Phthalates mixtures in bottled water in Iran: human health risk assessment using direct and indirect exposure assessment

Phthalates are diesters of phthalic acid that are widely used in industry and personal care products resulting in exposure via ingestion, inhalation and dermal routes. There is an interest in the safety evaluation of phthalate exposure because these compounds are ubiquitous environmental contaminants with endocrine-disrupting properties, suspected to interfere with developmental androgen action, possibly leading to adverse effects on reproductive function. Toxicological properties of phthalates, the presence of phthalates in polyethylene terephthalate (PET) bottles as impurities, the high and regular consumption of bottled water, and the uncertainty about the impact of storage conditions of PET bottled water on migration of phthalates into the water, initiated the interest in their presence in bottled water and the accompanying risk assessment. In this study, common Iranian brands of bottled water were screened for phthalates. The effect of storage temperature on selected target chemical concentrations was investigated. A toxicological risk assessment was conducted to determine the potential health risks associated with the consumption of the bottled water. Along with indirect exposure assessment, a human biomonitoring approach was applied to facilitate better human exposure assessment of individual phthalates and their mixtures providing important information for identifying exposure sources and the contribution of intake from bottled water to the total daily intake. Chapter 1 of the thesis presents an introduction to the topic, the toxicological properties of phthalates, risk assessment strategies and the regulatory status of phthalates. Chapter 2 of the thesis describes the development of a method to extract phthalates from bottled water by applying surface-functionalized magnetic particles (MPs) as the adsorbent used in Magnetic Solid-Phase Extraction (MSPE). Based on the results obtained, it was concluded that the MSPE-GC-MS method developed provides a new method for the determination of phthalates in water samples. To extend the work to real samples chapter 3 presents the occurrence and concentrations of common phthalates (dibutyl phthalate (DBP), butyl benzyl phthalate (BBP), and diethylhexyl phthalate (DEHP) ) in PET bottled water locally produced in the Iranian market and stored under various common storage conditions. According to the results obtained, an increase in temperature and/or in the duration of storage increases phthalate migration. The highest concentrations of all phthalates were observed when bottled water samples were kept at 40 °C for 45 days. DEHP in bottled water was the most abundant phthalate under all storage conditions, although the observed level of DEHP in the worst-case scenario (40 °C for 45 days) was still much lower than the DEHP maximum concentration limit (MCL) in bottled water (MCL= 6 µg/L) set by the U.S. Food and Drug Administration (U.S. FDA). When comparing the concentrations of DBP, BBP and DEHP with initial levels in the bottled water, the results demonstrate that the release of phthalates was not substantial under all storage conditions, and especially minimal at low temperatures ( In chapter 4, concentrations of diethyl phthalate (DEP) were measured in bottled water kept under various storage conditions, similar as those used in chapter 3 for DEHP, DBP and BBP, and the resulting risks of consumption of this water for children but also for other age groups were evaluated. The results indicate that storage duration and storage temperature also influence the release of DEP from PET bottles into water. In comparison to the initial level of DEP in bottled water samples, the migration of DEP appeared not considerable under most storage conditions, especially at low temperatures ( children > lactating women > teenagers > adults > pregnant women. However, for all age groups, none of the individuals exceeds existing intake limit values for DEP. Due to the anti-androgenic activity of some phthalates, in chapter 5 the cumulative health risks in pregnant and lactating women posed by combined exposure to BBP, DBP, and DEHP via consumption of bottled water was estimated. To this end, hazard quotient (HQ) values, representing the margin between health based guidance values (EPA RfD values) and estimated exposures, and hazard index (HI) values, representing the sum of HQ values of individual phthalates, were determined. The results of the study showed that the HQ values for individual phthalate intake via bottled water consumption in pregnant and lactating women were much lower than 1, and cumulative risk assessment for combined phthalate exposure demonstrated that the HIs for anti-androgenic effects were also lower than 1 which implies that adverse effects are unlikely to occur. In chapter 6 of the thesis a systematic review method was used to investigate whether the phthalate exposure would be a factor contributing to the development of autism spectrum disorders (ASD). The results of this systematic review revealed that only a limited number of studies has addressed phthalates in relation to autism. A total of five studies met the inclusion criteria and were included in the review. Of the 5 studies, two studies were cohort studies both from the U.S.A. and three were case-control studies conducted in the U.S.A., Italy and Turkey. Because of the heterogeneity in the type of included studies, different methods of assessing exposure to phthalates and the use of different statistics for summarizing the results, a meta-analysis could not be performed to combine the results of included studies. The review showed equivocal evidence for a possible connection between exposure to phthalates and ASD. Further comprehensive research is needed with appropriate attention to exposure assessment and relevant pre and post-natal confounders. In the next step we set our goal to get better insight in the total phthalate exposure of Iranian children, and to assess the proportion of phthalate intake from bottled water to the total daily intake. This was done using biomonitoring based exposure assessment. Chapter 7 of the thesis shows the data on the levels of phthalate metabolites in the spot urine samples of children and adolescents. We applied a calculation model based on the creatinine-adjusted urinary metabolite concentrations to obtain the EDIs for DEHP, DBP and BBP. The EDI values thus obtained were compared to available health-based guidance values (RfD and TDI values based on anti-androgenic effects). Assuming additive effects, the cumulative risk for combined exposure were estimated for three phthalates based on anti-androgenicity as the critical effect. The results from the risk assessment suggest that Iranian children and adolescents are exposed to low levels of a mixture of these phthalates. Risk assessment indicates that not only the exposure to the single phthalates, but also the combined exposure would not raise a safety concern. However, people typically come into contact with several chemicals with anti-androgenic properties in addition to the investigated phthalates in this study, which may also contribute to combined anti-androgenic effects. This indicates that a risk assessment of combined exposure including other anti-androgenic chemicals would be required to determine whether combined exposure to anti-androgenic chemicals is below acceptable levels. Comparison of the exposure values obtained to those obtained based on indirect estimates in earlier chapters of the thesis, revealed that bottled water provides only a limited contribution to total daily phthalates exposure in Iran. Chapter 8 presents a discussion of the results obtained and also presents some perspectives for future research and risk management of exposure to phthalates in Iran.</p

