Association of exposure to phenols and parabens mixtures with grip strength among adults in the United States: A cross-sectional study

Association of exposure to phenols and parabens mixtures with grip strength among adults in the United States: A cross-sectional study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Association of exposure to phenols and parabens mixtures with grip strength among adults in the United States: A cross-sectional study Yueyang Xu, Siyu Gui, Shaokun Qin, Neng Jin, Yuanyue Cheng, Shuming Ye This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4892050/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Previous research has indicated potential health hazards of phenols and parabens from environmental exposure to humans. However, studies examining their relationship with grip strength remain limited. Utilizing data from the National Health and Nutrition Examination Survey (NHANES), this study included 1,858 adults aged 20 years and older to explore the independent and combined associations of phenols and parabens with grip strength. In single exposure analyses, bisphenol A (BPA) exhibited a negative association with grip strength, while benzophenone-3 (BP3) and butyl paraben (BuP) showed positive associations. Restricted cubic splines (RCS) regression indicated a U-shaped nonlinear relationship between BPA and grip strength across all participants. Weighted quantile sum (WQS) regression models revealed a negative association between combined exposure to various metals in urine and grip strength. Quantile based g-computation (qgcomp) analysis suggested positive weights for urinary mixture of BuP, BPA, and methyl paraben (MeP), whereas 2,5-dichlorophenol (25-DCB), propyl paraben (PrP), and 2,4-dichlorophenol (24-DCB) had negative weights. Subgroup analyses indicated significant differences in results across age and gender subgroups. Given the limitations of cross-sectional studies, prospective and mechanistic investigations are warranted in future research. Phenols Parabens Grip strength Urinary metabolites Mixture NHANES Figures Figure 1 Figure 2 Figure 3 Figure 4 1. Introduction Phenols and parabens, as endocrine-disrupting chemicals, are widely present in everyday personal care and consumer products. Bisphenol A (BPA) is extensively used in the manufacture of polycarbonate plastics and epoxy resins for food container linings, dental composites, and sealants 1 . Benzophenone-3 (BP3) serves as a UV filter widely employed in sunscreen products 2 . Parabens are widely utilized in personal care products as antimicrobial preservatives and find application in pharmaceutical, food, and beverage processing 3 , 4 . Due to their non-persistence, these chemicals readily disseminate through environmental media such as food, water, air, and dust particles during production, contributing to environmental contamination. Elevated concentrations of phenols and parabens exceeding normal ranges have been detected in multiple regions, significantly heightening human exposure risks 5 – 7 . The environmental and dietary exposure to phenols and parabens has emerged as a serious global public health concern. Numerous studies have corroborated that exposure to these substances disrupts hormone secretion and increases risks of conditions including obesity, coronary heart disease, diabetes, and cancer 8 – 11 . Grip strength is a measure of the combined contraction force of intrinsic and extrinsic muscles of the hand and forearm. Individuals with greater forearm strength typically exhibit stronger overall musculature, making grip strength a general indicator for assessing muscle function status. Low grip strength has been reported as a marker for diagnosing sarcopenia 12 , and several prospective cohort studies have shown associations between grip strength and cardiovascular disease, pulmonary disease, cancer, and all-cause mortality 13 – 15 . Additionally, grip strength is closely linked to metabolic and bone health indicators such as fasting triglycerides, blood pressure, waist circumference, as well as ATP III, IDP, and bone mineral density (BMD) 16 – 18 . Importantly, research suggests that grip strength may influence associations with physical activity, diabetes, cardiovascular disease, and overall mortality risk 19 , 20 . These findings underscore the potential importance of grip strength in predicting disease risk and its underestimated significance in health assessments. The National Health and Nutrition Examination Survey (NHANES) is a cross-sectional survey covering a representative sample of the U.S. population. This study utilized data from the 2011–2012 and 2013–2014 NHANES cycles to investigate the independent and joint associations of phenols and parabens with grip strength. Generalized linear models (GLM) and restricted cubic splines (RCS) were employed to establish dose-response relationships, assessing the impact of individual chemical exposures on grip strength. Additionally, weighted quantile sum (WQS) regression models and quantile-based g computation (qgcomp) were utilized to explore the combined effects of multiple chemical exposures on grip strength. 2. Materials and methods 2.1. Study population and data sources NHANES, conducted by the Centers for Disease Control and Prevention (CDC), is a nationally representative cross-sectional survey conducted biennially. The survey aims to collect data on nutrition and physical health status of Americans, evaluating individual health and nutritional status, identifying disease prevalence, and related risk factors. This study included 16,112 participants across two consecutive NHANES cycles from 2011–2012 and 2013–2014. After excluding participants under 20 years old (n = 5205), those without grip strength data (n = 1103), and participants lacking exposure and covariate data (n = 7936), a total of 1858 participants were included in the final analysis. Detailed participant exclusion criteria are depicted in Fig. 1 . 2.2. Measurement of Grip Strength Using the Takei Digital Grip Strength Dynamometer, Model T.K.K.5401, grip strength was assessed to measure handgrip strength. During the testing procedure, participants, without physical limitations, were instructed to stand upright. Each participant squeezed the dynamometer with one hand as forcefully as possible, exhaling during the squeeze to prevent intra-thoracic pressure buildup. Subsequently, the other hand was tested in the same manner. Each hand underwent three trials with a 60-second interval between each trial. Hands were alternated between tests. Grip strength was calculated as the sum of the maximum readings from each hand, expressed in kilograms. Participants who only used one hand for testing were excluded from this variable calculation. Detailed testing protocol descriptions can be found on the NHANES website ( https://wwwn.cdc.gov/Nchs/Nhanes/2013-2014/MGX_H.htm ). Given that individuals with higher body weight often exhibit greater strength under similar conditions, grip strength was adjusted for Body Mass Index (BMI) in this study. The grip strength adjusted for BMI was calculated by dividing the combined grip strength by BMI, and it was used as the dependent variable 21 . 2.3. Measurement of urinary phenols and parabens Participants provided urine samples at mobile examination centers, which were frozen during transport to the National Center for Environmental Health, maintaining temperatures below − 20°C. We utilized online solid-phase extraction (SPE) coupled with high-performance liquid chromatography (HPLC) and tandem mass spectrometry (MS/MS) techniques to measure BPA, BP3, triclosan, and parabens in urine samples. Isotope-labeled internal standards were employed, enabling detection limits ranging from 0.1 to 2.3 nanograms per milliliter (ng/mL) in 100 µL urine samples, sufficient for measuring phenols in non-occupational exposure scenarios. Chemicals included in this study were those with the detection rates > 85%, namely BP3, BPA, 2,4-dichlorophenol (24-DCB), 2,5-dichlorophenol (25-DCB), butyl paraben (BuP), methyl paraben (MeP), and propyl paraben (PrP). For measurements below the limit of detection (LOD) of phenols and parabens, values were imputed using the LOD divided by the square root of 2. Detailed protocols and methods are available in reports accessible via the NHANES Laboratory Protocol webpage 22 . 2.4. Covariates In NHANES, participant demographic characteristics, lifestyle factors, and underlying health conditions are obtained through interviews or standardized questionnaires. Demographic variables include age (categorized as 20–59 years and 60 years and older), sex (male and female), race/ethnicity (Mexican American, non-Hispanic White, non-Hispanic Black, and other), education level (less than or greater than high school diploma), marital status (married or living with partner, unmarried or other), and economic status (based on Poverty Income Ratio (PIR) categorized as below poverty < 1.00 or at or above poverty ≥ 1.00). Lifestyle habits encompass smoking status (never, former, current), and alcohol consumption categorized as current heavy drinking (≥ 3 drinks per day for women or ≥ 4 drinks per day for men, or binge drinking ≥ 5 days per month), current moderate drinking (≥ 2 drinks per day for women or ≥ 3 drinks per day for men, or binge drinking ≥ 2 days per month), current light drinking (not meeting above criteria), former drinking, and never drinking. Detailed dietary intake information, including calorie, is collected through dietary interviews. Physical activity is assessed using total MET (Metabolic Equivalent) levels, calculated as the sum of frequencies, durations, and intensities of various physical activities. Underlying health conditions include diabetes and hypertension. Diabetes is defined based on diabetes history, fasting blood glucose ≥ 7.0 mmol/L (≥ 126 mg/dL), or glycated hemoglobin A1c > 6.5%. Hypertension is defined as average systolic blood pressure ≥ 140 mmHg, average diastolic blood pressure ≥ 90 mmHg, or self-reported diagnosis by a doctor. Additionally, urine creatinine is included as an independent variable to assess urine sample dilution and its relationship with grip strength. 2.5. Statistical analysis In describing participant characteristics, continuous variables were summarized using mean and standard deviation (SD), while categorical variables were described using frequencies and percentages. Phenols and parabens in urine were natural Ln-transformed and categorized into tertiles (Q1, Q2, Q3). Stratified analyses were conducted based on demographic characteristics, lifestyle habits, and underlying health conditions. Three statistical models were employed to assess the associations between phenols, parabens, and grip strength. Firstly, generalized linear models (GLM) were used to investigate the individual effects of phenols and parabens on grip strength. The first tertile (Q1) was set as the reference group, and effects were estimated using grip strength adjusted for BMI change with corresponding 95% confidence intervals (CI). Models were adjusted for all covariates including age, sex, race/ethnicity, economic status, marital status, education level, smoking, alcohol consumption, physical activity, calorie intake, diabetes, and hypertension. Secondly, restricted cubic spline (RCS) regression was employed to explore both linear and nonlinear relationships and dose-response effects of phenols and parabens on grip strength. The optimal number of knots, selected based on the Akaike Information Criterion, ranged from 3 to 7 23 . Finally, weighted quantile sum (WQS) regression analysis and quantile-based g computation (qgcomp) models were utilized to assess the overall impact of mixed phenols and parabens on grip strength. In WQS analysis, data were randomly split into training and validation sets at a 4:6 ratio, and compound weights were derived from 1000 bootstrap iterations in the training set to test the significance of the mixture in the validation set. WQS indices indicated the influence of adding a quantile to the outcome within the mixture. The qgcomp model corrected for directional homogeneity between assumed environmental exposures and outcomes by partitioning each urinary metabolite into quantiles and assigning positive and negative weighted indices. Overall analyses in the study population were conducted using generalized linear models, adjusting for various covariates to perform sensitivity analyses. Model A adjusted for urine creatinine only, Model B additionally adjusted for age, sex, and race/ethnicity, and Model C included all available covariates. Data analysis was performed using R software version 4.2.1, with restricted cubic spline analysis conducted using the "rms" package, WQS regression analysis using the "gWQS" package, and qgcomp analysis using the "qgcomp" package. 