Exposure to serum perfluoroalkyl substances and biomarkers of liver function: The Korean national environmental health survey 2015-2017.

BACKGROUND: Exposure to perfluoroalkyl substances (PFAS) may increase the risk of liver disease by disrupting cholesterol and lipid synthesis/metabolism, leading to higher liver-enzyme concentrations. However, most studies assessing association between PFAS and liver enzymes focused on individual PFAS. Moreover, PFAS concentrations differ based on sex and obesity status, and it remains unclear whether these factors affect associations with liver function. Therefore, we examined the association between exposure to both individual and combined PFAS and liver-function biomarkers and assessed sex and obesity as effect modifiers in Korean adults. METHODS: We measured serum concentrations of the five most abundant PFAS (PFOA, PFOS, PFHxS, PFDA, PFNA) and three liver enzymes (alanine transaminase [ALT], aspartate aminotransferase [AST], γ-glutamyl transferase [GGT]) in 1404 adults from the Korean National Environmental Health Survey Cycle 3, 2015-2017. We used linear regression to evaluate associations between individual PFAS and liver-function biomarkers, assessing sex and obesity as possible effect modifiers, and performed Bayesian kernel machine regression and quantile g-computation to evaluate the overall effect of PFAS mixture on biomarkers of liver function. RESULTS: Among 1404 Korean adults, all five PFAS were detected. Geometric mean concentration was highest for PFOS (16.11 µg/L), followed by PFOA (5.83 µg/L), PFHxS (2.21 µg/L), PFNA (2.03 µg/L), and PFDA (1.06 µg/L). In multivariable linear regression, all PFAS were positively associated with ALT, AST, and GGT; 2-fold increase in each PFAS was associated with 3.4-8.6% higher ALT, 2.4-4.6% higher AST, and 4.6-11.1% higher GGT (all p < 0.05). Positive associations for PFOA, PFDA, and PFNA with AST were stronger in men, and positive associations for PFOS with ALT and GGT were stronger in women. Compared to obese participants, nonobese participants had higher average percent changes in each enzyme, particularly GGT, when individual PFAS concentration doubled. Additionally, increased exposure to PFAS mixtures was associated with higher ALT, AST, and GGT. In quantile g-computations, simultaneous quartile increase in all PFAS was significantly associated with 6.9% (95%CI: 3.7, 10.2) higher ALT, 4.5% (95%CI: 2.4, 6.6) higher AST, and 8.3% (95%CI: 3.7, 13.1) higher GGT levels, on average. CONCLUSIONS: Exposure to individual and combined PFAS is associated with higher liver enzymes in Korean adults, providing additional evidence for the association between PFAS exposure and risk of liver disease.

Exposure to several polychlorinated biphenyls (PCBs) is associated with chronic kidney disease among general adults: Korean National Environmental Health Survey (KoNEHS) 2015-2017.

We investigated the association between major persistent organic pollutants (POPs) exposure and chronic kidney disease (CKD) among general adult population of Korea. For this purpose, a subset of the adult population (n = 1276) participated in Korean National Environmental Health Survey (KoNEHS) Cycle 3 (2015-2017) were analyzed for twenty-four POPs in serum, including organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs), and were derived for estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (uACR). Multivariable linear regression was conducted to assess the association between POPs exposure and CKD-related parameters including eGFR and uACR. As sensitivity analyses, principal component analysis was conducted. Moreover, the U.S. National Health and Nutrition Examination Survey (NHANES) 1999-2004 data were chosen to compare with the observations of the Korean adults. Approximately 7.7% of the Korean adult population possessed CKD based on either eGFR (<60 ml/min/1.73 m2) or uACR (≥30 mg/g) criteria. Among the POPs that were detected in ≥70% of the subjects, PCB153 (ß = -1.61, 95% CI: -2.55, -0.67, P = 0.001) and PCB180 (ß = -1.47, 95% CI: -2.53, -0.40, P = 0.007) exhibited significant associations with decreased eGFR, especially in females. In male participants, hexachlorobenzene (HCB) was associated with eGFR (ß = -0.79, 95% CI: -1.53, -0.04, P = 0.040). Sex-dependent associations with eGFR were also shown in the PCA model. Moreover, the sex-dependent associations of PCBs were similarly observed in the adult populations of the US NHANES. However, POPs exposure was not associated with uACR, regardless of association model or population. The observed associations of PCBs are supported by several experimental studies reported elsewhere. To our knowledge, it is the first report that suggests significant associations of PCBs and HCB with eGFR among general population, and further validations in other populations are warranted.

Profile of Environmental Chemicals in the Korean Population-Results of the Korean National Environmental Health Survey (KoNEHS) Cycle 3, 2015-2017.

The Korean National Environmental Health Survey (KoNEHS) program provides useful information on chemical exposure, serves as the basis for environmental health policies, and suggests appropriate measures to protect public health. Initiated on a three-year cycle in 2009, it reports the concentrations of major environmental chemicals among the representative Korean population. KoNEHS Cycle 3 introduced children and adolescents into the analysis, where the blood and urine samples of 6167 participants were measured for major metals, phthalates, phenolics, and other organic compounds. Lead, mercury, cadmium, metabolites of DEHP and DnBP, and 3-phenoxybenzoic acid levels of the Korean adult population tended to decrease compared to previous survey cycles but remained higher than those observed in the US or Canada. Both bisphenol A (BPA) and trans,trans-muconic acid concentrations have increased over time. Heavy metal concentrations (blood lead, and cadmium) in children and adolescents were approximately half that of adults, while some organic substances (e.g., phthalates and BPA) were high. BPA showed higher levels than in the US or Canada, whereas BPF and BPS showed lower detection rates in this cycle; however, as these are increasingly used as a substitute for BPA, further research is necessary. As environmental chemicals may affect childhood health and development, additional analyses should assess exposure sources and routes through continuous observations.

Association of exposure to phthalates and environmental phenolics with markers of kidney function: Korean National Environmental Health Survey (KoNEHS) 2015-2017.

Increasing number of consumer chemicals have been associated with chronic kidney disease (CKD) in human populations. However, many studies that investigated estimated glomerular filtration rate (eGRF) as an outcome reported inconsistent associations. In the present study, we employed a subset (n = 1292) of a nationally representative adult population participating in Korean National Environmental Health Survey (KoNEHS) 2015-2017, and assessed associations of major phthalates, bisphenol A (BPA), and parabens with both eGRF and albuminuria. In order to address a potential collider issue, a covariate-adjusted standardization method was applied, in addition to the conventional creatinine-correction, for adjusting urine dilution. Regardless of adjustment method, urinary DEHP metabolites showed significant positive associations with albumin to creatinine ratio (ACR). In addition, urinary metabolites of other heavy molecular weight phthalates such as MCOP and MCNP showed significant positive associations with ACR in the female population, but only following the covariate-adjusted standardization. For eGFR, conventional creatinine-correction resulted in positive associations with most of measured phthalate metabolites. However, with the covariate-adjusted standardization, most of positive associations with eGFR disappeared, and instead, significant negative associations were observed for MnBP, BPA, and EtP. Secondary analysis following stratification by CKD status, as well as principal component analysis (PCA), generally supported the observed associations. The present observations highlight the importance of urine dilution adjustment method for association studies on eGFR, and suggest potential effects of several consumer chemicals on adverse kidney function among humans.