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

Ammonium perfluorooctanoate is a potent synthetic surfactant used in indust rial applications. It rapidly dissociates in biologic media to perfluorooct anoate [CF3(CF2)(6)CO2-], which is the anion of perfluorooctanoic acid [PFO A, CF3(CF2)(6)COOH]. PFOA is a peroxisome proliferator known to increase th e incidence of hepatic, pancreas and Leydig cell adenomas in rats. The panc reas acinar cell adenomas may be the consequence of a mild but sustained in crease of cholecystokinin as a result of hepatic cholestasis. Although no s ignificant clinical hepatic toxicity was observed, PFOA was reported to hav e modulated hepatic responses to obesity and alcohol consumption among prod uction workers. To further assess these hypotheses, we examined medical sur veillance data of male workers involved in ammonium perfluorooctanoate prod uction in 1993 (n=111), 1995 (n=80) and 1997 (n=74). Serum PFOA was measure d by high-performance Liquid chromatography mass spectrometry methods. Plas ma cholecystokinin was measured (only in 1997) by the use of direct radioim munoassay. Serum biochemical tests included hepatic enzymes, cholesterol an d 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, media n 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 refere nce range (up to 80 pg/ml) for a 12 hour fast and were negatively, not posi tively, associated with employees' serum PFOA levels. Our findings continue to suggest there is no significant clinical hepatic toxicity associated wi th PFOA levels as measured in this workforce. Unlike a previously reported observation, PFOA did not appear to modulate hepatic responses to either ob esity or alcohol consumption. Limitations of these findings include: 1) the cross-sectional design as only 17 subjects were common for the three surve illance years; 2) the voluntary participation that ranged between 50 and 70 percent; and 3) the few subjects with serum levels greater than or equal t o 10 ppm.