Animal studies general considerations

Animal studies show considerable difference in sensitivity for the various species. The 4-hour LCso for guinea pigs and rabbits was approximately 770 ppm rats were slightly more sensitive with a 4-hour LCso of 660 ppm, and mice were the most sensitive species, with a 4-hour LCso of 145 ppm. All species followed a general pattern of eye irritation, loss of coordination, and, if death ensued, convulsions. For example, dogs exposed at 773 ppm had irritation of the eyes, nose, and extremities within 60 minutes at 458 ppm, tremors occurred within 15 minutes, and signs of irritation, including lacrimation, were apparent within 50 minutes 272 ppm produced tremors within... 

Animal studies on the neurotoxicity of carbon disulfide have usually been done in rats and provide histopathologic and neurochemical data that support a neurotoxic effect for carbon disulfide. In general, the doses used in these animal studies are considerably higher than the occupational exposures seen in epidemiological studies. 

A number of studies in humans show that PUFAs can generate significant immunomodulatory effects. Generally, these studies have utilized considerably lower amounts of fish oil to treat subjects than found in most animal studies. Numerous clinical trials have examined the effects of fish oil on rheumatoid arthritis and many have reported statistically significant benefits such as decreased morning stiffness and numbers of tender joints [57]. Several other studies have reported that PUFAs can provide therapeutic benefits for patients with IgA nephropathy, the most common primary human glomerulonephritis... 

The most relevant study to base a hazard assessment and derivation of a tolerable intake upon is a study that reflects the human exposure situation as well as possible. Eor numerous substances, data are only available from acute (single exposure), subacute (14—28 days), or subchronic (90 days) animal studies. In order to derive, e.g., a TDl or RfD for such a substance, it may be necessary to base the assessment on data from a shorter duration study. An assessment factor allowing for differences in the experimental exposure duration and the duration of exposure for the population and scenario under consideration needs to be considered taking into account that, in general, the experimental NOAEL will decrease with increasing exposure duration as well as other and more serious adverse effects may appear with increasing exposure duration. 

In general, the adverse effects of radium are believed to be the consequence of the radiation emitted from the element itself and its daughter products. Because there is already a considerable amount of information on the effects of radiation on humans and animals derived from studies on the effects of the atomic bomb and of therapeutic x-ray and gamma-ray treatments of malignancies, the experimental animal studies with radium have made no attempt to duplicate this information. They have instead concentrated on radium s most sensitive endpoint, cancer. For example, it can be predicted that the beta and gamma rays emitted by a radium source will produce local radiation burns and tissue damage when the source is placed on human or animal skin, hence there have been no valid reasons to conduct such studies with radium. 

For biomarkers such as the troponins and enzymes, timing and sample collection are particularly critical for the detection of cardiac injury, and consideration must be given to the half-life of the molecule and its mass. Although some data are available for humans, data are sparse for the same measurements in laboratory animals. In general, the half-lives of these molecules are less in smaller animals. The importance of sample times has been shown in several studies where myocardial lesions have been induced by the administration of toxic doses of sympathomimetics (O Brien et al. 1997a, 2006 York et al. 2007). 

General Considerations When Conducting Animal Studies... 

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