Prenatal Exposure to Mixtures of Nonpersistent Endocrine-Disrupting Chemicals and Angiogenic Biomarkers, Placental Function, and Fetal Growth

International audienceExposure to endocrine-disrupting chemicals (EDCs) during pregnancy may influence the placenta and fetal growth; however, evidence is scarce regarding EDC mixtures, newer chemicals, and the role of angiogenic biomarkers and fetoplacental hemodynamics. We aimed to examine the associations between nonpersistent EDC mixtures and fetal growth, fetoplacental hemodynamics, and angiogenic biomarkers. We included 734 pregnant participants from the Barcelona Life Study Cohort (BiSC), Spain (2018-2021). Metabolites of phthalates, DINCH, insecticides, polycyclic aromatic hydrocarbons, pesticides, flame retardants, and parent compounds of phenols and parabens were measured in pools of week-long maternal urine samples at 18 and 34 weeks' gestation. Penalized LASSO-type multigroup Bayesian Weighted Quantile Sum Regression estimated associations with fetal growth, fetoplacental hemodynamics, and angiogenic biomarkers. Birthweight z-score decreased with lowmolecular-weight phthalate (LMWP) (β = -0.119; CrI -0.224, -0.008) mixtures and increased with organophosphate mixtures (β = 0.143; CrI 0.042, 0.245). LMWP exposure was also associated with altered hemodynamics and angiogenic biomarkers; angiogenic biomarkers mediated the relationship with birthweight z-score (ACME = -0.032; 95% CI -0.062, -0.009; p = 0.002). This comprehensive study suggests that mixtures of low-molecular-weight phthalates and organophosphate compounds may alter fetal growth and that angiogenic biomarkers may play a role as mediator

Effects of ubiquitous plasticizers on olfactory perception in the buff-tailed bumble bee

International audienceThe rise in anthropogenic pollution poses a growing threat to pollinators, with some plastic pollutants such as phthalates being ubiquitous. Although the effects of pesticides have been extensively studied, little research explores how other contaminants affect pollinator health and behaviour. This article examines the influence of two phthalates predominant in the environment, Di-2-Ethylhexyl Phthalate (DEHP) and Di-n-Butyl Phthalate (DnBP), on the bumble bee Bombus terrestris, a key pollinator species. By exposing bumble bee workers to various concentrations and modalities of these contaminants, we assessed how these two phthalates affect the detection of common volatile organic compounds emitted by flowers. Findings show that phthalate exposure at environmental doses diminishes bumble bee antennal sensitivity to olfactory signals. This impairment could compromise pollination efficiency and accelerate pollinator decline. By revealing that phthalates disrupt bumble bee olfactory capacities, this study underscores the urgency of mitigating these ubiquitous pollutants to preserve biodiversity and ecosystem functions

Toxicity of polyethylene terephthalate and polylactic acid nanoplastics, pristine and weathered in environmentally-relevant conditions, to human intestinal cells representative of genetic susceptibility to Crohn's disease

International audienceEnvironmental pollution by micro-and nanoplastics (MNPs) raises concerns about their toxicity to humans, particularly through ingestion. While the impact of native MNPs is increasingly documented, environmentally degraded MNPs remain poorly studied. We assessed the intestinal impact of biodegradable and non-biodegradable nanoplastics (NPLs), polyethylene terephthalate (PET) and polylactic acid (PLA), both pristine and weathered in environmental conditions. The response of an in vitro intestinal model representative of healthy populations was compared with that of a model of genetic susceptibility to inflammatory bowel disease (IBD), using HT29-MTX cells cocultured with Caco-2 cells expressing either wild-type or mutated nucleotide-binding oligomerization domain 2 (NOD2). Nondifferentiated and differentiated cells were exposed for 24 h to these NPLs. Cellular uptake, cytotoxicity, genotoxicity, oxidative stress, inflammation, and epithelial barrier integrity were evaluated. Although PET and PLA accumulated in cells, they showed no significant toxicity. Therefore, as demonstrated for polystyrene NPLs, PLA and PET particles do not cause major toxic impact to intestinal cells upon acute exposure in vitro and, in this exposure scenario, weathering in environmental conditions does not increase their toxicity

Assessment of Pergafast 201 absorption and metabolism in viable human skin: A comparative study with bisphenol A and bisphenol S

