Factors affecting serum PFAS concentrations among US females with surgically and naturally induced menopause: data from NHANES 2003-2018.

Sex hormones influence excretion of the biopersistent per-and polyfluoroalkyl substances (PFAS) in rodents, but such influences in human studies are less clear. Data from National Health and Nutrition Examination Survey (NHANES) for 2003-2018 for US females aged ≥ 20 years who reported having hysterectomy (HYST, N=1064) and who reported being in natural menopause (MENOP, N=1505) were analyzed for associations of ever use of birth control pills, past pregnancies, live births, and other factors with serum concentrations of six per- and polyfluoroalkyl substances (PFAS). For both HYST and MENOP, PFAS concentrations computed as adjusted geometric means (AGM) were higher among those who took female replacement hormone therapy (HRT) compared to nonusers in multivariable adjusted models, for example PFOS in HRT takers (10.70 ng/mL; 95% C.I. 9.46-12.11) vs. 8.70 ng/mL (95% C.I. 8.07-9.37) in nonusers (p<0.01), and PFOA in HRT users was 2.85 ng/mL (95% C.I. 2.53-3.21) vs. 2.44 ng/mL (95% C.I. 2.32-2.36) in nonusers (p=0.01), with similar findings across race/ethnicity stratifications. HYST participants with retained ovaries sometimes had higher serum PFAS than those without ovaries in post-HYST participants not taking HRT, but results had overlapping confidence intervals in all cases and were inconsistent. PFASs were inversely associated with obesity and directly associated with higher SES as reflected in poverty income ratio (PIR) in most cases, yet HRT results for the entire population are robust to adjustments for obesity and PIR. The results suggest the hypothesis that exogenous hormone use, and specifically estrogen hormones, are associated with higher serum PFAS in postmenopausal women. We discuss potential explanations for the findings, including data from other populations that estrogens may delay the onset of kidney disease, a finding which might paradoxically increase serum PFAS among the HRT population to explain some or all of our findings in a menopausal population.

Co-variate adjusted associations between serum concentrations of selected perfluoroalkyl substances and urinary concentrations of selected arsenic species.

Data from National Health and Nutrition Examination Survey for 2011-2012 were used to estimate associations of the serum concentrations of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluoroundecanoic acid (PFUnDA), and 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (Me-PFOSA) with urinary concentrations of total arsenic (UAS), inorganic arsenic (IAS), arsenobetaine (UAB), and dimethyl arsinic acid (UDMA) among US adults aged > = 20 years. Concentrations of PFNA were positively associated with all four arsenic variables but statistical significance was observed for IAS only (ß = 0.33364, P = 0.04). Concentrations of PFDA were positively associated with UAS (ß = 0.20688, P = 0.01), IAS (ß = 0.23712, P = 0.02), and UAB (ß = 0.26049, P = 0.02). Concentrations of PFUnDA were positively associated with UAS (ß = 0.49946, P < 0.01), IAS (ß = 0.51782, P < 0.01), UAB (ß = 0.62924, P < 0.01), and UDMA (ß = 0.26375, P < 0.01). Concentrations of Me-PFOSA with PFAS were inversely associated with every PFAS but statistical significance was observed for UDMA only (ß = - 0.05613, P = 0.03). PFOA, PFHxS, and PFOS were, in general, negatively associated with concentrations of all four arsenic variables but without reaching statistical significance. Positive associations of PFDA, PFNA, and PFUnDA with arsenic necessitate investigation about impact of the co-exposure of these PFAS with arsenic and their impact on health. Fluorinated carbon chain length > 8 as opposed to ≤ 8 may have a role in defining associations of PFAS with arsenic.

Associations between concentrations of serum α-klotho and selected urinary monohydroxy metabolites of polycyclic aromatic hydrocarbons: data for US adults aged 40-79 years.

