Exposure to perfluoroalkyl substances (PFAS) and association with thyroid hormones in adolescent males

Background: Perfluoroalkyl substances (PFAS) are found in a wide range of consumer products. Exposure to PFAS in children and adolescents may be associated with alterations in thyroid hormones, which have critical roles in brain function. Objective: This study investigated the association between plasma concentrations of PFAS and serum levels of total triiodothyronine (T3), free thyroxine (T4), and thyroid-stimulating hormone (TSH) in adolescent males. Methods: In 2017–2019, 151 boys from the Environment and Childhood (INMA)-Granada birth cohort, Spain, participated in a clinical follow up visit at the age of 15–17 years. Plasma concentrations of ten PFAS (PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFDoDA, PFTrDA, PFOS, and PFHxS) and serum thyroid hormones were measured in 129 of these boys. Linear regression analysis was performed to determine associations of individual PFAS with total T3, free T4, TSH, and free T4/TSH ratio, and quantile g-computation models were performed to assess the mixture effect. Additional models considered iodine status as effect modifier. Results: PFOS was the most abundant PFAS in plasma (median = 2.22 μg/L), followed by PFOA (median = 1.00 μg/L), PFNA (median = 0.41 μg/L), and PFHxS (median = 0.40 μg/L). When adjusted by confounders (including age, maternal schooling, and fish intake), PFOA and PFUnDA were associated with an increase in free T4 (β [95% CI] = 0.72 [0.06; 1.38] and 0.36 [0.04; 0.68] pmol/L, respectively, per two-fold increase in plasma concentrations), with no change in TSH. PFOS, the sum of PFOA, PFNA, PFOS, and PFHxS, and the sum of long-chain PFAS were marginally associated with increases in free T4. Associations with higher free T4 and/or total T3 were seen for several PFAS in boys with lower iodine intake (<108 μ/day) alone. Moreover, the PFAS mixture was association with an increase in free T4 levels in boys with lower iodine intake (% change [95% CI] = 6.47 [–0.69; 14.11] per each quartile increase in the mixture concentration). Conclusions: Exposure to PFAS, considered individually or as a mixture, was associated with an increase in free T4 levels in boys with lower iodine intake. However, given the small sample size, the extent of these alterations remains uncertainSpanish Consortium for Research on Epidemiology and Public Health (CIBERESP)Instituto de Salud Carlos III (ISCIII) (grant no. CP16/00085

Association of exposure to perfluoroalkyl substances (PFAS) and phthalates with thyroid hormones in adolescents from HBM4EU aligned studies

Background: Perfluoroalkyl substances (PFAS) and phthalates are synthetic chemicals widely used in various types of consumer products. There is epidemiological and experimental evidence that PFAS and phthalates may alter thyroid hormone levels; however, studies in children and adolescents are limited. Aim: To investigate the association of exposure to PFAS and phthalate with serum levels of thyroid hormones in European adolescents. Methods: A cross-sectional study was conducted in 406 female and 327 male adolescents (14–17 years) from Belgium, Slovakia, and Spain participating in the Aligned Studies of the HBM4EU Project (FLEHS IV, PCB cohort, and BEA, respectively). Concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), free thyroxine (FT4), free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH) were measured in sera from study participants, and urinary metabolites of six phthalates (DEP, DiBP, DnBP, BBzP, DEHP, and DiNP) and the non-phthalate plasticizer DINCH® were quantified in spot urine samples. Associations were assessed with linear regression and g-computational models for mixtures. Effect modification by sex was examined. Results: In females, serum PFOA and the PFAS mixture concentrations were associated with lower FT4 and higher FT3 levels; MEP and the sums of DEHP, DiNP, and DINCH® metabolites ( ∑DEHP, ∑DiNP, and ∑DINCH) were associated with higher FT4; ∑DEHP with lower FT3; and the phthalate/DINCH® metabolite mixture with higher FT4 and lower FT3. In males, PFOA was associated with lower FT4 and the PFAS mixture with higher TSH levels and lower FT4/TSH ratio; MEP and ∑DiNP were associated with higher FT4; and MBzP, ∑DEHP, and the phthalate/DINCH® metabolite mixture with lower TSH and higher FT4/TSH. PFOA, mono-(2-ethyl-5-hydroxyhexyl) phthalate (OH-MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (oxo-MEHP), and monocarboxyoctyl phthalate (MCOP) made the greatest contribution to the mixture effect. Conclusions: Results suggest that exposure to PFAS and phthalates is associated with sex-specific differences in thyroid hormone levels in adolescent