3. Results 3.1 Population characteristics and Distribution of urinary phenols and parabens concentration Table 1 presents detailed demographic characteristics of the participants. The study included a total of 1858 adults aged 20 years and older across two cycles, comprising 977 males (52.6%) and 881 females (47.4%). Young and middle-aged participants aged 20–59 years accounted for 1348 individuals (72.8%). Overall, 44.6% of participants were non-Hispanic White, 83.3% had completed high school education or higher, and 79.7% reported household incomes at or above the poverty line. The mean grip strength adjusted for BMI was 2.68 ± 0.92 m², and the average concentrations of BP3, BPA, BuP, MeP, PrP, 24-DCB, and 25-DCB in urine were 313 ± 1,505.01 ng/ml, 3.12 ± 19.03 ng/ml, 1.89 ± 10.29 ng/ml, 211.30 ± 475.69 ng/ml, 53.33 ± 136.82 ng/ml, 93.39 ± 790.94 ng/ml, and 3.13 ± 19.64 ng/ml, respectively. Table 1 Baseline characteristics of participants in the NHANES 2011–2014 cycles. Categorical variables were presented as N (%), continuous variables were presented as mean ± standard. Characteristics Study Participants N 1858 Age, n(%) 20–59 1348 (72.6) ≥ 60 510 (27.4) Sex, n(%) Male 977 (52.6) Female 881 (47.4) Race/ethnicity, n(%) Mexican American 186 (10.0) Non-Hispanic Black 422 (22.7) Non-Hispanic White 829 (44.6) Other 421 (22.7) Marital status, n(%) Married or living with a partner 1084 (58.3) Unmarried or other 774 (41.7) Educational level, n(%) High School or above 1548 (83.3) Less than High school 310 (16.7) Smoke status, n(%) Current 354 (19.1) Former 421 (22.7) Never 1083 (58.3) Past-year alcohol drinking, n(%) Heavy 369 (19.9) Moderate 329 (17.7) Mild 656 (35.3) Former 278 (15.0) Never 226 (12.2) Diabetes mellitus, n(%) Yes 307 (16.5) No 1551 (83.5) Hypertension, n(%) Yes 710 (38.2) No 1148 (61.8) Poverty ratio, n(%) At or above poverty line (≥ 1.00) 1481 (79.7) Below poverty line (< 1.00) 377 (20.3) Physical activity, MET 4, 458.25 ± 6, 269.32 Calorie, kcal/d 2, 221.03 ± 1, 051.55 Urine creatinine, mg/min 123.79 ± 82.49 BP3, ng/mL 313.17 ± 1, 505.01 BPA, ng/mL 3.12 ± 19.03 BuP, ng/mL 1.89 ± 10.29 MeP, ng/mL 211.30 ± 475.69 PrP, ng/mL 53.33 ± 136.82 24-DCB, ng/mL 93.39 ± 790.94 25-DCB, ng/mL 3.13 ± 19.64 Grip strength/BMI, m 2 2.68 ± 0.92 3.2 Associations between single phenols and parabens exposure and grip strength Using generalized linear models adjusted for all covariates, we evaluated the associations between individual phenols and parabens with grip strength. Table 2 presents the relationships between phenols and parabens and grip strength after Ln-transformed and categorization into tertiles (Q1, Q2, Q3). Compared to Q1, higher tertiles (Q3) of BP3 and BuP in urine significantly increased grip strength (BP3: β = 0.09, 95% CI: 0.01, 0.16; BuP: β = 0.09, 95% CI: 0.01, 0.17). Conversely, middle (Q2) and higher tertiles (Q3) of BPA in urine were significantly negatively associated with grip strength (Q2: β = -0.13, 95% CI: -0.21, -0.06; Q3: β = -0.12, 95% CI: -0.21, -0.04). Each increment in Ln-BPA was associated with a grip strength decrease of 0.05 (95% CI: -0.08, -0.02). However, the association between Ln-BP3 and grip strength did not show statistically significant differences. Table 2 Associations of single phenols and parabens with grip strength in the NHANES 2011–2014 cycles. Models were adjusted for age, sex, race/ethnicity, Marital status, Educational level, Smoke status, Past-year alcohol drinking, Diabetes mellitus, Hypertension, Poverty ratio, Physical activity, Calorie, Urine creatinine. Continuous: Ln-transformed concentration of phenols and parabens; CI: confidence interval; β: β coefficient; Q: quartile; Ref: reference. *: P < 0.05. Exposure Q1 Q2 Q3 Continuous β(95% CI) P value β(95% CI) P value β(95% CI) P value BP3 Ref 0.05(-0.03, 0.12) 0.22 0.09( 0.01, 0.16) 0.03* 0.01(-0.01, 0.02) 0.210 BPA Ref -0.13(-0.21,-0.06) < 0.001* -0.12(-0.21,-0.04) 0.004* -0.05(-0.08,-0.02) 0.003* BuP Ref 0.06(-0.01, 0.13) 0.08 0.09( 0.01, 0.17) 0.03* 0.02( 0.00, 0.04) 0.040 MeP Ref 0(-0.09, 0.08) 0.93 0.08(-0.02, 0.19) 0.13 0.01(-0.02, 0.04) 0.530 PrP Ref 0.02(-0.06, 0.11) 0.60 -0.06(-0.17, 0.05) 0.31 0(-0.03, 0.02) 0.690 24-DCB Ref -0.02(-0.09, 0.06) 0.63 0(-0.09, 0.09) 0.93 0.01(-0.02, 0.03) 0.660 25-DCB Ref -0.05(-0.13, 0.03) 0.24 -0.05(-0.14, 0.04) 0.30 -0.03(-0.06, 0.01) 0.120 3.3 Dose-response relationship between phenols and parabens and grip strength After adjusting for all covariates, we further explored dose-response relationships between Ln-transformed individual phenols and parabens and grip strength using restricted cubic spline (RCS) analysis (Fig. 2 ). We observed a non-linear "U" shaped relationship between Ln-BPA and grip strength (non-linear P = 0.017), indicating that grip strength decreases with increasing concentrations of BPA at lower levels. Additionally, Ln-BP3 and Ln-MeP exhibited an "S" shaped dose-response curve with grip strength, while Ln-BuP and Ln-PrP showed an inverted "U" shaped curve, and Ln-24-DCB and Ln-25-DCB displayed a "U" shaped curve with grip strength. 3.4 Associations between mixture phenols and parabens exposure and grip strength This study employed WQS and qgcomp multi-pollutant models to investigate the relationship between phenols and parabens mixtures and grip strength. After adjusting for all covariates, each increment in a mixture quartile (WQS index) of phenols and parabens was associated with a decrease in BMI-adjusted grip strength by 0.058 (95% CI: 0.035, 0.081). Figure 3 depicts the regression weights of WQS indices for each phenol and paraben compound on the overall effect. BPA had the highest WQS weight, while BP3 and BuP contributed minimally. Additionally, qgcomp analysis revealed positive weights for BuP, BPA, and MeP (weights: 0.455, 0.281, 0.264, respectively), whereas BPA, 25-DCB, PrP, and 24-DCB showed negative weights, with BPA having the largest negative weight of 0.545. 3.5 subgroup analysis This study conducted subgroup analyses based on age, sex, race, poverty status, diabetes, hypertension, smoking, and alcohol consumption, as depicted in Figs. 4 and Tables S1-S6. Among young and middle-aged adults, BPA exhibited significant negative associations with grip strength at the second quartile (β = -0.14, 95% CI: -0.24, -0.05) and third quartile (β = -0.15, 95% CI: -0.25, -0.04), which persisted even after logarithmic transformation. Conversely, BuP showed significant positive associations with grip strength only at the third quartile (β = 0.12, 95% CI: 0.02, 0.22).Among older adults, Ln-transformed 25-DCB concentrations were associated with grip strength (P = 0.03), and BPA showed associations only at the second quartile (P = 0.04).In females, Ln-transformed BPA exhibited significant negative associations with grip strength (β = -0.06, 95% CI: -0.10, -0.02), particularly at the second quartile (β = -0.20, 95% CI: -0.29, -0.12) and third quartile (β = -0.17, 95% CI: -0.27, -0.07), compared to the first quartile. However, there were no statistically significant associations between chemical substances and grip strength in males. Stratified analyses by race revealed a significant negative association between BPA at the second quartile and grip strength among non-Hispanic White individuals (β = -0.15, 95% CI: -0.25, -0.04), and a significant positive association between BuP and grip strength among Mexican American individuals (β = 0.32, 95% CI: 0.10, 0.53). In the population above the poverty line, BPA showed a significant negative association with grip strength, whereas among low-income groups, significant negative associations were observed only at the second quartile of BPA (β = -0.22, 95% CI: -0.41, -0.04). Stratified analyses by underlying diseases indicated that the association between 25-DCB and grip strength was influenced by diabetes, showing a significant association among diabetic individuals (β = -0.10, 95% CI: -0.19, -0.01). In individuals with hypertension, the second quartile of BPA showed a negative association with grip strength (β = -0.12, 95% CI: -0.23, -0.01). No significant associations between phenols and parabens and grip strength were found among current and former smokers. Notably, among heavy drinkers, BP3 and MeP exhibited significant positive associations with grip strength (BP3: β = 0.06, 95% CI: 0.02, 0.10; MeP: β = 0.09, 95% CI: 0.02, 0.16), while PrP showed a significant negative association (PrP: β = -0.07, 95% CI: -0.12, -0.01). 3.6 Sensitivity analysis Table S7 presents the results of the sensitivity analysis. Comparisons among Model C GLM, which adjusted for all covariates; Model A, the crude model adjusting only for urine creatinine; and Model B, which adjusted for age, sex, race/ethnicity, marital status, educational level, poverty ratio, and urine creatinine, revealed statistically significant associations between phenols, parabens, and grip strength in all three models. 4. Discussion This study utilized data from two cycles of the 2011–2014 NHANES surveys, recruiting a total of 1858 participants, aimed at exploring the association between grip strength in U.S. adults aged 20 years and older and concentrations of phenols and parabens in urine. Using generalized linear models, we found a significant relationship between BPA and decreased grip strength, while BP3 and BuP were closely associated with increased grip strength. In contrast, MeP, PrP, 24-DCB, and 25-DCB showed no statistically significant impact on grip strength. Further exploration with dose-response curves revealed varying degrees of compound-specific dose dependency on grip strength. Utilizing mixed-effects models such as WQS and qgcomp, we identified significant statistical differences between phenols and parabens mixtures and decreased grip strength, with BPA contributing most significantly; in the qgcomp model, BuP, BPA, and MeP exhibited positive weights, whereas BPA, 25-DCB, PrP, and 24-DCB showed negative weights, with BPA having the most pronounced negative weight. Additionally, comprehensive subgroup analyses were conducted based on age, gender, race/ethnicity, poverty status, diabetes, hypertension, smoking, and alcohol consumption habits. Subgroup analysis results highlighted significant differences across demographic indicators, underlying diseases, and lifestyle habits, with demographic factors such as age and gender exerting the most notable influence on the association between phenols and parabens and grip strength, followed by underlying diseases, while the impact of lifestyle habits such as smoking and alcohol consumption was comparatively minor. BPA is a widely used endocrine-disrupting chemical employed primarily in the production of polycarbonate plastics, epoxy resins lining metal cans, and various plastic consumer goods. Findings from the Hartford County cohort 16 indicate that impaired grip strength is associated with features of metabolic syndrome such as elevated fasting triglycerides, blood pressure, and waist circumference, as well as insulin resistance. Moreover, research by Oliana Carnevali et al. 24 suggests that fish fed with BPA-contaminated feed exhibit decreased unsaturated fatty acids and increased triglycerides and saturated fatty acid chains, with alterations in protein content, affecting the composition and texture of skeletal muscle. Experimental studies by Kristina et al. 25 using rodent models suggest that maternal exposure to BPA may induce insulin resistance in offspring rats, thereby impacting skeletal muscle function. Additionally, it is noteworthy that we observed a positive correlation between elevated levels of BP3 and BuP with grip strength. Luo et al. 26 analyzing 2013–2014 NHANES data, demonstrated that grip strength correlates with BMD in non-adjacent skeletal regions, highlighting hand grip strength as an indicator for assessing BMD across different genders and menopausal statuses. Concurrently, a study 27 indicated an association