International audience

International audience | Humans are exposed to a growing list of synthetic chemicals, some of them becoming a major public health concern due to their capacity to impact multiple biological endpoints and contribute to a range of chronic diseases. The integration of endogenous (omic) biomarkers of effect in environmental health studies has been growing during the last decade, aiming to gain insight into potential mechanisms linking the exposures and the clinical conditions. The emergence of high-throughput omic platforms has raised a list of statistical challenges posed by the large dimension and complexity of data generated. Thus, the aim of the present study was to critically review the current state-of-the-science about statistical approaches used to integrate endogenous biomarkers in environmental-health studies linking chemical exposures with health outcomes. The present review specifically focused on internal exposure to environmental chemical pollutants, involving both persistent organic pollutants (POPs) and non-persistent pollutants like phthalates or bisphenols, and metals. We identified 42 eligible articles published since 2016, reporting 48 different statistical workflows, mostly focused on POPs and using metabolomic profiling in the intermediate layer. The outcomes were mainly binary and focused on metabolic disorders. A large diversity of statistical strategies were reported to integrate chemical mixtures and endogenous biomarkers to characterize their associations with health conditions. Multivariate regression models were the most predominant statistical method reported in the published workflows, however some studies applied latent based methods or multipollutant models to overcome the specific constraints of omic or exposure data. A minority of studies used formal mediation analysis to characterize the indirect effects mediated by the endogenous biomarkers. The principles of each specific statistical method and overall workflow set-up are summarized in the light of highlighting their applicability, strengths and weaknesses or interpretability to gain insight into the causal structures underlying the triad: exposure, effect-biomarker and outcome.

International audience | Trichothecenes (TCT) are very common mycotoxins. While the effects of DON, the most prevalent TCT, have been extensively studied, less is known about the effect of other trichothecenes. DON has ribotoxic, pro-inflammatory, and cytotoxic potential and induces multiple toxic effects in humans and animals. Although DON is not genotoxic by itself, it has recently been shown that this toxin exacerbates the genotoxicity induced by model or bacterial genotoxins. Here, we show that five TCT, namely T-2 toxin (T-2), diacetoxyscirpenol (DAS), nivalenol (NIV), fusarenon-X (FX), and the newly discovered NX toxin, also exacerbate the DNA damage inflicted by various genotoxins. The exacerbation was dose dependent and observed with phleomycin, a model genotoxin, captan, a pesticide with genotoxic potential, and colibactin, a bacterial genotoxin produced by the intestinal microbiota. For this newly described effect, the trichothecenes ranked in the following order: T-2>DAS > FX > NIV ≥ DON ≥ NX. The genotoxic exacerbating effect of TCT correlated with their ribotoxic potential, as measured by the inhibition of protein synthesis. In conclusion, our data demonstrate that TCT, which are not genotoxic by themselves, exacerbate DNA damage induced by various genotoxins. Therefore, foodborne TCT could enhance the carcinogenic potential of genotoxins present in the diet or produced by intestinal bacteria.

International audience | Green spaces may have beneficial impacts on children's cognition. However, few studies explored the exposure to green spaces beyond residential areas, and their availability, accessibility and uses at the same time. The aim of the present study was to describe patterns of availability, accessibility, and uses of green spaces among primary school children and to explore how these exposure dimensions are associated with cognitive development. Exposures to green space near home, school, commuting route, and other daily activity locations were assessed for 1607 children aged 6-11 years from six birth cohorts across Europe, and included variables related to: availability (NDVI buffers: 100, 300, 500 m), potential accessibility (proximity to a major green space: linear distance; within 300 m), and use (play time in green spaces: hours/year), and the number of visits to green spaces (times/previous week). Cognition measured as fluid intelligence, inattention, and working memory was assessed by computerized tests. We performed multiple linear regression analyses on pooled and imputed data adjusted for individual and area-level confounders. Availability, accessibility, and uses of green spaces showed a social gradient that was unfavorable in more vulnerable socioeconomic groups. NDVI was associated with more playing time in green spaces, but proximity to a major green space was not. Associations between green space exposures and cognitive function outcomes were not statistically significant in our overall study population. Stratification by socioeconomic variables showed that living within 300 m of a major green space was associated with improved working memory only in children in less deprived residential areas (β = 0.30, CI: 0.09,0.51), and that more time playing in green spaces was associated with better working memory only in children of highly educated mothers (β per IQR increase in hour/year = 0.10; 95% CI: 0.01, 0.19). However, studying within 300 m of a major green space increased inattention scores in children in more deprived areas (β = 15.45, 95% CI: 3.50, 27.40).

International audience | Pollinators have to cope with a wide range of stressful, not necessarily lethal factors limiting their performance and the ecological services they provide. Among these stressors are pesticides, chemicals that are originally designed to target crop-harming organisms but that also disrupt various functions in pollinators, including flight, communication, orientation and memory. Although all these functions are crucial for reproductive individuals when searching for mates or nesting places, it remains poorly understood how pesticides affect reproduction in pollinators. In this study, we investigated how a widely used fungicide, boscalid, affects reproduction in honey bees (Apis mellifera), an eusocial insect in which a single individual, the queen, fulfills the reproductive functions of the whole colony. Boscalid is a succinate dehydrogenase inhibitor (SDHI) fungicide mainly used on rapeseed flowers to target mitochondrial respiration in fungi but it is also suspected to disrupt foraging-linked functions in bees. We found that immature queen exposure to sublethal, field relevant doses of boscalid disrupted reproduction, as indicated by a dramatic increase in queen mortality during and shortly after the nuptial flights period and a decreased number of spermatozoa stored in the spermatheca of surviving queens. However, we did not observe a decreased paternity frequency in exposed queens that successfully established a colony. Queen exposure to boscalid had detrimental consequences on the colonies they later established regarding brood production, Varroa destructor infection and pollen storage but not nectar storage and population size. These perturbations at the colony-level correspond to nutritional stress conditions, and may have resulted from queen reduced energy provisioning to the eggs. Accordingly, we found that exposed queens had decreased gene expression levels of vitellogenin, a protein involved in egg-yolk formation. Overall, our results indicate that boscalid decreases honey bee queen reproductive quality, thus supporting the need to include reproduction in the traits measured during pesticide risk assessment procedures.

