COMPARISON OF LD₅₀ FOR BOTULINUM TOXIN TYPE A IN DIFFERENT ANIMAL SPECIES.

Patrícia dos Santos Carneiro (Serv. Bact./IBu); Mônica Colombini (Vac. Anaeróbicas/IBu); José Marcos Oliveira (Vac. Anaeróbicas/IBu); Dirce Sakauchi (Vac. Anaeróbicas/IBu); Patricia Reginato Facciotti (Vac. Anaeróbicas/IBu); Aryene Góes Trezena (Vac. Anaeróbicas/IBu); Hisako Gondo Higashi (D. Bioindustrial/IBu); Sally Müller Affonso Prado (Serv. Bact./IBu)

Introduction: Clostridium botulinum produces toxins that have been classified into 7 serotypes, A, B, C, D, E, F and G, according to their immunological characteristics. Toxin type A, and sometimes type B, have been used to treat dystonia and various other muscle hyperactivity syndromes in humans. The increase of botulinum toxins medical use has raised the need for precise analysis of the biological activity contained in the toxins preparations for both clinical use and laboratory investigation. One of the most important parameters that must be observed in pharmaceutical products used in humans is the LD₅₀ since it is directly related with safety. Objectives: The aim of this study was to compare the value of LD₅₀ for botulinum toxin type A in different animal species. Methods: According to international convention the fundamental unit (IU) of botulinum toxin biological activity is defined as the LD₅₀ for the toxin in a population of mice (1 LD₅₀ = 1 IU). It was conducted two LD₅₀ experiments with guinea pigs and rabbits (25 animals/specie). The doses varied between 2 and 4 IU to guinea pigs and 15 and 75 IU to rabbits. The administration of botulinum toxin type A into guinea pigs was performed by intraperitoneal injection, whereas in rabbits by intravenous injection. The LD₅₀ was determined by using a computerized PROBIT-LOG program. Results and discussion: To compare the value of LD₅₀ among species the results were converted in IU/Kg. The value to guinea pigs was calculated to 10.33 ± 1.95 IU/Kg and to rabbits was 17.31 ± 0.21 IU/Kg. Considering that the value to mice is stipulated according international convention in 50 IU/Kg, it is concluded that all these values has a statistical difference (p<0.001) among themselves. There are significant differences of sensibility to lethal effects of botulinum toxin type A into rodents, since mice are more resistant than guinea pigs. In the same way, mice are more resistant than rabbits. These data suggest that there are important differences in susceptibility to botulinum toxin type A among animal species, even into the same order (Rodentia) or between different orders (Rodentia x Lagomorpha).