Int J Environ Res Public Health

In 2015, the International Federation of Gynecology and Obstetrics established the prevention of exposures to environmental reprotoxic substances as a priority for health professionals. However, available information about reproductive hazards is voluminous, dispersed, and complex, and this is a severe limitation for physicians to incorporate the prevention of environmental exposure into standard preventive care. One difficulty frequently cited by physicians is the lack of evidence-based information. The objective of our study was to identify a list of environmental chemical hazards to reproduction. We used lists present in relevant regulations or included in scientific reports or databases to identify reproductive hazards. The reproductive hazards were prioritized according to the strength of evidence concerning their impact on fertility or development of the offspring. We identified 1251 reproductive hazards. Our prioritization approach resulted in a high-priority classification for 462 risk factors belonging to the following eight classes: drugs (n = 206), metals (n = 116), pesticides (n = 38), organic solvents (n = 27), synthesizing and/or processing agents in industrial processes (n = 23), phthalates (n = 13), perfluorinated compounds (n = 13), and other compounds (n = 26). Despite the limitations of this work, the generated lists constitute a useful working basis to put in place innovative environmental preventive measures according to the principle of evidence-based medicine

In vitro effects of nanoparticles on renal cells

<p>Abstract</p> <p>Background</p> <p>The ability of nanoparticles to cross the lung-blood barrier suggests that they may translocate to blood and to targets distant from their portal of entry. Nevertheless, nanotoxicity in organs has received little attention. The purpose of this study was to evaluate nanotoxicity in renal cells using <it>in vitro </it>models. Various carbon black (CB) (FW2–13 nm, Printex60-21 nm and LB101-95 nm) and titanium dioxide (TiO₂-15 and TiO₂-50 nm) nanoparticles were characterized on size by electron microscopy. We evaluated theirs effects on glomerular mesangial (IP15) and epithelial proximal tubular (LLC-PK₁) renal cells, using light microscopy, WST-1 assay, immunofluorescence labeling and DCFH-DA for reactive oxygen species (ROS) assay.</p> <p>Results</p> <p>Nanoparticles induced a variety of cell responses. On both IP15 and LLC-PK₁cells, the smallest FW2 NP was found to be the most cytotoxic with classic dose-behavior. For the other NPs tested, different cytotoxic profiles were found, with LLC-PK₁cells being more sensitive than IP15 cells. Exposure to FW2 NPs, evidenced in our experiments as the most cytotoxic particle type, significantly enhanced production of ROS in both IP15 and LLC-PK₁cells. Immunofluorescence microscopy using latex beads indicated that depending on their size, the cells internalized particles, which accumulated in the cell cytoplasm. Additionally using transmission electronic microscope micrographs show nanoparticles inside the cells and trapped in vesicles.</p> <p>Conclusion</p> <p>The present data constitute the first step towards determining <it>in vitro </it>dose effect of manufactured CB and TiO₂NPs in renal cells. Cytotoxicological assays using epithelial tubular and glomerular mesangial cell lines rapidly provide information and demonstrated that NP materials exhibit varying degrees of cytotoxicity. It seems clear that <it>in vitro </it>cellular systems will need to be further developed, standardized and validated (relative to <it>in vivo </it>effects) in order to provide useful screening data about the relative toxicity of nanoparticles.</p

Quantification of short and long asbestos fibers to assess asbestos exposure: a review of fiber size toxicity.

International audienceThe fibrogenicity and carcinogenicity of asbestos fibers are dependent on several fiber parameters including fiber dimensions. Based on the WHO (World Health Organization) definition, the current regulations focalise on long asbestos fibers (LAF) (Length: L ≥ 5 μm, Diameter: D  3). However air samples contain short asbestos fibers (SAF) (L < 5 μm). In a recent study we found that several air samples collected in buildings with asbestos containing materials (ACM) were composed only of SAF, sometimes in a concentration of ≥10 fibers.L-1. This exhaustive review focuses on available information from peer-review publications on the size-dependent pathogenetic effects of asbestos fibers reported in experimental in vivo and in vitro studies. In the literature, the findings that SAF are less pathogenic than LAF are based on experiments where a cut-off of 5 μm was generally made to differentiate short from long asbestos fibers. Nevertheless, the value of 5 μm as the limit for length is not based on scientific evidence, but is a limit for comparative analyses. From this review, it is clear that the pathogenicity of SAF cannot be completely ruled out, especially in high exposure situations. Therefore, the presence of SAF in air samples appears as an indicator of the degradation of ACM and inclusion of their systematic search should be considered in the regulation. Measurement of these fibers in air samples will then make it possible to identify pollution and anticipate health risk

