Data (N = 10336) from National Health and Nutrition Examination Survey for 2003–2016 for US adults aged ≥ 20 years were analyzed to evaluate the concentrations of blood and urine cadmium across the ...various stages of glomerular function. Estimated glomerular filtration rate (eGFR) > 90 mL/min/1.73 m2 was defined to be glomerular function stage 1 (GF-1), eGFR between 60 and 90 mL/min/1.73 m2 defined as GF-2, eGFR between 45 and 60 mL/min/1.73 m2 as GF-3A, and eGFR between 15 and 45 mL/min/1.73 m2 as GF-3B/4. Regression models stratified by GF-stages were fitted to estimate associations between the observed levels of blood and urine cadmium across stages of GF. Based on the results of stratified modes, there were consistent increases in adjusted geometric means (AGMSM) for both blood and urine cadmium from GF-1 to GF-3A although increases were not uniform from one GF stage to another. For the total population, AGMSM for blood and urine cadmium were GF-1 (0.47, 0.24), GF-2 (0.60, 0.37), GF-3A (0.72, 0.45), and GF-3B/4 (0.73, 0.45) μg/L. respectively. Although females had higher AGMSMs than males for both blood and urine cadmium, the difference in blood cadmium narrowed as kidney function deteriorated. Smokers had the steepest increases in AGMSMs for blood and urine cadmium across the stages of glomerular function and smoker-nonsmoker differences for blood cadmium narrowed as kidney function deteriorated but smoker-nonsmoker differences for urine cadmium widened as kidney function deteriorated. The important physiologic messages are that both blood and urine cadmium cease to increase from GF-3A to GF-3B/4, suggesting a new steady state based on renal failure. And, the narrowed difference in blood cadmium in smokers vs. nonsmokers suggests why this happens. Incremental exposures to cadmium are offset by excretion as renal failure progresses.
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•There were consistent increases in adjusted geometric means (AGM) for both blood and urine cadmium from GF-1 to GF-3A.•There was a narrowing down of female-male differences in blood cadmium as kidney function deteriorated.•Also, smoker-nonsmoker differences for blood cadmium narrowed as kidney function deteriorated.
Adjusted levels of blood and urine cadmium increase across various stages of glomerular function as the kidney function declines.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Data from National Health and Nutrition Examination Survey for 2003–2014 for US children aged 6–11 years (N = 2097), adolescents aged 12–19 ears (N = 2642), and adults aged ≥ 20 years (N = 9170) were ...analyzed to investigate the effects of dietary, demographic, disease, lifestyle, and other factors on concentrations of nine metabolites of polycyclic aromatic hydrocarbons (PAH) in urine. PAHs analyzed were: 1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyfluorene, 3-hydroxyfluorene, 9-hydroxyfluorene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, and 1-hydroxypyrene. Adults with diabetes were found to have higher adjusted levels of 1-hydroxynaphthalene (4139 vs. 3622 ng/L, p < 0.01) than nondiabetics. Adults with albuminuria had higher adjusted levels of 1-hydroxynaphthalene (4140 vs.3621 ng/L, p < 0.01) and 2-hydroxynaphthalene (6039 vs. 5468 ng/L, p < 0.01) than those without albuminuria. Children with albuminuria had lower adjusted levels of 9-hydroxyfluorene (162 vs. 187 ng/L, p = 0.04), 1-hydroxyphenanthrene (92 vs. 108 ng/L, p < 0.01), and 1-hydroxypyrene (118 vs. 138 ng/L, p < 0.01) than those without albuminuria. The ratios of smoker to nonsmoker adjusted levels for adults varied from a low of 1.4 for 2-hydroxyphenanthrene to a high of 5.6 for 3-hydroxyfluorene. Exposure to environmental tobacco smoke at home was associated with higher levels of most OH-PAHs among children, adolescents, and adults. Consumption of red meat not processed at high temperatures was associated with increased levels of 1-hydroxypyrene (β = 0.00040, p = 0.01), 1-, 2-, and 3-hydroxyphenanthrene, 3-, and 9-hydroxyfluorene. Consumption of red meat processed at high temperatures was associated with increased levels of 2-hydroxynaphthalene (β = 0.00046, p = 0.02) among adults. Consumption of fish processed at high temperatures was associated with decreased levels of 1-hydroxynaphtahlene (β = − 0.00088, p < 0.01), 2-, 3-, and 9-hydroxyfluorene, 1-, 2-, and 3-hydroxyphenanthrene. Among adults, alcohol consumption and caffeine may be associated with increased levels of certain OH-PAHs. Oxidative stress and inflammation associated with exposure to PAHs are associated with albuminuria and have the potential to lead to the development of diabetes.
