Mortality burden of cardiovascular disease attributable to ambient PM2.5 exposure in Portugal, 2011 to 2021.

BACKGROUND: Exposure to high levels of environmental air pollution causes several health outcomes and has been associated with increased mortality, premature mortality, and morbidity. Ambient exposure to PM2.5 is currently considered the leading environmental risk factor globally. A causal relationship between exposure to PM2.5 and the contribution of this exposure to cardiovascular morbidity and mortality was already demonstrated by the American Heart Association. METHODS: To estimate the burden of mortality attributable to environmental risk factors, a comparative risk assessment was performed, considering a "top-down" approach. This approach uses an existing estimate of mortality of the disease endpoint by all causes as a starting point. A population attributable fraction was calculated for the exposure to PM2.5the overall burden of IHD and stroke was multiplied by the PAF to determine the burden attributable to this risk factor. The avoidable burden was calculated using the potential impact fraction (PIF) and considering the WHO-AQG 2021 as an alternative scenario. RESULTS: Between 2011 and 2021, the ambient exposure to PM2.5 resulted in a total of 288,862.7 IHD YLL and a total of 420,432.3 stroke YLL in Portugal. This study found a decreasing trend in the mortality burden attributable to PM2.5 exposure, for both males and females and different age-groups. For different regions of Portugal, the same trend was observed in the last years. The mortality burden attributable to long-term exposure to PM2.5 was mainly concentrated in Lisbon Metropolitan Area, North and Centre. Changes in the exposure limits to the WHO recommended value of exposure (WHO-AQG 2021) have a reduction in the mortality burden due to IHD and stroke attributable to PM2.5 exposure, in Portugal. CONCLUSION: Between 2011 and 2021, approximately 22% and 23% of IHD and stroke deaths were attributable to PM2.5 exposure. Nevertheless, the mortality burden attributable to cardiovascular diseases has been decreasing in last years in Portugal. Our findings provide evidence of the impact of air pollution on human health, which are crucial for decision-making, at the national and regional level.

Burden of infectious disease studies in Europe and the United Kingdom: a review of methodological design choices.

This systematic literature review aimed to provide an overview of the characteristics and methods used in studies applying the disability-adjusted life years (DALY) concept for infectious diseases within European Union (EU)/European Economic Area (EEA)/European Free Trade Association (EFTA) countries and the United Kingdom. Electronic databases and grey literature were searched for articles reporting the assessment of DALY and its components. We considered studies in which researchers performed DALY calculations using primary epidemiological data input sources. We screened 3053 studies of which 2948 were excluded and 105 studies met our inclusion criteria. Of these studies, 22 were multi-country and 83 were single-country studies, of which 46 were from the Netherlands. Food- and water-borne diseases were the most frequently studied infectious diseases. Between 2015 and 2022, the number of burden of infectious disease studies was 1.6 times higher compared to that published between 2000 and 2014. Almost all studies (97%) estimated DALYs based on the incidence- and pathogen-based approach and without social weighting functions; however, there was less methodological consensus with regards to the disability weights and life tables that were applied. The number of burden of infectious disease studies undertaken across Europe has increased over time. Development and use of guidelines will promote performing burden of infectious disease studies and facilitate comparability of the results.

The increasing significance of disease severity in a burden of disease framework.

Recent estimates have reiterated that non-fatal causes of disease, such as low back pain, headaches and depressive disorders, are amongst the leading causes of disability-adjusted life years (DALYs). For these causes, the contribution of years lived with disability (YLD) - put simply, ill-health - is what drives DALYs, not mortality. Being able to monitor trends in YLD closely is particularly relevant for countries that sit high on the socio-demographic spectrum of development, as it contributes more than half of all DALYs. There is a paucity of data on how the population-level occurrence of disease is distributed according to severity, and as such, the majority of global and national efforts in monitoring YLD lack the ability to differentiate changes in severity across time and location. This raises uncertainties in interpreting these findings without triangulation with other relevant data sources. Our commentary aims to bring this issue to the forefront for users of burden of disease estimates, as its impact is often easily overlooked as part of the fundamental process of generating DALY estimates. Moreover, the wider health harms of the COVID-19 pandemic have underlined the likelihood of latent and delayed demand in accessing vital health and care services that will ultimately lead to exacerbated disease severity and health outcomes. This places increased importance on attempts to be able to differentiate by both the occurrence and severity of disease.

Nanomaterials in Foods and Human Digestion: An Important Layer in the Assessment of Potential Toxic Effects.

