Arito H, Takahashi M, Iwasaki T, Uchiyama I
National Institute of Industrial Health, Kawasaki, Japan.
Ind Health. 1997;35(1):78-86. doi: 10.2486/indhealth.35.78.
To evaluate the effect of age on toxicant-induced pulmonary and extrapulmonary changes, we examined the effect of inhalation exposure to oxone (O3) on the ventilatory and heart rate (HR) responses in 4-6 and 20-22-month-old male rats. The rats, chronically implanted with an electrocardiographic (ECG) electrodes, were placed in a head-out plethysmograph for continuous ventilatory measurements of tidal volume and breathing frequency. Simultaneous measurements of HR were also obtained. A 6-hr exposure of each rat to filtered air was followed 2 days later by a 5-hr exposure to 0.1 ppm O3, 5 days later by a 5-hr exposure to 0.3 ppm O3 and 10 days later by a 5-hr exposure to 0.5 ppm O3. Each of the O3 exposures was preceded by a 1-hr exposure to filtered air. Transient rapid shallow breathing with slightly increased HR appeared 1-2 min after the start of O3 exposure. It was suggested on the basis of the electroencephalographic (EEG) activity of the olfactory bulb that this transient response was mediated through olfactory sensation. Persistent rapid shallow breathing with a progressive decrease in HR occurred with a latent period of 1-2 hr. The last 90-min averaged values for relative minute ventilation tended to decrease with the increase in the level of exposure to O3 and these values for young rats were significantly lower than those for old rats. An exposure of young rats to 0.1 ppm O3 for shorter than 5 hr significantly decreased the tidal volume and HR and increased breathing frequency, but no significant changes were observed in old rats. There were no differences between young and old rats in non-observable-adverse-effect-levels (NOAELs) for the O3-induced persistent ventilatory and HR responses, when the NOAELs were determined by exposure to 0.3 and 0.5 ppm O3. The present results, as well as the reported decrease in body temperature and blood pressure, suggested that the age-related changes in patterns and magnitude of the persistent rapid shallow breathing with a progressive decrease in HR are mediated through some age-related defense mechanism acting against O3 inhalation. The validity of the occupational exposure limit for O3 in workplaces was discussed in the light of the present findings.
为评估年龄对毒物诱导的肺部和肺外变化的影响，我们研究了吸入臭氧（O₃）对4 - 6月龄和20 - 22月龄雄性大鼠通气和心率（HR）反应的影响。将长期植入心电图（ECG）电极的大鼠置于头出式体积描记器中，以连续测量潮气量和呼吸频率，并同时测量HR。每只大鼠先暴露于过滤空气中6小时，2天后暴露于0.1 ppm O₃中5小时，5天后暴露于0.3 ppm O₃中5小时，10天后暴露于0.5 ppm O₃中5小时。每次O₃暴露前均先暴露于过滤空气中1小时。O₃暴露开始后1 - 2分钟出现短暂的快速浅呼吸，HR略有增加。根据嗅球的脑电图（EEG）活动提示，这种短暂反应是通过嗅觉介导的。持续的快速浅呼吸伴HR逐渐下降，潜伏期为1 - 2小时。相对分钟通气量的最后90分钟平均值倾向于随O₃暴露水平的增加而降低，且幼鼠的这些值显著低于老年大鼠。幼鼠暴露于0.1 ppm O₃少于5小时会显著降低潮气量和HR并增加呼吸频率，但老年大鼠未观察到显著变化。当通过暴露于0.3和0.5 ppm O₃确定O₃诱导的持续通气和HR反应的未观察到有害作用水平（NOAELs）时，幼鼠和老年大鼠之间没有差异。目前的结果以及报道的体温和血压下降表明，与年龄相关的持续快速浅呼吸模式和幅度变化以及HR逐渐下降是通过某种针对吸入O₃的年龄相关防御机制介导的。根据目前的研究结果讨论了工作场所O₃职业接触限值的有效性。
