HAL du Programme national de recherche environnement-santé-travail (PNR EST)
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Navigating the complexities of docking tools with nicotinic receptors and acetylcholine binding proteins in the realm of neonicotinoids
No full textInternational audienceMolecular docking, pivotal in predicting small-molecule ligand binding modes, struggles with accurately identifying binding conformations and affinities. This is particularly true for neonicotinoids, insecticides whose impacts on ecosystems require precise molecular interaction modeling. This study scrutinizes the effectiveness of prominent docking software (Ledock, ADFR, Autodock Vina, CDOCKER) in simulating interactions of environmental chemicals, especially neonicotinoid-like molecules with nicotinic acetylcholine receptors (nAChRs) and acetylcholine binding proteins (AChBPs). We aimed to assess the accuracy and reliability of these tools in reproducing crystallographic data, focusing on semi-flexible and flexible docking approaches. Our analysis identified Ledock as the most accurate in semi-flexible docking, while Autodock Vina with Vinardo scoring function proved most reliable. However, no software consistently excelled in both accuracy and reliability. Additionally, our evaluation revealed that none of the tools could establish a clear correlation between docking scores and experimental dissociation constants (Kd) for neonicotinoid-like compounds. In contrast, a strong correlation was found with drug-like compounds, bringing to light a bias in considered software towards pharmaceuticals, thus limiting their applicability to environmental chemicals. The comparison between semi-flexible and flexible docking revealed that the increased computational complexity of the latter did not result in enhanced accuracy. In fact, the higher computational cost of flexible docking with its lack of enhanced predictive accuracy, rendered this approach useless for this class of compounds. Conclusively, our findings emphasize the need for continued development of docking methodologies, particularly for environmental chemicals. This study not only illuminates current software capabilities but also underscores the urgency for advancements in computational molecular docking as it is a relevant tool to environmental sciences
The abundance of snail hosts mediates the effects of antagonist interactions between trematodes on the transmission of human schistosomes
No full textInternational audienceBackground Combating infectious diseases and halting biodiversity loss are intertwined challenges crucial to ensure global health. Biodiversity can constrain the spread of vector-borne pathogens circulation, necessitating a deeper understanding of ecological mechanisms underlying this pattern. Our study evaluates the relative importance of biodiversity and the abundance of Bulinus truncatus , a major intermediate host for the trematode Schistosoma haematobium on the circulation of this human pathogen at aquatic transmission sites. Methods We combined mathematical modelling and a molecular based empirical study to specifically assess the effect of co-infections between S. haematobium and other trematodes within their B. truncatus snail hosts; and B. truncatus abundance at transmission sites, on the production of S. haematobium infective cercariae stages released into the aquatic environment.Results Our modelling approach shows that more competitive trematode species exploiting B. truncatus as an intermediate host at the transmission site level leads to higher co-infection rates within snail hosts, subsequently reducing the production of S. haematobium cercariae. Conversely, an increase in B. truncatus abundance results in lower co-infection rates, and a higher proportion of S. haematobium cercariae released into the environment. Our empirical data from the field support these findings, indicating a significant negative effect of local trematode species richness ( P -value = 0.029; AIC = 14.9) and co-infection rates ( P -value = 0.02, AIC = 17.4) on the dominance of S. haematobium based on our GLMM models, while B. truncatus abundance positively influences S. haematobium dominance ( P -value = 0.047, AIC = 20.1). Conclusions Our study highlights the importance of biodiversity in influencing the transmission of S. haematobium through the effect of antagonistic interactions between trematodes within bulinid snail hosts. This effect intensifies when B. truncatus populations are low, promoting co-infections within snails. In line with the One Health concept, our results suggest that maintaining high level of freshwater biodiversity to sustain global trematode diversity at transmission sites can help reducing the circulation of Schistosoma species locally
Evaluation des effets multiples (environnementaux et sociétaux) d’une contamination chimique complexe d’un écosystème aquatique : premier bilan sur le site atelier de la Cleurie (Vosges)
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Plastic pollution in terrestrial ecosystems: current knowledge on impacts of micro and nano fragments on invertebrates