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•Increased levels of selected OH-PAH were associated with red meat consumption.•Decreased levels of selected OH-PAH were associated with fried fish consumption.•Increased levels of OH-PAH were associated with alcohol and caffeine consumption.•Smokers had higher levels of selected OH-PAHs than nonsmokers.•Having diabetes and albuminuria were associated with higher levels of some OH-PAHs.
Smoking was associated with elevated levels of almost all OH-PAHs and consumption of red meat was associated with elevated levels of selected OH-PAHs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Data (N = 9650) for US adults aged ≥20 years downloaded from National Health and Nutrition Examination Survey for 2003–2014 were analyzed to study trends in adjusted and unadjusted concentrations of ...selected perfluoroalkyl substances (PFAS), namely, perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (PFDA), perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA). Over 2003–2014, unadjusted concentrations of PFOA decreased by 50%, by 75% for PFOS, by 32% for PFDA, by 27% for PFHxS, and by 30% for PFNA. Females not only had substantially lower concentrations of every PFAS than males but rate of decrease was also higher for females than males, for example, 36.7% for females and 30.6% for males every two years for PFOS. For each survey period of two years, percent decrease in adjusted concentrations was 17% for PFOA, 33.5% for PFOS, 11.5% for PFDA, 6.3% for PFHxS, and 7.6% for PFNA. However, these trend data must be examined within the context of design changes in NHANES over 2003–2014 resulting in oversampling of Hispanics other than Mexican Americans starting 2007–2008 survey cycle and oversampling of non-Hispanic Asians starting 2011–2012 survey cycle. In order to examine how design changes may have affected computations of adjusted and unadjusted concentrations, the data were analyzed using the racial/ethnic categories prior to and after oversampling of Hispanics other than Mexican Americans and non-Hispanic Asians was put into place.
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•Trends analysis over 2003–2014 was conducted for PFOA, PFOS, PFDA, PFHxS, and PFNA.•Over 2003–2014, levels of PFOA, PFOS, PFDA, PFHxS, and PFNA declined (p < 0.01).•Over 2003–2014, unadjusted levels declined by 27% for PFHxS to 75% for PFOS.•For 2-year survey period, adjusted levels declined by as much as 33.5% for PFOS.•Males had higher adjusted levels of PFOA, PFOS, PFDA, PFHxS, and PFNA than females.
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Data from National Health and Nutrition Examination Survey (NHANES) for 2005–2014 for those aged ≥20 years fasting for ≥8 h (N = 3629) were analyzed to evaluate the role that gender and obesity play ...in defining correlations between selected perfluoroalkyl substances (PFAS) and total cholesterol (TC), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), and triglycerides. PFAS considered for analyses were: perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (PFDA), perfluorononanoic acid (PFNA), perfluorohexane sulfonate (PFHxS), perfluoroundecanoic acid (PFUnDA), and 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (Me-FOSAA). Gender and obesity stratified regression models were fitted to estimate associations between PFAS and lipid/lipoproteins with adjustments made for confounders. For obese males, but not for nonobese males, positive associations were found between TC and LDL with PFOA (β = 0.0519, p = 0.01 for TC and β = 0.0822, p = 0.03 for LDL), and PFNA (β = 0.0328, p = 0.03 for TC and β = 0.0679, p = 0.04 for LDL). For obese females, adjusted concentrations of TC increased with increase in the concentrations of PFDA (β = 0.0247, p = 0.048), PFNA (β = 0.0286, p = 0.04), and Me-PFOSAA (β = 0.0274, p = 0.02), and there was a positive association of LDL with PFOS (β = 0.0375, p = 0.04), PFDA (β = 0.0397, p = 0.047), and PFNA (β = 0.0593, p = 0.02). The findings, concerning the relationship of longer chain PFAS to serum lipids, suggest greater susceptibility to elevated TC and LDL cholesterol in the obese participants, with some differences between men and women. The key contributing modifiable risk for nonalcoholic steatosis is obesity, and, the development of nonalcoholic steatosis is recognized to be sexually dimorphic. The epidemiologic observation of a susceptible obese subgroup in our data is consistent with toxicology literature findings of disrupted cholesterol metabolism via induced steatosis following PFAS exposure. Gender differences affect serum concentration of PFAS during the reproductive years, and our data add a secondary question concerning whether they also affect the interaction between PFAS exposure and lipid handling in males and females.
