Lubbers J R, Chauan S, Bianchine J R
Environ Health Perspect. 1982 Dec;46:57-62. doi: 10.1289/ehp.824657.
To assess the relative safety of chronically administered chlorine water disinfectants in man, a controlled study was undertaken. The clinical evaluation was conducted in the three phases common to investigational drug studies. Phase I, a rising dose tolerance investigation, examined the acute effects of progressively increasing single doses of chlorine disinfectants to normal healthy adult male volunteers. Phase II considered the impact on normal subjects of daily ingestion of the disinfectants at a concentration of 5 mg/l. for twelve consecutive weeks. Persons with a low level of glucose-6-phosphate dehydrogenase may be expected to be especially susceptible to oxidative stress; therefore, in Phase III, chlorite at a concentration of 5 mg/l. was administered daily for twelve consecutive weeks to a small group of potentially at-risk glucose-6-phosphate dehydrogenase-deficient subjects. Physiological impact was assessed by evaluation of a battery of qualitative and quantitative tests. The three phases of this controlled double-blind clinical evaluation of chlorine dioxide and its potential metabolites in human male volunteer subjects were completed uneventfully. There were no obvious undesirable clinical sequellae noted by any of the participating subjects or by the observing medical team. In several cases, statistically significant trends in certain biochemical or physiological parameters were associated with treatment; however, none of these trends was judged to have physiological consequence. One cannot rule out the possibility that, over a longer treatment period, these trends might indeed achieve proportions of clinical importance. However, by the absence of detrimental physiological responses within the limits of the study, the relative safety of oral ingestion of chlorine dioxide and its metabolites, chlorite and chlorate, was demonstrated.
为评估长期使用氯水消毒剂对人体的相对安全性，开展了一项对照研究。临床评估按照研究性药物研究共有的三个阶段进行。第一阶段，即递增剂量耐受性研究，检测了正常健康成年男性志愿者逐步增加单剂量氯消毒剂后的急性效应。第二阶段考察了连续十二周每日摄入浓度为5毫克/升的消毒剂对正常受试者的影响。葡萄糖-6-磷酸脱氢酶水平较低的人可能特别容易受到氧化应激的影响；因此，在第三阶段，对一小群可能有风险的葡萄糖-6-磷酸脱氢酶缺乏受试者连续十二周每日给予浓度为5毫克/升的亚氯酸盐。通过一系列定性和定量测试的评估来衡量生理影响。对男性志愿者受试者进行的二氧化氯及其潜在代谢物的这项对照双盲临床评估的三个阶段顺利完成。参与研究的任何受试者或观察医疗团队均未注意到明显的不良临床后遗症。在某些情况下，某些生化或生理参数的统计学显著趋势与治疗有关；然而，这些趋势均未被判定具有生理后果。不能排除在更长治疗期内这些趋势可能确实达到具有临床重要性程度的可能性。然而，通过在研究范围内未出现有害的生理反应，证明了口服二氧化氯及其代谢物亚氯酸盐和氯酸盐的相对安全性。
