An integrative risk assessment approach for persistent chemicals: A case study on dioxins, furans and dioxin-like PCBs in France

a b s t r a c t For persistent chemicals slowly eliminated from the body, the accumulated concentration (body burden), rather than the daily exposure, is considered the proper starting point for the risk assessment. This work introduces an integrative approach for persistent chemical risk assessment by means of a dynamic body burden approach. To reach this goal a Kinetic Dietary Exposure Model (KDEM) was extended with the long term time trend in the exposure (historic exposure) and the comparison of bioaccumulation with body burden references for toxicity. The usefulness of the model was illustrated on the dietary exposure to PolyChlorinatedDibenzo-p-Dioxins (PCDDs), PolyChlorinatedDibenzoFurans (PCDFs) and PolyChlorinated Biphenyls (PCBs) in France. Firstly the dietary exposure to these compounds was determined in 2009 and combined with its long term time trend. In order to take differences between the kinetics of PCDD/F and dl-PCBs into account, three groups of congeners were considered i.e. PCDD/Fs, PCB 126 and remaining dl-PCBs. The body burden was compared with reference body burdens corresponding to reproductive, hepatic and thyroid toxicity. In the case of thyroid toxicity this comparison indicated that in 2009 the probability of the body burden to exceed its reference ranged from 2.8% (95% CI: 1.5-4.9%) up to 3.9% (95% CI: 2.7-7.1%) (18-29 vs. 60-79 year olds). Notwithstanding the decreasing long-term time trend of the dietary dioxin exposure in France, this probability still is expected to be 1.5% (95% CI: 0.3-2.5%) in 2030 in 60-79 olds. In the case of reproductive toxicity the probability of the 2009 body burden to exceed its reference ranged from 3.1% (95% CI: 1.4-5.0%) (18-29 year olds) to 3.5% (95% CI: 2.2-5.2%) (30-44 year olds). In 2030 this probability is negligible in 18-29 year olds, however small though significant in 30-44 year olds (0.7%, 95% CI: 0-1.6%). In the case of hepatic toxicity the probability in 2009 even in 60-79 year olds already was negligible. In conclusion this approach indicates that in France dioxin levels in food form a declining, though still present, future health risk with respect to thyroid and reproductive toxicity

Deliverable 6.1 - Demonstration prototype of the EuroMix model toolbox

This document describes in short the new features in a demonstration prototype of the EuroMix toolbox, developed as MCRA 8.2. An important aim of the EuroMix project is to develop and implement a web-based platform (the EuroMix toolbox) including data and models accessible to all key-actors in risk assessment and risk management. In the EuroMix project the development of a mixture selection module based on exposure was prioritised, because the choice of chemicals for the experiments depended on this. A mixture selection module was therefore developed, based on a method called sparse non-negative matrix under-approximation (SNMU). The mixture selection module was then applied to French and Dutch data, leading to a list of suggested chemicals for each adverse outcome pathway in the project

A case study of neurodevelopmental risks from combined exposures to lead, methyl-mercury, inorganic arsenic, polychlorinated biphenyls, polybrominated diphenyl ethers and fluoride

