Johnson K A, Baker P C, Kan H L, Maurissen J P, Spencer P J, Marty M S
Department of Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI 48674, USA.
Food Chem Toxicol. 2005 Mar;43(3):467-81. doi: 10.1016/j.fct.2004.12.003.
Standard toxicologic endpoints, supplemented by additional examinations, were studied for groups of 10 Fischer 344 rats/sex given drinking water formulated to supply 0, 50, 250, or 1000 mg diethylene glycol monobutyl ether (DGBE)/kg/day for 13 weeks. These dose levels were based upon initial investigations using drinking water formulated to supply 0, 1000, 1500 or 2000 mg DGBE/kg/day for two weeks. All rats survived the respective treatment intervals with no adverse treatment-related in-life effects, including no alterations in a functional observational battery. In both studies, rats given > or = 1000 mg/kg/day consumed less water and feed and weighed slightly less than controls. For rats given > or = 1000 mg DGBE/kg/day, the liver and red blood cells (RBC) were the primary target organs although the effects were slight. In the 13-week study, rats given 1000 mg/kg/day had statistically significant increased relative liver weight (7-10%) and hepatic cytochrome P450s (24-39%) and UGT (approximately 16%) levels along with slight, statistically significant, decreases in serum total protein, cholesterol and aspartate aminotransferase. Histopathologically, very slight hepatocyte hypertrophy and increased individual hepatocyte degeneration were found in females only. At 1000 mg/kg/day, the RBC count, hemoglobin (Hgb) and hematocrit (Hct) were minimally, but statistically significantly, decreased (5.1-8.7%) but RBC morphology, RBC indices, reticuloctye count and bone marrow and spleen histopathology were unaffected. Absolute and relative kidney weights statistically significantly increased (6-13%) with an equivocal increase in minor histopathologic changes typical of early spontaneous nephropathy. There were no adverse effects on urinalysis, clinical chemistry, sperm parameters or testis histopathology. At 250 mg/kg/day, there were equivocal decreases (approximately 2-3%) in RBC count, Hgb and Hct that were statistically significant for the RBC count and Hgb, but these changes were within the historical control range. This dose level was considered the no adverse effect level (NOAEL).
对每组10只Fischer 344大鼠（雌雄各半）进行了标准毒理学终点研究，并辅以额外检查。这些大鼠饮用的饮用水中分别添加了0、50、250或1000毫克二乙二醇单丁醚（DGBE）/千克/天，持续13周。这些剂量水平是基于最初的研究确定的，最初的研究中大鼠饮用的饮用水中分别添加了0、1000、1500或2000毫克DGBE/千克/天，持续两周。所有大鼠在各自的治疗期间均存活，未出现与治疗相关的不良体内效应，包括功能观察组合未发生改变。在两项研究中，给予≥1000毫克/千克/天的大鼠饮水量和食量减少，体重略低于对照组。对于给予≥1000毫克DGBE/千克/天的大鼠，肝脏和红细胞（RBC）是主要靶器官，尽管影响轻微。在为期13周的研究中... 给予1000毫克/千克/天的大鼠相对肝脏重量（增加7 - 10%）、肝细胞色素P450（增加24 - 39%）和尿苷二磷酸葡萄糖醛酸转移酶（UGT，增加约16%）水平有统计学显著升高，同时血清总蛋白、胆固醇和天冬氨酸转氨酶有轻微的统计学显著降低。组织病理学上，仅在雌性大鼠中发现非常轻微的肝细胞肥大和个别肝细胞变性增加。给予1000毫克/千克/天剂量时，红细胞计数、血红蛋白（Hgb）和血细胞比容（Hct）有轻微但统计学显著的降低（5.1 - 8.7%），但红细胞形态、红细胞指数、网织红细胞计数以及骨髓和脾脏组织病理学未受影响。绝对和相对肾脏重量有统计学显著增加（6 - 13%），同时出现早期自发性肾病典型的轻微组织病理学变化增加，但不明确。对尿液分析、临床化学、精子参数或睾丸组织病理学无不良影响。给予250毫克/千克/天剂量时，红细胞计数、Hgb和Hct有不明确的降低（约2 - 3%），红细胞计数和Hgb有统计学显著降低，但这些变化在历史对照范围内。该剂量水平被认为是无不良反应水平（NOAEL）。