No full textInternational audienceThe increasing accumulation of small plastic particles, in particular microplastics (>1 µm to 5 mm) and nanoplastics (< 1 µm), in the environment is a hot topic in our rapidly changing world. Recently, studies were initiated to better understand the behavior of micro- and nanoplastics (MNP) within complex matrices like soil, as well as their characterization, incorporation and potential toxicity to terrestrial biota. However, there remains significant knowledge gaps in our understanding of the wide-extent impacts of MNP on terrestrial invertebrates. We first summarized facts on global plastic pollution and the generation of MNP. Then, we focused on compiling the existing literature examining the consequences of MNP exposure in terrestrial invertebrates. The diversity of investigated biological endpoints (from molecular to individual levels) were compiled to get a better comprehension of the effects of MNP according to different factors such as the shape, the polymer type, the organism, the concentration and the exposure duration. The sublethal effects of MNP are acknowledged in the literature, yet no general conclusion was drawn as their impacts are highly dependent on their characteristic and experimental design. Finally, the synthesis highlighted some research gaps and remediation strategies, as well as a protocol to standardize ecotoxicological studies
Central nervous system tumours and occupational ionising radiation exposure: a nested case–control study among the ORICAMs cohort of healthcare workers in France
No full textCorrection: central nervous system tumours and occupational ionising radiation exposure: a nested case-control study among the ORICAMs cohort of healthcare workers in France BMJ Open 2024;14:e084285.corr1. doi: 10.1136/bmjopen-2024-084285.corr1International audienceObjective This study aimed at investigating the relationship between occupational exposure to external ionising radiation and central nervous system (CNS) tumours mortality in healthcare workers working in France. Design and setting The Occupational Radiation-Induced Cancer in Medical staff (ORICAMs) nested case–control study was conducted based on the dosimetric records of the national register of occupational dosimetry (Système d’information de la surveillance de l’exposition aux rayonnements ionisants). Participants and methods 33 CNS tumour deaths occurred between 2002 and 2012 among the ORICAMs cohort composed of 164 015 healthcare workers. Each case was matched to five controls alive at the time of the corresponding case’s death, based on sex, year of birth, date of enrolment in the cohort and duration of follow-up. All participants were badge monitored for external radiation exposure, expressed in H p (10). Conditional logistic regression was used to analyse the dose–response relationship between radiation dose and CNS mortality. Results Cases were exposed to a mean cumulative career radiation dose of 5.8±13.7 (max: 54.3) millisievert (mSv) compared with 4.1±15.2 (142.2) mSv for controls. No statistically significant association was found between CNS tumour mortality and cumulative whole-body career dose (OR=1.00, 95% CI 0.98 to 1.03), duration of exposure (OR=1.03; 95% CI 0.95 to 1.12) or age at first exposure (OR=0.98; 95% CI 0.91 to 1.06). Conclusion We found no evidence of an association between external radiation exposure and CNS tumour risk in healthcare workers. Limitations of the study include low statistical power and short duration of follow-up
Population declines of a widespread amphibian in agricultural landscapes
No full textInternational audienceModern agricultural practices are suspected to play a major role in the ongoing erosion of biodiversity. In order to assess whether this biodiversity loss is linked to past habitat modifications (e.g. land consolidation) or to current consequences of modern agriculture (e.g. use of agrochemicals), it remains essential to monitor species that have persisted in agricultural landscapes to date. In this study, we assessed the presence, abundance and recent population trends of one such species, the spined toad (Bufo spinosus) along a gradient of habitats from preserved (forests) to highly agricultural sites in rural Western France. Our results showed that both presence and abundance of spined toads were markedly lower in reproductive ponds surrounded by intensive agriculture. The most salient result of our study is the ongoing decline of this species in farmland habitats. Indeed, this result suggests that unknown factors are currently affecting a widespread terrestrial amphibian previously thought to persist in agricultural landscapes. These factors have recently induced strong population declines over the course of a few years. Future investigations are required to identify these factors at a time when anthropogenic activities are currently leading to unprecedented rates of biodiversity loss
Prevalence of occupational co-exposure to biomechanical factors and neurotoxic chemicals in French workers