We performed a mixture risk assessment (MRA) case study of dietary exposure to the food contaminants lead, methylmercury, inorganic arsenic (iAs), fluoride, non-dioxin-like polychlorinated biphenyls (NDL-PCBs) and polybrominated diphenyl ethers (PBDEs), all substances associated with declines in cognitive abilities measured as IQ loss. Most of these chemicals are frequently measured in human biomonitoring studies. A component-based, personalised modified reference point index (mRPI) approach, in which we expressed the exposures and potencies of our chosen substances as lead equivalent values, was applied to perform a MRA for dietary exposures. We conducted the assessment for four different age groups (toddlers, children, adolescents, and women aged 18–45 years) in nine European countries. Populations in all countries considered exceeded combined tolerable levels at median exposure levels. NDL-PCBs in fish, other seafood and dairy, lead in grains and fruits, methylmercury in fish and other seafoods, and fluoride in water contributed most to the combined exposure. We identified uncertainties for the likelihood of co-exposure, assessment group membership, endpoint-specific reference values (ESRVs) based on epidemiological (lead, methylmercury, iAs, fluoride and NDL-PCBs) and animal data (PBDE), and exposure data. Those uncertainties lead to a complex pattern of under- and overestimations, which would require probabilistic modelling based on expert knowledge elicitation for integration of the identified uncertainties into an overall uncertainty estimate. In addition, the identified uncertainties could be used to refine future MRA for cognitive decline.European Union’s Horizon 2020 research and innovation programme under grant agreement number 874583—the Advancing Tools for Human Early Lifecourse Exposome Research and Translation (ATHLETE) project. The author Mousumi Chatterjee is grateful for a Daphne Jackson Trust (UK) fellowship. The authors would like to thank EFSA providing the food consumption databases, data owners for giving permission to use the data, and Gerda van Donkersgoed and Matthijs Sam (RIVM) for organising the food consumption data and chemical concentration data

The MCRA toolbox of models and data to support chemical mixture risk assessment

A model and data toolbox is presented to assess risks from combined exposure to multiple chemicals using probabilistic methods. The Monte Carlo Risk Assessment (MCRA) toolbox, also known as the EuroMix toolbox, has more than 40 modules addressing all areas of risk assessment, and includes a data repository with data collected in the EuroMix project. This paper gives an introduction to the toolbox and illustrates its use with examples from the EuroMix project. The toolbox can be used for hazard identification, hazard characterisation, exposure assessment and risk characterisation. Examples for hazard identification are selection of substances relevant for a specific adverse outcome based on adverse outcome pathways and QSAR models. Examples for hazard characterisation are calculation of benchmark doses and relative potency factors with uncertainty from dose response data, and use of kinetic models to perform in vitro to in vivo extrapolation. Examples for exposure assessment are assessing cumulative exposure at external or internal level, where the latter option is needed when dietary and non-dietary routes have to be aggregated. Finally, risk characterisation is illustrated by calculation and display of the margin of exposure for single substances and for the cumulation, including uncertainties derived from exposure and hazard characterisation estimates.</p

A plausibility database summarizing the level of evidence regarding the hazards induced by the exposome on children health

Supplementary data are available online at: https://www.sciencedirect.com/science/article/pii/S143846392300202X#appsec1 .Copyright © 2023 The Authors. Childhood diseases correspond to major public health issues. A large number of studies using different approaches provide evidence regarding effects of environmental exposures, encompassed in the exposome, on children's health. We aimed to summarize the overall level of evidence (LoE) from all streams of evidence regarding exposome effects on child health. For 88 selected chemical and urban factors, we retrieved the conclusions of agency reports or literature reviews published between 2015 and 2021 regarding effects on child health, including cardiovascular, metabolic, neurodevelopmental, respiratory and other health outcomes. Adapted versions of PRISMA flowchart and AMSTAR-2 tool were used to select and assess the quality of the systematic reviews retrieved from PubMed and SCOPUS databases. For each factor-outcome pair, conclusions in three streams of evidence (epidemiological, toxicological and mechanistic, the latter corresponding to in vitro and in silico approaches) were translated into stream-specific LoEs and then combined into an overall LoE ranging from “very unlikely” to “very likely”. The 88 environmental factors were implied in 611 factor-outcome pairs. Forty-four pairs (7%), corresponding to 16 factors, had a very likely overall LoE (≥80%); 127 pairs (21%), corresponding to 49 factors, had a likely or more overall LoE (≥60%). For 81 pairs (13%), no evidence was available in agency reports or published reviews, while for 275 pairs (45%), corresponding to 68 factors, the overall LoE was very unlikely (<20%). Exposure factors with the greatest number of associated health outcomes with a high overall LoE were HCB, PCBs, temperature (8 outcomes), PFOA (7 outcomes), PFOS, cotinine (6 outcomes), arsenic, lead (5 outcomes), bisphenols A and S, PFNA and PM2.5 (4 outcomes), DDT, DDE and DDD, PFHxA, PFDA, green space, UV radiation (3 outcomes). We developed an approach to extract and summarize the existing evidence about effects of environmental factors on health. The plausibility database built for children's health can be used to identify research gaps, conduct quantitative risk assessment studies. It could be expanded to consider a larger fraction of the exposome and other age groups and should be updated on a regular basis.The ATHLETE project was funded by The European Commission, through its Horizon 2020 Framework Program for Research and Innovation (grant agreement 874583). This work was also supported by HERA (Integrating Environment and Health Research: a Vision for the EU) Horizon 2020 project (grant agreement 825417). We acknowledge support from the grant CEX 2018-000806-S funded by MCIN/AEI/10.13039/501100011033, and support from the Generalitat de Catalunya through the CERCA Program

