Biological Test Systems

Compared to the physical/chemical test systems, the characterisation of biological test systems is quite another kettle of fish (literally ). Such test systems have not only to be described by a few specifications provided by the manufacturer , but they have to be cared for, properly housed or sited, they may need acclimatisation to the test environment before use, and their characteristics may need to be re-ascertained on a regular basis. They may react very sensitively to disturbances in their environment, and therefore the quality of the data obtained from these test systems can be ensured only through the establishment of the proper conditions. Consequently, the list of points to be observed with biological test systems for ensuring their GLP-compliance is more extensive than the one for the physical/chemical systems. 

As important as the identification of the test systems on their housing or containers is the appropriate identification of test system individuals or test system parts that may need to be temporarily removed. This may constitute no problem, if the test system consists of (larger) animals (or plants), where tags, tattoos, colour codes on fur or tail, implanted microchips or other suitable markers may be used to characterise and identify the single individuals. On the other hand, individual water fleas might have to be removed from the test 

Data about the physical characteristics of a bioreactor can provide only limited information. The complete characterization of a bioreactor requires additional studies involving biological test systems ( reference fermentations ). The fluid dynamics and rheological behavior of media are both directly and indirectly influenced by the presence of biological cells (Fiechter, 1978). Microbial processes whose growth or production kinetics are specifically dependent on changes in their medium or the reactor come into consideration as biological test systems (Karrer, 1978). Because of the central role of mass 

Excretion rates are correlated to peripheral stirrer speed increasing linearly for Mucor javanicus and Rhizopus javanicus and exponentially for P. pullulans  

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The area of nonsteroidal antiestrogens along with other classes of nonsteroidal antagonists of sex-steroid hormone action has been reviewed to 1986, and these compounds have been grouped by chemical stmcture as a basis of classification rather than any biochemical or biological test system utilized to assess antagonist activity (46). 

Lack of proper biological test systems to detect the causative agents ... 

Even cursory inspection of peptides collected in Table 2.1 provides compelling evidence that the diversity of endogenous peptides is comprised of a much broader set of components than traditional hormones, neuromodulators and antibiotics. In spite of the availability of scattered data on the activity of selected pool components the principal question on the biological role of peptide pools remains unanswered does the bulk of pool peptides represent transient products of protein substrate destmction on their way to reusable amino acid building blocks Or do these peptides perform a useful regulatory function The answer to these questions requires systematic study of a large number of samples in adequate biological test systems. 

In this review, drug concentrations or doses are assumed to be IC50 or ED50 values unless indicated otherwise. Abbreviations for routes of administration are p.o. (oral), i.p. (intraperitoneal) and i.v. (intravenous). The following abbreviations are used for common biological testing systems ... 

BIOLOGICAL TEST SYSTEMS FOR S-HT, RECEPTORS In vitro assays In vivo tests... 

Integrityofphysical/chemical test systems Biological test systems... 

Good Laboratory Practice is a quality system that is tailored to the needs of the modem laboratories. Its principles are very close to the principles of the modem quality management systems like ISO 9000 and ISO 17025. However, GLP is specific to the non-clinical health and environmental safety studies, it covers physical and chemical test systems, and gives emphasis to biological test systems. It is of utmost importance to note that GLP principles were set out by the Organization for Economic Cooperation and Development (OECD) and after being modified they were adopted by the Emopean Union and are now the Commission Directive 1999/11/EC. 

Like other medications also, psychopharmaceuticals can be classified according to various principles the chemist characterizes them by their chemical structure, the pharmacologist by their actions in representative biological test systems and the doctor by their therapeutic uses or indications. The classification according to clinical criteria today covers the following classes of psychopharmaceuticals ... 

Prerequisites are (1) a biological test system that is capable of registering the observed effect in an environmental system and (2) an applied concentration technique that acts as an interface between the environment and the test system. If biomonitoring indicates an unwanted exposure to chemicals, it must be translated in chemical terms. This chemical information can be used for control purposes to eliminate the exposure, preferably to a real no-effect level, so that no risk evaluation has to be made. This method requires a bioassay that is specific for an effect in an environmental system and a concentration technique that is specific for the collection and transition of compounds causing the effect. 

Substructurai analysis is substructure searching where weights are calculated, relating the presence of a specific substructure moiety in a molecule to the probability that the molecule is active in some biological test system [Cramer III et al, 1974 Craig, 1990 Klopman, 1992]. Examples of substructurai analysis are the - Klopman-Hender-son cumulative substructure count and the -+ Hodes statistical-heuristic method. 

The biological activities of sea cucumber glycosides and physical properties of these substances indicate an important external defensive function. Their functions must correlate with membranotropic action of glycosides against model biological test-systems. 

Whatever the biological test system is, ideally the identification and quantification of the metabolites would be based on a single analytical method. However the identification and the quantitation of metabolites and metabolite profiles remain a daunting task, even with the help of the most modern analytical tools. LC-MS is practical for small-molecular lipid-soluble chemicals (admittedly, a majority of compounds are such), but it does not cover many other types of chemicals. Consequently it is important to consider the scope or the chemical space of the chosen analytical method no single analytical technique is able to identify all potential metabolites [6],... 

Records related to the test system itself (for biological test systems acquisition, condition, suitability testing, etc. for physical-chemical test systems specifications, manufacturer, model, etc.) should be gathered and retained. 

It is certainly useful, in view of their divergent nature and properties, to distinguish between physical/chemical and biological test systems. The former ones consist of apparatus and instruments, the properties and specifications of which can be described in unequivocal, physical/chemical terms, while the latter ones may need much more intricate descriptions in order to fully characterise them. In consequence, the OECD GLP Principles are following this systematic differentiation. 

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