Workers at the cryolite mill in Copenhagen, Denmark, are unique because of their exposure to high levels of fluoride dust and their virtual lack of exposure to other occupational toxicants or carcinogens (1,2). We previously reported the cancer morbidity from 1943 through 1987 for 422 male cryolite workers employed for more than 6 months at the mill from 1924 through 1961 (1). We observed excess incidences of primary cancer of the lungs and of urinary bladder tumors (including bladder papilloma).

We have now extended the follow-up of this cohort by 12 years, at the end of which the total percentage of cohort members who had died exceeded 90%. As previously described (1), the personal identification numbers of the cohort were linked to the files of the Danish Cancer Registry. The period of observation for calculation of the risk of developing cancer began at the completion of 6 months of employment or on January 1, 1943, whichever occurred later. The end of the observation period was the date of death, the date of emigration, or December 31, 1999, which ever occurred first. Because most members of the cohort lived in the Copenhagen area, expected numbers of cancer cases were calculated by using the cancer-site–specific incidence rates for Copenhagen men.

The average length of follow-up increased from 29.2 years to 31.8 years. Forty-three new cancer cases occurred, including 12 cases of primary lung cancer and three bladder tumors. Most new cancer cases occurred in workers who were younger than 35 years when first employed at the mill and after a potential latency of more than 30 years (Table 1). These new cases augmented the tendency of increased risk, particularly in the subgroup with at least 10 years of employment, after an extended lag time and in workers who were young at the beginning of follow-up. The distribution of the 20 bladder tumors by grade was similar to that in the general population.

These findings amplify our previous observation of increased bladder cancer rates among cryolite workers. The lack of any increase in cardiovascular mortality (1), as well as the relatively greater excess in bladder cancer compared with the excess in lung cancer, suggested that cigarette smoking cannot account for the increased cancer risk in this cohort.

Cryolite is used for aluminum production, and an increased risk of both bladder cancer—and, to a lesser extent, lung cancer—has also been documented among aluminum production workers (3). Although this cancer risk has been attributed to coal tar pitch volatiles (3), an association between cancer risk and fluoride exposure has also been recorded among members of one cohort, where fluoride exposure data were available (4).

The plausibility of a cancer risk in fluoride-exposed workers must be judged in relation to the wide range of biochemical effects caused by low concentrations of this toxicant even though the experimental evidence for genotoxicity and carcinogenicity is equivocal (5). Following inhalation of cryolite dust, fluoride concentrations in urine may be very high (2), and fluoride retained in the skeleton may lead to elevated concentrations of fluoride in urine many years after exposure has ended (6). We therefore believe that fluoride should be considered a possible cause of bladder cancer and a contributory cause of primary lung cancer.

REFERENCES

(1) Grandjean P, Olsen JH, Jensen OM, Juel K. Cancer incidence and mortality in workers exposed to fluoride. J Natl Cancer Inst 1992; 84:1903–9.

(2) Grandjean P, Horder M, Thomassen Y. Fluoride, aluminum and phosphate kinetics in cryolite workers. J Occup Med 1990;32:58–63.

(3) International Agency for Research on Cancer. Overall evaluations of carcinogenicity: an updating of IARC monographs volumes 1 to 42. Geneva (Switzerland): World Health Organization, Distribution and Sales Service; 1987. p. 89–91.

(4) Romundstad P, Andersen A, Haldorsen T. Cancer incidence among workers in six Norwegian aluminum plants. Scand J Work Environ Health 2000;26:461–9.

(5) International Programme on Chemical Safety. Fluorides (Environmental Health Criteria 227). Geneva (Switzerland): World Health Organization; 2002.

(6) Grandjean P, Thomsen G. Reversibility of skeletal fluorosis. Br J Ind Med 1983;40:456 – 61.