Studies in Mammals

An illustration of the variable responses to nicotine concerns aphids. In an experiment, 2 per cent of an insect population died or became moribund when exposed to 0.0001 M nicotine solution, 48 per cent were affected when the concentration was 0.0025 M, and 98.5 per cent when the concentration was 0.012 M. The concentrations of nicotine required to affect all the insects alike varied more than 120-fold.21 The pharmacology of nicotine as studied in mammals is notably complex and unpredictable, partly because many sites of action are involved. Its effect on different human individuals is also diverse, but it has not been adequately investigated, particularly in view of the fairly well established fact that amblyopia and Buerger s disease occur in relatively rare cases directly because of its use.22... 

Developmental Toxicity. It is not known whether 1,2-diphenylhydrazine crosses the placenta, but there is no reason to assume that it (or its metabolites) would not do so. Developmental studies in mammals would provide information on possible fetotoxic and teratogenic effects of... 

In a number of reproductive studies in mammals, using a variety of selenium compounds, adverse effects have only been seen at doses that are associated with maternal toxicity "... 

Numerous laboratory studies in mammals have demonstrated that ricin and abrin are highly toxic and potentially fatal to animals and humans. Major symptoms of both ricin and abrin poisoning are dependent on the route of exposure, the dose (or number of beans) received, or the content of toxin in the seed (or age of seed). Upon ingestion, toxicity is dependent on the degree of mastication if the bean was... 

Mass Balance Studies. Mass balance studies may be performed using a combination of an aortic cannula, indwelling stomach tube (oral administration studies), urinary catheter, fecal catheter, and collection/extraction of flowing immersion water (branchial products). Unlike mass balance studies in mammals, such studies require this experimental format as the water serves as a common depot for all wastes and importantly serves as a confounding source for reuptake. These studies can be performed in restrained and free swimming animals, however, in either case require intensive effort and experimental diligence. 

The results of in vitro studies show that at least some chemical forms of manganese have mutagenic potential. However, as the results of in vivo studies in mammals are inconsistent, no overall conclusion can be made about the possible genotoxic hazard to humans from exposure to manganese compounds. 

The enzyme asparaginase has been extensively studied in mammals and microorganisms because of its potential antineoplastic activity (Wriston and Yellin, 1973). The presence of the enzyme was suggested in plant tissues by early workers (Chibnall, 1939 Kretovich, 1958 McKee, 1962), but never confirmed. 

The host-mediated assay is a simple technique that attempts to bridge the gap between in vitro microbial studies and definitive tests in mammals. The numerous advantages of microorganisms as determinants of hereditary change are utilized in an experimental mammal after it has had an opportunity to metabolize the compound under investigation. This assay was developed to determine the ability of laboratory animals to either potentiate or detoxify compounds in regard to their mutagenic activity. In addition to the studies in mammals, it is essential to conduct the in vitro assay as a control for the host-mediated assay. 

During the past five years, however, a new concept in toxicological evaluations has emerged.This new concept involves the implementation of shortterm in vitro and submammalian assays as indicators of chronic toxicity for mammals. Several factors have been instrumental in the increased emphasis on short-term tests, but the major one has been the increased costs associated with chronic toxicity studies in mammals. Costs for typical carcinogenicity studies in mice and rats in 1973 ranged from 65,000 to 75,000 per chemical. The... 

This brief listing of compounds for which humans report one of the four basic taste sensations supports the notion that these compounds have great ecological relevance for many species. This does not mean that each has equal relevance for all species, or that other stimuli do not have relevance for some species (c.f., 23). Indeed, within one taxonomic group, the responses of individual species to various chemical stimuli may differ considerably. The degree to which these differences represent adaptations to the unique ecological conditions encountered by each species has not been thoroughly studied in mammals. 

Although the L-arginine-NO pathway has been identified in many species including fish, birds, and bacteria, NOS has been best studied in mammals (Knowles and Moncada 1994 Nathan 1992). Based upon several criteria including cellular localization, regulation of activity, and substrate/inhibitor profiles, three isoforms of NOS enzymes have been described and subsequently cloned. Molecular cloning has shown these to share 50-60% homology. 

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