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•Gender and obesity stratified models were fitted to explore associations between PFAS and lipids.•PFOA and PFNA were positively associated with cholesterol and LDL for obese males.•PFDA and PFNA were positively associated with cholesterol and LDL for obese females.•PFOS, PFDA, and PFHxS were also positively associated with HDL cholesterol for non-obese females.•Obesity modifies the cross-sectional associations of PFAS with lipid concentrations.
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Data (N = 10644) for US adults aged ≥20 years for 2003–2016 from National Health and Nutrition Examination Survey were analyzed to evaluate the impact of co-occurrence of obesity with diabetes, ...anemia, albuminuria, and hypertension on concentrations of five perfluoroalkyl acids (PFAA), namely, perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA). For the total population, males, and females, co-occurrence of obesity with hypertension, albuminuria, anemia, and diabetes was found to be associated with lower adjusted geometric means (AGM) than nonobese for every PFAA. For example for females, for PFOS, AGMs for obese with no diseases, hypertension, albuminuria, anemia, and diabetes were 8.2, 10.8, 5.8, 4.6, and 7.7 ng/mL respectively. In comparison, for PFOS, for nonobese females, AGMs for those with no diseases, hypertension, albuminuria, anemia, and diabetes were found to be 8.9, 13.4, 7.7, 6.0, and 10.2 ng/mL respectively. This implies obesity is associated with higher excretion rates. Females, in general, had lower AGMs than males for both obese and nonobese for every PFAA for every disease group. For example, percent ratios of obese females to males AGMs for PFOA were 66.7%, 87.1%, 88.2%, 70.6%, and 90% for those with no diseases, hypertension, albuminuria, anemia, and diabetes respectively. The ratios of obese to nonobese AGMs for females were lower than males for every PFAA for those with no diseases and hypertension only. For example, for PFOA for those with no diseases, obese to nonobese AGM ratios were 87% for females and 100% for males. Thus, additional excretion of certain PFAAs due to obesity is higher in females than males for those with no diseases and hypertension only.
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•Obesity is associated with lower concentrations of PFAAs.•Anemia, albuminuria, and diabetes are associated with lower concentrations of PFAAs.•Hypertension is associated with higher concentrations of PFAAs.
Obesity is associated with lower PFAAs. Anemia, albuminuria, and diabetes are associated with decreased concentrations of PFAAs. Hypertension is associated with increased concentrations of PFAAs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Associations between selected perfluoroalkyl acids (PFAAs) and biomarkers of renal function were evaluated for US adult aged ≥ 20 years (N = 8220) in the National Health and Nutrition Examination ...Survey for 2005–2014. Glomerular filtration (GF) stage-stratified regression models were classified by estimated glomerular filtration rate (eGFR) with GF-1 (eGFR > 90 mL/min/1.73 m2), GF-2 (eGFR 60–89 mL/min/1.73 m2), GF-3A (45–59 mL/min/1.73 m2), and GF-3B/4 (15–44 mL/min/1.73 m2). For GF-1, PFOA, PFOS, and PFHxS were positively and significantly associated with serum creatinine. Serum albumin levels were positively associated with the PFAA considered at all stages and most associations were significant. Further, PFAS serum concentration associations to serum albumin were about 2–3 times stronger at GF-3B/4 than at GF-1. In contrast, urine albumin was negatively and significantly associated with PFOA and PFHxS serum concentrations at all stages of renal function, while, PFOS and PFNA were negatively and significantly associated to urine albumin at GF-3A and GF-3B/4. Urine albumin/creatinine ratios were negatively and significantly associated with PFOA, PFOS, and, and PFHxS serum concentrations at all stages of renal function, as well as with PFNA and PFDA at GF-3A and GF-3B/4. Recent work revealed that serum PFAAs have an inverted U-shaped association to the calculated stages of renal failure based on eGFR; this work adds that albuminuria makes additional negative contributions to already existing negative associations of PFAA to eGFR in advancing stages of renal failure. We hypothesize that both progressive renal failure per se and especially renal failure with albuminuria cause the kidneys to reabsorb less and to excrete more of the PFAAs studied. We suspect this finding may generalize to some other perfluoroalkyl substances (PFAS). The findings also imply study design considerations for evaluating associations to diseases and biomarkers associated with renal failure, such as diabetes.
