Inhalation exposure assessments under REACH - Problems encountered using the approach recommended by the ECHA guidance R.15.

Consumers experience inhalation exposure events that are characterized by fluctuating substance air concentrations and typically exposure durations of less than 24 h. To assess the risk of such exposure events, a comparison with toxicological derived limits based on 24 h exposure duration per day is often necessary. Therefore, adjustments are needed to bridge the different time durations. One approach to handle this issue was recommended by the European Chemical Agency (ECHA) for consumer exposure. This approach is especially noteworthy, because it does not rely on the validity of Haber's law (which states that only total intake matters) but uses a modified Haber's law (with coefficient n = 3) as default. However, the proposed algorithm for its implementation can lead to the situation that increasing the exposure duration leads to lower predicted risk, which logically makes no sense. In this article, the correct way to implement the modified Haber's law is presented, which avoids logical fallacies. The presented algorithm has consequences for the sensitivity of the predicted risk regarding changes of exposure duration and ventilation rate, which are investigated in this article.

Modelling Exposure by Spraying Activities-Status and Future Needs.

Spray applications enable a uniform distribution of substances on surfaces in a highly efficient manner, and thus can be found at workplaces as well as in consumer environments. A systematic literature review on modelling exposure by spraying activities has been conducted and status and further needs have been discussed with experts at a symposium. This review summarizes the current knowledge about models and their level of conservatism and accuracy. We found that extraction of relevant information on model performance for spraying from published studies and interpretation of model accuracy proved to be challenging, as the studies often accounted for only a small part of potential spray applications. To achieve a better quality of exposure estimates in the future, more systematic evaluation of models is beneficial, taking into account a representative variety of spray equipment and application patterns. Model predictions could be improved by more accurate consideration of variation in spray equipment. Inter-model harmonization with regard to spray input parameters and appropriate grouping of spray exposure situations is recommended. From a user perspective, a platform or database with information on different spraying equipment and techniques and agreed standard parameters for specific spraying scenarios from different regulations may be useful.

Insights Gained from an Approximate Analytical Solution of the Evaporation Model Used by ConsExpo Web.

Evaporation of chemicals is an important source of inhalative exposure. We analyzed here the ConsExpo evaporation model, which is characterized by a set of nonlinear differential equations only solvable by numerical means. It shows qualitatively different behavior for different parameters, but the exact conditions remain unclear. This article presents an approximate analytical solution of the ConsExpo evaporation model, derived by using a specific linearization of the nonlinear equations valid for small concentrations. From this solution, three different boundary cases or regimes are found: quick release, near equilibrium, and ventilation driven regime. Depending on the evaporation regime, different parameters influence peak substance air concentration: Quick release regime: total substance amount and room volume; near equilibrium regime: vapor pressure, substance concentration in the product, and molecular weight of the product matrix; ventilation driven regime: vapor pressure, substance concentration in the product, room volume, surface area, mass transfer coefficient, ventilation rate, and molecular weight of the product matrix. A graphical method is developed to display the position of a given scenario in relation to the three regimes. Thus, the approximate analytical solution allows for a given situation to prioritize research for reducing uncertainty of the most sensitive parameters and helps to identify promising risk management measures.

How does the ryanodine receptor in the ventricular myocyte wake up: by a single or by multiple open L-type Ca2+ channels?

We study here the early stage of Ca(2+)-induced Ca(2+) release (CICR) in the diadic cleft of cardiac ventricular myocytes. A crucial question for this mechanism is whether the activation of the ryanodine receptors (RyRs) is triggered by one or by multiple open L-type Ca(2+) channels (LCCs). We address the problem through a modelling approach that allows us to investigate both possibilities. The model is based on a spatially resolved description of a Ca(2+) release unit (CaRU), consisting of the junctional sarcoplasmic reticulum and the diadic cleft, with well-defined channel placement. By taking advantage of largely varying time scales of the Ca(2+) dynamics in the diadic cleft, the governing equations can be reduced to one ordinary differential equation that describes the Ca(2+) fluxes, the electric field due to surface charges and diffusion. Our study shows that the mechanisms of the early stage of CICR shape measurable properties of CICR in a characteristic way. From here we conclude that the activation of RyRs requires multiple open LCCs.

Efficient and detailed model of the local Ca2+ release unit in the ventricular cardiac myocyte.

We present here an efficient but detailed approach to modelling Ca(2+)-induced Ca(2+) release in the diadic cleft of cardiac ventricular myocytes. In this Framework we developed a spatial resolved Ca(2+) release unit (CaRU), consisting of the junctional sarcoplasmic reticulum and the diadic cleft, with a well defined channel placement. By taking advantage of time scale separation, the model could be finally reduced to only one ordinary differential equation for describing Ca(2+) fluxes and diffusion. Additionally the channel gating is described in a stochastic way. The resulting model is able to reproduce experimental findings like the gradedness of SR release, the voltage dependence of ECC gain and typical spark life time. Due to the numerical efficiency of the model, it is suitable to use for whole cell simulations. The approach we want to use extend the developed (CaRU) to such a whole cell model is already outlined in this work.