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An Animal Model to Study Health Effects During Long-Term Low Dose Exposure to Toxic Agents

An Animal Model to Study Health Effects During Long-Term Low Dose Exposure to Toxic Agents,Gudrun Cassel,David Rocksén,Ann Göransson Nyberg

An Animal Model to Study Health Effects During Long-Term Low Dose Exposure to Toxic Agents  
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The immediate and long term consequences of acute intoxication with nerve agents and other toxic substances are well known. Potential harmful delayed effects of repeated exposure to low levels of these agents have attracted less attention. These effects may be of relevance to military personnel possibly exposed to non-symptomatic levels of toxic substances during international peace-keeping operations, to agricultural workers and to the general population exposed to toxic substances of widespread use. To verify or deny if exposure has occurred analyses of biological samples from human material are of importance. When it comes to pre-medication and adequate medical treatment, it is necessary to find specific markers for the toxic agent as early as possible after exposure. Typical biomarkers of exposure include measurements of the toxin or its specific metabolite, while changes in for examples physiological parameters are biomarkers of effect. The aim of this investigation was to develop an animal model to study the long-term health effects of chronic intoxication in awake, freely moving rats. To exclude the influence of stress, male Wistar rats were instrumented with telemetry devices for continuous (24 hours) measurement of mean arterial pressure, heart rate, body temperature, activity and respiratory rate. Sustained subcutaneous release of low doses of the organophosphate substance VX was administrated through an osmotic pump. Once a week blood samples for analysis of exposure biomarkers were taken. The result shows that this rat model is a useful tool to study long term effects of different doses of toxic substances in freely moving rats.
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