Power matters in closing the phenotyping gap

Much of our understanding of physiology and metabolism is derived from investigating mouse mutants and transgenic mice, and open-access platforms for standardized mouse phenotyping such as the German Mouse Clinic (GMC) are currently viewed as one powerful tool for identifying novel gene-function relationships. Phenotyping or phenotypic screening involves the comparison of wild-type control mice with their mutant or transgenic littermates. In our study, we explored the extent to which standardized phenotyping will succeed in detecting biologically relevant phenotypic differences in mice generated and provided by different collaborators. We analyzed quantitative metabolic data (body mass, energy intake, and energy metabolized) collected at the GMC under the current workflow, and used them for statistical power considerations. Our results demonstrate that there is substantial variability in these parameters among lines of wild-type C57BL/6 (B6) mice from different sources. Given this variable background noise in mice that serve as controls, subtle phenotypes in mutant or transgenic littermates may be overlooked. Furthermore, a phenotype observed in one cohort of a mutant line may not be reproducible (to the same extent) in mice coming from a different environment or supplier. In the light of these constraints, we encourage researchers to incorporate information on intrastrain variability into future study planning, or to perform advanced hierarchical analyses. Both will ultimately improve the detectability of novel phenotypes by phenotypic screening. Carola W. Meyer and Ralf Elvert contributed equally to this work.     

Some pharmacokinetic aspects of PCDDs and PCDFs in mammals after administration of a fly ash extract from a municipal incinerator

Fly ash extracts were fed to male hamster (single dose), male rat (single dose and multiple dose), pregnant and lactating female rat (multiple dose). The retention of four isomers, 2,3,7,8-TCDD, 2,3,7,8-TCDF, 1,2,3,7,8-PnCDD and 2,3,4,7,8-PnCDF, was studied in the liver of the adults, foetuses and liver of the sucklings.

Liver retention was structure dependent and different for both species. Transportation of the isomers via the mother milk was 50–100 times more effective than via the placenta.

After a single intravenous dose of fly ash extract to male rats the elimination of these four isomers was studied in the liver, during a period of 10 days. Elimination rates for 2,3,7,8-TCDD, 1,2,3,7,8-PnCDD and 2,3,4,7,8-PnCDF were in the same range. Pharmacokinetic calculations were done on both tetra congeners, to obtain information about the validity of the published K_e values in the multiple dose experiments with male rats.

For 2,3,7,8-TCDF the K_e value was applicable, but for 2,3,7,8-TCDD the validity of the K_e could not be determined.     

Von der Erkenntnis zur Entscheidung

This contribution highlights the role and importance of ecotoxicology in regulatory decisions of chemicals legislation focussing on the responsibilities of the German Federal Environmental Agency (UBA). Therefore, organisational structures and processes relevant for making decisions concerning the risks of chemicals to men and the environment are described. As any regulatory decision starts with scientific findings, a brief overview of UBA’s activities with regard to own research and to initiate research in the area of ecotoxicology is provided. In addition, the vast importance of standardisation and international harmonisation of guidelines for testing and assessment of chemicals is illustrated, including the time- and ressource consuming character of these harmonisation processes. Subsequently, the involvement of regulatory decision making in intense and controversial scientific and political debates is emphasised. The transparency of these discussions and the independence of science is critically addressed in this context. In a final chapter the job requirements and options for qualification in Germany are described, ending up with a brief summary of the positive experiences with UBA’s contribution to the new advanced training course in ecotoxiciology realised by GDCh/SETAC GLB. A summary of the discussions on these different topics emphasises the specific challenge in regulatory ecotoxicology: To generate knowledge relevant for decision making, while acting in an area of conflict between scientific demands and economical as well as political interests.     

Exploring public perception of environmental technology over time

This paper analyses how new information shapes public perception of a controversially discussed technology over time. The test case analysed in this paper is solar radiation management (SRM), a potentially risky, environmental engineering technology, which aims to fight climate change by the injection of sulphate aerosols into the stratosphere. Using panel survey data, we show that most respondents initially show strong negative emotions towards SRM and reject the technology. However, public perception is not stable over time as emotions cool off and acceptance increases. The increase in acceptance is greater, the longer the cooling-off period between two surveys. Furthermore, we show that the cooling-off effect is more pronounced for more impulsive respondents.