For the first time, the associations between urinary concentrations of oxidant polycyclic aromatic hydrocarbon (PAH) metabolites and serum concentrations of anti-oxidant α-klotho were estimated for US adults aged 40-79 years. Multivariate regression models with α-klotho as dependent variable and one of the urinary metabolite of PAH as independent variables were fitted. In the absence of albuminuria and normal (eGFR > 90 mL/min/1.73 m2) kidney function, 10% increases in concentrations of 2-hydroxynaphthalene, 9-hydroxyfluorene, and ∑PAH were associated with 0.25%, 0.32%, and 0.19% decreases in serum α-klotho concentrations. In the absence of albuminuria and near normal (60 < = eGFR < 90 mL/min/1.73 m2) kidney function, 10% increases in concentrations of 1-hydroxynaphthalene, 9-hydroxyfluorene, 1-hydroxyphenanthrene, and ∑PAH were associated with 0.17%, 0.38%, 0.34%, and 0.18% decreases in serum α-klotho concentrations. To what degree, these mild decreases in α-klotho are a matter of concern, is a subject ripe for discussion and additional investigations. When kidney function was normal or near normal but albuminuria was present, the associations between α-klotho and different metabolites of PAH were, more or less, randomly positive or negative and none reached statistical significance. To conclude, exposure to polycyclic aromatic hydrocarbons may result in reduced concentrations of α-klotho, an antiaging protein.

Serum concentrations of perfluoro-1-heptane sulfonate (PFHpS) among US adults: variabilities across different stages of kidney function.

For the first time, data (N = 1311) from US National Health and Nutrition Examination Survey for 2017-2018 were analyzed for gender and racial/ethnic differences for perfluoro-1-heptane sulfonate (PFHpS) for US adults aged ≥ 20 years. In addition, variability in adjusted concentrations across various stages of glomerular filtration (GF) was also studied. While no racial/ethnic differences were observed, males had statistically significantly higher concentrations of PFHpS than females (0.30 vs. 0.19 ng/mL, p < 0.01). Concentrations of PFHpS across various stages of kidney function were located on inverted U-shaped curves with point of inflection located at GF-3A (45 ≤ eGFR < 60 mL/min/1.73 m2) for all participants, males, as well as females. After moderate increase from GF-1 (eGFR ≥ 60 mL/min/1.73 m2) to GF-2 (60 ≤ eGFR < 90 mL/min/1.73 m2), the increase in PFHpS concentration from GF-2 to GF-3A was quite steep. For example, for females, concentration from GF-1 to GF-2 increased from 0.17 ng/mL to 0.23 ng/mL for an increase of 35% but from GF-2 to GF-3A, concentrations of PFHpS increased from 0.23 ng/mL to 0.43 ng/mL for an increase of about 87%. Following this, at GF-3B/4 (15 ≤ eGFR < 45 mL/min/1.73 m2), concentrations decreased sharply to the almost the same levels as for GF-1. For example, for males, the decrease from GF-3A (0.67 ng/mL) to GF-3B/4 (0.21 ng/mL) was about 69%. Concentration curves for each race/ethnicity were also located on inverted U-shaped curves but relatively very small sample sizes for Hispanics and non-Hispanic Asians, and others at GF-3A and GF-3B/4 lead to substantial variability. The balance between reabsorption-excretion in favor of reabsorption at GF-1 and GF-2 switched to in favor of excretion starting at the end of GF-3A.

Associations of serum perfluoroalkyl substances with concentrations of blood manganese and selenium.

The aim of this study was to estimate the associations of blood manganese and selenium with serum concentrations of selected perfluoroalkyl substances (PFAS). The presence or absence of this association is important because PFAS have documented pro-oxidant properties, whereas manganese and selenium are critical to antioxidant responses. For this purpose, the data from NHANES for US adults aged ≥ 20 years (N = 3982), adolescents aged 12-19 years (N = 1524), and children aged 3-11 years (N = 639) were analyzed. Among adults, concentrations of blood manganese were found to be inversely associated with serum concentrations of perfluorooctanoic acid or PFOA (ß = - 0.04204, p < 0.01), perfluorononanoic acid or PFNA (ß = - 0.02700, p < 0.01), perfluorohexane sulfonate or PFHxS (ß = - 0.04306, p < 0.01), and perfluorooctane sulfonate or PFOS (ß = - 0.04494, p < 0.01). Blood concentrations of selenium were found to be positively associated with PFHxS only among adults (ß = 0.000678, p = 0.047) and adolescents (ß = 0.01377, p = 0.02). The Mn results but not the less consistent Se associations were robust to adjustments for serum albumin. Possible reasons for the inverse association of PFOA, PFHxS, PFNA, and PFOS with Mn among US adults are discussed. The finding raises concerns about manganese's diminished ability to mount antioxidant responses to PFAS exposure.