between hand grip strength and hand BMD in healthy individuals aged 19–50 years. Wang et al. 17 based on NHANES data, reported an association between BP3 and paraben compounds with increased BMD, supported by further validation from Gu et al. 18 . Thus, we hypothesize that the positive correlation between BP3 and BuP with grip strength may be related to BMD. Despite limited current research on the impact of BP3 and BuP on grip strength, their specific mechanisms remain unclear and warrant further investigation. Our study provides preliminary evidence of the association between BP3, BuP, and grip strength. The impairment of grip strength is associated with characteristics of metabolic syndrome and insulin resistance. BPA a common endocrine disruptor, has garnered particular attention for its involvement in insulin resistance, obesity, and type 2 diabetes (T2D) development. A previous study demonstrated 28 that exposure to BPA exacerbates insulin resistance during pregnancy, with reduced insulin-stimulated Akt phosphorylation observed in skeletal muscle and liver tissues of pregnant mice treated with bisphenol A. Concurrently, another study 29 indicated that BPA exposure may exacerbate existing metabolic stress, leading to increased cellular senescence. Currently, the mechanisms through which phenols and parabens impact grip strength remain unclear, lacking direct evidence and necessitating further research for validation. The association between environmental pollutants and grip strength has garnered increasing attention. Multiple studies have indicated a negative correlation between exposure to metal mixtures such as cadmium, copper, lead, strontium, and arsenic, and grip strength, while zinc shows a positive correlation 21 , 30 – 32 . Sun et al. found that phthalate exposure among American adults was inversely related to grip strength 33 . Additionally, glyphosate, a widely used herbicide globally, has been linked unfavorably with all grip strength measurements 34 . Both indoor and outdoor air pollution have also been reported to lower grip strength in adults 35 . Grip strength exhibits diverse associations with environmental pollutants. Phenols and parabens, prevalent pollutants in personal care and consumer products, are widely distributed in the environment. Therefore, it is imperative to conduct in-depth research into their relationship with grip strength. A study on serum testosterone levels and urinary concentrations of BPA, BP-3, triclosan, and parabens has demonstrated differential results influenced by age and sex 36 . Among adolescents, BPA shows a negative correlation with testosterone levels in boys but a positive correlation in girls, whereas BP-3 is significantly associated with decreased testosterone levels only in adolescent boys. Multiple studies 17 , 18 , 37 , 38 on phenols and parabens have also indicated gender-specific associations. In this study, significant variations in the relationship between phenols and parabens with grip strength were observed across gender and age groups. Our study has several strengths. Firstly, we utilized nationally representative NHANES data collected through standardized protocols and multiple measurement methods, ensuring high-quality data control. Additionally, we conducted subgroup analyses based on age, sex, economic status, race, underlying diseases, and lifestyle habits. Furthermore, we employed the qgcomp model to address the limitation of the WQS model, which assumes a single direction of effect. However, our study also has several limitations. Firstly, it is cross-sectional in design, thus precluding causal inference regarding the impact of mixed chemical exposures on cognitive function. Secondly, despite accounting for various covariates, residual and unmeasured confounding factors may still influence observational studies. Lastly, the rapid metabolism of phenols and parabens results in fluctuations in metabolite concentrations in urine over time. 5. Conclusion Our study identifies phenols and parabens as potential risk factors contributing to decreased grip strength. Further analysis reveals that BPA plays a crucial role in this association, with dose-response curves indicating a nonlinear relationship with grip strength. Given the limitations of our cross-sectional study design, future prospective cohort studies and mechanistic investigations are needed to validate and explore the relationship between phenols and parabens with grip strength. Declarations Data availability Publicly available datasets were analyzed in this study. This data can be found here: https://www.cdc.gov/nchs/nhanes/index.htm Author contributions Y.Y.X.: Conceptualization, methodology, data analysis, draft writing; S.Y.G.: Data analysis, interpretation of data, draft writing, revision; S.K.Q.: Data curation, visualization; N.J. and Y.Y.C.: Visualization, S.M.Y.: Funding acquisition, supervision. All authors reviewed the manuscript. Competing interests The authors declare no competing interests. References Ma, Y. et al. The adverse health effects of bisphenol A and related toxicity mechanisms. Environ Res 176 , 108575 (2019). Kim, S. & Choi, K. Occurrences, toxicities, and ecological risks of benzophenone-3, a common component of organic sunscreen products: a mini-review. Environ Int 70 , 143-157 (2014). Bolujoko, N. B. et al. Toxicity and removal of parabens from water: A critical review. Sci Total Environ 792 , 148092 (2021). van der Schyff, V., Suchankova, L., Kademoglou, K., Melymuk, L. & Klanova, J. Parabens and antimicrobial compounds in conventional and "green" personal care products. Chemosphere 297 , 134019 (2022). Rios-Fuster, B. et al. Assessing microplastic ingestion and occurrence of bisphenols and phthalates in bivalves, fish and holothurians from a Mediterranean marine protected area. Environ Res 214 , 114034 (2022). Errico, S. et al. Analysis and occurrence of some phenol endocrine disruptors in two marine sites of the northern coast of Sicily (Italy). Mar Pollut Bull 120 , 68-74 (2017). Arfaeinia, H. et al. Monitoring and eco-toxicity effect of paraben-based pollutants in sediments/seawater, north of the Persian Gulf. Environ Geochem Health 44 , 4499-4521 (2022). Shankar, A., Teppala, S. & Sabanayagam, C. Bisphenol A and peripheral arterial disease: results from the NHANES. Environ Health Perspect 120 , 1297-1300 (2012). Ward, J. B., Casagrande, S. S. & Cowie, C. C. Urinary phenols and parabens and diabetes among US adults, NHANES 2005-2014. Nutr Metab Cardiovasc Dis 30 , 768-776 (2020). Alwadi, D., Felty, Q., Roy, D., Yoo, C. & Deoraj, A. Environmental Phenol and Paraben Exposure Risks and Their Potential Influence on the Gene Expression Involved in the Prognosis of Prostate Cancer. Int J Mol Sci 23 (2022). Stevens, D. R. et al. Midpregnancy Phthalate and Phenol Biomarkers in Relation to Infant Body Composition: The Healthy Start Prospective Cohort. Environ Health Perspect 131 , 87017 (2023). Studenski, S. A. et al. The FNIH sarcopenia project: rationale, study description, conference recommendations, and final estimates. J Gerontol A Biol Sci Med Sci 69 , 547-558 (2014). Celis-Morales, C. A. et al. Associations of grip strength with cardiovascular, respiratory, and cancer outcomes and all cause mortality: prospective cohort study of half a million UK Biobank participants. BMJ 361 , k1651 (2018). Liu, W. et al. The association of grip strength with cardiovascular diseases and all-cause mortality in people with hypertension: Findings from the Prospective Urban Rural Epidemiology China Study. J Sport Health Sci 10 , 629-636 (2021). Dai, K. Z., Laber, E. B., Chen, H., Mentz, R. J. & Malhotra, C. Hand Grip Strength Predicts Mortality and Quality of Life in Heart Failure: Insights From the Singapore Cohort of Patients With Advanced Heart Failure. J Card Fail 29 , 911-918 (2023). Sayer, A. A. et al. Grip strength and the metabolic syndrome: findings from the Hertfordshire Cohort Study. QJM 100 , 707-713 (2007). Wang, N. et al. Association of bone mineral density with nine urinary personal care and consumer product chemicals and metabolites: A national-representative, population-based study. Environ Int 142 , 105865 (2020). Gu, L. et al. Associations between mixed urinary phenols and parabens metabolites and bone mineral density: Four statistical models. Chemosphere 311 , 137065 (2023). Celis-Morales, C. A. et al. The association between physical activity and risk of mortality is modulated by grip strength and cardiorespiratory fitness: evidence from 498 135 UK-Biobank participants. Eur Heart J 38 , 116-122 (2017). Celis-Morales, C. A. et al. Associations Between Diabetes and Both Cardiovascular Disease and All-Cause Mortality Are Modified by Grip Strength: Evidence From UK Biobank, a Prospective Population-Based Cohort Study. Diabetes Care 40 , 1710-1718 (2017). Chen, K., Zhou, J., Liu, N. & Meng, X. Association of Serum Concentrations of Copper, Selenium, and Zinc with Grip Strength Based on NHANES 2013-2014. Biol Trace Elem Res 202 , 824-834 (2024). Zhou, X., Ye, X. & Calafat, A. M. Automated on-line column-switching HPLC-MS/MS method for the quantification of triclocarban and its oxidative metabolites in human urine and serum. J Chromatogr B Analyt Technol Biomed Life Sci 881-882 , 27-33 (2012). Zhu, H., Xu, Y., Lin, D., Wang, X. & Niu, B. Relationship between social jetlag and body mass index in nurses working shift schedules: a cross-sectional study. Sci Rep 14 , 16911 (2024). Carnevali, O. et al. Diets contaminated with Bisphenol A and Di-isononyl phtalate modify skeletal muscle composition: A new target for environmental pollutant action. Sci Total Environ 658 , 250-259 (2019). Galyon, K. D. et al. Maternal bisphenol A exposure alters rat offspring hepatic and skeletal muscle insulin signaling protein abundance. Am J Obstet Gynecol 216 , 290 e291-290 e299 (2017). Luo, Y., Jiang, K. & He, M. Association between grip strength and bone mineral density in general US population of NHANES 2013-2014. Arch Osteoporos 15 , 47 (2020). Kaya, A., Ozgocmen, S., Ardicoglu, O., Kamanli, A. & Gudul, H. Relationship between grip strength and hand bone mineral density in healthy adults. Arch Med Res 36 , 603-606 (2005). Alonso-Magdalena, P. et al. Bisphenol A exposure during pregnancy disrupts glucose homeostasis in mothers and adult male offspring. Environ Health Perspect 118 , 1243-1250 (2010). Soundararajan, A. et al. Bisphenol A exposure under metabolic stress induces accelerated cellular senescence in vivo in a p53 independent manner. Sci Total Environ 689 , 1201-1211 (2019). Garcia-Esquinas, E., Carrasco-Rios, M., Navas-Acien, A., Ortola, R. & Rodriguez-Artalejo, F. Cadmium exposure is associated with reduced grip strength in US adults. Environ Res 180 , 108819 (2020). Liang, Y. J. et al. Correlation between Combined Urinary Metal Exposure and Grip Strength under Three Statistical Models: A Cross-sectional Study in Rural Guangxi. Biomed Environ Sci 37 , 3-18 (2024). Liang, Y. et al. Moderate selenium mitigates hand grip strength impairment associated with elevated blood cadmium and lead levels in middle-aged and elderly individuals: insights from NHANES 2011-2014. Front Pharmacol 14 , 1324583 (2023). Sun, L. et al. Exposure to phthalates is associated with grip strength in US adults. Ecotoxicol Environ Saf 209 , 111787 (2021). Fang, Y. W., Wang, C. & Lin, C. Y. Association between urinary glyphosate levels and hand grip strength in a representative sample of US adults: NHANES 2013-2014. Front Public Health 12 , 1352570 (2024). Lin, H. et al. Association of Indoor and Outdoor Air Pollution With Hand-Grip Strength Among Adults in Six Low- and Middle-Income Countries. J Gerontol A Biol Sci Med Sci 75 , 340-347 (2020). Scinicariello, F. & Buser, M. C. Serum Testosterone Concentrations and Urinary Bisphenol A, Benzophenone-3, Triclosan, and Paraben Levels in Male and Female Children and Adolescents: NHANES 2011-2012. Environ Health Perspect 124 , 1898-1904 (2016). Li, Y. et al. Associations of urinary levels of phenols and parabens with osteoarthritis among US adults in NHANES 2005-2014. Ecotoxicol Environ Saf 192 , 110293 (2020). Hu, P. et al. Associations between exposure to a mixture of phenols, parabens, and phthalates and sex steroid hormones in children 6-19 years from NHANES, 2013-2016. Sci Total Environ 822 , 153548 (2022). Additional Declarations No competing interests reported. Supplementary Files Supportingimformation.