Ram Baboo Jain

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 (pp=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.

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 (β = 0.33364, P = 0.04). Concentrations of PFDA were positively associated with UAS (β = 0.20688, P = 0.01), IAS (β = 0.23712, P = 0.02), and UAB (β = 0.26049, P = 0.02). Concentrations of PFUnDA were positively associated with UAS (β = 0.49946, P < 0.01), IAS (β = 0.51782, P < 0.01), UAB (β = 0.62924, P < 0.01), and UDMA (β = 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 (β = − 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.

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.

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.

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 (β = − 0.04204, p < 0.01), perfluorononanoic acid or PFNA (β = − 0.02700, p < 0.01), perfluorohexane sulfonate or PFHxS (β = − 0.04306, p < 0.01), and perfluorooctane sulfonate or PFOS (β = − 0.04494, p < 0.01). Blood concentrations of selenium were found to be positively associated with PFHxS only among adults (β = 0.000678, p = 0.047) and adolescents (β = 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.

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.

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.

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.