The results of the acute toxicit y studies of “Dolosan Forte ®” tablets

Abstract

This study aimed to evaluate the parameters of acute toxicity of the new combined tablets “Dolosan Forte®” (containing zirilon – 2,4-dichlorobenzoic acid potassium salt, pitofenone hydrochloride, fenpiverinium bromide) worked
out by PJSC “Red Star”. It has been shown that LD50 for these tablets administered intragastrically equals 13231 ± 2775 mg/kg in male rats, 13216 ± 3379 mg/kg in female rats, 14393 ± 1669 mg/kg in male mice and 11963 ± 2023 mg/kg in female mice, corresponding to the V class of practically nontoxic substances (5000 mg/kg < LD50 < 15000 mg/kg). The death of the rats and mice receiving the investigated tablets can be possibly caused by the neurotoxic action of the drug with the rapid development of convulsions. The survived animals demonstrated normal state during 14 days. Macroscopic examination showed the absence of the morphological signs of the toxic effect of “Dolosan Forte®” tablets on the visceral systems of the survived rats and mice (except for the increment of the relative organ weights in the groups of animals
receiving doses causing high lethality rate). Microscopic investigation did not reveal any pathological changes of the internal organs of rats after the single intragastric administration of “Dolosan Forte®” tablets at a dose of 6000 mg/kg. There were no interspecies as well as sex-specific differences in “Dolosan Forte®” toxic effects. The obtained results together with the data in the literature concerning LD50 for the components of “Dolosan Forte®” show that combined use of zirilon (2,4-dichlorobenzoic acid potassium salt), pitofenone hydrochloride, fenpiverinium bromide does not cause the increase in their acute toxicity.