Serum concentrations of selected perfluoroalkyl substances for US females compared to males as they age.

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.

Associations between the concentrations of α-klotho and selected perfluoroalkyl substances in the presence of eGFR based kidney function and albuminuria: Data for US adults aged 40-79 years.

Exposures to per- and polyfluoroalkyl substances (PFAS) cause oxidative stress, a risk factor for tissue damage leading to kidney and cardiovascular diseases. The antiaging protein klotho is known to act as an anti-oxidative agent, and how klotho homeostasis interacts with PFAS has not been reported. This study among 3981 US adults aged 40-79 years old evaluated relationships of internal PFAS contamination to α-klotho across stages of estimated glomerular filtration rate or eGFR-based kidney function and albuminuria defined as urinary albumin creatinine ratio of >30 mg/g creatinine. In the absence of albuminuria and when eGFR based kidney function was in stage GF-1 (eGFR ≥ 90 mL/min/1.73 m2), statistically significant inverse associations between α-klotho and PFNA (ß = -0.04930, p < 0.01), PFDA (ß = -0.03307, p = 0.02), and PFUnDA (ß = -0.03451, p = 0.01), PFHxS (ß = -0.03011, p = 0.04) and PFOS (ß = -0.03126, p = 0.03) were noted. No associations between α-klotho and PFAS were observed when kidney function was in stages GF-2 (60 ≤ eGFR < 90 mL/min/1.73 m2) or GF-3A (45 ≤ eGFR < 60 mL/min/1.73 m2) in the presence or absence of albuminuria. Unexpectedly, however, in the absence of albuminuria, with kidney function in stage GF-3B/4 (15 ≤ eGFR < 45 mL/min/1.73 m2), associations were positive between α-klotho and PFOA (ß = 0.20989, p < 0.01), PFNA (ß = 0.18373, p < 0.1), PFDA (ß = 0.20413, p < 0.01), PFUnDA (ß = 0.17660, p < 0.01), and PFOS (ß = 0.14267, p < 0.01). The inverse relationship of PFAS to the antioxidant protein α-klotho in those with healthy kidney function has not been previously reported and should be evaluated in other populations.

Serum klotho and its associations with blood and urine cadmium and lead across various stages of glomerular function: data for US adults aged 40-79 years.

Exposures to cadmium and lead can cause oxidative stress, leading to tissue damage resulting in kidney and cardiovascular diseases. The antiaging protein klotho, on the other hand, is known to act as an anti-oxidative agent. How klotho homeostasis interacts with exposure to cadmium and lead has not been reported. Thus, this study was carried to investigate associations of serum klotho with blood and urine cadmium and lead in US adults aged 40-79 years across stages of eGFR-based kidney function and albuminuria defined as urinary albumin/creatinine ratio of > 30 mg/g creatinine. As long as the kidney function was normal (eGFR ≥ 90 mL/min/1.73 m2) or near normal (60 ≤ eGFR < 90 mL/min/1.73 m2), there was no evidence of an association between cadmium exposure and klotho concentrations irrespective of the presence/absence of albuminuria. During kidney dysfunction (15 ≤ eGFR < 60 mL/min/1.73 m2), 10% increases in blood cadmium concentrations resulted in decreases in klotho concentrations between 0.27 and 0.84%. In addition, during severe kidney dysfunction (15 ≤ eGFR < 45 mL/min/1.73 m2), a positive association between urine cadmium and serum klotho concentrations was observed. In the absence of albuminuria and when kidney function was normal or near normal, 10% increases in blood lead concentrations were observed to be associated with modest decreases between 0.28% and 0.37% in serum klotho concentrations. Similar results were observed between the concentrations of urine lead and serum klotho during kidney dysfunction.

Contribution of diet and other factors for urinary concentrations of total arsenic and arsenic species: data for US children, adolescents, and adults.