The use of nanoparticles (e.g. titanium dioxide) in commercial food products to modify some properties, such as brightness and whiteness, increased in the last years and is nowadays widespread. Despite the inhalation of nanoparticles is already a topic of concern, the potential adverse health effects due to ingestion still present gaps of knowledge. In fact, gastrointestinal tract is the first interface between the body and the external environment and consequently could represent a target organ for compounds present in food, namely nanoparticles, that could exert toxic effects. The in vitro digestion models used to simulate the human digestion may contribute to fill these gaps. The applicability of the in vitro digestion methods is discussed concerning its potential use as a tool for addressing the toxicity of ingested nanomaterials or other food contaminants, mimicking the physiological processes.

Human health risk-benefit assessment of fish and other seafood: a scoping review.

Fish and other seafood are important sources of nutrients, but they are also sources of chemical contaminants that may cause adverse health effects. This article aimed to identify existing risk-benefit assessments (RBA) of fish, shellfish, and other seafood, compare methodologies, discuss differences and commonalities in findings, and identify limitations and ways forward for future studies. We conducted a scoping review of the scientific literature of studies in all languages published from 2000 through April 2019. We identified 106 RBA of fish and other seafood across Europe, Asia, North America, Africa, and at the global level. Studies were heterogeneous in terms of types of fish and other seafood considered, beneficial and adverse compounds assessed, and overall methodology. Collected data showed that a diet consisting of a variety of lean and fatty fish and other seafood is recommended for the overall population and that women of childbearing age and children should limit the consumption of fish and other seafood types that have a high likelihood of contamination. Our review emphasizes the need for evidence-based, up-to-date, and harmonized approaches in RBA in general.

From trihalomethanes chronic daily intake through multiple exposure routes to cancer and non-cancer health risk assessment: Evidence from public Portuguese indoor swimming pools facilities using a probabilistic approach.

This study aimed to estimate chronic daily intake (CDI) and to predict the attributable lifetime cancer risk (LCR) and hazard index (HI) from concurrent exposure to four trihalomethanes (THMs; chloroform, bromodichloromethane, dibromochloromethane and bromoform), via multiple exposure routes (oral ingestion, dermal contact and inhalation), among 238 non-competitive attendees of 10 Portuguese public indoor swimming pools (SPs), using a probabilistic approach based on Monte Carlo simulations. Exposure parameters of study participants were collected via questionnaires and THMs levels in SPs water were determined according the respective normative standards. The CDI for total THMs calculated for male and female participants considering all routes was 7.52 and 8.97 mg/kg/day, respectively. SP attendees presented higher CDI through inhalation than via the other two exposure routes, and chloroform was the compound contributing the most to total THMs CDI. The risk analysis indicated that the total LCR and HI from the targeted THMs were higher than the negligible risk levels (1 × 10-6 and 1, respectively) in the scenarios examined (central tendency exposure and reasonable maximum exposure), and the health risk for females was slightly higher than for males. This study suggests that there are possible adverse health risks, thus, to protect pool attendees, adequate mitigation measures, and comprehensive regulatory guidelines on individual THMs concentrations are needed.

Risk-Benefit Assessment of Cereal-Based Foods Consumed by Portuguese Children Aged 6 to 36 Months-A Case Study under the RiskBenefit4EU Project.

Cereal-based foods, including breakfast (BC) and infant cereals (IC), are among the first solid foods introduced to infants. BC and IC are sources of macro and micronutrients that have beneficial effects on health, but can also be sources of harmful chemical and microbiological contaminants and nutrients that may lead to adverse health effects at high consumption levels. This study was performed under the RiskBenefit4EU project with the aim of assessing the health impact associated with consumption of BC and IC by Portuguese children under 35 months. Adverse effects associated with the presence of aflatoxins, Bacillus cereus, sodium and free sugars were assessed against the benefits of fiber intake. We applied a risk-benefit assessment approach, and quantified the health impact of changes in consumption of BC and IC from current to various alternative consumption scenarios. Health impact was assessed in terms of disability-adjusted life years. Results showed that moving from the current consumption scenario to considered alternative scenarios results in a gain of healthy life years. Portuguese children can benefit from exchanging intake of IC to BC, if the BC consumed has an adequate nutritional profile in terms of fiber, sodium and free sugars, with levels of aflatoxins reduced as much as possible.

Burden of osteoporosis and costs associated with human biomonitored cadmium exposure in three European countries: France, Spain and Belgium.