Childhood and adolescent exposure to chemicals found in personal care products

Contexte : Les produits de soins personnels contiennent plusieurs substances chimiques dont l'exposition est préoccupante pour les jeunes vu leur plus grande susceptibilité aux expositions chimiques. Aucune revue publiée n’a étudié l'exposition des jeunes aux substances chimiques dans ces produits. Objectif : Cette revue de la portée vise à synthétiser des études de biosurveillance décrivant les concentrations de parabènes, phénols, phtalates et substances per- et polyfluoroalkylées (PFAS) après l'utilisation de produits de soins personnels chez les jeunes âgés de 5 à 19 ans. Méthodes : La recherche a été effectuée dans MEDLINE, Embase et Global Health. L’éligibilité des articles a été évaluée. Les résultats des études éligibles ont été résumées et décrites. Résultats : Trente-sept études ont été incluses, la première étant publiée en 2013. La majorité des études étaient transversales (n=35) et incluaient plus de 100 participants (n=27). Les substances chimiques les plus fréquemment étudiées étaient les phtalates (n=23), suivies des parabènes et des phénols (chacun n=18), puis des PFAS (n=1). La matrice biologique principalement utilisée était l'urine (n=36). Plusieurs études (n=31) ont rapporté au moins une association positive entre les produits de soins personnels et certaines classes chimiques, comme entre le maquillage et les parabènes; la lotion et les phénols; et le parfum et les phtalates. Conclusion : Plus d'études sur ce sujet sont nécessaires pour documenter l'importance relative de l'utilisation des produits de soins personnels par rapport à l'exposition totale aux substances chimiques. L’uniformisation des questionnaires de collecte de données pourrait aider à réduire l'hétérogénéité des résultats.Background: Personal care products (PCPs) contain a variety of chemicals including parabens, phenols, phthalates, and per- and polyfluoroalkyl substances (PFAS). Exposure to these chemicals is of concern for children and adolescents, as they are known possess an increased susceptibility to chemical exposures. To date, no published review has explored youth exposure to chemicals found in PCPs. Objective: This scoping review aimed to provide an overview of biomonitoring studies that describe the concentrations of parabens, phenols, phthalates, and PFAS following PCP use among children and adolescents of any age from 5 to 19 years old. Methods: The search was conducted in MEDLINE, Embase, and Global Health. Articles were screened and assessed for eligibility. From eligible studies, data were extracted to summarize and describe the findings. Results: Thirty-seven studies were included, the first of which appeared in 2013. The majority of studies were cross-sectional (n=35) and included more than 100 participants (n=27). The most frequently studied chemicals were phthalates (n=23), followed by parabens and phenols (each n=18), and then PFAS (n=1). The biological matrix mainly used was urine (n=36). Thirty-one studies reported at least one positive association between personal care products and certain chemical classes, such as between makeup and parabens; lotion and phenols; and perfume and phthalates