A comprehensive analysis of the associations between the consumptions of 17 food products with urinary concentrations of arsenobetaine, total arsenic, arsenous acid, dimethylarsinic acid (UDMA), monomethylarsonic acid (UMMA), and total inorganic arsenic for US children aged 3-5 years (N = 439), children aged 6-11 years (N = 2139), adolescents aged 12-19 years (N = 2434), and adults aged >= 20 years (N = 10902) was conducted. Data from National Health and Nutrition Examination Survey for 2005-2016 were used for this study. Concentrations of arsenobetaine were as much as > 15 times higher among consumers of fish/shellfish than non-consumers for children aged 6-11 years, > 12 times higher for children aged 3-5 years, > 13 times higher for adolescents, and > 7 times higher for adults. Consumption of rice as opposed to non-consumption of rice was associated with as much as 36.5% higher concentrations of total arsenic, 12.7% higher concentrations of arsenous acid, 43.9% higher concentrations of UDMA, 18.2% higher concentrations of UMMA, and 14.1% higher concentrations of total inorganic arsenic. Thus, consumption of fish/shell fish and rice was associated with higher concentrations of organic/inorganic arsenic. In addition, consumption of alcohol was also found to be associated with higher concentrations of organic/inorganic arsenic. However, consumption of milk and milk products, vegetables, organ and other meats, and nutritional drinks was found to be associated with lower concentrations of organic/inorganic arsenic. Thus, while consumption of several foods is associated with higher concentrations of arsenic, there are also foods whose consumption is associated with decreased concentrations of arsenic. Further studies are needed to identify foods that may lead to decreased concentrations of arsenic and as such arsenic toxicity.

Impact of the increasing concentrations of selected perfluoroalkyl acids on the observed concentrations of red blood cell folate among US adults aged ≥20 years.

For the first time (N = 6291), a study was undertaken to estimate associations between the concentratio ns of red blood cell folate (RBCF) and concentration of six perfluoroalkyl acids (PFAAs), namely, perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), perfluorodecanoic acid (PFDA), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUnDA) for US adults aged ≥20 years by fitting regression models for the data from National Health and Nutrition Examination Survey for 2007-2014. In almost consistent fashion, increasing concentrations of PFAAs were associated with decreasing concentrations of RBCF. For the total population, for a 10% increase in the concentrations of PFOA, PFOS, PFDA, PFHxS, PFNA, and PFUnDA, percent decreases in RBCF concentrations were found to be 0.33%, 0.66%, 0.83%, 0.16%, 0.89%, and 0.43%, respectively. RBCF concentrations of PFAAs were found to be 1104, 1042, 100, and 936 nmol/L across the four quartiles of PFOS; 112, 1068, 1009, and 948 nmol/L across the four quartiles of PFDA; 1125, 1054, 1005, and 967 nmol/L across the four quartiles of PFNA; and 1099, 1094, 989, and 952 nmol/L across the four quartiles of PFUnDA. Perfluorinated carboxylic acids with carbon chain length > 8 decreased concentrations of RBCF to a greater degree than those carbon chain length ≤ 8. Perfluorinated chemicals with a sulfonic group with carbon chain length > 6 decreased concentrations of RBCF to a greater degree than those carbon chain length ≤ 6. The degree to which concentrations of RBCF decrease varied by age, gender, and race/ethnicity. Non-Hispanic blacks as compared to non-Hispanic whites and Hispanics had the lowest decreases in RBCF concentrations. Mechanisms responsible for negative associations between RBCF and PFAA concentrations are not known and will need to be researched further.

Trends in concentrations of selected dioxins and furans across various stages of kidney function for US adults.