Cadmium (Cd) is a toxic heavy metal widespread in the environment leading to human exposure in particular through diet (when smoking is excluded), as documented by recent human biomonitoring (HBM) surveys. Exposure to Cd at environmental low-exposure levels has been associated with adverse effects such as renal toxicity and more recently bone effects. The implication, even if limited, of Cd in the etiology of osteoporosis can be of high importance at the population level given the significant prevalence of osteoporosis and the ubiquitous and life-long exposure to Cd. Therefore, the osteoporosis cases attributable to Cd exposure was estimated in three European countries (Belgium, France and Spain), based on measured urinary Cd levels from HBM studies conducted in these countries. The targeted population was women over 55 years old, for which risk levels associated with environmental Cd exposure were available. Around 23% of the cases were attributed to Cd exposure. Moreover, in a prospective simulation approach of lifelong urinary Cd concentrations assuming different intakes scenarios, future osteoporosis attributable cases were calculated, based on urinary Cd levels measured in women aged under 55. Between 6 and 34% of the considered populations under 55 years were at risk for osteoporosis. Finally, the costs associated to the burden of osteoporosis-related fractures attributable to Cd for each country targeted in this paper were assessed, standing for a major contributing role of Cd exposure in the overall social costs related to osteoporosis. Absolute costs ranged between 0.12 (low estimate in Belgium) and 2.6 billion Euros (high estimate in France) in women currently over 55 years old and at risk for fractures. Our results support the importance of reducing exposure of the general population to Cd.

Deoxynivalenol exposure assessment through a modelling approach of food intake and biomonitoring data - A contribution to the risk assessment of an enteropathogenic mycotoxin.

Deoxynivalenol (DON), an enteropathogenic mycotoxin produced by Fusarium species, is usually associated with adverse health outcomes such as gastrointestinal diseases and immunotoxicity. To estimate DON exposure of the Portuguese population at national level, a modelling approach, based on data from 94 Portuguese volunteers, was developed considering the inputs of the food consumption data generated within the National Food and Physical Activity Survey and the human biomonitoring data used to assess the exposure to DON. Ten models of association between DON urinary biomarkers and food items (pasta, cookies, biscuits, sweets, bread, rusks, nuts, oilseeds, beer, meat, milk) were established. Applying the most adequate model to the consumption data (n = 5811) of the general population, the exposure estimates of the Probable Daily Intake revealed that a fraction (0.1%) of the Portuguese population might exceed the Tolerable Daily Intake defined for DON. The analysis stratified by age revealed children (3.2%) and adolescents (6.0%) are more likely to exceed the Tolerable Daily Intake for DON. Although the unavoidable uncertainties, these results are important contributions to understand the exposure to this mycotoxin in Portugal, to assess the associated risk and the potential public health consequences.

Occupational Exposure to Mycotoxins-Different Sampling Strategies Telling a Common Story Regarding Occupational Studies Performed in Portugal (2012-2020).

In occupational settings where exposure to organic dust occurs (e.g., intensive animal production, waste management, farming and many others) workers can also be exposed to mycotoxins. However, recognizing exposure to mycotoxins in workplace environments does not happen commonly and, consequently, remains as a not identified occupational risk factor. In the last decade, work developed in different occupational settings, using different sampling approaches reported that occupational exposure to mycotoxins occurs and it's of upmost importance to be seen as an occupational concern that needs to be tackled. This paper intends to discuss the several possibilities available for assessing and characterizing the occupational exposure to mycotoxins through the description of the advantages and limitations of the different sampling strategies. Overviewing the approaches and the main achievements used in several field campaigns developed in Portugal, the knowledge obtained will be used to support the identification of the main aspects to consider when designing new occupational studies. The need for additional research work will also be discussed where new directions to follow will be debated.

Human biomonitoring in health risk assessment in Europe: Current practices and recommendations for the future.

