In Utero Exposure to Maternal Diabetes Impairs Vascular Expression of Prostacyclin Receptor in Rat Offspring

International audienc

Styrene toxicity values according to the scenario of exposure

Styrene is an aromatic hydrocarbon compound mostly used as a monomer in the manufacture of plastics. The presence of styrene in the environment is mainly anthropogenic. Styrene is a substance of interest in risk assessment and risk management for humans for which one need reference values. Depending on the exposure scenario, the reference values used are not the same. In the case of chronic exposure to styrene, the National Institute for Industrial Environment and Risks (INERIS) has made a choice among the existing toxicological reference values determined by international agencies. In the context of land use planning, acute toxicity threshold values were established by INERIS. For each of these scenarios, a methodology was developed by INERIS. In both cases, the first step is an extensive literature review of available data. Then, for chronic exposures, the toxicological reference values are selected according to their scientific quality and their relevance. For acute inhalation exposures in accidental situations, determination of threshold values is based on the Klimisch scoring from selected studies and on statistical modeling from experimental data. For chronic exposure, INERIS recommend the use of 0.2 mg kg-1 j-1 for oral chronic exposure to styrene (US EPA) and 0.2 ppm for inhalation chronic exposure (ATSDR). For acute inhalation in accidental situations, the inhaled doses corresponding to thresholds for acute lethal effects are 75,000-120,000 ppm min and 12,000-48,000 ppm min for the irreversible effects

Rôle du toxicologue dans la prévention des risques liés aux accidents industriels entraînant des émissions de substances chimiques dans l'atmosphère

PARIS-BIUP (751062107) / SudocSudocFranceF

Comparison of models to analyze mortality data and derive concentration-time response relationship of inhaled chemicals

International audienceThe derivation of thresholds for lethal effects for inhaled chemicals is a key issue in accidental risk management because they largely determine the outcome of land use planning, among which localization of habitations in the vicinity of a factory. This derivation is generally performed on the basis of rodent lethality data analyzed by statistical models able to extrapolate effects for different times and concentrations of exposure. A model commonly used in France is the standard probit model. In this model, effects is related to exposure concentration and duration according to the Haber's law and considers that individual thresholds, corresponding to the maximum tolerated effects before dying, are log-normally distributed among the population. This approach has been criticized for its lack of biological parameters and its inability to treat data characterized by only one time of exposure. In order to improve the current state of modeling, we proposed three alternative models. Two of them (DEBtox and Haber-TKTD models) incorporate the kinetics of the chemicals. The third one (Loguniform model) is a linearization of the standard probit model. We evaluated their performance by analyzing real data and simulated data generated with each model. For data characterized by several times of exposure, the standard probit model outperformed all other models in terms of goodness of fits and estimation of parameters. For data characterized by only one time of exposure, only DEBtox model was able to fit the data and estimate parameters, provided we dispose of several observation times, typically just after exposure and a long period afterwards

Defining the Human-Biota Thresholds of Toxicological Concern for Organic Chemicals in Freshwater: The Proposed Strategy of the LIFE VERMEER Project Using VEGA Tools

International audienceSeveral tons of chemicals are released every year into the environment and it is essential to assess the risk of adverse effects on human health and ecosystems. Risk assessment is expensive and time-consuming and only partial information is available for many compounds. A consolidated approach to overcome this limitation is the Threshold of Toxicological Concern (TTC) for assessment of the potential health impact and, more recently, eco-TTCs for the ecological aspect. The aim is to allow a safe assessment of substances with poor toxicological characterization. Only limited attempts have been made to integrate the human and ecological risk assessment procedures in a “One Health” perspective. We are proposing a strategy to define the Human-Biota TTCs (HB-TTCs) as concentrations of organic chemicals in freshwater preserving both humans and ecological receptors at the same time. Two sets of thresholds were derived: general HB-TTCs as preliminary screening levels for compounds with no eco- and toxicological information, and compound-specific HB-TTCs for chemicals with known hazard assessment, in terms of Predicted No effect Concentration (PNEC) values for freshwater ecosystems and acceptable doses for human health. The proposed strategy is based on freely available public data and tools to characterize and group chemicals according to their toxicological profiles. Five generic HB-TTCs were defined, based on the ecotoxicological profiles reflected by the Verhaar classes, and compound-specific thresholds for more than 400 organic chemicals with complete eco- and toxicological profiles. To complete the strategy, the use of in silico models is proposed to predict the required toxicological properties and suitable models already available on the VEGAHUB platform are listed

Development of a confidence index for choice of Toxicity Reference Value

Toxicological Reference Values (TRVs) are developed to protect humans exposed either by oral or inhalation routes. They are derived for threshold or non-threshold effects, depending on the mechanism of action of each substance. These values are issued by several international organisms (WHO, US EPA, ATSDR, OEHHA, ANSES, EFSA,...) and used in risk assessment. If several values are available, risk assessors may have to exert an expert judgment to choose the most appropriate. The confidence given to the selected value should be considered when interpreting the conclusions of the risk assessment. In order to make this choice transparent and consistent between assessors, we propose to associate each choice with a confidence index, based on commonly accepted criteria. To develop this index, the main parameters influencing quality of a TRV were identified and structured by groups of key elements. Three criteria are defined corresponding to experimental vs.human study, TRV elaboration method and complementary elements. A questionnaire was designed using factorial experimental design in order to collect the opinions of toxicological expert on the weight to be given to each parameter. The experiment was conducted in two steps. In the first part, experts were asked to score artificial cases in order to evaluate the most critical parameters. The second part consisted in four case studies used for validation of the confidence index. Preliminary results show that a confidence index with four levels corresponding to high confidence, medium confidence, moderate confidence, and retained by default can be proposed