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4892050","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":344945113,"identity":"4923ba8d-249c-4421-a16e-4e878361ad97","order_by":0,"name":"Yueyang Xu","email":"","orcid":"","institution":"Department of Clinical Medicine, The First School of Clinical Medicine, Anhui Medical University, 81 Meishan Road,Hefei, 230032","correspondingAuthor":false,"prefix":"","firstName":"Yueyang","middleName":"","lastName":"Xu","suffix":""},{"id":344945114,"identity":"a72aba92-462b-41a5-be11-71905860e54d","order_by":1,"name":"Siyu Gui","email":"","orcid":"","institution":"Department of Ophthalmology, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, 230601","correspondingAuthor":false,"prefix":"","firstName":"Siyu","middleName":"","lastName":"Gui","suffix":""},{"id":344945118,"identity":"605b3672-2048-4424-87af-059ff471752e","order_by":2,"name":"Shaokun Qin","email":"","orcid":"","institution":"Department of Clinical Medicine, The First School of Clinical Medicine, Anhui Medical University, 81 Meishan Road,Hefei, 230032","correspondingAuthor":false,"prefix":"","firstName":"Shaokun","middleName":"","lastName":"Qin","suffix":""},{"id":344945120,"identity":"a161380a-a2f2-4d67-9610-0ece85037ffe","order_by":3,"name":"Neng Jin","email":"","orcid":"","institution":"Department of Orthopaedics, Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601","correspondingAuthor":false,"prefix":"","firstName":"Neng","middleName":"","lastName":"Jin","suffix":""},{"id":344945122,"identity":"4dba4e98-e3a6-4312-ac11-d989f1ac4fbd","order_by":4,"name":"Yuanyue Cheng","email":"","orcid":"","institution":"Department of Clinical Medicine, The First School of Clinical Medicine, Anhui Medical University, 81 Meishan Road,Hefei, 230032","correspondingAuthor":false,"prefix":"","firstName":"Yuanyue","middleName":"","lastName":"Cheng","suffix":""},{"id":344945124,"identity":"d94f2661-3cc5-4bdd-bd67-83b31d3840a4","order_by":5,"name":"Shuming Ye","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5ElEQVRIiWNgGAWjYHACNiCWALMkGCok5ORJ1HLGwtiwgTgtECDB2FaRyHCAgHqD4+3PHvPmWOTJ+58xvPFznkQCYwPzw0c38Gk5c8bcmHebRLHhjRxjy95tEnnsDGzGxjn4tNzIYZMGakncOIPHTAKkl7GBh00ar5b7z59BtPSfMZP8O0ciseEAIS03GMzAWuYz5AAZDURokTyTYyY5F6hlg0RasbXMMQljw2YCfuE7fvyZxNttdYnz+w9vvPmmpk5Onr354WN8WhQOwFwIYzAw41EOAvIN6IxRMApGwSgYBegAAFrgSeuCrnLSAAAAAElFTkSuQmCC","orcid":"","institution":"Department of Orthopaedics, Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601","correspondingAuthor":true,"prefix":"","firstName":"Shuming","middleName":"","lastName":"Ye","suffix":""}],"badges":[],"createdAt":"2024-08-10 14:02:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4892050/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4892050/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":66632758,"identity":"023ea3ab-c7a3-4126-8ba3-e65d3e7dbeb0","added_by":"auto","created_at":"2024-10-15 05:01:06","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":120436,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of study participants selection.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-4892050/v1/28048301936ea5617d0734b8.png"},{"id":66632761,"identity":"6a36ef22-cad0-4f4d-87c1-7b0cffca89ae","added_by":"auto","created_at":"2024-10-15 05:01:08","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":137763,"visible":true,"origin":"","legend":"\u003cp\u003eRestricted cubic splines were used for the relationship between phenols and parabens exposure concentration and change in grip strength/BMI in adults. (A) Ln-BP3; (B) Ln-BPA; (C) Ln-BuP; (D)Ln-MeP; (E)Ln-PrP; (F)Ln-24-DCB; (G)Ln-25-DCB. Models were adjusted for age, sex, race/ethnicity, Marital status, Educational level, Smoke status, Past-year alcohol drinking, Diabetes mellitus, Hypertension, Poverty ratio, Physical activity, Calorie, Urine creatinine. Solid line: β \u003ca href=\"https://baike.baidu.com/item/coefficient/9517815?fromModule=lemma_inlink\" target=\"https://baike.baidu.com/item/%CE%B2%E7%B3%BB%E6%95%B0/_blank\"\u003ecoefficient\u003c/a\u003e; red-shade: 95 % CI.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-4892050/v1/aff8e312fbeb2f8748d09fd1.png"},{"id":66632757,"identity":"1a8ca7a7-3cac-4faf-82b5-3d9ec6c902b4","added_by":"auto","created_at":"2024-10-15 05:01:06","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":121663,"visible":true,"origin":"","legend":"\u003cp\u003eWeights for each phenols and parabens mixture contribute to the overall effect by (A) WQS and (B) qgcomp analyses. Models were adjusted for age, sex, race/ethnicity, Marital status, Educational level, Smoke status, Past-year alcohol drinking, Diabetes mellitus, Hypertension, Poverty ratio, Physical activity, Calorie, Urine creatinine.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-4892050/v1/3770360e270f7993de00c492.png"},{"id":66632762,"identity":"cb1fd322-c057-4e07-bd3d-85502d2413bc","added_by":"auto","created_at":"2024-10-15 05:01:08","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":354655,"visible":true,"origin":"","legend":"\u003cp\u003eThe association between phenols and parabens and grip strength Stratified by Age and Sex group. (A) Age(20-59); (B) Age(≥60); (C) Male; (D) Female. Models were adjusted for race/ethnicity, Marital status, Educational level, Smoke status, Past-year alcohol drinking, Diabetes mellitus, Hypertension, Poverty ratio, Physical activity, Calorie, Urine creatinine. *: P\u0026lt;0.05.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-4892050/v1/19948100f3f6131154cfd770.png"},{"id":89015718,"identity":"082233eb-26af-4de2-a909-b2d45edc7a8e","added_by":"auto","created_at":"2025-08-13 18:31:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1706618,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4892050/v1/dabb4d0e-c4e7-4d48-b5bd-ef7dfb9ddd5d.pdf"},{"id":66632759,"identity":"3d7f04f7-812c-40b3-bbf4-6faa7ec47f2a","added_by":"auto","created_at":"2024-10-15 05:01:07","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":65466,"visible":true,"origin":"","legend":"","description":"","filename":"Supportingimformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-4892050/v1/3a0b39518e847de88fd4acf2.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association of exposure to phenols and parabens mixtures with grip strength among adults in the United States: A cross-sectional study","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003ePhenols and parabens, as endocrine-disrupting chemicals, are widely present in everyday personal care and consumer products. Bisphenol A (BPA) is extensively used in the manufacture of polycarbonate plastics and epoxy resins for food container linings, dental composites, and sealants\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Benzophenone-3 (BP3) serves as a UV filter widely employed in sunscreen products\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Parabens are widely utilized in personal care products as antimicrobial preservatives and find application in pharmaceutical, food, and beverage processing\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Due to their non-persistence, these chemicals readily disseminate through environmental media such as food, water, air, and dust particles during production, contributing to environmental contamination. Elevated concentrations of phenols and parabens exceeding normal ranges have been detected in multiple regions, significantly heightening human exposure risks\u003csup\u003e\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. The environmental and dietary exposure to phenols and parabens has emerged as a serious global public health concern. Numerous studies have corroborated that exposure to these substances disrupts hormone secretion and increases risks of conditions including obesity, coronary heart disease, diabetes, and cancer\u003csup\u003e\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eGrip strength is a measure of the combined contraction force of intrinsic and extrinsic muscles of the hand and forearm. Individuals with greater forearm strength typically exhibit stronger overall musculature, making grip strength a general indicator for assessing muscle function status. Low grip strength has been reported as a marker for diagnosing sarcopenia\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e, and several prospective cohort studies have shown associations between grip strength and cardiovascular disease, pulmonary disease, cancer, and all-cause mortality\u003csup\u003e\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Additionally, grip strength is closely linked to metabolic and bone health indicators such as fasting triglycerides, blood pressure, waist circumference, as well as ATP III, IDP, and bone mineral density (BMD)\u003csup\u003e\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Importantly, research suggests that grip strength may influence associations with physical activity, diabetes, cardiovascular disease, and overall mortality risk\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. These findings underscore the potential importance of grip strength in predicting disease risk and its underestimated significance in health assessments.\u003c/p\u003e \u003cp\u003eThe National Health and Nutrition Examination Survey (NHANES) is a cross-sectional survey covering a representative sample of the U.S. population. This study utilized data from the 2011\u0026ndash;2012 and 2013\u0026ndash;2014 NHANES cycles to investigate the independent and joint associations of phenols and parabens with grip strength. Generalized linear models (GLM) and restricted cubic splines (RCS) were employed to establish dose-response relationships, assessing the impact of individual chemical exposures on grip strength. Additionally, weighted quantile sum (WQS) regression models and quantile-based g computation (qgcomp) were utilized to explore the combined effects of multiple chemical exposures on grip strength.\u003c/p\u003e"},{"header":"2. Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003e2.1. Study population and data sources\u003c/h2\u003e\n \u003cp\u003eNHANES, conducted by the Centers for Disease Control and Prevention (CDC), is a nationally representative cross-sectional survey conducted biennially. The survey aims to collect data on nutrition and physical health status of Americans, evaluating individual health and nutritional status, identifying disease prevalence, and related risk factors. This study included 16,112 participants across two consecutive NHANES cycles from 2011\u0026ndash;2012 and 2013\u0026ndash;2014. After excluding participants under 20 years old (n\u0026thinsp;=\u0026thinsp;5205), those without grip strength data (n\u0026thinsp;=\u0026thinsp;1103), and participants lacking exposure and covariate data (n\u0026thinsp;=\u0026thinsp;7936), a total of 1858 participants were included in the final analysis. Detailed participant exclusion criteria are depicted in Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n \u003ch2\u003e2.2. Measurement of Grip Strength\u003c/h2\u003e\n \u003cp\u003eUsing the Takei Digital Grip Strength Dynamometer, Model T.K.K.5401, grip strength was assessed to measure handgrip strength. During the testing procedure, participants, without physical limitations, were instructed to stand upright. Each participant squeezed the dynamometer with one hand as forcefully as possible, exhaling during the squeeze to prevent intra-thoracic pressure buildup. Subsequently, the other hand was tested in the same manner. Each hand underwent three trials with a 60-second interval between each trial. Hands were alternated between tests. Grip strength was calculated as the sum of the maximum readings from each hand, expressed in kilograms. Participants who only used one hand for testing were excluded from this variable calculation. Detailed testing protocol descriptions can be found on the NHANES website (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://wwwn.cdc.gov/Nchs/Nhanes/2013-2014/MGX_H.htm\u003c/span\u003e\u003c/span\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e).