International audienceFor 50 years, bisphenol A (BPA) has been extensively used as a colour developer in thermal printing papers. The European Union and several other countries have drastically restricted BPA's use in thermal paper, due to its endocrine-disrupting properties. Consequently, bisphenol S (BPS) and Pergafast 201 (PF201) are increasingly used as substitutes, despite their percutaneous absorption remains poorly documented. We conducted an ex vivo study to achieve a comparative assessment of the skin absorption and metabolism of BPA, BPS and PF201. Tritium-labelled compounds were topically applied to viable human skin explants mounted on static Franz diffusion cells, providing complete mass-balance data compliant with OECD recommendations (n° 428, 28, 156). Absorbed doses were 5.1 ± 2.4 % for BPA, and below 1 % for BPS and PF201 (BPA > BPS ∼ PF201). Dermal delivery reached 16.1 ± 3.5 % for BPA, 8.7 ± 4.2 % for BPS and 3.5 ± 1.3 % for PF201 (BPA > BPS > PF201). Additional experiments were conducted for PF201 at five different doses (7.8-638.5 ng/cm2) to determine skin permeation parameters. PF201's absorbed dose and dermal delivery remained constant, its permeability coefficient was found to range between 0.63 and 2.0 × 10⁻⁶ cm/h, and its flux between 0.75 and 84.0 × 10⁻3 ng/cm2/h. No PF201 metabolism or degradation were observed in skin explants. Our results demonstrate that despite limited absorption, PF201 remains in the skin after 24 h, suggesting prolonged bioavailability. This study closes major knowledge gaps related to the absorption and metabolism of PF201 through viable human skin and provides useful data for improved risk assessment

Liver steatosis induced by per- and polyfluoroalkyl substances exerts a limited influence on heterocyclic aromatic amine–mediated DNA damage at population-relevant exposure levels

International audienceThe human population is chronically exposed to complex mixtures of environmental contaminants. However, classical toxicological risk assessment still relies mainly on individual compound testing, often at high concentrations and over short treatment durations that poorly reflect real-life exposure. In this study, we investigated per- and polyfluoroalkyl substances (PFAS) and heterocyclic aromatic amines (HAA) mixtures at concentrations aligned with human serum measurements using mechanistic knowledge of each compound. To evaluate mixture effects, we employed Hepoid®, a 3D human liver model composed of polarized, proliferative, metabolically active, and highly differentiated HepaRG cells for long-term cultures. At human population internal exposure levels, PFAS and HAAs, alone or in combination, induced steatosis measured by automated lipid droplet quantification along with early transcriptional stress responses, without increased DNA damage under mixture conditions, as assessed by 3 complementary genotoxicity and mutagenesis assays (comet assay, γH2AX immunolabelling and micronucleus assay). Overall, this study highlights the importance of concentrations, treatment duration and human-relevant metabolic competence in determining toxic outcomes. By reproducing realistic exposure scenarios in an advanced human liver model sensitive to low-dose mixture effects, this work contributes to improving human relevance of chemical risk assessment

From bystander to key player: unveiling the gut microbiota's role in mediating cyanobacterial toxicity in aquatic animals

International audienceCyanobacterial blooms represent one prevalent stressor in aquatic ecosystems worldwide, exposing aquatic animals to complex mixtures of live cells and dissolved bioactive compounds, including cyanotoxins. The gut microbiota, which plays fundamental roles in digestion, immunity, and metabolic regulation, has been recognized as a key interface between environmental stressors and host health. Exposure to cyanobacteria occurs primarily through ingestion, making the gut the main site of interaction with live cells, cyanobacterial metabolites, and associated bacteria. While dissolved bioactive compounds can also penetrate via gills and skin, their role is secondary in most animals. Understanding how cyanobacteria interact with the host gut microbiota is therefore essential to fully assess their impacts on animal health. This review summarizes current knowledge of gut microbiota responses to cyanobacterial stress in crustaceans, mollusks, and chordates, highlighting dynamic and context-dependent changes in microbial communities. We discuss the cascading effects on host physiology, immune function, and metabolic homeostasis, and explore how the microbiota may modulate host resilience, including potential roles in cyanotoxin degradation.</div

Assessment of endocrine disruptor impact on carbohydrate metabolism in the HepaRG human hepatic cell line