Developing human biomonitoring as a 21st century toolbox within the European exposure science strategy 2020–2030

Human biomonitoring (HBM) is a crucial approach for exposure assessment, as emphasised in the European Commission’s Chemicals Strategy for Sustainability (CSS). HBM can help to improve chemical policies in five major key areas: (1) assessing internal and aggregate exposure in different target populations; 2) assessing exposure to chemicals across life stages; (3) assessing combined exposure to multiple chemicals (mixtures); (4) bridging regulatory silos on aggregate exposure; and (5) enhancing the effectiveness of risk management measures. In this strategy paper we propose a vision and a strategy for the use of HBM in chemical regulations and public health policy in Europe and beyond. We outline six strategic objectives and a roadmap to further strengthen HBM approaches and increase their implementation in the regulatory risk assessment of chemicals to enhance our understanding of exposure and health impacts, enabling timely and targeted policy interventions and risk management. These strategic objectives are: 1) further development of sampling strategies and sample preparation; 2) further development of chemical-analytical HBM methods; 3) improving harmonisation throughout the HBM research life cycle; 4) further development of quality control / quality assurance throughout the HBM research life cycle; 5) obtain sustained funding and reinforcement by legislation; and 6) extend target-specific communication with scientists, policymakers, citizens and other stakeholders. HBM approaches are essential in risk assessment to address scientific, regulatory and societal challenges. HBM requires full and strong support from the scientific and regulatory domain to reach its full potential in public and occupational health assessment and in regulatory decision-making

The Effect of Storage Time, Temperature and Type of Packaging on the Release of Phthalate Esters into Packed Acidic Liquids

