**7. Medicinal plant use in therapy**

**5. Toxicity of chemicals**

66 Herbal Medicine

**5.1. Acute toxicity**

**5.2.** *Chronic* **toxicity**

**6. Toxicity of medicinal plants**

*Datura* spp., *Digitalis* spp. [17].

Toxicity refers to the relative ability of a substance to cause adverse effects in living organisms [13]. It may also be defined as the extent to which an exposed tissue is damaged by a chemical substance and covers the effect on a whole organism and sub-structural component of an organism such as the cell (cytotoxicity) or organ (organotoxicity). Toxicity may further be defined to cover the study of the adverse effects of chemicals on living organisms as well as their symptoms, mechanisms and treatments. Toxicity studies may be classified as acute, subacute/subchronic and chronic effects depending upon the quantity and duration of administration of the agents [14].

Acute toxicological studies investigate the toxic effects produced by a single large-dose exposure to a toxicant lasting no longer than 24 h. This may result in severe biological effects (harm or death) to the organism. The results of acute toxicity are not only important in the consideration of accidental poisoning with a chemical but also are used for the planning of chronic toxicological studies [15]. The development of tolerance is usually revealed by an acute exposure. The starting point for toxicological classification of chemicals uses the LD50 value, which is the dose administered in acute toxicity testing that causes death in 50% of experimental animals [16].

Chronic exposure refers to the administration of a toxin over an extended period of time, usually measured in months or years; this can cause irreversible toxicity. Periods between acute and chronic exposure could be referred to as subacute or subchronic. The results of chronic and acute toxicological studies help in the evaluation of any possible hazardous effect of a new drug or a drug which is in use with little or no documentation of its systemic toxicity.

Generally, medicinal plants contain bioactive compounds which demonstrate both intra- and inter-species variation in type and content. Plants by virtue of their chemical constituents are potentially toxic; thus, some plants used in traditional medicine are intrinsically toxic. Some plants well known in traditional medicine to be toxic or poisonous include *Atropa belladonna*,

Many plants used in traditional medicine or used as food have demonstrated some toxicity (mutagenic and carcinogenic) effects [18]. The issue of the possible toxic, genotoxic and/or mutagenic effects of plants used in traditional medicine has been highlighted in the review by Fennell et al. [19]. However, some of the toxic plants are useful to man as medicines and also as poisons for hunting and for use as pesticides, for example, Datura (tropane alkaloids), Digitalis (cardiac glycosides) and Pyrethrum (pyrethrin insecticides). Well-known medicinal plants have demonstrated toxicity in laboratory studies and field observations. For example, *Lantana camara* used in the management of malaria and other diseases has been reported to be hepatotoxic in several animal species which could be of concern regarding its chronic use in man [20]. The basis for the medicinal use of the plants is the presence of mixtures of different biologically active plant constituents or phytochemicals (secondary metabolites) such as alkaloids, glycosides, terpenoids, and so on that may act individually, additively or in synergy to demonstrate an effect which may be useful or harmful to health. Some of these plants have been designated as poisonous plants because of their effects in impacting biological functions in other organisms which are harmful [24]. They are therefore damaging to either the survival or the normal function of the individual. The dose received may be due to either acute (short) or chronic (long-term) exposure. However, in TM, plants with toxic constituents are known and are avoided or used cautiously in herbal product formulations. Even if these are employed in medicinal products, they are employed below toxic levels and hence, if at all, hardly result in any fatality when administered by professional practitioners or experienced persons.