•Negative associations between urinary albumin and UACR and PFAAs increased incrementally from GF-1 to GF-3B/4.•Albuminuria is associated with and may drive enhanced excretion of PFAAs as kidney function declines.•We illustrate how results have implications for study design of biomarkers associated with renal failure.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Data for US adults aged ≥20 years from National Health and Nutrition Examination Survey for the years 2003–2014 were analyzed to evaluate how adjusted (N = 8481) and unadjusted (N = 9080) levels of ...selected perfluoroalkyl acids (PFAA) vary across the different stages of glomerular function (GF) among those who did not have diabetes, anemia, or albuminuria as compared to those who had diabetes only, anemia only, and albuminuria only. PFAAs selected for analyses were: perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA). Irrespective of GF stage, there was no noticeable evidence to suggest that adjusted levels of PFAA for those with diabetes only are any lower than those with no diabetes, no anemia, and no albuminuria. Those who had anemia only were found to have lower adjusted levels of at least PFOA, PFOS, PFDA, and PFHxS than those who had no diabetes, no anemia, and no albuminuria. These results were seen in the presence (eGFR < 60 mL/min/1.73 m2) as well as the absence of chronic kidney disease. For GF-1 (eGFR > 90 mL/min/1.73 m2), GF-2 (60 ≤ eGFR ≤ 90 mL/min/1.73 m2), and GF-3B/4 (15 < eGFR ≤ 45 mL/min/1.73 m2), those who had albuminuria only had lower adjusted levels of PFOA, PFOS, and PFHxS than those who had no diabetes, no anemia, and no albuminuria. In general, adjusted levels of those who had albuminuria only were lower than those who had anemia only at GF-3 and more often than not at GF-1 and GF-2. Rise in adjusted levels of PFAA from GF-1 to GF-3A (45 < eGFR < 60 mL/min/1.73 m2) was faster for those with anemia only than any other comparison group for the total population and females.
•Those with anemia only had among the lowest levels of PFAAs.•Those with albuminuria only had among the lowest levels of PFAAs.•Rise in adjusted levels of PFAA from GF-1 to GF-3A was fastest for those with anemia only.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Data from National Health and Nutrition Examination Survey for 2013–2016 were used to compare observed levels of cadmium, lead, and total mercury in blood among US residents aged ≥12 years who were ...users of cigars, cigarettes, cigars and cigarettes, e-cigarettes and dual users of cigarettes and e-cigarettes. Total sample size available for analysis was 1139. Adjusted geometric means (AGM) among cigarette, cigar, e-cigarette, cigarette and cigar, and cigarette-e-cigarette users were comparable for blood cadmium lead, and total mercury. Cigar only users had lower AGM than cigar and cigarette users for total mercury (0.56 vs. 0.97 μg/L, p = 0.03). There is no evidence yet that can show concentrations of blood and urine cadmium, lead, and mercury among e-cigarette users are any different than among cigarette and/or dual users of cigarettes and e-cigarettes.
