Klimisch H J, Gamer A O, Hellwig J, Kaufmann W, Jäckh R
Department of Toxicology, BASF Aktiensellschaft, Ludwigshafen, Germany.
Food Chem Toxicol. 1992 Nov;30(11):915-9. doi: 10.1016/0278-6915(92)90175-k.
In a study of the 28-day inhalation toxicity of di-(2-ethylhexyl) phthalate (DEHP) aerosols, 9-wk-old Wistar rats, 27 males (mean weight 226 g) and 17 females (mean weight 155 g) per group, were exposed in head-nose inhalation systems to DEHP aerosols of respirable particle size (mass median aerodynamic diameter < or = 1.2 microns) or air (controls). Exposure for 6 hr per day, 5 days per wk for 4 wk to target concentrations of 0, 0.01, 0.05 and 1.0 mg/litre gave estimated doses of 230, 11 and 2.3 mg/kg/day for the males, and 360, 18 and 3.6 mg/kg/day for females, on the assumption of 100% deposition and absorption. Clinical investigation and blood chemistry parameters did not reveal any treatment-related effects. At the end of exposure a statistically significant (16%) increase in relative lung weights, accompanied by increased foam-cell proliferation and thickening of the alveolar septi, was found in the males of the highest dose group. Absolute liver weights were significantly (8.75%) increased in females and relative liver weights were increased in both sexes in the highest dose group, but there were no corresponding histological effects. All these effects were reversed during the 8-wk post-exposure period. No testicular toxicity was observed histologically and no impact on mating performance and male fertility was detected after two matings of treated males with untreated females, 2 and 6 wk after the end of exposure. Electron microscopic examination of liver samples from two male and two female rats per group at the end of exposure and after the 8-wk post-exposure period did not reveal clear substructural changes that could be attributed to exposure or to peroxisome proliferation. The no-observed-effect level for all exposure-related findings was 0.05 mg/litre under the conditions used.
在一项关于邻苯二甲酸二（2-乙基己基）酯（DEHP）气雾剂28天吸入毒性的研究中，每组有9周龄的Wistar大鼠，雄性27只（平均体重226克），雌性17只（平均体重155克），在头鼻吸入系统中暴露于可吸入粒径（质量中位空气动力学直径≤1.2微米）的DEHP气雾剂或空气（对照组）中。每天暴露6小时，每周5天，共4周，目标浓度分别为0、0.01、0.05和1.0毫克/升，假设100%沉积和吸收，雄性大鼠的估计剂量分别为230、11和2.3毫克/千克/天，雌性大鼠分别为360、18和3.6毫克/千克/天。临床检查和血液化学参数未显示任何与治疗相关的影响。暴露结束时，在最高剂量组的雄性大鼠中发现相对肺重量有统计学意义的增加（16%），伴有泡沫细胞增殖增加和肺泡间隔增厚。最高剂量组雌性大鼠的绝对肝脏重量显著增加（8.75%），两性的相对肝脏重量均增加，但没有相应的组织学影响。在8周的暴露后期间，所有这些影响都得到了逆转。组织学上未观察到睾丸毒性，在暴露结束后2周和6周，用处理过的雄性大鼠与未处理的雌性大鼠进行两次交配后，未检测到对交配性能和雄性生育力的影响。在暴露结束时以及暴露后8周，对每组两只雄性和两只雌性大鼠的肝脏样本进行电子显微镜检查，未发现可归因于暴露或过氧化物酶体增殖的明显亚结构变化。在所使用的条件下，所有与暴露相关的发现的未观察到影响水平为0.05毫克/升。
