Animal relevance

The various types of transgenic animals relevant to a rational drug-finding and drug-development process... 

Select one or more available relevant models (e.g., age of animal, relevance to human disease). 

Henderson RF, Sabourin PJ, Medinsky MA, et al. 1992. Benzene dosimetry in experimental animals Relevance for risk assessment. In D Amato R, Slaga TJ, FarlandWH, et al. Relevance of animal studies to the evaluation of human cancer risk. New York, NY Wiley-Liss Inc. 93-105. 

Henderson, R. F, Sabourin, R. J., Medinsky, M. A., Birnbaum, L. S., and Lucier, G. L. (1992). Benzene dosimetry in experimental animals Relevance for risk assessment. Prog Clin Biol Res 374, 93-105. 

Canning B J (2007) Encoding of the cough reflex. Pulm Pharmacol Ther 20 396-401 Canning B1 (2008) The cough reflex in animals relevance to human cough research. Lung 186 S23-S28... 

It is good practice to keep concentrations of airborne nickel in any chemical form as low as possible and certainly below the relevant standard. Local exhaust ventilation is the preferred method, particularly for powders, but personal respirator protection may be employed where necessary. In the United States, the Occupational Safety and Health Administration (OSHA) personal exposure limit (PEL) for all forms of nickel except nickel carbonyl is 1 mg/m. The ACGIH TLVs are respectively 1 mg/m for Ni metal, insoluble compounds, and fume and dust from nickel sulfide roasting, and 0.1 mg/m for soluble nickel compounds. The ACGIH is considering whether to lower the TLVs for all forms of nickel to 0.05 mg/m, based on nonmalignant respiratory effects in experimental animals. 

These three nitrofurans have been used therapeutically for over 30 years with no reports of human neoplasia and the relevance of the animal findings to short term therapy in humans has not been estabUshed. 

Vimses contain either RNA or DNA, and this nucleic acid composition forms the basis for thek classification. Although vimses ate known to infect bactetia, insects, plants, animals, and humans, this discussion is restticted to the important vimses of vertebrates. The relevant vimses ate summarized in Table 2, using the nomenclature and taxonomy recommended by the International Committee on Taxonomy of Vimses (4,5). 

Within the constraints of this article it is impossible to be comprehensive in the coverage of the subject matter, in terms of the chemicals involved and in the widely varying practices and areas of the world in which the title compounds are ingested by farmed animals. This account is, however, intended to give an overview, citing some relevant examples, of the beneficial and adverse effects, in animals and on the environment, of man-made compounds and naturally produced compounds in extensive and commercial production systems. 

Compounds Affecting Rq>roduction Compounds that can affect reproductive function include several drugs and occupationally important chemicals such as solvents and pesticides as well as a number of environmentally relevant com-fxrunds. A group of chemical compounds that has received much attention recently is endocrine disrupters, many of which are halogenated hydrocarbons, e.g., PCBs. These are known to induce feminization in fish and other animal species.1.5/ There is intense debate about the significance of these compounds to human health. Tobacco smoke and ethyl alcohol also have major effects on human reproduction, the effects of alcohol being especially important. Table 5.17 lists compounds that may disturb the functions of female and male reproductive functions. 

A. Probably carcinogenic ro humans Limited evidence on carcinogenicity in humans and sufficient evidence on carcinogenicity in experimental animals and other relevant evidence... 

The biotransformation of a given chemical compound in experimental animals and in humans may differ. Furthermore, high doses of chemical compounds are used in studies with experimental animals, and this may cause alterations in biotransformation of the tested chemicals that do not occur at the lower doses relevant to the human exposure situation. For example, a metabolic pathway dominating at low doses may become saturated, and a salvage metabolic pathway, e.g., one that produces reactive intermediates of the compound, may become involved in the biotransformation of the chemical. Since this intermediate could never be produced at the exposure levels encountered in humans, the overall result... 

One way to do so is to look at the normal mode corresponding to the imaginary frequency and determine whether the displacements that compose it tend to lead in the directions of the structures that you think the transition structure connects. The symmetry of the normal mode is also relevant in some cases (see the following example). Animating the vibrations with a chemical visualization package is often very useful. Another, more accurate way to determine what reactants and products the transition structure coimects is to perform an IRC calculation to follow the reaction path and thereby determine the reactants and products explicity this technique is discussed in Chapter 8. 

There are no data on kinetics or metabolism in humans therefore, no conclusions can be drawn as to the relevance of animal data to human metabolism of these compormds. 

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