No full textInternational audienceObjectives -Little is known about occupational co-exposure. The objective was to assess the prevalence of exposure and co-exposure to biomechanical factors and neurotoxic chemicals in French workers in 2017. Methods - Data from the French representative survey SUMER 2017 (SUrveillance Médicale des Expositions aux Risques professionnels) were analyzed. A total of 25 118 workers were included. Exposure to 4 biomechanical factors (manual handling of loads, forceful joint exertion, repetitive movements, and hand-arm transmitted vibrations) and 18 neurotoxic chemicals (n-hexane, perchloroethylene, trichloroethylene, etc.) were assessed using a questionnaire during face-to-face interviews with occupational physicians. Results Among men, 22.9% were exposed to at least one biomechanical factor and 10.2% were exposed to at least one neurotoxic chemical, mainly single exposures. Among women, 10.8% were exposed to at least one biomechanical factor and 3.1% were exposed to at least one neurotoxic chemical, also mainly single exposures. Occupational co-exposure to biomechanical factors and neurotoxic chemicals was observed among 4.8% of men and 0.7% of women. Workers under 30 yr old, blue-collar workers and those working in small companies were more co-exposed than other workers. In men, the prevalence of co-exposure was higher in the construction sector compared to other economic activities. Discussion - This study stresses the importance of considering multiple occupational exposures while the current prevention measures are designed to focus on preventing occupational factors individually
The blue light hazard and its use on the evaluation of photochemical risk for domestic lighting. An in vivo study
No full textInternational audienceBackground: Nowadays artificial light highly increases human exposure to light leading to circadian rhythm and sleep perturbations. Moreover, excessive exposure of ocular structures to photons can induce irreversible retinal damage. Meta-analyses showed that sunlight exposure influences the age of onset and the progression of Age-related macular degeneration (AMD), the leading cause of blindness in people over fifty-year old. Currently, the blue-light hazard (BLH) curve is used in the evaluation of the phototoxicity of a light source for domestic lighting regulations.Objectives: Here, we analyze the phototoxicity threshold in rats and investigate the role played by the light spectrum, assessing the relevance of the use of the BLH-weighting to define phototoxicity.Methods: We exposed albino rats to increasing doses of blue and white light, or to lights of different colors to evaluate the impact of each component of the white light spectrum on phototoxicity. Cellular mechanisms of cell death and cellular stress induced by light were analyzed.Results: Our results show that the phototoxicity threshold currently accepted for rats is overestimated by a factor of 50 when considering blue light and by a factor of 550 concerning white light. This is the result of the toxicity induced by green light that increases white light toxicity by promoting an inflammatory response. The content of green in white light induces 8 fold more invasion of macrophages in the retina than the content of blue light. Moreover, the use of BLH-weighting does not evaluate the amount of red radiations contained in white light that mitigates damage by inhibiting the nuclear translocation of L-DNase II and reducing by 33% the number of TUNEL-positive cells.Discussion: These findings question the current methods to determine the phototoxicity of a light source and show the necessity to take into account the entire emission spectrum. As current human phototoxicity thresholds were estimated with the same methods used for rats, our results suggest that they might need to be reconsidered
Cadmium and phthalate impacts developmental growth and mortality of Spodoptera littoralis, but not reproductive success
No full textInternational audienceOur environment is increasingly polluted with various molecules, some of which are considered endocrine disruptors. Metals and phthalates, originating from industrial activities, agricultural practices, or consumer products, are prominent examples of such pollutants. We experimentally investigated the impacts of the heavy metal cadmium and the phthalate DEHP on the moth Spodoptera littoralis. More specifically, larvae were reared in laboratory conditions, where they were exposed to diets contaminated with either two doses of cadmium at concentrations of 62.5 µg/g or 125 µg/g, two doses of DEHP at 100 ng/g and 10 µg/g, or a combination of both low and high doses of the two compounds, with a control group for comparison. Our findings indicate that cadmium delays the developmental transition from larva to adult. Notably, the combination of cadmium and DEHP exacerbated this delay, highlighting a synergistic effect. In contrast, DEHP alone did not affect larval development. Additionally, we observed that cadmium exposure, both alone and in combination with DEHP, led to a lower mass at all larval stages. However, cadmium-exposed individuals that reached adulthood eventually reached a similar mass to those in other groups. Interestingly, while our results did not show any effect of the treatments on hatching success, there was a higher adult mortality rate in the cadmium-treated groups. This suggests that while moths may prioritize reproductive success, their survival at the adult stage is compromised by cadmium exposure. In conclusion, our study demonstrates the impact of cadmium on the development, mass, and adult survival of moths, and reveals synergistic effects when combined with DEHP. These results confirm cadmium as an endocrine disruptor, even at low doses. These insights underscore the importance of understanding the toxicological effects of low doses of pollutants like cadmium and DEHP, both individually and in combination