\u003c/span\u003e Given that individuals with higher body weight often exhibit greater strength under similar conditions, grip strength was adjusted for Body Mass Index (BMI) in this study. The grip strength adjusted for BMI was calculated by dividing the combined grip strength by BMI, and it was used as the dependent variable\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n \u003ch2\u003e2.3. Measurement of urinary phenols and parabens\u003c/h2\u003e\n \u003cp\u003eParticipants provided urine samples at mobile examination centers, which were frozen during transport to the National Center for Environmental Health, maintaining temperatures below \u0026minus;\u0026thinsp;20\u0026deg;C. We utilized online solid-phase extraction (SPE) coupled with high-performance liquid chromatography (HPLC) and tandem mass spectrometry (MS/MS) techniques to measure BPA, BP3, triclosan, and parabens in urine samples. Isotope-labeled internal standards were employed, enabling detection limits ranging from 0.1 to 2.3 nanograms per milliliter (ng/mL) in 100 \u0026micro;L urine samples, sufficient for measuring phenols in non-occupational exposure scenarios. Chemicals included in this study were those with the detection rates\u0026thinsp;\u0026gt;\u0026thinsp;85%, namely BP3, BPA, 2,4-dichlorophenol (24-DCB), 2,5-dichlorophenol (25-DCB), butyl paraben (BuP), methyl paraben (MeP), and propyl paraben (PrP). For measurements below the limit of detection (LOD) of phenols and parabens, values were imputed using the LOD divided by the square root of 2. Detailed protocols and methods are available in reports accessible via the NHANES Laboratory Protocol webpage\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n \u003ch2\u003e2.4. Covariates\u003c/h2\u003e\n \u003cp\u003eIn NHANES, participant demographic characteristics, lifestyle factors, and underlying health conditions are obtained through interviews or standardized questionnaires. Demographic variables include age (categorized as 20\u0026ndash;59 years and 60 years and older), sex (male and female), race/ethnicity (Mexican American, non-Hispanic White, non-Hispanic Black, and other), education level (less than or greater than high school diploma), marital status (married or living with partner, unmarried or other), and economic status (based on Poverty Income Ratio (PIR) categorized as below poverty\u0026thinsp;\u0026lt;\u0026thinsp;1.00 or at or above poverty\u0026thinsp;\u0026ge;\u0026thinsp;1.00). Lifestyle habits encompass smoking status (never, former, current), and alcohol consumption categorized as current heavy drinking (\u0026ge;\u0026thinsp;3 drinks per day for women or \u0026ge;\u0026thinsp;4 drinks per day for men, or binge drinking\u0026thinsp;\u0026ge;\u0026thinsp;5 days per month), current moderate drinking (\u0026ge;\u0026thinsp;2 drinks per day for women or \u0026ge;\u0026thinsp;3 drinks per day for men, or binge drinking\u0026thinsp;\u0026ge;\u0026thinsp;2 days per month), current light drinking (not meeting above criteria), former drinking, and never drinking. Detailed dietary intake information, including calorie, is collected through dietary interviews. Physical activity is assessed using total MET (Metabolic Equivalent) levels, calculated as the sum of frequencies, durations, and intensities of various physical activities. Underlying health conditions include diabetes and hypertension. Diabetes is defined based on diabetes history, fasting blood glucose\u0026thinsp;\u0026ge;\u0026thinsp;7.0 mmol/L (\u0026ge;\u0026thinsp;126 mg/dL), or glycated hemoglobin A1c\u0026thinsp;\u0026gt;\u0026thinsp;6.5%. Hypertension is defined as average systolic blood pressure\u0026thinsp;\u0026ge;\u0026thinsp;140 mmHg, average diastolic blood pressure\u0026thinsp;\u0026ge;\u0026thinsp;90 mmHg, or self-reported diagnosis by a doctor. Additionally, urine creatinine is included as an independent variable to assess urine sample dilution and its relationship with grip strength.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n \u003ch2\u003e2.5. Statistical analysis\u003c/h2\u003e\n \u003cp\u003eIn describing participant characteristics, continuous variables were summarized using mean and standard deviation (SD), while categorical variables were described using frequencies and percentages. Phenols and parabens in urine were natural Ln-transformed and categorized into tertiles (Q1, Q2, Q3). Stratified analyses were conducted based on demographic characteristics, lifestyle habits, and underlying health conditions.\u003c/p\u003e\n \u003cp\u003eThree statistical models were employed to assess the associations between phenols, parabens, and grip strength. Firstly, generalized linear models (GLM) were used to investigate the individual effects of phenols and parabens on grip strength. The first tertile (Q1) was set as the reference group, and effects were estimated using grip strength adjusted for BMI change with corresponding 95% confidence intervals (CI). Models were adjusted for all covariates including age, sex, race/ethnicity, economic status, marital status, education level, smoking, alcohol consumption, physical activity, calorie intake, diabetes, and hypertension. Secondly, restricted cubic spline (RCS) regression was employed to explore both linear and nonlinear relationships and dose-response effects of phenols and parabens on grip strength. The optimal number of knots, selected based on the Akaike Information Criterion, ranged from 3 to 7\u003csup\u003e23\u003c/sup\u003e. Finally, weighted quantile sum (WQS) regression analysis and quantile-based g computation (qgcomp) models were utilized to assess the overall impact of mixed phenols and parabens on grip strength. In WQS analysis, data were randomly split into training and validation sets at a 4:6 ratio, and compound weights were derived from 1000 bootstrap iterations in the training set to test the significance of the mixture in the validation set. WQS indices indicated the influence of adding a quantile to the outcome within the mixture. The qgcomp model corrected for directional homogeneity between assumed environmental exposures and outcomes by partitioning each urinary metabolite into quantiles and assigning positive and negative weighted indices. Overall analyses in the study population were conducted using generalized linear models, adjusting for various covariates to perform sensitivity analyses. Model A adjusted for urine creatinine only, Model B additionally adjusted for age, sex, and race/ethnicity, and Model C included all available covariates. Data analysis was performed using R software version 4.2.1, with restricted cubic spline analysis conducted using the \u0026quot;rms\u0026quot; package, WQS regression analysis using the \u0026quot;gWQS\u0026quot; package, and qgcomp analysis using the \u0026quot;qgcomp\u0026quot; package.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n \u003ch2\u003e3.1 Population characteristics and Distribution of urinary phenols and parabens concentration\u003c/h2\u003e\n \u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e presents detailed demographic characteristics of the participants. The study included a total of 1858 adults aged 20 years and older across two cycles, comprising 977 males (52.6%) and 881 females (47.4%). Young and middle-aged participants aged 20\u0026ndash;59 years accounted for 1348 individuals (72.8%). Overall, 44.6% of participants were non-Hispanic White, 83.3% had completed high school education or higher, and 79.7% reported household incomes at or above the poverty line. The mean grip strength adjusted for BMI was 2.68\u0026thinsp;\u0026plusmn;\u0026thinsp;0.92 m\u0026sup2;, and the average concentrations of BP3, BPA, BuP, MeP, PrP, 24-DCB, and 25-DCB in urine were 313\u0026thinsp;\u0026plusmn;\u0026thinsp;1,505.01 ng/ml, 3.12\u0026thinsp;\u0026plusmn;\u0026thinsp;19.03 ng/ml, 1.89\u0026thinsp;\u0026plusmn;\u0026thinsp;10.29 ng/ml, 211.30\u0026thinsp;\u0026plusmn;\u0026thinsp;475.69 ng/ml, 53.33\u0026thinsp;\u0026plusmn;\u0026thinsp;136.82 ng/ml, 93.39\u0026thinsp;\u0026plusmn;\u0026thinsp;790.94 ng/ml, and 3.13\u0026thinsp;\u0026plusmn;\u0026thinsp;19.64 ng/ml, respectively.\u003c/p\u003e\u003cbr\u003e\n \u003cdiv\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eBaseline characteristics of participants in the NHANES 2011\u0026ndash;2014 cycles. Categorical variables were presented as N (%), continuous variables were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003eCharacteristics\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\"\u003eStudy Participants\u003cbr\u003e\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eN\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e1858\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eAge, n(%)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e20\u0026ndash;59\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e1348 (72.6)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026ge;\u0026thinsp;60\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e510 (27.4)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eSex, n(%)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eMale\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e977 (52.6)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eFemale\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e881 (47.4)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eRace/ethnicity, n(%)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eMexican American\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e186 (10.0)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eNon-Hispanic Black\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e422 (22.7)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eNon-Hispanic White\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e829 (44.6)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eOther\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e421 (22.7)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eMarital status, n(%)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eMarried or living with a partner\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e1084 (58.3)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eUnmarried or other\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e774 (41.7)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eEducational level, n(%)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eHigh School or above\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e1548 (83.3)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eLess than High school\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e310 (16.7)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eSmoke status, n(%)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eCurrent\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e354 (19.1)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eFormer\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e421 (22.7)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eNever\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e1083 (58.3)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003ePast-year alcohol drinking, n(%)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eHeavy\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e369 (19.9)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eModerate\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e329 (17.7)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eMild\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e656 (35.3)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eFormer\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e278 (15.0)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eNever\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e226 (12.2)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eDiabetes mellitus, n(%)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eYes\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e307 (16.5)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eNo\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e1551 (83.5)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eHypertension, n(%)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eYes\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e710 (38.2)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eNo\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e1148 (61.8)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003ePoverty ratio, n(%)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eAt or above poverty line (\u0026ge;\u0026thinsp;1.00)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e1481 (79.7)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eBelow poverty line (\u0026lt;\u0026thinsp;1.00)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e377 (20.3)\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003ePhysical activity, MET\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e4, 458.25\u0026thinsp;\u0026plusmn;\u0026thinsp;6, 269.32\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eCalorie, kcal/d\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e2, 221.03\u0026thinsp;\u0026plusmn;\u0026thinsp;1, 051.55\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eUrine creatinine, mg/min\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e123.79\u0026thinsp;\u0026plusmn;\u0026thinsp;82.49\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eBP3, ng/mL\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e313.17\u0026thinsp;\u0026plusmn;\u0026thinsp;1, 505.01\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eBPA, ng/mL\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e3.12\u0026thinsp;\u0026plusmn;\u0026thinsp;19.03\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eBuP, ng/mL\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e1.89\u0026thinsp;\u0026plusmn;\u0026thinsp;10.29\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eMeP, ng/mL\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e211.30\u0026thinsp;\u0026plusmn;\u0026thinsp;475.69\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003ePrP, ng/mL\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e53.33\u0026thinsp;\u0026plusmn;\u0026thinsp;136.82\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e24-DCB, ng/mL\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e93.39\u0026thinsp;\u0026plusmn;\u0026thinsp;790.94\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e25-DCB, ng/mL\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e3.13\u0026thinsp;\u0026plusmn;\u0026thinsp;19.64\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eGrip strength/BMI, m\u003csup\u003e2\u003c/sup\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e2.68\u0026thinsp;\u0026plusmn;\u0026thinsp;0.92\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n \u003ch2\u003e3.2 Associations between single phenols and parabens exposure and grip strength\u003c/h2\u003e\n \u003cp\u003eUsing generalized linear models adjusted for all covariates, we evaluated the associations between individual phenols and parabens with grip strength. Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e presents the relationships between phenols and parabens and grip strength after Ln-transformed and categorization into tertiles (Q1, Q2, Q3). Compared to Q1, higher tertiles (Q3) of BP3 and BuP in urine significantly increased grip strength (BP3: \u0026beta;\u0026thinsp;=\u0026thinsp;0.09, 95% CI: 0.01, 0.16; BuP: \u0026beta;\u0026thinsp;=\u0026thinsp;0.09, 95% CI: 0.01, 0.17). Conversely, middle (Q2) and higher tertiles (Q3) of BPA in urine were significantly negatively associated with grip strength (Q2: \u0026beta; = -0.13, 95% CI: -0.21, -0.06; Q3: \u0026beta; = -0.12, 95% CI: -0.21, -0.04). Each increment in Ln-BPA was associated with a grip strength decrease of 0.05 (95% CI: -0.08, -0.02). However, the association between Ln-BP3 and grip strength did not show statistically significant differences.\u003c/p\u003e\u003cbr\u003e\n \u003cdiv\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eAssociations of single phenols and parabens with grip strength in the NHANES 2011\u0026ndash;2014 cycles. Models were adjusted for age, sex, race/ethnicity, Marital status, Educational level, Smoke status, Past-year alcohol drinking, Diabetes mellitus, Hypertension, Poverty ratio, Physical activity, Calorie, Urine creatinine. Continuous: Ln-transformed concentration of phenols and parabens; CI: confidence interval; \u0026beta;: \u0026beta; coefficient; Q: quartile; Ref: reference. *: P\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003eExposure\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\"\u003eQ1\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003eQ2\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003eQ3\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003eContinuous\u003cbr\u003e\u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026beta;(95% CI)\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u003cem\u003eP\u003c/em\u003e value\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026beta;(95% CI)\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u003cem\u003eP\u003c/em\u003e value\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026beta;(95% CI)\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u003cem\u003eP\u003c/em\u003e value\u003cbr\u003e\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eBP3\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eRef\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e0.05(-0.03, 0.12)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e0.22\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\u003cstrong\u003e0.09( 0.01, 0.16)\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\u003cstrong\u003e0.03*\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e0.01(-0.01, 0.02)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e0.210\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eBPA\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eRef\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\u003cstrong\u003e-0.13(-0.21,-0.06)\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001*\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\u003cstrong\u003e-0.12(-0.21,-0.04)\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\u003cstrong\u003e0.004*\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u003cstrong\u003e-0.05(-0.08,-0.02)\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\u003cstrong\u003e0.003*\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eBuP\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eRef\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e0.06(-0.01, 0.13)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e0.08\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\u003cstrong\u003e0.09( 0.01, 0.17)\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\u003cstrong\u003e0.03*\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e0.02( 0.00, 0.04)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e0.040\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eMeP\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eRef\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e0(-0.09, 0.08)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e0.93\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e0.08(-0.02, 0.19)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e0.13\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e0.01(-0.02, 0.04)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e0.530\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003ePrP\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eRef\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e0.02(-0.06, 0.11)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e0.60\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e-0.06(-0.17, 0.05)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e0.31\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e0(-0.03, 0.02)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e0.690\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e24-DCB\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eRef\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e-0.02(-0.09, 0.06)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e0.63\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e0(-0.09, 0.09)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e0.93\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e0.01(-0.02, 0.03)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e0.660\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e25-DCB\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003eRef\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e-0.05(-0.13, 0.03)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e0.24\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e-0.05(-0.14, 0.04)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e0.30\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e-0.03(-0.06, 0.01)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e0.120\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003e3.3 Dose-response relationship between phenols and parabens and grip strength\u003c/h2\u003e\n \u003cp\u003eAfter adjusting for all covariates, we further explored dose-response relationships between Ln-transformed individual phenols and parabens and grip strength using restricted cubic spline (RCS) analysis (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). We observed a non-linear \u0026quot;U\u0026quot; shaped relationship between Ln-BPA and grip strength (non-linear P\u0026thinsp;=\u0026thinsp;0.017), indicating that grip strength decreases with increasing concentrations of BPA at lower levels. Additionally, Ln-BP3 and Ln-MeP exhibited an \u0026quot;S\u0026quot; shaped dose-response curve with grip strength, while Ln-BuP and Ln-PrP showed an inverted \u0026quot;U\u0026quot; shaped curve, and Ln-24-DCB and Ln-25-DCB displayed a \u0026quot;U\u0026quot; shaped curve with grip strength.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n \u003ch2\u003e3.4 Associations between mixture phenols and parabens exposure and grip strength\u003c/h2\u003e\n \u003cp\u003eThis study employed WQS and qgcomp multi-pollutant models to investigate the relationship between phenols and parabens mixtures and grip strength. After adjusting for all covariates, each increment in a mixture quartile (WQS index) of phenols and parabens was associated with a decrease in BMI-adjusted grip strength by 0.058 (95% CI: 0.035, 0.081). Figure \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e depicts the regression weights of WQS indices for each phenol and paraben compound on the overall effect. BPA had the highest WQS weight, while BP3 and BuP contributed minimally. Additionally, qgcomp analysis revealed positive weights for BuP, BPA, and MeP (weights: 0.455, 0.281, 0.264, respectively), whereas BPA, 25-DCB, PrP, and 24-DCB showed negative weights, with BPA having the largest negative weight of 0.545.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n \u003ch2\u003e3.5 subgroup analysis\u003c/h2\u003e\n \u003cp\u003eThis study conducted subgroup analyses based on age, sex, race, poverty status, diabetes, hypertension, smoking, and alcohol consumption, as depicted in Figs. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e and Tables S1-S6. Among young and middle-aged adults, BPA exhibited significant negative associations with grip strength at the second quartile (\u0026beta; = -0.14, 95% CI: -0.24, -0.05) and third quartile (\u0026beta; = -0.15, 95% CI: -0.25, -0.04), which persisted even after logarithmic transformation. Conversely, BuP showed significant positive associations with grip strength only at the third quartile (\u0026beta;\u0026thinsp;=\u0026thinsp;0.12, 95% CI: 0.02, 0.22).Among older adults, Ln-transformed 25-DCB concentrations were associated with grip strength (P\u0026thinsp;=\u0026thinsp;0.03), and BPA showed associations only at the second quartile (P\u0026thinsp;=\u0026thinsp;0.04).In females, Ln-transformed BPA exhibited significant negative associations with grip strength (\u0026beta; = -0.06, 95% CI: -0.10, -0.02), particularly at the second quartile (\u0026beta; = -0.20, 95% CI: -0.29, -0.12) and third quartile (\u0026beta; = -0.17, 95% CI: -0.27, -0.07), compared to the first quartile. However, there were no statistically significant associations between chemical substances and grip strength in males.