Grandjean P, Olsen J H, Jensen O M, Juel K
Department of Environmental Medicine, Odense University, Denmark.
J Natl Cancer Inst. 1992 Dec 16;84(24):1903-9. doi: 10.1093/jnci/84.24.1903.
Although a recent bioassay showed increased frequency of bone cancer in rats with high oral intake of fluoride, the data are reported as equivocal evidence of carcinogenicity. In humans, occupational fluoride exposure may cause skeletal fluorosis, and our earlier follow-up of fluoride-exposed workers showed increased incidence of respiratory cancers.
To further evaluate occupational fluoride exposure as a carcinogenic risk factor, we extended by approximately one decade the follow-up of a cohort of 425 men and 97 women employed for at least 6 months in the period 1924-1961 at the Copenhagen cryolite processing plant. Cryolite ore contains about 50% fluoride.
Cancer mortality was determined for the period 1941-1989, and incidence for 1943-1987. For comparison, we used national mortality rates and cancer incidence rates for the Copenhagen area.
Among the men, 300 deaths occurred; 223 were expected. Respiratory (lung and laryngeal) cancers and violent death were responsible for most of this excess; rates for mortality from cardiovascular disease were close to the rates expected. Of the 423 male workers, 119 developed cancers; 103.6 were expected. There was excess incidence of cancers of the lungs (35 men; standard incidence ratio [SIR] = 1.35), larynx (5 men; SIR = 2.29), and urinary bladder (17 men; SIR = 1.84). Maximum incidence occurred after 10-19 years of employment, but otherwise, no stable relationship between cancer incidence and duration of employment was observed. The incidence of respiratory and urinary cancers was particularly high in men less than 35 years old at first employment. Cancers in female workers were too few to allow detailed evaluation.
The increased incidence of respiratory cancers suggests that cigarette smoking was frequent in this cohort, despite the unremarkable cardiovascular mortality, but the disproportionate increase in the incidence of bladder cancer is difficult to explain by smoking habits alone. Because this industrial cohort was exposed to high concentrations of fluoride dust, heavy respiratory exposure to fluoride may have contributed to the increased cancer risk. If these workers inhaled a carcinogenic substance partly excreted in the urine, an increased incidence of respiratory and bladder cancers would not be inconceivable.
The potential role of fluoride as a cause of bladder cancer needs to be explored.
尽管最近的一项生物测定显示，口服高剂量氟化物的大鼠患骨癌的频率增加，但这些数据被报告为致癌性的不明确证据。在人类中，职业性氟暴露可能导致氟骨症，我们早期对氟暴露工人的随访显示呼吸道癌症发病率增加。
为了进一步评估职业性氟暴露作为致癌风险因素，我们将一组在1924年至1961年期间于哥本哈根冰晶石加工厂工作至少6个月的425名男性和97名女性的随访时间延长了大约十年。冰晶石矿石含有约50%的氟化物。
确定了1941年至1989年期间的癌症死亡率以及1943年至1987年期间的发病率。为作比较，我们使用了哥本哈根地区的全国死亡率和癌症发病率。
在男性中，有300人死亡；预期死亡人数为223人。呼吸道（肺癌和喉癌）癌症和暴力死亡是造成这种超额死亡的主要原因；心血管疾病死亡率接近预期水平。在423名男性工人中，有119人患癌症；预期患癌人数为103.6人。肺癌（35名男性；标准化发病率[SIR]=1.35）、喉癌（5名男性；SIR=2.29）和膀胱癌（17名男性；SIR=1.84）的发病率均有超额增加。最高发病率出现在工作10至19年后，但除此之外，未观察到癌症发病率与工作时长之间存在稳定关系。首次就业时年龄小于35岁的男性中，呼吸道和膀胱癌的发病率尤其高。女性工人患癌人数过少，无法进行详细评估。
呼吸道癌症发病率增加表明，尽管心血管死亡率不显著，但该队列中吸烟情况较为普遍，但膀胱癌发病率不成比例的增加仅靠吸烟习惯难以解释。由于这个工业队列暴露于高浓度的氟尘中，重度呼吸道氟暴露可能导致了癌症风险增加。如果这些工人吸入了部分经尿液排泄的致癌物质，那么呼吸道和膀胱癌发病率增加就并非不可想象。
需要探究氟作为膀胱癌病因的潜在作用。