Identification and pathogenicity of Alternaria species associated with leaf blotch disease and premature defoliation in French apple orchards

Leaf blotch caused by Alternaria spp. is a common disease in apple-producing regions. The disease is usually associated with one phylogenetic species and one species complex, Alternaria alternata and the Alternaria arborescens species complex (A. arborescens SC), respectively. Both taxa may include the Alternaria apple pathotype, a quarantine or regulated pathogen in several countries. The apple pathotype is characterized by the production of a host-selective toxin (HST) which is involved in pathogenicity towards the apple. A cluster of genes located on conditionally dispensable chromosomes (CDCs) is involved in the production of this HST (namely AMT in the case of the apple pathotype). Since 2016, leaf blotch and premature tree defoliation attributed to Alternaria spp. have been observed in apple-producing regions of central and south-eastern France. Our study aimed to identify the Alternaria species involved in apple tree defoliation and assess the presence of the apple pathotype in French orchards. From 2016 to 2018, 166 isolates were collected and identified by multi-locus sequence typing (MLST). This analysis revealed that all these French isolates belonged to either the A. arborescens SC or A. alternata. Specific PCR detection targeting three genes located on the CDC did not indicate the presence of the apple pathotype in France. Pathogenicity was assessed under laboratory conditions on detached leaves of Golden Delicious and Gala apple cultivars for a representative subset of 28 Alternaria isolates. All the tested isolates were pathogenic on detached leaves of cultivars Golden Delicious and Gala, but no differences were observed between the pathogenicity levels of A. arborescens SC and A. alternata. However, the results of our pathogenicity test suggest that cultivar Golden Delicious is more susceptible than Gala to Alternaria leaf blotch. Implications in the detection of the Alternaria apple pathotype and the taxonomic assignment of Alternaria isolates involved in Alternaria leaf blotch are discussed

International Frameworks Dealing with Human Risk Assessment of Combined Exposure to Multiple Chemicals

The development of harmonised terminology and frameworks for the human risk assessment of combined exposure to multiple chemicals (“chemical mixtures”) is an important area for EFSA and a number of activities have already been undertaken, i.e. in the fields of pesticides and contaminants. The first step prior to a risk assessment of combined exposure to multiple chemicals is problem formulation defining the relevant exposure, hazard and population to be considered. In practice, risk assessment of multiple chemicals is conducted using a tiered approach for exposure assessment, hazard assessment and risk characterisation. Higher tiers require increasing knowledge about the group of chemicals under assessment and the tiers can range from tier 0 (default values, data poor situation) to tier 3 (full probabilistic models). This scientific report reviews the terminology, methodologies and frameworks developed by national and international agencies for the human risk assessment of combined exposure to multiple chemicals and provides recommendations for future activities at EFSA in this area

Guidance on the Use of Probabilistic Methodology for Modelling Dietary Exposure to Pesticide Residues

No abstract availabl