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By Dr. Harold C. Grice (auth.), H. C. Grice (eds.)

The foreign lifestyles Sciences Institute (lLSI) is a systematic beginning wh ich addresses serious health and wellbeing and issues of safety of nationwide and overseas difficulty. ILSI promotes foreign cooperation by way of professional­ viding the mechanism for scientists from executive, and universities to interact on cooperative courses to generate and disseminate medical facts. The individuals and trustees of the Institute think that questions relating to future health and defense are top resolved while scientists can ex amine and talk about concerns, as an self sustaining physique, se~arate from the political pressures of person international locations and the industrial issues of person businesses. usually, significant review of the danger of a try out substance is hindered by means of the inherent inconsistencies within the process. the advance and refinement of equipment and platforms to judge the security of chemical compounds have developed in a quick and principally unplanned type. makes an attempt to enhance the process have mostly been directed towards wide basic issues, with little awareness being given to precise difficulties or matters. A failure to solve those difficulties has often led to elevated checking out expenditures and issues within the review and extrapolation of the implications. exposure surrounding toxicologic concerns has created persistent public apprehension concerning the skill of technological know-how and govt to deal successfully with those difficulties. in line with those problems, ILSI has assembled hugely certified and popular scientists from learn institutes, universities, executive and undefined, with appropriate medical wisdom and services in regards to the matters that complicate threat evaluate procedures.

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Extra resources for Interpretation and Extrapolation of Chemical and Biological Carcinogenicity Data to Establish Human Safety Standards: The Use of Short-Term Tests for Mutagenicity and Carcinogenicity in Chemical Hazard Evaluation

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It is now believed that enzymes which cause the detoxification of chemicals are only rarely the same enzymes which cause activation. Evidence is accumulating that cytochrome P-450 is generally involved in detoxification reactions, whereas activation is usually caused by cytochrome P-448 (Parke and loannides, 1981 a). Since there are pronounced species differences in the predominance of these enzymes (both microsomal and cytosolic), major differences in the ratio of detoxification/ activation ofpre-carcinogens may occur in different species.

The reason for the proportionality of the activity of mixed function oxidases to body weight is probably that it is dependent on other factors besides the concentration of tissue oxygen. , 1967). Toxicity of oxygen in the tissues is another factor related to mixed function oxidase activity which should be considered. The free radical theory of oxygen toxicity attributes the damaging effects of hyperoxia to the production of reactive species like the singlet oxygen, hydroxyl radical and superoxide anion.

Synergism and Antagonism 47 In some cases, the mechanism involved may be more complex. For instance, phenobarbital antagonizes the anti-tumor and the immunodepressant effect of cyclophosphamide. , 1975). Antagonism mayaiso result from inhibition of metabolism of a drug which requires biotransformation to exhibit its effect. , 1980). In other cases, the duration of action characterizes the antagonism. A short-acting drug may antagonize the action of a long-acting drug with a similar effect. Pertinent examples in this respect are the antagonism between tetrabenazine and reserpine, two releasers of monoamines (Manara and Garattini, 1967) and tranylcypromine and iproniazide, two mono amine oxidase inhibitors (Pletscher and Besendorf, 1959).

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