OBJECTIVETo investigate the toxicity of fipronil in mice and the therapeutic effects of diazepam and phenobarbital sodium.

METHODSMice were administered by gastric tube with fipronil at six doses and their behavioral changes, pathological changes in their major viscera under light and electron microscopy and deaths were observed after acute poisoning. Distribution and quantity of nerve cells positive in glutamic acid (Glu) or gamma-aminobutyric acid (gamma-GABA) in the brain of mice were detected by immunohistochemical methods and micro-image analysis. The time of death time and survival rate were observed and compared between the varied groups of mice injected intraperitoneally with diazepam and phenobarbital sodium, respectively, 0.5 h after poisoning by fipronil at dose of 90 mg/kg.

RESULTSAll the mice acutely poisoned by fipronil at varied doses showed some exciting symptoms in the central nervous system (CNS), including convulsion. Nuclear membrane space slightly expanded, neuroglia cells vacuolized and nerve fiber demyelinated under electron microscopy. The number and area of cells positive in Glu in the cerebral cortex of mice acutely poisoned by fipronil increased significantly, as compared to those in control mice. There was no significant difference in the number and area of cells positive in gamma-GABA in the hippocampal CA(1) region between poisoned and normal control groups. Survival rate of mice treated with diazepam or phenobarbital sodium was 58 percent.

CONCLUSIONMice with acute poisoning by fipronil appeared exciting symptoms in CNS, leading to damage in its nerve cells. Immunohistochemical techniques showed the damage could be related with the over-expression of glutamate transmitter in CNS. Early use of diazepam or phenobarbital sodium in treatment for acutely poisoned mice by fipronil could get better therapeutic efficacy.