International audience | Settled dust can function as a pollutant sink for compounds, such as polycyclic aromatic hydrocarbons (PAHs) and metal(loid)s (MMs), which may lead to health issues. Thus, dust represents a hazard specifically for young children, because of their vulnerability and hand-to-mouth behavior favoring dust ingestion.The aim of the present study was to explore the influence of the season and the microenvironment on the concentrations of 15 PAHs and 17 MMs in indoor and outdoor settled dust in three preschools (suburban, urban, and industrial). Second, the potential sources and health risks among children associated with dust PAHs and MMs were assessed. Third, domestic factors (risk perception, knowledge and parental style) were described to explore protective parental behaviors toward dust hazards.The suburban preschool had the lowest concentrations of dust PAHs and MMs, while the industrial and urban preschools had higher but similar concentrations. Seasonal tendencies were not clearly observed. Indoor dusts reflected the outdoor environment, even if specific indoor sources were noted. Source analysis indicated mainly vehicular emissions, material release, and pyrogenic or industrial sources. The non-cancer health risks were nonexistent, but potential cancer health risks (between 1.10(-6) and 1.10(-4)) occurred at all sampling locations. Notably, the highest cancer risk was observed in a playground area (>1.10(-4)) and material release should be further addressed. Whereas we assessed higher risk indoors, parents perceived a higher risk in the open-air environment and at the preschool than at home. They also perceived a lower risk for their own children, revealing an optimism bias, which reduces parental anxiety.

International audience | Aflatoxin B1 (AFB1) is the most potent natural carcinogen among mycotoxins. Versicolorin A (VerA) is a precursor of AFB1 biosynthesis and is structurally related to the latter. Although VerA has already been identified as a genotoxin, data on the toxicity of VerA are still scarce, especially at low concentrations. The SOS/umu and miniaturised version of the Ames test in Salmonella Typhimurium strains used in the present study shows that VerA induces point mutations. This effect, like AFB1, depends primarily on metabolic activation of VerA. VerA also induced chromosomal damage in metabolically competent intestinal cells (IPEC-1) detected by the micronucleus assay. Furthermore, results from the standard and enzyme-modified comet assay confirmed the VerA-mediated DNA damage, and we observed that DNA repair pathways were activated upon exposure to VerA, as indicated by the phosphorylation and/or relocation of relevant DNA-repair biomarkers (γH2AX and 53BP1/FANCD2, respectively). In conclusion, VerA induces DNA damage without affecting cell viability at concentrations as low as 0.03 μM, highlighting the danger associated with VerA exposure and calling for more research on the carcinogenicity of this emerging food contaminant.

International audience | Recently, Comte et al. (2022) re-examined the natural degradation of chlordecone (CLD) in the soils of the French West Indies (FWI) by introducing an additional ‘dissipation parameter’ into the WISORCH model developed by Cabidoche et al. (2009). Recent data sets of CLD concentrations in FWI soils obtained by Comte et al. enabled them optimizing the model parameters, resulting in significantly shorter estimates of pollution persistence than in the original model. Their conclusions jeopardize the paradigm of a very limited degradation of CLD in FWI soils, which may lead to an entire revision of the management of CLD contamination. However, we believe that their study is questionable on several important aspects. This includes potential biases in the data sets and in the modeling approach. It results in an inconsistency between the estimated dissipation half-life time (DT50) of five years that the authors determined for CLD and the fate of CLD in soil from the application period 1972–1993 until nowadays. Most importantly, a rapid dissipation of CLD in the field as proposed by Comte et al. is not sufficiently supported by data and estimates. Hence, the paradigm of long-term persistence of CLD in FWI soils is still to be considered.

International audience | Per and polyfluoroalkyl substances (PFAS) are persistent compounds that are massively used in industry, consumer goods and fire-fighting foams. Soil contamination by PFAS is a major environmental concern, and there is a lack of knowledge on both their ecotoxicological mechanisms and the concentrations that induce adverse effects especially to non-target organisms, particularly in the case of PFAS mixtures. This study contributes to filling these gaps by assessing and modelling the effects of PFAS (in single and in mixtures for PFOS and PFOA at different environmental doses) on juvenile endogeic earthworms of a common species in European soils (Aporrectodea caliginosa) at different levels of biological organization (sub-individual and individual). The results showed for the first time combined strong ecotoxicological effects of PFAS on earthworm survival, integumental integrity, growth, sexual maturity and on genomic stability notably with the induction of DNA breaks associated with no abnormal oxidative DNA-lesion levels. Our results demonstrated significant effects at 0.3 mg kg − 1 and additive effects in case of mixtures. ☆ This paper has been recommended for acceptance by Jiayin Dai.