Watkinson W P, Wiester M J, Highfill J W
Pulmonary Toxicology Branch, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
J Appl Physiol (1985). 1995 Mar;78(3):1108-20. doi: 10.1152/jappl.1995.78.3.1108.
These studies examined the effects of exposure to near environmental levels of ozone (O3) on the unanesthetized unrestrained rat as well as the influence of changes in ambient temperature (Ta) on the observed responses. Male Fischer 344 rats were implanted with radiotelemetry transmitters that permitted continuous monitoring of electrocardiogram, heart rate, core body temperature (Tco), and activity. Telemetry animals (n = 4-5/group) were combined with nontelemetry animals to produce nine treatment groups (n = 44-50/group) composed of combinations of one of three O3 exposure regimens (0.0 ppm x 24 h/day, 0.5 ppm x 6 h/day, or 0.5 ppm x 23 h/day) paired with one of three Ta levels (10, 22, or 34 degrees C). The experimental protocol consisted of a Control Period (filtered air; 1 day), Treatment Period (O3; 5 days), and Recovery Period (filtered air; 7 days). At specific intervals during the experiment, subgroups (n = 6) of nontelemetry animals were randomly selected from each treatment group, anesthetized with urethan, and intubated, and their lungs were lavaged with warm saline. In general, results from the bronchoalveolar lavage procedure indicated that toxicity increased in magnitude and duration as the length of time of O3 exposure increased and the Ta decreased. Similarly, whereas minimal extrapulmonary effects were observed at an Ta of 34 degrees C, O3 exposures at Ta levels of 22 and 10 degrees C produced significant decreases in heart rate (160 and 210 beats/min, respectively), Tco (2.0 and 3.5 degrees C, respectively), and body weight (15 and 40 g, respectively). Decreases in these functional parameters reached their maxima over the first 2 exposure days and returned to control levels after the 3rd day of exposure. These data demonstrate the profound impact of Ta on Tco and other extrapulmonary parameters in the conscious unrestrained rat exposed to O3. Furthermore, these results suggest an integral role for both Tco and Ta in determination of the uptake of inhaled pollutants and modulation of the subsequent toxic effects and may have important implications with respect to the assessment of toxic risk.
这些研究考察了暴露于接近环境水平的臭氧(O₃)对未麻醉、未束缚大鼠的影响,以及环境温度(Ta)变化对所观察到的反应的影响。雄性Fischer 344大鼠被植入无线电遥测发射器,以便连续监测心电图、心率、核心体温(Tco)和活动情况。将遥测动物(每组n = 4 - 5只)与非遥测动物合并,形成九个处理组(每组n = 44 - 50只),这些处理组由三种O₃暴露方案(0.0 ppm×24小时/天、0.5 ppm×6小时/天或0.5 ppm×23小时/天)之一与三种Ta水平(10℃、22℃或34℃)之一的组合构成。实验方案包括一个对照期(过滤空气;1天)、一个处理期(O₃;5天)和一个恢复期(过滤空气;7天)。在实验期间的特定时间间隔,从每个处理组中随机选取非遥测动物亚组(n = 6只),用乌拉坦麻醉并插管,然后用温盐水对其肺部进行灌洗。一般来说,支气管肺泡灌洗程序的结果表明,随着O₃暴露时间的延长和Ta的降低,毒性在程度和持续时间上均增加。同样,在34℃的Ta条件下观察到的肺外效应最小,而在22℃和10℃的Ta水平下进行O₃暴露时,心率(分别为160次/分钟和210次/分钟)、Tco(分别为2.0℃和3.5℃)和体重(分别为15克和40克)均出现显著下降。这些功能参数的下降在最初2天暴露期间达到最大值,并在暴露第3天后恢复到对照水平。这些数据证明了Ta对暴露于O₃的清醒未束缚大鼠的Tco和其他肺外参数有深远影响。此外,这些结果表明Tco和Ta在决定吸入污染物的摄取以及调节随后的毒性效应方面都起着不可或缺的作用,并且可能对毒性风险评估具有重要意义。