assessment component, which is challenging regarding the actual amount of metal that is inhaled and the simulation of the smoking pattern. MATERIALS AND METHODS: Exposure assessment comprised an estimation of the proportion of cadmium inhaled through smoking and actual occurrence data in tobacco products and survey smoking habits, which were integrated in alternative scenarios through a deterministic and a probabilistic Monte Carlo simulation method. Risks were characterized through the comparison of the exposure with health-based guidance values, as well as through the assessment of the excess lifetime cancer risk (ELCR), the non-cancer hazard quotient (NCHQ), and the margin of exposure (MOE). The strengths, the uncertainties, and the limitations of the different methodologies were discussed. RESULTS AND DISCUSSION: Upper exposures are close or exceed the Permitted Daily Exposure. Respiratory ELCRs are unacceptable compared to the benchmark range of 1.0E-06 to 1.0E-04. Renal and respiratory NCHQs exceed the target value of 1.0 by 3- to 17-fold. MOEs are not protective enough for cancer and non-cancer effects. The amount of cadmium that reaches the lung is a key source of uncertainty. CONCLUSION: Probabilistic estimates provide a refined capture of the actual inhalation exposure. Risk estimates and gender and age profiles are alarming, especially for young smokers. Application of toxicological approaches, combined with realistic assessment of the inhalation exposure levels, can support risk communication and management.

Probabilistic risk assessment of nitrates for Austrian adults and estimation of the magnitude of their conversion into nitrites.

Nitrates occur in food naturally, as contaminants or additives. The health implications attributed to ingested nitrates result primarily from their conversion into nitrites and subsequent methemoglobinemia, carcinogenicity induced by N-nitroso-compounds and cardiovascular, endocrine, metabolic, reproductive and developmental effects. The present study comprises a probabilistic tiered risk assessment of nitrates for Austrian adults through the diet with the application of the Monte Carlo simulation method in alternative optimistic and pessimistic scenarios. Risk estimates are of concern regarding the upper exposures, which exceed the Acceptable Daily Intake (ADI) in almost all scenarios and population groups. Exposure is elevated when all dietary sources are considered and the ADI is exceeded by already the mean intake for vegetarians. Leafy vegetables are major contributors to the intake. Contribution of cured meat is very low. Estimates of the conversion of nitrates into nitrites were used to assess the combined exposure to both species. When the average intake of nitrates and nitrites is considered, the mean exposure to nitrites is lower or close to the ADI for individuals with average conversion capacity. However, upper tail combined intake can lead to a multifold exceedance of the ADI of nitrites for individuals with both high and average conversion capacity.

Risk assessment of nitrites for the Austrian adult population with probabilistic modelling of the dietary exposure.

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.

Joint venture on the further development of chemical exposure assessment by use of probabilistic modelling.

Exposure assessment is a fundamental component of the risk assessment process and has a significant contribution to the overall uncertainty of the risk estimates. The aim of the present project, implemented within the framework of the EU-FORA Fellowship, was to develop a structured approach for probabilistic modelling of the dietary exposure to chemical contaminants, which shall be used as a refined alternative to the more conservative deterministic approach or as part of a Tier 2 assessment. The fellow received training and worked in close cooperation with the project team on three case studies of contaminants in food (cadmium, acrylamide and deoxynivalenol). The modelling of the dietary intake was based on relevant EFSA Guidance and employed the Monte Carlo simulation methodology with the use of a standard software tool (Monte Carlo Risk Assessment (MCRA) platform) and/or a tailor-made risk model in the programming language R. The strengths and the limitations of every approach were explored and discussed. The conclusion from the critical comparison of the outputs was that the former can be a tool for the generation of fast preliminary estimates of the usual dietary exposure, whereas the latter may be used by the risk assessors as a more sophisticated, 'state-of-the-art' strategy, which will lead to more realistic estimates of the exposure. The outcomes of the project are being currently incorporated in a Guidance Document on probabilistic exposure assessment, which will highly contribute to more informed risk management decisions and to more effective risk communication.