Biomechanical and organisational constraints of pregnant women at work: definition of exposure levels using a consensus method (Delphi)

OBJECTIVES: To identify the biomechanical and organisational constraints that influence pregnancy outcomes and define the exposure levels at which the risks for pregnancy become significant. SETTING AND PARTICIPANTS: We applied a consensus method (Delphi) consisting of a literature review followed by expert opinions on exposure levels. The group of experts was made up of 12 people from different medical specialities and working in various structures in France. OUTCOME MEASURES: The studied variables were: (1) exposure: night work/shift work, weekly hours at work, lifting of heavy loads, prolonged standing and multiple exposure and (2) pregnancy outcomes: prematurity, low birth weight and spontaneous miscarriages. RESULTS: The consensus method resulted in the following recommendations. The time spent working must not exceed 40 hours/week; in the absence of a consensus on the level of exposure, night and/or shift work must be avoided; prolonged standing must not exceed 3 hours/day; lifting must be limited to carrying loads <11 kg, with a daily load <100 kg; multiple exposure must be avoided, in particular: vibration, night work/shift work, time spent working exceeding 40 hours/week, prolonged standing and lifting of heavy loads. CONCLUSIONS: These results could help the occupational physician to address the question of whether an exposed employee should remain at work, considering her individual characteristics (medical history, family situation, socioeconomic level, etc) in consultation with pregnancy specialists (obstetricians, midwives)

Physicochemical characteristics and bronchial epithelial cell cytotoxicity of Folpan 80 WG® and Myco 500®, two commercial forms of folpet

<p>Abstract</p> <p>Background</p> <p>Pesticides, in particular folpet, have been found in rural and urban air in France in the past few years. Folpet is a contact fungicide and has been widely used for the past 50 years in vineyards in France. Slightly water-soluble and mostly present as particles in the environment, it has been measured at average concentration of 40.1 μg/m³during its spraying, 0.16–1.2 μg/m³in rural air and around 0.01 μg/m³in urban air, potentially exposing both the workers and the general population. However, no study on its penetration by inhalation and on its respiratory toxicity has been published. The objective of this study was to determine the physicochemical characteristics of folpet particles (morphology, granulometry, stability) in its commercial forms under their typical application conditions. Moreover, the cytotoxic effect of these particles and the generation of reactive oxygen species were assessed <it>in vitro </it>on respiratory cells.</p> <p>Results</p> <p>Granulometry of two commercial forms of folpet (Folpan 80WG^®and Myco 500^®) under their typical application conditions showed that the majority of the particles (>75%) had a size under 5 μm, and therefore could be inhaled by humans. These particles were relatively stable over time: more than 75% of folpet remained in the particle suspension after 30 days under the typical application conditions. The inhibitory concentration (IC₅₀) on human bronchial epithelial cells (16HBE14o-) was found to be between 2.89 and 5.11 μg/cm²for folpet commercial products after 24 h of exposure. Folpet degradation products and vehicles of Folpan 80 WG^®did not show any cytotoxicity at tested concentrations. At non-cytotoxic and subtoxic concentrations, Folpan 80 WG^®was found to increase DCFH-DA fluorescence.</p> <p>Conclusion</p> <p>These results show that the particles of commercial forms of folpet are relatively stable over time. Particles could be easily inhaled by humans, could reach the conducting airways and are cytotoxic to respiratory cells in vitro. Folpet particles may mediate its toxicity directly or indirectly through ROS-mediated alterations. These data constitute the first step towards the risk assessment of folpet particles by inhalation for human health. This work confirms the need for further studies on the effect of environmental pesticides on the respiratory system.</p

