Toxicological Effects of Naturally Occurring Endocrine Disruptors on Various Human Health Targets: A Rapid Review.

Endocrine-disrupting compounds are chemicals that alter the normal functioning of the endocrine system of living organisms. They can be natural (N-EDCs) or synthetic compounds (S-EDCs). N-EDCs can belong to different groups, such as phytoestrogens (PEs), including flavonoids, or mycotoxins originating from plants or fungi, and cyanotoxins, derived from bacteria. Humans encounter these substances in their daily lives. The aim of this rapid review (RR) is to provide a fine mapping of N-EDCs and their toxicological effects on human health in terms of various medical conditions or adverse consequences. This work is based on an extensive literature search and follows a rigorous step-by-step approach (search strategy, analysis strategy and data extraction), to select eligible papers published between 2019 and 2023 in the PubMed database, and to define a set of aspects characterizing N-EDCs and the different human target systems. Of the N-EDCs identified in this RR, flavonoids are the most representative class. Male and female reproductive systems were the targets most affected by N-EDCs, followed by the endocrine, nervous, bone and cardiovascular systems. In addition, the perinatal, pubertal and pregnancy periods were found to be particularly susceptible to natural endocrine disruptors. Considering their current daily use, more toxicological research on N-EDCs is required.

Surveys as a valid tool for assessing food safety knowledge amongst pregnant women in high-income countries: a rapid review.

Pregnancy, being a vulnerable period, is the time when woman are most motivated to change their diet and lifestyle. Ensuring food safety during this susceptible time of life is essential for avoiding the related risks. Although a wealth of recommendations and guidelines have been issued for for pregnant women, further evidence is required regarding their effectiveness in implementing the knowledge and changing behaviour on food safety topics are needed. Surveys are often used as a research tool to investigate knowledge and awareness amongst pregnant women. Our main aim is to analyse and describe the results of an ad hoc research approach developed to characterise the main features of surveys identified in the PubMed database. The three major food safety issues - microbiological, chemical and nutritional- were analysed. We identified eight main key features to provide a summary of the evidence with a transparent and reproducible methodology. Our results help summarise the knowledge on the features of for pregnant women, by focusing on high-income countries over the last five years. We observed a high level of heterogeneity and methodological variability in food safety surveys. This is a novel approach that could be used to analyse surveys utilising a robust methodology. The outcomes are useful for guiding new survey design methodology and/or the modification existing surveys. Our findings could help to fill knowledge gaps by improving the use of innovative strategies for recommendations and guidelines on food safety for pregnant women. Non-high-income countries deserve separate and more comprehensive consideration.

Essential and toxic elements in sustainable and underutilized seafood species and derived semi-industrial ready-to-eat products.

Blue whiting (Micromesistius poutassou), pouting (Trisopterus luscus) and common dab (Limanda limanda) are underutilized fish species attractive in terms of sustainability. However, there is limited information about their nutritional characteristics as well as potential presence of environmental contaminants. Specimens caught in European waters were characterised for their content of essential and toxic elements. The three species, along with common carp and blue mussels, relevant for sustainable production too, were employed as raw materials for the development of semi-industrial ready-to-eat products. Calcium, copper, iodine, iron, selenium, zinc, cadmium, lead, mercury, and nickel were determined by ICP-MS, whereas methylmercury was determined by HPLC-ICP-MS. These two techniques were also used to determine arsenic and inorganic arsenic, respectively, in blue mussel and derived products. Differences in element contents were related to the biology and ecology of the examined species. Intake of nutrients and exposure to contaminants were assessed in relation to the relevant DRVs and HBGVs, respectively. All the species were found to be valuable dietary sources of selenium. Pouting was rich in iodine and mussels were good sources of iodine and iron. These two species had comparatively higher levels of mercury and lead, respectively. However, the levels of contaminants were generally of no concern in both raw materials and products. Iodine bioaccessibility was studied in blue whiting, a species with an intermediate iodine content, and found to be 98%. Selenium:mercury molar ratios were assessed and found to be favourable. The semi-industrial products were found to be good sources of selenium and many of them provided appreciable amounts of calcium, iron, copper and zinc.

The LIFE PERSUADED project approach on phthalates and bisphenol A biomonitoring in Italian mother-child pairs linking exposure and juvenile diseases.

Phthalates and bisphenol A (BPA), plasticizers used in several products of daily life, are considered as endocrine disrupters, therefore children exposure is particularly relevant. The LIFE PERSUADED project aims to define the following: (a) the evaluation of internal levels of DEHP's metabolites and BPA in Italian children and their mothers, (b) the association of the exposure with puberty development and obesity diseases, and (c) the effects of exposure in juvenile in vivo model. The cross-sectional study has involved 2160 mother-child pairs, including males and females, children and adolescents, from urban and rural areas of North, Center, and South Italy. A structured questionnaire and a food diary are designed to evaluate the association between lifestyle variables potentially related to DEHP/BPA exposure and internal levels, through univariate and multivariate analyses. Two pilot case-control studies are carried out on idiopathic premature thelarche and precocious puberty (30 girls each group, aged 2-7 years) and idiopathic obesity (30 boys and 30 girls, aged 6-10 years), matched to healthy controls. BPA and DEHP's metabolites are analyzed in urine samples from all recruited subjects. Clinical and toxicological biomarkers are evaluated in serum of case-control subjects. Moreover, the toxicity study is carried out in a juvenile rodent model exposed to mixtures of BPA and DEHP at dose levels recorded in children population. The scientific results of LIFE PERSUADED will contribute to risk assessment of BPA and DEHP.

