Mutagenicity assessment of indoxacarb in rats and cats.

Background: Pesticides are substances used for pest control. Due to 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. Choice of rats and cats used in this study is based on factors such as these animals have a high count of micronucleated polychromatic erythrocytes 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 effect of the micronucleus test on the mutagenicity of indoxacarb when administered in one and tenfold therapeutic doses in rats and cats. 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 degrees C +/- 2 degrees 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: Different animal species when young and adults may have different number of micronucleated erythrocytes and the presence of spontaneous micronucleus, especially in young animals. The species used in this study are considered excellent biomonitors mutagenicity by having high levels of micronucleated erythrocytes. The peripheral blood analysis also showed more favorable, since blood samples from the same animal can be conducted and evaluated at different times. The results of this study using the indoxacarb topically in rat and cat, corroborated with other authors, showing the absence of mutagenicity in rat and cat species, ease of reproduction, fast and inexpensive test, making it like this important mutagenicity bioassay.