PLoS One

The assessment of residential exposure to agricultural pesticides is a major issue for public health, regulatory and management purposes. In recent years, research into this field has developed considerably. The purpose of this scoping review is to provide an overview of scientific literature characterizing residential exposure to agricultural pesticides and to identify potential gaps in this research area. This work was conducted according to the JBI and PRISMA guidelines. Three databases were consulted. At least two experts selected the eligible studies. Our scoping review enabled us to identify 151 articles published between 1988 and 2019 dealing with the assessment of residential exposure to agricultural pesticides. Of these, 98 (64.9%) were epidemiological studies investigating possible links between pesticide exposure and the onset of adverse health effects, principally cancers and reproductive outcomes. They predominantly used Geographic Information Systems and sometimes surveys or interviews to calculate surrogate exposure metrics, the most common being the amounts of pesticides applied or the surface area of crops around the dwelling. Twenty-six (17.2%) were observational measurement studies conducted to quantify levels of pesticide exposure and identify their possible determinants. These studies assessed exposure by measuring pesticides in biological and environmental matrices, mostly in urines and house dust. Finally, we found only eight publications (5.3%) that quantified the risk to human health due to residential exposure for management purposes, in which exposure was mainly determined using probabilistic models. Pesticide exposure appears to be largely correlated with the spatial organization of agriculture activities in a territory. The determinants and routes of exposure remain to be explored to improve the conduct of epidemiological and risk assessment studies and to help prevent future exposures. Improvement could be expected from small-scale studies combining different methods of exposure assessment

Int J Environ Res Public Health

BACKGROUND: Female surgeons are exposed to physical and mental stressors that differ from those of other specialties. We aimed to assess whether female surgeons are more at risk of pregnancy complications than women in other medical specialties. METHODS: We used a cross-sectional electronic survey of female physicians working in the French Region Nouvelle-Aquitaine who were pregnant between 2013 and 2018. A pregnancy complication was defined as the occurrence of miscarriage, ectopic pregnancy, fetal growth restriction, prematurity, fetal congenital malformation, stillbirth, or medical termination of the pregnancy. Multivariate logistic regression models were used to evaluate the risk of pregnancy complications for female surgeons relative to women practicing in other medical specialties. RESULTS: Among the 270 women included, 52 (19.3%) experienced pregnancy complications and 28 (10.4%) were surgeons. In the multivariate analysis, female surgeons had a higher risk of pregnancy complications: adjusted odds ratio = 3.53, 95% confidence interval [1.27-9.84]. CONCLUSION: Further research is necessary to identify the hazards specifically involved in the practice of surgery to be able to propose preventive actions targeted to female surgeons during their pregnancy

Impairment of NO-Dependent Relaxation in Intralobar Pulmonary Arteries: Comparison of Urban Particulate Matter and Manufactured Nanoparticles

International audienceBACKGROUND AND OBJECTIVES: Because pulmonary circulation is the primary vascular target of inhaled particulate matter (PM), and nitric oxide is a major vasculoprotective agent, in this study we investigated the effect of various particles on the NO-cyclic guanosine monophosphate (cGMP) pathway in pulmonary arteries. METHODS: We used intrapulmonary arteries and/or endothelial cells, either exposed in vitro to particles or removed from PM-instilled animals for assessment of vasomotricity, cGMP and reactive oxygen species (ROS) levels, and cytokine/chemokine release. RESULTS: Endothelial NO-dependent relaxation and cGMP accumulation induced by acetylcholine (ACh) were both decreased after 24 hr exposure of rat intrapulmonary arteries to standard reference material 1648 (SRM1648; urban PM). Relaxation due to NO donors was also decreased by SRM1648, whereas responsiveness to cGMP analogue remained unaffected. Unlike SRM1648, ultrafine carbon black and ultrafine and fine titanium dioxide (TiO2) manufactured particles did not impair NO-mediated relaxation. SRM1648-induced decrease in relaxation response to ACh was prevented by dexamethasone (an anti-inflammatory agent) but not by antioxidants. Accordingly, SRM1648 increased the release of proinflammatory mediators (tumor necrosis factor-alpha, interleukin-8) from intrapulmonary arteries or pulmonary artery endothelial cells, but did not elevate ROS levels within intrapulmonary arteries. Decreased relaxation in response to ACh was also evidenced in intrapulmonary arteries removed from rats intratracheally instilled with SRM1648, but not with fine TiO2. CONCLUSION: In contrast to manufactured particles (including nanoparticles), urban PM impairs NO but not cGMP responsiveness in intrapulmonary arteries. We attribute this effect to oxidative-stress-independent inflammatory response, resulting in decreased guanylyl cyclase activation by NO. Such impairment of the NO pathway may contribute to urban-PM-induced cardiovascular dysfunction