\u003c/p\u003eStratified analyses by race revealed a significant negative association between BPA at the second quartile and grip strength among non-Hispanic White individuals (\u0026beta; = -0.15, 95% CI: -0.25, -0.04), and a significant positive association between BuP and grip strength among Mexican American individuals (\u0026beta;\u0026thinsp;=\u0026thinsp;0.32, 95% CI: 0.10, 0.53). In the population above the poverty line, BPA showed a significant negative association with grip strength, whereas among low-income groups, significant negative associations were observed only at the second quartile of BPA (\u0026beta; = -0.22, 95% CI: -0.41, -0.04). Stratified analyses by underlying diseases indicated that the association between 25-DCB and grip strength was influenced by diabetes, showing a significant association among diabetic individuals (\u0026beta; = -0.10, 95% CI: -0.19, -0.01). In individuals with hypertension, the second quartile of BPA showed a negative association with grip strength (\u0026beta; = -0.12, 95% CI: -0.23, -0.01). No significant associations between phenols and parabens and grip strength were found among current and former smokers. Notably, among heavy drinkers, BP3 and MeP exhibited significant positive associations with grip strength (BP3: \u0026beta;\u0026thinsp;=\u0026thinsp;0.06, 95% CI: 0.02, 0.10; MeP: \u0026beta;\u0026thinsp;=\u0026thinsp;0.09, 95% CI: 0.02, 0.16), while PrP showed a significant negative association (PrP: \u0026beta; = -0.07, 95% CI: -0.12, -0.01).\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\n \u003ch2\u003e3.6 Sensitivity analysis\u003c/h2\u003e\n \u003cp\u003eTable S7 presents the results of the sensitivity analysis. Comparisons among Model C GLM, which adjusted for all covariates; Model A, the crude model adjusting only for urine creatinine; and Model B, which adjusted for age, sex, race/ethnicity, marital status, educational level, poverty ratio, and urine creatinine, revealed statistically significant associations between phenols, parabens, and grip strength in all three models.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThis study utilized data from two cycles of the 2011\u0026ndash;2014 NHANES surveys, recruiting a total of 1858 participants, aimed at exploring the association between grip strength in U.S. adults aged 20 years and older and concentrations of phenols and parabens in urine. Using generalized linear models, we found a significant relationship between BPA and decreased grip strength, while BP3 and BuP were closely associated with increased grip strength. In contrast, MeP, PrP, 24-DCB, and 25-DCB showed no statistically significant impact on grip strength. Further exploration with dose-response curves revealed varying degrees of compound-specific dose dependency on grip strength. Utilizing mixed-effects models such as WQS and qgcomp, we identified significant statistical differences between phenols and parabens mixtures and decreased grip strength, with BPA contributing most significantly; in the qgcomp model, BuP, BPA, and MeP exhibited positive weights, whereas BPA, 25-DCB, PrP, and 24-DCB showed negative weights, with BPA having the most pronounced negative weight. Additionally, comprehensive subgroup analyses were conducted based on age, gender, race/ethnicity, poverty status, diabetes, hypertension, smoking, and alcohol consumption habits. Subgroup analysis results highlighted significant differences across demographic indicators, underlying diseases, and lifestyle habits, with demographic factors such as age and gender exerting the most notable influence on the association between phenols and parabens and grip strength, followed by underlying diseases, while the impact of lifestyle habits such as smoking and alcohol consumption was comparatively minor.\u003c/p\u003e \u003cp\u003eBPA is a widely used endocrine-disrupting chemical employed primarily in the production of polycarbonate plastics, epoxy resins lining metal cans, and various plastic consumer goods. Findings from the Hartford County cohort\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e indicate that impaired grip strength is associated with features of metabolic syndrome such as elevated fasting triglycerides, blood pressure, and waist circumference, as well as insulin resistance. Moreover, research by Oliana Carnevali et al.\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e suggests that fish fed with BPA-contaminated feed exhibit decreased unsaturated fatty acids and increased triglycerides and saturated fatty acid chains, with alterations in protein content, affecting the composition and texture of skeletal muscle. Experimental studies by Kristina et al. \u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003eusing rodent models suggest that maternal exposure to BPA may induce insulin resistance in offspring rats, thereby impacting skeletal muscle function.\u003c/p\u003e \u003cp\u003eAdditionally, it is noteworthy that we observed a positive correlation between elevated levels of BP3 and BuP with grip strength. Luo et al. \u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003eanalyzing 2013\u0026ndash;2014 NHANES data, demonstrated that grip strength correlates with BMD in non-adjacent skeletal regions, highlighting hand grip strength as an indicator for assessing BMD across different genders and menopausal statuses. Concurrently, a study\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003eindicated an association between hand grip strength and hand BMD in healthy individuals aged 19\u0026ndash;50 years. Wang et al.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e based on NHANES data, reported an association between BP3 and paraben compounds with increased BMD, supported by further validation from Gu et al. \u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Thus, we hypothesize that the positive correlation between BP3 and BuP with grip strength may be related to BMD. Despite limited current research on the impact of BP3 and BuP on grip strength, their specific mechanisms remain unclear and warrant further investigation. Our study provides preliminary evidence of the association between BP3, BuP, and grip strength.\u003c/p\u003e \u003cp\u003eThe impairment of grip strength is associated with characteristics of metabolic syndrome and insulin resistance. BPA a common endocrine disruptor, has garnered particular attention for its involvement in insulin resistance, obesity, and type 2 diabetes (T2D) development. A previous study demonstrated\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e that exposure to BPA exacerbates insulin resistance during pregnancy, with reduced insulin-stimulated Akt phosphorylation observed in skeletal muscle and liver tissues of pregnant mice treated with bisphenol A. Concurrently, another study\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e indicated that BPA exposure may exacerbate existing metabolic stress, leading to increased cellular senescence. Currently, the mechanisms through which phenols and parabens impact grip strength remain unclear, lacking direct evidence and necessitating further research for validation.\u003c/p\u003e \u003cp\u003eThe association between environmental pollutants and grip strength has garnered increasing attention. Multiple studies have indicated a negative correlation between exposure to metal mixtures such as cadmium, copper, lead, strontium, and arsenic, and grip strength, while zinc shows a positive correlation\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e. Sun et al. found that phthalate exposure among American adults was inversely related to grip strength\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e. Additionally, glyphosate, a widely used herbicide globally, has been linked unfavorably with all grip strength measurements\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e. Both indoor and outdoor air pollution have also been reported to lower grip strength in adults\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e. Grip strength exhibits diverse associations with environmental pollutants. Phenols and parabens, prevalent pollutants in personal care and consumer products, are widely distributed in the environment. Therefore, it is imperative to conduct in-depth research into their relationship with grip strength.\u003c/p\u003e \u003cp\u003eA study on serum testosterone levels and urinary concentrations of BPA, BP-3, triclosan, and parabens has demonstrated differential results influenced by age and sex \u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e. Among adolescents, BPA shows a negative correlation with testosterone levels in boys but a positive correlation in girls, whereas BP-3 is significantly associated with decreased testosterone levels only in adolescent boys. Multiple studies\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e,\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e on phenols and parabens have also indicated gender-specific associations. In this study, significant variations in the relationship between phenols and parabens with grip strength were observed across gender and age groups.\u003c/p\u003e \u003cp\u003eOur study has several strengths. Firstly, we utilized nationally representative NHANES data collected through standardized protocols and multiple measurement methods, ensuring high-quality data control. Additionally, we conducted subgroup analyses based on age, sex, economic status, race, underlying diseases, and lifestyle habits. Furthermore, we employed the qgcomp model to address the limitation of the WQS model, which assumes a single direction of effect. However, our study also has several limitations. Firstly, it is cross-sectional in design, thus precluding causal inference regarding the impact of mixed chemical exposures on cognitive function. Secondly, despite accounting for various covariates, residual and unmeasured confounding factors may still influence observational studies. Lastly, the rapid metabolism of phenols and parabens results in fluctuations in metabolite concentrations in urine over time.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eOur study identifies phenols and parabens as potential risk factors contributing to decreased grip strength. Further analysis reveals that BPA plays a crucial role in this association, with dose-response curves indicating a nonlinear relationship with grip strength. Given the limitations of our cross-sectional study design, future prospective cohort studies and mechanistic investigations are needed to validate and explore the relationship between phenols and parabens with grip strength.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePublicly available datasets were analyzed in this study. This data can be found here: https://www.cdc.gov/nchs/nhanes/index.htm\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eY.Y.X.: Conceptualization, methodology, data analysis, draft writing; S.Y.G.: Data analysis, interpretation of data, draft writing, revision; S.K.Q.: Data curation, visualization; N.J. and Y.Y.C.: Visualization, S.M.Y.: Funding acquisition, supervision. All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMa, Y.\u003cem\u003e et al.\u003c/em\u003e The adverse health effects of bisphenol A and related toxicity mechanisms. \u003cem\u003eEnviron Res\u003c/em\u003e \u003cstrong\u003e176\u003c/strong\u003e, 108575 (2019).\u003c/li\u003e\n\u003cli\u003eKim, S. \u0026amp; Choi, K. Occurrences, toxicities, and ecological risks of benzophenone-3, a common component of organic sunscreen products: a mini-review. \u003cem\u003eEnviron Int\u003c/em\u003e \u003cstrong\u003e70\u003c/strong\u003e, 143-157 (2014).\u003c/li\u003e\n\u003cli\u003eBolujoko, N. B.\u003cem\u003e et al.\u003c/em\u003e Toxicity and removal of parabens from water: A critical review. \u003cem\u003eSci Total Environ\u003c/em\u003e \u003cstrong\u003e792\u003c/strong\u003e, 148092 (2021).\u003c/li\u003e\n\u003cli\u003evan der Schyff, V., Suchankova, L., Kademoglou, K., Melymuk, L. \u0026amp; Klanova, J. Parabens and antimicrobial compounds in conventional and \u0026quot;green\u0026quot; personal care products. \u003cem\u003eChemosphere\u003c/em\u003e \u003cstrong\u003e297\u003c/strong\u003e, 134019 (2022).\u003c/li\u003e\n\u003cli\u003eRios-Fuster, B.\u003cem\u003e et al.\u003c/em\u003e Assessing microplastic ingestion and occurrence of bisphenols and phthalates in bivalves, fish and holothurians from a Mediterranean marine protected area. \u003cem\u003eEnviron Res\u003c/em\u003e \u003cstrong\u003e214\u003c/strong\u003e, 114034 (2022).\u003c/li\u003e\n\u003cli\u003eErrico, S.\u003cem\u003e et al.\u003c/em\u003e Analysis and occurrence of some phenol endocrine disruptors in two marine sites of the northern coast of Sicily (Italy). \u003cem\u003eMar Pollut Bull\u003c/em\u003e \u003cstrong\u003e120\u003c/strong\u003e, 68-74 (2017).\u003c/li\u003e\n\u003cli\u003eArfaeinia, H.