Multiple exposures to indoor contaminants: Derivation of benchmark doses and relative potency factors based on male reprotoxic effects

International audienceSemi-Volatile Organic Compounds (SVOCs) are commonly present in dwellings and several are suspected of having effects on male reproductive function mediated by an endocrine disruption mode of action. To improve knowledge of the health impact of these compounds, cumulative toxicity indicators are needed. This work derives Benchmark Doses (BMD) and Relative Potency Factors (RPF) for SVOCs acting on the male reproductive system through the same mode of action. We included SVOCs fulfilling the following conditions: detection frequency (>10%) in French dwellings, availability of data on the mechanism/mode of action for male reproductive toxicity, and availability of comparable dose-response relationships. Of 58 SVOCs selected, 18 induce a decrease in serum testosterone levels. Six have sufficient and comparable data to derive BMDs based on 10 or 50% of the response. The SVOCs inducing the largest decrease in serum testosterone concentration are: for 10%, bisphenol A (BMD10= 7.72E-07 mg/kg bw/d; RPF10= 7033679); for 50%, benzo[a]pyrene (BMD50= 0.030 mg/kg bw/d; RPF50= 1630), and the one inducing the smallest one is benzyl butyl phthalate (RPF10 and RPF50= 0.095). This approach encompasses contaminants from diverse chemical families acting through similar modes of action, and makes possible a cumulative risk assessment in indoor environments. The main limitation remains the lack of comparable toxicological data

Perspectives for integrating human and environmental risk assessment and synergies with socio-economic analysis

International audienceFor more than a decade, the integration of human and environmental risk assessment (RA) has become an attractive vision. At the same time, existing European regulations of chemical substances such as REACH (EC Regulation No. 1907/2006), the Plant Protection Products Regulation (EC regulation 1107/2009) and Biocide Regulation (EC Regulation 528/2012) continue to ask for sector-specific RAs, each of which have their individual information requirements regarding exposure and hazard data, and also use different methodologies for the ultimate risk quantification. In response to this difference between the vision for integration and the current scientific and regulatory practice, the present paper outlines five medium-term opportunities for integrating human and environmental RA, followed by detailed discussions of the associated major components and their state of the art. Current hazard assessment approaches are analyzed in terms of data availability and quality, and covering non-test tools, the integrated testing strategy (ITS) approach, the adverse outcome pathway (AOP) concept, methods for assessing uncertainty, and the issue of explicitly treating mixture toxicity. With respect to exposure, opportunities for integrating exposure assessment are discussed, taking into account the uncertainty, standardization and validation of exposure modeling as well as the availability of exposure data. A further focus is on ways to complement RA by a socio-economic assessment (SEA) in order to better inform about risk management options. In this way, the present analysis, developed as part of the EU FP7 project HEROIC, may contribute to paving the way for integrating, where useful and possible, human and environmental RA in a manner suitable for its coupling with SEA

Tools and techniques for solvent selection: green solvent selection guides

Driven by legislation and evolving attitudes towards environmental issues, establishing green solvents for extractions, separations, formulations and reaction chemistry has become an increasingly important area of research. Several general purpose solvent selection guides have now been published with the aim to reduce use of the most hazardous solvents. This review serves the purpose of explaining the role of these guides, highlighting their similarities and differences. How they can be used most effectively to enhance the greenness of chemical processes, particularly in laboratory organic synthesis and the pharmaceutical industry, is addressed in detail

Outcomes of polytrauma patients with diabetes mellitus.

BACKGROUND: The impact of diabetes mellitus in patients with multiple system injuries remains obscure. This study was designed to increase knowledge of outcomes of polytrauma in patients who have diabetes mellitus. METHODS: Data from the Trauma Audit and Research Network was used to identify patients who had suffered polytrauma during 2003 to 2011. These patients were filtered to those with known outcomes, then separated into those with diabetes, those known to have other co-morbidities but not diabetes and those known not to have any co-morbidities or diabetes. The data were analyzed to establish if patients with diabetes had differing outcomes associated with their diabetes versus the other groups. RESULTS: In total, 222 patients had diabetes, 2,558 had no past medical co-morbidities (PMC), 2,709 had PMC but no diabetes. The diabetic group of patients was found to be older than the other groups (P <0.05). A higher mortality rate was found in the diabetic group compared to the non-PMC group (32.4% versus 12.9%), P <0.05). Rates of many complications including renal failure, myocardial infarction, acute respiratory distress syndrome, pulmonary embolism and deep vein thrombosis were all found to be higher in the diabetic group. CONCLUSIONS: Close monitoring of diabetic patients may result in improved outcomes. Tighter glycemic control and earlier intervention for complications may reduce mortality and morbidity

Do patients with diabetes mellitus and polytrauma continue to have worse outcomes?

