Experimental animals, care

Anesthetics must be chosen according to the species used for experiments and the national and institutional regulations/ guidelines for experimental animal care. Euthanasia must follow the guidelines issue by relevant veterinary authority, e. g., https // www.avma.org/kb/poHcies/documents/euthanasia.pdf... 

Adequate data on individuals, taken over periods of time, are not available but it seems evident that, even though there may be substantial intra-individual fluctuations, the histological blood picture differs from individual to individual and follows a different pattern of change for each individual. Some types of cells are relatively abundant in the blood of certain individuals but are practically absent from the blood of others. Individuals who suffer from allergies are thought to have, under comparable environmental conditions, high eosinophil counts in their blood. Individual differences in blood histology are found in experimental animals which are kept under the same carefully controlled environmental conditions. 

Subsequent studies in experimental animals have yielded provocative results. Resveratrol is known to extend the lifespan of a number of organisms from yeast to vertebrates. Resveratrol is also known to prevent or slow the progression of cancer, cardiovascular diseases, diabetes, inflammation, and ischemic injuries in experimental animals. In short, the suggestion that resveratrol in red wine may be responsible for favorable outcomes in human health is supported by a number of studies in experimental animals. However, the support is suggestive but certainly not definitive. Carefully controlled clinical trials in people will be required to establish the role, if any, of resveratrol or related small molecules in human health. Such clinical trials are currently underway. 

In summary. Directive 86/609/EEC requires the premises in which animal research is undertaken and persons conducting such research, to be subject to local registration and inspection and imposes limitations upon the breeding and supply of experimental animals. There are specific provisions regarding the care of experimental animals, including, for example, minimum caging and temperature requirements. As a Directive, 86/609/EEC required implementation... 

Emulsions containing antigens are just as immunogenic to humans as to the experimental animal. Great care should be exercised during all the procedures. 

Chloromethyl methyl ether and bis-chloromethyl ether (CICH2 OCH2Cl) in common with several alkylating agents possess carcinogenic properties in experimental animals and have been listed as assumed human carcinogens similar hazardous properties associated with dichloromethyl methyl ether have not been reported but it would be prudent to handle this compound with due care. 

All experimental and surgical procedures were approved by the Animal Care and Ethics Committee of Kanazawa University. The subjects of our investigations were female Japanese macaque monkeys (Macaca fuscata). These were kept in air-conditioned cages sized approximately 1 m on a side. The monkeys were allowed free access to water and were daily fed with artificial animal food, and fruits or vegetables. In total, tissues from 29 monkeys were included in the present study one monkey was neonatal (14 days old, sacrificed on postnatal day 14 P14), while the rest of the monkeys were sexually mature (age of 5-13 years). 

Hl-KO, H3-KO, histamine HI, H3 receptor gene double knockout (HI/H3-DKO), HI, H2, and H3 receptor gene triple knockout (TKO), and their WT mice were used in this study. The mice were bred in our laboratory (Sakurai et al., 2008). All experiments were performed in accordance with institutional guidelines, and experimental protocols were approved by the Animal Care Committee of Tohoku University. 

Male C57/BL6 mice (20—22 g) (Charles River, Italy) were housed in a temperature (22 °C)- and humidity (65%)-controlled room and were maintained under a 12 h light/dark cycle (lights on from 7 00 a.m. to 7 00 p.m.), with ad libitum access to food and water. The experimental protocol was in accordance to the guidelines of the Ministry of Health for animal care (D.M. 116/1992). 

A commonly used test in experimental animals is the dominant-lethal test, generally assumed to monitor the induction of chromosomally abnormal sperm. There are reports of loss of fertility of human males exposed to various chemicals. It is difficult to attribute such effects to genetic events, rather them to cellular effects. An increase in genetically defective sperm, detected by a decrease in fertility, would require a very large and carefully controlled study. The use of birth control and the changing social patterns of family size virtually rule out evidence on fertility as useful in monitoring mutagenesis. 

For the acute dermal irritation/corrosion study, the albino rabbit is considered as the preferred species, although several mammalian species may be used. At least three healthy adult animals should be used. Additional animals may be required to clarify equivocal responses. All experimental animals should be individually caged. Feeding and maintenance of animals should be uniform as described for acute oral toxicity. Approximately 24 hours before the test, the fur from the dorsal area of the trunk should be clipped or shaved. Care should be taken to avoid abrading the skin. Only animals with healthy, intact skin should be used for the study. 

Animals that comprise the satellite group for follow-up studies should be kept under observation for 14 days without treatment. This procedure detects persistence of toxic effects (if any), as well as manner of recovery. A careful clinical examination should be made every day. Action should be taken to minimize the loss of experimental animals, (e.g., identifying animals that are moribund, doing necropsy, refrigeration of animals that are found dead, sacrificing weak or moribund animals). 

Many of the studies on the effects of chemical exposures on the growth and development of the lungs have been performed in experimental animals however, patterns of lung development differ between animals and humans. Because of these differences, extreme care must be taken when extrapolating the results from animal studies to human situations. 

To test whether or not respiratory exposure may have been a major source of contamination not accounted for in earlier studies, we studied the effect of respiratory exposure of lactating cows on excretion of pesticides in the milk. Holstein cows from the University of Arizona dairy herd were used as experimental animals. The animals were fed normally, with care to assure feed intake of less than 0.1 p.p.m. of chlorinated hydrocarbon pesticide. 

Neurotoxicity caused by chemical substances requires careful interpretation based on well confirmed data on experimental animals and surveys of workers and the general population. Neurotoxicity is one of several noncancer end-points that share common default assumptions and principles. The interpretation of data as indicative of a potential neurotoxic effect involves the evaluation of the validity of the database. Attention should be given to the existing gaps—for instance, (1) identification of the specific toxic substance, (2) knowing the observed effects and significance in terms of neurotoxicity, and (3) whether the conclusions made agree... 

As the historical examples at the beginning of the chapter demonstrated, it is essential that food additives be carefully tested for the potential to cause adverse or untoward effects before humans are exposed to them. The testing is normally carried out in experimental animals in vivo (in the living organism) but information from in vitro (in the test tube) experiments may also be taken into account. 

When reliable and good quality evidence fi om human experience or appropriate studies in experimental animals, as described in the criteria for substances, is available for the mixture, then the mixture can be classified by weight of evidence evaluation of these data. Care should be exercised in evaluating data on mixtures that the dose used does not render the results inconclusive. (For special labelling required by some competent authorities, see Notes 1, 3 and 5 to Table 3.4.1 of this chapter.)... 

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