Dataset Information

Modeled Perfluorooctanoic Acid (PFOA) Exposure and Liver Function in a Mid-Ohio Valley Community.

ABSTRACT:

Background

Perfluorooctanoic acid (PFOA or C8) has hepatotoxic effects in animals. Cross-sectional epidemiologic studies suggest PFOA is associated with liver injury biomarkers.

Objectives

We estimated associations between modeled historical PFOA exposures and liver injury biomarkers and medically validated liver disease.

Methods

Participants completed surveys during 2008-2011 reporting demographic, medical, and residential history information. Self-reported liver disease, including hepatitis, fatty liver, enlarged liver and cirrhosis, was validated with healthcare providers. Alanine aminotransferase (ALT), ?-glutamyltransferase (GGT) and direct bilirubin, markers of liver toxicity, were obtained from blood samples collected in the C8 Health Project (2005-2006). Historically modeled PFOA exposure, estimated using environmental fate and transport models and participant residential histories, was analyzed in relation to liver biomarkers (n = 30,723, including 1,892 workers) and liver disease (n = 32,254, including 3,713 workers).

Results

Modeled cumulative serum PFOA was positively associated with ALT levels (p for trend < 0.0001), indicating possible liver toxicity. An increase from the first to the fifth quintile of cumulative PFOA exposure was associated with a 6% increase in ALT levels (95% CI: 4, 8%) and a 16% increased odds of having above-normal ALT (95% CI: odds ratio: 1.02, 1.33%). There was no indication of association with either elevated direct bilirubin or GGT; however, PFOA was associated with decreased direct bilirubin. We observed no evidence of an effect of cumulative exposure (with or without a 10-year lag) on all liver disease (n = 647 cases), nor on enlarged liver, fatty liver, and cirrhosis only (n = 427 cases).

Conclusion

Results are consistent with previous cross-sectional studies showing association between PFOA and ALT, a marker of hepatocellular damage. We did not observe evidence that PFOA increases the risk of clinically diagnosed liver disease.

Citation

Darrow LA, Groth AC, Winquist A, Shin HM, Bartell SM, Steenland K. 2016. Modeled perfluorooctanoic acid (PFOA) exposure and liver function in a Mid-Ohio Valley community. Environ Health Perspect 124:1227-1233;?http://dx.doi.org/10.1289/ehp.1510391.

SUBMITTER: Darrow LA

PROVIDER: S-EPMC4977053 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Modeled Perfluorooctanoic Acid (PFOA) Exposure and Liver Function in a Mid-Ohio Valley Community.

Darrow Lyndsey A LA Groth Alyx C AC Winquist Andrea A Shin Hyeong-Moo HM Bartell Scott M SM Steenland Kyle K

Environmental health perspectives 20160315 8

<h4>Background</h4>Perfluorooctanoic acid (PFOA or C8) has hepatotoxic effects in animals. Cross-sectional epidemiologic studies suggest PFOA is associated with liver injury biomarkers.<h4>Objectives</h4>We estimated associations between modeled historical PFOA exposures and liver injury biomarkers and medically validated liver disease.<h4>Methods</h4>Participants completed surveys during 2008-2011 reporting demographic, medical, and residential history information. Self-reported liver disease, ...[more]

PMID: 26978841

Similar Datasets

Project description:Perfluorooctanoic acid (PFOA) is one of the most used perfluorinated compounds in numerous applications and can be detected in environmental samples from around the globe. The aquatic environment is an important site for PFOA deposit. Nevertheless, the exact mode of action and its resulting toxicological effects on aquatic organisms remain largely unknown. To gain a more extensive understanding of the mode of action of teleost PFOA toxicity, transcriptomics, proteomics, biochemical parameters and reproduction were integrated in the present study. Male and female zebrafish were exposed to nominal concentrations of 0.1; 0.5 and 1 mg/l PFOA for 4 and 28 days resulting in an accumulation which was higher in males compared to females. These gender-related differences were likely caused by different elimination rates due to distinct hormone levels and differences in transport activity by solute carriers. The general mode of action of PFOA was believed to be an increase of the mitochondrial membrane permeability which caused effects on the electron transport system at the biochemical level and resulted in alterations of the oxidative phosphorylation, oxidative stress and apoptosis at the gene transcript and protein level. As a consequence, evidence for the replacement of the affected cells and organelles to sustain tissue homeostasis was found at the molecular level. The higher energy demand, due to these adverse effects, was provided by lowering the glycogen stores. Despite this increase in metabolic expenditure, no effects on reproduction were found indicating that the fish seemed to cope with exposure to the tested concentrations of PFOA. Adult zebrafish (Danio rerio) were exposed to nominal concentrations of 0mg/l; 0.1mg/l; 1mg/l PFOA (perfluorooctanoic acid) for 28 days. Three different 25 litre aquaria per exposure concentration were used resulting in 3 biological replicates with each aquarium containing 8 male and 8 female zebrafish. The livers of 6 male fish and 6 female fish were pooled separately and snap frozen in liquid nitrogen. A reference sample was made by pooling equal amounts of RNA from all samples. A carriage wheel design was used in which all samples were connected to the reference sample and the main contrasts of interest were made directly on the same microarrays as frequently as possible. This design resulted in technical triplicates of each sample.

Dataset Information

Modeled Perfluorooctanoic Acid (PFOA) Exposure and Liver Function in a Mid-Ohio Valley Community.

Background

Objectives

Methods

Results

Conclusion

Citation

Publications

Modeled Perfluorooctanoic Acid (PFOA) Exposure and Liver Function in a Mid-Ohio Valley Community.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure