农药氟咯草酮在大鼠胚胎-胎仔发育毒性试验中的暴露评估  

Exposure assessment of flurochloridone in the rat embryo-foetal developmental toxicity study

作　　者：刘萍[1] 李睿[1] 周谡[1] 朱鸿雁 孙杰[1] 王涵[1] 严佳捷 唐黎明[1] LIU Ping;LI Rui;ZHOU Su;ZHU Hong-yan;SUN Jie;WANG Han;YAN Jia-jie;TANG Li-ming(Shanghai Institute for Drug and Food Control,Shanghai 201203,China)

机构地区：[1]上海市食品药品检验所,上海201203

出　　处：《毒理学杂志》2020年第3期246-249,250,共5页Journal of Toxicology

基　　金：上海市青年科技英才“扬帆计划”项目(17YF1417000)。

摘　　要：目的评价农药氟咯草酮(FLC)在大鼠胚胎-胎仔发育阶段的暴露水平和潜在风险。方法开展大鼠胚胎-胎仔发育毒性及毒代动力学试验。低、中、高剂量组雌性大鼠孕期每日灌胃染毒3、10和30 mg/kg·bw FLC。采集大鼠于末次暴露后0.25、0.5、1、2、4、6、8和24 h的血浆,并于次日收集大鼠胎盘样本。运用高效液相色谱-三重四级杆质谱法(LC-MS/MS)检测血浆及胎盘中的FLC浓度,计算FLC主要的毒代动力学参数和内剂量。使用非参数检验比较不同组间的胎盘残留。采用Pearson相关分析考察药时曲线下面积(AUC)与给药剂量、大鼠内剂量与胎盘残留之间的相关性。结果 FLC在妊娠大鼠体内分布广泛。AUC0-24与给药剂量呈有统计学意义的线性相关(P=0.019)。低、中、高剂量组大鼠内剂量暴露平均值分别为7.93、68.61和216.79μg/kg·bw。高剂量组中胎盘FLC残留的检出率达100%,几何均数为1.33 ng/ml。高剂量组胎盘中的FLC残留明显高于低、中剂量组,差异有统计学意义(P<0.001)。母体内FLC的内剂量越大,胎盘中的FLC残留越高(r=0.647,P=0.004)。结论高浓度FLC对子代存在潜在的发育毒性风险,亟需加强监管。Objective To evaluate the exposure levels and potential risk of flurochloridone during the period of embryo-fetal development in rats. Methods The embryo-fetal development toxicity study of flurochloridone and its toxicokinetics were performed. Female rats were treated during pregnancy with 3, 10 and 30 mg/kg·bw FLC. Plasma samples were collected at 0.25, 0.5, 1, 2, 4, 6, 8 and 24 h after the last exposure. Placental samples were also collected on the next day. Liquid chromatography tandem-mass spectrometry(LC-MS/MS) was used to detect the exposure levels in the plasma and placental samples. The main toxicokinetic parameters and maternal internal doses were calculated. Nonparametric test was used to compare residual levels for FLC in the placental samples from different groups. Pearson correlation analysis was conducted between the area under the curve(AUC) and the dose levels, also between maternal internal doses and the log-transformed residual exposure in placenta. Results FLC was widely distributed throughout the pregnant rats. Regression analysis of AUC0-24 by dose indicated that the relationship was linear(P=0.019). The means for maternal internal doses were 7.93, 68.61 and 216.79 μg/kg·bw, respectively. FLC was detected in 100% of the placental samples in the high-dose group, while the geometric mean was 1.33 ng/ml. The residual levels for FLC in placenta were significantly higher than other two groups(P<0.001). Furthermore, the maternal internal doses were significantly associated with residual levels in placenta(r=0.647, P=0.004). Conclusion It was suggested that the general population exposed to high levels of FLC was at the potential embryo-fetal developmental risk, which was warned of urgency to strengthen the supervision.

关 键 词：除草剂 毒代动力学 内剂量 发育毒性 胎盘 

分 类 号：R965.3[医药卫生—药理学] R114[医药卫生—药学]