Animal species determination population

This information may affect selection criteria for the study population and the choice of tests in addition to routine safety monitoring, and will certainly determine the starting dose, range of doses, maximum exposure and dose increments to be studied. Pharmacokinetics in man may be quite different from those in animal species so that plasma and, if possible, tissue concentrations are generally more important than dose. One exception to this may be hepatotox-icity resulting from exposure of the liver to portal blood drug concentrations, when the oral dose administered to the animals may be more relevant than the systemic plasma concentrations, which reflect first-pass metabolism as well as absorption. 

Organisms evolving under aimual temperature cycles and in environments with varying temperatures spatially have incorporated thermal cues in reproductive behavior, habitat selection, and certain other features which act at the population level. Thus, the balance of births and mortaUties, which determines whether a species survives, is akin to the metaboHc balance at the physiological level in being dependent upon the match, within certain limits, to prescribed temperatures at different times of year. At the ecosystem level, relationships among species, eg, predators, competitors, prey animals, and plant foods, are related to environmental temperatures in complex ways. Many of these interactions are poorly understood. 

The LD50 is the statistically derived single dosage of a substance that can be expected to cause death in 50% of the sample population. It is therefore an indicator of acute toxicity, usually determined by ingestion using rats or mice, although other animals may be used. LD50 is also determined by other routes, e.g. by skin absorption in rabbits. The values are affected by species, sex, age, etc. 

The determination of an acceptable dose for humans involves the application of uncertainty factors to reflect the fact that, unlike the experimental animal, there is wide variability and susceptibility of response in the genetically diverse human population. Variations in gender, age, hormonal and disease status can affect the response to a chemical. In order to minimise any potential risks, uncertainty factors are applied to the NOAEL to arrive at a reduced exposure that is considered tolerable - namely the acceptable daily intake or ADI. These are usually tenfold for variations in susceptibility amongst the human population (the intra-species factor) and tenfold for the potential... 

Data for lead effects on mammalian wildlife are scarce. Shore (1995) indicates that lead residues in soils could successfully predict lead concentrations in kidneys and livers of wood mice and field voles however, this could not be demonstrated for shrews. In view of the large interspecies differences in lead responses reported for domestic livestock and laboratory populations of small animals (Table 4.9), more research is needed to determine if lead criteria for these groups are applicable to sensitive species of mammalian wildlife. 

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