Kisele tekućine, poput soka od nezrelog voća, limunovog soka i octa često se konzumiraju u Iranu. Različite vrste kiselih sokova pakiraju se u boce od polietilen tereftalata (PET) i polietilena velike gustoće (HDPE). Postoje dokazi koji upućuju na mogućnost otpuštanja ftalata iz PET i HDPE boca. U ovom je radu ispitan utjecaj trajanja skladištenja, temperature i vrste pakiranja na migraciju ftalata u kisele tekućine, čuvane pri različitim uvjetima, i to prije skladištenja, te nakon 2, 4 i 6 mjeseci. Određene su srednje vrijednosti koncentracije ftalata od <0.04 do 0.501 μg/L u sokovima od nezrelog voća, od <0.04 do 0.231 μg/L u limunovom soku i <0.04 do 0.586 μg/L u octu. Najveće koncentracije dietil ftalata (DEP) i dietil heksil ftalata (DEHP) izmjerene su u PET i HDPE bocama. Rezultati prije i naklon skladištenja pokazuju da su se, pri određenim uvjetima skladištenja, koncentracije DEP, DEHP i dibutil ftalata (DBP) povećale u kiselim tekućinama. Rezultati dokazuju da je moguć prijelaz estera ftalne kiseline iz plastičnih pakiranja u sadržaj spremnika.Acidic liquids such as verjuice, lemon juice and vinegar are frequently consumed in Iran. Different kinds of acidic liquids are packaged in polyethylene terephthalate (PET) and high-density polyethylene (HDPE) bottles. There is evidence indicating that phthalates can leach from PET and HDPE bottles into their contents. In this work the effect of storage time, temperature and bottle type on the migration of phthalates from packaging materials into acidic liquids is studied by analyzing the samples stored under different conditions, before storage and after 2, 4 and 6 months of storage. The determined mean phthalate concentrations in μg/L were: <0.04 to 0.501 in verjuice, <0.04 to 0.231 in lemon juice and <0.04 to 0.586 in vinegar. The highest concentrations of diethyl phthalate (DEP) and diethyl hexyl phthalate (DEHP) were found in PET and HDPE bottles, respectively. Results of analyses before and after storage indicate that under some storage conditions, the concentrations of DEP, DEHP and dibutyl phthalate (DBP) increased in acidic liquids. The possible migration of phthalic acid esters from plastic packaging materials into the contents was indicated by the results of the present study

Initial impacts of global risk mitigation measures taken during the combatting of the COVID-19 pandemic

This paper presents an analysis of risk mitigation measures taken by countries around the world facing the current COVID-19 outbreak. In light of the current pandemic the authors collated and clustered (using harmonised terminology) the risk mitigation measures taken around the globe in the combat to contain, and since March 11 2020, to limiting the spread of the SARS-CoV-2 virus known to cause the Coronavirus disease 2019 (COVID-19). This overview gathers lessons learnt, provides an update on the current knowledge for authorities, sectors and first responders on the effectiveness and may allow enhanced prevention, preparedness and response for future outbreaks. Various measures such as mobility restrictions, physical distancing, hygienic measures, socio economic restrictions, communication and international support mechanisms have been clustered and are reviewed in terms of the nature of the actions taken and their qualitative early-perceived impact. At the time of writing, it is still too premature to express the quantitative effectiveness of each risk mitigation cluster, but it seems that the best mitigation results are reported when applying a combination of voluntary and enforceable measures.JRC.E.7-Knowledge for Security and Migratio

Microbial Evaluation of Fresh, Minimally-processed Vegetables and Bagged Sprouts from Chain Supermarkets

The aim of this study was to evaluate the bacterial and fungal quality of minimally-processed vegetables (MPV) and sprouts. A total of 116 samples of fresh-cut vegetables, ready-to-eat salads, and mung bean and wheat sprouts were randomly collected and analyzed. The load of aerobic mesophilic bacteria was minimum and maximum in the fresh-cut vegetables and fresh mung bean sprouts respectively, corresponding to populations of 5.3 and 8.5 log CFU/g. E. coli O157:H7 was found to be absent in all samples; however, other E. coli strains were detected in 21 samples (18.1%), and Salmonella spp. were found in one mung bean (3.1%) and one ready-to-eat salad sample (5%). Yeasts were the predominant organisms and were found in 100% of the samples. Geotrichum, Fusarium, and Penicillium spp. were the most prevalent molds in mung sprouts while Cladosporium and Penicillium spp. were most frequently found in ready-to-eat salad samples. According to results from the present study, effective control measures should be implemented to minimize the microbiological contamination of fresh produce sold in Tehran, Iran

Associations of Perfluoroalkyl Substances with Prevalence of Metabolic Syndrome in Highly Exposed Young Adult Community Residents-A Cross-Sectional Study in Veneto Region, Italy.