The Role of Endocrine Disrupting Chemicals in Gestation and Pregnancy Outcomes

This research was funded by the Plan Propio de Investigación de la Universidad de Granada of Spain (grant number PP2022.PP-07). J.M.T. and M.P.-J. are grateful to the Ph.D. Excellence Program “Nutrición y Ciencias de los Alimentos” from the University of Granada. J.M.T. was supported by an FPU contract with grant reference FPU21/04865 funded by the Ministry of Education of Spain.Endocrine disrupting chemicals (EDCs) are exogenous substances widely disseminated both in the environment and in daily-life products which can interfere with the regulation and function of the endocrine system. These substances have gradually entered the food chain, being frequently found in human blood and urine samples. This becomes a particularly serious issue when they reach vulnerable populations such as pregnant women, whose hormones are more unstable and vulnerable to EDCs. The proper formation and activity of the placenta, and therefore embryonic development, may get seriously affected by the presence of these chemicals, augmenting the risk of several pregnancy complications, including intrauterine growth restriction, preterm birth, preeclampsia, and gestational diabetes mellitus, among others. Additionally, some of them also exert a detrimental impact on fertility, thus hindering the reproductive process from the beginning. In several cases, EDCs even induce cross-generational effects, inherited by future generations through epigenetic mechanisms. These are the reasons why a proper understanding of the reproductive and gestational alterations derived from these substances is needed, along with efforts to establish regulations and preventive measures in order to avoid exposition (especially during this particular stage of life).Universidad de Granada PP2022.PP-07Ministry of Education of Spain FPU21/0486

PFASs: What can we learn from the European Human Biomonitoring Initiative HBM4EU

Per- and polyfluoroalkyl substances (PFASs) were one of the priority substance groups selected which have been investigated under the ambitious European Joint programme HBM4EU (2017–2022). In order to answer policy relevant questions concerning exposure and health effects of PFASs in Europe several activities were developed under HBM4EU namely i) synthesis of HBM data generated in Europe prior to HBM4EU by developing new platforms, ii) development of a Quality Assurance/Quality Control Program covering 12 biomarkers of PFASs, iii) aligned and harmonized human biomonitoring studies of PFASs. In addition, some cohort studies (on motherchild exposure, occupational exposure to hexavalent chromium) were initiated, and literature researches on risk assessment of mixtures of PFAS, health effects and effect biomarkers were performed. The HBM4EU Aligned Studies have generated internal exposure reference levels for 12 PFASs in 1957 European teenagers aged 12–18 years. The results showed that serum levels of 14.3% of the teenagers exceeded 6.9 μg/L PFASs, which corresponds to the EFSA guideline value for a tolerable weekly intake (TWI) of 4.4 ng/kg for some of the investigated PFASs (PFOA, PFOS, PFNA and PFHxS). In Northern and Western Europe, 24% of teenagers exceeded this level. The most relevant sources of exposure identified were drinking water and some foods (fish, eggs, offal and locally produced foods). HBM4EU occupational studies also revealed very high levels of PFASs exposure in workers (P95: 192 μg/L in chrome plating facilities), highlighting the importance of monitoring PFASs exposure in specific workplaces. In addition, environmental contaminated hotspots causing high exposure to the population were identified. In conclusion, the frequent and high PFASs exposure evidenced by HBM4EU strongly suggests the need to take all possible measures to prevent further contamination of the European population, in addition to adopting remediation measures in hotspot areas, to protect human health and the environment. HBM4EU findings also support the restriction of the whole group of PFASs. Further, research and definition for additional toxicological dose-effect relationship values for more PFASs compounds is neededEuropean Union’s Horizon 2020 research and innovation program under grant agreement No 73303

The insulin-like growth factor system : a target for endocrine disruptors?