Human biomonitoring (HBM) is an important tool to survey the internal exposure of humans which represents the real life chemical body burden to chemicals and/or their metabolites. It results from total exposure to chemical substances from different sources and via different routes. These substances may be regulated under different legislative frameworks on chemicals (e.g., environmental, occupational, food safety etc). In occupational health, HBM has long traditions to control the exposures at workplaces. By providing accurate data on internal exposure, HBM data can improve human health risk assessment (RA) for both the general population and workers. Although the past few years have shown good examples on the use of HBM in the RA of chemicals, there is still quite some work to be done to improve its use in a regulatory RA. Under the scope of the European Human Biomonitoring Initiative (project HBM4EU, 2017-2021), the current study reviews the state-of-the-art of HBM use in chemicals RA with a special focus in Europe, and attempts to identify hurdles and challenges faced by regulators. To gather information on the use of HBM, including the availability of guidance on how to use it in RA, the RA schemes applied by different European or international organizations were analysed. Examples of such use were identified for a few selected groups of chemicals of concern for human health. In addition, we present the results of a survey, aimed at collecting information from national regulatory risk assessors on their day-to-day RA practices, the use of HBM data, and the obstacles and challenges related to their use. The results evidenced and explained some of the current obstacles of using HBM data in RA. These included the lack of HBM guidance values or biomonitoring equivalents (BEs), limited toxicokinetic information to support the interpretation of HBM data and, in the occupational health and safety (OSH) field, the lack of legal enforcement. Therefore, to support the integration of HBM in regulatory RA, we recommend, on one hand, the elaboration of a EU level guidance on the use of HBM in RA and, on the other hand, the continuation of research efforts to integrate HBM with new RA approaches using in vitro/in silico data and Adverse Outcome Pathways (AOPs).

Defining the targets for the assessment of IgE-mediated allergenicity of new or modified food proteins.

Many food innovations rely on the introduction and use of new or modified proteins. New or modified food proteins may lead to major health risks due to their inherent potential to cause food allergy. Currently, the pre-market allergenicity assessment for new or modified food proteins and protein sources relies on methods for identifying allergenic hazards based on characteristics of known allergens. However, there is no general consensus on the allergenicity parameters to use and the criteria that should apply for the evaluation and decisions to be made. In this paper, we propose that the strategy for allergenicity risk assessment of new or modified food proteins and the methodologies applied should be governed by the risk management questions to be answered, reflected in the information needed by risk managers to enable their informed decision making. We generated an inventory of health outcome-related assessment parameters and criteria potentially important for risk management decision-making and we discuss the implications of selecting different optional criteria (e.g. cut-off values) for what could be accepted as safe with regards to the health outcomes in the (at risk) population. The impact of these various options on both method development and risk management practices was investigated.

Assessment of mycotoxin exposure and risk characterization using occurrence data in foods and urinary biomarkers in Brazil.

This study aimed to assess the exposure of Brazilian residents (N = 86) from rural areas to multiple mycotoxins and characterize the associated risk in two sampling periods (SP) (April-May and December/2016). Mycotoxins in food and urine samples were determined by liquid chromatography coupled to tandem mass spectrometry. Mean probable daily intake (PDI) values based on occurrence data in foods in both SP varied from 0.007 to 0.013, 0.069 to 1.002, 0.119 to 0.321 and 0.013-0.156 µg kg-1 body weight (bw) day-1 for aflatoxins (AFs), deoxynivalenol (DON), fumonisins (FBs) and zearalenone (ZEN), respectively. Mean PDI values based on urinary biomarkers were 0.001, 84.914, 0.031, 0.377 and 0.002 µg kg-1 bw day-1 for AFB1, DON, ochratoxin A (OTA), FB1 and ZEN, respectively. Hazard quotient (HQ) calculated using food data revealed a potential health concern for ZEN in 2nd SP. HQ > 1 based on urinary biomarkers were observed for DON in the two SP. Although OTA was not detected in any food sample, the HQ based on urinary OTA levels was >1 in the 1st SP. Margin of exposure values for AF from food and urine data in the 1st SP were below 10,000, indicating potential health risks.

Exposure Assessment to Mycotoxins in a Portuguese Fresh Bread Dough Company by Using a Multi-Biomarker Approach.

Mycotoxins are toxic mold metabolites that can persist in environment long after the fungi species responsible for their production disappear. Critical workplace for mycotoxins presence has already been studied and nowadays it is possible to recognize that exposure to mycotoxins through inhalation occurs due to their presence in dust. This study aimed to assess occupational co-exposure to multiple mycotoxins in a fresh bread dough company, an occupational setting not studied until now. Occupational exposure assessment to mycotoxins was done using a LC-MS/MS urinary multi-biomarker approach. Twenty-one workers and nineteen individuals that were used as controls participated in the study. Workers/controls (spot-urine) and environment (settled dust) samples were collected and analyzed. Concerning workers group, DON-GlcA, and OTA were the most prevalent biomarkers (>LOD), 66% and 90.5%, respectively. In the control group, OTA was also one of the most detected (68%) followed by CIT (58%) and DON-GlcA (58%). DON was the mycotoxin measured in high amounts in the settled dust sample (58.2 ng/g). Both workers and controls are exposed to several mycotoxins simultaneously. The workers group, due to their high contact with flour dust, revealed a higher exposure to DON. Considering these results, risk management measures must be applied including specific and adequate health surveillance programs in order to avoid exposure and consequently the associated health consequences.