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•Data on blood Cd, Pb, and total Hg were analyzed for cigarette, cigar, and e-cigarette users.•Levels of Cd, Pb, and total Hg were comparable among cigarette, cigar, and e-cigarette users.•Due to changing patterns of e-cigarette use, biomonitoring data in future need to be collected.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Gender-age specific linear statistical models were fitted to analyze gender-based differences in serum concentrations of PFOA, PFNA, PFHxS, and PFOS for US adults and adolescents (N = 17,932) and ...children age < 12 years (N = 637) using nationally representative data for US for 2003–2018. Around the age of about 11–12 years for PFOS, PFNA, and PFNA, and around 15 years for PFOA, females begin to have reliably lower serum PFAS than males. This divergence is maximized around the ages of about 35 to 40 years for the alkylate compounds PFOA and PFNA, and from around 24–52 years for the sulfonate compounds PFOS and PFHxS. For example, for PFOS, gender divergence was 1.15 ng/mL at age 15, compared to 5.6 ng/mL at the age of 37 years. Uniquely, PFOS remained lower in females in most years after age 56, a contrast to the convergence in other PFAS studied. For males, increasing patterns were followed by somewhat decreasing patterns of concentration for most PFAS, the reverse was observed for females. The findings have implications for study design. Based on the results provided in detailed tables and figures for this study, we recommend separate analyses of male and female data. In addition, female serum concentration data should be considered for stratified analysis for pre- and post-menopausal time periods. From a mechanistic perspective, the data add support to existing questions about influences on gender differences in serum PFAS that may be attributed to causes other than menstruation, pregnancy, and lactation. These are amenable to further study.
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•Nonlinear age and sex related changes in serum PFAS motivated this study.•From late teens to late 30's/early 40's, serum PFAS levels for females decrease.•From late 30's/early 40's to early 50's, serum PFAS levels for females increase.•Menstruation, lactation, and childbirth do not fully explain sex differences.•PFAS concentrations should be modeled separately for males and females.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Data (N = 6844) from National Health and Nutrition Examination Survey for US adults aged ≥ 20 years for the years 2007–2014 were analyzed to evaluate distributional characteristics of selected ...perfluoroalkyl substances (PFAS) - perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (PFDA), perfluorohexane sulfonate (PFHxS) and perfluorononanoic acid (PFNA) with declining glomerular function. The population was stratified according to the estimated glomerular filtration rates (eGFR) that accompany the stages of kidney disease, designated as glomerular function-1 (GF-1, eGFR>90 mL/min/1.73 m2); GF-2 (eGFR 60–89 mL/min/1.73 m2), GF-3A (eGFR 45–59 mL/min/1.73 m2), and GF-3B and 4 combined (eGFR 15–44 mL/min/1.73 m2). Unadjusted as well as adjusted geometric means for serum PFOA, PFDA, PFHxS, and PFNA increased as expected through stage GF-3A but decreased below the concentrations associated with GF-1 for those who were in GF-3B/4. For example, unadjusted geometric means for PFOA were 2.59, 3.02, 3.01, and 2.22 ng/mL for GF-1, GF-2, GF-3A, and GF-3B/4 respectively. Adjusted geometric means for PFOA were 2.34, 2.83, 2.83, and 1.81 ng/mL for GF-1, GF-2, GF-3A, and GF-3B/4 respectively. Thus, PFAS were found to follow inverted U-shaped distributions across different stages of glomerular function. For females, decreases in adjusted PFAS serum levels were initiated at GF-3A, while decreases for males began as early as GF-2. Usually, females are known to have lower levels of PFAS but when in GF-3A and GF-3B/4, females were found to have higher levels of PFAS than males. Thus, inverted U-shaped curves for males and females intersected between GF-2 and GF-3A for PFOA and PFHxS and at GF-3A for PFOS and PFNA. Associations between PFAS and biomarkers of kidney function may be modified in both magnitude and even in direction as kidney function deteriorates. These findings have implications for studies that evaluate associations between PFAS and disease states that affect kidney function, as well as outcome biomarkers known to be affected by kidney function.
•PFAS follow an inverted U-shaped distribution across declining stages of glomerular function.•Shape of the inverted U-shaped distributions for PFAS differ by gender.•Points of inflection are located at GF-2 for males and GF-3A for females.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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