PubMed · 11301738
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
T Faragher. 2001. To 'e' or not to 'e'.. https://pubmed.ncbi.nlm.nih.gov/11301738/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Toxicity of a compound for an organism is dependent on the route of exposure, the amount (or concentration), the way in which the compound is taken up, distributes and is eliminated from the organism (ADME, kinetics) and the intrinsic properties (reactivity; mode of action, dynamics) of the compound towards the organism. These three elements: exposure, kinetics and dynamics form the basis of hazard and risk evaluations. Developments in our knowledge of the way in which physico-chemical properties of chemicals (on the one side) and physiological processes in the organism (on the other side) determine a compound's toxicity have greatly increased our understanding of toxicological processes and our ability to interpret experimental results. This has now resulted in the development of model systems in which the above-mentioned processes can be described mathematically. Biokinetic modelling is currently of great interest, but the further development of toxicodynamic modelling is equally important. The combination of both allows the estimation of a compound's critical amount/concentration on the critical site of action, which ideally would be the basis for hazard and risk assessments. In vitro systems have been extremely useful in studying the molecular basis of a chemical's biological activity, including its mechanism(s) of toxic action. Other achievements include the prediction of biological reactivity on the basis of a compound's physico-chemical properties and the construction of quantitative structure-activity relationships (QSARs). However, for the incorporation of in vitro-derived data as well as the results of QSARs, kinetic modelling is indispensable. Thus, biokinetic and toxicodynamic modelling are important (if not crucial) tools in toxicological research and there are increasing opportunities to incorporate the results of this work in hazard and risk assessments. Their implementation will allow a much more scientifically-based and a better structured risk assessment, which will be to a much lesser extent relying on animal experimentation.
This study compared in vivo bioactivity with the in vitro apatite-forming ability of biomaterials. Granules of five kinds of P(2)O(5)-free Na(2)O-CaO-SiO(2) glasses, showing different apatite-forming ability in simulated body fluid (SBF), were implanted into a defect on the femoral condyle of rabbits. Bone ingrowth was evaluated using scanning electron microscopy among five kinds of glasses at 1, 2, 3, 6, and 12 weeks. Quantitative analysis was performed measuring the depth of new bone ingrowth from the periphery. In addition, the total areas of newly formed bone among glass particles were examined at 3 and 6 weeks using confocal laser scanning microscopy (CLSM) after weekly administration of fluorescent calcein. The depth of bone ingrowth among glass particles increased in proportion to their apatite-forming ability in vitro. The CLSM study showed a correlation between the quantities of labeled newly formed bone and in vitro apatite-forming ability. In the P(2)O(5)-free Na(2)O-CaO-SiO(2) glasses, the periods within 3-6 days for inducing apatite in SBF considered a necessary condition to convey bioactivity in vivo, and in vivo evaluations at 2-3 weeks is important to determine this. The in vivo bioactivity was precisely reproduced by apatite-forming ability in SBF. Therefore, evaluating apatite formation in SBF is a good screening test for the in vivo bioactivity of materials, resulting in reduction of the need for animal sacrifices and savings in experimental time.
For licensing the efficacy of vaccines for veterinary use has to be demonstrated by well-controlled laboratory experiments in which vaccinated and untreated animals of the target species are challenged. Erysipelas challenge tests cause extreme suffering of the unprotected animals with high fever, apathy, large skin lesions, and even death. This paper describes a standardised procedure for the vaccination challenge test and gives due consideration to the welfare of the animals. By monitoring and using clinical signs observed during the test it is possible to minimise animal pain and distress, thus preventing unnecessary animal suffering.