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Background: The substitution of hazardous chemicals with safer alternatives is an important objective in European chemical policy, but implementation has been slower than expected. We conduct a comprehensive analysis and comparison of the implementation of the substitution principle in European regulations for pesticides, biocides, and industrial chemicals. Specifically, we examine and compare the criteria and processes associated with the identification of candidates for substitution and the assessment of alternatives. Results: We find only minor differences in the criteria applied to identify candidates for substitution amongst pesticides, biocides, and industrial chemicals, but larger differences concerning the processes used. While all substances that are to be approved as a pesticide and biocide are systematically evaluated against the established criteria for substitution, the substitution process for industrial chemicals only focuses on those substances identified as substances of very high concern. The main reason candidates for substitution remain on the market is the lack of identified safer chemical alternatives and the insufficient consideration of non-chemical alternatives, caused, at least to a large extent, by the comparatively weak incentives provided by current regulations. Conclusions: The systematic approach for the identification of industrial substances of very high concern (SVHC) under ECHAs "Integrated Regulatory Strategy" is much welcome. However, no final conclusion on SVHC properties or the need for regulatory action has been drawn for approximately 90% of the REACH-registered substances, as often even basic hazard and exposure data are missing. Hence, at least a screening-level evaluation of SVHC properties should become a mandatory part of the substance registration under REACH. To reduce the risk of strategic behaviour in the search for alternatives to industrial chemicals identified as SVHC, a setup in which regulatory authorities play a larger role as information and knowledge brokers should be considered. Investments in innovation as well as improved sharing of information and a better distribution of the workloads amongst European authorities might also improve the identification of safer alternatives. However, without stronger incentives, making it more costly for companies to continue using hazardous substances relative to safer alternatives, initiatives to promote substitution are likely to have limited success. [ABSTRACT FROM AUTHOR]

The sustainable production of fuels and chemicals using microbial cell factories is now well established. However, many microbial production processes are still limited in scale due to inhibition from compounds that are present in the feedstock or are produced during fermentation. Some of these inhibitors interfere with cellular membranes and change the physicochemical properties of the membranes. Another group of molecules is dependent on their permeation rate through the membrane for their inhibition. We have investigated the use of membrane engineering to counteract the negative effects of inhibitors on the microorganism with focus on modulating the abundance of complex sphingolipids in the cell membrane of Saccharomyces cerevisiae. Overexpression of ELO3, involved in fatty acid elongation, and AUR1, which catalyses the formation of complex sphingolipids, had no effect on the membrane lipid profile or on cellular physiology. Deletion of the genes ORM1 and ORM2, encoding negative regulators of sphingolipid biosynthesis, decreased cell viability and considerably reduced phosphatidylinositol and complex sphingolipids. Additionally, combining ELO3 and AUR1 overexpression with orm1/2Δ improved cell viability and increased fatty acyl chain length compared with only orm1/2Δ. These findings can be used to further study the sphingolipid metabolism, as well as giving guidance in membrane engineering. [ABSTRACT FROM AUTHOR]