Experiments in Animals

Once absorbed into the general circulation, regardless of the route of exposure, americium is excreted in both feces and urine. Evidence for this derives from experiments in animals that received an intravenous or intramuscular injection of americium (see Section 3.4.4.4). 

Frederick Gowland Hopkins, analytical chemist, physician and biochemist, had conducted numerous experiments in animal feeding prior to his famous comment in 1906 that no animal could live on a diet of pure protein, fat, carbohydrate, minerals and water. He cited the simple fact that animals live upon plants or other animals whose tissues contain many other substances besides those usually considered adequate for a normal diet, "...it is certain that there are many minor factors in all diets of which the body takes account." (11)... 

A) The study of the types of adverse health effects produced by chemicals under various conditions of exposure. Epidemiologists are similarly engaged in their studies of exposed human populations. Toxicologists are usually in the laboratory, carrying out experiments in animals and other test systems. 

Human data may provide direct information on the potential carcinogenicity of a substance. Human data may also reveal the carcinogenic potential of a substance for which experiments in animals either do not exist or have failed to indicate the carcinogenic potential of the substance. 

Several in vivo experiments in animals and humans suggest the existence of potentiators of histamine toxicity in spoiled fish. Parrot and Nicot (24) demonstrated that putrescine enhanced the lethality of orally administered histamine in guinea pigs. 

Metronidazole is effective in the treatment of acne rosacea although for this indication its mechanism of action is not clearly understood. Long-term topical use for this indication is not recommended. This advice is founded on experiments in animals showing a carcinogenic effect by oral administration of metronidazole. There is inadequate evidence of the safety of metronidazole in human pregnancy. Metronidazole is classified in Lactation Risk Category L3 (moderately safe). 

Biber A, Noldner M, Schlegelmilch R. Development of a formulation of Kava-Kava extract through pharmacokinetic experiments in animals. Naunyn Schmiedeberg s Arch Pharmacol 1992 345 R24. 

Isophorone can enter your body if you breathe its vapor, have skin contact with it, drink contaminated water, or eat contaminated food. If isophorone is present at a waste site near homes that use local wells as a source of water, the well water could be contaminated with isophorone. Experiments in animals show that after doses by mouth, isophorone enters easily and spreads to many organs of the body, but most of it leaves the body within 24 hours in the breath and in urine. Isophorone may enter the lungs of workers exposed to isophorone where it is used indoors as a solvent. Isophorone disappears quickly from outside air, so the chance of breathing outdoor air contaminated with isophorone is small. If isophorone is spilled at a waste site and evaporates, however, a person nearby may breathe isophorone before it disappears from the air. In addition, soil around waste sites may contain isophorone, and a person, such as a child playing in the dirt, may eat or have skin contact with the contaminated soil. How much isophorone enters the body through the skin is not known. More information on how isophorone can enter and leave the body can be found in Chapter 2. 

If human data are not available, other data on experiments in animals may be considered. However, models that involve feeding of low levels of antimicrobials to animals to determine the effects on intestinal bacterial populations are... 

It has been known for a long time that external agents (carcinogens) are capable of causing cancer, namely viruses, radiation, and chemicals, both natural and man-made. This information has been derived from both epidemiology and experiments in animals. 

Until recently, these bleeding diseases were treated by regular injections of the appropriate factors isolated from human plasma. This was both costly and carried a high risk of infection by HIV, hepatitis, or other contaminating viruses. Now, cloned genes are used for commercial production of the factors.572 573 Experiments in animals, designed to lead to eventual gene... 

Candidate genes can be selected using a variety of approaches such as literature searches, genes resulting from experiments in animal models, homology searches, and gene expression experiments. Studies testing even dozens of candidates at once exist for many complex diseases cardiovascular disease (83), osteoarthritis (84), and asthma (85) to name a few. 

Interest in investigating the relationship between dietary factors and carcinogenesis dates back to the early part of the century. Over the past four or five decades, epidemiological investigations and laboratory experiments in animals have generated abundant data about cancer and its relationship to dietary patterns, to individual foodstuffs, nutrients, food additives, and dietary contaminants (16). This vast body of literature was recently analyzed by the Committee on Diet, Nutrition, and Cancer of the National Research Council (6), and the committee reached the major conclusions outlined in Tables I to III. 

Total Caloric Intake. Neither the epidemiological studies nor the experiments in animals permit a clear interpretation of the specific effect of total caloric intake on the risk of cancer. Nonetheless, the studies conducted in animals show that a reduction in the total food intake decreases the age-specific incidence of cancer. The evidence is less clear for human beings ... 

Several studies of animals exposed to barium by parenteral routes indicate that barium decreases in serum potassium (Foster et al. 1977 Jaklinski et al. 1967 Roza and Berman 1971 Schott and McArdle 1974). In one study, dogs intravenously administered barium chloride demonstrated a decrease in serum potassium accompanied by an increase in red blood cell potassium concentration (Roza and Berman 1971). The authors concluded that the observed hypokalemia was due to a shift of potassium from extracellular to intracellular compartments and not to excretion. Additional intravenous studies have linked the observed hypokalemia to muscle paralysis in rats (Schott and McArdle 1974) and cardiac arrhythmias in dogs (Foster et al. 1977). These experiments in animals strongly support the suggestive human case study evidence indicating hypokalemia is an important effect of acute barium toxicity. 

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