Acknowledgments: Figures were created with BioRender.com Funding: This work was supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie project PROTECTED (grant agreement No. 722634) and FREIA project (grant agreement No. 825100). The authors declare no conflicts of interest regarding this studyPeer reviewedPublisher PD

Report of the Scientific Committee of the Spanish Agency for Food Safety and Nutrition (AESAN) on the available evidence in relation to the potential obesogenic activity of certain chemical compounds that may be present in foods

*This record is given in both English and Spanish According to the World Health Organization (WHO), obesity and overweight have reached epidemic proportions globally. In Spain, the prevalence of obesity is high, especially in childhood, with an upward trend in the last two decades. While improving dietary habits and increasing physical activity has been the main focus on reducing obesity, its rapid increase in countries with different dietary habits and physical activity patterns suggests the possible existence of environmental factors, such as exposure to chemicals with obesogenic activity. Obesogens have been defined functionally as chemical compounds that promote obesity by increasing the number of adipose cells and/or the accumulation of fat in existing adipocytes. Among the most studied obesogens are substances used in the plastic industry such as bisphenols and phthalates, organotin compounds, flame retardants, perfluorinated compounds, polychlorinated biphenyls and dioxins, pesticides and metals, among others. Because the term obesogens includes a large number of compounds, exposure to them can occur by different routes such as inhalation, dermal exposure or ingestion, the latter being the main route of exposure. The mechanisms of action of obesogens are diverse, and they can act by activating or antagonizing the action of nuclear hormone receptors that directly regulate the expression of genes involved in the differentiation of adipocytes, body weight and metabolism, such as oestrogen, androgen and thyroid hormone receptors, and the peroxisome proliferator activated receptor-γ, among others. They can also act in the regulation of different immune-neuroendocrine metabolic pathways, which can lead to pathophysiological consequences in adipogenesis, lipogenesis, lipolysis, immunity, in the influence on the central regulations of appetite and energy expenditure, and changes in the intestinal microbiota, among other processes. It is important to highlight that the most critical periods of exposure to obesogens are preconception, pregnancy and childhood given their importance for metabolism, and may result in permanent changes in adolescence and in adulthood. In this context, the Scientific Committee of the Spanish Agency of Food Safety and Nutrition (AESAN) has carried out a review of the evidence that exists on food exposure to obesogens and its possible effect on health. Scientific literature shows in in vivo and in vitro studies the obesogenic effect of some chemical compounds present in food, and epidemiological studies reinforce this hypothesis. The Scientific Committee recommends that a greater number of studies be carried out to assess the effect of exposure to these compounds, standardizing biomarkers of exposure and effect in order to predict and evaluate their obesogenic capacity and the possible transmission of the effect to other generations through epigenetic mechanisms. Once all the necessary evidence is available, there must be coordination and communication between scientists, clinicians and national and international regulatory bodies, in order to develop a global and efficient strategy in the implementation of risk management measures to reduce exposure to these substances as much as possible.ES; PDF; [email protected]

A vision for safer food contact materials: Public health concerns as drivers for improved testing

Food contact materials (FCMs) and food contact articles are ubiquitous in today's globalized food system. Chemicals migrate from FCMs into foodstuffs, so called food contact chemicals (FCCs), but current regulatory requirements do not sufficiently protect public health from hazardous FCCs because only individual substances used to make FCMs are tested and mostly only for genotoxicity while endocrine disruption and other hazard properties are disregarded. Indeed, FCMs are a known source of a wide range of hazardous chemicals, and they likely contribute to highly prevalent non-communicable diseases. FCMs can also include non-intentionally added substances (NIAS), which often are unknown and therefore not subject to risk assessment. To address these important shortcomings, we outline how the safety of FCMs may be improved by (1) testing the overall migrate, including (unknown) NIAS, of finished food contact articles, and (2) expanding toxicological testing beyond genotoxicity to multiple endpoints associated with non-communicable diseases relevant to human health. To identify mechanistic endpoints for testing, we group chronic health outcomes associated with chemical exposure into Six Clusters of Disease (SCOD) and we propose that finished food contact articles should be tested for their impacts on these SCOD. Research should focus on developing robust, relevant, and sensitive in-vitro assays based on mechanistic information linked to the SCOD, e.g., through Adverse Outcome Pathways (AOPs) or Key Characteristics of Toxicants. Implementing this vision will improve prevention of chronic diseases that are associated with hazardous chemical exposures, including from FCMs