Exposure to dioxins and furans has the potential to affect kidney function and could be associated with chronic kidney disease. Data for US adults aged ≥ 20 years from the National Health and Nutrition Examination Survey for 1999-2004 (N = 4433) were analyzed to study trends in adjusted concentrations (AGM) of 1,2,3,7,8-pentachlorodibenzo-p-dioxin, 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin, 1,2,3,4,6,7,8-heptachlororodibenzo-p-dioxin, 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin, 2,3,4,7,8-pentachlorodibenzofuran, 1,2,3,4,7,8-hexachlorodibenzofuran, 1,2,3,6,7,8-hexachlorodibenzofuran, and 1,2,3,4,6,7,8-heptachlorodibenzofuran across the stages of kidney function (KF). Stages of KF were defined based on estimated glomerular filtration rate or eGFR expressed in mL/min/1.73 m2. For KF-1, eGFR was > 90, between 60 and 90 for KF-2, between 45 and 60 for KF-3A, and between 15 and 45 for KF-3B/4. AGMs for 1,2,3,7,8-pentachlorodibenzo-p-dioxin and 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin increased consistently across the full spectrum of kidney function. For example, AGMs for the total population for 1,2,3,7,8-pentachlorodibenzo-p-dioxin were 2.5, 4.5, 9.3, and 14.9 fg/g lipid for KF-1, KF-2, KF-3A, and KF-3B/4, respectively. For other six dioxins/furans, AGMs increased over KF-1 through KF-3A but then decreased for KF-3B/4, for example, 1,2,3,4,6,7,8-heptachlorodibenzofuran for males, and AGMs for KF-1, KF-2, KF-3A, and KF-3B/4 were 7.9, 8.4, 10.7, and 7.5 fg/g lipid, respectively. For 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin and 1,2,3,6,7,8-hexachlorodibenzofuran, smokers were found to have lower AGMs than nonsmokers. For example, for 1,2,3,4,6,7,8-heptaachlorodibenzo-p-dioxin, smoker-nonsmoker AGMs were 22.2 vs. 39.4 fg/g lipid at KF-1, 29.5 vs. 51.4 fg/g lipid at KF-2, 61.6 vs. 72.8 fg/g lipid at KF-3A, and 34.9 vs. 66.4 fg/g lipid at KF-3B/4. The reverse more often than not, was, however, observed for other six dioxins/furans. Smoker-nonsmoker AGMs for 1,2,3,7,8-pentachlorodibenzo-p-dioxin were 2.4 vs. 2.6 fg/g lipid at KF-1, 5.1 vs. 4.0 fg/g lipid at KF-2, 12.7 vs. 6.7 fg/g lipid at KF-3A, and 18.6 vs. 11.9 fg/g lipid at KF-3B/4. In conclusion, lipid-adjusted serum concentrations of dioxins and furans continue increasing as kidney function keeps deteriorating until KF-3A. However, these increases in serum concentrations until KF-3A may be followed by substantial decreases for selected dioxins/furans during KF-3B/4.

Concentrations of serum hydroxycotinine for US adult smokers aged ≥ 20 years by type of smoker.

Cross-sectional survey data (N = 3264) from the National Health and Nutrition Examination Survey for 2013-2018 were used to investigate how serum hydroxycotinine concentrations vary among US adult smokers aged ≥ 20 years by smoker type. Those reporting using tobacco products during the last 5 days were classified as smokers. Smokers were classified as being cigarette only smokers, cigar only smokers, cigar and cigarette smokers, dual cigarette and e-cigarette smokers, e-cigarette only smokers, smokeless tobacco only users, and all other smokers. Regression models stratified by smoker type with log10 transformed values of serum hydroxycotinine as dependent variable were fitted to compute adjusted geometric means (AGM) for each type of smoker. The order in which various types of smokers were found to have AGMs for serum hydroxycotinine was cigarette and e-cigarette users (64.61 ng/mL), cigarette only smokers (53.17 ng/mL), smokeless tobacco only users (44.89 ng/mL), cigar and cigarette smokers (36.99 ng/mL), e-cigarette only users (32.52 ng/mL), smokers of miscellaneous tobacco products (20.32 ng/mL), and cigar smokers only (10.75 ng/mL). Compared to this as presented in a recent study, the order in which serum cotinine AGMs were: smokeless tobacco only users (272 ng/mL), cigarette only smokers (152.5 ng/mL), cigarette-e-cigarette or e-cigarette only users (146.3 ng/mL), smokers of miscellaneous tobacco products (105.5 ng/mL), cigar and cigarette smokers (92.5 ng/mL), cigar smokers only (65.1 ng/mL). Among cigarette only smokers, males had lower AGM than females (47.18 vs. 59.91 ng/mL, p < 0.01), but the reverse was true for smokeless tobacco only and miscellaneous smokers. In general, differences for hydroxycotinine levels did not exist among non-Hispanic white and non-Hispanic black smokers. Among US adults, cigarette only and dual cigarette-e-cigarette smokers had the highest, and cigar smokers had the lowest concentrations of serum hydroxycotinine.

