* Toxicology and Environmental Research & Consulting, The Dow Chemical Company, Midland, Michigan;
Toxicol Sci. 2013 Dec;136(2):527-47. doi: 10.1093/toxsci/kft213. Epub 2013 Sep 26.
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.
2,4-二氯苯氧乙酸（2,4-D）被评估为全身毒性、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 800（雄性）ppm 2,4-D 饮食中。高剂量下显示出非线性毒代动力学行为；雌性动物的 2,4-D 肾清除率饱和度阈值明显超过，雄性动物略有超过。暴露于交配前 4 周，交配后 P1 雄性持续 7 周，P1 雌性通过哺乳期。F1 后代检查存活率和发育情况，在断奶时，根据性别和剂量，将幼崽分为 10 个队列，用于系统毒性（10）、DNT（10）、DIT（20）和生殖毒性（≥23）。其余断奶幼崽评估系统毒性和神经病理学（10-12）。哺乳期高剂量 P1 雌性和 F1 幼崽体重下降。肾脏是主要靶器官，高剂量 P1 雄性和高剂量 F1 雄性和雌性观察到近端曲管轻微退化。F1 后代肾脏毒性的轻微代际差异归因于 2,4-D 摄入量增加。F1 雄性幼鼠睾丸重量减轻和包皮分离延迟归因于体重下降。内分泌相关影响仅限于高剂量 GD 17 母体中的甲状腺激素变化和适应性组织病理学变化，仅在非线性毒代动力学剂量下可见。2,4-D 不会引起生殖毒性、DNT 或 DIT。雄性（16.6mg/kg/天）和雌性（20.6mg/kg/天）的全身毒性“无观察到不良效应水平”为 300ppm，分别是人类生物监测研究中报告的 2,4-D 暴露量的约 6700 至 93000 倍。
