Avaliação da Mutagenicidade do Indoxacarbe em Ratos e Gatos

Abstract

Background: Pesticides are substances used for pest control. Because of their persistence in the environment, they can induce toxicity in humans and animals. Indoxacarb is an oxadiazine insecticide that acts against insects of the order Lepidoptera. Furthermore, indoxacarb has demonstrated strong insecticide activity against fleas; therefore, it is used in ectoparasite treatment. Choice of species used in this study (rats and cats) is based on several factors such as these animals have a high count of micronucleated polychromatic erythrocytes, thereby facilitating the execution of the chosen assay; rats are the standard animal model for mutagenicity studies; and the product is intended for use in cats. Limited data in literature pertaining to the mutagenic effects of this product motivated this study. The aim of this study was to evaluate the mutagenicity of indoxacarb when administered in one and tenfold therapeutic doses in rats and cats. This evaluation was performed using the micronucleus test. Materials, Methods & Results: Forty male Wistar rats aged 70 days and weighing 280 ± 10 g and 20 mixed breed male and female adult cats weighing 4 ± 0.2 kg were selected. These animals were obtained from the central animal facility and cattery, respectively, of the university of origin. Rats were reared in individual cages with a controlled temperature of 22°C ± 2°C, humidity of 55% ± 5% and 12-h light dark cycle. Cats were reared in individual stalls with water and food ad libitum. Animals were randomly distributed into four groups comprising 10 rats and 5 cats in respective groups: negative control group, which received 0.9% sodium chloride solution as a single topical administration; positive control group, which received 50 mg/kg cyclophosphamide as a single intra-peritoneal (rats) or intravenous injection (cats); indoxacarb group, which received indoxacarb as a single topical dose according to the manufacturer s recommendations; and high dose indoxacarb group, which also received indoxacarb in a single topical dose, but at a tenfold concentration. Rats were evaluated 24 h after indoxacarb administration. After euthanasia, rat femurs were obtained and their medullary canals were washed using fetal bovine serum. The content was centrifuged and used for smear preparations. Cats were evaluated using the micronucleus test before and 24 h after indoxacarb administration. For smear preparations, a drop of peripheral blood samples was obtained from the tail tip. Smear fixation, staining, and microscopic analysis were similar for cats and rats. Statistical analyses were performed using analysis of variance with contrast through Tukey s method and paired t test to compare time points. The significance level was 5%. Indoxacarb showed no mutagenic activity in the two species and doses evaluated. Even in animals subjected to high doses, the micronuclei count remained within the normal range (p > 0.05). Discussion: The results of this study corroborate those of other studies, where in the mutagenic capacity of indoxacarb was similar in different animal species and product delivery routes. In addition, it is of note the speed and ease of micronucleus testing, which makes it an important mutagenicity bioassay.