Animal study procedures

Schechter et al. (7) in their studies on DDT in milk found that interfering extractives are largely removed by treatment with strong sulfuric acid. Furman and Hoskins (2) found the same treatment effective when hexachlorocyclohexane was the contaminating substance, and it has been applied in later work to numerous extracts of plants and animals. The procedure now used when either DDT or hexachlorocyclohexane is suspected is as follows ... 

The purpose of the regulations was to ensure proper operation of laboratories that generated data to support either INDs or NDAs. In particular, they addressed animal studies, including animal care and animal accountability. They also involved the equipment used to do the various procedures for analysis and the maintenance and calibration of the equipment. In general, these regulations now cover the operation of the laboratories and how the data are collected and... 

Ex vivo procedures involve removing cells and transfecting or transducing them. The cells should be checked to confirm that they are all healthy and that they are still expressing their normal surface markers, etc observations of normal growth characteristics can also be reassuring. Animal studies are of limited value to test the safety of transfected or transduced human cells. 

An alternative method of assessing interoceptive drug effects is the behavioral drug discrimination procedure, which relies on observable behavioral responses to determine whether a drug s stimulus effects have been perceived by the subject (Preston 1991 Overton 1991). Behavioral drug discrimination is widely used in animal studies (Holtzman 1990 see chapter by Stolerman, this volume) because it... 

Data from epidemiological studies, of sufficient quality, are generally preferred for estimating risks. When the evaluation is based on animal studies, the estimation of a human-equivalent dose should utilize toxicokinetic data for cross-species dose scaling if adequate data are available. Otherwise, a default procedure should be applied. The aim of the cross-species dose scaling is to define exposure levels for humans and animals that are expected to produce the same degree of effect, taking into account differences in scale between test animals and humans, such as size and life span. 

Several studies have suggested increased sensitivity of older persons to effects of benzodiazepines (Table 3). For example, midazolam, widely used for rapid sedation for procedures, requires lower doses to reach defined end points of sedation that is attributable to a 59% reduction in the EC50 (the concentration that produces 50% of the maximum effect) and not to changes in pharmacokinetics, as shown in Fig. 3. The reasons for this increased sensitivity are not known. Animal studies have not shown any difference in brain benzodiazepine receptor density or affinity or effects on the associated chloride channel function with ageing. In any event, benzodiazepine doses should be reduced in older patients. 

There exists no scientific basis for the use of animal studies to predict the antitumor effect of a compound however, a fairly good correlation has been shown between the antitumor effects seen in animal studies and those observed in the clinical setting [210], In order to produce an animal model which possesses the requirements listed above, the variable factors present in the experimental procedure, and the characteristics of the tumor and animals must be addressed. 

To evaluate the safety aspects of a drug intended for use in food-producing animals, multistep procedures have to be applied. A major portion of these procedures refer to toxicity studies. Over the last 30 years, a broadly accepted package... 

Another important dietary source of trans fat is conjugated linoleic acid, a class of compounds collectively known as CLA. Many CLA isomers contain conjugated cis/trans and trans/trans double bonds. Interest in CLA research has increased significantly in the past few years because several cis/trans CLA isomers have been reported to exhibit different beneficial physiological effects in animal studies (Yurawecz et al., 1999). The reader is referred to a collection of analytical papers published in a dossier (Mossoba, 2001, and references therein) that details several chromatographic and spectroscopic techniques and procedures that have been successfully applied to CLA analysis. 

The safety factor Itself may vary, depending upon the nature of the test data available and on other Judgmental factors. When long-term animal studies are available, the 100-fold safety factor generally Is applied. The food additive procedural regulations (21-CFR 170.22) refer to a safety factor of 100 to 1 in applying animal test data to humans. Exceptions to the 100-fold safety factor may be allowed for certain substances and under certain circumstances of use for example, in the case of micronutrients or macronutrients, or when information on dose-response effects in humans Is available. 

As the procedure of the animal study part of this method is well established, modifications occur mainly in the technological part by improvement... 

This was adopted in 1995 (OECD 1995c). In principle this test is a combination of the study for effects on fertility and early embryonic development (also called fertility study) and the study for effects on embryo-fetal development for drugs (also called teratogenicity study ), of the ICH test guideline for drags. The study procedure is extended up to four days after parturition. The experimental male animals are continuously exposed to the chemical up to the end of the mating attempts and the females are continuously exposed throughout the study up to day four after parturition. 

Statements on which regulatory guidelines, such as 21 CFR 58 for FDA GLP compliance, will be followed and on Animal Care Committee protocol review Information on the drug substance, which commonly includes the test article name or number, identification criteria, physical description, who is responsible for test article characterization, the concentration(s) to be used, recommended storage conditions, inventory maintenance, formulation procedures, reserve samples, retention samples, analyses for content and homogeneity (if necessary), disposition, and safety precautions Information on the animal species to be studied, animal husbandry procedures, such as housing, food, water, contaminants, environment conditions, acclimation, and justification of selection... 

Data for assessing reproductive or developmental toxicity are derived both from observations of humans and from experimental animal studies. It is beyond the scope of this document to enumerate the kinds of data that can permit a complete assessment of reproductive and developmental toxicity that covers all situations. The definition of a sufficient data set changes as scientific knowledge accumulates on specific agents and as the understanding of the predictive capabilities of animal models and other procedures improves. Appendix C and Appendix D of this document describe studies that commonly provide such information and offer guidance in their interpretation. 

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