FMC Corporation, Stine Research Center, 1090 Elkton Rd, Newark, DE, 19711, USA.
FMC Corporation, Stine Research Center, 1090 Elkton Rd, Newark, DE, 19711, USA.
Regul Toxicol Pharmacol. 2019 Nov;108:104425. doi: 10.1016/j.yrtph.2019.104425. Epub 2019 Jul 17.
Developmental neurotoxicity (DNT) studies via dietary method of administration have been conducted for zeta-cypermethrin, a pyrethroid insecticide. The objectives of the current study were to determine the toxicokinetics (TK) of zeta-cypermethrin in postnatal day (PND) 11, 21 and 90 rats after gavage doses and use the internal exposure data from the DNT and TK studies to calculate an offspring NOAEL in mg/kg/day during lactation. The DNT studies showed that zeta-cypermethrin is not a developmental neurotoxicant. The NOAEL for maternal and offspring was determined to be 125 ppm (9.0 and 21.4 mg/kg/day for dams during gestation and lactation, respectively), based on systemic toxicity of reductions in maternal body weight, body weight gains and food consumption and offspring body weight at 300 ppm (LOAEL). The TK data from the gavage study showed that dose normalized C and AUC is approximately 3-fold and 2-fold higher in PND 11 and 21 than those in PND 90 rats. By using the mean maternal/offspring plasma concentrations (535/245 ng/mL) during lactation day LD/PND 5-21 from the range-finding DNT studies, a conservative 3.1X relative TK factor (exposure ratio from the gavage study) and equation 3.1 × 535/21.4 = 245/x, the offspring NOAEL of 125 ppm was calculated to be 3.2 mg/kg/day during lactation. The offspring NOAEL based on internal exposure data from DNT studies and TK data after gavage doses is considered conservative for risk assessment for all human populations including infants and children for zeta-cypermethrin.
通过经口途径给予的方法进行了 Zeta-氯氰菊酯（一种拟除虫菊酯类杀虫剂）的发育神经毒性（DNT）研究。本研究的目的是确定经灌胃给予后，新生 11 天（PND11）、21 天（PND21）和 90 天（PND90）大鼠的 Zeta-氯氰菊酯的毒代动力学（TK），并使用 DNT 和 TK 研究中的内暴露数据来计算哺乳期的后代无观察到不良作用水平（NOAEL）。DNT 研究表明 Zeta-氯氰菊酯不是一种发育神经毒物。基于母体体重、体重增加和食物消耗以及 300ppm（LOAEL）时后代体重的系统毒性降低，母体和后代的 NOAEL 确定为 125ppm（妊娠和哺乳期母体分别为 9.0 和 21.4mg/kg/天）。灌胃研究的 TK 数据表明，PND11 和 PND21 的剂量归一化 C 和 AUC 大约是 PND90 大鼠的 3 倍和 2 倍。通过使用范围发现 DNT 研究中哺乳期 LD/PND5-21 期间的母体/后代平均血浆浓度（535/245ng/mL），保守的 3.1X 相对 TK 因子（灌胃研究中的暴露比）和方程 3.1×535/21.4=245/x，计算出哺乳期的后代 NOAEL 为 125ppm 时为 3.2mg/kg/天。基于 DNT 研究中的内暴露数据和灌胃剂量后的 TK 数据计算得出的后代 NOAEL 被认为是 Zeta-氯氰菊酯对所有人群（包括婴儿和儿童）的风险评估是保守的。
