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Abstract：
2,4-Dichlorophenoxyacetic acid (2,4-D) was assessed for systemic toxicity, reproductive toxicity, developmental neurotoxicity (DNT), developmental immunotoxicity (DIT), and endocrine toxicity. CD rats (27/sex/dose) were exposed to 0, 100, 300, 600 (female), or 800 (male) ppm 2,4-D in diet. Nonlinear toxicokinetic behavior was shown at high doses; the renal clearance saturation threshold for 2,4-D was exceeded markedly in females and slightly exceeded in males. Exposure was 4 weeks premating, 7 weeks postmating for P1 males and through lactation for P1 females. F1 offspring were examined for survival and development, and at weaning, pups were divided in cohorts, by sex and dose, and by systemic toxicity (10), DNT (10), DIT (20), and reproductive toxicity (≥ 23). Remaining weanlings were evaluated for systemic toxicity and neuropathology (10-12). Body weight decreased during lactation in high-dose P1 females and in F1 pups. Kidney was the primary target organ, with slight degeneration of proximal convoluted tubules observed in high-dose P1 males and in high-dose F1 males and females. A slight intergenerational difference in kidney toxicity was attributed to increased intake of 2,4-D in F1 offspring. Decreased weanling testes weights and delayed preputial separation in F1 males were attributed to decreased body weights. Endocrine-related effects were limited to slight thyroid hormone changes and adaptive histopathology in high-dose GD 17 dams seen only at a nonlinear toxicokinetic dose. 2,4-D did not cause reproductive toxicity, DNT, or DIT. The \"No Observed Adverse Effect Level\" for systemic toxicity was 300 ppm in both males (16.6 mg/kg/day) and females (20.6 mg/kg/day), which is approximately 6700- to 93 000-fold higher than that reported for 2,4-D exposures in human biomonitoring studies.
摘要：
评估2,4-二氯苯氧基乙酸（2,4-D）的全身毒性，生殖毒性，发育神经毒性（DNT），发育免疫毒性（DIT），和内分泌毒性。CD大鼠（27/性别/剂量）暴露于0、100、300、600（雌性），或饮食中800（男性）ppm2,4-D。在高剂量下显示出非线性毒代动力学行为；女性明显超过2,4-D的肾脏清除率饱和度阈值，而男性则略微超过。暴露是提前4周，P1雄性和P1雌性在哺乳后7周。对F1后代进行了生存和发育检查，在断奶时，幼崽被分成队列，按性别和剂量，和系统毒性（10），DNT(10),DIT(20),和生殖毒性（≥23）。评估剩余断奶的全身毒性和神经病理学(10-12)。高剂量P1雌性和F1幼仔的哺乳期体重下降。肾脏是主要的靶器官,在高剂量P1男性和高剂量F1男性和女性中观察到近曲小管轻度变性。肾脏毒性的代际差异轻微归因于F1后代中2,4-D的摄入量增加。F1雄性断奶睾丸重量降低和包皮分离延迟归因于体重降低。仅在非线性毒代动力学剂量下观察到的高剂量GD17大坝中，内分泌相关作用仅限于轻微的甲状腺激素变化和适应性组织病理学。2,4-D没有引起生殖毒性，DNT,或DIT。在男性（16.6mg/kg/天）和女性（20.6mg/kg/天）中，全身毒性的“未观察到不良反应水平”为300ppm，这比人类生物监测研究中报道的2,4-D暴露高约6700至93000倍。