BACKGROUND: Studies on the association between perfluoroalkyl substances (PFAS) and metabolic syndrome (MetS) are limited, and results are inconsistent. We aimed to examine the associations between PFAS serum levels and the prevalence of MetS among highly exposed young adults (ages 20-39) residents of a large area of the Veneto Region (North-Eastern Italy) primarily stemming from PFAS water contamination before September 2013. A total of 15,876 eligible young adult residents living in the investigated municipalities were enrolled in the study from January 2017 to July 2019. METHODS: MetS was defined by using a modified harmonized definition requiring the presence of 3 of the following: obesity (body mass index ≥30), elevated triglyceride (TG), reduced high-density lipoprotein cholesterol, elevated blood pressure, and hemoglobin A1c ≥ 6.1% or self-reported diabetes mellitus or drug treatment for hyperglycemia. Multivariable generalized additive models were performed to identify the associations between four serum PFAS, including perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA), and risk of MetS controlling for potential confounders. RESULTS: A total of 1282 participants (8.1%) met the criteria of MetS with a higher prevalence among men. PFOA, PFHxS, and PFNA were not associated with the risk of MetS, whereas PFOS showed a consistent protective effect against the risk of MetS (OR 0.76, (95% CI: 0.69, 0.85) per ln-PFOS). However, we found statistically significant positive associations between PFAS serum levels and individual components of MetS, mainly elevated blood pressure and elevated TG. CONCLUSION: Our results did not support a consistent association between PFAS and MetS and conflicting findings were observed for individual components of MetS

The association between perfluoroalkyl substances and lipid profile in exposed pregnant women in the Veneto region, Italy.

BACKGROUND: Residents of a large area of North-Eastern Italy were exposed for decades to high concentrations of perfluoroalkyl and polyfluoroalkyl substances (PFAS) via drinking water. Serum PFAS levels have been consistently associated with elevated serum lipids, but few studies have been conducted among pregnant women, and none has stratified analyses by trimester of gestation. Elevated serum lipid levels during pregnancy can have both immediate and long-lasting effects on pregnant women and the developing fetus. We evaluated the association between perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluoro-hexanesulfonate (PFHxS) levels in relation to lipid profiles in highly-exposed pregnant women. METHODS: A cross-sectional analysis was conducted in 319 pregnant women (age 14-48 years) enrolled in the Regional health surveillance program. Non-fasting blood samples were obtained in any trimester of pregnancy and analyzed for PFOA, PFOS and PFHxS, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C). Low-density lipoprotein cholesterol (LDL-C) was calculated. The associations between ln-transformed PFAS (and categorized into quartiles) and lipids were assessed using generalized additive models. Analyses were adjusted for potential confounders and stratified according to pregnancy trimester. RESULTS: The geometric means of PFOA, PFOS and PFHxS were 14.78 ng/mL, 2.67 ng/mL and 1.89 ng/mL, respectively. The plasma levels of TC, HDL-C and LDL-C increased steadily throughout the trimesters. In the 1st trimester, PFOS was positively associated with TC and PFHxS with HDL-C. In the 3rd trimester, instead, an inverse relationship was seen between PFOA and PFHxS and both TC and LDL-C. CONCLUSIONS: Results suggest the associations between PFAS concentrations and lipid profiles in pregnant women might differ by trimesters of pregnancy. In the first trimester, patterns are similar to those of non-pregnant women, while they differ late in pregnancy. Different independent behavior of PFAS and lipid levels throughout the pregnancy might explain our observations. These findings support the ubiquitous exposure to PFAS and possible influence on lipid metabolisms during pregnancy and suggest a careful evaluation of the timing of PFAS measurement, when examining effects of PFAS during pregnancy on gestational outcomes related to serum lipids amounts

Exposure modelling in Europe : how to pave the road for the future as part of the European Exposure Science Strategy 2020-2030

