Evaluation of biological data

In spite of the temporal and spatial variability of aquatic populations, statistical techniques are available for the design of sampling program and for the evaluation of biological data. 

Kosta L, and Byrne AR (1982) Analytical evaluation of comparative data on trace elements in biological materials. J Radioanal Nud Chem 69 117-129. 

The first step of the dose-response assessment is the evaluation of the data within the range of observation. If there are sufficient quantitative data and adequate understanding of the carcinogenic process, a biologically based model may be developed to relate dose and response data. Otherwise, as a default procedure, a standard model can be used to curve-fit the data. For each mmor response, a POD from the observed data is estimated to mark the beginning of extrapolation to lower doses. The POD is an estimated dose (expressed in human-equivalent terms) near the lower end of the observed range, without significant extrapolation to lower doses. 

Due to the limited availability of test materials, the evaluation of biological materials often involves more statistical analysis to extract data than is typically used for the other materials classes. In this exercise, the use of statistics and spreadsheets will be illustrated in order to compare the experimental results of wear data for the candidate materials. 

Table 6-4. Biological evaluation of phytotoxicity of metal contaminated substrates with Phaseolus vulgaris as the test plant. Classification of biological data into phytotoxicity classes, depending on the magnitude of the effect (% of control for morphological parameters and enzymes capacities) (after Van Assche and Clijsters, 1990 Vangronsveld and Clijsters, 1992).

The accuracy of LD50 determinations cannot be verified in a given experiment since it can only be done once with one group of animals. Provided that normal healthy animals are used and the correct doses are administered by the proper route, the result must be accepted. The precision is another matter. Repetition of the study with animals of the same strain, sex, age, etc., may lead to somewhat different values because of biological variability. This can be dealt with by expressing the results in terms of confidence limits derived from a statistical evaluation of the data. These differences between experiments may not be great but it would not be unexpected if they were greater than those observed in chemical determinations. As a practical matter they are usually sufficiently accurate and precise for their intended purpose which is to indicate the relative lethality of the compound. 

Action. OCDM has in process two research projects having to do with collation and evaluation of available data on biological and chemical warfare in order to ascertain the hazards to the survival of the Nation from such attacks. 

Given the same dataset, different choices of preprocessing, clustering algorithms, and distance measures could lead to varied clustering results. Therefore, the assessment of cluster validity is of utmost important. However, in practice, the cluster quality is hard to evaluate, particularly in the analysis of biological data. 

LC/NMR in various combinations with LC/UV-DAD, LC/MS, LC/MSMS, LC/IR, and/or LC/CD has been used in many applications related to the online identification of natural products. In this field, the challenge for hyphenated techniques is important since often the characterization of completely unknown molecules is required in very complex biological matrices. In this case, LC hyphenated techniques are used for the chemical evaluation of biologically active fractions or extracts and for dereplication purposes. As full structure assignment is often needed, all online spectroscopic data are taken into consideration. Most applications are performed in the stop-flow mode and extensive 2D NMR correlation experiments are measured. For unknown online determination the need for data is often mandatory. This type of information can be deduced from HSQC and HMBC indirect measurements and very recently it has been demonstrated that even direct measurements were possible in a crude plant extract. For this application the LC peak of interest was preconcentrated by trapping on SPE and the measurement was performed on a cryogenic flow... 

It must be emphasized that reference values are statistically derived and do not represent toxicologically derived biological exposure limits. Thus, they cannot be used for health-related evaluation of HBM data. Nevertheless, the reference values permit to assess the exposure of individuals or population groups compared to the ubiquitous background exposure. 

The scope of ICH QIE addresses the evaluation of stability data that should be submitted in registration applications for new molecular entities and their associated drug products. A systematic approach should be adopted in the presentation and evaluation of the stability information. The stability information should include, as appropriate, results from physical, chemical, biological, and microbiological tests. Mass balance should be assessed and the factors that can cause an apparent lack of mass balance the mechanism of degradation and the stability-indicating capability and inherent variability of the analytical procedures. 

For all three compounds, biological data relevant to the evaluation of carcinogenic risk to humans are summarized in the World Health Organization International Agency for Research on Cancer monograph (70). 

The first step is to identify the substances present at the workplace. As a starting point, knowledge of the process is needed in order to formulate a list of all chemical agents used in the establishment. The list should include not only primary products but also intermediate and final products, as well as reaction products and by-products. For the chemical agents in the list, it is necessary to know their chemical properties, especially hazardous ones their OEL values, including biological limit values and, where these are not available, other technical criteria that can be used to evaluate the risk. It is also helpful to include any information on the safety and health risks of those substances provided by the supplier or other readily available sources. This information on dangerous substances and preparations, in the form of safety data sheets, is intended primarily for industrial users, to enable them to take the measures necessary to ensure the safety and health of workers. 

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