SUB-CHRONIC TOXICITY STUDY OF METHANOL AERIAL PART EXTRACT OF INDIGOFERA STENOPHYLLA ON WISTER RAT

INTRODUCTION 1.1 Background to the study Toxicity is the degree to which a substance can harm humans or animals. It can be measured by its effects on the target organism, organ, tissue or cells. The toxic effects of a substance on animal physiology can range from minor changes such as reduced weight gain, small physiological alteration or change in the levels of circulating hormones, to severe effects in organ functional loss leading to death. Intermediate levels of toxicity may cause pain and suffering (Raji, 2014). During toxicity studies, five major aspects are put into consideration. These include organs affected by the chemical, relevance of quantification effect, concentration of chemical to be tested, in vitro markers of toxicity that are relevant to the chemical and how to use the data from in vitro test for risk assessment. . The most poisonous substances are neurotoxins which affect the nervous system, followed by cytotoxins and metabolic poisons that disturb liver, heart, kidneys, respiration, muscles and reproduction. Toxic plants are plants that have in their constitution chemical compounds or active principles, which through contact, inhalation or ingestion, are capable of causing injury, disease and even death in humans and animals. These compounds may be alkaloids, glycosides, saponins, oxalates, tannins, among others. [Mendieta, et al., 2018] These compounds are part of the secondary metabolites of plants and although they are considered toxic to humans and certain animals, they have a reason to exist because they play important roles in protecting the plant against certain predators and pathogens. The toxicity of plants differs from plant to plant and depends on several factors, namely the different chemicals that characterize it. The part of the plant ingested, its concentration, the chemical substances present, the age, the physical conditions for its development (type of soil, humidity, temperature, time of year), and the ripening state of its fruits are aspects to consider. Fortunately, most poisonings are characterized by irritations of the gastrointestinal tract, such as nausea, vomiting, diarrhea and some dermatological discomfort, such as dermatitis. There are, however, more severe poisonings in which cytotoxicity or central nervous system depression can occur, which can lead to respiratory and cardiac failure, leading to death. The best way to minimize accidental intoxication with toxic plants is to be aware of them. This knowledge should be disseminated by the population in general, especially to childhood educators and to official entities that do mapping drawings of parks and gardens. In case of accidental ingestion, the remainder of the plant should be removed from the mouth, which should be rinsed with water. The plant must be stored for identification so that the most appropriate treatment can be obtained. It is important to avoid inducing vomiting, as it may cause blockage of the glottis and suffocation. [Mendieta, et al., 2018]. Toxicological studies in the pharmaceutical field have been growing exponentially. These developments have been prompted by discovery of teratogenic effects of drugs such as thalidomide, exposure of chemicals to the environment and employees and by conduct and assessment of toxicity studiesas part of good manufacturing practice (Traina, 2016). Meanwhile, Acute toxicity is caused by an agent when it is administered in one or more doses over a period not exceeding 24 hour and involves harmful effects to the organism through single or short- term exposure. Acute toxicity studies have also been used during the selection of starting doses for phase-I human and animal studies, and provide information relevant to acute overdosing in humans and animals. The testing is based on the route of substance administration to the animal and therefore it is classified from Class-1 to Class-5 for oral, dermal, gas inhalation, vapor/dust/mist inhalation and injection. Dosing can be repeated during the administration of test material by a variety of routes of exposure, including gavaging which involves stomach intubation or forced feeding, injection, skin, painting and inhalation. The acute toxic class method, a step-wise procedure, involves the use of three animals of a single sex per step. Depending on the mortality and/or moribund status of the animals, on average 2 to 4 steps maybe necessary to allow judgment on the acute toxicity of the substance. The subchronic toxicity studies method is a step wise procedure that last for 28 days after the acute toxicity was determine. The graded doses of sub-chronic toxicity study are 150,300,600mg/kg were use during the experiment.