Portuguese children dietary exposure to multiple mycotoxins - An overview of risk assessment under MYCOMIX project.

Mycotoxins are secondary fungi metabolites that induce acute and chronic toxic effects in humans and animals. Simultaneous contamination of cereal-based products by multiple mycotoxins has been increasingly reported, including in food products usually consumed by children. Although some previous authors assessed the health risk of children exposed to multiple mycotoxins, scarce data are available on the risk associated with the ingestion of multiple mycotoxins through different food products. MYCOMIX, a national funded project, intended to contribute to fill this gap. The present study aimed to overview the risk assessment of multiple mycotoxins performed under MYCOMIX, assessing for the first time, the risk associated with the exposure to 13 mycotoxins in breakfast cereals, infant cereals and biscuits consumed by children from Lisbon region, Portugal. Results on mycotoxins occurrence showed that 94% of samples were contaminated with at least one mycotoxin, although at levels below the legislated limits. Co-contamination was observed in 75% of the analysed samples. Estimated aflatoxins exposure suggested a potential adverse health effect for percentiles of intake above or equal to P50. The obtained results suggested that future research actions should be set in motion in order to protect children health.

Assessment of multiple mycotoxins in breakfast cereals available in the Portuguese market.

Mycotoxins are secondary metabolites of fungi that cause toxic and carcinogenic effects. Human exposure to multiple mycotoxins constitutes an increasing health concern due to potential mycotoxins combined effects. The presence of mycotoxins mixtures in foodstuffs as cereals has been reported over the last years, but few studies are available concerning its occurrence in cereals primarily marketed for children, a particular vulnerable population group. The present study aims to assess the co-occurrence of twenty-one mycotoxins and metabolites present in breakfast cereals primarily marketed for children in Portugal. Results showed that 96% of the analysed breakfast cereal samples were contaminated with several mycotoxins. Twenty-two combinations were identified including two to seven different mycotoxins. Conclusions pointed out an urgent need to review legislative limits in food matrices consumed by children and to perform a more accurate risk assessment of children's exposure to mycotoxins mixtures in food.

Patulin in fruit juices: occurrence, bioaccessibility, and risk assessment for Serbian population.

This paper reports the first study of patulin occurrence in fruit juices and risk assessment related to patulin intake by children, adolescents and adults in Serbia. During 3 consecutive years (2013-2015), 142 fruit (apple or multi-fruit) juices were collected from the market and analysed using HPLC-UV. Patulin was found in 51.4% of juices with 0.7% of the samples in excess of the legal limit of 50 µg kg-1 (mean 4.3 µg kg-1). Apple juices showed significantly higher percentage of contaminated samples (74.0% vs 27.5%), as well as higher mean patulin content (6.4 vs 2.1 µg kg-1) when compared with the multi-fruit ones. Bioaccessibility of patulin in fruit juices was studied using the standardised in vitro digestion method. A mean of 21.6% of the initial patulin amount reached the end of the intestinal phase showing a significant reduction of this toxin during the human digestion process. Risk assessment of patulin intake by Serbian children, adolescents and adults, conducted by deterministic and probabilistic approaches and including the bioaccessibility results, revealed no health concern. Although patulin alone does not represent risk, further research should consider its co-occurrence with other toxic substances in food and potential adverse effects of their mixtures.

Risk assessment of patulin intake through apple-based food by infants and preschool children in Serbia.

This study reports for the first time in Serbia the occurrence of patulin in apple-based food and the risk assessment associated with patulin intake by infants and preschool children. In total, 214 samples of infant fruit juices (48), infant purée (66), and juices for children (small package with straw, 100) were collected over 3 years (2013-15) and analysed using HPLC with ultraviolet detection. Patulin was found in 43.8% of infant juices and 16.7% of infant purée, with all values below the legal limit of 10 µg kg-1 (maximum 8.3 and 7.7 µg kg-1, respectively). The proportion of contaminated samples among fruit juices for children was 43.0%, with the highest patulin concentration at 30.2 µg kg-1, not exceeding the maximum allowed level of 50 µg kg-1. Risk assessment of patulin intake by Serbian infants and preschool children, conducted by deterministic and probabilistic approaches, revealed a hazard quotient well below 1, indicating a tolerable exposure level and no health concern.