Associations between perfluoroalkyl acids in serum and lead and mercury in whole blood among US children aged 3-11 years.

Data for 639 US children aged 3-11 years who participated in the National Health and Nutrition Examination Survey during 2013-2014 were analyzed by fitting regression models with log10-transformed values of blood lead and methyl and total mercury as dependent variables and log10-transformed values of perfluoroalkyl acids (PFAA) as one of the independent variables. PFAAs considered were 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (MPAH), linear isomer of perfluorooctanoic acid (NPFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorohexane sulfonic acid (PFHxS), linear isomer of perfluorooctane sulfonic acid (NPFOS), and monomethyl branch isomer of perfluorooctane sulfonic acid (MPFOS). Adjusted regression slopes (ß) indicating associations between the concentrations of PFAAs with blood lead and mercury were estimated. Statistically significant associations between concentrations of each PFAA and blood lead were observed. For 10% increases in concentrations of MPAH, NPFOA, PFNA, PFDA, PFHxS, NPFOS, and MPFOS, percent increases in the concentrations of blood lead were 0.45%, 1.59%, 0.78%, 0.32%, 0.65%, 1.32%, and 0.89% respectively. For 10% increases in concentrations of MPAH, PFNA, PFDA, and NPFOS, percent increases in the concentrations of total mercury in the blood were 1.62%, 1.44%, and 3.24% respectively. For 10% increases in concentrations of PFDA and NPFOS, percent increases in the concentrations of methyl mercury in the blood were 2.07% and 4.57% respectively. While concentrations of each of the seven PFAAs were positively associated with the concentrations of blood lead, concentrations of only PFDA and NPFOS were positively associated with increases in total and methyl mercury. PFAAs having positive associations with lead and mercury imply co-exposure and/or co-existence of high concentrations of PFAAs and lead/mercury. Since PFAAs as well as lead/mercury are known to be neurotoxic, nephrotoxic, and endocrine disruptors, their co-existence/co-exposure may lead to neurodevelopmental deficits that are additive/synergistic than neurodevelopmental deficits associated with exposures to PFAAs and lead/mercury alone. Future studies are needed to investigate additive/synergistic neurodevelopmental deficits associated with co-exposures to PFAAs and lead/mercury.

Associations between concentrations of selected perfluoroalkyl acids and concentrations of blood cadmium, lead, and total mercury.

Data (N = 2552) from National Health and Nutrition Examination Survey for US adults aged ≥ 20 years for 2011-2016 were analyzed to estimate the associations between the concentrations of blood cadmium, lead, and total mercury and the concentrations of seven perfluoroalkyl acids (PFAA), namely, 2-(N-Methyl-perfluorooctane sulfonamido) acetic acid (MPAH), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS). Concentrations of blood cadmium were negatively associated with the concentrations of PFHxS (ß = - 0.05428, p < 0.01) and PFOS (ß = - 0.0212, p = 0.02). Concentrations of blood lead were positively associated with the concentrations of MPAH (ß = 0.03301, p < 0.01), PFOA (ß = 0.04783, p = 0.01), PFNA (ß = 0.11761, p < 0.01), PFDA (ß = 0.08007, p < 0.01), PFUA (ß = 0.11382, p < 0.01), and PFOS (ß = 0.04996, p = 0.02). Percent increases in the concentration of blood lead were 0.32%, 0.46%, 1.13%, 0.77%, 1.09%, and 0.48% for 10% increases in the concentrations of MPAH, PFOA, PFNA, PFDA, PFUA, and PFOS, respectively. Concentrations of blood total mercury were positively associated with the concentrations of PFNA (ß = 0.37105, p < 0.01), PFDA (ß = 0.46875, p < 0.01), PFUA (ß = 0.56934, p < 0.01), and PFOS (ß = 0.17557, p < 0.01). Percent increases in the concentration of blood total mercury were 3.6%, 4.57%, 5.58%, and 1.69% for 10% increases in the concentrations of PFNA, PFDA, PFUA, and PFOS, respectively. Associations between the concentrations of PFAAs with blood total mercury were substantially stronger than the concentrations with blood lead. Higher the carbon chain length for PFAAs, stronger were the associations between PFAAs with lead and mercury.

