Modelling the exposure to chemicals for risk assessment: a comprehensive library of multimedia and PBPK models for integration, prediction, uncertainty and sensitivity analysis - the MERLIN-Expo tool.

MERLIN-Expo is a library of models that was developed in the frame of the FP7 EU project 4FUN in order to provide an integrated assessment tool for state-of-the-art exposure assessment for environment, biota and humans, allowing the detection of scientific uncertainties at each step of the exposure process. This paper describes the main features of the MERLIN-Expo tool. The main challenges in exposure modelling that MERLIN-Expo has tackled are: (i) the integration of multimedia (MM) models simulating the fate of chemicals in environmental media, and of physiologically based pharmacokinetic (PBPK) models simulating the fate of chemicals in human body. MERLIN-Expo thus allows the determination of internal effective chemical concentrations; (ii) the incorporation of a set of functionalities for uncertainty/sensitivity analysis, from screening to variance-based approaches. The availability of such tools for uncertainty and sensitivity analysis aimed to facilitate the incorporation of such issues in future decision making; (iii) the integration of human and wildlife biota targets with common fate modelling in the environment. MERLIN-Expo is composed of a library of fate models dedicated to non biological receptor media (surface waters, soils, outdoor air), biological media of concern for humans (several cultivated crops, mammals, milk, fish), as well as wildlife biota (primary producers in rivers, invertebrates, fish) and humans. These models can be linked together to create flexible scenarios relevant for both human and wildlife biota exposure. Standardized documentation for each model and training material were prepared to support an accurate use of the tool by end-users. One of the objectives of the 4FUN project was also to increase the confidence in the applicability of the MERLIN-Expo tool through targeted realistic case studies. In particular, we aimed at demonstrating the feasibility of building complex realistic exposure scenarios and the accuracy of the modelling predictions through a comparison with actual measurements.

Effects of a fungicide (imazalil) and an insecticide (diazinon) on stream fungi and invertebrates associated with litter breakdown.

The intensification of agriculture has promoted the use of pesticides such as fungicides and insecticides. Many pesticides readily leach into natural water bodies and affect both organisms and ecosystem processes such as leaf breakdown, a crucial process in headwater streams. As leaf breakdown in streams involves sequential steps by different groups of organisms (first microbial conditioning, then invertebrate shredding), pesticides targeting different organisms are likely to affect one or the other step, and a mixture of contaminants might have interactive effects. Our objective was to evaluate the effect of a fungicide (imazalil) and an insecticide (diazinon) on stream fungal and invertebrate activities, and their effects on leaf consumption. After an initial assay to define 'effective concentration' of both pesticides in a laboratory experiment, we manipulated pesticide presence/absence during the conditioning and shredding phases. Both pesticides affected fungal community and reduced the performance of the shredding amphipod Echinogammarus berilloni, and leaf consumption. The impact of pesticides on fungal sporulation depended on the length of the exposure period. In addition, pesticides seemed to cause an energetic imbalance in the amphipod, affecting body condition and mortality. The combined effect of both pesticides was similar to those of the fungicide. Overall, our results show that the effects of pesticide mixtures on leaf breakdown are hard to predict from those observed in either fungi or macroinvertebrate performance.

Evidence for a role of EGF receptor in the progression of human lung carcinoma.

Sixty-three primary lung carcinomas were examined immunohistochemically for the presence of epidermal growth factor receptors (EGF-R). Of these tumors 35 (55.5%) were positive for EGF-R. A positive correlation between overexpression of EGF-R, on the one hand, and high metastatic rate, poor tumor differentiation and high rate of tumor proliferation, on the other hand, was found. From one tumor with an extremely high amount of EGF-R a primary cell culture was established. The addition of anti-EGF-R serum to this culture decreased cell proliferation. Our results support the evidence for a positive relationship between overexpression of EGF-R and invasiveness, poor differentiation and high growth rate of tumor cells. The blockade of EGF-R with specific antibodies suppressed tumor cell proliferation, suggesting a role of EGF-R in tumor progression.