TOXICITY (Greek toxikos the employee for greasing of arrows, i.e. poisonous) — ability of chemicals of a synthetic and natural origin at receipt in an organism in the quantity exceeding a measure of their pharmacological activity to break the normal course of processes of life activity that is expressed in emergence of toxic effects of a different orientation, intensity and duration up to development of poisoning. This article is devoted preferential to toxicity of pharmaceuticals.
Depending on frequency rate and duration of administration of substances in an organism distinguish acute and chronic T. V to medical practice toxic effect of medicines is usually connected with their overdose and is the most serious complication of medicinal therapy. Along with a dose intensity of toxic effect is influenced by duration of influence of medicinal substances and their ability to collect in an organism (See. Cumulation ).
Separate manifestations of toxic effect of medicines can be observed also at use of therapeutic doses, but it, as a rule, disappears after drug withdrawal and rather easily give in pharmakol. corrections (see. Side effects of pharmaceuticals ). Character of T. it can be connected with the basic pharmakol. by effect of drug (e.g., antikholinesterazny action of a prozerin), but in some cases it is distinguished from it (e.g., ototoksichesky action of nek-ry antibiotics). Distinguish the general and selective T. Depending on preferential localization of toxic defeat selective T. subdivide into a hepatotoxic, nephrotoxicity, a neurotoxicity, etc.
In addition to properties of the substance (a chemical structure, physical. - chemical properties, etc.), on degree of its T. conditions of the environment (air temperature and other physical factors), a condition of an organism influence (e.g., T. sharply increases at decrease in detoksitsiruyushchy function of a liver, at a delay of removal of toxicants and their metabolites owing to disturbance of secretory function of kidneys), and also specific, age, sexual and specific features of an organism. Besides, T. can raise at combined use of nek-ry pharmaceuticals.
Measure of T. the doses causing toxic effect or death of animals are. At a number of medicines range between medical and minimum toxic doses (width of therapeutic action) small therefore their use demands extra care, at others — the width of therapeutic action is rather big (see. Doses ). For assessment of degree of danger of the chemical substances applied in the industry establish maximum allowable concentrations (see).
Determination of T. enters the program of obligatory preclinical studying of new pharmaceuticals. At the same time acute T. (DL 50 ) define on several animal species taking into account a sex, age and the general state. If drug is intended for pediatric practice, its lethal dose is established also on young animals. Chronic T. study on three animal species. At the same time conduct overseeing by the general condition of animals, weight (weight) of their body, a picture of blood and the main fiziol. functions. After the end of a research or in case of death of animals conduct a pathoanatomical research. In the course of studying of chronic T. establish a possibility of manifestation embriotoksichesky, teratogenic and other types of toxic action. Duration of a research of chronic T. is defined by duration of use of drug in medical practice and makes 16 — 26 weeks, and in nek-ry cases exceeds these terms. Research T. new drugs it is conducted in strict accordance with the existing requirements (see. Control of pharmaceuticals ).
Bibliography: Methods of definition of toxicity and danger of chemicals, under the editorship of I. V. Sanotsky, M., 1970; Acute management at acute poisonings, under the editorship of S. N. Golikov, M., 1977; Albert A. Selective toxicity (The physicochemical basis of therapy), L., 1979; Hauschild F. Pharmakologie und Grundlagen Toxikologie, Lpz., 1973; Methods in toxicology, ed. by G. E. Paget, Philadelphia, 1970; Toxicology, The basic science of poisons, ed. by L. J. Casarett a. J. Doull, N. Y., 1975.