Impact of kidney hyperfiltration on concentrations of selected perfluoroalkyl acids among US adults for various disease groups.

Data from the National Health and Nutrition Examination Survey (N = 6141) for the years 2003-2016 for US adults were analyzed to evaluate the impact of glomerular hyperfiltration on the observed concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid, perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) for several disease groups. Hyperfiltrators were defined as having an estimated glomerular filtration rate (eGFR) ≥ 110 mL/min/1.73 m2, and normal filtrators were defined as those having an eGFR between 90 and 110 mL/min/1.73 m2. The seven disease groups for which the data were analyzed were as follows: those (i) without any diseases; (ii) with hypertension only; (iii) with albuminuria only; (iv) with anemia only; (v) with diabetes only; (vi) with hypertension and one or more of diabetes, anemia, and albuminuria; and (vii) with two or more of diabetes, anemia, and albuminuria without hypertension. For almost every PFAA, for all seven disease groups except the albuminuria only group, hyperfiltrators had lower adjusted geometric means (AGM) than normal filtrators. For example, for the disease group with hypertension only, for PFOS, the AGMs for hyperfiltrators and normal filtrators were 8.3 and 10.6 ng/mL, respectively, for the total population. For the group with albuminuria only, normal filtrators were found to have higher AGMs than hyperfiltrators for the total population and males. For example, for PFHxS, the AGMs for normal and hyperfiltrators were 0.98 and 1.05 ng/mL, respectively, for the total population. For females, these AGMs for normal and hyperfiltrators were 0.96 and 0.86 ng/mL respectively. Males usually had higher AGMs than females, but the reverse was also true occasionally. Usually, male-female differences were substantially narrower for normal filtrators than hyperfiltrators. Irrespective of the filtration status, the disease group with hypertension only had the highest AGMs for every PFAA. AGMs for the anemia only group were the lowest for every PFAA as compared with other disease groups among hyperfiltrators.

Concentrations of selected monohydroxy polycyclic aromatic hydrocarbons across various stages of glomerular function.

The objective of this study was to evaluate the variabilities in the concentrations of selected monohydroxy polycyclic aromatic hydrocarbons (OH-PAH) in urine across various stages of glomerular function. Data from National Health and Nutrition Examination Survey for US adult smokers (N = 3125) and nonsmokers (N = 6793) were selected for analysis to meet the objectives of the study. OH-PAHs selected for analysis were as follows: 1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyfluorene, 3-hydroxyfluorene, 9-hydroxyfluorene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, and 1-hydroxypyrene. Stages of glomerular function (GF) considered were as follows: hyperfiltrators (GF-1A, eGFR ≥ 110 mL/min/1.73 m2), normal filtrators (GF-1B, 90 < eGFR < 110 mL/min/1.73 m2), GF-2 (60 ≤ eGFR < 90 mL/min/1.73 m2), GF-3A (45 ≤ eGFR < 60 mL/min/1.73 m2), and GF-3B/4 (15 ≤ eGFR < 45 mL/min/1.73 m2). For the analysis of data for smokers, however, data for GF-3A and GF-3B/4 were merged because of small sample sizes for these GF stages for smokers. Among nonsmokers, (i) there was almost a straight-line decrease in adjusted concentrations of 2-hydroxyfluorene, 3-hydroxyfluorene, 9-hydroxyfluorene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, and 1-hydroxypyrene over GF-1A through GF-3B/4; (ii) concentrations of these OH-PAHs at GF-3B/4 varied from being 37.5% for 1-hydroxypyrene to being 87% for 9-hydroxyfluorene of what they were at GF-1A; and (iii) while concentrations of 1-hydroxynaphthalene were located on an inverted U-shaped curve, concentrations of 2-hydroxynaphthalene were located on a U-shaped curve with pints of inflections at GF-3A. Among smokers, concentrations of all nine OH-PAHs in urine were located on inverted U-shaped curves with points of inflections located at GF-2 and concentrations of these OH-PAHs at GF-3/4 varied from being 48.7% for 1-hydroxypyrene to being 116.1% for 9-hydroxyfluorene of what they were at GF-1A. The kidneys differ in how they process urinary metabolites of PAHs among smokers and nonsmokers.

Perfluoroalkyl acids and their isomers, diabetes, anemia, and albuminuria: Variabilities with deteriorating kidney function.

