International workshop. Internal exposure--linking bioavailability to effects.
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Environmental Exposure↗
Biomedical subjects
Beate Escher
Publications and source records attributed to Beate Escher.
The EU-project ERAPharm. Incentives for the further development of guidance documents?
Triggered by the detection of a large variety of pharmaceuticals in surface waters, soils and groundwaters across the world (e.g. Halling-Sørensen et al. 1998, Daughton & Ternes 1999, Jones et al. 2001, Heberer 2002) and the widespread occurrence of endocrine active compounds and related effects in the environment (e.g. Purdom et al. 1994, Tyler et al. 1998, Vethaak et al. 2002), pharmaceuticals in the environment have become an issue for both the scientific and the public community. During the last few years, our understanding of the fate and effects of pharmaceuticals in the environment has progressed significantly. However, there are still a number of uncertainties concerning the effects of pharmaceuticals on the environment and the assessment of potential exposure (e.g. Hanisch et al. 2004, Salomon 2005). These uncertainties will be addressed by the EU-project 'Environmental risk assessment of pharmaceuticals' (ERAPharm). This project, a specific targeted research project, is carried out within the priority 'Global change and ecosystems' of the 6th framework programme of the European Union. ERAPharm has started on 1st October 2004; the project duration is three years.
Drug-Related Side Effects and Adverse Reactions↗
Evidence for heterodimers of 2,4,5-trichlorophenol on planar lipid layers. A FTIR-ATR investigation.
Trichlorophenols are weak acids of high hydrophobicity and are able to transport protons across the mitochondrial membrane. Thus the proton motive force is dissipated and the ATP production decreased. In situ Fourier Transform Infrared-Attenuated Total Reflection (FTIR-ATR) experiments with 2,4,5-trichlorophenol (TCP) adsorbed to model membranes resulted in good evidence for the formation of the TCP-heterodimer. Two surfaces were examined: a dipalmitoyl phosphatidic acid (DPPA) monolayer and a planar DPPA/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer. TCP was adsorbed from 1 to 3 mM solutions at pH 6.0 to the lipid layers leading to surface layers at the water/lipid interface. Difference spectra showed an effect on DPPA acyl chains even when it was covered with POPC. Time-resolved measurements revealed two distinct adsorption processes, which were assigned to TCP and its deprotonated anion (phenoxide), respectively. For DPPA/POPC bilayers, the adsorption of TCP was faster than that of its phenoxide, whereas adsorption of both species to DPPA monolayers proceeded with similar velocity. In both cases, phenoxide formation at the membrane was found to be delayed with respect to phenol adsorption. Phenoxide and phenol were retained after replacing the TCP solution with buffer. For the retained species, we estimated a phenol/phenoxide molar ratio of 1 at pH 6.0 (pKa=6.94 for TCP), demonstrating strong evidence for heterodimer formation.
Adsorption↗
Probabilistic approaches in the effect assessment of toxic chemicals. What are the benefits and limitations?
There is an ongoing discussion whether in the environmental risk assessment for chemicals the so called 'deterministic' approach using point estimates of exposure and effect concentrations is still appropriate. Instead, the more detailed and scientifically sounder probabilistic methods that have been developed over the last years are widely recommended. Here, we present the results of a probabilistic effect assessment for the aquatic environment performed for the pesticide methyl parathion and compare them with the results obtained with the common deterministic approach as described in the EU Technical Guidance Document. Methyl parathion was chosen because a sufficient data set (acute toxicity data for about 70 species) was available. The assumptions underlying the probabilistic effect assessment are discussed in the light of the results obtained for methyl parathion. Two important assumptions made by many studies are: (i) a sufficient number of ecologically relevant toxicity data is available, (ii) the toxicity data follow a certain distribution such as log-normal. Considering the scarcity of data for many industrial chemicals, we conclude that these assumptions would not be fulfilled in many cases if the probabilistic assessment was applied to the majority of industrial chemicals. Therefore, despite the well-known limitations of the deterministic approach, it should not be replaced by probabilistic methods unless the assumptions of these methods are carefully checked in each individual case, which would significantly increase the effort for the assessment procedure.
Animals↗