Baxter Healthcare Corporation, Suzhou, China.
Baxter Healthcare Corporation, PreClinical, Lund, Sweden.
Regul Toxicol Pharmacol. 2019 Jun;104:50-55. doi: 10.1016/j.yrtph.2019.02.016. Epub 2019 Feb 28.
Di (2-ethylhexyl) adipate (DEHA) is a potential plasticizer alternative for di-2-ethylhexyl phthalate (DEHP). Toxicity of DEHA has been studied mostly via oral exposure but not assessed after repeated intravenous exposure. The present study shows the toxicity effects after intravenous administration for 28 consecutive days and the reversibility of the effects following a 14-day recovery period. The study was conducted under GLP conditions. Four groups of rats (15/sex/group) each received either vehicle or DEHA in vehicle (100, 200, or 450 mg/kg/day). Criteria for evaluation included clinical observations, body weight, food consumption, clinical pathology (hematology, serum chemistry, coagulation, urinalyses), gross (necropsy) evaluation, organ weight and histopathological evaluation. There were no DEHA-related changes in all the endpoints evaluated at 100 or 200 mg/kg/day. There were no test article-related changes in clinical pathology or gross necropsy observation at 450 mg/kg/day. At the high-dose, DEHA-related findings included clinical observations, decreased body weight gain and food consumption, increased liver weight in females associated with minimal hepatocellular hypertrophy, and decreased thymus weight in males and females without histopathology findings. All these findings were completely reversible within a 14-day recovery period. Therefore, the 200 mg/kg/day dose is considered to be the No-Observed-Effect Level (NOEL).
己二酸二（2-乙基己基）酯（DEHA）是邻苯二甲酸二（2-乙基己基）酯（DEHP）的一种潜在的增塑剂替代品。DEHA 的毒性主要通过口服暴露进行研究，但未评估重复静脉暴露后的毒性。本研究显示了连续 28 天静脉给药后的毒性作用，以及 14 天恢复期后毒性作用的可逆性。该研究是在 GLP 条件下进行的。四组大鼠（每组 15 只，雌雄各半）分别给予赋形剂或赋形剂中的 DEHA（100、200 或 450mg/kg/天）。评估标准包括临床观察、体重、食物消耗、临床病理学（血液学、血清化学、凝血、尿液分析）、大体（尸检）评估、器官重量和组织病理学评估。在 100 或 200mg/kg/天剂量下，所有评估终点均与 DEHA 无关。在 450mg/kg/天剂量下，临床病理学或大体尸检观察均与试验药物无关。在高剂量下，与 DEHA 相关的发现包括临床观察、体重增加和食物消耗减少、雌性动物肝脏重量增加与最小的肝细胞肥大有关，以及雄性和雌性动物的胸腺重量减少，但无组织病理学发现。所有这些发现均在 14 天恢复期内完全可逆。因此，200mg/kg/天的剂量被认为是无观察到效应水平（NOEL）。
