虫螨腈原药致畸毒性实验研究

Study on the teratogenicity of chlorfenapyr in rats

目的通过在胚胎器官形成期连续经口给药，探讨虫螨腈原药对大鼠是否存在胚胎毒性和致畸毒性。方法无特定病原体级健康性成熟期未交配的雌、雄性sD大鼠各200只，按1：1比例同笼交配。受孕成功的雌鼠（孕鼠）随机分配到各组。低、中、高3个剂量组孕鼠于妊娠第6～15天经口灌胃给予虫螨腈原药，每天1次，染毒剂量分别为12．2、61．2和306．2mg／kg体质量。阳性对照组采用1．0mg／kg体质量敌枯双灌胃，阴性对照组给予质量分数为3％粟米淀粉糊灌胃，灌胃时间和次数同3个剂量组。实验期间观察母体毒性。在妊娠第20天，断头处死孕鼠取胎鼠，观察胚胎毒性和胎鼠骨骼和内脏畸形情况。结果虫螨腈原药在大鼠致畸敏感期经口灌胃染毒后，中、高剂量组孕鼠净增体质量均较阴性对照组降低[53．79（39．81，60．65）vs67．09（47．27，73．92）g，42．34（31．04，53．46）vs67．09（47．27，73．92）g，P〈0．05，P〈0．01]。高剂量组活胎率低于阴性对照组（87．78％vs92．75％，P〈0．05），死胎率高于阴性对照组（4．18％vs1．30％，P〈0．05）。阳性对照组可观察到明显的母体毒性、胚胎毒性和胎鼠致畸性。高剂量组观察到母体毒性和胚胎毒性，但未观察到对胎鼠的骨骼和内脏致畸性。低剂量组未观察到与受试物有关的母体毒性、胚胎毒性及胎鼠致畸性。结论本实验条件下虫螨腈原药在306．2mg／kg体质量剂量染毒后可见一定程度的母体毒性和胚胎毒性，未见胎鼠骨骼和内脏的致畸毒性，其最小致畸量为大于306．2mg／kg；虫螨腈原药对SD大鼠基本无致畸危害。

Objective To study the teratogenicity and embryotoxicity of chlorfenapyr in rats by oral administration during the period of embryonic organ formation. Methods Totally 200 female and 200 male specific pathogen free healthy mature and nulliparous SD rats were selected. A male and a female rat in 1：1 ratio were selected as the mating pairs for mating in one cage. The pregnant rats were randomly divided into 3 dose groups, a negative- and a positive- control group. On the gestation of day 6-15, rats in low-, median- and high-dose groups were given chlorfenapyr by gavage daily at the doses of 12.2, 61.2 and 306.2 mg/kg body weight （bw）. N, N-methylena-bis （2-amino-1, 3,4-thiadiazole） was used for the positive control and the vehicle （3% starch paste） was used for the negative control. Pregnant rats were euthanized and executed on day 20 of gestation. Indexes of the weight, length, visceral and skeletal changes of the fetuses were examined. Results After the administration of chlorfenapyr in the sensitive teratogenic period, the net weight gain of the rats in me- dian- and high-dose groups were lower than those of the negative control group [ 53.79 （39. 81,60. 65 ） vs 67.09 （47.27, 73.92） g, 42. 34 （31.04, 53.46） vs 67. 09 （47.27,73.92） g, P 〈 0. 05, P 〈 0. 01 ]. The live birth rate in the high- dose group was lower than that in the negative control group （87. 78% vs 92. 75%, P 〈0. 05 ）. The stillbirth rate in the high-dose group was higher than that in the negative control group （4. 18% vs 1.30% , P 〈0. 05）. Maternal toxicity, em- bryo toxicity and teratogenicity in fetal rats could be found in the positive group. Maternal toxicity and embryo toxicity occurred in high-dose group, however, teratogenicities in bones and internal organs could not be found in the fetal rats. Maternal toxicity, embryo toxicity and teratogenicity of fetal rats could not be found in low dose group. Conclusion At the dose of 306. 2 mg/kg bw, maternal toxicity and embryotoxicity were observed, while teratogenicities of bones and internal organs could not be found in the fetal rats. The minimum teratogenic dose of chlorfenapyr on SD rats was greater than 306. 2 mg/kg. Chlorfenapyr was judged to be non-teratogenic in SD rats.