International audienceEndocrine-disrupting chemicals (EDCs) are increasingly implicated in the development of metabolic disorders such as type 2 diabetes mellitus (T2DM). As hepatic dysfunction is a hallmark of early metabolic disease, we investigated how EDCs may contribute to glucose dysregulation using human HepaRG cells. Ten EDCs-bisphenol A (BPA), bisphenol F (BPF), bisphenol S (BPS), cadmium chloride (CdCl2, 1 µM), butylparaben (BP), 1,1-dichloro-2,2-bis(4-chlorophenyl)ethene (p,p'-DDE), dibutyl phthalate (DBP), di(2-ethylhexyl) phthalate (DEHP), perfluorooctanoic acid (PFOA), and perfluorooctanesulfonic acid (PFOS)-were tested at 25 µM for 5 days. We assessed multiple endpoints related to carbohydrate metabolism, including gene expression, mitochondrial function, glycogen content, glucose export, glycolytic capacity, and lactate release. Among the tested compounds, p,p'-DDE induced the most pronounced metabolic disruption, significantly reducing glycogen storage, glycolytic capacity, lactate export, and the expression of key genes involved in glucose metabolism. Using luciferase-based reporter cell lines, p,p'-DDE was found to activate primarily the nuclear receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR). However, siRNA-mediated knockdown of these receptors did not reverse the changes induced by p,p'-DDE in gene expression, suggesting a more complex or alternative mechanism of action. These findings demonstrate that p,p'-DDE perturbs hepatic carbohydrate metabolism and may contribute to the pathogenesis of T2DM, highlighting the need for further mechanistic investigation

Optimized methods for adsorbable organic halides (AOX) and halogen‑specific speciation for tracking disinfection by-products from source to tap

International audienceDisinfection by-products (DBPs) formed during drinking water treatment pose a significant public health risk due to their ubiquity and documented toxicity, including carcinogenic, genotoxic, and developmental effects. While European regulations currently limit monitoring to trihalomethanes (THMs) and haloacetic acids (HAAs), they overlook highly toxic brominated and iodinated DBPs, which exhibit greater toxicity than their chlorinated counterparts. To address this gap, adsorbable organic halides (AOX) have emerged as a promising bulk parameter, integrating both the total concentration and potential toxicity of halogenated DBPs. Halogen-specific AOX speciation (AOCl, AOBr, AOI) and the distinction between purgeable (POX) and non-purgeable organic halides (NPOX) further refine risk assessments, as these fractions differ in toxicity and exposure pathways.This study optimizes and validates analytical methods for AOX, NPOX, and halogen-specific AOX, focusing on critical parameters -including adsorption efficiency, volatilization, matrix interferences, and ion chromatography conditions-to enhance method robustness. The optimized protocol achieved limits of quantification (LOQs) of 25 µg Cl•L⁻¹ for AOX/NPOX and 0.9 and 2.8 µg Cl•L⁻¹ for AOBr/AOI, respectively.The optimized method was successfully applied to drinking water samples collected from four distribution networks across three regions in France, with multiple sampling points along each network. AOX concentrations ranged from &lt;25 to 200 µg Cl•L⁻¹. NPOX represented 50-90% of AOX. AOCl dominated at one site (&gt;90%), whereas others exhibited substantial AOBr (8-77%) and minor AOI (2-10%, rarely detected). Regulated THMs and HAAs accounted for only 0-54% of total AOX (≤20% at two sites), indicating that most organohalogens remain unidentified. These findings highlight the prevalence of unmonitored organohalogens and underscore the need for broader DBP surveillance to improve water safety assessments.</p

Is short-term exposure to low and high ambient temperatures associated with an increased risk of sudden unexpected death in infancy? A case-crossover study in France (2015-2022)

International audienceBackgroundSudden unexpected death in infancy (SUDI) is a leading cause of infant mortality. Although ambient temperature affects many health outcomes, evidence on its association with SUDI remains limited. We examined short-term effects of high and low temperatures on SUDI in France.MethodsWe performed a time-stratified case-crossover study including lag periods up to six days before death. Conditional logistic regression models assessed associations with both binary temperature indicators (based on percentiles) and continuous metrics using a distributed lag nonlinear model (DLNM). Effect modification by season, sex, social deprivation, urban or rural residence, age at death, and sleeping position was examined.ResultsWe included 1078 SUDI cases in France from 2015 to 2022. Results suggested an increased risk with heat on days close to death. Estimates were imprecise due to the limited sample size, leading to wide confidence intervals for several associations. However, we observed a linear association between temperature and SUDI during summer, particularly for minimum temperature in the last week of life (OR: 1.16, 1.07-1.26). DLNM analyses suggested similar patterns, with elevated risk for minimum temperatures above 15 °C and below 0 °C, though these estimates remain uncertainty.ConclusionsShort-term exposure to both high and low temperatures showed patterns of association with SUDI, with particularly notable effects of heat during summer. Although statistical support for many trends was limited, the alignment of these signals with previous studies suggests that preventive measures to reduce temperature-related risks for infants may be considered, particularly in the context of rising temperatures

Metabolic characterization of seven bee pollens: Molecular network, metabolite isolation and antioxidant activity assessment

International audienc