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.

Comparative analysis of the concentrations of serum cotinine and hydroxycotinine for US children, adolescents, and adults: impact of exposure to environmental tobacco smoke at home and other indoor environments.

This study was carried out to investigate how serum cotinine and hydroxycotinine concentrations compare and vary by age, gender, race/ethnicity, smoking, and exposure to environmental tobacco smoke (ETS) at home and other indoor environments. Data from NHANES for 2013-2018 for US children aged 3-11 years (N = 3834), nonsmoker (N = 1963) and smoker (N = 247) adolescents aged 12-19 years, and nonsmoker (N = 10,334) and smoker (N = 3264) adults aged ≥ 20 years were analyzed by fitting regression models with log10 transformed values of serum cotinine and hydroxycotinine as dependent variables. Models stratified by age and smoking status were fitted. Those reporting using tobacco products during the last 5 days were classified as smokers. For cotinine, males had higher cotinine concentrations than females for children, adolescent smokers, and nonsmoker adults. Non-Hispanic Blacks were found to have lower concentrations of both cotinine and hydroxycotinine than non-Hispanic Whites for adult smokers (p < 0.01) only. The ratio of concentrations of those exposed to ETS at home to those not exposed to ETS at home for hydroxycotinine was 6.3 for nonsmoker adults and as low as 1.39 for adult smokers.

Associations between apolipoprotein B and selected perfluoroalkyl substances among diabetics and nondiabetics.

Previous population investigation of perfluoroalkyl substances (PFAS) features associations with lipids in a number of populations; these investigations have seldom included consideration of apolipoproteins. Apolipoprotein B (Apo B) fractions were considered in this descriptive analysis because they are essential to the assembly, transport, and cellular uptake of lipid classes associated with poorer health outcomes, and they are associated with incident and prevalent disease. Regression models stratified by diabetes and lipid lowering medication (LLM) status for data from National Health and Nutrition Examination Survey for 2007-2014 were fitted to interrogate associations between selected PFAS and Apo B for US adults aged ≥ 20 years. Adjusted concentrations of Apo B were positively associated with perfluorooctanoic acid (PFOA ß = 0.03878, p < 0.01), perfluorooctane sulfonic acid (PFOS ß = .02029, p = 0.02), and perfluorononanoic acid (PFNA ß = .01968, p = .03) for nondiabetics who were not taking lipid lowering medications. These associations were not seen among diabetic participants, except for perfluorodecanoic acid (PFDA) in those taking LLMs (ß = 0.03831, p = 0.02). We also note that LLMs have an inferred greater impact on Apo B in the diabetics compared to the nondiabetic populations. We have considered several sources of confounding and think the data are most consistent with a weak causal association that PFAS exposure increases Apo B. The rodent toxicology literature also contains evidence that PFAS disrupt fatty acid trafficking including Apo B, although how the specific findings may relate to circulating human Apo B concentrations is unclear. We therefore advocate for attempts to replicate the findings in other populations and to consider additional types of mechanistic studies.

Re-visiting serum cotinine concentrations among various types of smokers including cigarette only smokers: some new, previously unreported results.

Data (N = 11614) from National Health and Nutrition Examination Survey (NHANES) for 1999-2016 for US adults aged ≥ 20 years were analyzed by fitting regression models to estimate unadjusted and adjusted geometric means (AGM) for several different groups of smokers. Serum cotinine level ≥ 3.3 ng/mL was used to distinguish smokers from nonsmokers. AGMs for cigarette only, cigar only, dual cigarette/cigar, e-cigarette or dual e-cigarette/cigarette, and smokeless tobacco only smokers were estimated to be 152.5, 65.1, 92.5, 146.3, and 272.0 ng/mL, respectively. Males were found to have higher cotinine levels than females for dual cigarette and cigar smokers, but the reverse was observed for smokeless tobacco users. Non-Hispanic blacks had higher AGMs than non-Hispanic whites for cigarette only smokers, but the reverse was observed for dual cigarette and cigar smokers. For the first time, serum cotinine estimates for those self-reported nonsmokers who were classified to be smokers (29.4 ng/mL) and those smokers for whom self-reported data for use of tobacco products were missing were also estimated (113.8 ng/mL).