Exposure models are essential in almost all relevant contexts for exposure science. To address the numerous challenges and gaps that exist, exposure modelling is one of the priority areas of the European Exposure Science Strategy developed by the European Chapter of the International Society of Exposure Science (ISES Europe). A strategy was developed for the priority area of exposure modelling in Europe with four strategic objectives. These objectives are (1) improvement of models and tools, (2) development of new methodologies and support for understudied fields, (3) improvement of model use and (4) regulatory needs for modelling. In a bottom-up approach, exposure modellers from different European countries and institutions who are active in the fields of occupational, population and environmental exposure science pooled their expertise under the umbrella of the ISES Europe Working Group on exposure models. This working group assessed the state-of-the-art of exposure modelling in Europe by developing an inventory of exposure models used in Europe and reviewing the existing literature on pitfalls for exposure modelling, in order to identify crucial modelling-related strategy elements. Decisive actions were defined for ISES Europe stakeholders, including collecting available models and accompanying information in a living document curated and published by ISES Europe, as well as a long-term goal of developing a best-practices handbook. Alongside these actions, recommendations were developed and addressed to stakeholders outside of ISES Europe. Four strategic objectives were identified with an associated action plan and roadmap for the implementation of the European Exposure Science Strategy for exposure modelling. This strategic plan will foster a common understanding of modelling-related methodology, terminology and future research in Europe, and have a broader impact on strategic considerations globally.Peer reviewe

an ISES Europe statement

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FAIR environmental and health registry (FAIREHR)- supporting the science to policy interface and life science research, development and innovation

Funding Information: Most co-authors were financialy supported with their respective inistitution. Some of the co-authors were financialy supportrd by the “Safe and Efficient Chemistry by Design (SafeChem)” project (grant no. DIA 2018/11) funded by the Swedish Foundation for Strategic Environmental Research, and by the PARC project (grant no. 101057014) funded under the European Union’s Horizon Europe Research and Innovation program. Publisher Copyright: Copyright © 2023 Zare Jeddi, Galea, Viegas, Fantke, Louro, Theunis, Govarts, Denys, Fillol, Rambaud, Kolossa-Gehring, Santonen, van der Voet, Ghosh, Costa, Teixeira, Verhagen, Duca, Van Nieuwenhuyse, Jones, Sams, Sepai, Tranfo, Bakker, Palmen, van Klaveren, Scheepers, Paini, Canova, von Goetz, Katsonouri, Karakitsios, Sarigiannis, Bessems, Machera, Harrad and Hopf.The environmental impact on health is an inevitable by-product of human activity. Environmental health sciences is a multidisciplinary field addressing complex issues on how people are exposed to hazardous chemicals that can potentially affect adversely the health of present and future generations. Exposure sciences and environmental epidemiology are becoming increasingly data-driven and their efficiency and effectiveness can significantly improve by implementing the FAIR (findable, accessible, interoperable, reusable) principles for scientific data management and stewardship. This will enable data integration, interoperability and (re)use while also facilitating the use of new and powerful analytical tools such as artificial intelligence and machine learning in the benefit of public health policy, and research, development and innovation (RDI). Early research planning is critical to ensuring data is FAIR at the outset. This entails a well-informed and planned strategy concerning the identification of appropriate data and metadata to be gathered, along with established procedures for their collection, documentation, and management. Furthermore, suitable approaches must be implemented to evaluate and ensure the quality of the data. Therefore, the ‘Europe Regional Chapter of the International Society of Exposure Science’ (ISES Europe) human biomonitoring working group (ISES Europe HBM WG) proposes the development of a FAIR Environment and health registry (FAIREHR) (hereafter FAIREHR). FAIR Environment and health registry offers preregistration of studies on exposure sciences and environmental epidemiology using HBM (as a starting point) across all areas of environmental and occupational health globally. The registry is proposed to receive a dedicated web-based interface, to be electronically searchable and to be available to all relevant data providers, users and stakeholders. Planned Human biomonitoring studies would ideally be registered before formal recruitment of study participants. The resulting FAIREHR would contain public records of metadata such as study design, data management, an audit trail of major changes to planned methods, details of when the study will be completed, and links to resulting publications and data repositories when provided by the authors. The FAIREHR would function as an integrated platform designed to cater to the needs of scientists, companies, publishers, and policymakers by providing user-friendly features. The implementation of FAIREHR is expected to yield significant benefits in terms of enabling more effective utilization of human biomonitoring (HBM) data.publishersversionpublishe