Plasma Cholecystokinin and Hepatic Enzymes, Cholesterol and Lipoproteins in Ammonium Perfluorooctanoate Production Workers

Abstract

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.

Peer Reviewed: Perfluorochemical Surfactants in the Environment

“…PFOS and PFOA were found up to 12.8 and 114 µg/mL, respectively (24,25). HPLC/MS/MS has detected PFOS, FOSA, PFOA, and PFHS in blood sera of the general population, with PFOS concentrations four-to five-fold greater than those of PFOA (13).…”

Assessment of lipid, hepatic, and thyroid parameters with serum perfluorooctanoate (PFOA) concentrations in fluorochemical production workers

“…As a manufacturer and user of APFO until its phase-out beginning in 2000, the 3M Company (3M) has reported several periodic medical surveillance analyses of its fluorochemical production workers at its Antwerp, Belgium; Cottage Grove, MN; and Decatur, AL manufacturing facilities (Ubel et al 1980;Gilliland and Mandel 1996;Olsen et al 1998Olsen et al , 2000Olsen et al , 2003a. These analyses compared workers' clinical chemistry and hormone results in relation to their serum measurements of either PFOA or perfluorooctanesulfonate (PFOS, C 8 F 17 SO 3 -).…”

“…Both PFOS and PFOA have been shown to result in hypolipidemia in rats at high concentrations and thus the causal model hypothesized in these earlier analyses concentrated on testing for this effect, not hyperlipidemia. Finally, there was no overall analysis of the three manufacturing facilities (Antwerp, Belgium; Cottage Grove, MN; and Decatur, AL) as the Cottage Grove analysis has historically been reported separately (Ubel et al 1980;Gilliland and Mandel 1996;Olsen et al 2000Olsen et al , 2003a due to differences in fluorochemical production activities.…”

Perfluoroctansäure und ihre anorganischen Salze [BAT Value Documentation in German language, 2007]

“…zwischen der PFOA-Konzentration und den Serumspiegeln verschiedener Hormone kein Zusammenhang. Die Autoren merken allerdings einschränkend an, dass die Zahl der Untersuchten mit Blutspiegeln �30 ppm sehr niedrig war und die Blutspiegel vermutlich unter denen lagen, die bei Ratten Hormonstörungen verursacht und hormonabhängige Tumoren induziert hatten (Olsen et al 1998(Olsen et al , 2000.…”