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Per- and poly-fluoroalkyl substances and bone mineral density: Results from the Bayesian weighted quantile sum regression.

ABSTRACT: Per- and poly-fluoroalkyl substances (PFAS) are chemicals, detected in 95% of Americans, that induce osteotoxicity and modulate hormones, thereby influencing bone health. Previous studies found associations between individual PFAS and bone mineral density in adults but did not analyze their combined effects. Objective:To extend weighted quantile sum (WQS) regression to a Bayesian framework (Bayesian extension of the WQS regression [BWQS]) and determine the association between a mixture of serum PFAS and mineral density in lumbar spine, total, and neck femur in 499 adults from the 2013 to 2014 National Health and Nutrition Examination Survey (NHANES). Methods:We used BWQS to assess the combined association of eight PFAS, as a mixture, with bone mineral density in adults. As secondary analyses, we focused on vulnerable populations (men over 50 years and postmenopausal women). Analyses were adjusted for sociodemographic factors. Sensitivity analyses included bone mineral density associations with individual compounds and results from WQS regressions. Results:The mean age was 55 years old (SD = 1) with average spine, total, and neck femur mineral densities of 1.01 (SD = 0.01), 0.95 (SD = 0.01), and 0.78 (SD = 0.01) gm/cm2, respectively. PFAS mixture levels showed no evidence of association with mineral density (spine: ? = -0.004; 95% credible interval [CrI] = -0.04, 0.04; total femur: ? = 0.002; 95% CrI = -0.04, 0.05; femur neck: ? = 0.005; 95%CrI = -0.03, 0.04) in the overall population. Results were also null in vulnerable populations. Findings were consistent across sensitivity analyses. Conclusions:We introduced a Bayesian extension of WQS and found no evidence of the association between PFAS mixture and bone mineral density.

SUBMITTER: Colicino E

PROVIDER: S-EPMC7289141 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Per- and poly-fluoroalkyl substances and bone mineral density: Results from the Bayesian weighted quantile sum regression.

Colicino Elena E Pedretti Nicolo Foppa NF Busgang Stefanie A SA Gennings Chris C

Environmental epidemiology (Philadelphia, Pa.) 20200430 3

Per- and poly-fluoroalkyl substances (PFAS) are chemicals, detected in 95% of Americans, that induce osteotoxicity and modulate hormones, thereby influencing bone health. Previous studies found associations between individual PFAS and bone mineral density in adults but did not analyze their combined effects.<h4>Objective</h4>To extend weighted quantile sum (WQS) regression to a Bayesian framework (Bayesian extension of the WQS regression [BWQS]) and determine the association between a mixture of ...[more]

PMID: 32613152

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Project description:Human ingestion of per- and polyfluoroalkyl substances (PFAS) from contaminated food and water is linked to the development of several cancers, birth defects and other illnesses. The complete mineralisation of aqueous PFAS by ultrasound (sonolysis) into harmless inorganics has been demonstrated in many studies. However, the range and interconnected nature of reaction parameters (frequency, power, temperature etc.), and variety of reaction metrics used, limits understanding of degradation mechanisms and parametric trends. This work summarises the state-of-the-art for PFAS sonolysis, considering reaction mechanisms, kinetics, intermediates, products, rate limiting steps, reactant and product measurement techniques, and effects of co-contaminants. The meta-analysis showed that mid-high frequency (100 - 1,000 kHz) sonolysis mechanisms are similar, regardless of reaction conditions, while the low frequency (20 - 100 kHz) mechanisms are specific to oxidative species added, less well understood, and generally slower than mid-high frequency mechanisms. Arguments suggest that PFAS degradation occurs via adsorption (not absorption) at the bubble interface, followed by headgroup cleavage. Further mechanistic steps toward mineralisation remain to be proven. For the first time, complete stoichiometric reaction equations are derived for perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) sonolysis, which add H2 as a reaction product and consider CO an intermediate. Fluorinated intermediate products are derived for common, and more novel PFAS, and a naming system proposed for novel perfluoroether carboxylates. The meta-analysis also revealed the transition between pseudo first and zero order PFOA/S kinetics commonly occurs at 15 - 40 µM. Optimum values of; ultrasonic frequency (300 - 500 kHz), concentration (>15 - 40 μM), temperature (≈20 °C), and pH range (3.2 - 4) for rapid PFOX degradation are derived by evaluation of prior works, while optimum values for the dilution factor applied to PFAS containing firefighting foams and applied power require further work. Rate limiting steps are debated and F- is shown to be rate enhancing, while SO42- and CO2 by products are theorised to be rate limiting. Sonolysis was compared to other PFAS destructive technologies and shown to be the only treatment which fully mineralises PFAS, degrades different PFAS in order of decreasing hydrophobicity, is parametrically well studied, and has low-moderate energy requirements (several kWh g-1 PFAS). It is concluded that sonolysis of PFAS in environmental samples would be well incorporated within a treatment train for improved efficiency.

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Project description:Background and objectiveThe growing impact of the COVID-19 pandemic has heightened the urgency of identifying individuals most at risk of infection. Per- and poly-fluoroalkyl substances (PFASs) are manufactured fluorinated chemicals widely used in many industrial and household products. The objective of this case-control study was to assess the association between PFASs exposure and COVID-19 susceptibility and to elucidate the metabolic dysregulation associated with PFASs exposure in COVID-19 patients.MethodsTotal 160 subjects (80 COVID-19 patients and 80 symptom-free controls) were recruited from Shanxi and Shandong provinces, two regions heavily polluted by PFASs in China. Twelve common PFASs were quantified in both urine and serum. Urine metabolome profiling was performed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS).ResultsIn unadjusted models, the risk of COVID-19 infection was positively associated with urinary levels of perfluorooctanesulfonic acid (PFOS) (Odds ratio: 2.29 [95% CI: 1.52-3.22]), perfluorooctanoic acid (PFOA) (2.91, [1.95-4.83], and total PFASs (∑ (12) PFASs) (3.31, [2.05-4.65]). After controlling for age, sex, body mass index (BMI), comorbidities, and urine albumin-to-creatinine ratio (UACR), the associations remained statistically significant (Adjusted odds ratio of 1.94 [95% CI: 1.39-2.96] for PFOS, 2.73 [1.71-4.55] for PFOA, and 2.82 [1.97-3.51] for ∑ (12) PFASs). Urine metabolome-PFASs association analysis revealed that 59% of PFASs-associated urinary endogenous metabolites in COVID-19 patients were identified to be produced or largely regulated by mitochondrial function. In addition, the increase of PFASs exposure was associated with the accumulation of key metabolites in kynurenine metabolism, which are involved in immune responses (Combined β coefficient of 0.60 [95% CI: 0.25-0.95, P = 0.001]). Moreover, alternations in PFASs-associated metabolites in mitochondrial and kynurenine metabolism were also correlated with clinical lab biomarkers for mitochondrial function (serum growth/differentiation factor-15) and immune activity (lymphocyte percentage), respectively.ConclusionElevated exposure to PFASs was independently associated with an increased risk of COVID-19 infection. PFASs-associated metabolites were implicated in mitochondrial function and immune activity. Larger studies are needed to confirm our findings and further understand the underlying mechanisms of PFASs exposure in the pathogenesis of SARS-CoV2 infection.

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Dataset Information

Per- and poly-fluoroalkyl substances and bone mineral density: Results from the Bayesian weighted quantile sum regression.

Publications

Per- and poly-fluoroalkyl substances and bone mineral density: Results from the Bayesian weighted quantile sum regression.

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