Mortality of employees of a perfluorooctanesulphonyl fluoride manufacturing facility.

AIM: To evaluate the mortality experience of a cohort of employees of a perfluorooctanesulphonyl fluoride (POSF) based fluorochemical production facility. METHODS: A retrospective cohort mortality study followed all workers with at least one year of cumulative employment at the facility. The jobs held by cohort members were assigned to one of three exposure subgroups; high exposed, low exposed, and non-exposed, based on biological monitoring data for perfluorooctane sulphonate (PFOS). RESULTS: A total of 145 deaths were identified in the 2083 cohort members. Sixty five deaths occurred among workers ever employed in high exposed jobs. The overall mortality rates for the cohort and the exposure subcohorts were lower than expected in the general population. Two deaths from liver cancer were observed in the workers with at least one year of high or low exposure (standardised mortality ratio (SMR) 3.08, 95% CI 0.37 to 11.10). The risk of death from bladder cancer was increased for the entire cohort (three observed, SMR 4.81, 95% CI 0.99 to 14.06). All three bladder cancers occurred among workers who held a high exposure job (SMR 12.77, 95% CI 2.63 to 37.35). The bladder cancer cases primarily worked in non-production jobs, including maintenance and incinerator and wastewater treatment plant operations. CONCLUSION: Workers employed in high exposure jobs had an increased number of deaths from bladder cancer; however it is not clear whether these three cases can be attributed to fluorochemical exposure, an unknown bladder carcinogen encountered during the course of maintenance work, and/or non-occupational exposures. With only three observed cases the possibility of a chance finding cannot be ruled out.

Plasma cholecystokinin and hepatic enzymes, cholesterol and lipoproteins in ammonium perfluorooctanoate production workers.

Ammonium perfluorooctanoate is a potent synthetic surfactant used in industrial applications. It rapidly dissociates in biologic media to perfluorooctanoate [CF3(CF2)6CO2-], which is the anion of perfluorooctanoic acid [PFOA, CF3(CF2)6COOH]. PFOA is a peroxisome proliferator known to increase the incidence of hepatic, pancreas and Leydig cell adenomas in rats. The pancreas acinar cell adenomas may be the consequence of a mild but sustained increase of cholecystokinin as a result of hepatic cholestasis. Although no significant clinical hepatic toxicity was observed, PFOA was reported to have modulated hepatic responses to obesity and alcohol consumption among production workers. To further assess these hypotheses, we examined medical surveillance data of male workers involved in ammonium perfluorooctanoate production in 1993 (n=111), 1995 (n=80) and 1997 (n=74). Serum PFOA was measured by high-performance liquid chromatography mass spectrometry methods. Plasma cholecystokinin was measured (only in 1997) by the use of direct radioimmunoassay. Serum biochemical tests included hepatic enzymes, cholesterol and lipoproteins. Serum PFOA levels, by year, were: 1993 (mean 5.0 ppm, SD 12.2, median 1.1 ppm, range 0.0-80.0 ppm); 1995 (mean 6.8 ppm, SD 16.0, median 1.2 ppm, range 0.0-114.1 ppm); and 1997 (mean 6.4 ppm, SD 14.3, median 1.3 ppm, range 0.1-81.3 ppm). Cholecystokinin values (mean 28.5 pg/ml, SD 17.1, median 22.7 pg/ml, range 8.8-86.7 pg/ml) approximated the assay's reference range (up to 80 pg/ml) for a 12 hour fast and were negatively, not positively, associated with employees' serum PFOA levels. Our findings continue to suggest there is no significant clinical hepatic toxicity associated with PFOA levels as measured in this workforce. Unlike a previously reported observation, PFOA did not appear to modulate hepatic responses to either obesity or alcohol consumption. Limitations of these findings include: 1) the cross-sectional design as only 17 subjects were common for the three surveillance years; 2) the voluntary participation that ranged between 50 and 70 percent; and 3) the few subjects with serum levels > or = 10 ppm.

