In current ethics debates, the protection of animals and the environment are central themes. In this context, reference is made to "ethics of responsibility". In the reality of scientific life and the conduct of science, "ethics of responsibility" have only had a modest impact.
Reflection based on the history of thought may explain this finding. Upon abolishing God, man has redirected an initially religious love and devotion toward himself. The postulate of unfettered dominion over the Earth has become the supreme principle. "Theoria" in the sense of its original meaning, that is a celebratory admiration for sacred Nature, is incomprehensible to modern man. Nature has been stripped of its sanctity and transformed into something to be exploited for its human utility. Consequently, today the credo applies that to interpret the freedom of science according to ethical principles is utterly untenable. The author pleads for reconsideration.

The legislation of the European Union captures experimental animal research only in part. Binding standards can be found in various legal records of the community-legislation, and in particular in the so-called guideline for animal experimentation 86/609/EWG. But these guidelines do not represent an actual animal protection measure but rather one of harmonisation with the primary goal of unification of the regulations of the participating states in order to prevent distortions of competition and trade barriers which could harm the common market. Although the guideline contains some practicable approaches in the direction of an up-to-date animal experimentation law, it only defines general goals which allows for considerable leeway in national implementation within the individual EU countries, and it has only a limited area of legal operation. On the one hand, only vertebrae are being included, and on the other, the law is only being applied in the area of applied research and protects only animals used in product- and substance-development or test procedures as well as those used in the framework of environmental protection. Various important fields of research are thus not subject to a common regulation and are assigned to national regulation. This concerns animal experimentation in education and training or for military or so-called defence-relevant medical purposes and, in particular, the whole area of basic research including the field of genetic engineering in animals with it's growing significance.
The guideline is in need of widening it's scope of application as well as of various adjustments to recent scientific findings and developments in order to become suitable as a more restrictive animal protection law on the community level. It could also be desirable to include animal protection into the catalogue of community-goals in order to make it an independent component of the politics of the Union and to establish the groundwork for a decree of comprehensive and efficient regulations.

The legislation of the European Union captures experimental animal research only in part. Binding standards can be found in various legal records of the community-legislation, and in particular in the so-called guideline for animal experimentation 86/609/EWG. But these guidelines do not represent an actual animal protection measure but rather one of harmonisation with the primary goal of unification of the regulations of the participating states in order to prevent distortions of competition and trade barriers which could harm the common market. Although the guideline contains some practicable approaches in the direction of an up-to-date animal experimentation law, it only defines general goals which allows for considerable leeway in national implementation within the individual EU countries, and it has only a limited area of legal operation. On the one hand, only vertebrae are being included, and on the other, the law is only being applied in the area of applied research and protects only animals used in product- and substance-development or test procedures as well as those used in the framework of environmental protection. Various important fields of research are thus not subject to a common regulation and are assigned to national regulation. This concerns animal experimentation in education and training or for military or so-called defence-relevant medical purposes and, in particular, the whole area of basic research including the field of genetic engineering in animals with it's growing significance.
The guideline is in need of widening it's scope of application as well as of various adjustments to recent scientific findings and developments in order to become suitable as a more restrictive animal protection law on the community level. It could also be desirable to include animal protection into the catalogue of community-goals in order to make it an independent component of the politics of the Union and to establish the groundwork for a decree of comprehensive and efficient regulations.

The European Commission is planning to put forward drafts for a new chemicals legislation by June 2002. In fulfillment of an Environmental Council Conclusion, Working Groups have been set up for consultation during the ongoing preparatory stage. There, members of the General Directorates Environment and Enterprise discuss relevant topics with representatives from authorities, industry, environmental and animal protection organisations. There is agreement that animal tests shall be reduced to a minimum. However it is still unclear how this goal can best be achieved. In this context, the designing of testing strategies will play a major role. It is explained, why fixed test catalogues should be replaced by flexible tiered testing strategies and how concrete waiving strategies can contribute to avoiding animal tests. Another important aspect is the EU-wide implementation of a clause on the avoidance of duplicate testing, which is already enforced in Germany and Austria. In these Member States, first parties have to provide data from previously performed animal tests to second parties. Finally, it is discussed that the application of new non-animal tests can be promoted, if the revised EU chemicals policy once again contains the legal framework for an EU-specific acceptance of new test methods.

