Comparative assessement of the toxicity of Chlorpheniramine and Dexchlorpheniramine in mice and rats and their influence on the hematological indices in the chronic toxicity in rats.

personАвтори: N. Bojadjeva, T. Dimitrov

Summary.

In the experiment, there is made a comparative analysis of the toxicity of the H1-antagonists Chlorpheniramine and Dexchlorpheniramine in relation of their acute toxicity and the influence of their chronic toxicity on hematological indices. Acute toxity is studied on 120 male and 120 female rats Wistar and 120 male and 120 famale mice in two ways of aministration – per os and i.p. Dexchlorpheniramine, the dexrarotatory isomer of Chlorpheniramine, has the characteristic toxicity of Chlorpheniramine as the average lethal doses (LD50) are almost the same for Chlorpheniramine and Dexchlorpheniramine in rats and mice of both sexes as per os also i.p. The chronic toxicity is studied in the course of 120 days in 175 male and 175 famale rats Wistar. Chlorpheniramine and Dexchlorpheniramine are administered per os daily in doses 15, 30 and 60 mg/kg (correspondend to 1/20, 1/10 and 1/5 from LD50) and in the controls respectively 0,5 ml per l00 g body weight 0,9% NaCl. At 30th, 60th and 90th day after the daily administration of Chlorpheniramine and Dexchlorpheniramine in doses 15, 30 and 60 mg/kg, there are not established statistical reliable changes in the levels of hematocrit (Hct), hemoglobin (Hb), erythrocytes (Er), leucocytes (Leu) and platelets (Thr) as in the male also in the famale rats in comparison with the control groups. After cessation of the treatment with H1-antagonists at 30th day, i.e. on 120th day from the beginning of the trial, there are observed by 60 mg/kg Chlorpheniramine moderate increase in the levels of Hct and Er in the male rats, while after 60 mg/kg Dexchlorpheniramine in the female rats there is insignificantly decreased Hct and Er and Thr. This late effect on the blood count has to be taken into account if Chlorpheniramine and Dexchlorpheniramine are applied in very high doses and for a long time. The results from the toxicological investigation point out that Dexchlorpheniramine retains the properties of Chlorpheniramine in relation of the acute toxicity and the influence of the chronic toxicity on the blood count in experimental animals.

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