Primary Prevention of Congenital Anomalies: Special Focus on Environmental Chemicals and other Toxicants, Maternal Health and Health Services and Infectious Diseases.

Congenital anomalies (CA) represent an important fraction of rare diseases, due to the critical role of non-genetic factors in their pathogenesis. CA are the main group of rare diseases in which primary prevention measures will have a beneficial impact. Indeed, since 2013 the European Union has endorsed a body of evidence-based recommendations for CA primary prevention; the recommendations aim at facilitating the inclusion of primary prevention actions the National Rare Disease Plans of EU Member States and encompass different public health fields, from environment through to maternal diseases and lifestyles.The chapter overviews and discusses the assessment of main risk factors for CA, such as environmental toxicants, maternal health and lifestyles and infections, with a special attention to issues that are emerging or need more knowledge.Overall, the availability of CA registries is important for estimating the health burden of CA, identifying possible hotspots, assessing the impact of interventions and addressing further, fit-to-purpose research.The integration of relevant public health actions that are already in place (e.g., control of noxious chemicals, vaccination programmes, public health services addressing chronic maternal conditions) can increase the affordability and sustainability of CA primary prevention. In developing countries with less primary prevention in place and limited overall resources, a first recognition phase may be pivotal in order to identify priority targets. In the meanwhile, policy makers should be made aware that primary prevention of RD supports publicly endorsed societal values like the knowledge-based promotion of health, empowerment, equity and social inclusiveness.

European recommendations for primary prevention of congenital anomalies: a joined effort of EUROCAT and EUROPLAN projects to facilitate inclusion of this topic in the National Rare Disease Plans.

Congenital anomalies (CA) are the paradigm example of rare diseases liable to primary prevention actions due to the multifactorial etiology of many of them, involving a number of environmental factors together with genetic predispositions. Yet despite the preventive potential, lack of attention to an integrated preventive strategy has led to the prevalence of CA remaining relatively stable in recent decades. The 2 European projects, EUROCAT and EUROPLAN, have joined efforts to provide the first science-based and comprehensive set of recommendations for the primary prevention of CA in the European Union. The resulting EUROCAT-EUROPLAN 'Recommendations on Policies to Be Considered for the Primary Prevention of Congenital Anomalies in National Plans and Strategies on Rare Diseases' were issued in 2012 and endorsed by EUCERD (European Union Committee of Experts on Rare Diseases) in 2013. The recommendations exploit interdisciplinary expertise encompassing drugs, diet, lifestyles, maternal health status, and the environment. The recommendations include evidence-based actions aimed at reducing risk factors and at increasing protective factors and behaviors at both individual and population level. Moreover, consideration is given to topics specifically related to CA (e.g. folate status, teratogens) as well as of broad public health impact (e.g. obesity, smoking) which call for specific attention to their relevance in the pre- and periconceptional period. The recommendations, reported entirely in this paper, are a comprehensive tool to implement primary prevention into national policies on rare diseases in Europe.

Folic acid and primary prevention of birth defects.

Birth defects (BDs) are an important public health problem, due to their overall incidence, occurring in 2-3% of live births in European Union. Neural tube defects (NTDs) are among major NTDs, due to their severity and relatively high incidence; in the meanwhile NTDs are also the most effectively preventable BDs to date. In particular, an adequate folic acid (FA) intake reduces both the occurrence and the recurrence of NTDs; FA is the synthetic form of folates, naturally occurring vitamins in a number of foods, especially vegetables. The daily intake of 0.4 mg of FA should be recommended to all women of childbearing age who plan to become pregnant. The Italian Network for Primary Prevention of BDs through FA Promotion has achieved a significant improvement in FA awareness and use in the periconceptional period. Nevertheless, primary prevention of BDs needs to make further progress; the Italian National Centre for Rare Diseases participates in european sureveillance of congenital anomalies (EUROCAT) Joint Action as coordinator of activities on the effectiveness of BDs prevention. Mandatory food fortification with FA has not been introduced in any European country. The health benefits of FA in reducing the risk of NTDs are undisputed; however mechanistic and animal studies suggest a relationship between high FA intakes and increased cancer promotion, while human studies are still inconsistent and inconclusive. A Working Group organized by the European Food Safety Authority pointed out significant uncertainties about fortification safety and the need for more studies; currently, FA intake from fortified foods and supplements should not exceed 1 mg/day in adults. In conclusion, based on up-to-date scientific evidence, the Italian Network strategy pivots on periconceptional supplementation integrated with promotion of healthy eating habits, support to health education, enhancing the role of women in managing life choices about their health and pregnancy and increasing the scientific knowledge about BDs primary prevention.

A new database for food safety: EDID (Endocrine disrupting chemicals - Diet Interaction Database).

Diet is a significant source of exposure to endocrine disrupting chemicals (EDC); health risks cannot be excluded, in particular long-term effects in vulnerable Groups such as children. However, food safety assessment must also consider the effects of natural food components modulating the endocrine system. The scientific evidence on the complex interactions between EDC and food components is still limited. The new EDC-Diet Interactions Database (EDID) within the ISS EDC area (www.iss.it/inte/) aims to stimulate further research in the field of food toxicology: a database on international literature's studies, either on experimental systems and on animal population and humans, easy to consult and periodically updated. Examples of studies contained in EDID are provided concerning EDC with iodine, vitamins and phytoestrogens.