The European Commission is planning to put forward drafts for a new chemicals legislation by June 2002. In fulfillment of an Environmental Council Conclusion, Working Groups have been set up for consultation during the ongoing preparatory stage. There, members of the General Directorates Environment and Enterprise discuss relevant topics with representatives from authorities, industry, environmental and animal protection organisations. There is agreement that animal tests shall be reduced to a minimum. However it is still unclear how this goal can best be achieved. In this context, the designing of testing strategies will play a major role. It is explained, why fixed test catalogues should be replaced by flexible tiered testing strategies and how concrete waiving strategies can contribute to avoiding animal tests. Another important aspect is the EU-wide implementation of a clause on the avoidance of duplicate testing, which is already enforced in Germany and Austria. In these Member States, first parties have to provide data from previously performed animal tests to second parties. Finally, it is discussed that the application of new non-animal tests can be promoted, if the revised EU chemicals policy once again contains the legal framework for an EU-specific acceptance of new test methods.

The acute fish test is an animal test whose ecotoxicological relevance is worthy of discussion. The primary aim of protection in ecotoxicology is the population and not the individual. Furthermore the concentration of pollutants in the environment is normally not in the lethal range. Therefore the acute fish test covers solely the situation after chemical spills. Nevertheless, acute fish toxicity data still belong to the base set used for the assessment of chemicals. The embryo test with the zebrafish Danio rerio (DarT) is recommended as a substitute for the acute fish test. For validation an international laboratory comparison test was carried out. A summary of the results is presented in this paper. Based on the promising results of testing chemicals and waste water the test design was validated by the DIN-working group "7.6 Fischei-Test". A normed test guideline for testing waste water with fish is available. The test duration is short (48 h) and within the test different toxicological endpoints can be examined. Endpoints from the embryo test are suitable for QSAR-studies. Besides the use in ecotoxicology the introduction as a toxicological model was investigated. Disturbance of pigmentation and effects on the frequency of heart-beat were examined. A further important application is testing of teratogenic chemicals. Based on the results DarT could be a screening test within preclinical studies.

Botulism is one of the most important bird diseases world-wide and is caused by the intoxication with Botulinum-Neurotoxin-C1 (BoNt-C1), which is produced by toxigenic clostridia under appropriate conditions. Avian botulism leads regularly to large losses among the migrating bird populations breeding and resting at the saltwater pools of the Austrian national park Neusiedler See-Seewinkel. Despite of its ethical dubiousness and its high technical expense the mouse-bioassay is still used as the routine standard method for the detection of BoNt-C1. According to the 3R-concept, in vitro alternative methods for the qualitative detection of BoNt-C1 (immunostick-ELISA) and a corresponding BoNt-C1 gene fragment (nested-PCR) were established. In order to estimate the BoNt-C1 production potential the methods were tested with sediment samples from different saltwater pools subjected to cultivation conditions appropriate for in vitro BoNt-C1-production. With the mouse-bioassay, 52 out of 77 samples were found to have a positive toxin production potential. The immunostick-ELISA showed a similar sensitivity as the mouse-bioassay and exhibited a highly significant positive correlation (r=0.94; p<0.001) with the mouse-bioassay in detecting BoNt-C1. The nested-PCR approach revealed higher numbers of positive BoNt-C1 gene fragment detections as compared to the direct toxin analysis approaches. A weak correlation (r=0.21; p=0.07) with the mouse-bioassay was discernible, no correlation was found with the immunostick-ELISA (r=0.09; p=0.46). Obviously, the PCR approach detected the BoNt-C1 gene fragment in some of the samples where no toxin expression has occurred. Thus it is suggested that the qualitative immunostick-ELISA represents a potential in vitro alternative to the mouse-bioassay for assessing the BoNt-C1 production potential in environmental samples. In contrast, qualitative BoNt-C1 gene fragment detection via PCR led to an overestimation of the actual toxin production potential.