The management of patients with multiple injuries remains challenging. Patients presenting with comorbidities, such as diabetes mellitus, may have additional unpredictable outcomes with increased mortality. Therefore, we aim to investigate the impact of major trauma centres in the UK on the outcomes of polytrauma patients with diabetes. The Trauma Audit and Research Network was used to identify polytrauma patients presenting to centres in England and Wales between 2012 and 2019. In total, 32,345 patients were thereby included and divided into three groups: 2271 with diabetes, 16,319 with comorbidities other than diabetes and 13,755 who had no comorbidities. Despite an overall increase in diabetic prevalence compared to previously published data, mortality was reduced in all groups, but diabetic patient mortality remained higher than in the other groups. Interestingly, increasing Injury Severity Score (ISS) and age were associated with increasing mortality, whereas the presence of diabetes, even when taking into consideration age, ISS and Glasgow Coma Score, led to an increase in the prediction of mortality with an odds ratio of 1.36 (p < 0.0001). The prevalence of diabetes mellitus in polytrauma patients has increased, and diabetes remains an independent risk factor for mortality following polytrauma

Nomadic Making; enacting difference through collaborative performance practice

This article considers how scored, collaborative performance practice enacts Braidotti’s Nomadic subject and disrupts advanced capitalism’s suture of object and subject formation (Lepecki) thereby offering a means for posthumans to ‘become imperceptible’ (Braidotti after Deleuze). Collaborative performance practice, I argue offers a lived experience of the non-unitary subject and political potential of pure difference. I suggest also that ‘spectator studies’ (Melrose) reconsiders its focus on object over process by arguing that choreographic knowledge resides not in the event or the performance score but the processes of assemblage and in-between relations of people and practices (Manning)

Analysis of community-level mesocosm data based on ecologically meaningful dissimilarity measures and data transformation

The principal response curve (PRC) method is a constrained ordination method developed specifically for the analysis of community data collected in mesocosm experiments, which provides easily understood summaries and graphical representations of community response to stress. It is a redundancy analysis method and is usually performed on log-transformed abundance data. The choice of a measure of dissimilarity between samples and the choice of the data transformation significantly affect the results of multivariate analysis. Dissimilarity measures that are more ecologically meaningful than the Euclidean distance can be incorporated into the PRC using distance-based redundancy analysis. The present study investigates the ordinations produced by a small selection of dissimilarity measures: the Euclidean distance using log-transformed and Hellinger-transformed data and the Bray-Curtis dissimilarity using raw and log-transformed data. It compares 2 data sets from experiments on the effect of the anti-inflammatory drug diclofenac and the insecticide chlorpyrifos on macroinvertebrate communities. The choice of dissimilarity measure can determine the outcome of a risk assessment. For the diclofenac data set, the PRCs were different depending on the dissimilarity measure: the community no-effect concentration was lowest for the Bray-Curtis on log-transformed data and Hellinger dissimilarity measures. For chlorpyrifos, however, the PRCs were similar for all dissimilarity measures

A quantitative AOP of mitochondrial toxicity based on data from three cell lines

Adverse Outcome Pathways (AOPs) are increasingly used to support the integration of in vitro data in hazard assessment for chemicals. Quantitative AOPs (qAOPs) use mathematical models to describe the relationship between key events (KEs). In this paper, data obtained in three cell lines, LHUMES, HepG2 and RPTEC/TERT1, using similar experimental protocols, was used to calibrate a qAOP of mitochondrial toxicity for two chemicals, rotenone and deguelin. The objectives were to determine whether the same qAOP could be used for the three cell types, and to test chemical-independence by cross-validation with a dataset obtained on eight other chemicals in LHUMES cells. Repeating the calibration approach for both chemicals in three cell lines highlighted various practical difficulties. Even when the same readouts of KEs are measured, the mathematical functions used to describe the key event relationships may not be the same. Cross-validation in LHUMES cells was attempted by estimating chemical-specific potency at the molecular initiating events and using the rest of the calibrated qAOP to predict downstream KEs: toxicity of azoxystrobin, carboxine, mepronil and thifluzamide was underestimated. Selection of most relevant readouts and accurate characterization of the molecular initiating event for cross-validation are critical when designing in vitro experiments targeted at calibrating qAOPs.Toxicolog