Estimation and validation of biomarker-based exposures for historical ammonium perfluorooctanoate.

Ammonium perfluorooctanoate (APFO) exposures were estimated for use in an occupational mortality study using detailed work histories of cohort members and an exposure reconstruction model developed from occupational information and serum PFO(-) data collected in 2004 as part of a cross-sectional health survey. Measured serum PFO(-) levels of the health survey participants were linked with the job title held by the individuals at the time of sampling. The median, range, and distribution of serum levels were calculated to determine the typical exposure intensity for each job title. High variability was observed in the serum levels of workers within the same job titles. In addition, working in many "APFO-use" jobs did not result in higher exposure than working in "no APFO-use" jobs. Each job title was then assigned to one of three relative APFO job exposure categories (low, medium, or high). Participants' length of time in their job was examined in relation to their serum PFO(-) level and found unlikely to contribute to misclassification of job titles within exposure categories. The mean of the serum PFO(-) measurements for each job exposure category served as the mean intensity factor. Subsequently, the job exposure categories were applied to all historical job titles of the mortality cohort based on their correspondence with job titles represented in the health survey. The resulting job exposure matrix was validated with additional historical blood data collected between 1979 through 2002 from voluntary participants in a separate biomonitoring program. The validation analyses showed general agreement between estimated and measured exposure, reflecting the within-job-title variability observed in measured serum levels used to classify job exposure.

Mortality among workers exposed to acrylonitrile in fiber production: an update.

OBJECTIVE: The investigation updates the mortality experience through 2002 for a cohort of workers exposed to acrylonitrile (AN). METHODS: Standardized mortality ratios (SMR) were estimated based on two reference populations: the US population and a regional employee population. Exposure-response analyses were conducted using Cox regression models for cumulative and mean intensity exposure measures. RESULTS: In the cohort of 2548 workers, 839 deaths have occurred with 91 deaths due to respiratory system cancer. Most standardized mortality ratio estimates are at or near no-effects levels. Hazard ratio (HR) estimates indicate no increased mortality risk for respiratory system cancer (adjusted HR = 0.96, 95% confidence interval: 0.74, 1.25). CONCLUSIONS: In summary, no mortality outcome of a priori interest, principally respiratory system cancer, is associated with increased AN exposure among fiber production workers over five decades of follow-up.

Retrospective cohort mortality study of workers in a polymer production plant including a reference population of regional workers.

PURPOSE: Based on previous reports of increased serum lipid levels in workers at a U.S. polymer manufacturing facility, the study objective was to investigate ischemic heart disease (IHD) mortality as well as a broad range of mortality causes for an occupational cohort at the facility. METHODS: The cohort comprised 6,027 men and women who had worked at the facility between 1948 and 2002; these years delimit the mortality follow-up period. Standardized mortality ratios (SMR) were estimated to compare observed numbers of deaths to expected numbers derived from mortality rates for 3 reference populations: the U.S. population, the West Virginia state population, and an 8-state regional employee population from the same company. RESULTS: Most SMR estimates based on U.S. and state populations were below 100. Comparison to the employee population also resulted in many SMR estimates at or near a no-effect level. Relative to the regional worker population, a nonsignificant elevation for IHD mortality was observed (SMR = 109, 95% confidence interval [CI]: 96, 124). Mortality associated with diabetes was significantly increased compared to the regional worker population (SMR = 197, 95% CI: 123, 298). A corresponding increase in the SMR for IHD and diabetes mortality was not detected for comparisons with the two general populations. CONCLUSIONS: The results reported herein show little evidence of increased cause-specific mortality risks for workers at the plant. This study demonstrates the utility of comparing occupational cohorts with a similar worker reference population in order to reduce bias associated with the healthy worker effect.

Cross-sectional study of lipids and liver enzymes related to a serum biomarker of exposure (ammonium perfluorooctanoate or APFO) as part of a general health survey in a cohort of occupationally exposed workers.