Blastocyst-derived pluripotent embryonic stem (ES) cells of the mouse can be induced to differentiate in culture into a variety of cell types, including cardiac muscle cells. In the embryonic stem cell test (EST) the capacity of ES cells of the mouse cell line D3 to differentiate into contracting cardiomyocytes is used to assess the embryotoxic potential of test compounds and in addition, the effects on the viability of ES cells and differentiated mouse fibroblasts (cell line 3T3) are compared. The three endpoints are used to classify the embryotoxic potential of chemicals after 10 days of exposure: (i) the inhibition of differentiation of ES cells into cardiomyocytes (ID50) and (ii) the decrease of viability of 3T3 cells (IC503T3) and (iii) ES cells (IC50D3) in a MTT cytotoxicity test. Applying linear analysis of discriminance, a biostatistical prediction model (PM) was developed to assign test chemicals to three classes of embryotoxicity. In an international validation study funded by ECVAM it could be demonstrated that the EST can predict the embryotoxic potential of a test compound as good as frequently used mammalian systems based on pregnant animals. In a joint project with major German pharmaceutical companies we are attempting to improve the EST by establishing molecular endpoints of differentiation (e.g. cardiac, neuronal, chondrogenic) in cultured ES cells. We have studied the expression of tissue specific proteins in ES cell cultures in the presence of embryotoxic chemicals by immunofluorescent antibody techniques, e.g. FACS analysis. The other groups are focusing on endogenous gene expression in early development by RT-PCR methods or the DNA microarray technique. The results obtained recently using molecular markers specific for cardiac differentiation and employing intracellular flow cytometry for quantification will be presented. Molecular endpoints will allow improvement of the EST by measuring gene expression patterns in a small number of murine ES cells.

In view of the increasing need for laboratory primates in biomedical research it is desirable to develop appropriate primate-specific cell culture models that could prevent or significantly reduce the increasing use of primary cultures and experiments with living animals. Follicular granulosa and theca cells are essential for the control of hormone-dependent processes such as the ovarian cycle and pregnancy, but also for the occurrence of hormone-dependent diseases. For this reason it is of great interest to know more about control mechanisms existing in these follicular cell types and the effect of pharmacological or toxicological agents on them. An immortalisation protocol for the two ovarian cell types of the marmoset monkey (Callithrix jacchus) has been developed . All cell lines established so far were examined with regard to the maintenance of known, tissue-specific features (e.g. hormone responsiveness and enzyme expression). The results obtained indicate that it is worth while cloning and characterising the cell lines in more detail so that they could be used after an adequate validation as a defined test system both for basic research as well as for pharmacological or toxicological screening.

A comparative study of rabbit pyrogen test and human whole blood assay was performed on released preparations of human serum albumin. In addition, the samples were spiked with 5 IU/ml (in whole blood 0.5 IU/ml too) and 10 IU endotoxin/ml. The unspiked samples were negative in both assays.
The human whole blood test resulted in the same level of security for the products as the rabbit pyrogen test did. Both, the borderline 5 IU/kg and the 10 IU/kg-Spike partially lead to results of the rabbit test which would cause further testing with additional animals. In contrast, the human whole blood assay resulted in a 100% detection for the 5 IU/ml and 10 IU/ml-Spike. We designed a study protocol for a minimised number of test animals and were able to show the general usefulness of the human whole blood assay.

Bacteria and viruses may be transmitted through contaminated biological materials such as transplantable tumors, cell lines, sera or other biological material.
Currently, the screening of biological material is being done using the mouse or rat antibody production (MAP/RAP) test (serological testing).
We decided to test and validate an alternative assay using polymerase chain reaction (PCR / RT-PCR) technology to detect viral contamination directly in biological material.
The aim of this study therefore is the validation of our new PCR assays and the comparison of PCR and MAP test.
For 6/14 viruses the conventional PCR seems to be more sensitive and more specific in detecting murine viruses. In 12/14 viruses the RT-PCR is more sensitive than the MAP-test. In 2/14 cases all detection methods have the same sensitivity. Furthermore, PCR screening clearly contributes to the principles of 3R as a replacement technique as it eliminates the need for using animals to screen for murine viruses in biological material.

During the last decade there have been many clinical case reports on severe arrhythmias following drug administration. These potentially fatal heart rhythm disturbances are often associated with a QT interval prolongation in the ECG. The aim of the present study was to evaluate, whether isolated hemoperfused porcine hearts from slaughter pigs are suitable to detect a drug effect on the ECG. In the absence of test substances heart rate, QT or QRS interval remained fairly constant during 4 hours of perfusion. In contrast, after application of the positive control sotalol a reproducible, concentration-dependent QT interval prolongation as well as adverse effects such as described in clinical case reports were observed. Lidocaine, which served as a negative control, did not change QT interval duration. As a complex model the isolated hemoperfused porcine heart is a versatile system for monitoring drug effects on heart electrophysiology. Therefore, the model might reduce or even replace certain in vivo dog experiments in heart toxicology and safety pharmacology.