\u003cem\u003e et al.\u003c/em\u003e Monitoring and eco-toxicity effect of paraben-based pollutants in sediments/seawater, north of the Persian Gulf. \u003cem\u003eEnviron Geochem Health\u003c/em\u003e \u003cstrong\u003e44\u003c/strong\u003e, 4499-4521 (2022).\u003c/li\u003e\n\u003cli\u003eShankar, A., Teppala, S. \u0026amp; Sabanayagam, C. Bisphenol A and peripheral arterial disease: results from the NHANES. \u003cem\u003eEnviron Health Perspect\u003c/em\u003e \u003cstrong\u003e120\u003c/strong\u003e, 1297-1300 (2012).\u003c/li\u003e\n\u003cli\u003eWard, J. B., Casagrande, S. S. \u0026amp; Cowie, C. C. Urinary phenols and parabens and diabetes among US adults, NHANES 2005-2014. \u003cem\u003eNutr Metab Cardiovasc Dis\u003c/em\u003e \u003cstrong\u003e30\u003c/strong\u003e, 768-776 (2020).\u003c/li\u003e\n\u003cli\u003eAlwadi, D., Felty, Q., Roy, D., Yoo, C. \u0026amp; Deoraj, A. Environmental Phenol and Paraben Exposure Risks and Their Potential Influence on the Gene Expression Involved in the Prognosis of Prostate Cancer. \u003cem\u003eInt J Mol Sci\u003c/em\u003e \u003cstrong\u003e23\u003c/strong\u003e (2022).\u003c/li\u003e\n\u003cli\u003eStevens, D. R.\u003cem\u003e et al.\u003c/em\u003e Midpregnancy Phthalate and Phenol Biomarkers in Relation to Infant Body Composition: The Healthy Start Prospective Cohort. \u003cem\u003eEnviron Health Perspect\u003c/em\u003e \u003cstrong\u003e131\u003c/strong\u003e, 87017 (2023).\u003c/li\u003e\n\u003cli\u003eStudenski, S. A.\u003cem\u003e et al.\u003c/em\u003e The FNIH sarcopenia project: rationale, study description, conference recommendations, and final estimates. \u003cem\u003eJ Gerontol A Biol Sci Med Sci\u003c/em\u003e \u003cstrong\u003e69\u003c/strong\u003e, 547-558 (2014).\u003c/li\u003e\n\u003cli\u003eCelis-Morales, C. A.\u003cem\u003e et al.\u003c/em\u003e Associations of grip strength with cardiovascular, respiratory, and cancer outcomes and all cause mortality: prospective cohort study of half a million UK Biobank participants. \u003cem\u003eBMJ\u003c/em\u003e \u003cstrong\u003e361\u003c/strong\u003e, k1651 (2018).\u003c/li\u003e\n\u003cli\u003eLiu, W.\u003cem\u003e et al.\u003c/em\u003e The association of grip strength with cardiovascular diseases and all-cause mortality in people with hypertension: Findings from the Prospective Urban Rural Epidemiology China Study. \u003cem\u003eJ Sport Health Sci\u003c/em\u003e \u003cstrong\u003e10\u003c/strong\u003e, 629-636 (2021).\u003c/li\u003e\n\u003cli\u003eDai, K. Z., Laber, E. B., Chen, H., Mentz, R. J. \u0026amp; Malhotra, C. Hand Grip Strength Predicts Mortality and Quality of Life in Heart Failure: Insights From the Singapore Cohort of Patients With Advanced Heart Failure. \u003cem\u003eJ Card Fail\u003c/em\u003e \u003cstrong\u003e29\u003c/strong\u003e, 911-918 (2023).\u003c/li\u003e\n\u003cli\u003eSayer, A. A.\u003cem\u003e et al.\u003c/em\u003e Grip strength and the metabolic syndrome: findings from the Hertfordshire Cohort Study. \u003cem\u003eQJM\u003c/em\u003e \u003cstrong\u003e100\u003c/strong\u003e, 707-713 (2007).\u003c/li\u003e\n\u003cli\u003eWang, N.\u003cem\u003e et al.\u003c/em\u003e Association of bone mineral density with nine urinary personal care and consumer product chemicals and metabolites: A national-representative, population-based study. \u003cem\u003eEnviron Int\u003c/em\u003e \u003cstrong\u003e142\u003c/strong\u003e, 105865 (2020).\u003c/li\u003e\n\u003cli\u003eGu, L.\u003cem\u003e et al.\u003c/em\u003e Associations between mixed urinary phenols and parabens metabolites and bone mineral density: Four statistical models. \u003cem\u003eChemosphere\u003c/em\u003e \u003cstrong\u003e311\u003c/strong\u003e, 137065 (2023).\u003c/li\u003e\n\u003cli\u003eCelis-Morales, C. A.\u003cem\u003e et al.\u003c/em\u003e The association between physical activity and risk of mortality is modulated by grip strength and cardiorespiratory fitness: evidence from 498 135 UK-Biobank participants. \u003cem\u003eEur Heart J\u003c/em\u003e \u003cstrong\u003e38\u003c/strong\u003e, 116-122 (2017).\u003c/li\u003e\n\u003cli\u003eCelis-Morales, C. A.\u003cem\u003e et al.\u003c/em\u003e Associations Between Diabetes and Both Cardiovascular Disease and All-Cause Mortality Are Modified by Grip Strength: Evidence From UK Biobank, a Prospective Population-Based Cohort Study. \u003cem\u003eDiabetes Care\u003c/em\u003e \u003cstrong\u003e40\u003c/strong\u003e, 1710-1718 (2017).\u003c/li\u003e\n\u003cli\u003eChen, K., Zhou, J., Liu, N. \u0026amp; Meng, X. Association of Serum Concentrations of Copper, Selenium, and Zinc with Grip Strength Based on NHANES 2013-2014. \u003cem\u003eBiol Trace Elem Res\u003c/em\u003e \u003cstrong\u003e202\u003c/strong\u003e, 824-834 (2024).\u003c/li\u003e\n\u003cli\u003eZhou, X., Ye, X. \u0026amp; Calafat, A. M. Automated on-line column-switching HPLC-MS/MS method for the quantification of triclocarban and its oxidative metabolites in human urine and serum. \u003cem\u003eJ Chromatogr B Analyt Technol Biomed Life Sci\u003c/em\u003e \u003cstrong\u003e881-882\u003c/strong\u003e, 27-33 (2012).\u003c/li\u003e\n\u003cli\u003eZhu, H., Xu, Y., Lin, D., Wang, X. \u0026amp; Niu, B. Relationship between social jetlag and body mass index in nurses working shift schedules: a cross-sectional study. \u003cem\u003eSci Rep\u003c/em\u003e \u003cstrong\u003e14\u003c/strong\u003e, 16911 (2024).\u003c/li\u003e\n\u003cli\u003eCarnevali, O.\u003cem\u003e et al.\u003c/em\u003e Diets contaminated with Bisphenol A and Di-isononyl phtalate modify skeletal muscle composition: A new target for environmental pollutant action. \u003cem\u003eSci Total Environ\u003c/em\u003e \u003cstrong\u003e658\u003c/strong\u003e, 250-259 (2019).\u003c/li\u003e\n\u003cli\u003eGalyon, K. D.\u003cem\u003e et al.\u003c/em\u003e Maternal bisphenol A exposure alters rat offspring hepatic and skeletal muscle insulin signaling protein abundance. \u003cem\u003eAm J Obstet Gynecol\u003c/em\u003e \u003cstrong\u003e216\u003c/strong\u003e, 290 e291-290 e299 (2017).\u003c/li\u003e\n\u003cli\u003eLuo, Y., Jiang, K. \u0026amp; He, M. Association between grip strength and bone mineral density in general US population of NHANES 2013-2014. \u003cem\u003eArch Osteoporos\u003c/em\u003e \u003cstrong\u003e15\u003c/strong\u003e, 47 (2020).\u003c/li\u003e\n\u003cli\u003eKaya, A., Ozgocmen, S., Ardicoglu, O., Kamanli, A. \u0026amp; Gudul, H. Relationship between grip strength and hand bone mineral density in healthy adults. \u003cem\u003eArch Med Res\u003c/em\u003e \u003cstrong\u003e36\u003c/strong\u003e, 603-606 (2005).\u003c/li\u003e\n\u003cli\u003eAlonso-Magdalena, P.\u003cem\u003e et al.\u003c/em\u003e Bisphenol A exposure during pregnancy disrupts glucose homeostasis in mothers and adult male offspring. \u003cem\u003eEnviron Health Perspect\u003c/em\u003e \u003cstrong\u003e118\u003c/strong\u003e, 1243-1250 (2010).\u003c/li\u003e\n\u003cli\u003eSoundararajan, A.\u003cem\u003e et al.\u003c/em\u003e Bisphenol A exposure under metabolic stress induces accelerated cellular senescence in vivo in a p53 independent manner. \u003cem\u003eSci Total Environ\u003c/em\u003e \u003cstrong\u003e689\u003c/strong\u003e, 1201-1211 (2019).\u003c/li\u003e\n\u003cli\u003eGarcia-Esquinas, E., Carrasco-Rios, M., Navas-Acien, A., Ortola, R. \u0026amp; Rodriguez-Artalejo, F. Cadmium exposure is associated with reduced grip strength in US adults. \u003cem\u003eEnviron Res\u003c/em\u003e \u003cstrong\u003e180\u003c/strong\u003e, 108819 (2020).\u003c/li\u003e\n\u003cli\u003eLiang, Y. J.\u003cem\u003e et al.\u003c/em\u003e Correlation between Combined Urinary Metal Exposure and Grip Strength under Three Statistical Models: A Cross-sectional Study in Rural Guangxi. \u003cem\u003eBiomed Environ Sci\u003c/em\u003e \u003cstrong\u003e37\u003c/strong\u003e, 3-18 (2024).\u003c/li\u003e\n\u003cli\u003eLiang, Y.\u003cem\u003e et al.\u003c/em\u003e Moderate selenium mitigates hand grip strength impairment associated with elevated blood cadmium and lead levels in middle-aged and elderly individuals: insights from NHANES 2011-2014. \u003cem\u003eFront Pharmacol\u003c/em\u003e \u003cstrong\u003e14\u003c/strong\u003e, 1324583 (2023).\u003c/li\u003e\n\u003cli\u003eSun, L.\u003cem\u003e et al.\u003c/em\u003e Exposure to phthalates is associated with grip strength in US adults. \u003cem\u003eEcotoxicol Environ Saf\u003c/em\u003e \u003cstrong\u003e209\u003c/strong\u003e, 111787 (2021).\u003c/li\u003e\n\u003cli\u003eFang, Y. W., Wang, C. \u0026amp; Lin, C. Y. Association between urinary glyphosate levels and hand grip strength in a representative sample of US adults: NHANES 2013-2014. \u003cem\u003eFront Public Health\u003c/em\u003e \u003cstrong\u003e12\u003c/strong\u003e, 1352570 (2024).\u003c/li\u003e\n\u003cli\u003eLin, H.\u003cem\u003e et al.\u003c/em\u003e Association of Indoor and Outdoor Air Pollution With Hand-Grip Strength Among Adults in Six Low- and Middle-Income Countries. \u003cem\u003eJ Gerontol A Biol Sci Med Sci\u003c/em\u003e \u003cstrong\u003e75\u003c/strong\u003e, 340-347 (2020).\u003c/li\u003e\n\u003cli\u003eScinicariello, F. \u0026amp; Buser, M. C. Serum Testosterone Concentrations and Urinary Bisphenol A, Benzophenone-3, Triclosan, and Paraben Levels in Male and Female Children and Adolescents: NHANES 2011-2012. \u003cem\u003eEnviron Health Perspect\u003c/em\u003e \u003cstrong\u003e124\u003c/strong\u003e, 1898-1904 (2016).\u003c/li\u003e\n\u003cli\u003eLi, Y.\u003cem\u003e et al.\u003c/em\u003e Associations of urinary levels of phenols and parabens with osteoarthritis among US adults in NHANES 2005-2014. \u003cem\u003eEcotoxicol Environ Saf\u003c/em\u003e \u003cstrong\u003e192\u003c/strong\u003e, 110293 (2020).\u003c/li\u003e\n\u003cli\u003eHu, P.\u003cem\u003e et al.\u003c/em\u003e Associations between exposure to a mixture of phenols, parabens, and phthalates and sex steroid hormones in children 6-19 years from NHANES, 2013-2016. \u003cem\u003eSci Total Environ\u003c/em\u003e \u003cstrong\u003e822\u003c/strong\u003e, 153548 (2022).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Phenols, Parabens, Grip strength, Urinary metabolites, Mixture, NHANES","lastPublishedDoi":"10.21203/rs.3.rs-4892050/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4892050/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePrevious research has indicated potential health hazards of phenols and parabens from environmental exposure to humans. However, studies examining their relationship with grip strength remain limited. Utilizing data from the National Health and Nutrition Examination Survey (NHANES), this study included 1,858 adults aged 20 years and older to explore the independent and combined associations of phenols and parabens with grip strength. In single exposure analyses, bisphenol A (BPA) exhibited a negative association with grip strength, while benzophenone-3 (BP3) and butyl paraben (BuP) showed positive associations. Restricted cubic splines (RCS) regression indicated a U-shaped nonlinear relationship between BPA and grip strength across all participants. Weighted quantile sum (WQS) regression models revealed a negative association between combined exposure to various metals in urine and grip strength. Quantile based g-computation (qgcomp) analysis suggested positive weights for urinary mixture of BuP, BPA, and methyl paraben (MeP), whereas 2,5-dichlorophenol (25-DCB), propyl paraben (PrP), and 2,4-dichlorophenol (24-DCB) had negative weights. Subgroup analyses indicated significant differences in results across age and gender subgroups. Given the limitations of cross-sectional studies, prospective and mechanistic investigations are warranted in future research.\u003c/p\u003e","manuscriptTitle":"Association of exposure to phenols and parabens mixtures with grip strength among adults in the United States: A cross-sectional study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-15 05:00:54","doi":"10.21203/rs.3.rs-4892050/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ac11466f-ecaf-4d8c-bd15-56d56e86d8e7","owner":[],"postedDate":"October 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-13T18:23:28+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-15 05:00:54","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4892050","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4892050","identity":"rs-4892050","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}