OBJECTIVE: To examine the relationship between serum perfluorooctanoate (PFOA), a biomarker of ammonium perfluorooctanoate (APFO) exposure, and lipids and liver enzymes in a cross-sectional study among workers with potential occupational exposure to APFO. METHODS: We conducted a cross-sectional study of 1,025 active workers with potential exposure to APFO using linear regression to examine the relationship between PFOA and selected outcomes from a standard metabolic health screening survey, emphasizing lipids and liver enzymes. RESULTS: Most outcome parameters were within normal limits. After adjusting for potential confounders, we observed a modest but statistically significant, positive relationship between serum PFOA and total cholesterol, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and gamma glutamyl aminotransferase (GGT). No associations were seen for high-density lipoprotein (HDL) or bilirubin; associations with AST (aspartate aminotransferase) and ALT (alanine transpeptidase) did not reach statistical significance. CONCLUSIONS: Our findings indicate a modest positive association of PFOA on some lipid parameters and a need for follow-up studies.

Longitudinal study of serum lipids and liver enzymes in workers with occupational exposure to ammonium perfluorooctanoate.

OBJECTIVE: To examine the relationship between serum perfluorooctanoate (PFOA), a biomarker of ammonium perfluorooctanoate exposure, and lipids and liver enzymes. METHODS: We conducted a longitudinal study on 454 workers and used mixed models to examine the relationship between serum PFOA and lipids and liver enzymes. RESULTS: One part per million (ppm) increase in serum PFOA was associated with a 1.06 mg/dL increase in total cholesterol, but was not associated with changes in triglycerides or other lipoproteins, after adjusting for potential confounders. Serum PFOA was also associated with total bilirubin (0.008 mg/dL decline/ppm) and serum aspartate aminotransferase (0.35 units increase/ppm) but not with the other liver enzymes. CONCLUSIONS: These medical surveillance data collected on workers for up to 25 years contributes useful information on the effects of ammonium perfluorooctanoate exposure on human liver and lipid chemistry.

Comparison of standardized mortality ratios (SMRs) obtained from use of reference populations based on a company-wide registry cohort to SMRs calculated against local and national rates.

The DuPont Company has maintained a mortality registry for all active and pensioned U.S. employees since 1957. Standardized mortality ratios (SMRs) for each plant site in the U.S. can be calculated based on the comparison with the entire U.S. DuPont population or with a regional subset of DuPont employees. We compared the SMRs derived from a large, international cohort mortality study of chloroprene workers (IISRP study) with those derived from the entire DuPont Registry and appropriate subpopulations of the registry for two U.S. neoprene plants--Louisville (Kentucky) and Pontchartrain (Louisiana). SMRs from the IISRP study for the Louisville cohort based on national rates for all causes of death, all cancers, respiratory cancer, and liver cancer are higher than those based on local mortality rates. Both the national and local comparisons (several counties surrounding each plant) for all-cancer SMRs are lower than 1.0, the local comparison being statistically significantly reduced. In contrast, the SMRs based on the total U.S. DuPont worker mortality rates for all causes of death (1.13), all cancers (1.11), and respiratory cancers (1.37) are statistically significantly increased. The SMR for liver cancer (1.27), although elevated, is not statistically significant. SMRs based on DuPont Region 1 were closer to 1.0, and the SMR for all cancers was no longer significant. Stratification of the Louisville subcohort of males using the same cumulative exposure categories used in the IISRP study yielded SMRs calculated against DuPont Region 1 that were generally higher than those calculated against U.S. and local rates. Only the third exposure category showed SMRs statistically significantly above 1.0 for all cancers and for cancer of bronchus, trachea, and lung. However, there does not appear to be an exposure-response trend. The SMRs from the IISRP study for the Pontchartrain cohort based on national rates are higher than those based on local rates for all causes of death, but all are less than 1.0. The all-cause SMRs for both local and national comparisons are significantly reduced. There were no deaths from liver cancers observed in this cohort. Comparisons of the Pontchartrain cohort against the total U.S. DuPont worker mortality rates resulted in higher SMRs for all causes of death (0.98), all cancers (1.03), and respiratory cancer (1.08), but none were statistically significant. SMRs based on DuPont Region 2 showed very little change from those based on the total registry. The use of reference rates based on regional workers in the same large company produces SMRs lower than those based on the entire company population (regional socio-cultural effects) but higher than those based on geographically closer local general populations (healthy worker effect). The healthy worker effect is seen in cancer mortality rates as well as in other chronic diseases.