Document xz0n14EB7VNpyOpaOy7EYwmrQ
Name:
Chine Sakr, MD MPH ' Robin Leonard, PhD 2 Mark Cullen, MD 1
Program Affiliation:
Address: Phone: Fax: Email:
`-Yale Occupational and Environmental Medicine Program 2Epidemiology Program at DuPont Haskell Laboratory for Health and Environmental Sciences 135 College Street, 3rd floor New Haven, CT 06510 856-816-1539 203-785-7391 carine.sakr@ yale.edu
TITLE
Twenty-five year longitudinal study of serum total cholesterol related to a serum biomarker of exposure (serum perfluorooctanoate or PFOA) in a polymer production plant.
BACKGROUND
l Perfluorooctanoate (PFOA, C7Ft$OO) is a peffluorinated carboxylate, primarily used as a surfactant in the production of fluoropolymer high-performance materials. Fluoropolymers are used in architectural fabrics; chemical processing piping and vessels; automotive fuel systems; telecommunications and electronic wiring insulation; and computer chip processing equipment and systems- in addition to consumer products such as cookware and apparel.
l PFOA has been found in the serum of production workers with occupational exposure (l-3). Lower levels of PFOA have been reported in serum samples of nonoccupationally exposed men and women in the USA as well as in other countries, which suggests a widespread, albeit low, exposure to the general population (4-8).
l Animal studies suggested that the liver is the primary target organ for PFOA-induced toxicity in rats and monkeys. PFOA produced hypolipemia in rodents (9, 10) and increased liver weight as a result of mitochondrial proliferation in monkeys (11). PFOA exposure also increased incidence of adenomas of the liver, pancreas, and testes in rats (12).
l Previous studies in exposed workers evaluating the association between PFOA and total cholesterol have yielded conflicting results (13,14).
d
METHODS
l The relationship between total cholesterol and serum PFOA was examined in a 25year longitudinal study (1979-2004) with repeated measurements using a mixed effects model in a cohort of 454 workers with occupational exposure to PFOA.
l The serum PFOA levels used were part of an industrial hygiene surveillance program. The blood cholesterol levels and other covariates were abstracted from the medical surveillance program at the plant. There were no available data on use of lipid lowering medications. Unless cholesterol was measured in the same year as PFOA, the cholesterol level corresponding to a PFOA test was interpolated from the values of the 2 nearest before and after dates.
l Univariate analyses were utilized to' determine the distributions of PFOA and cholesterol.
l All analyses were conducted using a 95% level of confidence (alpha = 0.05) in SAS version 9.01.
RESULTS
l The cohort included 334 males and 120 females. l At the end of the study, 49.3% of the subjects were still employed; the rest were
either terminated (43.4%) or dead (7.3%). l For those still employed, the mean age was 51.3 years. o The mean serum PFOA for the entire cohort was 1.69 ppm (SD 3.24). Serum
PFOA seemed to decrease with calendar time (Figure 1). l All the people in the cohort had at least 2 measurements of serum PFOA (median:
3; range 2-17). l Total cholesterol increased with age for both men and women (Figure 2) and had
a close to normal distribution in the cohort (Figure 3). l After adjusting for age, BMI, and gender, there was a statistically significant
positive association between serum PFOA and total cholesterol (Table 1).
CONCLUSIONS
l Serum PFOA is positively associated (p = 0.007) with total cholesterol in a longitudinal analysis of exposed workers. The parameter estimate is 1.152 mg/dl/ppm PFOA. However, this result is not adjusted for use of lipid lowering medications. The true relationship might be in fact stronger.
l Further studies should be considered to further understand the relationship between exposure to PFOA and total cholesterol.
ACKNOWLEDGMENTS
The authors thank Kim Kreckmann and Craig Marshall of the Epidemiology Program at DuPont Haskell Laboratory for Health and Environmental Sciences, Martin Slade MPH of the Yale Occupational and Environmental Medicine Program, and Ellen Eisen ScD of the Harvard School of Public Health.
3
Fimre 1 Blood PFOA (ppm) versus calendar time
241 221 20: 181 16: 141 12: 101
87 6: 42 2:
01/01/75
01/01/80
01/01/85
01/01/90
Calendar
time
01/01/95
01/01/00
- PFOA [ppm) -30 -28 -26 -24 -22 T20 r18 -16
14 12 10
8 6 4 2 0 01/01/05
Figure 2
Total Chol .
Total cholesterol (mg/dl) versus age stratified by gender
Total Chol . Img/dl I ;soo
100
SEX
1.11.1 F -m
-_
Firmre 3
17.5
Distribution of total cholesterol (mg/dl)
15.0
12.5
/
E 10.0 tc e " t 7.5
5.0
2.5
0
82.5
112.5
142.5
172.5
202.5
232.5
262.5
292.5
322.5
352.5
382.5
412.5
442.5
472.5
Total Cholesterol
(mg/dlI
6
Table 1
Longitudinal analysis of total cholesterol (mg/dl) by blood PFOA (ppm) and other covariates
REFERENCES
1. Ubel FA, Sorenson SD, Roach DE. Health Status of plant workers exposed to fluorochemicals-a preliminary report. Am Ind Hyg Assoc J. 1980.41:584-589.
2. Olsen GW, Gilliland FD, BUrlew MM, Burris JM, Mandel JS, Mandel JH. An epidemiologic investigation of reproductive hormones in men with occupational exposure to perfluorooctanoic acid. J Occup Env Environ Med. 1998.40: 614622.
3. Olsen GW, Burris JM, BUrlew MM, Mandel JH. Epidemiologic assessment of worker serum Perfluorooctanesulfonate (PFOS) and Perfluorooctanoate (PFOA) concentrations and Medical Surveillance Examination. J Occup Env Environ Med. 2003.45:260-270.
4. Olsen GW, Church TR, Miller JP, Burris JM, Hansen KJ, Lundberg JK et al. Perfluooctanoate and other fluorochemicals in the serum of American red cross adult blood donors. Environ HeaZth Perspect. 2003. 111: 1892- 190 1.
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9. Haughom B, Spydevold 0. The mechanism underlying the hypolipemic effect of perflurooctanoic acid (PFOA), perfluorooctanesulphonic acid (PFOSA), and clofibric acid. Biochemica et Biophysics Acta. 1992.1128:65-72.
10. Pastoor TP, Lee KP, Perri MA, Gillies PJ. Biochemical and morphological studies of ammonium perfluorooctanoate-induced hepatomegaly and peroxisome proliferation. Exp A4ol Pathol. 1987.47:98-109.
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12. Biegel LB, Hurt ME, Frame SR, O'Connor JL, Cook JC. Mechanisms of extrahepatic tumor induction by peroxisome proliferators in male CD rats. Toxicol Sci. 2001.60:44-55.
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