Serum perfluorooctane sulfonate and hepatic and lipid clinical chemistry tests in fluorochemical production employees.

The 3M Company manufactures fluorochemicals, which have as a precursor perfluorooctane sulfonyl fluoride (C8F17SO2F). These compounds may be expected to transform metabolically, to an undetermined degree, to perfluorooctane sulfonate (PFOS, C8F17SO3-) as an end-stage metabolite. Subchronic studies in rats and primates indicate a potential for cumulative toxicity with PFOS with the primary effect related to metabolic wasting with hypolipidemia as a consistent finding. Biennial medical surveillance has been offered to the company's fluorochemical production workers located in Decatur, Alabama, and Antwerp, Belgium. In 1995, the mean serum PFOS level, as measured by high-performance liquid chromatography mass spectrometry, for 178 male employees was 2.19 parts per million (ppm; range, 0.00 to 12.83 ppm), and in 1997, for 149 male employees, it was 1.75 ppm (0.10 to 9.93 ppm). Our analyses suggest that among these production employees, there were no substantial changes in serum hepatic enzymes, cholesterol, or lipoproteins associated with PFOS levels less than 6 ppm. It was not possible to derive inferences from the few employees who had serum PFOS levels > or = 6 ppm. These results may be due to the lower levels of serum PFOS measured among these production employees, compared to those suspected to cause effects in laboratory animals.

An epidemiologic investigation of reproductive hormones in men with occupational exposure to perfluorooctanoic acid.

Perfluorooctanoic acid (PFOA), a potent synthetic surfactant used in industrial applications, is a peroxisome proliferator that has resulted in dose-related increases in hepatic, pancreatic acinar, and Leydig cell adenomas in laboratory animals. In addition, PFOA increased serum estradiol levels through the induction of hepatic aromatase activity. In 1993 and 1995, we conducted two cross-sectional studies of 111 and 80 production workers, respectively, and specifically measured their serum PFOA in relation to several reproductive hormones to determine whether such an effect occurs in humans. PFOA was not significantly associated with estradiol or testosterone in either year's study. A 10% increase in mean estradiol levels was observed among employees who had the highest levels of serum PFOA, although this association was confounded by body mass index. Neither was PFOA consistently associated with the other measured hormones. Our results provide reasonable assurance that, in this production setting, there were no significant hormonal changes associated with PFOA at the serum levels measured. Limitations of this investigation include its cross-sectional design, the few subjects exposed at the highest levels, and the lower levels of serum PFOA measured, compared with those levels reported to cause effects in laboratory animal studies.

Absenteeism among employees who participated in a workplace influenza immunization program.

To assess the effectiveness of a free workplace immunization program at 3M's St. Paul, Minnesota locations, we examined the difference in sick leave hours taken from November 15, 1996, through March 15, 1997, for employees who had and did not have an influenza vaccination prior to the previous year's four-month influenza season (November 15, 1995-March 15, 1996). Among the 2,622 employees who self-reported that they were not immunized in the previous year, there were, on average, 1.2 fewer hours of sick leave taken during the 1996-1997 influenza season than the comparable time period one year earlier (P < 0.05), although the exact reason for the absenteeism was not determined. In particular, we observed that female employees younger than 50 years of age with two or more children took 3.1 hours less sick leave in the year they were immunized, compared with the preceding year (P < 0.0001). Among the 895 subjects who were immunized in both years, employees took 0.7 hours more sick leave during the 1996-1997 influenza season than the previous year (P = 0.46). Based on our findings, consideration should be given to workplace immunization programs. However, we urge caution in applying a "one-size fits all" approach to any cost-savings analysis from a company-sponsored immunization program because the workplace is not a homogeneous [corrected] environment, with regard to employees' age, gender, medical history, and home environment. All of these factors may directly or indirectly contribute to the risk of acquiring influenza and any of its complications.