Interstitial Lung Abnormalities Detected by CT in Asbestos-Exposed Subjects Are More Likely Associated to Age

OBJECTIVE: the aim of this study was to evaluate the association between interstitial lung abnormalities, asbestos exposure and age in a population of retired workers previously occupationally exposed to asbestos. METHODS: previously occupationally exposed former workers to asbestos eligible for a survey conducted between 2003 and 2005 in four regions of France, underwent chest CT examinations and pulmonary function testing. Industrial hygienists evaluated asbestos exposure and calculated for each subject a cumulative exposure index (CEI) to asbestos. Smoking status information was also collected in this second round of screening. Expert radiologists performed blinded independent double reading of chest CT-scans and classified interstitial lung abnormalities into: no abnormality, minor interstitial findings, interstitial findings inconsistent with UIP, possible or definite UIP. In addition, emphysema was assessed visually (none, minor: emphysema 50% of the lung). Logistic regression models adjusted for age and smoking were used to assess the relationship between interstitial lung abnormalities and occupational asbestos exposure. RESULTS: the study population consisted of 2157 male subjects. Interstitial lung abnormalities were present in 365 (16.7%) and emphysema in 444 (20.4%). Significant positive association was found between definite or possible UIP pattern and age (OR adjusted =1.08 (95% CI: 1.02-1.13)). No association was found between interstitial abnormalities and CEI or the level of asbestos exposure. CONCLUSION: presence of interstitial abnormalities at HRCT was associated to aging but not to cumulative exposure index in this cohort of former workers previously occupationally exposed to asbestos

Deep Learning for the Automatic Quantification of Pleural Plaques in Asbestos-Exposed Subjects

OBJECTIVE: This study aimed to develop and validate an automated artificial intelligence (AI)-driven quantification of pleural plaques in a population of retired workers previously occupationally exposed to asbestos. METHODS: CT scans of former workers previously occupationally exposed to asbestos who participated in the multicenter APEXS (Asbestos PostExposure Survey) study were collected retrospectively between 2010 and 2017 during the second and the third rounds of the survey. A hundred and forty-one participants with pleural plaques identified by expert radiologists at the 2nd and the 3rd CT screenings were included. Maximum Intensity Projection (MIP) with 5 mm thickness was used to reduce the number of CT slices for manual delineation. A Deep Learning AI algorithm using 2D-convolutional neural networks was trained with 8280 images from 138 CT scans of 69 participants for the semantic labeling of Pleural Plaques (PP). In all, 2160 CT images from 36 CT scans of 18 participants were used for AI testing versus ground-truth labels (GT). The clinical validity of the method was evaluated longitudinally in 54 participants with pleural plaques. RESULTS: The concordance correlation coefficient (CCC) between AI-driven and GT was almost perfect (>0.98) for the volume extent of both PP and calcified PP. The 2D pixel similarity overlap of AI versus GT was good (DICE = 0.63) for PP, whether they were calcified or not, and very good (DICE = 0.82) for calcified PP. A longitudinal comparison of the volumetric extent of PP showed a significant increase in PP volumes (p < 0.001) between the 2nd and the 3rd CT screenings with an average delay of 5 years. CONCLUSIONS: AI allows a fully automated volumetric quantification of pleural plaques showing volumetric progression of PP over a five-year period. The reproducible PP volume evaluation may enable further investigations for the comprehension of the unclear relationships between pleural plaques and both respiratory function and occurrence of thoracic malignancy